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Transition metal complexes of pyridylphosphine and dipyridylborate ligands in dehydrogenation reactions

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Transition metal complexes of pyridylphosphine and dipyridylborate ligands in dehydrogenation reactions

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Content TRANSITION METAL COMPLEXES OF PYRIDYLPHOSPHINE AND DIPYRIDYLBORATE LIGANDS IN DEHYDROGENATION REACTIONS by Jeff Joseph A. Celaje A Dissertation Presented to the FACULTY OF THE USC GRADUATE SCHOOL UNIVERSITY OF SOUTHERN CALIFORNIA In Partial Fulfillment of the Requirements for the Degree DOCTOR OF PHILOSOPHY (CHEMISTRY) December 2016 Copyright 2016 Jeff Joseph A. Celaje ii Dedication To my wife Jasmin, my daughters Julianne and Jessie, Mom, Dad, and Brothers and Sisters. iii Acknowledgments Firstly, I would like to thank my advisor, Professor Travis J. Williams, for his guidance these last five years. I very much enjoyed working for someone who has great love and enthusiasm for chemistry. I learned a lot about organometallic chemistry while having a blast working on very cool, practical, and impactful projects. I am very thankful and very lucky to have had such a wonderful advisor. A special thank you to my qualification and dissertation committee members: Professors Richard A. Brutchey, Karl O. Christe, Kyung W. Jung, and John A. Petruska for their time, advice and support. Thanks to Prof. G. K. Surya Prakash for his support and advice, and to Dr. Miklos Czaun of the Prakash group for all his help. Thanks to Prof. Mike Richmond of the University of North Texas for helping us with computational studies and to Prof. Ralf Haiges for his invaluable help with X-ray crystallography. Moreover, I would like to thank all the Professors I’ve had in organic chemistry for instilling in me a great love for organic chemistry: Prof. Matthias Selke, Prof. Carlos Gutierrez, Prof. Jafargholi Amirmoazzami, Prof. Erik Sorensen, Prof. Chulbom Lee, Prof. John Groves, Prof. Martin Semmelhack, Prof. Jeffrey Schwartz, Prof. Travis Williams, Prof. Kyung Jung, and Prof. Nicos Petasis. Thanks to all the Professors I worked for as a teaching assistant: Prof. Maitland Jones, Dr. Henry Gingrich, Dr. Jennifer Moore, Dr. Rebecca Broyer, Prof. Anna Krylov, Dr. Jessica Parr, Prof. Travis Williams, Prof. Kyung Jung, Prof. Hogen-Esch, and Prof. Valery Fokin. And a special thanks to Prof. Valery Fokin for taking me as a postdoc. I am very excited about joining your lab. I also want to thank my previous research advisors. A special thanks to Professor Matthias Selke of California State University, Los Angeles. You inspired me when I was just starting to do research and you helped me resurrect my career and passion for chemistry when I was at a low point in my career. Maraming salamat po! A special thanks to Professor Erik iv Sorensen of Princeton University, who has been instrumental in my development as a scientist. Thanks for being a great PI. Total synthesis is very difficult (“like climbing Mount Everest”) and I am not the first to fail in my endeavors. I apologize I hadn’t the mental fortitude then to stick it out. Thanks to all former and current Williams’ group members for making the lab a pleasant place to work: Dr. Brian Conley, Dr. Emine Boz, Dr. Jessica Herron, Dr. Megan- Pennington Boggio, Dr. Anna Dawsey, Dr. Vincent Li, Dr. Xinping Wu, Dr. Zhiyao Lu, Dr. Xingyue Zhang, Ivan Demianets, Valery Cherapakhin, Jonathan Lo, Robinson Flaig, Elyse Kedzie, Forrest Zhang, Lisa Kam, Nicholas Terrile, Lena Foellmer, Kathryn Hathaway, Christina Ratto, Ana Victoria Flores, Brock Malinoski, Denver Guess, and Christine Epperson. A special thanks to my graduate student co-workers Megan, Yao, Lily, and Jon, as well as my undergraduate co-workers Robinson, Elyse, Forrest, Lisa, and Nicky for our collaborations. Not only are you great co-workers but great friends as well. Thank you for your help and support. Thanks to Dr. Mario Vargas and Kim Nguyen for being good friends and helping me with my problems in graduate school. And a special thanks to my friend and mentor Vicki- Kubo Anderson, who has listened to me talk about my problems and has encouraged me to be more positive and believe in myself since I was an undergraduate. Thanks also to my friends Dr. David Ho, Ha-Yong Chung, Dr. Ruomei Gao, Dr. Dong Zhang, Dr. Lixin Shi, Dr. Lorilee Tallorin, Alon Agua, Eric Fromer, Prof. Yiyun Chen, Dr. Hao Xie, Prof. Jimin Kim, Dr. Jinglong Chen, Dr. Carmen Drahl, Prof. Erik Alexanian, Dr. William Shipe, Dr. Robert Moreau, Annie Nalbandian, Dr. Christoph Zapf, Prof. Brian Goess, Prof. Glen Sammis, Dr. David Richard and so many other people who have had a great influence in my career and development as a chemist. Thanks to the excellent staff of the Loker Hydrocarbon Institute and the USC Department of Chemistry: David Hunter, Michele Dea, Carole Phillips, Magnolia Benitez, Jessie May, Dr. v Robert Anizfeld, Allan Kershaw, Michael Nonezyan, Marie de la Torre, and Katie McKissick. Last but not least, a heartfelt thank you to my wonderful family: Jasmin, Julianne, Jessie, Mom, Dad, Jill, Jaye, Jaul, Rachel, Rick, Jeck, and all of my aunts, uncles, and cousins. Your love and support have carried me on every step of this journey and I could not have done it without you. A special thank you to my Mom and Dad who have given everything they have to support my endeavors throughout my life. And a special thank you to my wife whose love and support allowed me to have all the fun with chemistry at work while she took care of our precious daughters at home. You are God’s gift to me and I love you with all my heart! vi Table of Contents Dedication ii Acknowledgments iii List of Tables ix List of Figures xi List of Schemes xviii Preparative Procedures xx Abstract xxviii Chapter 1. Pyridylphosphine and Dipyridylborate as Proposed Ligands for Cooperative Catalysis 1 1.1. Complexes of Dipyridylborate Ligands 1 1.2. Complexes of Pyridylphosphine Ligands 3 1.3. Overview of Thesis Content 6 1.4. References 7 Chapter 2. Synthesis and Characterization of Dimethyldi(2-pyridyl)borate Nickel(II) Complexes: A Unimolecular Square-Planar to Square-Planar Rotation Around Nickel(II) 9 2.1. Introduction 9 2.2. Experimental Support for Unimolecular Square-Planar to Square-Planar Rotation Around a Nickel(II) Center 11 2.3. Analysis of the Possible Mechanisms of Isomerization 24 2.4. Unimolecular Rotation of Nickel 2.4 26 2.5. Conclusion 30 vii 2.6. References 31 Chapter 3. A Prolific Catalyst for Dehydrogenation of Neat Formic Acid 36 3.1. Introduction 36 3.2. Dehydrogenation of Neat Formic Acid (Reactivity Overview) 39 3.3. Mechanistic Studies 51 3.4. Systematic Ligand Variation to Probe the Importance of the Pyridylphosphine Ligand in Formic Acid Dehydrogenation 63 3.5. Conclusion 65 3.6. References 66 Chapter 4. A Base-Free, Solvent-Free Ruthenium-Catalyzed Benzylic N-Alkylation of Amines 69 4.1. Introduction 69 4.2. Synthesis and Characterization of Ruthenium Precatalyst 4.1 72 4.3. Screen for Acceptorless Dehydrogenation (AD) Reactions Using Ruthenium 4.1 73 4.4. Finding Conditions for Dehydrative Coupling of Benzylic Alcohols and Amines 75 4.5. Substrate Scope for the Dehydrative Coupling of Benzylic Alcohols and Amines 76 4.6. Mechanism of Dehydrative Coupling 79 4.6. Conclusion 89 4.7. References 90 Chapter 5. Complexes with Pyridylphosphine and Dipyridylborate Ligands: Syntheses and Evaluation of Catalytic Activity 99 5.1. Introduction 99 5.2. Studies on Direct Borylation of sp 3 C‒H Bonds Using Dipyridylborate Complexes 101 viii 5.3. Synthesis of Ruthenium, Iridium, and Rhodium Pyridylphosphine Complexes 104 5.4. Studies on CO2 Hydrogenation 106 5.5. Studies on Acceptorless Dehydrogenation Reactions 111 5.6. Studies on the Possibility of Metal-Ligand Cooperation in Complexes with Bidentate Pyridylphosphine Ligands 114 5.7. Conclusion 117 5.8. References 118 Chapter 6. Experimental and Spectral Data 120 6.1. General Procedures 120 6.2. Chapter 2 Experimental and Spectral Data 123 6.3. Chapter 3 Experimental and Spectral Data 149 6.4. Chapter 4 Experimental and Spectral Data 196 6.5. Chapter 5 Experimental and Spectral Data 251 6.6. X-ray Crystallography Data 282 6.7. References 320 ix List of Tables Table 3.1. Selected homogeneous catalysts for formic acid dehydrogenation. 38 Table 3.2. Evaluation of the effect of different bases and different Lewis acids on formic acid dehydrogenation. 42 Table 3.3. Initial rates of dehydrogenation in the presence and absence of air. 43 Table 3.4. Catalyst performance over iterative uses. 44 Table 3.5. Data used to obtain maximum turnover number. 45 Table 3.6. Kinetic isotope effect data. 56 Table 3.7. Reaction kinetics for rate law determination. 60 Table 4.1. Coupling of benzylic alcohols with tryptamine. 75 Table 4.2. Substrate scope for coupling of benzyl alcohol (and derivatives) with amines. 77 Table 4.3. Substrate scope for coupling of 1-phenylethanol (and derivatives) with amines. 78 Table 6.2.1. Rotation rate constants obtained from inversion recovery experiments. 132 Table 6.2.2. Rotation rate constants with added (n-Bu)4NCl. 136 Table 6.2.3. Rotation rate constants with added LiCl. 136 Table 6.2.4. Rotation rate constants with added Tl(OTf). 138 Table 6.2.5. Data for Eyring analysis of rotation. 139 Table 6.2.6. Data for Eyring analysis of ring flip in CD2Cl2. 140 Table 6.2.7. Data for Eyring analysis of ring flip in C6D6. 141 Table 6.3.1. Data used to obtain the double logarithmic plot for determining reaction order in water (formic acid solvent). 161 Table 6.3.2. Data showing reusability of the catalyst in air. 164 Table 6.3.3. Data for kinetic isotope effect studies. 174 x Table 6.3.4. Data used for the Eyring plot. 177 Table 6.3.5. Data used to obtain the double logarithmic plot for determining reaction order in iridium (formic acid solvent). 179 Table 6.3.6. Data used to obtain the double logarithmic plot for determining reaction order in sodium formate (formic acid solvent). 180 Table 6.3.7. Data used to obtain the double logarithmic plot for determining reaction order in iridium (tetraglyme solvent). 182 Table 6.3.8. Data used to obtain the double logarithmic plot for determining reaction order in formate (tetraglyme solvent). 183 Table 6.3.9. Data used to obtain the double logarithmic plot for determining reaction order in formic acid (tetraglyme solvent). 184 xi List of Figures Figure 1.1. Mechanism of alcohol oxidation by the Shvo catalyst. 2 Figure 1.2. Ruthenium complexes possessing a directing boron atom in a bidentate borate ligand. 2 Figure 1.3. Mechanism and reactivity of Milstein pincer complexes. 4 Figure 1.4. Designed dipyridylborate complex functionalized with a hydrogen splitting ligand. 5 Figure 2.1. A. Ru(II) complexes possessing an anionic bidentate borate ligand. B. The dimethyldi(2-pyridyl)borate ligand 2.1. 10 Figure 2.2. ORTEP diagrams of complex 2.2 and complex 2.4. 12 Figure 2.3. Variable temperature 1 H NMR spectra of complex 2.2. 13 Figure 2.4. A. Observed isomerization in complex 2.2. B. Isomerization of a dihydrobis(pyrazolyl)borate (Bp) complex (2.5). 14 Figure 2.5. 1 H NMR spectrum of nickel 2.2 at -40 °C. (Methyl)boron groups are assigned by 1D-NOESY spectroscopy. 16 Figure 2.6. Double logarithmic plot of the dependence of isomerization rate of 2.2 on [PPh3]. 17 Figure 2.7. 31 P NMR inversion recovery experiment at -42.4 °C. 17 Figure 2.8. Dependence of isomerization rate of 2.2 on [Cl‾]. 18 Figure 2.9. Eyring Plots for unimolecular rotation and ring flip. 21 Figure 2.10. Eyring plot for ring flip in C6D6. 22 Figure 2.11. PBE-optimized structures for the singlet (A) and triplet (B) species [Me2B(2- py)2]NiCl(PMe3) and the potential energy surface for the low-energy rotational xii isomerization of the PMe3 and Cl ligands via T S B B ’. 23 Figure 3.1. Synthesis and structure of catalyst precursor cation 3.1. 39 Figure 3.2. Plot of moles of formic acid decomposed versus time. 41 Figure 3.3. Plot of log (rate of formic acid decomposition) versus log [water] (formic acid solvent). 42 Figure 3.4. A. GC trace of gaseous products from a dehydrogenation reaction performed in the presence of air. B. GC trace of gaseous products from a dehydrogenation reaction performed in the absence of air. 46 Figure 3.5. A. IR spectrum of commercial CO2. 47 Figure 3.5. B. IR spectrum of gaseous products from neat formic acid. 48 Figure 3.6. IR spectrum of the headspace of a reaction flask containing neat formic acid heated to 90 °C for 2 hours. 48 Figure 3.7. Comparison of IR spectra of gaseous products from 90% formic acid/H2O and ca. 10 ppm CO in air matrix. 49 Figure 3.8. Comparison of IR spectra of gaseous products from a supersaturated sodium formate solution of neat formic acid heated at 90 °C for 2 hours and ca. 10 ppm CO in air matrix. 50 Figure 3.9. In acetonitrile, species 3.1 is converted to 3.2 in the presence of FA or H2, which is analogous to Pfaltz’s dimer whose X-ray structure is known. 51 Figure 3.10. A 1 H NMR time course experiment began ca. 20 minutes after addition of 1 equiv of sodium formate and 10 equiv of formic acid (CD3CN solvent). 52 Figure 3.11. 1 H NMR spectrum of the products in the reaction of precatalyst 3.1 with FA in CD3CN: dimer 3.2 and cyclooctene. 53 xiii Figure 3.12. Catalyst initiation and molecular structure of active catalyst homologue 3.3b. 54 Figure 3.13. 1 H NMR spectrum of the iridium catalyst in formic acid. 55 Figure 3.14. Time course 1 H NMR experiment at 70 °C showing H‒D formation. 58 Figure 3.15. Eyring plot for formic acid dehydrogenation using catalyst 3.1. 59 Figure 3.16. Double logarithmic plots for determination of the rate law in formic acid solvent. 60 Figure 3.17. Double logarithmic plots for determination of the rate law in tetraglyme solvent. 61 Figure 3.18. Complexes with systematic ligand variation and their rates in formic acid dehydrogenation. 64 Figure 4.1. A. Synthesis of ruthenium 4.1. B. ORTEP diagram of 4.1. 72 Figure 4.2. 13 C NMR stacked spectra of the crude reaction mixture after 0, 2, 8, and 24 hours of heating at 110 °C. 80 Figure 4.3AB. 13 C NMR of the coupling of benzyl alcohol-d1 and n-hexylamine (1.1:1 mol ratio) after heating to 110 °C for A) 0 hour and B) 2 hours under neat reaction conditions. 81 Figure 4.3CD. 13 C NMR of the coupling of benzyl alcohol-d1 and n-hexylamine (1.1:1 mol ratio) after heating to 110 °C for C) 8 hours and D) 24 hours under neat reaction conditions. 82 Figure 4.4. 1 H NMR spectrum of the crude reaction mixture after 15 minutes of heating at 110 °C in 1,2-dichlorobenzene-d4. 85 Figure 4.5. 1 H NMR stacked spectra of a time-course experiment for the homocoupling of benzyl alcohol 4.6-1-d1 in 1,2-dichlorobenzene-d4. 86 xiv Figure 4.6. 1 H NMR of the crude reaction mixture after 48 hours of heating at 110 ºC in 1,2-dichlorobenzene-d4. 87 Figure 4.7. 1 H NMR spectrum of an aliquot of the crude reaction mixture after 12 hours of heating at 110 °C under neat conditions (solvent: CDCl3). 88 Figure 5.1. Ruthenium 1.7 is a poor borylation catalyst. 101 Figure 5.2. Complex 1.8 exhibits poor substrate scope in direct borylation reactions. 103 Figure 5.3. Putative transition state for C‒H activation. 103 Figure 5.4. Pyridylphosphine complexes synthesized thus far. 105 Figure 5.5. GC-MS data for hydrogenation of benzophenone 5.8. 109 Figure 5.6. Reactivity of iridium 5.4. 113 Figure 5.7. 1 H NMR spectrum of isolated 5.17. 115 Figure 5.8. Dearomatized iridium and rhodium complexes. 115 Figure 5.9. Product of the reaction of species 5.17 with H2: a Pfaltz/Fryzuk-type dimer and cyclooctene. 116 Figure 6.2.1. 1D NOESY spectrum of 2.2 at -50 °C in CD2Cl2 (the upfield B(Me) is exo). 127 Figure 6.2.2. 1D NOESY Spectrum of 2.2 at -50 °C in CD2Cl2 (the downfield B(Me) is endo). 127 Figure 6.2.3. 31 P NMR spectrum of 2.2 and free PPh3 at -42.4 °C. 133 Figure 6.2.4. Stacked spectra of 31 P NMR inversion recovery data. 134 Figure 6.2.5. 1 H NMR spectrum of 2.2 in the presence of 1 equiv (n-Bu)4NCl at -43.0 °C. 135 Figure 6.2.6. 1 H NMR spectrum of 2.2 at 25 °C 1 hour after addition of 2 equiv Tl(OTf). 137 xv Figure 6.2.7. 1 H NMR spectrum of 2.2 at 25 °C 4 days after addition of 2 equiv Tl(OTf). 138 Figure 6.3.1. Comparison of IR spectra of gaseous products from supersaturated sodium formate solution of neat FA heated at 70 °C for 6 hours and ca. 10 ppm CO in air matrix. 170 Figure 6.3.2. Sample plot of moles of formic acid decomposed versus time (Eyring plot data). 176 Figure 6.3.3. Sample plot of moles of formic acid decomposed versus time (formic acid solvent). 178 Figure 6.3.4. Sample plot of log of formic acid decomposed versus time (tetraglyme solvent). 182 Figure 6.4.1. 1 H NMR spectrum of the crude reaction mixture showing product 4.3 after 24 hours of heating at 110 °C. 200 Figure 6.4.2. 1 H NMR spectrum of the crude reaction mixture showing a diastereomeric mixture of ether product 4.5 after 8 hours of heating at 110 °C. 201 Figure 6.4.3. 1 H NMR spectrum of the crude reaction mixture showing formation of trace amounts of 4.7 and 4.8 after 24 hours of heating at 110 °C. 202 Figure 6.4.4. 1 H NMR spectrum of the crude reaction mixture showing formation of 4.9 after 24 hours of heating at 110 °C. 203 Figure 6.4.5. 1 H NMR spectrum of the crude reaction mixture showing formation of 4.11 after 24 hours of heating at 110 °C. 204 Figure 6.4.6. 1 H NMR spectrum of the crude reaction mixture showing formation of 4.12 after 24 hours of heating at 110 °C. 205 xvi Figure 6.4.7. 1 H NMR spectrum of the crude reaction mixture for the coupling of benzyl alcohol and tryptamine under a stream of nitrogen gas at 110 °C. 206 Figure 6.4.8. 1 H NMR spectrum of the crude reaction mixture for the coupling of benzyl alcohol and tryptamine in a sealed flask at 110 °C. 207 Figure 6.4.9. 1 H NMR spectrum of the crude reaction mixture for the coupling of 1-phenylethanol and tryptamine under a stream of nitrogen gas at 110 °C. 208 Figure 6.4.10. 1 H NMR spectrum of the crude reaction mixture for the coupling of 1-phenylethanol and tryptamine in a sealed flask at 130 °C. 209 Figure 6.4.11. 1 H NMR spectrum of benzyl alcohol 4.6-1-d1. 224 Figure 6.4.12. 13 C NMR stacked spectra of the crude reaction mixture after 0, 2, 8, and 24 hours of heating at 110 ºC. 225 Figure 6.4.13. 13 C NMR spectra of the crude reaction mixture upon heating to 110 °C. 226 Figure 6.4.14. GC chromatogram of the crude reaction mixture for the coupling of 4.6-1-d1 and n-hexylamine after 24 hours of heating at 110 °C. 228 Figure 6.4.15. Mass spectrum of the GC peak at 12.1 minutes (the desired benzyl(hexyl)amine product). 229 Figure 6.4.16. Mass spectrum of the GC peak at 9.3 minutes (the dihexylamine side product). 229 Figure 6.4.17. Mass spectrum of the GC peak at 16.2 minutes (the dibenzyl ether side product). 230 Figure 6.4.18. Mass spectrum of the GC peak at 18.9 minutes (the benzyl(dihexyl)amine side product). 230 xvii Figure 6.4.19. Mass spectrum of the GC peak at 22.4 minutes (the dibenzyl(hexyl)amine side product). 231 Figure 6.4.20. 31 P NMR spectrum of the crude reaction mixture after 24 hours of heating at 110 °C. 232 Figure 6.5.1. 1 H NMR spectrum of 5.2 and toluene external standard for yield determination. 251 Figure 6.5.2. 1 H NMR spectrum of complex 1.18 at 25 °C in CD3CN. 253 Figure 6.5.3. 1 H NMR spectrum of complex 1.18 after heating to 110 °C in CD3CN for 12 hours. 253 Figure 6.5.4. 1 H NMR spectrum of the crude reaction mixture showing glycerol and lactate 272 Figure 6.6.1. ORTEP diagram of iridium 3.1. 282 Figure 6.6.2. ORTEP diagram of ruthenium 4.1. 292 Figure 6.6.3. ORTEP diagram of iridium 5.4. 310 xviii List of Schemes Scheme 2.1. Syntheses of Complexes 2.2 and 2.4. 11 Scheme 2.2. Possible Mechanisms of Isomerization. 15 Scheme 2.3. A Possible Mechanism of Isomerization Involving Dissociation of Ligand 2.1. 20 Scheme 2.4. Ring Flip Places the (Methyl)Boron Groups of 2.2 in a Different Chemical Environment Whereas Rotation Places Them in the Same Chemical Environment. 20 Scheme 3.1. Catalyst Resting States Observed by NMR. 56 Scheme 3.2. Proton-Hydride Fidelity in the Mechanism of Formic Acid Dehydrogenation. 59 Scheme 3.3. Proposed Formic Acid Dehydrogenation Mechanism. 62 Scheme 4.1. Amination by Hydrogen Borrowing. 70 Scheme 4.2. Screen for Acceptorless Dehydrogenation Reactions. 74 Scheme 5.1. Lead Result for Direct Borylation Using Precatalyst 1.8. 102 Scheme 5.2. Synthesis of Complex 1.18. 104 Scheme 5.3. Reduction of CO2 to Methanol Using NH3BH3 and Complex 1.8 observed by Dr. Brian Conley. 106 Scheme 5.4. Reversible Deuteration of the PN-ligand Methylene Arm in Acetonitrile. 107 Scheme 5.5. Hydrogenation of Benzophenone Using Catalyst 1.18. 109 Scheme 5.6. Complex 1.18 is Not a Good Catalyst for CO2 Hydrogenation. 110 Scheme 5.7. Conversion of Glycerol to Lactate Using Ruthenium 5.3. 112 xix Scheme 5.8. Dearomatization and N‒H Activation of a Pyridylphosphine Ligand in a Palladium Complex. 114 Scheme 5.9. Dearomatization of Complex 3.1. 115 xx Preparative Procedures Nickel 2.2: 123 Nickel 2.4: 129 Iridium 3.1: 149 Iridium 3.3b: 153 Iridium 3.9: 185 Iridium 3.10: 188 xxi Iridium 3.11: 191 Ruthenium 4.1: 196 Coupling of 4.2 in the presence of KOtBu: 200 Coupling of 4.2 in the absence of KOtBu: 201 Coupling of 4.6 in the presence of KOtBu: 202 Coupling of 4.6 in the absence of KOtBu: 203 xxii Coupling of 4.10 in the presence of KOtBu: 204 Coupling of 4.10 in the absence of KOtBu: 205 Amine 4.15: 210 Amine 4.17: 210 Amine 4.27: 211 Amine 4.28: 212 Amine 4.29: 212 xxiii Amine 4.30: 213 Amine 4.31: 214 Amine 4.32: 214 Amine 4.33: 215 Amine 4.34: 215 Amine 4.35: 216 Amine 4.36: 217 xxiv Amine 4.40: 217 Amine 4.41: 218 Amine 4.42: 219 Amine 4.43: 219 Amine 4.44: 220 Amine 4.45: 221 xxv Amine 4.46: 221 Benzyl alcohol 4.6-1-d1 223 Borylated ether 5.2: 251 Ruthenium 1.18: 252 Ruthenium 5.3: 256 Iridium 5.4: 259 xxvi Rhodium 5.5: 262 Rhodium 5.6: 265 Rhodium 5.7: 268 Glycerol to lactate: 272 Guerbet reaction of 1-octanol: 273 Guerbet reaction of ethanol: 273 xxvii Iridium 5.17: 274 Iridium 5.18: 276 Rhodium 5.20: 278 Rhodium 5.21: 280 xxviii Abstract Research presented in this work describes the syntheses, characterization, and reactivity studies of transition metal complexes of two classes of bidentate ligands, namely (1) dipyridylborate and (2) pyridylphosphine. These ligands are proposed to work via cooperative catalysis, wherein the ligand and metal work together to effect catalytic transformations. Our group initially investigated the dipyridylborate ligand to develop catalysts with a pendant Lewis acid, specifically boron, which can function to direct substrates to transition metal centers. Here, the syntheses and solution dynamics of novel nickel complexes supported by this ligand are reported. Using one of these complexes, the first experimental proof for the viability of a square-planar to square-planar rotation around a nickel(II) center is provided. NMR inversion recovery kinetics experiments were used to determine the rates as well as the activation parameters (∆H ‡ and ∆S ‡ ) of this process. The development of the pyridylphosphine ligand was inspired by Milstein’s PNP and PNN pincer complexes, which function via a metal-ligand cooperation mechanism. These pincer complexes have proven to be very versatile and useful catalysts, exhibiting excellent reactivity in a wide range of reactions from hydrogenation of esters and amides to acceptorless dehydrogenation reactions to water splitting. Whereas pincer ligands are tridentate, the pyridylphosphine is a bidentate ligand which we hypothesized to be capable of functioning via a metal-ligand cooperation mechanism. We reasoned that the use of a bidentate instead of a tridentate ligand might be advantageous because of a) more facile ligand synthesis and b) flexibility in the synthesis and electronic tuning of possible catalysts. Our initial motivation for developing complexes with a pyridylphosphine ligand was to investigate its reactivity in CO2 activation. Although we have not found the desired reactivity in xxix this regard, we have discovered an iridium pyridylphosphine complex with excellent reactivity toward formic acid dehydrogenation. This reaction is important because the hydrogen gas that is released can be used in fuel cells to generate electricity cleanly, producing only water as a byproduct. The iridium catalyst is robust (affording millions of turnovers), stable to air and water, and selective, producing less than 10 ppm carbon monoxide, a fuel cell poison. The mechanism of catalysis, which was studied in great detail, is discussed. Furthermore, we have also discovered a ruthenium pyridylphosphine complex that has great reactivity in the dehydrative coupling of amines with benzylic alcohols. This reaction is of great significance in organic synthesis because alkylated amines are intermediates in a wide range of useful compounds such as polymers, agrochemicals, and pharmaceuticals; moreover, this reaction does not require the use of stoichiometric amounts of inorganic oxidants nor hydrogen acceptors and is therefore environmentally benign and atom economical. The ruthenium catalyst works under mild conditions and exhibits excellent functional group compatibility. The mechanism of catalysis is discussed in detail. 1 Chapter 1. Pyridylphosphine and Dipyridylborate as Proposed Ligands for Cooperative Catalysis 1.1. Complexes of Dipyridylborate Ligands Our group has a long standing interest in developing dual site catalysts—wherein two sites in an organometallic complex work cooperatively—for hydride manipulation. 1,2 Initial efforts involved studies of the Shvo catalyst that, by using a hydrogen bonding interaction between a substrate O‒H and a carbonyl oxygen of a cyclopentadienone ligand as a coordinating element, directs a hydride transfer (i.e. a C‒H activation) by placing the substrate C‒H bond in the proximity of the ruthenium center (Figure 1.1). 3 The process is initiated by disproportionation of the ruthenium dimer 1.1 to the catalytically-active monomeric complexes 1.2 and 1.3 (Figure 1.1A). The oxidation of the alcohol to a ketone is mediated by 1.3 via a concomitant transfer of a proton (from the O‒H) and a hydride (from the C‒H)—essentially a transfer of an H2 equivalent—from the substrate alcohol to the ruthenium catalyst in a single, concerted transition state (Figure 1.1 B). Based on the Shvo catalyst mechanism, we designed novel complexes wherein a boron atom is used as a template for coordinating and directing a substrate to ruthenium (Figure 1.1 C). Along these lines, a modified Shvo catalyst possessing a boronic ester (1.5) was synthesized and was found to be inactive in alcohol oxidation, likely because the boronic ester is cleaved. Thus, we designed a more robust dipyridylborate ligand platform (1.6). 2c,2d This concept has led to the synthesis of a number of complexes, including those shown in Figure 1.2. Ruthenium complex 1.7, which was synthesized and developed by Brian Conley, is a very efficient, robust, air- and water-tolerant ruthenium catalyst for ammonia borane dehydrogenation. 2d The dipyrazolylborate ruthenium complex 1.9, which was synthesized and developed by Zhiyao Lu, is a mild, selective catalyst for nitrile reduction. 2g Because this design concept led to the discovery of useful catalysts, 2 our group has to date synthesized various dipyridylborate complexes, including ruthenium, rhodium, iridium, cobalt, and nickel complexes. In Chapter 2, studies on the syntheses, characterization, and solution dynamics of the nickel complexes are described. In Chapter 5, studies to develop a method for direct borylation of sp 3 C‒H bonds are discussed. Figure 1.1. Mechanism of alcohol oxidation by the Shvo catalyst. A. Ruthenium dimer 1.1 disproportionates to form active catalysts 1.2 and 1.3. B. The coordinatively unsaturated ruthenium center of 1.3 and the cyclopentadienone work cooperatively to dehydrogenate the alcohol via transition state 1.4. C. Rational design of a mechanistic analog of the Shvo catalyst possessing a pendant boron directing group. Figure 1.2. Ruthenium complexes possessing a directing boron atom in a bidentate borate ligand. 3 1.2. Complexes of Pyridylphosphine Ligands Our group observed that the ruthenium complexes 1.8 and 1.9 (Figure 1.2) are capable of reducing carbon dioxide (CO2) into methanol—via trimethylborate—using ammonia borane or sodium borohydride as reducing agents. Accordingly, we became interested in developing a catalyst for CO2 hydrogenation. However, these complexes do not cleave hydrogen (the H‒H σ bond) efficiently. We therefore became interested to see if we could derivatize the dipyridylborate complexes we had in hand such that they would gain the ability to split H2 and, hopefully, to hydrogenate CO2. In search of an appropriate ligand for hydrogenation, we found inspiration from ruthenium pincer complexes developed by Milstein, such as the PNN (1.10) and PNP (1.11) complexes shown in Figure 1.3A. 4 These pincer complexes efficiently split H 2 and catalyze hydrogenation of difficult substrates like esters 5 (into alcohols) and amides 6 (into alcohols and amines) via a metal-ligand cooperation mechanism. This mechanism involves initial deprotonation of the relatively acidic methylene group of the ligand arm with potassium tert- butoxide, resulting in the dearomatization of the pyridine ring and extrusion of the chloride ligand (Figure 1.3B). This results in both the formation of a reactive deprotonated ligand that participates in catalysis and formation of an open coordination site on ruthenium. Hydrogen is then split via a reversible aromatization-dearomatization of the pyridine ring, which is made possible by reversible protonation-deprotonation of the methylene group. Thus, hydrogen is split by the cooperative action of the ruthenium center and the ligand arm. Through this mechanism, Milstein pincer complexes have proven to be remarkably useful and versatile catalysts for a plethora of hydrogenation and dehydrogenation reactions. 4 Moreover, Sanford has shown that complex 1.12 is capable of activating CO2 (Figure 1.3C). 7 Additionally, Nozaki utilized an iridium(III) PNP pincer complex for the hydrogenation of CO2 to formic acid with a remarkable turnover number 4 of 3.5 million. 8 Thus, these pincer complexes possess the desired hydrogenation and CO2 activation reactivities that are important considerations for designing CO2 hydrogenation catalysts. Figure 1.3. Mechanism and reactivity of Milstein pincer complexes. A. PNN and PNP complexes. B. The mechanism of H2 splitting involves metal-ligand cooperation. C. The dearomatized complex activates and reversibly binds CO2. Although the Milstein ligands possess promising reactivity for CO2 hydrogenation, it is not possible to derivatize our dipyridylborate complexes with tridentate ligands. However, because the reactivity of the pincer ligand is mediated by the methylene arm and the pyridine ring, we reasoned that we might be able to take just the reactive portion of the pincer ligand and simply use a bidentate pyridylphosphine ligand for H2 splitting (Figure 1.4A). We hypothesized that complexes supported by this ligand would likewise function via a metal-ligand cooperation mechanism. We thus designed the derivatization of our dipyridylborate complexes (i.e. 2-((di-tert- butylphosphino)methyl)pyridine 9 1.15 should react with complex 1.7 to form 1.18; Figure 1.4 B). Because complexes possessing a combination of dipyridylborate and pyridylphosphine ligands 5 would contain many donor ligands, such complexes if synthesized should be highly electron rich, strongly reducing complexes. This is important to our catalyst design because such complexes might be capable of reducing CO2. Moreover, a closer examination of several Milstein pincer complexes reveals that the other ligands present on the metal are almost invariably H, CO, and Cl, indicating that other than changing the steric and electronic properties of the pincer ligand, options for substituting other ligands for H, CO, and Cl are limited. We therefore found the idea of using pyridylphosphine ligands particularly appealing because the use of a bidentate instead of a tridentate ligand should give us flexibility in the syntheses and electronic tuning of possible catalysts. Furthermore, in a broader context, syntheses of complexes with varying electronic properties should give us access to reactivity in reactions other than CO2 hydrogenation. Indeed, although we have not found the desired CO2 hydrogenation reactivity, pyridylphosphine complexes with excellent reactivity in dehydrogenation reactions have been discovered and are discussed in later chapters. Figure 1.4. Designed dipyridylborate complex functionalized with a hydrogen splitting ligand. A. The reactivity of the pincer ligand comes from the pyridylphosphine portion. B. Proposed synthesis of a complex possessing both a dipyridylborate ligand and a pyridylphosphine ligand. 6 1.3. Overview of Thesis Content Cooperative catalysis has been extensively developed over the past decade as it has proven to be an effective concept for the development of novel, highly reactive catalysts for a variety of reactions including small molecule activation (for production of value-added chemicals such as methanol and hydrogen, for example, which are likely to play a major role in meeting the world’s future energy needs) and organic methods development (for synthesis of pharmaceuticals, agrochemicals, polymers, etc.). The following chapters describe our studies on transition metal complexes of dipyridylborate and pyridylphosphine ligands, which we designed as cooperative catalysts. Chapter 2 describes the synthesis, characterization, and solution dynamics of nickel(II) dimethyldipyridylborate complexes. In this study, we show comprehensive experimental evidence for the viability of a square-planar to square-planar rotation around a nickel(II) center, which we corroborated with computational data. Chapter 3 describes our discovery of the first homogeneous catalyst for dehydrogenation of neat formic acid. The pyridylphosphine iridium catalyst is robust (> 50 cycles; > 2.1 M turnovers), air- and water-tolerant, and selective (< 10 ppm CO output). The conditions for this catalytic reaction is an excellent method to generate H2 gas for powering fuel cells because, whereas formic acid can be decomposed neat, the fuel weight loading is much better than for known catalyst systems as these require solvents and/or additives. Chapter 4 discusses a pyridylphosphine ruthenium catalyst for dehydrative coupling of benzylic alcohols with amines. The catalyst works under mild conditions, neat, and without additives. Importantly, the catalyst tolerates a great number of functional groups including unprotected indoles, phenols, and anilines. Chapter 5 describes our efforts to develop various complexes of dipyridylborate and pyridylphosphine ligands. This chapter includes studies on direct borylation of sp 3 C‒H bonds, hydrogenation of CO2, and acceptorless dehydrogenation reactions. 7 1.4. References 1. For reviews, see: (a) Conley, B. L.; Williams, T. J. Dual site catalysts for hydride manipulation. Comments Inorg. Chem. 2012, 32, 195-218. (b) Conley, B. L.; Pennington-Boggio, M. K.; Boz, E.; Williams, T. J. Discovery, applications, and catalytic mechanisms of Shvo’s catalyst. Chem. Rev. 2010, 110, 2294-2312. 2. For research papers, see: (a) Thorson, M. K.; Klinkel, K. L.; Wang, J.; Williams, T. J. Mechanism of hydride abstraction by cyclopentadienone-ligated carbonylmetal complexes (M = Ru, Fe). Eur. J. Inorg. Chem. 2009, 2, 295-302 (b) Conley, B. L.; Williams, T. J. Thermochemistry and molecular structure of a remarkable agostic interaction in a heterobifunctional ruthenium−boron complex. J. Am. Chem. Soc. 2010, 132, 1764-1765. (c) Conley, B. L.; Williams, T. J. Dehydrogenation of ammonia-borane by Shvo's catalyst. Chem. Commun. 2010, 46, 4815-4817. (d) Conley, B. L.; Williams, T. J. A robust, air-stable, reusable ruthenium catalyst for dehydrogenation of ammonia borane. J. Am. Chem. Soc. 2011, 133, 14212-14215. (e) Lu, Z.; Conley, B. L.; Williams, T. J. A three-stage mechanistic model for ammonia–borane dehydrogenation by shvo’s catalyst. Organometallics 2012, 31, 6705-6714. (f) Lu, Z.; Malinoski, B.; Flores, A. V.; Guess, D.; Conley, B. L.; Williams, T. J. Alcohol dehydrogenation with a dual site ruthenium, boron catalyst occurs at ruthenium. Catalysts 2012, 2, 412-421. (g) Lu, Z.; Williams, T. J. A dual site catalyst for mild, selective nitrile reduction. Chem. Commun. 2014, 50, 5391-5393. (h) Celaje, J. A.; Pennington-Boggio, M. K.; Flaig, R. W.; Richmond, M. G.; Williams, T. J. Synthesis and characterization of dimethylbis(2-pyridyl)borate nickel(II) complexes: unimolecular square-planar to square- planar rotation around nickel(II). Organometallics 2014, 33, 2019-2026. (i) Pennington- Boggio, M. K.; Conley, B. L.; Richmond, M. G.; Williams, T. J. Synthesis, structure, and conformational dynamics of rhodium and iridium complexes of dimethylbis(2-pyridyl)borate. Polyhedron 2014, 84, 24-31. (j) Zhang, X.; Lu, Z.; Foellmer, L. K.; Williams, T. J. Nitrogen- based ligands accelerate ammonia borane dehydrogenation with the Shvo catalyst. Organometallics 2015, 34, 3732-3738. (k) Lu, Z.; Demianets, I.; Hamze, R.; Terrile, N. J.; Williams, T. J. A prolific catalyst for selective conversion of neat glycerol to lactic acid. ACS Catal. 2016, 6, 2014-2017. (l) Zhang, X.; Kam, L.; Williams, T. J. Dehydrogenation of ammonia borane through the third equivalent of hydrogen. Dalton Trans. 2016, 45, 7672-7677. (m) Celaje, J. J. A.; Lu, Z.; Kedzie, E.; Terrile, N. J.; Lo, J. N. A prolific catalyst for dehydrogenation of neat formic acid. Nat. Commun. 2016, 7, 11308. (n) Lu, Z.; Williams, T. J. Di(carbene)-supported nickel systems for CO2 reduction under ambient conditions. ACS Catal. 2016, 6, 6670–6673. 3. For mechanistic studies on the Shvo catalyst, see references 2a, 2f, 2j and: (a) Casey, C. P.; Beetner, S. E.; Johnson, J. B. Spectroscopic determination of hydrogenation rates and intermediates during carbonyl hydrogenation catalyzed by shvo's hydroxycyclopentadienyl diruthenium hydride agrees with kinetic modeling based on independently measured rates of elementary reactions. J. Am. Chem. Soc. 2008, 130, 2285-2295. (b) Casey, C. P.; Singer, S. W.; Hayashi, R. K.; Kavana, M. Hydrogen transfer to carbonyls and imines from a hydroxycyclopentadienyl ruthenium hydride: evidence for concerted hydride and proton 8 transfer. J. Am. Chem. Soc. 2001, 123, 1090-1100. (c) Blum, Y.; Czarkie, D.; Rahamim, Y.; Shvo, Y. (Cyclopentadienone)ruthenium carbonyl complexes - a new class of homogeneous hydrogenation catalysts. Organometallics 1985, 4, 1459-1461. 4. For reviews, see: (a) Khusnutdinova, J. R.; Milstein, D. Metal-ligand cooperation. Angew. Chem. Int. Ed. 2015, 54, 12236-12273. (b) Zell, T.; Milstein, D. Hydrogenation and dehydrogenation iron pincer catalysts capable of metal-ligand cooperation by aromatization/dearomatization. Acc. Chem. Res. 2015, 48, 1979-1994. (c) Gunanathan, C.; Milstein, D. Bond activation and catalysis by ruthenium pincer complexes. Chem. Rev. 2014, 114, 12024-12087. (d) Gunanathan, C.; Milstein, D. Applications of acceptorless dehydrogenation and related transformations in chemical synthesis. Science 2013, 341, 249- 260. (e) Gunanathan, C.; Milstein, D. Metal-ligand cooperation by aromatization- dearomatization: a new paradigm in bond activation and "green" catalysis. Acc. Chem. Res. 2011, 44, 588-602. (f) Milstein, D. Discovery of environmentally benign catalytic reactions of alcohols catalyzed by pyridine-based pincer Ru complexes, based on metal-ligand cooperation. Top. Catal. 2010, 53, 915-923. 5. Zhang, J.; Leitus, G.; Ben-David, Y; Milstein, D. Efficient homogeneous catalytic hydrogenation of esters to alcohols. Angew. Chem. Int. Ed., 2006, 45, 1113-1115. 6. Balaraman, E.; Gnanaprakasam, B.; Shimon, L. J. W.; Milstein, D. Direct hydrogenation of amides to alcohols and amines under mild conditions. J. Am. Chem. Soc. 2010, 132, 16756- 16758. 7. Huff, C.; Kampf, J. W.; Sanford, M. S. Role of a noninnocent pincer ligand in the activation of CO2 at (PNN)Ru(H)(CO). Organometallics 2012, 31, 4643-4645. 8. Tanaka, R.; Yamashita, M.; Nozaki, K. Catalytic hydrogenation of carbon dioxide using Ir(III)−pincer complexes. J. Am. Chem. Soc. 2009, 131, 14168. 9. Beddie, C.; Wei, P.; Douglas, S. Titanium pyridyl-phosphinimide complexes: synthesis, structure, and ethylene polymerization catalysis. Can. J. Chem. 2006, 84, 755-761. 9 Chapter 2. Synthesis and Characterization of Dimethyldi(2- pyridyl)borate Nickel(II) Complexes: A Unimolecular Square-Planar to Square-Planar Rotation Around Nickel(II) The complexes studied in this chapter were synthesized and characterized by Megan- Pennington Boggio in her efforts to develop base metal catalysts supported by dipyridylborate ligands. She studied the solution dynamics of nickel 2.2 using NMR, and discovered that this complex is isomerizing in solution, possibly via rotation around the nickel(II) center. My undergraduate coworker, Robinson Flaig, and I gathered comprehensive experimental evidence to support this claim, which are discussed in this chapter. Our conclusions are corroborated by DFT studies performed by Prof. Michael G. Richmond of the University of North Texas. A manuscript about this work has been published in Organometallics. 1 2.1. Introduction A variety of low-valent nickel complexes have important reactivity in reactions ranging from the cycloisomerization of C=C 2 and C=O 3 π-systems to the reduction of carbon dioxide (CO2). 4 In line with the latter, we have recently observed that ammonia borane dehydrogenation catalysts 1.8 and 1.9 (Figure 2.1A), 5 each bearing an anionic bidentate borate ligand, are capable of CO2 reduction concurrent with ammonia borane dehydrogenation. We therefore became interested in investigating the reactivity of other nickel complexes of the anionic bidentate ligand dimethyldi(2-pyridyl)borate (2.1, Figure 2.1B). In developing synthesis of such complexes, we found an unexpected unimolecular square-planar to square-planar mutarotation of diamagnetic (borate)nickel(II) complex 2.2. Rotations of this class, e.g. cis/trans isomerization of diamagnetic, square-planar late metal complexes, are generally known not to proceed through unimolecular mechanisms. 6 Nickel(II) has a possible exception, however, in that these species can equilibrate 10 between diamagnetic square-planar and paramagnetic tetrahedral configurations. 6,7 Nonetheless, no case has been carefully documented wherein a diamagnetic square-planar metal undergoes facile, unimolecular ligand rotation. Figure 2.1. A. Ru(II) complexes possessing an anionic bidentate borate ligand. B. The dimethyldi(2-pyridyl)borate ligand 2.1. This chapter discusses the synthesis, characterization, and solution dynamics of the novel nickel(II) complexes (dimethyldi(2-pyridyl)borate)(triphenylphosphine)nickel(II) chloride (2.2) and (dimethyldi(2-pyridyl)borate)nickel(II) acetylacetonate (2.4, Scheme 2.1). Complex 2.2 undergoes isomerization via two different isomerization mechanisms: (1) a unimolecular square- planar to square-planar rotation around the nickel(II) center and (2) a relatively slower ring flip. The activation parameters (∆H ‡ and ∆S ‡ ) for both mechanisms were measured using 1 H NMR inversion recovery experiments. 8 Studies to show that rotation around the metal center is indeed unimolecular—not the usual associative or dissociative isomerization pathways that have been studied for many four-coordinate square planar metals 9 —are discussed. 11 2.2. Experimental Support for Unimolecular Square-Planar to Square- Planar Rotation Around a Nickel(II) Center 2.2.1. Synthesis and Characterization of Complexes 2.2 and 2.4 Complexes 2.2 and 2.4 were synthesized via metatheses reactions. The reaction of one equivalent of bis(triphenylphosphine)nickel(II) chloride with borate 2.1 in dichloromethane gives complex 2.2 in 71% isolated yield (Scheme 2.1). The formation of complex 2.2 is accompanied by formation of a small amount of the thermodynamically favored bis(borate)nickel complex 2.3, which is known to form with facility when 2.1 is treated with nickel(II) salts. 10 Acetylacetonate- ligated nickel complex 2.4 was readily prepared by treating an excess of Ni(acac)2 (2.5 equivalent) with sodium borate 2.1, which yielded complex 2.4 (67%, Scheme 2.1). By contrast, the reactions of one equivalent of either nickel(II) acetate tetrahydrate (Ni(OAc)2 ∙ 4 H2O) or nickel(II) acetylacetonate (Ni(acac)2) with 2.1 exclusively provide bisborate nickel 2.3. Scheme 2.1. Syntheses of Complexes 2.2 and 2.4. Both 2.2 and 2.4 were characterized by single crystal X-ray crystallography (Figure 2.2). Both complexes are square planar. However, complex 2.2 exhibits a slight distortion. Whereas in complex 2.4 the sum of the bond angles around the nickel is 360.03(7) , the sum of angles around 12 nickel for complex 2.2 is 361.6(2) , with the P‒Ni‒Cl plane tilted 14  relative to the N‒Ni‒N plane. An analogous nickel complex of the bidentate borate ligand dihydrobis(pyrazolyl)borate (Bp) has recently been reported and similarly adopts a square planar structure. 11 As in all previous complexes of 2.1, the metal-chelate six membered ring exhibits a boat conformation in both 2.2 and 2.4. 5,12 The dihedral angle between metal and pyridine planes in complex 2.4 is 53.3(4) . However, the dihedral angle in complex 2.2 is 47.9(2) , indicating that the dimethyldi(2-pyridyl)borate ligand is tilted farther out of plane in complex 2.2. Consistent with the observation of the increased tilt is the decreased distance between nickel and the carbon in the endo-configured (methyl)boron group in complex 2.2 (3.143 Å versus 3.171 Å in complex 2.4). Complex 2.2 exhibits the expected trans effect with the Ni‒N bond trans to PPh3 longer than that trans to the Cl‾ (1.945(2) and 1.893(3) Å, respectively). On the other hand, Ni‒N bonds are equivalent (1.8943(8) and 1.8955(8) Å), and the Ni‒O bonds are similar (1.8567(7) and 1.8615(7) Å) in complex 2.4. The Ni‒N bond lengths in both 2.2 and 2.4 are consistent with those observed for 2.3 (1.906(2) and 1.902(2) Å). 10 Figure 2.2. ORTEP diagrams of complex 2.2 (A) and complex 2.4 (B). Ellipsoids are drawn at the 50% probability level. Complex 2.2 co-crystallizes with 0.5 equiv hexanes, which is omitted for clarity. 13 2.2.2. Low-Temperature NMR Studies on Nickel Complex 2.2 The 1 H NMR spectrum of nickel complex 2.2 in CD2Cl2 at 25 C shows that 2.2 is predominantly diamagnetic in solution. Further, it undergoes a dynamic process in solution, which is observed in variable temperature (VT) NMR studies (Figure 2.3). Whereas the pyridyl α hydrogens of the bound dimethyldi(2-pyridyl)borate ligand give a coalesced singlet ( δ = 8.55 ppm) at 25 C, two distinct singlets are observed at lower temperatures (i.e. δ = 8.12 and 8.82 ppm at - 40 C). This means that complex 2.2 is isomerizing in solution (Figure 2.4A). A similar isomerization has been observed for an analogous Bp complex, 2.5 (Figure 2.4B). 11 Figure 2.3. Variable temperature 1 H NMR spectra of complex 2.2. 14 Figure 2.4. A. Observed isomerization in complex 2.2. B. Isomerization of a dihydrobis(pyrazolyl)borate (Bp) complex (2.5). Isomerization of square-planar complexes usually proceed via either an associative or a dissociative mechanism (Scheme 2.2). 9 However, we were intrigued by the possibility that we were observing isomerization via a mechanism involving a unimolecular (first-order) square- planar to square-planar rotation around a metal center. Such a process could explain the observation from the 1 H NMR VT studies. 15 Scheme 2.2. Possible Mechanisms of Isomerization. a a Proposed associative and dissociative mechanisms involving PPh3 are shown, but it is possible that the other two ligands, Cl‾ and 2.1, could also be responsible for effecting either of these mechanisms. 2.2.3. Kinetic Studies of the Conformational Dynamics of 2.2 To show that neither an associative nor dissociative mechanism is responsible for the isomerization of nickel 2.2, we analyzed the dependence of the rate of isomerization with respect to the three ligands present in 2.2: PPh3, chloride, and 2.1. The 1 H NMR spectrum of nickel 2.2 at -40 C shows a well differentiated pyridyl α hydrogens of the borate ligand (Figure 2.5). This presents an ideal opportunity to use 1 H NMR inversion recovery experiments to determine the rate of this isomerization. For example, when the pyridyl proton at 8.82 ppm is pulsed (selectively labeled by inversion), magnetization transfer to 16 the pyridyl proton at 8.12 ppm can be observed. By acquiring data with different mixing times, a rate constant for the isomerization can be obtained. 8 Figure 2.5. 1 H NMR spectrum of nickel 2.2 at -40 C. (Methyl)boron groups are assigned by 1D- NOESY spectroscopy (see Chapter 6, Figures 6.2.1 and 6.2.2). 2.2.4. Rate Dependence on PPh3 The rate constants for the isomerization of 2.2 as a function of [PPh3] at -41.1 C were obtained by using 1 H NMR inversion recovery experiments and fitting the data into CIFIT. 8 The plot of ln kobs vs ln [PPh3] (Figure 2.6; see Chapter 6.2.2 for experimental details) shows that the rate of isomerization is independent of [PPh3]. The rate of isomerization was unchanged upon addition of up to ten equivalents of PPh3, and the slope of the ln/ln plot comparing the concentration of PPh3 with the observed rate of rotation had a slope of 0.0, which indicates that PPh3 is of kinetic order 0.0 in the rotation mechanism. 17 Figure 2.6. Double logarithmic plot of the dependence of isomerization rate of 2.2 on [PPh3]. Inversion recovery data were collected at -41.1 C using a 12 mM CD2Cl2 solution of 2.2 with [PPh3] ranging from 0.1 to 10.0 equiv Slope = 0.00(1). Also, to ensure that PPh3 exchange is not occurring, we performed a 31 P NMR inversion recovery study to see whether magnetization transfer from coordinated PPh 3 to free PPh3 would occur. No magnetization transfer was observed at -42.4 C (Figure 2.7; see Chapter 6.2.3 for experimental details), indicating that PPh3 exchange is indeed not occurring at a temperature where rotation is fast, t1/2 = 30 ms. Figure 2.7. 31 P NMR inversion recovery experiment at -42.4 C. Data were collected using a 12 mM CD2Cl2 solution of 2.2 with 0.5 equiv added PPh3: ( ○) coordinated PPh3,  ( 31 P) = 12.60, 31 P T1 = 213(3) ms; ( □) free PPh3,  ( 31 P) = -7.23, linear slope = 0.00(0). 0 1 2 3 4 5 6 -7 -6 -5 -4 -3 -2 ln(k obs ) ln[PPh 3 ] y = m1 + m2 * M0 Error Value 0.045725 3.2805 m1 0.0095771 0.0051408 m2 NA 0.016556 Chisq NA 0.028007 R 2 -1 -0.5 0 0.5 1 0 5 10 15 20 integration (relative) t (s) y = m1 + m2*(1 - exp(-x/m3)) Error Value 0.0064432 -0.76701 m1 0.0073478 1.767 m2 0.002823 0.21355 m3 NA 0.020616 Chisq NA 0.99919 R 2 y = m1 + m2 * M0 Error Value 0.0022898 0.52845 m1 0.00040232 0.00041336 m2 NA 0.010868 Chisq NA 0.020278 R 2 18 2.2.5. Rate Dependence on Chloride The rate of isomerization of 2.2 is also independent of the concentration of the chloride ligand. Because of the insolubility of the chloride anion in CD2Cl2, the isomerization is unlikely to be proceeding via a chloride dissociation mechanism. We nonetheless examined the rate of isomerization in the presence of tetra-n-butylammonium chloride ((n-Bu)4NCl), a soluble source of chloride. Addition of (n-Bu)4NCl leads to a reaction wherein a small portion of an unidentified paramagnetic species is formed, regardless, 2.2 is observed in the 1 H NMR spectrum, we recorded rate constants for the rotation in the presence of up to two equivalents of (n-Bu)4NCl. The rate of isomerization was unchanged by the presence of excess (n-Bu)4NCl (Figure 2.8, left; see Chapter 6.2.4 for experimental details). We also examined the rate of isomerization in the presence of excess LiCl, which is insoluble in CD2Cl2 and does not react with 2.2. The rate of isomerization at -42.0 C is unaffected by addition of an excess of LiCl (Figure 2.8, right). Figure 2.8. Dependence of the isomerization rate of 2.2 on [Cl‾]. Left: double logarithmic plot for dependence on [(n-Bu)4NCl]. Inversion recovery data were collected at -43.0 C using a 12 mM CD2Cl2 solution of 2.2 with [(n-Bu)4NCl] ranging among 0.4, 0.7, 1.1, 1.5, and 2.0 equiv versus Ni atom. Slope = -0.01(3). Right: plot of the dependence of isomerization rate of 2.2 on added LiCl (insoluble). Slope = -0.02(3). 0 1 2 3 4 5 6 -5.5 -5 -4.5 -4 -3.5 ln(k obs ) ln[nBu 4 NCl] y = m1 + m2 * M0 Error Value 0.14289 3.0222 m1 0.031932 -0.010799 m2 NA 0.0049539 Chisq NA 0.036727 R 2 0 10 20 30 40 0 10 20 30 40 50 k obs s -1 [LiCl] (equiv) 19 While the dissociation of the chloride ligand to form a positively charged tricoordinate intermediate in a non-coordinating solvent (CD2Cl2) is unlikely, if the chloride ligand is dissociating from 2.2, addition of thallium triflate (Tl(OTf)) should lead to formation of thallium chloride and to the removal of chloride from the coordination sphere of 2.2. To test for this situation, we treated a solution of 2.2 with two molar equivalents of Tl(OTf). The 1 H NMR spectrum of this sample is unaltered by the addition of Tl(OTf): 2.2 is stable in the presence of Tl(OTf) at room temperature for days, which indicates that the Cl‾ ligand does not dissociate (see Chapter 6.2.5 for experimental details). Moreover, the presence of two equivalents of Tl(OTf) does not alter the rate of isomerization at -42.0 C (23.1(4) s -1 immediately after addition; 23.5(6) s -1 four days after addition). 2.2.6. Consideration of Borate 2.1 and Observation of a Second, Relatively Slower Isomerization Pathway A mechanism of isomerization involving (a) dissociation of one of the pyridine rings of ligand 2.1, followed by (b) rotation around the Ni‒N bond of the bound pyridine, and then (c) re- coordination of the free pyridine ring (Scheme 2.3) can be envisaged. This process leads to an isomerized product equivalent to an isomerized product of a ring flip. Since the two (methyl)boron groups are differentiated in the 1 H NMR spectrum of 2.2 (singlets at 2.22 and 0.32 ppm, Figure 2.5), inversion recovery experiments to measure the rate of this process are possible. When a 1 H NMR inversion recovery experiment is performed at -40 C, no magnetization transfer is observed from one methyl group to the other. Even at 0 C, the magnetization transfer is too slow to permit measurement of a rate constant. Only at 13.7 C were we able to obtain a rate constant; kobs = 2.69(4) s -1 . This ring flip is therefore a different, slower isomerization pathway for nickel 2.2 20 (Scheme 2.4). Since this separate process is much slower than the rotation, we find that the observed rotation behavior cannot be accounted for on the basis of a ring flip. Scheme 2.3. A Possible Mechanism of Isomerization Involving Dissociation of Ligand 2.1. a a Ring flip is possible with or without initial dissociation of a pyridyl nitrogen. The measured rate of ring flip is slower than the rate of rotation by greater than two orders of magnitude. Scheme 2.4. Ring Flip Places the (Methyl)Boron Groups of 2.2 in a Different Chemical Environment Whereas Rotation Places Them in the Same Chemical Environment. a a Magnetization transfer between endo and exo (methyl)boron groups is not observed at low temperatures because rotation places the methyl groups in the same chemical environment (by symmetry). By contrast, magnetization transfer can be observed at higher temperatures via ring flip. 21 2.2.7. Activation Parameters for Square-Planar Rotation and Ring Flip To determine activation parameters, we used Eyring plots constructed from rate constants obtained by NMR inversion recovery experiments. For the square-planar rotation of 2.2, we obtained values of ∆H ‡ = 12.2(1) kcal mol -1 and ∆S ‡ = 0.8(5) eu (Figure 2.9, left; see Chapter 6.2.6 for experimental details). For the ring flip, we measured values of ∆H ‡ = 15.0(2) kcal mol -1 and ∆S ‡ = -4.2(7) eu (Figure 2.9, right; see Chapter 6.2.7 for experimental details). 13 Note that the rates for rotation and ring flip differ by greater than two orders of magnitude (ca. 3 kcal/mol), with rotation being faster. Figure 2.9. Eyring plots for unimolecular rotation (left) and ring flip (right). Left: inversion recovery data were collected using a 12 mM CD2Cl2 solution of 2.2 at -61.6, -61.4, -53.7, -46.8, - 42.0, -32.6, -31.8, -18.9 C. ∆H ‡ = 12.2(1) kcal mol -1 and ∆S ‡ = 0.8(5) eu. Right: Data were collected using a 12 mM CD2Cl2 solution of 2.2 at 13.7, 18.8, 28.1, and 38.2 C. ∆H ‡ = 15.0(2) kcal mol -1 and ∆S ‡ = -4.2(7) eu. Because CD2Cl2 boils at 39 C, we were only able to obtain ring flip rates from 13.8 to 38.2 C (a range of 25.1 C) in this solvent. To obtain reliable values for ∆S ‡ , a range of at least 40 C is recommended. The activation parameters were thus measured in benzene from rates obtained over a wider temperature range of 37.2 C (7.0 to 44.2 C) and similar values for the activation parameters were obtained (∆H ‡ = 15.5(3) kcal mol -1 and ∆S ‡ = -3.3(11) eu) (Figure 2.10; -57 -56 -55 -54 -53 -52 3.2 3.25 3.3 3.35 3.4 3.45 3.5 Rln(k/T)-Rln(h/kB) (cal/mol-K) 1000/T (K -1 ) -58 -56 -54 -52 -50 -48 -46 3.8 4 4.2 4.4 4.6 4.8 Rln(k/T)-Rln(h/kB) (cal/mol-K) 1000/T (K -1 ) 22 see Chapter 6.2.7 for experimental details). These values support the activation parameters obtained in CD2Cl2. Figure 2.10. Eyring plot for ring flip in C6D6. Inversion recovery data were collected using a 12 mM C6D6 solution of 2.2 at 7.0, 13.8, 24.0, 34.3, 44.2 C. ∆H ‡ = 15.5(3) kcal mol -1 and ∆S ‡ = - 3.3(11) eu. 2.2.8. DFT Studies The potential energy surface for rotational isomerization of the PMe3 analogue of nickel 2.2 was evaluated computationally by DFT (Figure 2.11, see Chapter 6.2.8 for details). The geometry-optimized structure of singlet A shows an excellent correspondence with the experimentally determined structure of 2.2, which reinforces the use of this model as a probe for the isomerization in 2.2. Diamagnetic A is the thermodynamically preferred isomer, and the pseudotetrahedral triplet B lies 8.8 kcal mol −1 above A. The computed free energy difference between A and B is 9.9 kcal mol −1 , leading to a K eq value of ca. 10 −8 for the triplet at room temperature, whose concentration is negligible and is in keeping with the silent EPR spectrum and magnetic susceptibility data recorded for 2.2 (vide infra). B is formed by a directionally specific clockwise rotation of the PMe3 and Cl‾ ligands in A, and continued rotation of these groups furnishes the transition structure T S B B ’ that exhibits Cs symmetry. Here the PMe3 ligand -59 -58 -57 -56 -55 -54 -53 -52 -51 3.1 3.2 3.3 3.4 3.5 3.6 Rln(k/T)-Rln(h/k B ) (cal/mol-K) 1000/T (K -1 ) 23 maintains a proximal orientation with respect to the BMe2 moiety throughout the isomerization; PMe3 rotation away from the BMe2 moiety and under the pyridyl rings leads to deleterious steric interactions. The computed enthalpic barrier of 11.1 kcal mol −1 closely matches the experimentally determined ΔH ‡ value for the process. Figure 2.11. PBE-optimized structures for the singlet (A) and triplet (B) species [Me2B(2- py)2]NiCl(PMe3) and the potential energy surface for the low-energy rotational isomerization of the PMe3 and Cl‾ ligands via T S B B ’. Energy values are ΔH in kcal mol -1 . 24 2.3. Analysis of the Possible Mechanisms of Isomerization While no example of a unimolecular square-planar to square-planar rotation around a diamagnetic late metal complex has been documented, prior studies show that such a rotation is possible for some nickel(II) systems. In non-coordinating solvents, four-coordinate d 8 nickel(II) complexes that exist in equilibrium as diamagnetic (S = 0) square planar and paramagnetic (S = 1) tetrahedral isomers have been well documented. 14 Eaton used the Woodward-Hoffman rules to obtain the selection rules for isomerization of four-coordinate nickel(II) complexes and showed that the isomerization from square planar to tetrahedral should be a facile, thermally allowed process. 15 Likewise, using orbital correspondence analysis with maximum symmetry, Halevi and Knorr showed that tetrahedral triplet to planar singlet isomerizations of nickel(II) complexes accompanied by a spin-flip is thermally allowed. 16 Indeed, the reported rates of isomerizations for several nickel(II) species are fast. For example, lifetimes of 10 -5 seconds for each isomer have been measured for nickel(II) aminotroponeiminates, 14a bis(salicylaldimine)nickel(II), 14b,c and a series of bis(n-alkyldiphenylphosphine)nickel(II) dihalides. 14j Moreover, the racemization of optically active diastereomeric (∆ and Λ) nickel(II) species was noted to be so fast that each diastereomer could not be observed by NMR. 14g,j Thermodynamic studies show that this equilibrium is affected by ligand sterics, with the presence of bulkier ligands favoring formation of the usually less thermodynamically stable tetrahedral complex. 14 The effects on equilibrium by electronic factors are also important. 14a,i,j,k,o Although the literature suggests that a rotation around a square-planar nickel(II) center is possible, only two classes of isomerization have been mechanistically characterized by studies of a large number of diamagnetic square-planar complexes: (1) associative and (2) dissociative, with associative mechanisms being more frequently reported. 9,17 Associative isomerization can proceed 25 through two mechanisms: Berry pseudorotation or consecutive displacement. These associative isomerizations initiate by coordination of a catalytic ligand to metal to form a five-coordinate intermediate. This ligand can be an added base, solvent, or any metal-coordinating group. In the case of the Berry pseudorotation, the five coordinate intermediate isomerizes to a trigonal bipyramid in which ligands can be isomerized, followed by dissociation of the catalytic ligand. In the consecutive displacement mechanism, coordination of the catalytic ligand is followed by either loss of an anionic ligand to generate a cationic metal species or dissociation of a neutral ligand to generate a neutral metal species. This is followed by re-coordination of the original ligand and loss of the catalytic ligand. Some authors contend that displacement of a neutral ligand would not result in isomerization due to the stereospecific nature of ligand substitutions, 9 while others claim to have definitively proven the existence of the neutral intermediate. 18 There is also debate about the existence of complexes which isomerize via a pseudorotation mechanism and disagreement about what evidence definitively proves a pseudorotation mechanism over a consecutive displacement mechanism. While it is difficult to distinguish among the mechanisms of associative isomerization, it is straightforward to classify an isomerization as associative: by showing first order rate dependence on added ligand. By contrast, dissociative isomerization proceeds through loss of a ligand to generate a tricoordinate complex. Diminution of rate in the presence of excess ligand, isomerization in the absence of potential ligands, including coordinating solvents, and positive ∆S ‡ are often taken as evidence of a dissociative process, but evidence of the existence of a three- coordinate intermediate is required to conclude confidently a dissociative mechanism. 26 2.4. Unimolecular Rotation of Nickel 2.2 Previous studies on square-planar to tetrahedral equilibria of nickel(II) complexes, which include molecular orbital analyses, indicate the possibility of isomerization via a unimolecular square planar to square-planar rotation around a nickel center (i.e. a 90  rotation from square planar to tetrahedral followed by another 90  rotation from tetrahedral to square planar). 14,15,16 However, no study that systematically shows—by excluding the associative or dissociative isomerization pathways—unimolecular rotation around a diamagnetic square-planar nickel complex has been reported. These cases involve equilibrium between two observable geometric isomers at nickel: a diamagnetic square-planar complex and a paramagnetic tetrahedral complex. Moreover, ligands in some of these complexes are known to be substitutionally labile. For example, in the presence of excess phosphine, bis(n-alkyldiphenylphosphine)nickel(II) dihalides undergo phosphine exchange to give a second-order ligand exchange mechanism that contributes to the rate of isomerization. 14j Similarly, bis(salicylaldimine)nickel(II) 14d and bis( β-ketoimine)nickel(II) 14g complexes undergo facile mixed ligand exchange. The studies mentioned in Section 2.2 show that the rotation of complex 2.2 in a non- coordinating solvent involves neither an associative nor a dissociative mechanism at the temperatures studied. The most likely ligand to be involved in associative or dissociative isomerization is PPh3. The observation that the rate of isomerization is independent of [PPh3] excludes an associative process, and provides evidence against a dissociative process. Moreover, 31 P NMR inversion recovery experiments show that in the presence of excess PPh 3, exchange between coordinated and free PPh3 is not occurring and thus excludes a dissociative mechanism involving PPh3. 27 The rate of isomerization is also unaffected by the presence of excess (n-Bu)4NCl or LiCl, which precludes an associative mechanism with respect to the chloride ligand. This result is not surprising given the low dielectric constant of CD2Cl2, which disfavors charge separation. A dissociative process is ruled out by the fact that addition of two equivalents of Tl(OTf) does not alter the 1 H NMR spectrum of complex 2.2. If dissociation of the chloride ligand is occurring, the addition of thallium, which has strong affinity for halides, would sequester free chloride in solution and alter the 1 H NMR spectrum. Moreover, the rate of isomerization at -42.0 C was unaffected by the presence of two equivalents of Tl(OTf), even after allowing the solution to stand at room temperature for four days. This shows that (a) the structure and (b) the conformational dynamics of 2.2 are unaffected by the presence of Tl(OTf), which is inconsistent with chloride dissociation in these conditions. Studies of the dependence of the rate of isomerization on [2.1] are not possible because addition of excess 2.1 results in fast formation of bisborate nickel complex 2.3. However, the isomerization proceeds in the absence of excess 2.1 so an associative process involving 2.1 is unlikely. Also, the ∆S ‡ for isomerization (0.8(5) eu) is inconsistent with ligand association (which generally has ∆S ‡ = -10 to -15 eu). 19 Likewise, the ∆S ‡ is too small to be consistent with ligand dissociation (which generally has ∆S ‡ = 10 to 15 eu). 19 For example, the ∆S ‡ for the dissociative substitution of CO in Ni(CO)4 range from +8 to +13 eu, depending on solvent. 20 Moreover, the bond enthalpy of a Ni‒N(pyridine) bond (ca. 26 kcal mol -1 ) 21 is much higher than the measured ∆H ‡ for the isomerization (12.2(1) kcal mol -1 ), which indicates that the Ni‒N bond is not broken during the isomerization process. Furthermore, an isomerization involving the dissociation of 2.1 (Scheme 2.3), which leads to a product equivalent to a ring flip product, was considered. This process was found to be a separate, 28 slower isomerization pathway: ring flip is > 100-fold slower than rotation at a given temperature. The ∆S ‡ for the ring flip (-4.2(7) eu) indicates a more ordered transition state and thus argues against a dissociative mechanism (i.e. the ring flip occurs without hemi-dissociation of 2.1). If hemi-dissociation is not occurring at higher temperatures where the ring flip is observed (as high as 38.2 C), then it is unlikely that hemi-dissociation is occurring at temperatures as low as -61.6 C where rotation is observed. Lastly, the presence of excess PPh 3 should affect the rate of isomerization if hemi-dissociation is occurring, but this is not observed. Based on these observations, we believe that association or dissociation of ligand 2.1 is not involved in the rotation mechanism. A further associative rotation mechanism that fits these kinetic data is one that involves formation of an agostic Ni‒HC interaction 22 to the endo (methyl)boron group to generate a transient 5-coordinate nickel center. We believe that such an agostic interaction is not forming for three key reasons: (1) the 1 H NMR peak width of the endo-positioned (methyl)boron group in 2.2 is invariant over a range of 75 C (6.9 +/- 1.0 Hz, Figure 2.3). (2) The 1 H chemical shift of the same is invariant over the same temperature range, 2.22 +/- 0.09 ppm. (3) The solid-state Ni‒H distance is 2.43 Å, which is longer than those observed for agostic interactions between this ligand and ruthenium(II) (1.72 Å) 5a or platinum(IV) (2.02 Å). 12b Moreover, the agostic Ni‒H distance in a (NacNac)Ni( ղ 2 -C2H5) complex is 1.66 Å, 23 which is far smaller than our observed Ni‒H distance (NacNac = N,N’-bis(2,6-(CH3)2C6H3)CH3C(N)CHC(N)CH3 anion). Whereas none of our observations are consistent with known agostic complexes involving borate 2.1, we predict that no agostic intermediate is involved in the unimolecular rotation of 2.2. We expect that the unimolecular rotation of 2.2 involves the intermediacy of a paramagnetic, tetrahedral (or pseudo-tetrahedral) complex, but this species is not present in an 29 observable concentration. For example, the phosphine crossover experiment shown in Figure 2.7 shows that under the isomerization conditions, the 31 P NMR integrations of 2.2 and PPh3 in solution match the portions added to the sample. This provides evidence that there is not a large portion of phosphine associated to an NMR-invisible paramagnetic species. Furthermore, an EPR spectrum of 2.2 (X-band, 25 C, toluene) showed no signals. 24 Moreover, whereas the paramagnetic susceptibility of many nickel(II) complexes which exhibit square-planar to tetrahedral equilibria can be measured using the Evans method, 14a,i,j,k we observe no paramagnetic susceptibility of complex 2.2 even at high concentrations (127 mM, 25 C, see Chapter 6.2.9 for details) using this method. 25 Thus, although we predict that a paramagnetic species is involved in the rotation mechanism, it appears to be of high energy and vanishingly low concentration. DFT studies support both the feasibility of rotation and the presence of a high energy triplet intermediate. These computational studies show that the activation energy for rotation in the PMe3 analog (∆E ‡ = 11.1 kcal mol -1 ) of nickel 2.2 is very close to the activation energy for rotation that was experimentally measured for nickel 2.2 (∆H ‡ = 12.2(1) kcal mol -1 ). The presence of a high energy triplet intermediate (∆E = 8.8 kcal mol -1 ) was also corroborated by these studies. Based on the forgoing evidence, we believe that the internal rotation of 2.2 is the first documented case of a unimolecular square-planar to square-planar rotation around a late metal center. We believe that this mechanism proceeds through a high energy paramagnetic tetrahedral (or pseudo-tetrahedral) nickel(II) intermediate species. We propose that no ligand coordination or dissociation, including agostic coordination of a (methyl)boron group is requisite to the mechanism. 30 2.5. Conclusion Novel dimethyldi(2-pyridyl)borate nickel complexes (2.2 and 2.4) were synthesized and characterized. The solution dynamics of complex 2.2 were studied and it was found to isomerize via two different mechanisms: a) a unimolecular square-planar to square-planar rotation around the nickel center and b) a relatively slower ring flip. 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Bis(fluoromesityl) palladium complexes, archetypes of steric crowding and axial protection by ortho effect − evidence for dissociative substitution processes − observation of 19 F− 19 F through-space couplings. Eur. J. Inorg. Chem. 2004, 2326-2337. (e) Yang, F.-Z.; Wang, Y.-H.; Chang, M.-C.; Yu, K.-H.; Huang, S.- L.; Liu, Y.-H.; Wang, Y.; Liu, S.-T.; Chen, J.-T. Kinetic and mechanistic studies of geometrical isomerism in neutral square-planar methylpalladium complexes bearing unsymmetrical bidentate ligands of α-aminoaldimines. Inorg. Chem. 2009, 48, 7639-7644. 18) Redfield, D. A.; Nelson, J. H. Mechanism of cis-trans isomerization for square planar complexes of the type ML2X2. J. Am. Chem. Soc. 1974, 96, 6219-6220. 19) Crabtree, R. H. The Organometallic Chemistry of the Transition Metals, 4 th Ed.; Wiley Interscience: New Jersey, 2005; pp 104-112. 20) Collman, J. P.; Hegedus, L. S.; Norton, J. R.; Finke, R. G. Principles and Applications of Organotransition Metal Chemistry. University Science Books: Mill Valley, 1987; p 247. 21) (a) Kappes, M. M.; Staley, R. H. Relative bond dissociation energies for two-ligand complexes of nickel(+) with organic molecules in the gas phase. J. Am. Chem. Soc. 1982, 104, 1813-1819. (b) Hettich, R. L.; Jackson, T. C.; Stanko, E. M.; Freiser, B. S. Gas-phase photodissociation of organometallic ions. Bond energy and structure determinations. J. Am. Chem. Soc. 1986, 108, 5086-5093. (c) Jacobson, D. B.; Freiser, B. S. Reactions of group 8 transition-metal ions (Iron(1+), cobalt(1+), and nickel(1+)) with cyclic hydrocarbons in the gas phase. J. Am. Chem. Soc. 1983, 105, 7492-7500. 22) Brookhart, M.; Green, M. L. H.; Parkin, G. Agostic interactions in transition metal compounds. Proc. Natl. Acad. Sci. USA 2007, 104, 6908-6914. 23) Kogut, E.; Zeller, A.; Warren, T. H.; Strassner, T. Structure and dynamics of neutral β-H agostic nickel alkyls: a combined experimental and theoretical study. J. Am. Chem. Soc. 2004, 126, 11984-11994. 24) This does not necessarily discount the presence of a paramagnetic nickel(II), because standard EPR spectroscopy at conventional microwave frequencies can be ineffective for detecting transition metals with integer spin ground states: Krzystek, J.; Park, J.-H.; Meisel, M. W.; Hitchman, M. A.; Stratemeier, H.; Brunel, L.-C.; Telser, J. EPR spectra from “EPR- Silent” species: high-frequency and high-field EPR spectroscopy of pseudotetrahedral complexes of nickel(II). Inorg. Chem. 2002, 41, 4478-4487. 25) (a) Schubert, E. M. Utilizing the evans method with a superconducting nmr spectrometer in the undergraduate laboratory. J. Chem. Educ. 1992, 69, 62. (b) Evans, D. F. The 35 determination of the paramagnetic susceptibility of substances in solution by nuclear magnetic resonance. J. Chem. Soc. 1959, 2003-2005. 36 Chapter 3. A Prolific Catalyst for Dehydrogenation of Neat Formic Acid In our efforts to develop complexes for hydrogenation of carbon dioxide (CO2; see Chapter 1), I ended up synthesizing several complexes possessing a bidentate pyridylphosphine ligand. During attempts to hydrogenate formic acid to model the CO2 hydrogenation reaction, I observed that the pyridylphosphine iridium complex 3.1 effected dehydrogenation of formic acid instead. Whereas catalysis could be accomplished efficiently using neat formic acid, which at the time had not been reported, we decided to study this catalysis in detail. This chapter describes the work that resulted, which were performed in collaboration with my graduate co-workers Zhiyao Lu and Jonathan Lo, my undergraduate co-worker Elyse Kedzie, and my high school co-worker Nicholas Terrile. Yao performed mechanistic studies to isolate catalyst intermediates and crystallized the catalyst resting state homolog 3.3b. Elyse and Nicky helped obtain kinetics data. Jon helped obtain IR data. A manuscript for this work has been published in Nature Communications, as well as in international and US patents. 1 3.1. Introduction Many strategies for the conversion of solar energy into chemical bonds involve electrocatalytic (or photocatalytic) cleavage of water to form hydrogen and oxygen. The reducing equivalent, H2, is thus an energy carrier because it can be re-oxidized, either by combustion to give heat or catalytically in a fuel cell to give electricity. There is a disabling problem with large-scale utilization of hydrogen as a fuel, since it is a gas under ambient conditions, thus limiting its volume-energy density (0.013 MJ L -1 ). As a result, physical-based hydrogen storage technologies (compression, cryogenic liquefaction, adsorption) involve low capacity, high costs, or safety issues. Therefore, the discovery of highly weight-efficient strategies for on-demand hydrogen 37 release from hydrogen-rich liquids has value. Formic acid (HCO2H, FA, 7.5 MJ L -1 ) is a hydrogen carrier, 2 owing to its ability to release hydrogen under mild conditions with only CO 2 as a by- product, which can then be recycled, in principle, to give a carbon-neutral fuel cycle. 3 To date, many efficient heterogeneous 4 and homogeneous 3c,5 catalysts for formic dehydrogenation have been developed. Heterogeneous catalysts have advantages of separability and reusability 4b , while homogeneous catalysts are generally more efficient. When we began these studies, the best turnover numbers (TONs) achieved in homogeneous catalysis were 1) > 1 M by a catalyst system composed of [RuCl2(benzene)]2, the ligand diphenylphosphinoethane, and a formic acid/Et3N adduct as substrate developed by Beller 3c and 2) 983,642 by a system composed of an iron pincer complex and LiBF4 developed by Hazari and Schneider. 5p The highest turnover frequency achieved is 228,000 h -1 by an iridium catalyst developed by Hull and Fujita. 5g Table 3.1 shows a more complete comparison table of homogeneous catalysts for this reaction. 6 In heterogeneous catalysis, the highest TOF achieved is 7256 h -1 by palladium nanoparticles immobilized on carbon nanospheres developed by Xu. 4n Also, homogeneous catalysts generally are more selective, producing less carbon monoxide, a common byproduct of formic acid dehydrogenation. This is essential, because CO is a fuel cell catalyst poison. Still, no known system is stable and reactive through multiple uses, air and water tolerant, selective against CO formation, and functions in neat formic acid liquid. Each of these is critical to achieving a usable hydrogen generation system based on formic acid. The pyridylphosphine-supported iridium complex 3.1 is a novel catalytic system that meets all of these criteria. 38 Table 3.1. Selected homogeneous catalysts for formic acid dehydrogenation. 6 Catalyst Solvent / Medium Additive T (°C) TON max TOF (h -1 ) CO produced Ref. 1 Neat FA SF 90 2.16 M 13,000 (vide infra) This work I FA/Et3N dppe 25 >1 M 1000 < 2 ppm 3c II dioxane 10% LiBF4 80 983,642 196,728 9 ppm 4p III 1 M 1:1 FA/SF SF 90 308,000 228,000 ND 4g IV PC 3 equiv PP3 80 92,417 9,425 ND 4f IV PC rac-P4 60 6061 1737 ND 4s V THF Et3N 40 100,000 836 ND 4l VI 1 M aq. FA None 80 10,000 34,000 ND 4n VII 5:2 FA/Et3N Et3N 40 NR 147,000 ND 4h VIII 2 M aq. FA None 90 NR 14,000 ND 4c IX Dioxane None 85 3000 3271 ND 4j X THF Et3N 65 2200 5200 ND 4o XI H2O SF 25 142 426 ND 4e XII H2O SF, TPPTS 120 NR 460 ND 4b XIII FA/ Et3N Et3N 120 18,000 17,800 250 ppm 4d FA = formic acid; SF = sodium formate; PC = propylene carbonate; dppe = diphenylphosphinoethane; PP3 = tris[2-diphenylphosphino)ethyl]phosphine; rac-P4 = 1,1,4,7,10,10-hexaphenyl-1,4,7,10-tetraphosphadecane; TPPTS = 3,3’,3’’-phosphanetriyltris trisodium salt; ND = not detected; NR = not reported. 39 3.2. Reactivity of Complex 3.1 in Formic Acid Dehydrogenation 3.2.1. Dehydrogenation of Neat Formic Acid Iridium complex 3.1, which is easily prepared from known materials (Figure 3.1), is an excellent catalyst for the decomposition of formic acid into H2 and CO2. To the best of our knowledge, complex 3.1 is the first efficient homogeneous catalyst for the dehydrogenation of neat formic acid. Complex 3.1 works under mild conditions in the presence of air, is remarkably robust giving a turnover number (TON) greater than 2,000,000, and is reusable without regeneration (> 50 cycles). Furthermore, the decomposition reaction proceeds with high selectivity: carbon monoxide (CO), a possible byproduct which poisons fuel cell catalysts, is produced at < 10 ppm. This is the first truly practicable, high throughput system for generating H 2 from formic acid for fuel cell applications. Figure 3.1. Synthesis and structure of catalyst precursor cation 3.1. Elipsoids are drawn at the 50% probability level. The reaction is operationally simple. The catalytic materials are weighed out in a reactor, which is attached to a vent line for the gaseous products. Liquid formic acid is added, and the reaction is initiated by heating. Upon completion, the catalyst system remains as a pale-colored precipitate at the bottom of the vessel for re-use. The active catalyst is homogeneous on the basis of physical appearance, clean kinetics, tolerance of liquid mercury, and proportional inhibition by phenanthroline. Thus, the system 40 exhibits the reactivity and selectivity advantages of homogeneous catalysis. Nonetheless, because the catalytic materials are deposited cleanly in the reactor at the end of the reaction, the system enjoys many of the catalyst separability and reusability benefits of heterogeneous conditions. Sections 3.2.2 – 3.2.6 discuss the formic acid dehydrogenation reactivity of complex 3.1 in more detail. See Chapter 6.3 for experimental details. 3.2.2. Kinetic Profile of Formic Acid Dehydrogenation The kinetic profile for decomposition of neat formic acid using complex 3.1 as catalyst was obtained by running a reaction to completion and recording the dehydrogenation rate during the course of the reaction. Thus, formic acid (500 L, 12.7 mmol) with NaO2CH co-catalyst (5 mol%) at 50 ppm loading of complex 3.1 was heated to 90 C, resulting in the production of 386 mL of gas (62% conversion; TON = 12530). The mass balance of formic acid condenses as a liquid in the reactor out of reach of the catalyst. Figure 3.2 shows the kinetic profile for dehydrogenation. The rate is constant through ca. 20% of conversion before it accelerates as formic acid disappears. At the end of the reaction, a pale orange solid (the catalyst system: an iridium complex and sodium formate), remains at the bottom of the reaction vessel. Recharging the reaction flask with formic acid and reheating to 90 C results in continued H2 production without any catalyst regeneration. 41 Figure 3.2. Plot of moles of formic acid decomposed versus time. Because the rate of formic acid dehydrogenation is constant at the beginning of the reaction, the method of initial rates can be used to obtain kinetics data. The method of initial rates was used to determine the effect on dehydrogenation rates by different bases, by water, and by different poisons (i.e. mercury and phenanthroline). It was used to construct an Eyring plot and to measure kinetic isotope effects. Moreover, it was used to study the reaction order in the iridium catalyst, the base, and formic acid to determine the rate law. These data were instrumental for gaining understanding of the mechanism of catalysis (vide infra). 3.2.3. Effect of Base, Lewis Acid, and Water on Dehydrogenation The reaction requires base as co-catalyst, but the source of the base is not specific: the reaction rates are similar when 5 mol% NaO2CH, KO2CH, KOH, NaOH, LiOH, or nBu4NOH or 2.5 mol% of Na2CO3 or K2CO3 is used (Table 3.2). Any of these are converted rapidly to the corresponding formate, which comprises the bulk of the catalytic material and gives it its pale color. These experiments also show that the dehydrogenation rate is not affected by the Lewis acids Li + , Na + , K + , and Ca 2+ . Moreover, the effect of water on the dehydrogenation reaction was 0 1000 2000 3000 4000 5000 6000 7000 8000 9000 0 10000 20000 30000 40000 50000 Moles of HCO 2 H Decomposed (x10 -6 ) Time (s) 0.005 mol% Ir, 5% Sodium Formate 42 evaluated and was found not to significantly affect the dehydrogenation rate—the double logarithmic plot of water concentration versus rate of formic acid dehydrogenation yields a slope of 0.11(5) (Figure 3.3). Table 3.2. Evaluation of the effect of different bases and different Lewis acids on formic acid dehydrogenation. Base Used Added Base (mg) 3.1 (ppm) Base (mol%) Rate (×10 -8 mol s -1 ) a None 0 50 0% 0.1 b LiOH c 63 50 5% 4.7(1) NaOH c 106 50 5% 5.2(1) KOH c 149 50 5% 5.4(1) NaO2CH 180 50 5% 6.1(2) KO2CH 223 50 5% 6.4(2) Na2CO3 c 140 50 2.5% 5.6(3) K2CO3 c 183 50 2.5% 5.3(5) CaCO3 c,d 133 50 2.5% 2.5(1) a Obtained at 86 °C; average of two runs, error is one standard deviation. b Average rate over 5 hours; the rate decreases upon further heating. c 2.1 mL of formic acid was added; 0.1 mL reacts with the base. d Copious amounts of precipitates formed. Figure 3.3. Plot of log (rate of formic acid decomposition) versus log [water] (formic acid solvent). y = 0.1074x - 7.322 R² = 0.6612 -7.6 -7.5 -7.4 -7.3 -7.2 -7.1 -7 -6.9 -0.4 0.1 0.6 1.1 log (Rate of HCO 2 H Decomposition) log [Water] Water Dependence 43 3.2.4. The Catalyst is Highly Stable in Air The catalysts (the iridium and sodium formate) are air stable. Although dehydrogenation is slower when the catalysts are prepared in air, the system remains active, even when the solution is allowed to sit on the bench top for two weeks before dehydrogenation rates are measured (Table 3.3). Under these conditions, the catalysts can be re-loaded in an air atmosphere and re-used repeatedly. For example, a reaction flask containing iridium 3.1 (6.1 mg, 8.9 μmol) and NaO2CH (185 mg, 2.72 mmol) was charged with formic acid through 50 cycles (see Chapter 6, Table 6.3.2). In this experiment 28.85 L of gas were produced from 25 mL of formic acid, corresponding to a turnover number of 66,403 and 89% conversion. Note that these values exclude the formic acid liquid that condenses in the flask out of the reach of catalyst in each run and accounts all mechanical leaks or engineering challenges in the laboratory-scale setup. In a particular, representative single run, we converted formic acid (2 mL) to gaseous products in 97% conversion with 140 ppm 3.1 and 280 ppm sodium formate. Over the course of 50 loadings, we measured the initial rates and maximum turnover frequencies during certain runs (Table 3.4). Interestingly, these increased over the course of ten cycles before slowing over time. Table 3.3. Initial rates of dehydrogenation in the presence and absence of air. Experiment Iridium 3.1 NaO2CH Initial Rate (10 -8 mol s -1 ) a Air b 0.005% 5% 2.1(5) Air c 0.005% 5% 1.8(1) No Air b 0.005% 5% 6.1(2) a Obtained at 86 °C; average of two runs, error is one standard deviation. b Obtained 1 day after solution preparation. c Obtained 2 weeks after solution preparation. 44 Table 3.4. Catalyst performance over iterative uses. Entry Loading Initial Rate ( mol s -1 ) a Maximum Turnover Frequency (h -1 ) b 1 1 st 0.52 1378 3 10 th 2.35 3032 4 20 th 2.77 2756 5 30 th 2.82 2618 6 40 th 2.51 2205 7 50 th 1.46 1519 a Obtained from a plot of rate of formic acid decomposition versus time. b Obtained from the highest volume of gas formed over a period of 1 minute. 3.2.5. The Catalyst is Remarkably Robust The iridium catalyst delivers very high turnover numbers at low loading with repeated re- use. For example, we prepared in the drybox a reaction flask containing 3.1 (90 μg, 0.13 μmol) and NaO2CH (184 mg, 2.65 mmol) and repeatedly charged it with formic acid, which was decomposed until a pale yellow solid remained at the bottom of the flask. After 40 cycles over a period of four months, 13.71 L of gas were produced, which corresponds to a turnover number of 2.16 million (Table 3.5). Although unoptimized, this is one of the best turnover number for a formic acid dehydrogenation catalyst known to date, surpassed only by an iridium diamine complex developed by Li that reached a turnover number of 2.4 million. 6 Under these conditions, the maximum TOF was measured to be 3.7 s -1 . 45 Table 3.5. Data used to obtain maximum turnover number. Run Volume FA Loaded (mL) Volume of Gas Produced (mL) a Time (h) b Run Volume FA Loaded (mL) Volume of Gas Produced (mL) a Time (h) b 1 0.6 420 24 21 0.2 160 20 2 0.6 490 21 22 0.2 110 16 3 0.8 560 32 23 0.2 140 18 4 0.6 500 26 24 0.6 360 72 5 1.0 800 60 25 0.6 360 72 6 0.6 420 27 26 0.6 300 72 7 0.5 450 27 27 0.6 310 72 8 0.5 310 22 28 0.6 320 72 9 0.5 410 36 29 0.6 360 80 10 0.8 480 60 30 0.6 290 72 11 0.3 290 30 31 0.6 380 80 12 0.3 290 24 32 0.6 320 72 13 0.2 230 16 33 0.6 400 80 14 0.2 210 20 34 0.6 330 72 15 0.8 460 70 35 0.6 380 96 16 0.3 200 24 36 0.6 300 72 17 0.3 220 90 37 0.6 400 120 18 0.2 160 18 38 0.6 360 120 19 0.2 180 20 39 0.6 310 120 20 0.6 440 72 40 0.6 300 120 a Measured using a 1000 mL gas buret. b Heating was stopped when mostly solid sodium formate and catalyst was present in the reaction flask. 46 3.2.6. The Dehydrogenation Reaction is Selective To be useful in fuel cells, formic acid decomposition must be selective for H2 and CO2 over H2O and CO, because CO is a poison for PEM fuel cell catalysts such as platinum. The composition of gas produced from our conditions was determined by gas chromatography (GC), which showed only H2 and CO2 (1:1 ratio) and no detectable CO (< 1 part per thousand) (Figure 3.4). Figure 3.4. A. GC trace of gaseous products from a dehydrogenation reaction performed in the presence of air. B. GC trace of gaseous products from a dehydrogenation reaction performed in the absence of air. 47 However, further analysis of the product gas by IR spectroscopy revealed that when the reaction is conducted using neat formic acid, CO is observed at a concentration near the detection limit of the GC (Figure 3.5B). It is known that neat formic acid decomposes in the presence of concentrated acid 7 or at high temperatures 8,9 to form H2O and CO. We therefore hypothesized that much of the CO produced in our reaction conditions may be formed by thermal, uncatalyzed decomposition pathways. To test for this situation, we dissolved 180 mg of sodium formate in 1 mL of formic acid and heated this solution in a sealed 100 mL pear flask for 2 hours at 90 °C. The solution was then allowed to cool to room temperature and a sample of the headspace gases was analyzed by IR. Indeed, even after only 2 hours of heating, copious amounts of CO (which was estimated to > 5000 ppm) had formed as seen in the IR spectrum in Figure 3.6. Figure 3.5. A. IR spectrum of commercial CO2. 48 Figure 3.5. B. IR spectrum of gaseous products from neat formic acid. Figure 3.6. IR spectrum of the headspace of a reaction flask containing neat formic acid heated to 90 °C for 2 hours. 49 Because it is known that neat formic acid thermally decomposes to produce H2O and CO, and that the presence of water decreases the rate of this decomposition, we reasoned that we might be able to suppress CO production by using 10 v% H2O/formic acid mixture instead of neat formic acid as the dehydrogenation medium. Thus, we performed the dehydrogenation in the presence of a portion of water, and observed that under these conditions the CO in the bulk gaseous products is < 10 ppm by IR spectroscopy (Figure 3.7). Figure 3.7. Comparison of IR spectra of gaseous products from 90% formic acid/H2O and ca. 10 ppm CO in air matrix. 50 Moreover, we hypothesized that the thermal decomposition of neat formic acid might be suppressed by running the reaction using higher sodium formate loading. Indeed, heating 1 mL of neat formic acid in 26 mg of the iridium precatalyst and 900 mg of sodium formate (50 mol%) to 90 C for two hours yields a product mixture with less than 10 ppm CO (Figure 3.8). A similarly low level of CO is observed when dehydrogenation is performed at 70 C for 6 hours (see Chapter 6.3.9). While these strategies for CO minimization are known in the formic acid literature, this collection of demonstrations enables practitioners to select the level of humidity and CO content in the reaction’s gas eluent stream simply by adjusting the water and base loading in the formic acid supply. The optimum of these parameters might be different for any particular fuel cell application, but the reaction affords flexibility to adjust them. Figure 3.8. Comparison of IR spectra of gaseous products from a supersaturated sodium formate solution of neat formic acid heated at 90 C for 2 hours and ca. 10 ppm CO in air matrix. 51 3.3. Mechanistic Studies Equally remarkable as the reactivity of this new catalytic system is the unique, two metal mechanism through which it operates. We used three approaches to gain insight into this mechanism: stoichiometric model reactions, reaction kinetics, and isotope labeling studies. 3.3.1. Formation of Iridium Dimer 3.2 in Acetonitrile Solvent Species 3.1 is a catalyst precursor from which an active catalyst is generated. To determine the nature of this active species, we conducted stoichiometric reactions of 3.1. Species 3.1 loses its cyclooctadiene ligand as cyclooctene in a solution of either H2 or buffered formic acid and dimerizes to form 3.2 (solv = CD3CN; Figure 3.9). In acetonitrile solvent, the final product is complex 3.2, which has analogy to {[(P‒N)Ir(CH2Cl2)(H)]2(  2 ‒H)2} 2+ characterized by Pfaltz (P‒ N = SimplePHOX; Figure 3.9) 10 as well as to a complex characterized by Fryzuk. 11 Figure 3.9. In acetonitrile, species 3.1 is converted to 3.2 in the presence of FA or H2, which is analogous to Pfaltz’s dimer whose X-ray structure is known. Data regarding the elementary steps of the conversion of the precatalyst to dimer 3.2 were obtained using NMR. Room temperature 1 H NMR studies in CD3CN show that addition of one equivalent of sodium formate and ten equivalents of formic acid to a solution of iridium precatalyst 3.1 leads to formation of a new species (intermediate A) with a hydride signal at -19.43 ppm (Figure 3.10). Data for this species is consistent with oxidative addition of formic acid to 3.1. About 20 minutes after addition of sodium formate and formic acid, a time course experiment was collected over a period of 66 minutes. The resulting stacked 1 H NMR spectra shows that the peak 52 Figure 3.10. A 1 H NMR time course experiment began ca. 20 minutes after addition of 1 equiv of sodium formate and 10 equiv formic acid (CD3CN solvent). Top: aliphatic and aromatic region. Bottom: hydride region. 53 for intermediate A grows then intermediate B appears ca. 30 minutes after addition of sodium formate and formic acid. Because coordination of double bonds to iridium result in an upfield shift of the vinyl hydrogens, intermediate B is consistent with a species where one of the cyclooctadiene double bonds is bound to iridium and the other is free. The final product (a Pfaltz/Fryzuk-type dimer) then appears ca. 1 hour after addition. The 1 H NMR spectrum of the final product is consistent with dimer 3.2 (Figure 3.11). 10,11 The cyclooctadiene in the iridium precatalyst is reduced to cyclooctene and free cyclooctene is seen in the 1 H NMR spectrum of the products. It is worth noting that, in CD3CN, iridium 3.1 reacts in the absence of base with formic acid to form 3.2, but in a much slower rate. Figure 3.11. 1 H NMR spectrum of the products in the reaction of precatalyst 3.1 with FA in CD3CN: dimer 3.2 and cyclooctene. The formation of dimer 3.2 is also observed upon reaction of precatalyst 3.1 with H2. Figure 3.11 shows a similar 1 H NMR spectrum of the Pfaltz/Fryzuk-type dimer and cyclooctene that 54 forms from this reaction in CD3CN solvent. In the presence of H2, cyclooctene is slowly hydrogenated when the reaction mixture is allowed to sit at room temperature. 3.3.2. Formation of a Formate-Bridged Iridium Dimer in Formic Acid Solvent When the solvent is formic acid, we believe that complex 3.1 is converted to complex 3.2 (Figure 3.12; solv = HCO2H), but is further derivatized to a formate-bridged complex 3.3a. This species is observable by NMR, but it is not amenable to isolation in our hands, likely because this species is unstable. By contrast, its acetate homolog (3.3b), was crystallized by my graduate student coworker Zhiyao Lu, which enabled determination of its structure (Figure 3.12). Species 3.3a is relevant in catalysis: we observe it by NMR as the minor form of the working catalyst (Figure 3.13). We see a second, major resting species by NMR, which has a spectrum consistent with a structure formulated as 3.4, featuring three differentiated metal hydride groups (Scheme 3.1). Figure 3.12. Catalyst initiation and molecular structure of active catalyst homolog 3.3b. 3.3b = {[(tBu2PCH2(2-py))Ir(H)]2(  2 -H)(  2 - , ’-O2CCH3)2} + . Hydrogen atoms omitted. Ellipsoids are drawn at the 50% probability level. solv = solvent; counterion = triflate. 55 Figure 3.13. 1 H NMR spectrum of the iridium catalyst in formic acid. Top: aliphatic and aromatic region. Bottom: hydride region. 56 Scheme 3.1. Catalyst Resting States Observed by NMR. 3.3.3. Kinetic Isotope Effect Studies and Proton-Hydride Fidelity in the Dehydrogenation Reaction Kinetic isotope effect data indicate that both the C –H and O–H groups of formic acid are involved in (or before) the rate-determining transition state. Table 3.6 summarizes the reaction rates for four selectively labeled formic acid isotopologs. The combined isotope effect (kCHOH/kCDOD = 6.5(2)) is comparable to the product of the average separate C –H and O –H isotope effects (6.5(4)). This is consistent with a mechanism in which bonds to proton and hydride are transformed in a single kinetically relevant step. Table 3.6. Kinetic isotope effect data. Conditions are 50 ppm 3.1, 5 mol% base, 86 °C. Compound krel KIE (observed) HCO2H 6.5(2) kCHOH/kCHOD 1.8(3) HCO2D 3.6(2) kCDOH/kCDOD 1.65(3) DCO2H 1.6(2) kCHOH/kCDOH 3.9(2) DCO2D 1.00(2) kCHOD/kCDOD 3.6(2) kCHOH/kCDOD 6.5(2) Hydrogen loss from 3.4 involves protonation of an iridium hydride (which comes from formic acid’s C –H group) by a formic acid group. Further, we observe that in a sample of formic acid-(O)-d1, NMR reveals H –D gas as the catalytic product. We performed a 1 H NMR time course experiment at 70 °C to observe the dehydrogenation products when 3.1 is reacted with formic acid- (O)-d1. Under these conditions, formation of predominantly H –D with a small amount of H2 is observed (Figure 3.14). This observation is consistent with a formic acid dehydrogenation 57 mechanism that proceeds through formation of an iridium monohydride where the hydride comes from the formyl C –H bond of formic acid. This iridium monohydride is then protonated (or technically deuterated) by the formic acid O –D. We expect that an iridium dihydride that undergoes reductive elimination to yield H2 should enable scrambling of proton and hydride, thus we disfavor this possibility. A schematic of the proton-hydride fidelity in the dehydrogenation mechanism is shown in Scheme 3.2. This observation also shows that the reaction is irreversible at ambient pressure, so we assign the isotope effects as kinetic. The small amount of H2 that forms can be rationalized by the presence of small amounts of formic acid O –H bonds which protonates the iridium monohydride. Interestingly, the H –D gas signal disappears after extended heating, which is consistent with a slow reverse reaction when the reaction is run in a sealed vessel. Such back reaction is impossible under our kinetics acquisition conditions because the H2 product is sequestered and quantified in an eudiometer. 58 Figure 3.14. Time course 1 H NMR experiment at 70 C showing H‒D formation. The bottom, zoomed in region, more clearly shows H‒D formation. 59 Scheme 3.2. Proton-Hydride Fidelity in the Mechanism of Formic Acid Dehydrogenation. 3.3.4. Activation Parameters of Dehydrogenation Eyring analysis reveals activation parameters of ∆H ‡ = +29.0(3) kcal mol -1 and ∆S ‡ = +16(1) eu (Figure 3.15; see Chapter 6.3 for experimental details). This strongly favorable entropy of activation is consistent with the release of at least one gaseous product in the rate determining transition state. We expect that this is H2 release in the conversion of 3.4 to 3.6 because of the strong isotope effects. Figure 3.15. Eyring plot for formic acid dehydrogenation using catalyst 3.1. y = -29.026x + 16.043 R² = 0.9995 -72 -70 -68 -66 -64 -62 -60 2.6 2.7 2.8 2.9 3 3.1 Rln(k/T) - Rln(h/k B ) (cal/mol-K) 1000/T (K -1 ) Eyring Plot 60 3.3.5. The Rate Law of Formic Acid Dehydrogenation The dependence of the rate of formic acid dehydrogenation in the three components present in the reaction (the iridium catalyst, sodium formate, and formic acid) were determined using double logarithmic plots. The observed rate law for formic acid dehydrogenation has rate ~ [Ir] 1 [base] 0.5 [FA] -1 (Table 3.7), which is based on the slopes of double logarithmic plots recorded both in neat formic acid (Figure 3.16) and dilute in tetraglyme solution (Figure 3.17). Neat a Solution a,d [Ir] 0.95(3) b 0.96(4) e [base] 0.64(5) c 0.44(2) f [FA] - -0.94(9) g Table 3.7. Reaction kinetics for rate law determination. a. Data were collected at 86 °C as an average of two runs. b. Data collected using 0.63 M [NaO2CH] (2.5 mol%) and [Ir] ranging among 0.63, 1.86, 2.59, 3.25, and 4.41 mM. c. Data were collected using 0.66 mM [Ir], and [NaO 2CH] ranging among 0.26, 0.53, 1.06, 1.59, 2.11, and 2.65 M. d. Tetraglyme was used as solvent. Base was delivered as (n-Bu)4NOH to generate soluble (n-Bu)4N(O2CH). e. Data were collected using 13.2 mM [(n-Bu)4N(O2CH)] (5 mol%) and [Ir] concentration ranging among 0.066, 0.13, 0.20, 0.26, and 0.33 mM. f. Data were collected using 0.066 mM [Ir] and [(n-Bu)4N(O2CH)] ranging among 13.2, 26.4, 39.6, 52.8, and 66.0 mM. g. Data were collected using 0.026 [Ir], 13.2 mM [(n- Bu)4N(O2CH)], and [FA] ranging among 265, 331, 398, 530 and 662 mM. Figure 3.16. Double logarithmic plots for determination of the rate law in formic acid solvent. 61 Figure 3.17. Double logarithmic plots for determination of the rate law in tetraglyme solvent. 3.3.6. Proposed Mechanism of Catalysis The rate law has [Ir] first order, which indicates a dimeric iridium species that does not dissociate once formed. Inverse order in [FA] implies inhibition, but the origins of this inhibition are unclear. The half order in [NaO2CH] requires that two sites of the catalyst are activated by a single equivalent of formate, thus causing half order dependence on base. We propose a possible catalytic cycle in Scheme 3.3. Precatalyst 3.1 is first converted to the active catalyst 3.3a under buffered formic acid conditions. The catalytic cycle begins with 3.3a, which reacts with NaO2CH to open up one active site. After the first equivalent of H2 is lost in the conversion of 3.4 to 3.6, a second equivalent forms from the iridium hydride on the complementary metal center. We propose that the latter is more rapid than the former, and that the single equivalent of formate enables both by opening a formate bridge in dimer 3.3a. 62 Scheme 3.3. Proposed Formic Acid Dehydrogenation Mechanism. We believe that the inhibition by formic acid might arise from the reversible interconversion of 3.3a to 3.4. Acid is known to favor closure of carboxylate bridges in ruthenium species similar to ours, 5d which enables several opportunities for formic acid inhibition in our mechanism. Moreover, formic acid has potential roles in the conversion of 3.4 and as solvent. We are currently studying this complex system of interactions. 63 3.4. Systematic Ligand Variation to Probe the Importance of the Pyridylphosphine Ligand in Formic Acid Dehydrogenation Because of the great reactivity of complex 3.1, complexes 3.9 – 3.16 (Figure 3.18; see Chapter 6.3 for experimental details), wherein the ligands are systematically varied, were screened for formic acid dehydrogenation reactivity to probe the effect of the pyridylphosphine ligand. Our aim is to understand what makes the pyridylphosphine ligand effective and hopefully design and discover a better catalyst. Table 3.8 shows the rates of formic acid dehydrogenation using complexes 3.9 – 3.16. Complexes possessing a pyridylphosphine ligand (3.9 – 3.16, entries 2 – 4) are more efficient than those that possess a bidentate bisphosphine ligand (3.12 – 3.13, entries 5 – 6). However, changing the 2-((di-tert-butylphosphino)methyl)pyridine ligand in 3.1 results in slower rates. For example, putting a methyl group on the pyridine ring (3.9) decreases the rate by a third. Likewise changing the substituents on the phosphine from di-tert-butyl to diisopropyl (3.10) or to diphenyl (3.11) results in much decreased rates. Replacing the pyridylphosphine with dipyridine also results in a much slower rate. Interestingly, complex 3.15, which has a monodentate pyridine cis to a monodentate phosphine, exhibits modest reactivity initially, but the rate dramatically decreases over several hours presumably because of catalyst decomposition. These results show that the pyridylphosphine ligand is necessary for high formic acid dehydrogenation reactivity but how it modulates reactivity remains unclear. We believe, however, that formation of a formate-bridged dimer (such as complex 3.3a) is required for effective catalysis. This is supported by the fact that the most effective catalysts in the table (complexes 3.1, 3.9, and 3.10) all easily form a Pfaltz/Fyzuk-type dimer in CD3CN. 10,11 64 Figure 3.18. Complexes with systematic ligand variation and their rates (shown in parenthesis) in formic acid dehydrogenation. a. 50 ppm iridium and 5 mol% NaO2CH were used; data were collected at 86 °C as an average of two runs. b. The catalyst decomposes within a period of several hours. 65 3.5. Conclusion We show here a new catalytic system for the repeated conversion of formic acid to CO2 and hydrogen. This has translation potential because it is the first known homogeneous system to operate in neat formic acid, thus enabling far greater weight content of H2 release than any other known catalyst for formic acid dehydrogenation. Moreover, it is one of the highest turnover system, because, in part, it can be re-used directly with formic acid substrate that is not rigorously purified or dried. We further propose a novel mechanism to account for kinetic, thermochemical, stoichiometric, and labeling data that we have collected for the catalytic reaction. 66 3.6. References 1. Most of the studies described in this chapter was derived from published work: a) Celaje, J. J. A.; Lu, Z.; Kedzie, E.; Terrile, N. J.; Lo, J. N. A prolific catalyst for dehydrogenation of neat formic acid. Nat. Commun. 2016, 7, 11308. International and US Patents have also been published: b) Williams, T. J.; Celaje, J. A. 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(c) Himeda, Y. Highly efficient hydrogen evolution by decomposition of formic acid using an iridium catalyst with 4,4’-dihydroxy-2,2’-bipyridine. Green Chem. 2009, 11, 2018-2022. (d) Morris, D. J.; Clarkson, G. J.; Wills, M. Insights into hydrogen generation from formic acid using ruthenium complexes. Organometallics 2009, 28, 4133-4140. (e) Fukuzumi, S.; Kobayashi, T.; Suenobu, T. Unusually large tunneling effect on highly efficient generation of hydrogen and hydrogen isotopes in pH-selective decomposition of formic acid catalyzed by a heterodinuclear iridium –ruthenium complex in water. J. Am. Chem. Soc. 2010, 132, 1496- 1497. (f) Boddien, A.; Mellmann, D.; Gärtner, F.; Jackstell, R.; Junge, H.; Dyson, P. J.; Laurenczy, G.; Ludwig, R.; Beller, M. Efficient dehydrogenation of formic acid using an iron catalyst. Science 2011, 333, 1733-1736. (g) Hull, J. F.; Himeda, Y.; Wang, W. H.; Hashiguchi, B.; Periana, R.; Szalda, D. J.; Muckerman, J. T.; Fujita, E. 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Lewis acid-assisted formic acid dehydrogenation using a pincer- supported iron catalyst. J. Am. Chem. Soc. 2014, 136, 10234-10237. (q) Oldenhof, S.; Lutz, M.; de Bruin, B.; van der Vlugt, J. I.; Reek, J. N. H. Dehydrogenation of formic acid by Ir- bisMETAMORPhos complexes: experimental and computational insight into the role of a cooperative ligand. Chem. Sci. 2015, 6, 1026-1034. (r) Thevenon, A.; Frost-Pennington, E., Weijia, G.; Dalebrook, A. F.; Laurenczy, G. Formic acid dehydrogenation catalyzed by Tris(TPPTS) ruthenium species: mechanism of the initial “fast” cycle. ChemCatChem 2015, 6, 3146-3152. (s) Bertini, F.; Mellone, I.; Ienco, A.; Peruzzini, M.; Gonsalvi, L. Iron(II) complexes of the linear rac-tetraphos-1 ligand as efficient homogeneous catalysts for sodium bicarbonate hydrogenation and formic acid dehydrogenation. ACS Catal. 2015, 5, 1254-1265. 6. The highest turnover number for formic acid dehydrogenation is now 2.4 M: Wang, Z.; Lu, S.- M.; Li, J.; Wang, J.; Li, C. Unprecedentedly high formic acid dehydrogenation activity on an iridium complex with an N,N′-diimine ligand in water. Chem. – Eur. J. 2015, 21, 12592-12595. 7. DeRight, R. E. The decomposition of formic acid by sulfuric acid. J. Am. Chem. Soc. 1933, 55, 4761-4764. 8. Yu, J.; Savage, P. E. Decomposition of formic acid under hydrothermal conditions. Ind. Eng. Chem. Res. 1998, 37, 2-10. 9. Akiya, N.; Savage, P. E. Role of water in formic acid decomposition. AIChE J. 1998, 44, 405- 415. 10. Gruber, S.; Neuburger, M.; Pfaltz, A. Characterization and reactivity studies of dinuclear iridium hydride complexes prepared from iridium catalysts with N,P and C,N ligands under hydrogenation conditions. Organometallics 2013, 32, 4702-4711. 11. Wambach, T. C.; Ahn, J. M.; Patrick, B. O.; Fryzuk, M. D. Use of the imine–enamine equilibrium in cooperative ligand design. Organometallics 2013, 32, 4431- 4439. 69 Chapter 4. A Base-Free, Solvent-Free Ruthenium-Catalyzed Benzylic N-Alkylation of Amines Several pyridylphosphine complexes of ruthenium, rhodium, and iridium were synthesized and screened for acceptorless dehydrogenation reactions. Ruthenium 4.1 was identified as a good precatalyst for dehydrative coupling of benzylic alcohols with amines, which is described in this chapter. This work was performed in collaboration with my graduate co-worker Xingyue (Lily) Zhang and my undergraduate co-workers Forrest Zhang and Lisa Kam. Lily determined the conditions for benzyl alcohol coupling and synthesized several of the coupling products. Forrest and Lisa helped in the synthesis and purification of the coupling products. A manuscript about this work is in preparation. 4.1. Introduction Amines alkylation is a quintessential synthetic transformation. 1 Recently, classical methods like alkylation with alkyl halides 2 and reductive amination 3 are being replaced with catalytic reactions like coupling of amines with aryl halides, 4 hydroamination, 5 and direct coupling of amines and alcohols. 6,7 Unlike classical methods, this latter approach does not require the use of an alkyl halide or a borohydride co-reagent, so it presents a very cost-competitive, sustainable approach for decoration of amines. The most common catalysts for this method are ruthenium 8 and iridium 9 complexes, but many other noble (Au, 10 Ag, 11 Pd, 12 Rh, 13 Os 14 ) and non-noble (Cu, 15 Ni, 16 Co, 17 Fe, 18,17a Re 19 ) transition metals will work. Scheme 4.1 shows a general mechanism for these reactions, the hydrogen borrowing strategy, which involves the following steps: 1) dehydrogenation of the alcohol to a carbonyl, 2) condensation of the amine to form an imine, and 3) hydrogenation of the imine to the alkylated amine product. 70 Scheme 4.1. Amination by Hydrogen Borrowing. Given the utility of these reactions, a great amount of work has been reported on developing substrate scope, although need remains for conditions that tolerate fragile functionality, particularly protic and base-sensitive groups. Further, although there is consensus about the organic transformations in the mechanism (Scheme 4.1), there are few studies on the organometallic redox events in this process, which are those that govern rate and selectivity. 20,21 In this study, we report base-free conditions for amine-alcohol coupling and show that these are advantageous in enabling functional group tolerance that cannot be realized with other conditions. We will also show that this is possible by enabling a relatively rapid C‒H oxidation step—a situation unseen in the amine-alcohol coupling literature—and demonstrate that under these conditions both alcohol and amine oxidation are rapid, thus necessitating thermodynamic control of product selectivity. We decided to pursue this line of study because we have a long-standing interest in devising dual site catalysts for C‒H hydride abstraction. 22 We further observed that although bisphosphines have been widely used as ligands for ruthenium-catalyzed coupling of amines with alcohols, 23, 8s, 8v, 8x the utility of phosphinopyridine (P‒N) ligands—which I have found to be excellent for dehydrogenation applications 24 —have not been studied in these reactions. We were interested in 71 studying a (pyridylphosphine)ruthenium complex, because we thought it could act as a bidentate analog to Milstein’s PNP and PNN pincer ligands, which are remarkably useful and versatile catalysts for many acceptorless dehydrogenation applications. 25,8c In this chapter, we report the synthesis, characterization, and reactivity of a novel precatalyst (4.1) possessing a simple (P‒N) ligand, and we find it to be a very convenient system for coupling of amines with benzylic alcohols, requiring no solvent, inorganic base, or other additive. 26 A variety of functional groups that are traditionally incompatible with these coupling reactions, including unprotected phenols and anilines, 27 are tolerated in our conditions. 72 4.2. Synthesis and Characterization of Ruthenium Precatalyst 4.1 Ruthenium complex 4.1 was synthesized in 73% yield from the reaction of [RuCl2(Cym)]2 and 2-((di-tert-butylphosphino)methyl)pyridine 28 in the presence of excess sodium triflate (Figure 4.1A). Single crystals of complex 4.1 suitable for X-ray analysis was obtained from a dichloromethane/toluene solution (Figure 4.1B). Figure 4.1. A. Synthesis of ruthenium 4.1. B. ORTEP diagram of 4.1. Ellipsoids are drawn at the 50% probability level. Complex 4.1 co-crystallizes with 0.5 equiv of dichloromethane, which, along with the triflate counterion, is omitted for clarity. 73 4.3. Screen for Acceptorless Dehydrogenation (AD) Reactions Using Ruthenium 4.1 Acceptorless dehydrogenation (AD) reactions are powerful oxidative methods, because they do not require a stoichiometric oxidant and are therefore atom economical and environmentally friendly. AD reactions of alcohol and amine moieties are frequently conducted in the presence of base, nominally to facilitate the initial substrate oxidation by deprotonation. Analogously, we heated neat 1-phenylethanol 4.2 with 1 mol% of precatalyst 4.1 and 5 mol% of KOtBu to 110 °C for 24 hours under a stream of nitrogen gas (Scheme 4.2A). Under these conditions, the C‒C coupling product 4.3 is formed as the major product along with a small amount of acetophenone (4.4) in ca. 95% conversion by NMR. 29 By contrast, when alcohol 4.2 is heated with catalyst 4.1 in the absence of base, dehydrative coupling occurs to yield a diastereomeric mixture of ethers as the major products in ca. 95% conversion after 10 hours. Thus, distinct reaction pathways are observed, suggesting different mechanisms are operating in the presence or absence of base. We then examined benzyl alcohol and 1-octanol as substrates (Scheme 4.2BC). In the presence of KOtBu at 110 °C, both give Tischenko esterification as the major pathway, albeit with poor conversions. In the absence of KOtBu, benzyl alcohol gives efficient ether formation, while 1-octanol gives modest conversion to the aldehyde. We were intrigued by the mild reaction conditions for the coupling of benzylic alcohols and wondered whether we could apply these conditions in the coupling of benzylic alcohols with amines. To date, the coupling of alcohols and amines under neat conditions without inorganic base or other additives is rare. 26 74 Scheme 4.2. Screen for Acceptorless Dehydrogenation Reactions. a a All reactions were performed neat at 110 °C under a slow, steady stream of nitrogen gas. The reaction time is 24 hours unless indicated. 75 4.4. Finding Conditions for Dehydrative Coupling of Benzylic Alcohols and Amines Based on the initial screening studies, we searched for conditions for selective N- benzylation of amines using ruthenium 4.1. We first attempted the coupling of tryptamine with benzyl alcohol and 1-phenylethanol under a nitrogen stream. These gave the corresponding imines 4.14 and 4.15, with little or no N-benzylated amine product (Table 4.1, entries 1 and 3). By contrast, when benzyl alcohol and tryptamine are heated with 1 mol% 4.1 in a sealed flask, complete conversion to the desired benzylated amine is observed after 24 hours. 1-Phenylethanol can also be coupled at 5 mol% catalyst loading. Thus, ruthenium species 4.1 is an effective precatalyst for coupling both primary and secondary benzyl alcohols to amines. It functions under mild, neutral conditions and does not require solvents or additives. 26 Table 4.1. Coupling of benzylic alcohols with tryptamine. 76 4.5. Substrate Scope for the Dehydrative Coupling of Benzylic Alcohols and Amines Using these conditions, we studied the substrate scope for this dehydrative coupling reaction. We find excellent substrate scope and functional group tolerance with yields varying among different amines (Table 4.2). For example, benzyl alcohol is coupled to tryptamine and tyramine (products 4.15 and 4.27) without the need for protection of the indole nitrogen or the phenol hydroxyl group. 27 Likewise, a free aniline ‒NH2 group behaves as an orthogonal functionality as 3- and 4-aminobenzyl alcohols are smoothly converted to aminoanilines 4.33 – 4.36. 27 For these reactions, it is necessary to utilize the amines in excess because using the aminobenzyl alcohols in excess result in further alkylation of the free anilines in the products. Secondary benzylic alcohols also couple to amines in good yields (Table 4.3). The coupling of 1-phenylethanol to various amines exhibits a similar functional group compatibility as benzyl alcohol. Free indole and phenol groups are also tolerated. Likewise, 1-phenylethanol derivatives possessing different substituents from electron rich to electron poor are good coupling partners to tryptamine (products 4.44 – 4.46). 77 Table 4.2. Substrate scope for coupling of benzyl alcohol (and derivatives) with amines. a a For entries 1-7, the amines were the limiting reagents and 1.5 equiv of the benzylic alcohols were used. For entries 8-11, the benzylic alcohols were the limiting reagents and 1.2 equiv of the amines were used. b An unstirrable mass forms. The reaction was stopped after 12 hours (ca. 70% conversion by NMR). 78 Table 4.3. Substrate scope for coupling of 1-phenylethanol (and derivatives) with amines. a a The amines were the limiting reagents; 7 – 7.5 equiv of the benzylic alcohols were used. 79 4.6. Mechanism of Dehydrative Coupling We were surprised competing amine coordination is usually not discussed in work on this reaction, because amine decomplexation has been proposed by Crabtree and Eisenstein to be the rate determining step in catalysis involving a d 6 iridium(III) catalyst. 20e In the same paper, the coordination of both amine and alcohol substrates were analyzed and a more facile β-hydride elimination in alcohols was determined to be responsible for the observed selectivity. 20e Accordingly, we collected evidence to show redox reversibility and product stability under our neat reaction conditions. Thus, we performed a 13 C NMR time-course study for the coupling of benzyl alcohol-1-d1 (4.6-1-d1, ca. 93% D) and n-hexylamine in the presence of 1 mol% of precatalyst 4.1. The disappearance of the starting materials and formation of the benzylated amine can be observed clearly (Figures 4.2 and 4.3AD). Prior to heating, the deuterated benzylic carbon appears as a three-line 13 C‒ 2 H coupling pattern centered at 63.5 ppm in the 13 C spectrum along with a trace (ca. 7%) of the 1 H isotopomer at 63.8 ppm; the α-carbon of the n-hexylamine is a singlet at 42.3 ppm (Figure 4.3A). After heating for two hours, the 1 H isotopomer of benzyl alcohol increases, indicating its equilibration with n-hexylamine through an intermediate benzaldehyde (Figure 4.3B). Deuterium is incorporated into the n-hexylamine starting material, confirming that it is the 1 H donor to benzyl alcohol, and that this exchange is rapid relative to product formation. The formation of an imine intermediate at 161.0 ppm is observed but no aldehyde is detected (Figure 4.2). Thus, we show that both the amine and alcohol substrates coordinate to ruthenium and that both can be dehydrogenated. Surprisingly, the alcohol/aldehyde and amine/imine equilibria are both faster than either Tishchenko dimerization of the alcohol or the desired amination. Further, imine formation could enable amine dimerization to form di-n- hexylamine and NH3. Indeed, di-n-hexylamine is present in the reaction mixture (Figure 4.3B). 30 80 Because the major pathway is coupling to the alcohol, product formation seems to be governed by thermodynamics. Figure 4.2. 13 C NMR stacked spectra of the crude reaction mixture after 0, 2, 8, and 24 hours of heating at 110 °C. 81 Figure 4.3AB. 13 C NMR of the coupling of 2-1-d1 and n-hexylamine (1.1:1 mol ratio) after heating to 110 °C for A) 0 hour and B) 2 hours under neat reaction conditions. The deuterated carbons appear as 3-line patterns immediately upfield of the corresponding non-deuterated singlets. 82 Figure 4.3CD. 13 C NMR of the coupling of 2-1-d1 and n-hexylamine (1.1:1 mol ratio) after heating to 110 °C for C) 8 hour and D) 24 hours under neat reaction conditions. The deuterated carbons appear as 3-line patterns immediately upfield of the corresponding non-deuterated singlets. 83 Figures 4.3B-D show formation of the N-benzylated amine product. The benzylic carbon is shifted upfield, as it is transformed from an alcohol to an amine, and appears as a three-line pattern at 53.7 ppm ( 13 C‒ 2 H) and a singlet at 54.0 ppm ( 13 C‒ 1 H). The α-carbon of the hexyl group is shifted downfield, as it is transformed from a primary to a secondary amine, and appears as a three-line pattern at 49.1 ppm ( 13 C‒ 2 H) and a singlet at 49.5 ppm ( 13 C‒ 1 H). As the mixture is heated over 24 hours, hexylamine is consumed almost completely and the major product is benzylhexylamine. Small amounts of side products—Bn2O, nHex2NH, Bn2NnHex, and BnNnHex2—are also observed. 30 We observe in 31 P NMR studies that the bidentate pyridylphosphine ligand remains coordinated to ruthenium during catalysis. After 24 hours of heating the reaction mixture, the 31 P spectrum shows five peaks: the major species is a broad triplet at 92.1 ppm, consistent with a protonated (uncharged), metal-bound ligand. Free ligand, which has δ = 36 ppm (singlet), is not observed. We attempted to determine whether the cymene ligand remains bound during catalysis by following the conversion of 4.6-1-d1 to the dibenzyl ether product in 1,2-dichlorobenzene-d4 and following the reaction by 1 H NMR. Exclusion of hexylamine simplifies analysis and the mechanism of this transformation should similarly proceed through a benzaldehyde intermediate via the same hydrogen borrowing mechanism and is therefore a valid comparison. Moreover, analysis of deuterium transfer from the starting benzyl alcohol to products would allow us to determine whether a ruthenium monohydride or a ruthenium dihydride is involved in catalysis. 31 Thus, we performed a 1 H NMR time course study for the homocoupling of 4.6-1-d1 in 1,2- dichlorobenzene-d4. Upon heating the reaction mixture, the cymene dissociates from the ruthenium, and catalysis continues (Figures 4.4 and 4.5). We thus find that cymene is unimportant 84 in the catalytic reaction. Also, the aldehyde intermediate is observed in low concentrations throughout the reaction. We also find a doublet (JHP = 40 Hz) at δ = -8.90 ppm in the 1 H NMR spectrum, which we assign as a transient ruthenium hydride species (the JHP is consistent with a hydride cis to the phosphine ligand) that disappears with prolonged heating. After 48 hours of heating, the deuterium content of the starting benzyl alcohol and the product dibenzyl ether were determined to be both ca. 90% (Figure 4.6), which is consistent with a ruthenium monohydride active catalyst, based on Bäckvall’s studies of ruthenium-catalyzed transfer hydrogenation reactions. 31 The absence of deuterium scrambling indicates that the intermediate ruthenium hydride is derived solely from the alcohol’s C‒H bond, and not from the O‒H. The ruthenium hydride is then used in the reduction of the intermediate imine, thus only C—H hydrogens (not OHs) are transferred to the benzylic carbon of the product ether. Moreover, we performed the homocoupling of benzyl alcohol 4.6-1-d1 under neat conditions and determined that the deuterium content in the dibenzyl ether product and the remaining starting material were both ca. 90% (Figure 4.7). This indicates that the experiment in 1,2-dichlorobenzene-d4 solvent is a valid comparison to experiments performed neat. 85 Figure 4.4. 1 H NMR spectrum of the crude reaction mixture after 15 minutes of heating at 110 °C in 1,2-dichlorobenzene-d4. 86 Figure 4.5. 1 H NMR stacked spectra of a time-course experiment for the homocoupling of benzyl alcohol 4.6-1-d1 in 1,2-dichlorobenzene-d4. A) The disappearance of the starting material and formation of the coupled benzyl ether product is observed. The figure also shows formation of a benzaldehyde intermediate. B) Formation of a transient ruthenium hydride species and disappearance of ruthenium-bound cymene are observed. 87 Figure 4.6. 1 H NMR of the crude reaction mixture after 48 hours of heating at 110 °C in 1,2- dichlorobenzene-d4. A) The spectrum clearly shows free cymene. B) The spectrum shows that the ratio of deuterated:non-deuterated starting material and the ratio of deuterated:non-deuterated product is ca. 90%. 88 Figure 4.7. 1 H NMR spectrum of an aliquot of the crude reaction mixture after 12 h of heating at 110 °C under neat conditions (solvent: CDCl3). The spectrum shows that the ratio of deuterated:non-deuerated starting material and the ratio of deuterated:non-deuterated product is ca. 90%. Based on the studies mentioned above, we propose a hydrogen borrowing mechanism wherein the pyridylphosphine ligand remains coordinated to ruthenium, the cymene is uncoordinated, both substrates—the benzyl alcohol and the amine—coordinate the metal, and the catalytically active ruthenium species is a monohydride. 89 4.6. Conclusion The novel ruthenium(II) complex is a good catalyst for dehydrative coupling of benzyl alcohols and amines. 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C–N Bond formation between alcohols and Aamines using an iron cyclopentadienone catalyst. Org. Lett. 2015, 17, 1086-1089. (c) Pan, H.-J.; Ng. T. W.; Zhao, Y. Iron-catalyzed amination of alcohols assisted by Lewis acid. Chem. Commun. 2015, 51, 11907-11910. (d) Yan, T.; Feringa, B. L.; Barta, K. Iron catalysed direct alkylation of amines with alcohols. Nat. Commun. 2014, 5, 5602. (e) Bala, M.; Verma, P. K.; Sharma, U.; Kumar, N.; Singh, B. Iron phthalocyanine as an efficient and versatile catalyst for N-alkylation of heterocyclic amines with alcohols: one-pot synthesis of 2-substituted benzimidazoles, benzothiazoles and benzoxazoles. Green Chem. 2013, 15, 1687-1693. (f) Zhao, Y.; Foo, S. W.; Saito, S. Iron/amino acid catalyzed direct N-alkylation of amines with alcohols. Angew. Chem. Int. Ed. 2011, 50, 3006-3009. (g) Gonzalez-Arellano, C.; Yoshida, K.; Luque, R.; Gai, P. L. Highly 96 active and selective supported iron oxide nanoparticles in microwave-assisted N-alkylations of amines with alcohols. Green Chem. 2010, 12, 1281-1287. (h) Cui, X.; Shi, F.; Zhang, Y.; Deng, Y. Fe(II)-catalyzed N-alkylation of sulfonamides with benzylic alcohols. Tetrahedron Lett. 2010, 51, 2048-2051. (i) Jana, U.; Maiti, S.; Biswas, S. An efficient FeCl3-catalyzed amidation reaction of secondary benzylic and allylic alcohols with carboxamides or p- toluenesulfonamide. Tetrahedron Lett. 2008, 49, 858-862. 19. Abdukader, A.; Jin, H.; Cheng, Y.; Zhu, C. Rhenium-catalyzed amination of alcohols by hydrogen transfer process. Tetrahedron Lett. 2014, 55, 4172-4174. 20. For mechanistic studies on ruthenium-catalyzed N-alkylation of amines, see: (a) Nova, A.; Balcells, D.; Schley, N. D.; Dobereiner, G. E.; Crabtree, R. H.; Eisenstein, O. An experimental−theoretical study of the factors that affect the switch between ruthenium- catalyzed dehydrogenative amide formation versus amine alkylation. Organometallics 2010, 29, 6548-6558. For studies on iridium-catalyzed N-alkylation of amines, see: (b) Bartoszewicz, A.; Miera, G. G.; Marcos, R.; Norrby, P.-O.; Matín-Matute, B. Mechanistic studies on the alkylation of amines with alcohols catalyzed by a bifunctional iridium complex. ACS Catal. 2015, 5, 3704-3716. (c) Zhao, G.-M.; Liu, H.-L.; Huang, X.-R.; Zhang, D.-D.; Yang, X. Mechanistic study on the Cp*iridium-catalyzed N-alkylation of amines with alcohols. RSC Adv. 2015, 5, 22996-23008. (d) Fristrup, P.; Tursky, M.; Madsen, R. Mechanistic investigation of the iridium-catalysed alkylation of amines with alcohols. Org. Biomol. Chem. 2012, 10, 2569-2577. (e) Balcells, D.; Nova, A.; Clot, E.; Gnanamgari, D.; Crabtree, R. H.; Eisenstein, O. Mechanism of homogeneous iridium-catalyzed alkylation of amines with alcohols from a DFT study. Organometallics 2008, 27, 2529-2535. For mechanistic studies on N-alkylation using other metals, see ref. 12a, 15c, and: (f) Zhao, G.-M; Liu, H.-L.; Zhang, D.-D.; Huang, X.-R.; Yang, X. DFT study on mechanism of N-alkylation of amino derivatives with primary alcohols catalyzed by copper(II) acetate. ACS Catal. 2014, 4, 2231-2240. (g) Cui, X.; Shi, F.; Tse, M. K.; Gördes, D.; Thurow, K.; Beller, M.; Deng, Y. Copper-catalyzed N-alkylation of sulfonamides with benzylic alcohols: catalysis and mechanistic studies. Adv. Synth. Catal. 2009, 351, 2949-4958 21. For mechanistic studies on C‒C bond formation via the hydrogen borrowing strategy, see: (a) Song, C.; Qu, S.; Tao, Y.; Dang, Y.; Wang, Z.-X. Efficient catalyst for acceptorless alcohol dehydrogenation: interplay of theoretical and experimental studies. ACS Catal. 2014, 4, 2854- 2865. (b) Chan, L. K. M.; Poole, D. L.; Shen, D.; Healy, M. P.; Donohoe, T. J. Rhodium- catalyzed ketone methylation using methanol under mild conditions: formation of α-branched products. Angew. Chem. Int. Ed. 2014, 53, 761-765. (c) Burling, S.; Paine, B. M.; Nama, D.; Brown, V. S.; Mahon, M. F.; Prior, T. J.; Pregosin, P. S.; Whittlesey, M. K.; Williams, J. M. J. C H Activation reactions of ruthenium N-heterocyclic carbene complexes: application in a catalytic tandem reaction involving C C bond formation from alcohols. J. Am. Chem. Soc. 2007, 129, 1987-1995. 22. Conley, B. L.; Williams, T. J. Dual site catalysts for hydride manipulation. Comments Inorg. Chem. 2012, 32, 195-218. 97 23. (a) Dowson, G. R. M.; Haddow, M. F.; Lee, J.; Wingad, R. L.; Wass, D. F. Catalytic conversion of ethanol into an advanced biofuel: unprecedented selectivity for n-butanol. Angew. Chem. Int. Ed. 2013, 52, 9005-9008. (b) Baumann, W.; Spannenberg, A.; Pfeffer, J.; Haas, T.; Köckritz,A.; Martin, J.; Deutsch, J. Utilization of common ligands for the ruthenium-catalyzed amination of alcohols. Chem. Eur. J. 2013, 19, 17702-17706. 24. Celaje, J. J. A.; Lu, Z.; Kedzie, E. A.; Terrile, N. J.; Lo, J. N.; Williams, T. J. A prolific catalyst for dehydrogenation of neat formic acid. Nature Commun. 2016, 7, 11308. 25. For reviews, see ref. 6b and: (a) Khusnutdinova, J. R.; Milstein, D. Metal-ligand cooperation. Angew. Chem. Int. Ed. 2015, 54, 12236-12273. (b) Zell, T.; Milstein, D. Hydrogenation and dehydrogenation iron pincer catalysts capable of metal-ligand cooperation by aromatization/dearomatization. Acc. Chem. Res. 2015, 48, 1979-1994. (c) Gunanathan, C.; Milstein, D. Bond activation and catalysis by ruthenium pincer complexes. Chem. Rev. 2014, 114, 12024-12087. (d) Gunanathan, C.; Milstein, D. Metal-ligand cooperation by aromatization-dearomatization: a new paradigm in bond activation and "green" catalysis. Acc. Chem. Res. 2011, 44, 588-602. (e) Milstein, D. Discovery of environmentally benign catalytic reactions of alcohols catalyzed by pyridine-based pincer Ru complexes, based on metal-ligand cooperation. Top. Catal. 2010, 53, 915-923. 26. To the best of our knowledge, there is one report wherein the catalyst for N-alkylation of amines with alcohols works without solvent, inorganic base, or additives (reference 8h); two more papers report catalysts that function in neat conditions but require either an inorganic base (reference 8j) or an additive (references 8s and 9c). 27. For examples of N-alkylation in the presence of unprotected phenol or aniline, see references 8v and 18g. For examples of selective monoamination of 1,2-diols, see: a) Putra, A. E.; Oe, Y.; Ohta, T. Ruthenium-catalyzed enantioselective synthesis of β-amino alcohols from 1,2- diols by “borrowing hydrogen”. Eur. J. Org. Chem. 2013, 6146-6151. b) Bähn, S.; Tillack, A.; Imm, S.; Mevius, K.; Michalik, D.; Hollmann, D.; Neubert, L.; Beller, M. Ruthenium- catalyzed selective monoamination of vicinal diols. ChemSusChem 2009, 2, 551-557. For selective N-alkylation of sulfonamides, see: c) Lu, L.; Ma, J.; Qu, P.; Li, F. Effective recognition of different types of amino groups: from aminobenzenesulfonamides to amino-(N- alkyl)benzenesulfonamides via iridium-catalyzed N-alkylation with alcohols. Org. Lett. 2015, 17, 2350-2353. 28. Beddie, C.; Wei, P.; Douglas, S. Titanium pyridyl-phosphinimide complexes: synthesis, structure, and ethylene polymerization catalysis. Can. J. Chem. 2006, 84, 755-761. 29. For reviews of C-alkylation via the hydrogen borrowing strategy, see: (d) Huang, F.; Liu, Z.; Y, Z. C-Alkylation of ketones and related compounds by alcohols: transition-metal-catalyzed dehydrogenation. Angew. Chem. Int. Ed. 2016, 55, 862-875. (e) Ketcham, J. M.; Shin, I.; Montgomery, T. P.; Krische, M. J. Catalytic enantioselective C‒H functionalization of alcohols by redox-triggered carbonyl addition: borrowing hydrogen, returning carbon. Angew. Chem. Int. Ed. 2014, 53, 9142. (f) Obora, Y. Recent advances in α-alkylation reactions using alcohols with hydrogen borrowing methodologies. ACS Catal. 2014, 4, 3972-3981. (d) Guillena, G.; 98 Ramόn, D. J.; Yus, M. Alcohols as electrophiles in C—C bond-forming reactions: the hydrogen autotransfer process. Angew. Chem. Int. Ed. 2007, 46, 2358-2364. 30. We confirmed the presence of di-n-hexylamine by spiking a solution of benzyl alcohol-1-d1 and n-hexylamine with an authentic sample of di-n-hexylamine. The presence of the side products (Bn2O, nHex2NH, Bn2NnHex, BnNnHex2) were observed by GC-MS. 31. (a) Pàmies, O.; Bäckvall, J.-E. Studies on the mechanism of metal-catalyzed hydrogen transfer from alcohols to ketones. Chem. Eur. J. 2001, 7, 5052-5058. (b) Santosh Laxmi, Y. R.; Bäckvall, J.-E. Mechanistic studies on ruthenium-catalyzed hydrogen transfer reactions. Chem. Commun. 2000, 611-612. (c) Aranyos, A.; Csjernyik, G.; Szabό, K.; Bäckvall, J.-E. Evidence for a ruthenium dihydride species as the active catalyst in the RuCl2(PPh3)-catalyzed hydrogen transfer reaction in the presence of base. Chem. Commun. 1999, 351-352. 99 Chapter 5. Complexes with Pyridylphosphine and Dipyridylborate Ligands: Syntheses and Evaluation of Catalytic Activity Complexes 1.7 and 1.8 were graciously provided by my graduate co-worker Zhiyao Lu for the borylation studies. The acceptorless dehydrogenation studies were performed in collaboration with my graduate co-worker Xingyue (Lily) Zhang and my undergraduate co-worker Elyse Kedzie. Lily discovered the Guerbet reaction of complex 5.4 and Elyse discovered the conversion of glycerol to lactate using complex 5.3. 5.1. Introduction This chapter discusses the results of research projects that have been investigated but have not led to a manuscript for publication, or has been abandoned. As discussed in Chapter 1, we designed dipyridylborate complexes as dual site catalysts for C‒H activation wherein a pendant boron atom functions to coordinate and direct substrates to the metal center. This design concept led to the development of complex 1.7 (Chapter 1.1), 1 one of the best ammonia-borane dehydrogenation catalysts known to date. In Section 5.2 of this chapter, we describe our efforts to extend the scope of reactivity from activation of N‒H bonds to activation of C‒H bonds by studying the utility of dipyridylborate complexes in direct borylation of sp 3 C‒H bonds. Also, as discussed in Chapter 1, we designed the pyridylphosphine ligand for H 2 splitting via a metal-ligand cooperation mechanism. Our initial motivation was to develop complexes possessing a combination of this ligand and a dipyridylborate ligand, which should be highly electron-rich complexes, for hydrogenation of CO2 to methanol. Section 5.4 discusses our studies on CO2 hydrogenation. Although we have not been able to find conditions for effecting CO 2 hydrogenation, we have found pyridylphosphine complexes with excellent reactivity in 100 dehydrogenation reactions. Chapter 3 discussed an iridium complex that to date is one of the best known catalysts for formic acid dehydrogenation. Chapter 4 discussed a ruthenium complex which has exquisite functional group compatibility for dehydrative coupling of benzylic alcohols with amines, compatible with even unprotected phenols and anilines. Because we have discovered useful pyridylphosphine complexes, we have synthesized complexes of ruthenium, rhodium, and iridium, which are described in Section 5.3. Section 5.5 discusses the reactivity of these complexes in acceptorless dehydrogenation reactions. Finally, Section 5.6 comments on the possibility of metal-ligand cooperation as the mechanism of catalysis for pyridylphosphine complexes, at least for certain reactions. 101 5.2. Studies on Direct Borylation of sp 3 C‒H Bonds Using Dipyridylborate Complexes The direct borylation of C‒H bonds is of great importance in organic chemistry because the resulting borylated products are useful intermediates for the synthesis of compounds. 2 Thus, much work has been done for functionalization of C‒H bonds with boron. 2 Given the high reactivity of dipyridylborate ruthenium 1.7 (see Chapter 1.1) in the dehydrogenation of ammonia borane, we decided to examine 1.7 as catalyst for the direct borylation of alkanes. We were hopeful that its high reactivity in the activation of N‒H bonds would translate into activation (and functionalization) of C‒H bonds. 5.2.1. Borylation Using Ruthenium 1.7 Ruthenium 1.7 turns out to be a poor catalyst for direct borylation of C‒H bonds, likely because of its low solubility in the substrates, which are used neat following examples from literature. 2 For example, attempted borylation of n-octane or n-butylether with bis(picolinato)diboron (B2Pin2) using 1.7 (5 mol%) at 150 °C for 2 days leads to very poor conversion and only trace amounts of borylated products (< 5%) are observed (Figure 5.1). When m-xylene is used as the substrate, the borylation of the sp 2 C‒H bond ortho to the methyl groups proceeds in only about 50% conversion after 3 days of heating. The poor reactivity of 1.7 led us to study other complexes for borylation. Figure 5.1. Ruthenium 1.7 is a poor borylation catalyst. 102 5.2.2. Borylation Using Ruthenium 1.8 Ruthenium 1.8 gave more promising results initially. Heating n-butylether 5.1 with B2Pin2 to 150 °C for 21 hours in the presence of 5 mol% 1.8 gave 100% conversion (64% NMR yield) to give product 5.2, which is borylated at the terminal methyl carbon (Scheme 5.1, see Chapter 6.5.1 for details). We thus examined a few substrates to determine the scope of this reaction using these conditions. Unfortunately, all substrates tested either gave poor yields of borylated products by NMR (< 10%) or decomposed (Figure 5.2). Ethers containing propyl, ethyl, and methyl groups all gave poor yields. Interestingly, another butyl ether (butyl norbornyl ether) also gave a poor yield (< 10%). We do not know why we obtain poor yields with most substrates. We reasoned, however, that the unique reactivity of dibutyl ether might be due to a coordination-assisted six-membered transition state in the C‒H activation step wherein the oxygen coordinates the ruthenium and directs the terminal methyl group to ruthenium (Figure 5.3). Scheme 5.1. Lead Result for Direct Borylation Using Precatalyst 1.8. 103 Figure 5.2. Complex 1.8 exhibits poor substrate scope in direct borylation reactions. Conditions: 5 mol% 1.8, 150 °C, sealed vessel, 24 h. Figure 5.3. Putative transition state for C‒H activation. 104 5.3. Synthesis of Ruthenium, Iridium, and Rhodium Pyridylphosphine Complexes As discussed in Chapter 1, our initial motivation to develop the bidentate pyridylphosphine ligand was to synthesize complexes possessing a combination of dipyridylborate and pyridylphosphine ligands and investigate their reactivity in CO2 hydrogenation. Thus, we attempted to derivatize dipyridylborate complexes that have been previously synthesized in our group with the ligand 2-((di-tert-butylphosphino)methyl)pyridine. 3 Attempts to derivatize complexes 1.8, 1.9, and other borate-supported complexes were unsuccessful. Complex 1.7, however, reacts with 1.15 upon heating to 80 °C for 3 days, forming complex 1.18 (Scheme 5.2). The reactivity of 1.18 in hydrogenation reactions was studied and is discussed in Section 5.4. We have since synthesized several pyridylphosphine complexes (see Chapter 6 for procedures and characterization data) and studied their reactivities in various hydrogenation and dehydrogenation reactions (Figure 5.4). It is worth noting that we have found excellent reactivity from some of these complexes. For example, 3.1 is an excellent catalyst for dehydrogenation of neat formic acid and 4.1 exhibits great functional group tolerance in the dehydrative coupling of benzylic alcohols with amines. Scheme 5.2. Synthesis of Complex 1.18. 105 Figure 5.4. Pyridylphosphine complexes synthesized thus far. 106 5.4. Studies on CO2 Hydrogenation Direct reduction of carbon dioxide (CO2) to fuel and commodity chemical feedstocks is a central goal of the catalysis community, because managing global carbon balance relies on our ability to recycle CO2 efficiently. The impact potential of this research is significant: (1) CO2 is a greenhouse gas that must be managed to stop global warming, 4 and (2) methanol is gaining momentum as a drop-in gas alternative or additive that will play an expanding role in the world’s energy future; thus, improved methanol synthesis from CO2 would be of transformative value. 5 Much work has therefore been done to find catalysts for CO2 hydrogenation. 6 We entered this area because Brian Conley and Zhiyao Lu observed borohydride reduction of CO2 to trimethylborate using dipyridylborate complexes 1.8 and 1.9, respectively (Scheme 5.3). Whereas these complexes do not split H2 efficiently, we attempted to functionalize them with a pyridylphosphine ligand which we hoped would give them the ability to split H2 and provide a catalyst for CO2 hydrogenation (see Chapter 1.2 for a more detailed discussion). Scheme 5.3. Reduction of CO2 to Methanol Using NH3BH3 and Complex 1.8 observed by Dr. Brian Conley. Using complex 1.18, which possesses the desired combination of both a dipyridylborate and a pyridylphosphine ligands, we began our studies on CO2 hydrogenation. We first determined whether 1.18 does split H2 or not and that the methylene arm is involved or not in this process. It is interesting to note that when complex 1.18 is heated to 100 °C in deuterated acetonitrile and in the absence of an external base, the hydrogens of the methylene arm of the pyridylphosphine ligand are replaced with deuterium atoms, which is indicated by the 107 disappearance of the methylene hydrogens in the 1 H NMR spectrum of 1.18 (Scheme 5.4). Conversely, heating the deuterated complex 1.18-d6 in proteo acetonitrile leads to the exchange of the deuteurium atoms for hydrogens. Since hydrogen-deuterium exchange on the pyridine rings was not observed, it is likely that the hydrogen-deuterium exchange occurring on the ligand arm is proceeding through an acid base reaction. Attempted deprotonation of the ligand arm of 1.18 in deuterated acetonitrile using potassium tert-butoxide (KOtBu) failed to give the dearomatized complex. Instead, the deuterated complex 1.18-d6 forms. There is no change in the 1 H NMR spectrum except for the disappearance of the exchangeable protons (the methylene of the pyridylphosphine arm, the O‒H, and acetonitrile methyl). These protons can be recovered by simply heating 1.18-d6 in CH3CN. Thus, this observation shows that the hydrogen-deuterium exchange is very likely occurring through an acid-base mechanism. Attempted deprotonation with KOtBu in toluene-d8 and methylene chloride-d2 led to formation of multiple products. Scheme 5.4. Reversible Deuteration of the PN-ligand Methylene Arm in Acetonitrile. We then tested for hydrogenation reactivity using benzophenone as a model substrate. To our delight, we observed that heating benzophenone in toluene-d8 with 1 mol% of 1.18, stoichiometric KOtBu, and 1 atmosphere of hydrogen at 100 °C in a J-Young tube (which was recharged with hydrogen repeatedly) for 3 days led to a ca. 1:1 mixture of two products 5.9 and 5.10 (Scheme 5.5), along with other unidentified sideproducts. The GC-MS data showed a distribution of masses for the reduced products (Figure 5.5): 1) a distribution of peaks with m/z 108 ratio ranging from 186-192, consistent with 5.9 and 2) a distribution of peaks with m/z ratio ranging from 197-208, consistent with 5.10. The observed distribution of peaks is indicative of hydrogen-deuterium exchange on the phenyl rings of the benzophenone, where the deuterium is coming from hydrogen-deuterium exchange on the deuterated toluene solvent. The yield of the reduced products, however, were low (< 30% mass balance), suggesting that the catalyst might be causing benzophenone to decompose into volatile side products. We also examined the hydrogenation of other aromatics (i.e. phenol, benzyl alcohol, and 1-phenylethanol) but even small amounts of hydrogenated products were surprisingly not observed. 109 Scheme 5.5. Hydrogenation of Benzophenone Using Catalyst 1.18. Figure 5.5. GC-MS data for hydrogenation of benzophenone 5.8. 110 Having confirmed that complex 1.18 is capable of splitting H2 and hydrogenating the aryl rings of benzophenone, I attempted hydrogenation of carbon dioxide. Various conditions were examined but, unfortunately, even conducting the reaction at 80 atmospheres of 1:1 H2/CO2 at 100 °C for 90 hours, methanol formation is not observed and only a very small amount of formic acid is detected. Complex 1.18 is not reactive towards CO2 hydrogenation. Scheme 5.6. Complex 1.18 is Not a Good Catalyst for CO2 Hydrogenation. 111 5.5. Studies on Acceptorless Dehydrogenation Reactions As discussed in Section 5.3, we have synthesized several complexes possessing a pyridylphosphine ligand (Figure 5.4). Given the remarkable versatility of the PNP and PNN pincer complexes in efficiently catalyzing acceptorless dehydrogenative/dehydrative coupling of alcohols to generate a diversity of functional groups from esters, 7 amides, 8 and amines, 9 to hetereroaromatics, 10 to peptides, 11 we decided to screen our complexes for acceptorless dehydrogenation reactivity. There has been an explosion in the amount of research to develop these reactions because they do not require stoichiometric oxidants or hydrogen acceptors and are thus environmentally benign and atom economical. Our preliminary screen led to the discovery that ruthenium 4.1 efficiently effects the dehydrative homocoupling of 1-phenylethanol 4.2 to a diastereomeric mixture of ethers 4.3 (see Chapter 4.3). This discovery and further studies eventually led to the development of 4.1 as a precatalyst for coupling of benzylic alcohols with amines, which is discussed in detail in Chapter 4. In this section, our screening studies on the reactivity of ruthenium 5.3 and iridium 5.4 are discussed. 5.5.1. Reactivity of Ruthenium 5.3 Complex 5.4 was found to catalyze a number of acceptorless dehydrogenation reactions including the Tischenko reaction and coupling of alcohols with aniline. Most noteworthy is its high reactivity in the dehydrogenation of glycerol to form lactate. This reaction is gaining significance in light of the very low price of glycerol, which is a byproduct of biodiesel production. Conversion of glycerol to value-added products is currently receiving much attention from the catalysis community. 12 Elyse Kedzie, my undergraduate co-worker, discovered that 5.4 efficiently dehydrogenates glycerol under conditions comparable to the best known catalysts. For example, heating glycerol 5.11 neat with 1.1 equivalent of potassium hydroxide (KOH) and 0.6 mol% of 5.4 112 to 145 °C for 16 hours leads to formation of 940 mL of gas. Analysis of the composition of the crude reaction mixture shows clean formation of lactate 5.12 (Scheme 5.7). However, the reaction proceeds to only 50% conversion. Whereas production of one equivalent of H2 would lead to production of ca. 680 mL of gas, the amount of gas produced indicated that glycerol might be getting decomposed to something other than just hydrogen and lactate, possibly to carbon monoxide. However, because the crude reaction mixture formed an insoluble organic solid that was difficult to analyze and Zhiyao Lu found a better catalyst, 12 we decided not to pursue further studies. Scheme 5.7. Conversion of Glycerol to Lactate Using Ruthenium 5.3. 5.5.2. Reactivity of Iridium 5.4 My graduate student co-worker Xingyue (Lily) Zhang discovered that 5.4 catalyzes the coupling of 1-octanol 4.10 to form the branched alcohol 5.11, not the usual Tischenko ester product (Figure 5.6A). 13 This reaction proceeds by oxidation of the alcohol to the aldehyde, followed by condensation via an enolate to form an α,β-unsaturated aldehyde. The condensation product is then hydrogenated in situ to form 5.11 (Figure 5.6B). This transformation is known as the Guerbet reaction and is important in its use for the conversion of inexpensive alcohols such as ethanol into longer chain alcohols such as butanol, which can be used as alternative fuels. 14 Butanol, for example, is a non-corrosive gasoline substitute with a similar energy profile to gasoline. 15 Lily therefore tested the conversion of ethanol to butanol using catalyst 5.4. Heating a mixture of ethanol, 0.2 mol% 5.4, and 10 mol% KOH to 150 °C for 90 hours leads to 34% conversion to butanol (Figure 5.6C). This conversion is almost at par with the lead example in the literature for 113 this transformation (37% yield). 14 Optimization of reaction conditions might therefore lead to the development of a good catalyst for butanol synthesis for biofuel purposes. Figure 5.6. Reactivity of iridium 5.4. A. Conversion of 1-octanol to branched alcohol 5.13. B. Mechanism of the Guerbet reaction. C. Conversion of ethanol to n-butanol. 114 5.6. Studies on the Possibility of Metal-Ligand Cooperation in Complexes with Bidentate Pyridylphosphine Ligands The success of the Milstein pincer complexes in catalyzing a plethora of reactions has made metal-ligand cooperation an attractive strategy for designing new catalysts. Not surprisingly, our group was not the first to hypothesize that a bidentate pyridylphosphine ligand might function via metal-ligand cooperation to catalyze reactions. In 2012, van der Vlugt and his group reported the reactivity of complex 5.14, and observed that upon treatment with KOtBu, dearomatization to form 5.15 occurs. 16 Reaction of 5.15 with trifluorosulfonylamide (H2NTf) gives complex 5.16 (Scheme 5.8), although the authors are unsure of the exact mechanism of this reaction. A similar reactivity was observed for a copper complex. 16 And, in a recent paper, van der Vlugt characterized dearomatized pyridylphosphine complexes of boron, aluminum, and gallium. 17 Scheme 5.8. Dearomatization and N‒H Activation of a Pyridylphosphine Ligand in a Palladium Complex. Similarly, dearomatization of our iridium and rhodium complexes occur with facility. For example, treatment of iridium complex 3.1 with KOtBu at room temperature leads to a color change from orange to purple and clean conversion of 3.1 to complex 5.17 (Scheme 5.9), which can be isolated as a purple solid. Complex 5.17 was characterized by NMR (Figure 5.7, see Chapter 6.5.5 for details), but was not amenable to crystallization in our hands. Complexes 3.10, 3.11, 5.5, and 5.6 can also be deprotonated to give the complexes shown in Figure 5.8. Interestingly, the ruthenium complexes 1.18, 4.1, and 5.3 led to formation of several compounds upon treatment with KOtBu, indicating that the dearomatized complexes are unstable. 115 Scheme 5.9. Dearomatization of Complex 3.1. Figure 5.7. 1 H NMR spectrum of isolated 5.17. Figure 5.8. Dearomatized iridium and rhodium complexes. 116 We have not performed thorough studies to prove or disprove that these complexes can catalyze via metal-ligand cooperation. However, preliminary studies reveal that iridium 5.17 splits H2 in CD2Cl2, giving a stable product (see Figure 5.9) which is consistent with species 3.2 (See Chapter 3.3.1). Although this does not prove metal-ligand cooperation, it shows that it might be possible. Also, whereas complex 3.1 does not catalyze transfer hydrogenation between isopropanol and benzophenone, the isolated dearomatized complex 5.17 catalyzed the transfer hydrogenation without base. We also studied the reactivity of 5.17 with CO2 in toluene-d8, however the reaction gives only unreacted starting materials even upon standing for one week. Figure 5.9. Product of the reaction of species 5.17 with H2: a Pfaltz/Fryzuk-type dimer and cyclooctene (cf. Figure 3.11). 117 5.7. Conclusion Complexes with either a dipyridylborate and a pyridylphosphine ligand, or both have been synthesized and studied. To our delight, theses complexes have exhibited good reactivity in a variety of reactions ranging from dehydrogenation of ammonia borane and formic acid to dehydrative coupling of alcohols and amines to hydrogenation of arenes. Efforts to extend the reactivity scope of these complexes and to study their mechanisms of action are currently underway in our laboratory. 118 5.8. References 1. Conley, B. L.; Williams, T. J. A robust, air-stable, reusable ruthenium catalyst for dehydrogenation of ammonia borane. J. Am. Chem. Soc. 2011, 133, 14212-14215. 2. For reviews, see: (a) Zhang, L.-S.; Chen, G.; Wang, X.; Guo, Q.-Y.; Zhang, X.-S.; Pan, F.; Chen, K.; Shi, Z.-J. Direct borylation of primary C‒H bonds in functionalized molecules by palladium catalysis. Angew. Chem. Int. Ed. 2014, 53, 3899-3903. (b) Ros, A.; Fernandez, R.; Lassaletta, J. M. Functional group directed C‒H borylation. Chem. Soc. Rev. 2014, 43, 3229- 3243. (c) Mkhalid, I. A. I. Barnard, J. H.; Marder, T. B.; Murphy, J. M. Hartwig, J. F. C−H activation for the construction of C−B bonds. Chem. Rev. 2010, 110, 890-931. (d) Hartwig F. Borylation and silylation of C–H bonds: a platform for diverse C–H bond functionalizations. Acc. Chem. Res. 2012, 45, 864-873. 3. Beddie, C.; Wei, P.; Douglas, S. Titanium pyridyl-phosphinimide complexes: synthesis, structure, and ethylene polymerization catalysis. Can. J. Chem. 2006, 84, 755-761. 4. Federsel, C.; Jackstell, R.; Beller, M. State-of-the-art catalysts for hydrogenation of carbon dioxide. Angew. Chem. Int. Ed. 2010, 49, 6254-6257. 5. (a) Prakash, G. K. S.; Olah, G.; Goeppert, A. Beyond oil and gas: the methanol economy. ECS Trans. 2011, 35, 31-40. (b) Olah, G. A. Beyond oil and gas: the methanol economy. Angew. Chem. Int. Ed. 2005, 44, 2636-2639. 6. For reviews, see: (a) Du, X.-L.; Jiang, Z.; Su, D. S.; Wang, J.-Q. Research progress on the indirect hydrogenation of carbon dioxide to methanol. ChemSusChem 2016, 9, 322-332. (b) Alberico, E.; Nielsen, M. Towards a methanol economy based on homogeneous catalysis: methanol to H2 and CO2 to methanol. Chem. Commun. 2015, 51, 6714-6725. (c) Li, Y.-N.; Ma, R.; He, L.-N.; Diao, Z.-F. Homogeneous hydrogenation of carbon dioxide to methanol. Catal. Sci. Technol. 2014, 4, 1498-1512. 7. Zhang, J.; Leitus, G.; Ben-David, Y.; Milstein, D. Facile conversion of alcohols into esters and dihydrogen catalyzed by new ruthenium complexes. J. Am. Chem. Soc. 2005, 127, 10840- 10841. 8. Gunanathan, C.; Ben-David, Y.; Milstein, D. Direct synthesis of amides from alcohols and amines with liberation of H2. Science 2007, 317, 790. 9. Gunanathan, C.; Milstein, D. Selective synthesis of primary amines directly from alcohols and ammonia. Angew. Chem. Int. Ed. 2008, 47, 8661-8664. 10. Srimani, D.; Ben-David, Y.; Milstein, D. Direct synthesis of pyrroles by dehydrogenative coupling of β-aminoalcohols with secondary alcohols catalyzed by ruthenium pincer complexes. Angew. Chem. Int. Ed. Engl. 2013, 52, 4012-4015. 119 11. Hu, P; Fogler, E.; Diskin-Posner, Y.; Iron, M. A.; Milstein, D. A novel liquid organic hydrogen carrier system based on catalytic peptide formation and hydrogenation. Nat. Commun. 2015, 6, 6859. 12. Lu, Z.; Demianets, I.; Hamze, R.; Terrile, N. J.; Williams, T. J. A prolific catalyst for selective conversion of neat glycerol to lactic acid. ACS Catal. 2016, 6, 2014-2017. 13. Zhang, X. Ruthenium catalysis for ammonia borane dehydrogenation and dehydrative coupling. Ph.D. Dissertation, University of Southern California, Los Angeles, CA, 2016. 14. Chakraborty, S.; Piszel, P. E.; Hayes, C. E.; Baker, R. T.; Jones, W. D. Highly selective formation of n-butanol from ethanol through the Guerbet process: a tandem catalytic approach. J. Am. Chem. Soc. 2015, 137, 14264–14267. 15. (a) Dürre, P. Biobutanol: An Attractive Biofuel. Biotechnol. J. 2007, 2, 1525– 1534. (b) Harvey, B. G.; Meylemans, H. A. The role of butanol in the development of sustainable fuel technologies. J. Chem. Technol. Biotechnol. 2011, 86, 2– 9. 16. de Boer, S. Y.; Gloaguen, Y.; Reek, J. N.; Lutz, M.; van der Vlugt, J. I. N-H bond activation by palladium(II) and copper(I) complexes featuring a reactive bidentate PN-ligand. Dalton Trans. 2012, 41, 11276-11283. 17. Devillard, M.; Alvarez Lamsfus, C.; Vreeken, V.; Maron, L.; van der Vlugt, J. I. Versatile coordination of a reactive P,N-ligand toward boron, aluminum and gallium and interconversion reactivity. Dalton Trans. 2016, 45, 10989-10998. 120 Chapter 6. Experimental and Spectral Data 6.1. General Procedures 6.1.1. Chemical Reagents Dichloromethane, ethyl ether, and hexanes were purchased from VWR and dried in a J. C. Meyer solvent purification system with alumina/copper(II) oxide columns. Deuterated solvents were purchased from Cambridge Isotopes Laboratories, except for formic acid-d2, which was purchased from SynQuest Laboratories. Silica gel (230-400 mesh) was purchased as pre-packed columns from Teledyne, and silica gel (free flowing) was purchased from VWR. Organic reagents were purchased from Sigma-Aldrich Co., Alfa-Aesar, J. T. Baker, Lancaster Chemicals, EMD Millipore and TCI America and used as received. Organometallic reagents were purchased from Strem. 6.1.2. Prepared Reagents All air and water sensitive procedures were carried out either in a Vacuum Atmosphere glove box under nitrogen (2-10 ppm O2 for all manipulations) or using standard Schlenk techniques under nitrogen. Benzene-d6, toluene-d8, benzene, and toluene were dried over sodium benzophenone ketyl and distilled prior to use. Acetonitrile, acetonitrile-d3, and dichloromethane- d2 were dried and distilled over CaH2. Methanol was distilled from sodium methoxide and stored in the glovebox over molecular sieves. Ethanol was distilled from sodium ethoxide and stored in the glovebox over molecular sieves. Benzyl alcohol-1-d1 was synthesized by reduction of benzaldehyde with NaBD4; 2-((di-tert-butylphosphino)methyl)pyridine was synthesized using a literature procedure. 1 This procedure was adopted for the synthesis of the ligands 2-((di-tert- butylphosphino)methyl)-6-methylpyridine and 2-((diisopropylphosphino)methyl)pyridine. 1 Complexes 1.7 and 1.8 for borylation studies and derivatization with pyridylphosphine ligands 121 were graciously provided by Zhiyao Lu. Bis(picolinato)diboron (B2Pin2) was recrystallized prior to use. 6.1.3. Instrumentation NMR spectra were recorded on a Varian VNMRS 500 or VNMRS 600 spectrometer. All chemical shifts are reported in units of ppm and referenced to the residual 1 H or 13 C solvent peak and line-listed according to (s) singlet, (bs) broad singlet, (d) doublet, (t) triplet, (dd) double doublet, etc. 13 C spectra are delimited by carbon peaks, not carbon count. 31 P chemical shifts are referenced to an 85% phosphoric acid external standard. Air-sensitive NMR spectra were taken in 8” J-Young tubes (Wilmad or Norell) with Teflon valve plugs. Infrared spectra were recorded on Bruker OPUS FTIR spectrometer. X-ray crystallography data were obtained on a Bruker APEX DUO single-crystal diffractometer equipped with an APEX2 CCD detector, Mo fine-focus and Cu micro-focus X-ray sources. Elemental analysis data were obtained on a Thermo Flash 2000 CHNS Elemental Analyzer. Gas chromatography data for analysis of gaseous products were obtained on a Thermo gas chromatograph (Supelco Carboxen ® -1010 plot, 30 m × 0.53 mm) equipped with a TCD detector (detection limit: 0.099 v/v %). IR data for analysis carbon monoxide concentration were obtained on a Bruker Vertex 80v FT-IR using a deuterated triglycine sulfate (DTGS) detector. High resolution mass spectrometry data were obtained from UC Riverside’s High Resolution Mass Spectrometry Facility. GC-MS data for analysis of crude reaction mixtures were obtained on a Hewlett Packard HP 6890 Series GC System with Agilent Technologies 5973 Inert Mass Selective Detector. MALDI mass spectra were obtained on an Applied Biosystems Voyager spectrometer using the evaporated drop method on a coated 96 well plate. CHN elemental analyses of compounds 2.2 and 2.4 were collected at the University of Illinois at Urbana Champaign at the School of Chemical Sciences Microanalysis Laboratory. Inversion recovery kinetics data were 122 fitted using CIFIT 2.0 by Alex Bain. 2 Temperatures for NMR experiments were calibrated using an external methanol standard. Errors in Eyring parameters are calculated using the equations derived by Girolami et. al. 3 123 6.2. Chapter 2 Experimental and Spectral Data 6.2.1. Synthesis and Characterization of Nickel Complexes 2.2 and 2.4 Nickel 2.2 The synthesis and characterization of complex 2.2 were carried out by Megan Pennington Boggio. 4 In the dry box under nitrogen, (PPh3)2NiCl2 (65.4 mg, 0.10 mmol) was dissolved in 10 mL of dry dichloromethane in a dry vial containing a Teflon stir bar. In another vial, [(py)2BMe2]Na 5 (22.0 mg, 0.10 mmol) was dissolved in 5 mL of dry dichloromethane and added slowly to the (PPh3)2NiCl2 solution. The [(py)2BMe2]Na vial was rinsed with 5 mL of dichloromethane and added to the (PPh3)2NiCl2 solution. The dark green solution turned brown and then orange upon addition of [(py)2BMe2]Na. The solution was stirred for two hours and then filtered. The solvent was removed under reduced pressure. Dry diethyl ether was added to the residue and the vial was sonicated briefly. The residue was then cooled using a cold well and cold, dry hexanes was added. The suspension was filtered and washed with cold, dry ether. The suspension was dissolved with cold, dry benzene. The benzene was then removed by lyophilization to yield 39.5 mg (0.071 mmol, 71%) of [(py)2BMe2]Ni(PPh3)Cl as a pale pink solid. Crystallization from dichloromethane and hexanes produced crystals suitable for X-ray crystallographic analysis. 1 H NMR (600 MHz, Methylene Chloride-d2, 25 °C) δ: 8.55 (br s, 2H), 7.77-7.61 (m, 6H), 7.44 (t, J = 7.3 Hz, 3H), 7.40 (d, J = 7.6 Hz, 2H), 7.33 (t, J = 7.6 Hz, 6H), 7.16 (br s, 2H), 6.41 (br s, 2H), 2.22 (s, 3H), 0.32 (s, 3H) 1 H NMR (600 MHz, Methylene Chloride-d2, -40 °C) δ: 8.82 (s, 1H), 8.12 (s, 1H), 8.02-7.02 (m, 18H), 6.94 (s, 1H), 6.86 (s, 1H), 5.92 (s, 1H), 2.15 (s, 3H), 0.26 (s, 3H). 124 13 C NMR (150 MHz, Methylene Chloride-d2, 25 °C) δ: 189.72 (br), 151.89, 135.07, 134.86, 131.08, 129.91, 128.91, 127.00, 119.75, 19.51 (br), 9.48 (br). 11 B NMR (192 MHz, Methylene Chloride-d2) δ: -12.68. 31 P NMR (243 MHz, Methylene Chloride-d2, -40 °C): δ: 12.42. MALDI: m/z = 552.8941 g/mol, calc’d. for C30H29BClNiN2P + [M] + : 552.1203 g/mol. FT-IR (thin film / cm -1 ) ν = 3067.76, 2912.82, 2823.99, 1963.28, 1896.13, 1817.39, 1592.78, 1553.13, 149.62, 1435.29, 1290.62, 1217.84, 1093.77, 1012.64, 744.01. Elemental Analysis: Anal. Calc’d. for C30H29BClNiN2P: C, 65.10; H, 5.28; N, 5.06. Found: C, 65.04; H, 5.47; N, 5.28. 1 H NMR spectrum of 2.2 at 25 °C in CD2Cl2. 125 1 H NMR spectrum of 2.2 at -40 °C in CD2Cl2. 13 C NMR spectrum of 2.2 at 25 °C in CD2Cl2. 126 11 B NMR spectrum of 2.2 at 25 °C in CD2Cl2. 31 P NMR spectrum of 2.2 at -40 °C in CD2Cl2. 127 Figure 6.2.1. 1D NOESY spectrum of 2.2 at -50 °C in CD2Cl2 (the upfield B(Me) is exo). Figure 6.2.2. 1D NOESY spectrum of 2.2 at -50 °C in CD2Cl2 (the downfield B(Me) is endo). 128 IR Spectrum of 2.2. 129 Nickel 2.4 The synthesis and characterization of complex 2.4 were carried out by Megan-Pennington Boggio. In the dry box under nitrogen, Ni(acac)2 (64.2 mg, 0.25 mmol) was suspended in 10 mL of dry dichloromethane in a dry vial containing a Teflon stir bar. In another dry vial, [(py) 2BMe2]Na 5 (22.0 mg, 0.10 mmol) was dissolved in 5 mL of dichloromethane and added slowly to the solution of Ni(acac)2. Another 5 mL of dichloromethane was used to rinse the vial and added slowly to the solution of Ni(acac)2. The green solution turned orange on addition of [(py)2BMe2]Na. The solution was stirred for 2 hours at room temperature and then filtered through Celite. The solvent was removed in vacuo. Dry hexanes (10 mL) was added to the residue and the vial was treated with sonication briefly. The suspension was then cooled using a cold well, filtered and washed with cold, dry hexanes. The solid was dried under vacuum to yield 23.7 mg (0.067 mmol, 67%) of [(py)2BMe2]Ni(acac) as an orange solid. Crystallization from dichloromethane and hexanes produced crystals suitable for X-ray crystallographic analysis. 1 H NMR (600 MHz, Methylene Chloride-d2) δ: 8.30 (d, J = 5.6 Hz, 2H), 7.40 (d, J = 7.5 Hz, 2H), 7.34 (t, J = 7.3 Hz, 2H), 6.83 (t, J = 6.3 Hz, 2H), 5.55 (s, 1H), 2.27 (br s, 2H), 1.88 (s, 6H), 0.27 (br s, 3H). 13 C NMR (150 MHz, Methylene Chloride-d2) δ: 189.81 (q, J = 48 Hz) 188.11, 149.89, 135.23, 125.93, 119.71, 102.04, 26.09, 18.93 (br), 8.93 (br). 11 B NMR (192 MHz, Methylene Chloride-d2) δ: -12.68. FT-IR (thin film / cm -1 ): v = 2891.92, 2821.81, 1586.41, 1532.39, 1388.63, 1289.47, 122.57, 1159.73, 1015.71, 934.76, 788.67, 753.86, 738.46. HR-MS (+ESI): m/z = 355.1129 g/mol, calc’d. for C17H22BN2O2Ni + [MH] + : 355.1122 g/mol. 130 1 H NMR spectrum of 2.4 at 25 °C in CD2Cl2. 13 C NMR spectrum of 2.4 at 25 °C in CD2Cl2. 131 11 B NMR spectrum of 2.4 at 25 °C in CD2Cl2. IR spectrum of 2.4. 132 6.2.2. Studies on the Effect of PPh3 Addition on the Rate of Rotation Inversion recovery data were acquired on a VNMRS 500 or a VNMRS 600 according to previously published procedures. 2 Inversion recovery data were then fitted into CIFIT 2.0 2b to obtain a rate constant (with a corresponding error) for each set of inversion recovery data. Inversion recovery data were acquired using a screw cap NMR tube beginning with a 12.0 mM CD2Cl2 solution (1 mL) of nickel 2.2 and 0 equivalent of PPh3. Inversion recovery data were then obtained for solutions of 2.2 with 0.1, 0.2, 0.3, 0.4, 0.5, 0.75, 1, 1.25, 1.5, 2.0, 5, and 10 equivalents of PPh3 -41.1 °C. The PPh3 was added via syringe as a concentrated solution (1.0 M PPh3; 0.3 μL solution is added to obtain 0.1 equivalent). The temperature was calibrated (tempcal) using a methanol standard. Table 6.2.1 shows the rate constants obtained when each set of inversion recovery data were fitted into CIFIT 2.0. A plot of ln [PPh3] vs ln kobs (Chapter 2, Figure 2.6) shows that the rate of rotation is independent of [PPh3]. The error on the slope of the trend line and the y-intercept were calculated using a least squares optimization: 0.005(10) and 3.28(5), respectively. Table 6.2.1. Rotation rate constants obtained from inversion recovery experiments. Run [Ni] (M) [PPh 3] (M) PPh 3 equiv k obs (s -1 ) er(k obs) (s -1 ) ln[PPh 3] ln k obs er (ln k obs) 1 0.0120 0.0000 0 24.6496 0.3624 3.2048 0.0147 2 0.0120 0.0012 0.1 25.1335 0.1980 -6.7254 3.2242 0.007877 3 0.0119 0.0024 0.2 24.7189 0.4233 -6.0323 3.2076 0.017126 4 0.0119 0.0036 0.3 25.0113 0.2475 -5.6268 3.2193 0.009897 5 0.0119 0.0048 0.4 25.6950 0.2316 -5.3391 3.2463 0.009012 6 0.0118 0.0059 0.5 27.8497 0.5792 -5.1309 3.3268 0.020796 7 0.0118 0.0089 0.75 27.4584 0.4796 -4.7217 3.3127 0.017467 8 0.0118 0.0118 1 26.2667 0.3792 -4.4436 3.2683 0.014436 9 0.0117 0.0120 1.25 27.1725 0.3685 -4.4228 3.3022 0.01356 10 0.0117 0.0175 1.5 25.7745 0.2856 -4.0440 3.2494 0.011081 11 0.0116 0.0232 2 24.9912 0.3304 -3.7622 3.2185 0.013222 12 0.0112 0.0561 5 26.1666 0.3257 -2.8801 3.2645 0.012446 14 0.0106 0.1063 10 25.5716 0.3028 -2.2416 3.2415 0.011841 133 6.2.3. 31 P NMR Inversion Recovery Experiment for PPh3 Exchange To a 1 mL 12 mM CD2Cl2 solution of 2.2, 0.5 equivalent PPh3 (6 μmol; 1.5 μL of a 1 M PPh3 stock solution) was added via syringe. 31 P NMR inversion recovery was performed using a Varian VNMRS 500 at -42.4 °C. The temperature was calibrated (tempcal) using a methanol standard. When coordinated PPh3 (Figure 6.2.3; 12.60 ppm) is pulsed, magnetization transfer from coordinated PPh3 to free PPh3 (-7.23 ppm) is not observed. The inversion recovery stacked NMR spectra using different mixing times (d2) is shown in Figure 6.2.4. A plot of integration vs d2 is shown in Chapter 2, Figure 2.7. The integration for the free PPh3 peak does not change, indicating that no magnetization transfer is occurring. Figure 6.2.3. 31 P NMR spectrum of 2.2 and free PPh3 at -42.4 °C. 134 Figure 6.2.4. Stacked spectra of 31 P NMR inversion recovery data. 135 6.2.4. Studies on the Effect of (n-Bu)4NCl and LiCl Addition on the Rate of Rotation Addition of (n-Bu)4NCl to a solution of complex 2.2 results in a reaction leading to formation of an unidentified paramagnetic side product (Figure 6.2.5). Nevertheless, a small amount of complex 2.2 remains in solution and measurement of the rate of rotation using inversion recovery experiments is possible. Figure 6.2.5. 1 H NMR spectrum of 2.2 in the presence of 1 equiv (n-Bu)4NCl at -43.0 °C. Inversion recovery data were acquired using a J-Young NMR tube beginning with a 12.0 mM solution (1 mL) of nickel 2.2 and 0.4 equivalent (n-Bu)4NCl. Inversion recovery data were then obtained for solutions of 2.2 with 0.7, 1.1, 1.5, and 2.0 equivalents of (n-Bu)4NCl at -43.0 °C. (n-Bu)4NCl were added in one portion into the J-Young tube containing nickel complex 2.2 in the glove box. The temperature was calibrated using a methanol standard (tempcal). Table 6.2.2 shows the rate constants obtained when each set of inversion recovery data were fitted into CIFIT 2.0. A plot of ln[(n-Bu)4NCl] added vs ln kobs (Chapter 2, Figure 2.8, left) shows that the rate of 136 rotation is independent of added (n-Bu)4NCl. The error on the slope of the trend line and the y- intercept were calculated using a least squares optimization: -0.01(3) and 3.0(1), respectively. Table 6.2.2. Rotation rate constants with added (n-Bu)4NCl. Run Equiv NBu4Cl [NBu4Cl] (M) k(s -1 ) 1 0.4 0.0048 21.5(4) 2 0.7 0.0084 21.4(7) 3 1.1 0.0132 22.2(12) 4 1.5 0.018 22.3(5) 5 2 0.024 20.4(8) The rate of rotation was also measured in the presence of excess LiCl, which is insoluble in CD2Cl2. Unlike addition (n-Bu)4NCl, no reaction occurs upon addition of LiCl. Inversion recovery data were acquired using a J-Young NMR tube beginning with a 12.0 mM solution (1 mL) of nickel 2.2 and 0 equivalent of LiCl. Inversion recovery data were then obtained for solutions of 2.2 with 6, 12, 24, and 48 equivalents of LiCl at -42.0 °C. LiCl was added in one portion into the J-Young tube containing nickel complex 2.2 in the glove box. The temperature was calibrated (tempcal) using a methanol standard. Table 6.2.3 shows the rate constants obtained when each set of inversion recovery data were fitted into CIFIT 2.0. A plot of equivalents of LiCl added vs kobs (Chapter 2, Figure 2.8, right) shows that the rate of rotation is independent of added LiCl. The error on the slope of the trend line and the y-intercept were calculated using a least squares optimization: -0.02(3) and 22.7(7), respectively. Table 6.2.3. Rotation rate constants with added LiCl. Run Equiv LiCl kobs (s -1 ) 1 0 21.3(4) 2 6 23.3(2) 3 12 23.1(2) 4 24 22.6(4) 5 48 21.0(3) 137 6.2.5. Tl(OTf) Experiments To a solution of 2.2 (5.0 mg, 9 μmol) in CD2Cl2, Tl(OTf) (6.5 mg, 18.4 μmol) was added. The 1 H NMR spectrum of 2.2 remained largely the same even after standing for 4 days at room temperature (Figures 6.2.6 and 6.2.7). 1 H NMR inversion recovery experiments were performed and rate constants ca. 1 h and 4 d after addition were obtained at -42.0 °C. The rate constants of rotation for both experiments were the same as the rate constant in the absence of thallium (Table 6.2.4). Figure 6.2.6. 1 H NMR spectrum of 2.2 at 25 °C 1 hour after addition of 2 equiv Tl(OTf). 138 Figure 6.2.7. 1 H NMR spectrum of 2.2 at 25 °C 4 days after addition of 2 equiv Tl(OTf). Table 6.2.4. Rotation rate constants with added Tl(OTf). Run Time Tl(OTf) equiv kobs (s -1 ) 1 1 h 2 23.1(4) 2 4d 2 23.5(6) 139 6.2.6. Eyring Plot for Rotation Inversion recovery data were acquired on a Varian VNMRS 500 and VNMRS 600 (using a 12 mM CD2Cl2 solution of nickel 2.2) according to previously published procedure. 2 Inversion recovery data were then fitted into CIFIT 2.0 to obtain a rate constant of each set of inversion recovery data. Table 6.2.5 shows the rate constants of rotation at different temperatures obtained from inversion recovery data. Standard error values for the activation parameters, σ(∆H ‡ ) and σ(∆S ‡ ), were calculated based on the equations derived by Girolami et al. 3 Temperatures were calibrated using a methanol standard. From the Eyring plot (Chapter 2, Figure 2.9, left), ∆H ‡ = 12.2(1) kcal mol -1 and ∆S ‡ = 0.8(5) eu. Table 6.2.5. Data for Eyring analysis of rotation. T (K) T (°C) kobs (s -1 ) 1000/T (K -1 ) Rln(k/T) - Rln(kB/h) σ(∆H ‡ ) (kcal/mol) σ(∆S ‡ ) (eu) -61.6 211.5 1.10 4.73 -57.63 0.10 0.43 -61.4 211.8 1.92 4.72 -56.53 0.11 0.45 -53.7 219.5 6.00 4.56 -54.33 0.10 0.41 -46.8 226.3 12.78 4.42 -52.89 0.09 0.40 -42.0 231.2 23.23 4.33 -51.74 0.10 0.16 -32.6 240.5 60.20 4.16 -49.93 0.09 0.19 -31.8 241.3 81.68 4.14 -49.33 0.22 0.87 -18.9 254.2 204.53 3.93 -47.61 0.23 0.94 <σ(∆H ‡ )> 0.13 <σ(∆S ‡ )> 0.48 140 6.2.7. Eyring Plot for Ring Flip Inversion recovery data were acquired on a Varian VNMRS 600 (using a 12 mM CD 2Cl2 solution of nickel 2.2) according to previously published procedure. 2 Inversion recovery data were then fitted into CIFIT 2.0 to obtain a rate constant of each set of inversion recovery data. Table 6.2.6 shows the rate constants of ring flip in CD2Cl2 at different temperatures obtained from inversion recovery data. Standard error values for the activation parameters, σ(∆Hq) and σ(∆Sq), were calculated based on the equations derived by Girolami et al. 3 Temperatures were calibrated using a methanol standard. From the Eyring plot (Chapter 2, Figure 2.9, right), ∆H ‡ = 15.0(2) kcal mol -1 and ∆S ‡ = ‒4.2(7) eu. Table 6.2.6. Data for Eyring analysis of ring flip in CD2Cl2. T (°C) T (K) kobs (s -1 ) 1000/T (K -1 ) Rln(k/T) - Rln(kB/h) σ(∆H ‡ ) (kcal/mol) σ(∆S ‡ ) (eu) 286.8 13.7 2.69 (4) 3.49 -56.45 0.25 0.82 292.0 18.8 4.35 (2) 3.43 -55.54 0.17 0.63 301.3 28.1 10.02 (4) 3.32 -53.94 0.17 0.61 311.4 38.2 23.16 (17) 3.21 -52.34 0.18 0.63 <σ(∆H ‡ )> 0.19 <σ(∆S ‡ )> 0.67 Ring flip rate constants in CD2Cl2 were collected over a temperature range of only 24.5 °C because the solvent boils at 40 °C. Because it is recommended that data collected over a temperature range of 40 °C be obtained for accurate values of ∆S ‡ , we attempted to obtain an Eyring plot for the ring flip in C6D6. Table 6.2.7 shows the rate constants of ring flip (using a 12 mM C6D6 solution of 2.2) at different temperatures. Data were collected over a temperature range of 37 °C because attempts to obtain a rate constant at 47 °C were unsuccessful (data would not converge when fitted into CIFIT). From the Eyring plot (Chapter 2, Figure 2.10), ∆H ‡ = 15.5(3) kcal mol -1 and ∆S ‡ = ‒3.3(11) eu. 141 Table 6.2.7. Data for Eyring analysis of ring flip in C6D6. T (°C) T (K) kobs (s -1 ) 1000/T (K -1 ) Rln(k/T) - Rln(kB/h) σ(∆H ‡ ) (kcal/mol) σ(∆S ‡ ) (eu) 7.0 280.2 1.13 3.57 -58.14 0.68 2.28 13.8 287.0 1.61 3.48 -57.47 0.15 0.50 24.0 297.1 3.88 3.37 -55.79 0.18 0.61 34.3 307.4 11.71 3.25 -53.67 0.17 0.57 44.2 317.3 31.59 3.15 -51.76 0.42 1.41 <σ(∆H ‡ )> 0.32 <σ(∆S ‡ )> 1.07 142 6.2.8. DFT Studies We gratefully acknowledge Prof. Michael G. Richmond of the University of North Texas for performing these studies. The geometry optimizations were performed with the DFT gradient-corrected correlation functional PBE, as implemented by the Gaussian 09 program package. 6 The Ni atom was described by a Stuttgart−Dresden effective core potential (ecp) and an SDD basis set, while the 6- 31G(d′) basis set was employed for the remaining Cl, P, N, C, B, and H atoms. All structures were fully optimized and evaluated for the correct number of imaginary frequencies through calculation of the vibrational frequencies, using the analytical Hessian (positive eigenvalues ground- state minima and one negative eigenvalue for a transition state). The computed frequencies were used to make zero-point and thermal corrections to the electronic energies, and the reported enthalpies are quoted in kcal/mol relative to singlet species A. The computed triplet species B and TSBB′ revealed no significant spin contamination from higher order spin states. The geometry-optimized structures have been drawn with the JIMP2 molecular visualization and manipulation program. 7 B3LYP geometries and energies for all optimized minima and transition structures Species A HF energy = -1691.10366444 No imaginary frequency Zero-point correction = 0.347339 (Hartree/Particle) Thermal correction to Energy = 0.371984 Thermal correction to Enthalpy = 0.372928 Thermal correction to Gibbs Free Energy = 0.295084 Sum of electronic and zero-point Energies = -1690.756325 Sum of electronic and thermal Energies = -1690.731681 Sum of electronic and thermal Enthalpies = -1690.730736 Sum of electronic and thermal Free Energies = -1690.808580 143 Coordinates: A Cl 8.57840000 3.96570000 6.39970000 Ni 10.09160000 3.12510000 7.78110000 N 11.46530000 2.26390000 8.76260000 P 11.33100000 4.87390000 7.23970000 N 8.86800000 1.76460000 8.43260000 C 8.07900000 1.06180000 7.58400000 H 8.20280000 1.28560000 6.52010000 C 12.57110000 1.81010000 8.11610000 H 12.60110000 1.98670000 7.03440000 C 13.60580000 1.15530000 8.78050000 H 14.47510000 0.79780000 8.21920000 C 13.48910000 0.97980000 10.17040000 H 14.28810000 0.48570000 10.73690000 C 12.33100000 1.42400000 10.81210000 H 12.20180000 1.27390000 11.88860000 C 11.27980000 2.05630000 10.10280000 B 9.82950000 2.43330000 10.76000000 C 9.73430000 1.95220000 12.32250000 H 9.90600000 0.86790000 12.48920000 H 8.74100000 2.18300000 12.75780000 H 10.46530000 2.48940000 12.96110000 C 8.79510000 1.60090000 9.78890000 C 7.14590000 0.13180000 8.04130000 H 6.53350000 -0.42230000 7.32250000 C 7.01610000 -0.04930000 9.42670000 H 10.28100000 4.65390000 11.18350000 H 8.53660000 4.29730000 11.09340000 H 9.47760000 4.42980000 9.59690000 C 10.49260000 6.48050000 7.59190000 H 10.26940000 6.53880000 8.67100000 H 11.14040000 7.32780000 7.30170000 H 9.54240000 6.51300000 7.03570000 C 11.80270000 4.99500000 5.45770000 H 10.87860000 4.95300000 4.85770000 H 12.34680000 5.93470000 5.25190000 H 12.44150000 4.13840000 5.18000000 C 12.93990000 5.08990000 8.13360000 H 12.74700000 5.09760000 9.22040000 H 13.62990000 4.25820000 7.91520000 H 13.41640000 6.04310000 7.84150000 144 Species B HF energy = -1691.08876337 no imaginary frequency Zero-point correction = 0.345759 (Hartree/Particle) Thermal correction to Energy = 0.371132 Thermal correction to Enthalpy = 0.372076 Thermal correction to Gibbs Free Energy = 0.290622 Sum of electronic and zero-point Energies = -1690.743004 Sum of electronic and thermal Energies = -1690.717631 Sum of electronic and thermal Enthalpies = -1690.716687 Sum of electronic and thermal Free Energies = -1690.798141 Coordinates: B Cl 9.87520000 2.74130000 5.67950000 Ni 10.08950000 3.20370000 7.91860000 N 11.54140000 2.04430000 8.63670000 P 11.18320000 5.19120000 7.36630000 N 8.65950000 1.98410000 8.65350000 C 7.61730000 1.55820000 7.90130000 H 7.61040000 1.90860000 6.86250000 C 12.55820000 1.61570000 7.85250000 H 12.51750000 1.93520000 6.80450000 C 13.57530000 0.79700000 8.34440000 H 14.38260000 0.46770000 7.68200000 C 13.51810000 0.41440000 9.69470000 B 10.10470000 2.16330000 10.78600000 C 10.13530000 1.64820000 12.33830000 H 10.17600000 0.54470000 12.45390000 H 9.24080000 1.98630000 12.89980000 H 11.00710000 2.05190000 12.89280000 C 8.81300000 1.58550000 9.95590000 C 6.63200000 0.70970000 8.40920000 H 5.80230000 0.39100000 7.76970000 C 6.74960000 0.28280000 9.74070000 H 5.99970000 -0.38920000 10.17700000 C 7.84040000 0.71840000 10.50100000 H 7.95750000 0.39330000 11.54000000 C 10.00530000 3.81500000 10.73850000 H 10.90520000 4.30950000 11.15530000 H 9.12570000 4.17720000 11.30740000 H 9.87020000 4.25970000 9.71290000 C 10.09010000 6.34340000 6.41870000 H 9.23840000 6.65060000 7.05060000 H 10.63940000 7.24360000 6.08720000 H 9.69650000 5.79980000 5.54290000 C 12.62810000 4.96950000 6.23600000 145 H 12.29760000 4.37470000 5.36760000 H 13.02380000 5.94430000 5.89740000 H 13.42700000 4.41730000 6.76050000 C 11.87120000 6.26770000 8.70950000 H 11.06420000 6.55750000 9.40410000 H 12.62290000 5.70070000 9.28580000 H 12.34210000 7.17830000 8.29610000 Species TSBB’ HF energy = -1691.08394573 Imaginary frequency: 83i Zero-point correction = 0.345215 (Hartree/Particle) Thermal correction to Energy = 0.370008 Thermal correction to Enthalpy = 0.370952 Thermal correction to Gibbs Free Energy = 0.291136 Sum of electronic and zero-point Energies = -1690.738731 Sum of electronic and thermal Energies = -1690.713938 Sum of electronic and thermal Enthalpies = -1690.712994 Sum of electronic and thermal Free Energies = -1690.792810 Coordinates: TSBB’ Cl 2.25980000 1.65030000 0.00000000 Ni 0.18750000 0.64680000 0.00000000 N 0.38820000 -0.72730000 1.42600000 P -0.78810000 2.82980000 0.00000000 N 0.38820000 -0.72730000 -1.42600000 C 1.22290000 -0.51110000 -2.47100000 H 1.79010000 0.42610000 -2.43880000 C 1.22290000 -0.51110000 2.47100000 H 1.79010000 0.42610000 2.43880000 C 1.36900000 -1.43800000 3.50380000 H 2.05230000 -1.22840000 4.33320000 C 0.62940000 -2.62900000 3.43200000 H 0.71810000 -3.38610000 4.22130000 C -0.21190000 -2.84270000 2.33560000 H -0.79090000 -3.76810000 2.25140000 C -0.34020000 -1.87970000 1.30840000 B -1.31220000 -2.05420000 0.00000000 C -2.11020000 -3.48150000 0.00000000 H -1.45050000 -4.37460000 0.00000000 H -2.77330000 -3.58380000 -0.88310000 H -2.77330000 -3.58380000 0.88310000 C -0.34020000 -1.87970000 -1.30840000 C 1.36900000 -1.43800000 -3.50380000 146 H 2.05230000 -1.22840000 -4.33320000 C 0.62940000 -2.62900000 -3.43200000 H 0.71810000 -3.38610000 -4.22130000 C -0.21190000 -2.84270000 -2.33560000 H -0.79090000 -3.76810000 -2.25140000 C -2.38190000 -0.79140000 0.00000000 H -3.03510000 -0.79640000 0.89560000 H -3.03510000 -0.79640000 -0.89560000 H -1.89620000 0.22210000 0.00000000 C -0.23890000 3.84170000 -1.44680000 H -0.63850000 3.40470000 -2.37860000 H -0.58180000 4.88900000 -1.35990000 H 0.86300000 3.80600000 -1.48640000 C -0.23890000 3.84170000 1.44680000 H 0.86300000 3.80600000 1.48640000 H -0.58180000 4.88900000 1.35990000 H -0.63850000 3.40470000 2.37860000 C -2.62790000 3.05690000 0.00000000 H -3.06020000 2.57050000 -0.89150000 H -3.06020000 2.57050000 0.89150000 H -2.90280000 4.12760000 0.00000000 Comparison of Selected Bond Distances and Angles for Compounds 4/A Metric Diffraction data DFT data Bond Distances Å Ni(1)-P(1) 2.2260(9) 2.2108 Ni(1)-Cl(1) 2.1742(9) 2.2146 Ni(1)-N(1) 1.893(3) 1.895 Ni(1)-N(2) 1.945(2) 1.942 Bond Angles o P(1)-Ni(1)-N(2) 170.48(8) 171.65 P(1)-Ni(1)-N(1) 94.08(8) 94.58 P(1)-Ni(1)-Cl(1) 86.82(3) 85.99 Cl(1)-Ni(1)-N(1) 169.87(9) 172.19 Cl(1)-Ni(1)-N(2) 92.31(8) 92.56 N(1)-Ni(1)-N(2) 88.44(10) 87.97 147 6.2.9. Determination of Magnetic Susceptibility and Magnetic Moment We attempted to determine the mass susceptibility of complex 2.2 using the Evans method modified by Schubert (equation 1). 8 In the drybox, a solution of complex 2.2 (35.0 mg, 48 μmol) in 0.5 mL of CD2Cl2 was placed into an insert tube and sealed. The insert tube was placed into an NMR tube containing only CD2Cl2. The 1 H NMR spectrum (600 MHz) was obtained at 25 C. No shift in the solvent peak could be detected. Thus, we calculated an upper limit on the mass magnetic susceptibility using the width at half-height (4.0 Hz) of the solvent peak as the value for Δf. Using equation 1, an upper limit for the mass magnetic susceptibility of 2.6 × 10 -7 cm 3 g -1 was calculated for this solution of complex 2.2. χm = (-3Δf / 4πfm) + χo + ( [χo(do – ds)] / m ) (eq. 1) where: χm = mass magnetic susceptibility of the solute (cm 3 g -1 ) Δf = observed frequency shift of reference resonance (4.0 Hz) f = spectrometer frequency (600 MHz) m = mass of substance per cm 3 of solution (0.070 g) χo = mass magnetic susceptibility of solvent (5.4 × 10 -7 cm 3 g -1 ; calculated from molar magnetic solubility of dichloromethane) do = density of solution (1.362 g cm -3 ) ds = density of solvent (1.3606 g cm -3 ) The upper limit for the magnetic moment was calculated from the Curie law (equation 2) to be 0.11 BM. μeff = 2.83(χMT) 1/2 (eq. 2) where: 148 μeff = magnetic moment (in Bohr Magneton) χM = molar magnetic susceptibility (1.41 × 10 -4 cm 3 mol -1 ; calculated from χm) T = temperature (Kelvin) For a system wherein an equilibrium between a diamagnetic (singlet) and paramagnetic (triplet) species exists, the ΔG can be calculated using equation 3. 6a Using equation 3, a lower limit for the ΔG between square planar (singlet) complex 2.2 and a paramagnetic tetrahedral (or pseudotetrahedral) intermediate was calculated to be 2.57 kcal/mol. ΔG = RT ln [3((μ∞ 2 / μeff 2 ) – 1)] (eq. 3) where: R = ideal gas constant (1.897 × 10 -3 kcal mol -1 K -1 ) T = temperature (Kelvin) μ∞ = magnetic moment of the fully paramagnetic species (ca. 3.3 BM) 5 μeff = measured magnetic moment (0.57 BM) 149 6.3. Chapter 3 Experimental and Spectral Data 6.3.1. Synthesis and Characterization of Iridium Complexes 3.1 and 3.3b Iridium 3.1 In the drybox under nitrogen, 2-((di-tert-butylphosphino)methyl)pyridine 1 (105.3 mg, 0.44 mmol) was dissolved in a dry vial in 5 mL of dry dichloromethane. In another vial containing a Teflon stir bar, chloro(1,5-cyclooctadiene)iridium(I) dimer (149.0 mg, 0.22 mmol) and sodium trifluoromethanesulfonate (130 mg, 0.75 mmol) were suspended in 10 mL of dry dichloromethane. The suspension was stirred vigorously and then the phosphinopyridine solution was added slowly dropwise. The phosphinopyridine vial was rinsed with 5 mL of dichloromethane and added to the stirred suspension. After stirring for 1 hour, the solution was filtered to remove the sodium chloride byproduct and the excess sodium triflate. The solvent was evaporated under reduced pressure to yield an orange glassy solid. A 5:1 mixture of dry hexanes/ethyl ether (10 mL) was added to the residue, and then triturated by sonication. The hexane was decanted and the residue washed with an additional 10 mL of hexanes/ethyl ether. The pure iridium complex was dried under reduced pressure to give an orange solid (235 mg, 77.3%). Recrystallization from dichloromethane and toluene produced crystals suitable for X-ray crystallography. 1 H NMR (500 MHz, Methylene Chloride-d2) δ 8.27 (d, J = 4.5 Hz, 1H), 8.10 (t, J = 7.5 Hz, 1H), 8.02 (d, J = 7.5 Hz, 1H), 7.47 (d, J = 5.5 Hz, 1H), 4.89 (s, 2H), 4.51 (s, 2H), 3.66 (d, J = 9.1 Hz, 2H), 2.39 (m, 2H), 2.33-2.17 (m, 4H), 1.96 (m, 2H), 1.34 (d, J = 13.9 Hz, 18H). 13 C NMR (126 MHz, Methylene Chloride-d2) δ 169.60 (d, J = 20.2 Hz), 149.37, 141.94, 125.25 (d, J = 8.8 Hz), 124.74, 90.70, 90.61, 63.70, 37.64 (d, J = 20.2 Hz), 34.79 (d, J = 25.2 Hz), 33.57, 33.55, 30.27, 30.25, 28.41, 28.40. 31 P NMR (202 MHz, Methylene Chloride-d2) δ 57.98. 150 19 F NMR (470 MHz, Methylene Chloride-d2) δ -78.91. Elemental Analysis (CHNS) Anal. Calcd for C23H36F3IrNO3PS: C, 40.22; H, 5.28; N, 2.04; S, 4.67. Found: C, 40.54; H, 5.40; N, 2.01; S, 4.63. FT-IR (thin film/cm -1 ) ν = 2954, 2889, 2836, 1608, 1475, 1389, 1370, 1319, 1273, 1223, 1148, 1108, 1080, 1031, 1001, 967, 894, 875, 821, 776, 636. 1 H NMR spectrum of complex 3.1 at 25 °C in CD2Cl2. 151 13 C NMR spectrum of complex 3.1 at 25 °C in CD2Cl2. 31 P NMR spectrum of complex 3.1 at 25 °C in CD2Cl2. 152 19 F NMR spectrum of complex 3.1 at 25 °C in CD2Cl2. IR spectrum of complex 3.1. 153 Iridium 3.3b The synthesis and characterization of complex 3.3b were carried out by Zhiyao Lu. In the drybox under nitrogen, complex 3.1 (10 mg, 14.9 μmol) was dissolved in 0.6 mL dichloromethane- d2 in a J-Young NMR tube. Dry acetic acid (8.6 μL, 149 μmol) was also added to this solution. The tube was then degassed, put under 1 atm head pressure of H2 gas, and shaken. After ca. 5 minutes, a 1 H NMR spectrum of the crude reaction mixture was obtained, which confirmed the formation of 2. The solution was then poured into a dry one dram vial. Hexane was carefully layered on top of this dichloromethane solution, and the vial was left in a desiccator for 1 week. A crystal suitable for X-ray diffraction was isolated from the vial. Although the crystal of 3.3b is stable for days, the pure crystal of 3.3b re-dissolved in dichloromethane-d2 appears to be in equilibrium with 3.2 and potentially other form of the iridium complex. 1 H NMR (600 MHz, Methylene Chloride-d2): δ = 9.23 (dd, J = 5.9, 1.6 Hz, py 2H), 7.93 (tt, J = 7.7, 1.4 Hz, py 2H), 7.70 (d, J = 7.9 Hz, py 2H), 7.36 (ddd, J = 7.4, 5.8, 1.5 Hz, py 2H), 3.58 (dd, J = 16.7, 9.6 Hz, methylene 2H), 3.43 (dd, J = 16.7, 10.9 Hz, methylene 2H), 2.07 (d, J = 1.6 Hz, -acetate 6H) 1.25 (d, J = 14.0 Hz, tBu 18H), 1.19 (d, J = 13.9 Hz, tBu 18H), -26.30 (dd, J = 19.0, 3.1 Hz, Ir-H 2H), -28.76 (m, -H 1H). 13 C NMR (150 MHz, Methylene Chloride-d2): δ = 184.63 (acetate), 163.84 (py), 149.59 (py), 138.94 (py), 123.42 (py), 123.16 (py), 36.78 (d, J = 30.0 Hz, P-C), 36.38 (d, J = 27.5 Hz, P-C), 34.88 (d, J = 26.9 Hz, P-C), 29.79 (d, J = 25.6 Hz, P-C), 28.95 (tBu methyl), 28.69 (tBu methyl), 24.27 (acetate methyl). Other small peaks on the spectrum appeared overtime due to the instability of this compound in solution. 31 P NMR (243 MHz, Methylene Chloride-d2): δ = 44.97. 19 F NMR (564 MHz, Methylene Chloride-d2): δ = -79.43. 154 FT-IR (thin film/cm -1 ) ν = 3584, 3441, 2956, 2917, 2238, 2078, 1589, 1479, 1433, 1392, 1371, 1264, 1224, 1158, 1031, 822, 770, 638. MS (MALDI) calc’d for [C30H53Ir2N2O4P2] + 951.3 g/mol, found 951.1 g/mol. 1 H NMR spectrum of complex 3.3b at 25 °C in CD2Cl2. 155 13 C NMR spectrum of complex 3.3b at 25 °C in CD2Cl2. 31 P NMR spectrum of complex 3.3b at 25 °C in CD2Cl2. 156 19 F NMR spectrum of complex 3.3b at 25 °C in CD2Cl2. 157 6.3.2. Dehydrogenation Procedures Dehydrogenation Procedures The dehydrogenation of formic acid can generally be performed by preparing a stock solution of the catalysts. In the drybox, formate and the iridium precatalyst are dissolved in either formic acid or tetraglyme solvent. The resulting orange solution slowly turns pale yellow over the course of ca. 1 hour. The solution is allowed to sit for several hours or overnight before the catalyst is used for dehydrogenation reactions. Method 1: Reactions Followed to Completion In the drybox, a 0.5 mL aliquot of a stock solution is transferred into a 5 mL high pressure reaction flask possessing a side arm and a large bore plug valve. The flask is then taken out of the drybox and connected to a vent line leading to a gas burette filled with oil (a eudiometer). To follow the reaction to completion, a 1000 mL gas burette is used. The reaction flask is heated to 90 °C in an oil bath for ca. 15 minutes before opening the valve. The volume of gas produced over time is recorded. Some portion of the liquid formic acid vaporizes and re-condenses in the head space of the flask and gas evacuation tube, which prevents complete conversion. Method 2: Accurate Measurements of Initial Rates In the dry box, a 0.5 mL aliquot of a stock solution is transferred into a 5 mL reaction flask possessing a large bore plug valve and a side arm. This flask is taken out of the drybox and the sidearm is connected to a three-way valve, which is connected to a nitrogen line and a 50.00 mL gas buret. The tubing and gas burette are purged with nitrogen for ca. 15 minutes. The reaction flask is then heated in an oil bath to 86 °C. Because the oil bath temperature increases after initial heating, the reaction is heated for ca. 15 minutes before readings are taken to allow the temperature to equilibrate. The volume of gas formed over time was then recorded. The initial rate of formic 158 acid decomposition (average of two runs) was obtained from a plot of moles of formic acid decomposed versus time (20 data points were obtained in each experiment). 159 6.3.3. Kinetic Profile for Dehydrogenation of Formic Acid Allows Use of the Method of Initial Rates The dehydrogenation of a formic acid solution which was initially 0.005 mol% (50 ppm) in iridium atoms and 5 mol% in sodium formate was followed. The volume of gas produced can be recorded and converted to the number of moles of formic acid decomposed. One mole of formic acid produces 48.91 L of gas (24.49 L of H2 and 24.42 L of CO2). 9 A plot of moles of formic acid decomposed versus time can then be constructed and the rate of formic acid decomposition at any point over the course of the reaction can be measured (Chapter 3, Figure 3.2). Because the rate is constant at the beginning of the reaction, we can use the method of initial rates to study the reaction order of the three reagents involved in the reaction: the iridium catalyst, the base, and formic acid. We also used the method of initial rates to directly compare the dehydrogenation rates when different bases are utilized, to construct an Eyring plot, to measure kinetic isotope effects, and to determine the effect of water and of different poisons (i.e. mercury and phenanthroline). 160 6.3.4. Dehydrogenation Rates Using Different Bases Formic acid stock solutions that were 0.005 mol% (50 ppm) in [Ir atom] and 5 mol% in base were prepared in the drybox by adding measured amounts of the iridium catalyst (1.8 mg, 2.6 μmol) and base (see Chapter 3, Table 3.2) into a vial. Formic acid (2.0 mL) was then added to dissolve the base and the catalyst. These experiments were aimed to determine the effect of different bases on the rate of dehydrogenation. In addition, these experiments allowed evaluation of the effect on dehydrogenation by the Lewis acids Li + , Na + , K + , and Ca 2+ . The initial rates of formic acid decomposition (average of two runs) were obtained using Method 2 (see Section 6.3.2). According to Table 3.2, base is required for dehydrogenation to occur efficiently. However, the types of bases and Lewis acids do not have an effect on the rate of dehydrogenation. One outlier, the data for calcium carbonate, gives a much lower decomposition rate because copious amounts of calcium formate precipitates. 161 6.3.5. Effect of Water on the Dehydrogenation Rate In the drybox, a formic acid stock solution that was 0.005 mol% (50 ppm) in iridium precatalyst 1 and 5 mol% in sodium formate was prepared by dissolving 1.8 mg (2.6 μmol) of 3.1 and 180 mg (2.64 mmol) of sodium formate in 2.0 mL of formic acid. 0.5 mL of this stock solution was transferred into a 5 mL reaction flask possessing a large bore plug valve and a side arm. Water is added according to the amounts shown in Table 6.3.1. Additional formic acid is added accordingly to make a 0.55 mL solution, which was used to measure the rates of formic acid decomposition using Method 2 (see Section 6.3.2). A log/log plot of the rate of formic acid decomposition versus the water concentration (Chapter 3, Figure 3.3) yields a slope of 0.11(5). Thus, water does not inhibit the rate of dehydrogenation. Table 6.3.1. Data used to obtain the double logarithmic plot for determining reaction order in water (formic acid solvent). Water added (μL) [Water] (M) [Ir] (mM) [NaO2CH] (M) [FA] (M) Rate (10 -8 mol s -1 ) a 10 1.14 1.14 1.14 24.96 5.0(3) 20 2.28 1.14 1.14 24.48 4.9(8) 40 4.54 1.14 1.14 23.52 5.4(6) 50 5.68 1.14 1.14 23.04 6.1(3) a Obtained at 86 °C; average of two runs, error is one standard deviation. 162 6.3.6. Comparison of Dehydrogenation Rates in the Presence and Absence of Air A formic acid stock solution that is 0.005 mol% in the iridium precatalyst and 5 mol% in sodium was prepared in air by adding 1.8 mg (2.6 μmol) of the iridium precatalyst and 180 mg (2.64 mmol) of sodium formate into a vial. In air, formic acid (2.0 mL) was then added to dissolve the base and the precatalyst. Dehydrogenation rates were obtained 1 day and 2 weeks after preparation of the stock solution using Method 2 (see Section 6.3.1). Under otherwise identical conditions, the dehydrogenation of reaction mixtures prepared in air is ca. 3 times slower (see Chapter 3, Table 3.3). 163 6.3.7. Catalyst Reusability in the Presence of Air A high pressure reaction flask possessing a side arm and a large bore plug valve was charged with the iridium catalyst (6.1 mg, 8.8 μmol) and sodium formate (184.1 mg, 2.7 mmol). In air, formic acid (0.5 mL, 13.2 mmol) was added. The color of the solution slowly changes from orange to pale yellow over the course of 1 hour. The flask was connected to a gas burette and heated to 90 °C. Formic acid decomposition was allowed to proceed until mostly solid catalysts remained. The volume of gas produced over time was recorded. The flask was then allowed to cool to room temperature, opened in air, and recharged with 0.5 mL of formic acid. This procedure was repeated dozens of times without significant loss in catalyst activity (Table 6.3.2). We measured the initial rates and the maximum turnover frequencies for the 1 st , 10 th , 20 th , 30 th , 40 th and 50 th loadings (Chapter 3, Table 3.4). Indeed, the rates and maximum turnover frequencies are comparable and the catalyst activity is still high after the 50 th loading. Interestingly, we note that both the initial rates and the maximum turnover frequencies increased over ten cycles before gradually slowing. After 50 loadings, 28.85 L of gas were produced, corresponding to a turnover number of 66,403 and 89% conversion. 164 Table 6.3.2. Data showing reusability of the catalyst in air. Run Volume (mL) a Time (min) b Run Volume (mL) a Time (min) b 1 c 417 120 26 570 90 2 505 90 27 600 90 3 c 512 150 28 610 90 4 513 120 29 580 75 5 560 120 30 a 565 60 6 570 75 31 510 120 7 541 90 32 540 90 8 620 90 33 620 90 9 585 120 34 570 120 10 c 619 90 35 610 120 11 607 80 36 600 75 12 550 60 37 600 75 13 605 120 38 590 120 14 600 90 39 565 90 15 605 130 40 a 580 75 16 585 90 41 600 120 17 584 90 42 570 120 18 583 90 43 570 120 19 580 90 44 560 120 20 c 595 80 45 590 120 21 549 150 46 580 120 22 540 110 47 640 120 23 580 90 48 650 120 24 580 80 49 600 120 25 530 90 50 a 670 120 a Measured using a 1000 mL gas buret. b Heating was stopped when mostly solid sodium formate and catalyst was present in the reaction flask. c The initial rates and maximum turnover frequencies were measured (Chapter 3, Table 3.4). 165 6.3.8. High Turnover Number and High Turnover Frequency Experiments High Turnover Number Experiments In the drybox, a 5 mL high pressure reaction flask with a side arm and a large bore plug valve was charged with sodium formate (0.18 g, 2.64 mmol), which was then dissolved in 0.6 mL of formic acid. A stock solution of the iridium precatalyst (which is actually a stock solution of the iridium dimer catalyst) in formic acid was added (100 μL, 1.26 mM precatalyst stock solution, 0.13 μmol precatalyst). The reaction flask was taken out of the drybox and connected to a vent line leading to a 1 L gas burette filled with oil. The flask was heated to 90 °C for 24 hours. After 24 h, 420 mL of gas was produced. One mole of formic acid decomposes to form 48.91 L of gas (24.49 L of H 2 and 24.42 L of CO2), 9 420 mL of gas produced therefore corresponds to 8.6 mmol of formic acid decomposed and a turnover number of 67,615. At the end of the reaction, a white solid residue remains at the bottom of the flask. Not all of the formic acid is decomposed because some of the formic acid ends up on the neck and the side arm of the flask and does not mix with the catalyst. Nevertheless, we can recharge the reaction flask with formic acid. To do this, we disconnect the sealed reaction flask from the gas buret, clean the side arm with acetone, and take the flask back into the drybox to be refilled with formic acid. Then we repeat this procedure through 40 cycles. After 40 cycles over a period of 4 months, 13.71 L of gas were produced (Chapter 3, Table 3.5). This corresponds to 0.28 mol of formic acid decomposed and 2.16 M turnovers. The catalyst has slowly lost its catalytic activity. After 4 months, ca. 15% of the initial catalytic activity remains. 166 High Turnover Frequency Experiment In the drybox, a 5 mL high pressure reaction flask with a side arm is charged with sodium formate (180 mg, 2.64 mmol) and formic acid (0.3 mL). A stock solution in formic acid of the iridium precatalyst (which is actually a stock solution of the iridium dimer catalyst) was added (100 μL, 1.26 mM precatalyst stock solution, 0.13 μmol precatalyst). The reaction flask was taken out of the drybox and connected to a 1000 mL gas burette filled with oil. The flask was heated to 90 °C. The reaction progress was followed and volume readings were collected towards the end of the reaction, when the rate of formic decomposition was fastest. The fastest rate of gas production recorded was 21 mL over a period of 15 minutes. This corresponds to a maximum turnover frequency of 3.7 s -1 . 167 6.3.9. GC and IR Analyses of the Composition of the Gaseous Products from Formic Acid Dehydrogenation Dehydrogenation in the Presence of Air (GC Data) To a Schlenk test tube containing the iridium precatalyst (5.8 mg, 8.4 μmol) and NaO2CH (182.6 mg, 2.7 mmol) was added, in air, 0.5 mL of formic acid. The Schlenk test tube was connected to a three-way valve which was connected to a balloon. The reaction flask was heated to 90 °C. The gaseous products were collected in the balloon until almost all formic acid was decomposed and their composition analyzed by gas chromatography using a thermal conductivity detector. Three runs were performed. A 1:1 mole ratio of H2 and CO2 was detected along with small amounts of oxygen and nitrogen (Chapter 3, Figure 3.4A, carbon monoxide was not detected; thus, the carbon monoxide level is < 0.099 v/v %). Dehydrogenation in the Absence of Air (GC Data) In the drybox, a Schlenk test tube containing a solution of the iridium precatalyst (0.7 mg, 1.0 μmol) and Na2CO3 (85 mg, 0.8 mmol) in 0.35 mL of formic acid was prepared and sealed. The Schlenk test tube was taken out of the drybox and connected to a three-way valve, which was connected to a nitrogen valve and a balloon. The balloon was purged with nitrogen three times. The reaction flask was heated to 110 °C. The gaseous products were collected in the balloon, emptying and refilling twice before collecting the sample for analysis in order to remove as much nitrogen gas as possible. The composition of the gaseous products was analyzed by gas chromatography using a thermal conductivity detector. Three runs were performed. A 1:1 mole ratio of H2 and CO2 was detected along with a small amount of residual nitrogen (Chapter 3, Figure 3.4B, carbon monoxide was not detected; thus, the carbon monoxide level is < 0.099 v/v %). 168 Setting a Lower Boundary on the CO Byproduct (IR Data) For long-term fuel cell applications, the amount of CO byproduct should be on the order of a few ppm. Since the detection limit of the GC utilized is 1000 ppm, we used IR spectroscopy, which can detect CO levels to a few ppm, to estimate the amount of CO produced in our dehydrogenation conditions. A 50 mL Schlenk tube was charged with iridium precatalyst 3.1 (6.1 mg, 8.9 μmol) and sodium formate (184.0 mg, 2.7 mmol), which were dissolved, in air, in 1.0 mL formic acid. The Schlenk test tube was connected to a three-way valve, which was connected to a 2 L gas burette. The gas burette was fitted with a vent line connected to a three-way valve, which allows for direct sampling of the gaseous products for IR analysis. The reaction flask was heated to 90 °C. Gaseous products were collected until 1.1 L of gas was produced (ca. 5 hours). An aliquot for IR analysis was transferred using a syringe into a Harrick temperature controlled gas cell (10 cm path length, 17 mL cell volume), which had been evacuated under reduced pressure. IR data (1 cm -1 resolution) was then obtained on a Bruker Vertex 80v FT-IR instrument equipped with a DTGS detector. Unlike a spectrum of commercial gaseous CO2 (Chapter 3, Figure 3.5A), CO can be observed in the IR spectrum of the gaseous reaction products (Figure 3.5B). Using a calibration curve of different CO concentrations in air matrix, we estimated the CO concentration to be ca. 500 ppm. We also performed dehydrogenation of 5 mL of neat formic using the same catalyst loading over a period of 60 hours. In this case, the CO concentration was estimated to be ca. 2000 ppm. It is known that neat formic acid decomposes in the presence of concentrated acid 10 or at high temperatures 11 to form H2O and CO. We therefore hypothesized that much of the CO produced in our reaction conditions may be forming because of thermal, uncatalyzed decomposition of neat formic acid. To test for this situation, we dissolved 180 mg of sodium 169 formate in 1 mL of formic acid and heated this solution in a sealed 100 mL pear flask for 2 hours at 90 C. The solution was then allowed to cool to room temperature and a sample of the headspace gases was analyzed by IR. Indeed, even after only 2 hours of heating, copious amounts of CO (which was estimated to > 5000 ppm) had formed as seen in the IR spectrum in Chapter 3, Figure 3.6. Because it is known that neat formic acid thermally decomposes to produce H 2O and CO, and that the presence of water decreases the rate of this decomposition, 11 we reasoned that we might be able to suppress CO production by using 10 vol% H2O/FA instead of neat formic acid as the dehydrogenation medium. Thus, a 50 mL Schlenk tube was charged with iridium precatalyst 3.1 (30.2 mg, 44.0 μmol) and sodium formate (181.0 mg, 2.7 mmol), which were dissolved, in air, in 1.0 mL formic acid. The mixture was allowed to sit overnight. The light orange homogeneous solution was then heated to 90 °C for 1 hour forming 840 mL of gas. Gratifyingly, the IR spectrum of the gaseous products shows much lower levels of CO. Comparing the CO signal from the gaseous products to an independently-prepared ca. 10 ppm CO solution in air, we estimate that the CO produced is less than 10 ppm. Moreover, we reasoned that we might be able to decrease the CO production using neat formic acid by using solutions that are highly concentrated in sodium formate. Thus, in the drybox, we prepared a solution of 26 mg (38 μmol) of the iridium precatalyst and 900 mg (13.2 mmol) of sodium formate in 1 mL formic acid and allowed the mixture to sit overnight. The mixture was then taken out of the drybox and exposed to air. The supersaturated, very viscous mixture was heated to 90 °C for 2 hours, producing 950 mL of gaseous products. Gratifyingly, the IR spectrum of the products shows almost undetectable levels of CO (Chapter 3, Figure 3.7). We then repeated this reaction at a lower temperature. A solution of 30 mg (44 μmol) of the iridium precatalyst and 170 900 mg of the sodium formate in 1 mL formic acid was prepared in the drybox and allowed to sit overnight. Taking the Schlenk tube out of the box and heating the supersaturated solution to 70 °C for 6 hours results in the production 550 mL of gas. IR analysis of the gaseous products shows levels of CO below 10 ppm (Figure 6.3.1). Figure 6.3.1. Comparison of IR spectra of gaseous products from supersaturated sodium formate solution of neat FA heated at 70 C for 6 hours and ca. 10 ppm CO in air matrix. 171 6.3.10. Experiments that Support Homogeneous Catalysis Visual Appearance The reaction mixture is a translucent pale yellow solution during catalysis, with no dark precipitates forming. At the end of the reaction, a pale orange solid (the catalysts) remains. Well Behaved Kinetics The reaction follows well-behaved saturation catalysis kinetics through its pseudo-zero order region, which persists until solvent level drops appreciably as solvent is consumed (see Chapter 3, Figure 3.2). Mercury Drop Test The mercury drop test was performed by placing 0.5 mL of a formic acid stock solution with 0.01 mol% in iridium precatalyst 3.1 and 5 mol% sodium formate into a 5 mL reaction flask possessing a large bore plug valve and a side arm. A drop of mercury was then added to this solution. The rate of formic acid decomposition (average of two runs) was then measured to be 1.24 ×10 -7 mol s -1 at 90 °C, which is just slightly slower compared to the measured rate of formic acid decomposition in the absence of mercury (1.35 ×10 -7 mol s -1 ). Quantitative Poisoning Phenanthroline was utilized as catalytic poison. 1.00 mL (1.26 μmol iridium) of a formic acid solution that is 1.26 mM in iridium atom and 1.26 M in sodium formate was placed in a 2 mL volumetric flask. One-half mole equivalent of the poison relative to the iridium catalyst was added as a stock solution in formic acid (100 μL of 6.3 mM solution, 0.63 μmol). The solution was diluted to 2.00 mL. Using 0.5 mL of this solution, the rate of formic acid decomposition (average of two runs) was measured to be 1.27 ×10 -8 mol s -1 at 86 °C, which is 62% of the formic acid decomposition rate in the absence of phenanthroline (which was measured as 2.04 ×10 -8 mol s -1 ). 172 6.3.11. Observation of Catalyst Intermediates by NMR Data regarding the elementary steps of the conversion of the precatalyst to the active dimer catalyst were obtained using NMR. We can observe the formation of a Pfaltz/Fryzuk-type dimer 3.2 from precatalyst 3.1 in two different ways: 1) reaction of 3.1 with formic acid in a coordinating solvent such as acetonitrile or 2) reaction of 3.1 with H2 in various solvents. In formic acid solvent, iridium dimer 3.2 is converted further into the (di- -formate)iridium dimer 3.3a (see Scheme 3.3). Observation of Intermediate 3.2 in CD3CN Room temperature 1 H NMR studies in CD3CN show that addition of one equivalent of sodium formate and ten equivalents of formic acid to a solution of iridium precatalyst 1 leads to formation of a new species (intermediate A) with a hydride signal at -19.43 ppm (Chapter 3, Figures 3.8 and 3.9). Data for this species is consistent with oxidative addition of formic acid to the iridium precatalyst. 20 minutes after addition of sodium formate and formic acid, a time course experiment was collected over a period of 66 minutes. The resulting stacked 1 H NMR spectra shows that intermediate A grows then intermediate B appears ca. 30 minutes after addition of sodium formate and formic acid. Intermediate B is consistent with a species where one of the cyclooctadiene double bonds is bound to iridium and the other is free. Then the final product (a Pfaltz/Fryzuk-type dimer) appears ca. 1 hour after addition. The 1 H NMR spectrum of the final product is consistent with dimer 3.2 (Figure 3.9; solv = CD3CN). The cyclooctadiene in the iridium precatalyst is reduced to cyclooctene and free cyclooctene is seen in the 1 H NMR spectrum of the products. Although 3.3 does not form in CD3CN, it is reasonable to conclude that formation of the catalyst resting state (diformate 3.3a) proceeds in a similar fashion through the intermediacy of 3.2 when formic acid or tetraglyme is used as solvent. It is worth noting that, in CD3CN, iridium 3.1 reacts in the absence of base with formic acid to form 3.2, but in a much slower rate. 173 Observation of Intermediates 3.3a and 3.4 in Formic Acid We studied the catalyst resting state(s) in formic acid by dissolving, in the drybox, 10.0 mg of the iridium precatalyst and 10.0 mg of sodium formate in 1.0 mL of proteo formic acid in a J- Young tube. The J-Young tube was taken out of the drybox and was connected to a three-way valve, which was connected to a nitrogen line and a 50.0 mL gas buret. The tubing and the gas burette were purged with nitrogen for ca. 15 minutes. The plug valve and the three-way valve were opened such that gas produced go directly to the gas buret. The reaction flask was heated in an oil bath to 70 °C. About 15 mL of gas was produced during heating. The solution was then allowed to cool to room temperature. The proteo formic acid solvent was evaporated under high vacuum and the resulting residue was left under high vacuum overnight. The residue was then dissolved in formic acid-d2. The 1 H NMR spectrum of the residue is shown in Chapter 3, Figure 3.11. Examination of the hydride region reveals two resting states: (A) a minor resting state with two different hydrides at -27.24 and -28.51 ppm that integrate in a 2:1 ratio (consistent with the hydrides in the 1 H NMR of 3.3b, whose X-ray structure is known). We formulate this species as dimer 3.3a. (B) The major resting state contains three different hydrides at -19.41, -25.05, and - 27.13 ppm. We formulate this species as dimer 3.4 (see Section 3.3.2). 174 6.3.12. Kinetic Isotope Effect Studies To obtain values for kH/kD, the initial rates of dehydrogenation using formic acid, formic acid-d2, formic acid-d1 (O–D), and formic acid-d1 (C–D) were obtained. Stock solutions of formic acid, formic acid-d2, formic acid-d1 (C‒D), and formic acid-d1 (O‒D) that were 0.005 mol% (50 ppm) in iridium precatalyst 3.1 and 5 mol% in formate were prepared. In the drybox, a vial was charged with 1.8 mg (2.6 μmol) of the iridium precatalyst and 180 mg of either sodium formate (for the FA and FA-d1 (O‒D) solutions) or sodium formate-d1 (for the FA-d2 and FA-d1 (C‒D) solutions). The appropriate proteo/deutero formic acid (2.0 mL) was then added to dissolve the base and the precatalyst. The solution was allowed to sit overnight before use. The initial rates of formic acid decomposition were obtained using Method 2 (see Section 6.3.2). Table 6.3.3 shows the initial rates of dehydrogenation using different isotopologues of formic acid. See Section 3.3.3 for the obtained kinetic isotope effects. Table 6.3.3. Data for kinetic isotope effect studies. Compound Rate (10 -8 mol s -1 ) a HCO2H 6.1(2) HCO2D 1.55(14) DCO2H 3.4(2) DCO2D 0.94(2) a Obtained at 86 °C; average of two runs, error is one standard deviation. 175 6.3.13. Proton-Hydride Fidelity Experiment In the drybox, a J-Young tube was charged with the iridium precatalyst (1.8 mg, 2.64 μmol), sodium formate (1.7 mg, 25.0 μmol), formic acid-d1 (O‒D; 5 μL, 0.13 mmol), and 0.6 mL of methanol-d4. A 1 H NMR time course experiment spanning over 72 minutes was performed at 70 °C. Before the time course experiment was begun, the NMR tube had been heated ca. 10 minutes at 70 °C and much H‒D had formed (see Chapter 3, Figure 3.14). Nevertheless, formation of predominantly H‒D with a small amount of H2 is observed. This observation is consistent with a formic acid dehydrogenation mechanism that proceeds through formation of an iridium monohydride where the hydride comes from the formyl C‒H bond of formic acid. This iridium monohydride is then protonated (or, technically, deuterated) by the formic acid O‒D. We expect that an iridium dihydride that undergoes reductive elimination to yield H2 should enable scrambling of proton and hydride, thus we disfavor this possibility. The small amount of H2 that forms can be rationalized by the presence of small amounts of formic acid O‒H bonds which protonates the iridium monohydride. Interestingly, the H‒D signal disappears after extended heating, which is consistent with a slow reverse reaction when the reaction is run in a sealed vessel. Such back reaction is impossible under our kinetics acquisition conditions because the H2 product is sequestered and quantified in an eudiometer. 176 6.3.14. Eyring Plot In the drybox, a formic acid solution that is 5 mol% in sodium formate was prepared by dissolving sodium formate (901 mg, 13.2 mmol) in formic acid (10.0 mL, 265 mmol). To this solution was added the iridium precatalyst (18.2 mg, 26.2 μmol) to make a stock solution of the catalyst (2.52 mM based on monoiridium). The solution is allowed to sit overnight before use. The initial rates of formic acid decomposition were obtained using Method 2 (see Section 6.3.2). Figure 6.3.2 is a sample plot showing a constant initial formic acid decomposition rate. Table 6.3.4 shows the initial rates and turnover frequencies at 60, 70, 80, 90, and 100 °C. An Eyring plot was constructed utilizing the measured turnover frequencies (Chapter 3, Figure 3.15). From the Eyring plot, ∆H ‡ = +29.0(4) kcal mol -1 and ∆S ‡ = +16.0(10) eu. Figure 6.3.2. Sample plot of moles of formic acid decomposed versus time (Eyring plot data). 177 Table 6.3.4. Data used for the Eyring plot. Temperature (°C) Rate (10 -9 mol s -1 ) a Turnover Frequency (10 -3 s -1 ) b 60 2.5(2) 2.0 70 9(1) 7.2 80 32(2) 24.9 90 109(3) 86.1 100 296(5) 233.8 a Obtained at 86 °C; average of two runs, error is one standard deviation. b Obtained by dividing the rate of formic acid decomposition with the moles of iridium precatalyst in a 0.5 mL aliquot of the stock solution (2.52 mM in iridium). 178 6.3.15. Kinetic Studies on Iridium Dependence in Neat Formic Acid In the drybox, a formic acid solution that is 5 mol% in sodium formate was prepared by dissolving sodium formate (901 mg, 13.2 mmol) in formic acid (10.0 mL, 265 mmol). To this solution was added the iridium precatalyst (9.1 mg, 13.1 μmol) to make a stock solution that is 0.005 mol% in the precatalyst (1.26 mM, 50 ppm, based on iridium atom). To set-up solutions for kinetics experiments, in the drybox, 1.0 mL of the catalyst stock solution is transferred via syringe to a 2 mL volumetric flask. A weighed amount of solid catalyst is added (see Table 6.3.5 for exact amounts). Formic acid is then added to make 2.00 mL of solution. The initial rates of formic acid decomposition were obtained using Method 2 (see Section 6.3.2). Figure 6.3.3 is a sample plot showing a constant initial formic acid decomposition rate. Table 6.3.5 shows the initial rates at different [Ir]. A plot of log (rate of formic acid decomposition) versus log [Ir] shows that the reaction order is 0.95(3) in iridium catalyst (Chapter 3, Figure 3.16, left; the error is standard error of fit). Thus, the reaction is first order in iridium. Figure 6.3.3. Sample plot of moles of formic acid decomposed versus time (formic acid solvent). y = 0.0206x + 5.2221 R² = 0.999 0 20 40 60 80 100 120 0 1000 2000 3000 4000 5000 Moles of HCO 2 H Decomposed (× 10 - 6 ) Time (s) 0.63 mM Ir - Run 1 179 Table 6.3.5. Data used to obtain the double logarithmic plot for determining reaction order in iridium (formic acid solvent). Additional mass of Ir added (mg) [Ir] in reaction mixture (mM) [NaO2CH] in reaction mixture (M) [FA] in reaction mixture (M) Rate of HCO2H Decomposition (10 -8 mol s -1 ) a 0 0.63 0.63 25.9 2.0(1) 1.7 1.86 0.63 25.9 6.0(6) 2.7 2.59 0.63 25.9 8.0(2) 3.6 3.25 0.63 25.9 9.3(5) 5.2 4.41 0.63 25.9 13(1) a Obtained at 86 °C; average of two runs, error is one standard deviation. 180 6.3.16. Kinetic Studies on Sodium Formate Dependence in Neat Formic Acid In the drybox, a formic acid stock solution that is 0.53 mM in sodium formate was prepared by dissolving sodium formate (360 mg, 5.3 mmol) in formic acid (10.0 mL, 265 mmol). To this solution was added iridium complex 1 (9.1 mg, 13.1 μmol). To set up solutions for kinetics experiments, 1.0 mL of the catalyst stock solution is transferred via syringe to a 2 mL volumetric flask in the drybox. A portion of sodium formate is added (see Table 6.3.6). Formic acid is then added to make 2.00 mL of solution. The initial rates of formic acid decomposition were obtained using Method 2 (see Section 6.3.2). Table 6.3.6 shows the initial rates at different [NaO2CH]. A plot of log (rate of formic acid decomposition) versus log [NaO2CH] shows that the reaction order is 0.64(5) in sodium formate (Chapter 3, Figure 3.16, right; the error is standard error of fit). Thus, the reaction is half-order in NaO2CH. Table 6.3.6. Data used to obtain the double logarithmic plot for determining reaction order in sodium formate (formic acid solvent). Added NaO2CH (mg) [Ir] (mM) [NaO2CH] (M) [FA] (M) Rate (10 -8 mol s -1 ) a 0 0.66 0.26 26.26 1.4(3) 72 0.66 0.53 26.01 1.8(1) 144 0.66 1.06 25.51 2.8(1) 216 0.66 1.59 25.01 3.6(2) 288 0.66 2.11 24.51 5.3(1) 360 0.66 2.65 24.01 6.0(4) a Obtained at 86 °C; average of two runs, error is one standard deviation. 181 6.3.17. Kinetic Studies on Iridium Dependence in Tetraglyme Solvent In the drybox, a stock solution of iridium in tetraglyme (2.64 mM) was prepared by dissolving the iridium precatalyst 3.1 (18.2 mg, 26.46 mmol) in a volumetric flask to make 10.00 mL of stock solution in tetraglyme. Because sodium formate is insoluble in tetraglyme, we generated soluble (n-Bu)4N(HCO2) by deprotonating formic acid with 1.20 M (n-Bu)4N(OH) in methanol. (n-Bu)4N(OH) was titrated using benzoic acid and bromothymol blue as indicator. To set-up solutions for kinetics experiments, a 2 mL volumetric flask is filled with ca. 1 mL of tetraglyme in the drybox. Then 22 μL of 1.21 M (n-Bu)4N(OH) in methanol and 21 μL of formic acid are added and the solution thoroughly mixed. A measured amount of the iridium catalyst stock solution (see Table 6.3.7) is added and the solution thoroughly mixed. The color of the solution changes immediately from orange to very pale yellow. Tetraglyme is then added to make 2.00 mL of solution. Using this freshly prepared solution, the initial rates of formic acid decomposition were obtained using Method 2 (see Section 6.3.2), except that a Schlenk test tube with a side-arm is utilized instead of a 5 mL high pressure reaction vessel. Figure 6.3.4 is a sample plot showing a constant initial formic acid decomposition rate. Table 6.3.7 shows the initial rates at diffirent [Ir]. A plot of log (rate of formic acid decomposition) versus log [Ir] shows that the reaction order is 0.96(4) in iridium catalyst (Chapter 3, Figure 3.17, top left; error is standard error of fit). Thus, the reaction is first order in iridium. 182 Figure 6.3.4. Sample plot of log of formic acid decomposed versus time (tetraglyme solvent). Table 6.3.7. Data used to obtain double logarithmic plot for determining reaction order in iridium (tetraglyme solvent). FA added (nBu)4N(OH) solution Ir solution [Ir] ( M) [(nBu)4N(O2CH)] (mM) [FA] (mM) Rate (10 -8 mol s -1 ) a 21 μL, 0.53 mmol 22 μL, 26.4 μmol 50 μL, 0.13 μmol 66 13.2 265 1.3(1) 21 μL, 0.53 mmol 22 μL, 26.4 μmol 100 μL 0.26 μmol 130 13.2 265 2.7(2) 21 μL, 0.53 mmol 22 μL, 26.4 μmol 150 μL 0.39 μmol 200 13.2 265 3.6(2) 21 μL, 0.53 mmol 22 μL, 26.4 μmol 200 μL 0.52 μmol 260 13.2 265 5.3(1) 21 μL, 0.53 mmol 22 μL, 26.4 μmol 250 μL 0.65 μmol 330 13.2 265 6.1(1) a Obtained at 86 °C; average of two runs, error is one standard deviation. y = 0.0132x + 0.1606 R² = 0.9996 0 10 20 30 40 50 60 70 80 0 1000 2000 3000 4000 5000 6000 Moles of HCO 2 H Decomposed (× 10 -6 ) Time (s) 0.066 mM Ir in Tetraglyme - Run 1 183 6.3.18. Kinetic Studies on Tetra-n-butylammonium Formate Dependence in Tetraglyme Solvent In the drybox, a stock solution of the iridium precatalyst in tetraglyme (1.32 mM) was prepared by dissolving the iridium precatalyst (9.1 mg, 13.23 mmol) in a volumetric flask to make 10.00 mL of solution. Using this stock solution, kinetics data were obtained according to the procedure described in Section 6.3.13 except that (n-Bu)4N(O2CH) concentration was varied instead of iridium concentration. Also, methanol was added so that each solution had the same amount of methanol. The concentrations of (n-Bu)4N(O2CH) used are shown in Table 6.3.8. A log/log plot of rate of formic acid decomposition versus (n-Bu)4N(O2CH) concentration shows a reaction order of 0.44(2) (Chapter 3, Figure 3.17, top right; error is standard error of fit). This indicates a reaction order of 0.5 with respect to (n-Bu)4N(O2CH). Table 6.3.8. Data used to obtain double logarithmic plot for determining reaction order in formate (tetraglyme solvent). FA added (nBu)4N(OH) solution Ir solution [Ir] ( M) [(nBu)4N(O2CH)] (mM) [FA] (mM) Rate (10 -8 mol s -1 ) a 21 μL, 0.53 mmol 22 μL, 26.4 μmol 100 μL 0.13 μmol 66 13.2 265 1.3(1) b 22 μL, 0.53 mmol 44 μL, 52.8 μmol 100 μL 0.13 μmol 66 26.4 265 1.7(1) 23 μL, 0.53 mmol 66 μL, 79.2 μmol 100 μL 0.13 μmol 66 39.6 265 2.0(1) 24 μL, 0.53 mmol 88 μL, 105.6 μmol 100 μL 0.13 μmol 66 52.8 265 2.4(1) 25 μL, 0.53 mmol 110 μL, 132 μmol 100 μL 0.13 μmol 66 66.0 265 2.6(1) a Obtained at 86 °C; average of two runs, error is one standard deviation. b Data from Table 6.3.7. 184 6.3.19. Kinetic Studies on Formic Acid Dependence in Tetraglyme Solvent In the drybox, a stock solution of the iridium precatalyst in tetraglyme (2.64 mM) was prepared by dissolving the iridium precatalyst (18.2 mg, 26.46 mmol) in a volumetric flask to make 10.00 mL of solution. Using this stock solution, kinetics data were obtained according to the procedure described in Section 7.3.13 except that formic acid concentration was varied instead of iridium concentration. The concentrations of formic acid used are shown in Table 6.3.9. A log/log plot of rate of formic acid decomposition versus formic acid concentration shows a reaction order of -0.94(9) (Chapter 3, Figure 3.17, bottom; error is standard error of fit). This indicates a reaction order of -1.0 with respect to formic acid. Table 6.3.9. Data used to obtain double logarithmic plot for determining reaction order in formic acid (tetraglyme solvent). FA added (nBu)4N(OH) solution Ir solution [Ir] ( M) [(nBu)4N(O2CH)] (mM) [FA] (mM) Rate (10 -8 mol s -1 ) a 21 μL, 0.53 mmol 22 μL, 26.4 μmol 200 μL 0.52 μmol 260 13.2 265 5.3(1) b 26 μL, 0.66 mmol 22 μL, 26.4 μmol 200 μL 0.52 μmol 260 13.2 331 3.8(2) 31 μL, 0.80 mmol 22 μL, 26.4 μmol 200 μL 0.52 μmol 260 13.2 398 3.5(1) 41 μL, 1.06 mmol 22 μL, 26.4 μmol 200 μL 0.52 μmol 260 13.2 530 2.6(1) 51 μL, 1.32 mmol 22 μL, 26.4 μmol 200 μL 0.52 μmol 260 13.2 662 2.2(1) a Obtained at 86 °C; average of two runs, error is one standard deviation. b Data from Table 6.3.7. 185 6.3.20. Synthesis of Complexes for the Systematic Ligand Variation Studies Formic acid dehydrogenation rates were measured using method 2 (see Section 6.3.2). Iridium complexes 3.9, 3.10, and 3.11 were synthesized using the same procedure used for the synthesis of complex 3.1 (see Section 6.3.1). The ligands 2-((di-tert-butylphosphino)methyl)-6- methylpyridine and 2-((diisopropylphosphino)methyl)pyridine were synthesized using the same procedure used for the synthesis of 2-((di-tert-butylphosphino)methyl)pyridine. 1 2- ((diphenylphosphino)methyl)pyridine was synthesized using a modified procedure (vide infra). Complex 3.12 was synthesized using a published procedure. 12 Complexes 3.13 and 3.14 were synthesized by Zhiyao Lu. And complexes 3.15 and 3.16 were purchased from Strem. Iridium 3.9 Complex 3.9 was synthesized using the procedure used for the synthesis of complex 3.1 (see Section 6.3.1). 2-(di-tert-butylphosphino)-6-methylpyridine (31.0 mg, 0.12 mmol), chloro(1,5-cyclooctadiene)iridium(I) dimer, (41.4 mg, 0.062 mmol), and sodium trifluoromethanesulfonate (39.0 mg, 0.22 mmol) were used. Pure product was isolated as an orange solid (74.0 mg, 85% yield). 1 H NMR (500 MHz, Methylene Chloride-d2) δ 8.08 (d, J = 5.9 Hz, 1H), 7.85 (d, J = 7.7 Hz, 1H), 7.36 (t, J = 6.8 Hz, 1H), 4.48 (d, J = 3.9 Hz, 4H), 3.46 (d, J = 8.9 Hz, 2H), 2.59 (s, 3H), 2.32 (d, J = 9.9 Hz, 4H), 1.31 (d, J = 13.6 Hz, 18H). 13 C NMR (126 MHz, Methylene Chloride-d2) δ 164.83, 146.75, 141.56, 134.09, 134.02, 124.25, 37.29, 37.15, 32.02, 31.83, 29.79, 29.76, 22.04. 31 P NMR (202 MHz, Methylene Chloride-d2) δ 54.11. HRMS (ESI/APCI): m/z = 552.2341 g/mol, calc’d. for C23H38IrNP + [M] + : 552.2366 g/mol. FT-IR (thin film/cm -1 ) ν = 2947, 2923, 2876, 2834, 2427, 2297, 1733, 1594, 1559, 1540, 1466, 1430, 1391, 1371, 1333, 1269, 1222, 1149, 1113, 1088, 1031, 966, 937, 893, 879, 825, 808. 186 1 H NMR spectrum of complex 3.9 at 25 °C in CD2Cl2. 13 C NMR spectrum of complex 3.9 at 25 °C in CD2Cl2. 187 NMR spectrum of complex 3.9 at 25 °C in CD2Cl2. IR spectrum of complex 3.9. 188 Iridium 3.10 Complex 3.10 was synthesized using the procedure used for the synthesis of complex 3.1 (see Section 6.3.1). 2-((diisopropylphosphino)methyl)pyridine (63.4 mg, 0.28 mmol), chloro(1,5- cyclooctadiene)iridium(I) dimer, (95 mg, 0.14 mmol), and sodium trifluoromethanesulfonate (100 mg, 0.58 mmol) were used. Pure product was isolated as an orange solid (99 mg, 70% yield). 1 H NMR (600 MHz, Methylene Chloride-d2) δ 8.33 – 8.28 (m, 1H), 8.08 (tt, J = 7.7, 1.3 Hz, 1H), 7.99 (d, J = 8.0 Hz, 1H), 7.48 (ddd, J = 7.4, 5.9, 1.5 Hz, 1H), 5.00 (tt, J = 4.9, 2.1 Hz, 2H), 4.16 (dt, J = 5.7, 2.3 Hz, 2H), 3.58 (d, J = 10.1 Hz, 2H), 2.45 (dp, J = 8.8, 7.1 Hz, 2H), 2.41 – 2.31 (m, 2H), 2.31 – 2.19 (m, 4H), 2.05 – 1.94 (m, 2H), 1.26 (dd, J = 16.6, 7.1 Hz, 6H), 1.12 (dd, J = 15.2, 6.9 Hz, 6H). 13 C NMR (151 MHz, Methylene Chloride-d2) δ 166.80, 149.79, 141.46, 125.10, 125.04, 124.44, 93.86, 93.79, 62.10, 33.47, 33.25, 33.06, 28.32, 24.51, 24.32, 18.53, 17.81. 31 P NMR (202 MHz, Methylene Chloride-d2) δ 47.68. MALDI: m/z = 510.2 g/mol, calc’d. for C20H32IrNP + [M] + : 509.7 g/mol. FT-IR (thin film/cm -1 ) ν = 3126, 3066, 2964, 2925, 2884, 2838, 2430, 2367, 1999,1720, 1609, 1564, 1542, 1471, 1450, 1390, 1373, 1334, 1270, 1224, 1152, 1109, 1083, 1083, 1069, 1032, 1002, 966, 934, 84, 823. 189 1 H NMR spectrum of complex 3.10 at 25 °C in CD2Cl2. 13 C NMR spectrum of complex 3.10 at 25 °C in CD2Cl2. 31 P NMR spectrum of complex 3.10 at 25 °C in CD2Cl2. 190 IR spectrum of complex 3.10. 191 Iridium 3.11 Complex 3.11 was synthesized using the procedure used for the synthesis of complex 3.1 (see Section 6.3.1). 2-((diphenylphosphino)methyl)pyridine (80.5 mg, 0.29 mmol), chloro(1,5- cyclooctadiene)iridium(I) dimer, (97.0 mg, 0.14 mmol), and sodium trifluoromethanesulfonate (39.0 mg, 0.22 mmol) were used. Pure product was isolated as an orange solid (140.0 mg, 67% yield). 1 H NMR (600 MHz, Methylene Chloride-d2) δ 8.42 (dd, J = 5.9, 1.5 Hz, 1H), 8.03 (tt, J = 7.8, 1.4 Hz, 1H), 7.86 (d, J = 7.9 Hz, 1H), 7.65 – 7.55 (m, 5H), 7.54 – 7.47 (m, 4H), 7.20 – 7.11 (m, 1H), 5.23 (d, J = 5.7 Hz, 2H), 4.30 (d, J = 10.9 Hz, 2H), 3.68 (d, J = 4.7 Hz, 2H), 2.35 (d, J = 16.9 Hz, 5H), 2.11 (t, J = 8.6 Hz, 4H). 13 C NMR (126 MHz, Methylene Chloride-d2) δ 163.65, 163.60, 150.44, 141.42, 138.02, 133.30, 133.21, 132.34, 132.32, 129.61, 129.53, 129.01, 128.20, 127.54, 127.11, 125.69, 125.60, 125.28, 124.94, 122.40, 119.84, 95.90, 95.80, 63.75, 41.42, 41.17, 32.91, 28.86, 21.20. 31 P NMR (202 MHz, Methylene Chloride-d2) δ 34.47. HRMS (ESI/APCI): m/z = 578.1605 g/mol, calc’d. for C26H28IrNP + [M] + : 578.1583 g/mol. FT-IR (thin film/cm -1 ) ν = 3056, 2963, 2919, 2886, 2836, 1608, 1564, 1475, 1436, 1475, 1436, 1400, 1334, 1310, 1267, 1223, 1152, 1104, 1066, 1030, 999, 966, 895, 842, 817. 192 1 H NMR spectrum of complex 3.11 at 25 °C in CD2Cl2. 13 C NMR spectrum of complex 3.11 at 25 °C in CD2Cl2. 193 31 P NMR spectrum of complex 3.11 at 25 °C in CD2Cl2. IR spectrum of complex 3.11. 194 2-((Diphenylphosphino)methyl)pyridine Ligand All reactions were kept strictly air-free using Schlenk and drybox techniques. The ligand was synthesized using a modified literature procedure. 13 A solution of 2-picoline (270 μL, 2.69 mmol) in 18 mL THF was cooled to -78 °C. n-BuLi (1.7 mL of a 1.56 M solution in hexanes, 2.69 mmol) was added dropwise over 15 minutes and the solution turns orange. The solution was allowed to warm to room temperature and stirred for 1 hour. A solution of diphenylchlorophosphine (0.5 mL 2.56 mmol) in 20 mL THF was then cooled to -94 °C in an acetone/liquid nitrogen slush bath. The orange pyridin-2-ylmethanide solution was added very slowly dropwise over 75 minutes while the slush bath was kept cold throughout. The resulting light yellow solution was allowed to warm slowly and stirred overnight. The solvent was evaporated in vacuo. The product was extracted with dichloromethane. The dichloromethane was evaporated in vacuo resulting in a mixture of yellow liquid and solid. The product was extracted with hexanes. After evaporation of the hexanes in vacuo, the product was obtained as a white solid (260 mg, 35% yield). 1 H NMR (600 MHz, Acetonitrile-d3) δ 8.39 (d, J = 2.6 Hz, 1H), 7.53 (t, J = 7.6 Hz, 1H), 7.50 – 7.41 (m, 4H), 7.34 (s, 6H), 7.09 (d, J = 7.8 Hz, 2H), 3.66 (s, 2H). 31 P NMR (202 MHz, Acetonitrile-d3) δ -11.55. Spectra are consistent with a known compound. 13 195 1 H NMR spectrum of 2-((diphenylphosphino)methyl)pyridine in CD3CN. 31 P NMR spectrum of 2-((diphenylphosphino)methyl)pyridine in CD3CN. 196 6.4. Chapter 4 Experimental and Spectral Data 6.4.1. Synthesis of Ruthenium 4.1 Complex 4.1 In the drybox under nitrogen, 2-((di-tert-butylphosphino)methyl)pyridine 1 (237 mg, 0.10 mmol) was dissolved in a dry vial in 5 mL of dry dichloromethane. In another vial containing a Teflon stir bar, dichloro(p-cymene)ruthenium(II) dimer (310 mg, 0.50 mmol) and sodium trifluoromethanesulfonate (330 mg, 1.90 mmol) were suspended in 10 mL of dry dichloromethane. The suspension was stirred vigorously and then the phosphinopyridine solution was added slowly dropwise. The phosphinopyridine vial was rinsed with 5 mL of dichloromethane and added to the stirred suspension. After stirring for 1 hour, the solution was filtered to remove the sodium chloride byproduct and the excess sodium triflate. The solvent was evaporated under reduced pressure to yield a glassy solid. Dry ether (10 mL) was added to the residue, which was then triturated by sonication. The ethyl ether was decanted and the residue washed with an additional 10 mL of ethyl ether. The pure ruthenium complex was dried under reduced pressure to give a yellow-orange solid (480 mg, 73%). Recrystallization from dichloromethane and toluene produced crystals suitable for X-ray crystallography. 1 H NMR (600 MHz, Methylene Chloride-d2) δ 9.21 (d, J = 5.7 Hz, 1H), 7.82 (t, J = 7.6 Hz, 1H), 7.50 – 7.39 (m, 2H), 6.30 (d, J = 6.6 Hz, 1H), 6.20 (d, J = 6.6 Hz, 1H), 6.09 (d, J = 6.0 Hz, 1H), 5.80 (d, J = 6.0 Hz, 1H), 3.76 (dd, J = 16.4, 8.5 Hz, 1H), 3.33 (dd, J = 16.4, 12.8 Hz, 1H), 2.80 (dt, J = 13.8, 6.8 Hz, 1H), 2.17 (s, 3H), 1.53 (d, J = 14.2 Hz, 9H), 1.35 (t, J = 7.0 Hz, 3H), 1.30 (d, J = 6.9 Hz, 3H), 1.22 (d, J = 13.2 Hz, 9H). 13 C NMR (126 MHz, Methylene Chloride-d2) δ 163.30 (d, J = 3.3 Hz), 157.46, 139.71, 124.96 124.42 (d, J = 9.1 Hz), 107.44, 99.74, 94.43 (d, J = 5.4 Hz), 93.38 (d, J = 6.2 Hz), 39.01 (d, J = 197 15.7 Hz), 38.37 (d, J = 15.7 Hz), 33.39 (d, J = 22.6 Hz), 31.21, 30.88 (d, J = 2.1 Hz), 29.92 (d, J = 2.7 Hz), 23.47, 21.41, 17.97. 31 P NMR (243 MHz, Methylene Chloride-d2) δ 87.31. 19 F NMR (470 MHz, Methylene Chloride-d2) δ -78.84. HRMS (ASI/EPCI) for C24H38NPClRu [M] + : calc’d 508.1468, found 508.1470. FT-IR (thin film/cm -1 ) ν = 3062, 2969, 2928, 2876, 2052, 1987, 1605, 1474, 1389, 1373,1265, 1224, 1154, 1107, 1087, 1056, 1031, 874, 830, 807. 1 H NMR spectrum of complex 4.1 at 25 C in CD2Cl2. 198 13 C NMR spectrum of complex 4.1 at 25 C in CD2Cl2. 31 P NMR spectrum of complex 4.1 at 25 C in CD2Cl2. 199 IR spectrum of complex 4.1. 200 6.4.2. Reactivity Studies Reactivity of 1-Phenylethanol in the Presence of KOtBu In the drybox, a 5 mL Schlenk bomb with a conical bottom was charged with 1- phenylethanol (55 µL, 0.46 mmol), 1 mol% of ruthenium 4.1 (3.0 mg, 4.6 µmol), and 5 mol% KOtBu (3.0 mg, 23 µmol). The vessel was taken out of the box and connected to a nitrogen line. Under a slow, steady stream of nitrogen gas, the solution was heated to 110 C. The solution turned red-brown. After 24 hours, the crude reaction mixture was analyzed by 1 H NMR in CDCl3. The reaction proceeds with 95% conversion and yields 4.3 as the major product. The spectrum of 4.3 (Figure 6.4.1) in the crude reaction mixture matches reported spectra. 14 Trace amounts of what appears to be the α,β-unsaturated ketone is also observed in the crude spectrum. Figure 6.4.1. 1 H NMR spectrum of the crude reaction mixture showing product 4.3 after 24 hours of heating at 110 C. 201 Reactivity of 1-Phenylethanol in the Absence of KOtBu In the drybox, a 5 mL Schlenk bomb with a conical bottom was charged with 1- phenylethanol (55 µL, 0.46 mmol) and ruthenium 4.1 (3.0 mg, 4.6 µmol). The vessel was taken out of the box and connected to a nitrogen line. Under a slow, steady stream of nitrogen gas, the solution was heated to 110 C. The solution turned green over a few hours. After 5 hours, the crude reaction mixture was allowed to cool to room temperature. The reaction proceeded with 80% conversion by NMR. The reaction mixture was heated for another 5 hours, reaching 95% conversion to produce the diastereomeric ethers of 4.5 as the major product. The spectrum of 4.5 (Figure 6.4.2) in the crude reaction mixture matches reported spectra. 15 Figure 6.4.2. 1 H NMR spectrum of the crude reaction mixture showing a diastereomeric mixture of ether product 4.5 after 8 hours of heating at 110 C. 202 Reactivity of Benzyl Alcohol in the Presence of KOtBu In the drybox, a 5 mL Schlenk bomb with a conical bottom was charged with benzyl alcohol (47 µL, 0.46 mmol), ruthenium 4.1 (3.0 mg, 4.6 µmol), and KOtBu (3.0 mg, 23 µmol). The vessel was taken out of the box and connected to a nitrogen line. Under a slow, steady stream of nitrogen gas, the solution was heated to 110 C. The solution turned red-brown. Over time, the solution slowly turns a light green color. After 24 hours, the crude reaction mixture was allowed to cool to room temperature. An aliquot was obtained for 1 H NMR analysis in CDCl3. The reaction proceeds in ca. 10% conversion and produces both 4.7 and 4.8. The spectrum of 4.7 and 4.8 (Figure 6.4.3) in the crude reaction mixture matches those reported in the literature. 16 Figure 6.4.3. 1 H NMR spectrum of the crude reaction mixture showing formation of trace amounts of 4.7 and 4.8 after 24 hours of heating at 110 C. 203 Reactivity of Benzyl Alcohol in the Absence of KOtBu In the drybox, a 5 mL Schlenk bomb with a conical bottom was charged with benzyl alcohol (47 µL, 0.46 mmol) and ruthenium 4.1 (3.0 mg, 4.6 µmol). The vessel was taken out of the box and connected to a nitrogen line. Under a slow, steady stream of nitrogen gas, the solution was heated to 110 C. The solution turned green over a few hours. After 5 hours, the crude reaction mixture was allowed to cool to room temperature and analyzed by 1 H NMR in CDCl3. The reaction proceeded with 15% conversion. The reaction mixture was heated for another 19 hours, reaching ca. 95% conversion to produce the diastereomeric ethers of 4.5 as the major product. The spectrum of 4.9 (Figure 6.4.4) in the crude reaction mixture matches those reported in the literature. 17 Figure 6.4.4. 1 H NMR spectrum of the crude reaction mixture showing formation of 4.9 after 24 hours of heating at 110 C. 204 Reactivity of 1-Octanol in the Presence of KOtBu In the drybox, a 5 mL Schlenk bomb with a conical bottom was charged with 1-octanol (72 µL, 0.46 mmol), ruthenium 4.1 (3.0 mg, 4.6 µmol), and KOtBu (3.0 mg, 23 µmol). The vessel was taken out of the box and connected to a nitrogen line. Under a slow, steady stream of nitrogen gas, the solution was heated to 110 C. The solution turned red-brown. After 24 hours, the crude reaction mixture was allowed to cool to room temperature. An aliquot was obtained for 1 H NMR analysis in CDCl3. The reaction proceeds in ca. 45% conversion and produces 4.11 as major product, with a very small amount of 4.8. The spectrum of the crude reaction mixture is shown in Figure 6.4.5. The spectra of the products were consistent with reported values in the literature. 18,19 Figure 6.4.5. 1 H NMR spectrum of the crude reaction mixture showing formation of 4.11 after 24 hours of heating at 110 C. 205 Reactivity of 1-Octanol in the Absence of KOtBu In the drybox, a 5 mL Schlenk bomb with a conical bottom was charged with 1-octanol (72 µL, 0.46 mmol) and ruthenium 4.1 (3.0 mg, 4.6 µmol). The vessel was taken out of the box and connected to a nitrogen line. Under a slow, steady stream of nitrogen gas, the solution was heated to 110 C. The solution turned yellow-green over time. After 24 hours, the crude reaction mixture was allowed to cool to room temperature. An aliquot was obtained for 1 H NMR analysis in CDCl3. The reaction proceeded with ca. 15% conversion. The spectrum of the crude reaction mixture is shown in Figure 6.4.6. The spectrum of 4.12 matches spectrum reported in the literature. 19 Figure 6.4.6. 1 H NMR spectrum of the crude reaction mixture showing formation of 4.12 after 24 hours of heating at 110 C. 206 6.4.3. Optimization of Benzylic Alcohol-Amine Coupling Coupling of Benzyl Alcohol and Tryptamine (Open Flask) In the drybox, a 5 mL Schlenk bomb with a conical bottom was charged with benzyl alcohol (70 µL, 0.67 mmol, 2.2 equiv), tryptamine (48 mg, 0.3 mmol) and 1 mol% ruthenium 4.1 (2.0 mg, 3.0 µmol). The vessel was taken out of the box and connected to a nitrogen line. Under a slow, steady stream of nitrogen gas, the solution was heated to 110 C. The solution turned dark brown. After 24 hours, the crude mixture was analyzed by 1 H NMR. The reaction proceeded with ca. 75% conversion, forming a 3:1 product mixture of 4.14 and 4.15. The spectrum of the crude reaction mixture is shown in Figure 6.4.7. The data are consistent with known compounds. 20,21 Figure 6.4.7. 1 H NMR spectrum of the crude reaction mixture for the coupling of benzyl alcohol and tryptamine under a stream of nitrogen gas at 110 C. 207 Coupling of Benzyl Alcohol and Tryptamine (Sealed Flask) In the drybox, a 5 mL Schlenk bomb with a conical bottom was charged with benzyl alcohol (70 µL, 0.67 mmol, 2.2 equiv), tryptamine (48 mg, 0.3 mmol) and 1 mol% ruthenium 4.1 (2.0 mg, 3.0 µmol). The vessel was sealed, taken out of the box, and heated to 110 C. The solution turned dark brown. After 24 hours, the crude reaction mixture was allowed to cool to room temperature. An aliquot was obtained for 1 H NMR analysis in CDCl3. The reaction proceeded with ca. 100% conversion, forming 4.15 as the major product. The spectrum of the crude reaction mixture is shown in Figure 6.4.8. The data are consistent with known compounds. 21 Figure 6.4.8. 1 H NMR spectrum of the crude reaction mixture for the coupling of benzyl alcohol and tryptamine in a sealed flask at 110 C. 208 Coupling of 1-Phenylethanol and Tryptamine (Open Flask) In the drybox, a 5 mL Schlenk bomb with a conical bottom was charged with 1- phenylethanol (100 µL, 0.83 mmol, 1.5 equiv), tryptamine (90 mg, 0.56 mmol, 1 equiv) and 1 mol% ruthenium 4.1 (3.6 mg, 5.5 µmol). The vessel was taken out of the box and connected to a nitrogen line. Under a slow, steady stream of nitrogen gas, the solution was heated to 110 C. The solution turned dark brown. After 18 hours, the crude reaction mixture was allowed to cool to room temperature. An aliquot was obtained for 1 H NMR analysis in CDCl3. The reaction proceeded with ca. 33% conversion, forming only the imine as the major product with almost no trace of the amine product. The spectrum of the crude reaction mixture is shown in Figure 6.4.9. Figure 6.4.9. 1 H NMR spectrum of the crude reaction mixture for the coupling of 1-phenylethanol and tryptamine under a stream of nitrogen gas at 110 C. 209 Coupling of 1-Phenylethanol and Tryptamine (Sealed Flask) In the drybox, a 5 mL Schlenk bomb with a conical bottom was charged with 1- phenylethanol (100 µL, 0.83 mmol, 7.5 equiv), tryptamine (17.6 mg, 0.11 mmol, 1 equiv) and 5 mol% ruthenium 4.1 (3.6 mg, 5.5 µmol). The vessel was sealed, taken out of the box, and heated to 130 C. The solution turned dark brown. After 24 hours, the crude reaction mixture was allowed to cool to room temperature. An aliquot was obtained for 1 H NMR analysis in CDCl3. The reaction proceeded with ca. 100% conversion, forming 4.15 as the major product. The spectrum of the crude reaction mixture is shown in Figure 6.4. The data are consistent with known compounds. 22 Figure 6.4.10. 1 H NMR spectrum of the crude reaction mixture for the coupling of 1- phenylethanol and tryptamine in a sealed flask at 130 C. 210 6.4.4. Substrate Scope Coupling of Benzyl Alcohol with Various Amines Amine 4.15: In the drybox, a 5 mL Schlenk bomb with a conical bottom was charged with benzyl alcohol 4.6 (25 µL, 0.24 mmol, 1.5 equiv), tryptamine 4.13 (25.6 mg, 0.16 mmol, 1 equiv), and 1.0 mol% of 4.1 (1.1 mg, 1.6 µmol). The reaction was sealed, removed from the glove box, and placed into a 110 °C oil bath for 20 hours. After 20 hours, an aliquot from the solution was dissolved in CDCl3 (0.6 mL), and a 1 H NMR spectrum was taken to determine conversion. When complete, the reaction was dissolved in minimal DCM and loaded into a silica column that had been treated with 1% triethylamine. Flash column chromatography (1:1 hexanes/ethyl acetate) yielded 28 mg of 4.15 (72%). Data are consistent with a known compound. 20 1 H NMR (600 MHz, Methylene Chloride-d2) δ 8.15 (s, 1H), 7.60 (dd, J = 8.0, 1.0 Hz, 1H), 7.36 (dt, J = 8.1, 1.0 Hz, 1H), 7.34 – 7.25 (m, 4H), 7.25 – 7.19 (m, 1H), 7.16 (ddd, J = 8.2, 7.0, 1.2 Hz, 1H), 7.11 – 7.01 (m, 2H), 3.80 (s, 2H), 2.97 (m, 4H). 13 C NMR (151 MHz, Methylene Chloride-d2) δ 140.95, 136.48, 128.27, 128.10, 127.64, 126.74, 122.01, 121.88, 119.13, 118.85, 114.20, 111.10, 53.76, 49.58, 25.81. Amine 4.17: In the drybox, a 5 mL Schlenk bomb with a conical bottom was charged with 1-phenylethanol 4.2 (100 µL, 0.81 mmol, 7.4 equiv), tryptamine 4.13 (17.6 mg, 0.11 mmol, 1 equiv), and 5.0 mol% of 1 (3.6 mg, 5.5 µmol). The reaction was sealed, removed from the glove box, and placed into a 130 211 °C oil bath for 24 hours. After 24 hours, an aliquot from the solution was dissolved in CDCl3 (0.6 mL), and a 1 H NMR spectrum was taken to determine conversion. When complete, the reaction was dissolved in minimal DCM and loaded into a silica column. Flash column chromatography (100% ethyl acetate) yielded 21 mg of 4.17 (72%). Data are consistent with a known compound. 21 1 H NMR (500 MHz, Chloroform-d) δ 8.12 (br s, 1H), 7.55 (d, J = 7.9 Hz, 1H), 7.39 – 7.34 (m, 1H), 7.34 – 7.22 (m, 5H), 7.22 – 7.17 (m, 1H), 7.10 (td, J = 7.5, 7.0, 0.9 Hz, 1H), 7.00 (s, 1H), 3.85 (q, J = 6.6 Hz, 1H), 2.99 (td, J = 6.4, 5.8, 2.2 Hz, 2H), 2.91 (dt, J = 18.1, 7.0 Hz, 1H), 2.83 (dt, J = 11.3, 7.2 Hz, 1H), 2.74 (br s, 1H), 1.38 (d, J = 6.6 Hz, 3H). 13 C NMR (126 MHz, Chloroform-d) δ 144.78, 136.56, 128.70, 127.56, 127.30, 126.85, 122.24, 122.20, 119.45, 119.06, 113.76, 111.32, 58.47, 47.64, 25.64, 24.01. Amine 4.27: In the drybox, a 5 mL Schlenk bomb with a conical bottom was charged with benzyl alcohol 4.6 (25 µL, 0.24 mmol, 1.5 equiv), tyramine 4.21 (22.4 mg, 0.16 mmol, 1 equiv), and 1.0 mol% of 4.1 (1.1 mg, 1.6 µmol). The reaction was sealed, removed from the glove box, and placed into a 110 °C oil bath for 5 hours. After 5 hours, an aliquot from the solution was dissolved in CDCl3 (0.6 mL), and a 1 H NMR spectrum was taken to determine conversion. When complete, the reaction was dissolved in minimal DCM and loaded into an HPLC. Flash column chromatography (1:1 hexanes/ethyl acetate) yielded 25.8 mg of 4.27 (72%). Data are consistent with a known compound. 23 1 H NMR (400 MHz, Chloroform-d) δ 7.37 – 7.19 (m, 5H), 7.03 (d, J = 8.4 Hz, 2H), 6.71 (d, J = 8.4 Hz, 2H), 3.81 (s, 2H), 2.89 (t, J = 7.2 Hz, 2H), 2.76 (t, J = 7.2 Hz, 2H). 13 C NMR (101 MHz, Chloroform-d) δ 154.28, 139.63, 131.45, 129.77, 128.45, 128.18, 127.06, 115.42, 53.67, 50.40, 35.09. 212 Amine 4.28: In the drybox, a 5 mL Schlenk bomb with a conical bottom was charged with benzyl alcohol 4.6 (25 µL, 0.24 mmol, 1.5 equiv), homoveratrylamine 4.22 (27 µL, 0.16 mmol, 1 equiv), and 1.0 mol% of 4.1 (1.1 mg, 1.6 µmol). The reaction was sealed, removed from the glove box, and placed into a 110 °C oil bath for 72 hours. After 72 hours, an aliquot from the solution was dissolved in CDCl3 (0.6 mL), and a 1 H NMR spectrum was taken to determine conversion. When complete, the reaction was dissolved in minimal DCM and loaded into a silica column that had been pretreated with 1% triethylamine. Flash column chromatography (1:1 hexanes/ethyl acetate) yielded 38.4 mg of 4.28 (90%). Data are consistent with a known compound. 24 1 H NMR (600 MHz, Chloroform-d) δ 7.35 – 7.18 (m, 5H), 6.78 (dd, J = 8.1, 2.2 Hz, 1H), 6.73 (dt, J = 8.1, 2.2 Hz, 1H), 6.71 (s, 1H), 3.84 (m, 6H), 3.79 (d, J = 2.2 Hz, 2H), 2.88 (td, J = 7.0, 2.0 Hz, 2H), 2.77 (td, J = 7.1, 2.1 Hz, 2H). 13 C NMR (151 MHz, Chloroform-d) δ 148.90, 147.43, 140.17, 132.55, 128.37, 128.08, 126.92, 120.59, 111.92, 111.29, 55.92, 55.81, 53.85, 50.54, 35.85. Amine 4.29: In the drybox, a 5 mL Schlenk bomb with a conical bottom was charged with benzyl alcohol 4.6 (25 µL, 0.24 mmol, 1.5 equiv), hexadecylamine 4.23 (38.6 mg, 0.16 mmol, 1 equiv), and 1.0 mol% of 4.1 (1.1 mg, 1.6 µmol). The reaction was sealed, removed from the glove box, and placed into a 110 °C oil bath for 20 hours. After 20 hours, an aliquot from the solution was dissolved in CDCl3 (0.6 mL), and a 1 H NMR spectrum was taken to determine conversion. When complete, the 213 reaction was dissolved in minimal DCM and loaded into a silica column. Flash column chromatography (2:1 hexanes/ethyl acetate) yielded 38 mg of 4.29 (79%). The starting material 4.23 was only 90% pure. Data are consistent with a known compound. 25 1 H NMR (600 MHz, Chloroform-d) δ 7.32 (d, J = 4.4 Hz, 4H), 7.26 – 7.21 (m, 1H), 3.79 (s, 2H), 2.63 (t, J = 7.3 Hz, 2H), 1.51 (p, J = 7.3 Hz, 2H), 1.25 (s, 26H), 0.88 (t, J = 7.0 Hz, 3H). 13 C NMR (151 MHz, Chloroform-d) δ 140.31, 128.37, 128.15, 126.89, 53.99, 49.43, 31.92, 30.00, 29.69 (br), 29.68, 29.66, 29.66, 29.61, 29.61, 29.56, 29.36, 27.35, 22.69, 14.11. Amine 4.30: In the drybox, a 5 mL Schlenk bomb with a conical bottom was charged with benzyl alcohol 4.6 (25 µL, 0.24 mmol, 1.5 equiv), cyclohexylamine 4.24 (19 µL, 0.16 mmol, 1 equiv), and 1.0 mol% of 4.1 (1.1 mg, 1.6 µmol). The reaction was sealed, removed from the glove box, and placed into a 110 °C oil bath for 24 hours. After 24 hours, an aliquot from the solution was dissolved in CDCl3 (0.6 mL), and a 1 H NMR spectra was taken to determine conversion. When complete, the reaction was purified by flash column chromatography (1:1 hexanes/ethyl acetate) to give 18 mg of 4.30 (58%). Data are consistent with a known compound. 26 1 H NMR (400 MHz, Chloroform-d) δ 7.38 – 7.28 (m, 4H), 7.26 – 7.21 (m, 1H), 3.82 (s, 2H), 2.49 (tt, J = 10.2, 3.7 Hz, 1H), 1.98 – 1.87 (m, 2H), 1.80 – 1.68 (m, 2H), 1.67 – 1.56 (m, 1H), 1.48 (br s, 1H), 1.30 – 1.09 (m, 5H). 214 Amine 4.31: In the drybox, a 5 mL Schlenk bomb with a conical bottom was charged with benzyl alcohol 4.6 (25 µL, 0.24 mmol, 1.5 equiv), 3,5-dimethylaniline 4.25 (19 µL, 0.16 mmol, 1 equiv), and 1.0 mol% of 4.1 (1.1 mg, 1.6 µmol). The reaction was sealed, removed from the glove box, and placed into a 110 °C oil bath for 24 hours. After 24 hours, an aliquot from the solution was dissolved in CDCl3 (0.6 mL), and a 1 H NMR spectrum was taken to determine conversion. When complete, the product was purified by flash column chromatography (3:1 hexanes/ethyl acetate) to yield 18.6 mg of 4.31 (58%). Data are consistent with a known compound. 27 1 H NMR (400 MHz, Chloroform-d) δ 7.39 – 7.27 (m, 5H), 6.42 (s, 1H), 6.33 (s, 2H), 4.31 (s, 2H), 2.23 (s, 6H). Amine 4.32: In the drybox, a 5 mL Schlenk bomb with a conical bottom was charged with 4-iodobenzyl alcohol 4.18 (84 mg, 0.36 mmol, 1.2 equiv), n-hexylamine 4.26 (39 µL, 0.3 mmol, 1 equiv), and 1.0 mol% of 4.1 (2.0 mg, 3.0 µmol). The reaction was sealed, removed from the glove box, and placed into a 110 °C oil bath for 20 hours. After 20 hours, an aliquot from the solution was dissolved in CDCl3 (0.6 mL), and a 1 H NMR spectrum was taken to determine conversion. When complete, the product was purified by flash column chromatography (3:1 hexanes/ethyl acetate) to yield 62 mg of 4.32 (65%) as a yellow-green oil. 4.32 is a commercial compound (CAS No. 1496214-93-7). 215 1 H NMR (500 MHz, Chloroform-d) δ 7.64 (d, J = 8.0 Hz, 2H), 7.08 (d, J = 8.0 Hz, 2H), 3.73 (s, 2H), 2.59 (t, J = 5.0 Hz, 2H), 1.48 (d, J = 14.7 Hz, 4H), 1.37 – 1.19 (m, 7H), 0.89 (t, J = 5.0 Hz, 3H). 13 C NMR (126 MHz, Chloroform-d) δ 140.19, 137.38, 130.11, 92.05, 53.41, 49.43, 31.75, 30.02, 27.00, 22.61, 14.04. Amine 4.33: In the drybox, a 5 mL pear-shaped Schlenk bomb was charged with 4-aminobenzyl alcohol 4.19 (37 mg, 0.30 mmol, 1.0 equiv), hexylamine 4.26 (48 µL, 0.36 mmol, 1.2 equiv), and 1.0 mol% of 4.1 (2.0 mg, 3.0 µmol). The reaction was sealed, removed from the glove box, and placed into a 110 °C oil bath for 12 hours. 1 H NMR spectra were taken to determine conversion after 3, 6, and 12 hours. When complete, the reaction was purified by flash column chromatography (95:5:1 dichloromethane/methanol/triethylamine) to yield 51 mg of 4.33 (77%) as a viscous yellow oil. 4.33 is a known compound 28 and is commercially available (CAS No. 1502166-32-6). 1 H NMR (600 MHz, Chloroform-d) δ 7.13 (d, J = 12.0 Hz, 2H), 6.65 (d, J = 12.0 Hz, 2H), 3.70 (s, 2H), 3.62 (s, 2H), 2.67 – 2.59 (m, 2H), 1.53 (p, J = 7.5 Hz, 2H), 1.34 – 1.23 (m, 6H), 0.87 (t, J = 6.7 Hz, 3H). 13 C NMR (151 MHz, Chloroform-d) δ 145.52, 129.61, 128.85, 115.10, 53.13, 48.84, 31.70, 29.41, 26.98, 22.59, 14.03. Amine 4.34: In the drybox, a 5 mL pear-shaped Schlenk bomb was charged with 3-aminobenzyl alcohol 4.20 (37 mg, 0.30 mmol, 1.0 equiv), hexylamine 4.26 (48 µL, 0.36 mmol, 1.2 equiv), and 1.0 mol% of 4.1 (2.0 mg, 3.0 µmol). The reaction was sealed, removed from the glove box, and placed into a 110 °C oil bath for 3 hours. After 3, an aliquot from the solution was dissolved in CDCl 3 (0.6 216 mL), and a 1 H NMR spectrum was taken to determine conversion. The crude reaction mixture was subjected to flash column chromatography (95:5:1 dichloromethane/methanol/triethylamine) to yield 48 mg of 4.34 (74%) as a viscous yellow oil. 4.34 is a known compound 29 and is commercially available (CAS No. 1554148-06-9). 1 H NMR (600 MHz, Chloroform-d) δ 7.10 (t, J = 7.9 Hz, 1H), 6.70 (dd, J = 4.6, 2.2 Hz, 2H), 6.58 (dd, J = 8.0, 2.2 Hz, 1H), 3.72 (s, 2H), 2.64 (t, J = 7.4 Hz, 2H), 1.53 (q, J = 7.5 Hz, 2H), 1.33 – 1.22 (m, 6H), 0.87 (t, J = 6.8 Hz, 3H). 13 C NMR (151 MHz, Chloroform-d) δ 146.62, 140.14, 129.33, 118.56, 114.97, 114.00, 53.53, 49.02, 31.66, 29.37, 26.91, 22.56, 14.00. Amine 4.35: In the drybox, a 5 mL pear-shaped Schlenk bomb was charged with 4-aminobenzyl alcohol 4.19 (37 mg, 0.30 mmol, 1.0 equiv), tryptamine 4.13 (58 mg, 0.36 mmol, 1.2 equiv), and 1.0 mol% of 4.1 (2.0 mg, 3.0 µmol). The reaction was sealed, removed from the glove box, and placed into a 110 °C oil bath for 12 hours. After 12 hours, an unstirrable solid forms. A 1 H NMR spectrum of the crude reaction mixture was taken to determine conversion (70%). The mixture was purified by flash column chromatography (90:10:1 dichloromethane/methanol/triethylamine) to yield 45 mg of 4.35 (57%) as a brown solid. 4.35 is a commercial compound (CAS No. 1506350-12-4). 1 H NMR (600 MHz, Chloroform-d) δ 7.97 (s, 1H), 7.61 (d, J = 7.9 Hz, 1H), 7.36 (d, J = 8.2 Hz, 1H), 7.19 (t, J = 7.6 Hz, 1H), 7.11 (t, J = 7.5 Hz, 1H), 7.07 (d, J = 7.9 Hz, 2H), 7.02 (s, 1H), 6.62 (d, J = 7.8 Hz, 2H), 3.70 (s, 2H), 2.99 (m, 4H). 13 C NMR (151 MHz, Chloroform-d) δ 145.24, 136.35, 130.16, 129.30, 127.47, 121.99, 121.87, 119.25, 118.94, 115.08, 114.08, 111.06, 53.39, 49.17, 25.66. 217 Amine 4.36: In the drybox, a 5 mL pear-shaped Schlenk bomb was charged with 3-aminobenzyl alcohol 4.20 (37 mg, 0.30 mmol, 1.0 equiv), homoveratrylamine 4.22 (65 mg, 0.36 mmol, 1.2 equiv), and 1.0 mol% of 4.1 (2.0 mg, 3.0 µmol). The reaction was sealed, removed from the glove box, and placed into a 110 °C oil bath for 3 hours. After 3 hours, an aliquot from the solution was dissolved in CDCl3 (0.6 mL), and a 1 H NMR spectrum was taken to determine conversion. The crude reaction mixture was subjected to flash column chromatography (95:5:1 dichloromethane/methanol/triethylamine) to yield 62 mg of 4.36 (72%). 4.36 is a commercial compound (CAS No. 1556153-38-8). 1 H NMR (600 MHz, Chloroform-d) δ 7.09 (t, J = 7.7 Hz, 1H), 6.80 (d, J = 8.1 Hz, 1H), 6.77 – 6.71 (m, 2H), 6.65 (d, J = 7.5 Hz, 1H), 6.62 (d, J = 2.1 Hz, 1H), 6.59 – 6.55 (m, 1H), 3.86 (s, 6H), 3.73 (s, 2H), 3.63 (br s, 2H), 2.89 (t, J = 7.1 Hz, 2H), 2.79 (t, J = 7.0 Hz, 2H). 13 C NMR (151 MHz, Chloroform-d) δ 148.89, 147.43, 146.54, 140.82, 132.35, 129.30, 120.62, 118.39, 114.75, 113.84, 111.93, 111.28, 55.90, 55.81, 53.63, 50.34, 35.59. Amine 4.40: In the drybox, a 5 mL Schlenk bomb with a conical bottom was charged with 1-phenylethanol 4.2 (100 µL, 0.81 mmol, 7.4 equiv), tyramine 4.21 (15 mg, 0.16 mmol, 1 equiv), and 5.0 mol% of 4.1 (3.6 mg, 5.5 µmol). The reaction was sealed and removed from the glove box and into a 130 °C oil bath for 24 hours. After 24 hours, an aliquot from the solution was dissolved in CDCl3 (0.6 218 mL), and a 1 H NMR spectra was taken to determine conversion. Flash column chromatography (1:1 hexanes:ethyl acetate) yielded 23 mg of 4.40 (85%). 4.40 is a known compound. 30 1 H NMR (600 MHz, Methylene Chloride-d2) δ 7.44 – 7.17 (m, 5H), 6.94 (d, J = 8.5 Hz, 2H), 6.68 (d, J = 8.4 Hz, 2H), 4.39 (bs, 1H), 3.86 (q, J = 6.7 Hz, 1H), 2.79 – 2.62 (m, 4H), 1.37 (d, J = 6.6 Hz, 3H). 13 C NMR (151 MHz, Methylene Chloride-d2) δ 155.26, 144.22, 131.09, 130.08, 128.94, 127.71, 127.15, 115.83, 58.59, 48.92, 34.87, 23.42. Amine 4.41: In the drybox, a 5 mL Schlenk bomb with a conical bottom was charged with 1-phenylethanol 4.6 (100 µL, 0.81 mmol, 7.4 equiv), homoveratrylamine 4.22 (19 µL, 0.11 mmol, 1 equiv), and 5.0 mol% of 4.1 (3.6 mg, 5.5 µmol). The reaction was sealed, removed from the glove box, and into a 130 °C oil bath for 24 hours. After 24 hours, an aliquot from the solution was dissolved in CDCl3 (0.6 mL), and a 1 H NMR spectra was taken to determine conversion. Flash column chromatography (1:1 hexanes:ethyl acetate) yielded 21 mg 4.41 (67%) as a clear oil. Data are consistent with a known compound. 31 1 H NMR (600 MHz, Chloroform-d) δ 7.32 – 7.28 (m, 2H), 7.27 – 7.20 (m, 3H), 6.76 (d, J = 8.1 Hz, 1H), 6.68 (dd, J = 8.1, 2.0 Hz, 1H), 6.65 (d, J = 1.9 Hz, 1H), 3.86 – 3.77 (m, 7H, including benzylic CH), 2.81 – 2.63 (m, 4H), 1.36 (d, J = 6.6 Hz, 3H). 13 C NMR (151 MHz, Chloroform-d) δ 148.87, 147.44, 144.47, 132.16, 128.48, 127.12, 126.61, 120.58, 111.85, 111.23, 58.22, 55.89, 55.78, 48.63, 35.37, 23.75. 219 Amine 4.42: In the drybox, a 5 mL Schlenk bomb with a conical bottom was charged with 1-phenylethanol 4.6 (100 µL, 0.81 mmol, 7.4 equiv), hexadecylamine 4.23 (26.5 mg, 0.11 mmol, 1 equiv), and 5.0 mol% of 4.1 (3.6 mg, 5.5 µmol). The reaction was sealed, removed from the glove box, and placed into a 130 °C oil bath for 24 hours. After 24 hours, an aliquot from the solution was dissolved in CDCl3 (0.6 mL), and a 1 H NMR spectra was taken to determine conversion. Flash column chromatography (4:1 hexanes:ethyl acetate) yielded 24.4 mg of 4.42 (79%). The starting material 24 was only 90% pure. 24 is a known compound. 32 1 H NMR (600 MHz, Chloroform-d) δ 7.35 – 7.28 (m, 3H), 7.27 – 7.21 (m, 2H), 3.76 (q, J = 6.5, 6.0 Hz, 1H), 2.55 – 2.45 (m, 1H), 2.46 – 2.36 (m, 1H), 1.46 (d, J = 7.2 Hz, 4H), 1.39 – 1.33 (m, 3H), 1.33 – 1.10 (m, 24H), 0.92 – 0.86 (m, 3H). 13 C NMR (151 MHz, Chloroform-d) δ 145.95, 128.61, 127.05, 126.79, 58.63, 48.09, 32.15, 30.43, 29.92 (br), 29.90, 29.88, 29.83, 29.81, 29.77, 29.59, 27.59, 24.50, 22.92, 14.34. Amine 4.43: In the drybox, a 5 mL Schlenk bomb with a conical bottom was charged with 1-phenylethanol 4.6 (100 µL, 0.81 mmol, 7.4 equiv), cyclohexylamine 4.24 (26.5 mg, 0.11 mmol, 1 equiv), and 5.0 mol% of 4.1 (3.6 mg, 5.5 µmol). The reaction was sealed, removed from the glove box, and placed into a 130 °C oil bath for 19 hours. After 19 hours, an aliquot from the solution was dissolved in 220 CDCl3 (0.6 mL), and a 1 H NMR spectrum was taken to determine conversion. Flash column chromatography (2:1 hexanes/ethyl acetate) yielded 15 mg of the product (66%). Data are consistent with a known compound. 33 1 H NMR (500 MHz, Methylene Chloride-d2) δ 7.39 – 7.26 (m, 4H), 7.21 (m, 1H), 3.95 (qd, J = 6.6, 0.8 Hz, 1H), 2.26 (tt, J = 10.2, 3.8 Hz, 1H), 2.01 – 1.91 (m, 1H), 1.66 (tdt, J = 19.8, 10.0, 4.0 Hz, 3H), 1.54 (m, 1H), 1.28 (d, J = 6.6 Hz, 4H, including NH), 1.19 – 1.09 (m, 3H), 1.09 – 0.95 (m, 2H). 13 C NMR (126 MHz, Methylene Chloride-d2) δ 147.32, 128.78, 127.08, 127.07, 54.94, 35.08, 33.81, 26.81, 25.79, 25.53, 25.39. Amine 4.44: In the drybox, a 5 mL Schlenk bomb with a conical bottom was charged with 1-(4- methylphenyl)ethanol 4.37 (100 µL, 0.72 mmol, 6.5 equiv), tryptamine 4.13 (17.6 mg, 0.11 mmol, 1 equiv), and 5.0 mol% of 4.1 (3.6 mg, 5.5 µmol). The reaction was sealed, removed from the glove box, and placed into a 130 °C oil bath for 24 hours. After 24 hours, an aliquot from the solution was dissolved in CDCl3 (0.6 mL), and a 1 H NMR spectrum was taken to determine conversion. Flash column chromatography (100% ethyl acetate) yielded 21 mg of 4.44 (69%). 4.44 is a known compound. 34 1 H NMR (400 MHz, Chloroform-d) δ 8.05 (br s, 1H), 7.54 (d, J = 7.9 Hz, 1H), 7.35 (d, J = 8.1 Hz, 1H), 7.22 – 7.14 (m, 3H), 7.14 – 7.05 (m, 3H), 7.00 (d, J = 2.2 Hz, 1H), 3.79 (q, J = 6.6 Hz, 1H), 2.97 (dd, J = 8.6, 6.5 Hz, 2H), 2.92 – 2.78 (m, 2H), 2.33 (s, 4H, including NH), 1.34 (d, J = 6.6 Hz, 3H). 13 C NMR (101 MHz, Chloroform-d) δ 141.88, 136.55, 136.34, 129.11, 127.38, 126.50, 121.96, 121.93, 119.20, 118.88, 113.76, 111.06, 57.97, 47.52, 25.58, 24.00, 21.03. 221 Amine 4.45: In the drybox, a 5 mL Schlenk bomb with a conical bottom was charged with 1-(4- methoxyphenyl)ethanol 4.38 (100 µL, 0.71 mmol, 6.5 equiv), tryptamine 4.13 (17.6 mg, 0.11 mmol, 1 equiv), and 5.0 mol% of 4.1 (3.6 mg, 5.5 µmol). The reaction was sealed, removed from the glove box, and placed into a 130 °C oil bath for 24 hours. After 24 hours, an aliquot from the solution was dissolved in CDCl3 (0.6 mL), and a 1 H NMR spectrum was taken to determine conversion. Flash column chromatography (100% ethyl acetate) yielded 23 mg of 4.45 (72%). 1 H NMR (600 MHz, Chloroform-d) δ 8.13 (br s, 1H), 7.53 (d, J = 7.9 Hz, 1H), 7.35 (dd, J = 8.2, 1.8 Hz, 1H), 7.23 – 7.17 (m, 2H), 7.18 – 7.12 (m, 1H), 7.05 (ddd, J = 8.7, 7.2, 1.8 Hz, 1H), 7.02 (d, J = 2.3 Hz, 1H), 6.82 (dd, J = 8.7, 2.1 Hz, 2H), 3.83 – 3.69 (m, 4H, including OCH3 and benzylic CH), 2.95 – 2.86 (m, 2H), 2.85 – 2.79 (m, 1H), 2.77 – 2.72 (m, 1H), 1.28 – 1.26 (m, 3H). 13 C NMR (151 MHz, Chloroform-d) δ 159.10, 138.60, 136.96, 128.15, 128.11, 122.43, 122.35, 119.59, 119.34, 114.72, 114.15, 111.57, 58.00, 55.74, 48.27, 26.35, 24.72. Amine 4.46: In the drybox, a 5 mL Schlenk bomb with a conical bottom was charged with 1-(4- fluorophenyl)ethanol 4.39 (100 µL, 0.80 mmol, 7.3 equiv), tryptamine 4.13 (17.6 mg, 0.11 mmol, 1 equiv), and 5.0 mol% of 4.1 (3.6 mg, 5.5 µmol). The reaction was sealed, removed from the glove box, and placed into a 130 °C oil bath for 24 hours. After 24 hours, an aliquot from the solution was dissolved in CDCl3 (0.6 mL), and a 1 H NMR spectrum was taken to determine conversion. Flash column chromatography (100% ethyl acetate) yielded 24 mg of 4.46 (77%). 222 4.46 is a known compound. 34 1 H NMR (500 MHz, Methylene Chloride-d2) δ 8.17 (br s, 1H), 7.51 (d, J = 7.9 Hz, 1H), 7.35 (dd, J = 8.2, 1.0 Hz, 1H), 7.30 – 7.23 (m, 2H), 7.18 – 7.12 (m, 1H), 7.09 – 7.01 (m, 2H), 7.01 – 6.94 (m, 2H), 3.84 (q, J = 6.6 Hz, 1H), 2.98 – 2.91 (m, 2H), 2.86 (m, 1H), 2.76 (m, 3H, including NH), 1.32 (d, J = 6.6 Hz, 3H). 13 C NMR (126 MHz, Methylene Chloride-d2) δ 162.45 (d, J = 244.6 Hz), 141.05, 136.97, 128.87 (d, J = 7.9 Hz), 127.93, 122.68, 122.46, 119.70, 119.22, 115.60 (d, J = 21.17 Hz), 113.97, 111.65, 58.11, 47.99, 25.85, 24.20. 223 6.4.5. NMR Studies to Probe the Mechanism of Coupling Synthesis of 4.6-1-d1 The benzyl alcohol 4.6-1-d1 was synthesized by reduction of benzaldehyde using sodium borodeuteride (98% D, Sigma-Aldrich). To an ice-water bath cooled solution of benzaldehyde (2 mL, 19.6 mmol) dissolved in 1:1 ethanol/dichloromethane was added NaBD4 (0.6 g, 14.3 mmol). The solution was stirred for 30 minutes at 0 °C then at room temperature for 15 minutes. The solution was again cooled to 0 °C then 6 M HCl was added slowly until effervescence stopped. The mixture was filtered and the filtrate extracted with dichloromethane (3 x 25 mL). The organic layer was washed with saturated aqueous NaHCO3 (25 mL), water (25 mL), and brine (25 mL). The solvent was evaporated in vacuo. Flash column chromatography (9:1 hexanes/ethyl acetate) yielded 1.2 g of pure product (57%). 1 H NMR (16 scans, 10 second delay) analysis shows 93% deuterium incorporation (Figure 6.4.11). 224 Figure 6.4.11. 1 H NMR spectrum of benzyl alcohol 4.6-1-d1. 13 C NMR Studies of the Coupling of Benzyl Alcohol-d1 and n-Hexylamine In the drybox, a J-Young NMR tube was charged 4.6-1-d1 (350 µL, 3.15 mmol, 1.1 equiv), hexylamine (400 µL, 3.0 mmol, 1.0 equiv), and ruthenium 4.1 (20.0 mg, x mmol, 1 mol%). The J- Young tube was sealed, taken out of the drybox, and heated to 110 °C. After 2 hours, the reaction mixture was allowed to cool to room temperature and a 13 C NMR spectrum was taken (a separate NMR tube containing a deuterated solvent was used to lock and shim the NMR). The reaction mixture was then heated again. 13 C NMR spectra were taken at 0, 2, 8, and 24 hours of heating, which are shown in Figures 6.4.12 and 6.4.13A-D. Disappearance of the starting materials, 4.6-1- d1 and hexylamine, and formation of the benzylated amine is observed. Figures 6.4.13A-D are zoomed in views of the region of the 13 C NMR spectra showing the changes described in the main text that occur as the starting materials are coupled. Figures 6.4.13B-D clearly show the 13 C‒ 2 H coupling pattern described in the main text. Also, Figure 6.4.12 shows formation of small amounts 225 of the imine intermediate; the benzaldehyde intermediate is not observed. After 24 hours of heating, the side products dibenzyl ether, dihexylamine, and dibenzyl(hexyl)amine are seen in Figure 6.4.13D. These side products are detected in the GC-MS of the crude reaction mixture (see next section for GC-MS data). Also, the crude reaction mixture was spiked with dihexylamine to confirm the corresponding dihexylamine peaks present in the 13 C NMR spectrum of the crude reaction mixture. Figure 6.4.12. 13 C NMR stacked spectra of the crude reaction mixture after 0, 2, 8, and 24 hours of heating at 110 °C. 226 Figure 6.4.13A. 13 C NMR spectrum of the crude reaction mixture prior to heating to 110 °C. Figure 6.4.13B. 13 C NMR spectrum of the crude reaction mixture after 2 h of heating at 110 °C. 227 Figure 6.4.13C. 13 C NMR spectrum of the crude reaction mixture after 8 h of heating at 110 °C. Figure 6.4.13D. 13 C NMR spectrum of the crude reaction mixture after 24 h of heating at 110 °C. 228 Side Products from the Coupling of 4.6-1-d1 and Hexylamine The crude reaction mixture for the coupling of 4.6-1-d1 and n-hexylamine after 24 hours of heating at 110 °C was analyzed by GC-MS. The chromatogram of the crude mixture is shown in Figure 6.4.14. The desired product and four coupling side products—Hex2NH, Bn2O, BnN(Hex)2 and Bn2Hex—are observed in the chromatogram. These were identified by their corresponding mass spectra (Figure 6.4.15 – 6.4.19). Small amounts of other side products, which are not analyzed here, can also be observed. Figure 6.4.14. GC chromatogram of the crude reaction mixture for the coupling of 4.6-1-d1 and n-hexylamine after 24 h of heating at 110 °C. 229 Figure 6.4.15. Mass spectrum of the GC peak at 12.1 min (the desired benzyl(hexyl)amine product). Figure 6.4.16. Mass spectrum of the GC peak at 9.3 min (the dihexylamine side product). 230 Figure 6.4.17. Mass spectrum of the GC peak at 16.2 min (the dibenzyl ether side product). Figure 6.4.18. Mass spectrum of the GC peak at 18.9 min (the benzyl(dihexyl)amine side product). 231 Figure 6.4.19. Mass spectrum of the GC peak at 22.4 min (the dibenzyl(hexyl)amine side product). 232 31 P NMR Showing Bound PN Ligand After 48 h of Heating A 31 P NMR spectrum of the crude reaction mixture from the 13 C NMR studies above was taken after 24 hours of heating. The spectrum does not show a peak corresponding to the free phosphinopyridine ligand. Thus, we believe that the PN ligand remains bound to the catalyst. The 31 P spectrum shows five peaks: the major species is a broad triplet at 92.1 ppm, consistent with a protonated (uncharged), metal-bound ligand, but four unidentified singlets at 97.9, 84.0, 65.5, and 60.5 ppm are also present. Figure 6.4.20. 31 P NMR spectrum of the crude reaction mixture after 24 hours of heating at 110 °C. 233 1 H NMR Studies in 1,2-Dichlorobenzene-d4 In the dry box, a J-Young tube was charged with a 10:1 mixture of benzyl alcohol 4.6-1-d1 (ca. 93% D, 8 µL, 77 µmol) and ruthenium 4.1 (5 mg, 7.6 µmol) dissolved in 0.6 mL of 1,2- dichlorobenzene-d4. The J-Young tube was sealed, removed from the drybox, and heated to 110 ºC in an oil bath. After 15 minutes, heating was stopped and a 1 H NMR spectrum of the crude reaction mixture was taken. Heating was continued and NMR were taken after 2, 6, 8, 24, and 48 hours of heating. See Chapter 4.6 for a discussion of the results. 234 6.4.6. NMR Spectra of Coupling Products 1 H NMR spectrum of compound 4.16 at 25 C in CD2Cl2. 13 C NMR spectrum of compound 4.16 at 25 C in CD2Cl2. 235 1 H NMR spectrum of compound 4.17 at 25 C in CDCl3. 13 C NMR spectrum of compound 4.17 at 25 C in CDCl3. 236 1 H NMR spectrum of compound 4.27 at 25 C in CDCl3. 13 C NMR spectrum of compound 4.27 at 25 C in CDCl3. 237 1 H NMR spectrum of compound 4.28 at 25 C in CDCl3. 13 C NMR spectrum of compound 4.28 at 25 C in CDCl3. 238 1 H NMR spectrum of compound 4.29 at 25 C in CDCl3. 13 C NMR spectrum of compound 4.29 at 25 C in CDCl3. 239 1 H NMR spectrum of compound 4.32 at 25 C in CDCl3. 13 C NMR spectrum of compound 4.32 at 25 C in CDCl3. 240 1 H NMR spectrum of compound 4.33 at 25 C in CDCl3. 13 C NMR spectrum of compound 4.33 at 25 C in CDCl3. 241 1 H NMR spectrum of compound 4.34 at 25 C in CDCl3. 13 C NMR spectrum of compound 4.34 at 25 C in CDCl3. 242 1 H NMR spectrum of compound 4.35 at 25 C in CDCl3. 13 C NMR spectrum of compound 4.35 at 25 C in CDCl3. 243 1 H NMR spectrum of compound 4.36 at 25 C in CDCl3. 13 C NMR spectrum of compound 4.36 at 25 C in CDCl3. 244 1 H NMR spectrum of compound 4.40 at 25 C in CD2Cl2. 13 C NMR spectrum of compound 4.40 at 25 C in CD2Cl2. 245 1 H NMR spectrum of compound 4.41 at 25 C in CDCl3. 13 C NMR spectrum of compound 4.41 at 25 C in CDCl3. 246 1 H NMR spectrum of compound 4.42 at 25 C in CDCl3. 13 C NMR spectrum of compound 4.42 at 25 C in CDCl3. 247 1 H NMR spectrum of compound 4.43 at 25 C in CD2Cl2. 13 H NMR spectrum of compound 4.43 at 25 C in CD2Cl2. 248 1 H NMR spectrum of compound 4.44 at 25 C in CDCl3. 13 C NMR spectrum of compound 4.44 at 25 C in CDCl3. 249 1 H NMR spectrum of compound 4.45 at 25 C in CD2Cl2. 13 C NMR spectrum of compound 4.45 at 25 C in CD2Cl2. 250 1 H NMR spectrum of compound 4.46 at 25 C in CD2Cl2. 13 C NMR spectrum of compound 4.46 at 25 C in CD2Cl2. 251 6.5. Chapter 5 Experimental and Spectral Data 6.5.1. Borylation Procedures Complexes 1.7 and 1.8 were graciously provided by Zhiyao Lu. A representative procedure is as follows: A 5 mL bomb was flame dried and taken into the drybox. The bomb was charged with catalyst 1.8 (1.9 mg, 2.7 µmol), B2Pin2 (16.2 mg, 65 µmol), and dibutylether (1.0 mL, 5.9 mmol). The bomb was sealed, taken out of the drybox, and heated in an oil bath to 150 C for 21 hours. The mixture was allowed to cool to room temperature and an aliquot for GC-MS analysis was obtained. To determine the NMR yield of borylation product 5.2, an external toluene standard was used. The solvent was first removed under reduced pressure for 2 days. The remaining residue was taken up in chloroform-d and toluene (15 µL, 140 µmol) was added. Using this external standard, the yield of the borylated product was calculated to 68% based on B2Pin2 (Figure 6.5.1). Figure 6.5.1. 1 H NMR spectrum of 5.2 and toluene external standard for yield determination. 252 6.5.2. Syntheses and Characterization of Complexes 1.18 and 5.3 – 5.7 Ruthenium 1.18 In the drybox, a clean, dry 4 dram vial was charged with 1.7 (24 mg, 38.9 µmol), 2-((di- tert-butylphosphino)methyl)pyridine 1 (15.0 mg, 63.2 µmol), and 2 mL acetonitrile solvent. The mixture was heated in a 90 C oil bath for 3 days. The solvent was evirated and the residue was triturated by sonication in ether. The ether was decanted and the solid dried in vacuo. The resulting yellow solid (24 mg, 85% yield) was characterized by NMR and high resolution mass spectrometry for the deuterated compound was obtained. The NMR shows presence of possible geometric isomers. 1 H NMR (500 MHz, Acetonitrile-d3) δ 9.22 – 9.10 (m, 1H), 8.75 – 8.65 (m, 2H), 7.75 – 7.63 (m, 2H), 7.57 (d, J = 7.8 Hz, 1H), 7.55 – 7.46 (m, 2H), 7.34 (dd, J = 7.6, 1.3 Hz, 1H), 7.32 – 7.25 (m, 1H), 6.95 (ddt, J = 7.3, 5.7, 1.5 Hz, 1H), 3.72 (dd, J = 16.9, 10.8 Hz, 1H), 3.32 (dd, J = 17.1, 7.7 Hz, 1H), 2.57 (d, J = 1.1 Hz, 3H), 2.13 (s, 1H, OH proton), 1.24 – 1.18 (m, 9H), 0.99 (dd, J = 12.5, 1.1 Hz, 9H). 31 P NMR (202 MHz, Acetonitrile-d3) δ 82.05. 11 B NMR (192 MHz, Acetonitrile-d3) δ 0.85. HRMS (ESI/APCI): m/z = 585.230 g/mol, calc’d. for C27H33D6RuBN4OP + [M] + : 585.2375 g/mol. FT-IR (thin film/cm -1 ) ν = 3402 (br), 3058, 2950, 2921, 2871, 2254, 2209, 2105, 2052, 1984, 1732, 1596, 1474, 1456, 1437, 1402, 1393, 1368, 1277, 1260, 1225, 1155, 1031, 949, 846, 810. 253 Figure 6.5.2. 1 H NMR spectrum of complex 1.18 at 25 °C in CD3CN. Figure 6.5.3. 1 H NMR spectrum of complex 1.18 after heating to 110 °C in CD3CN for 12 hours. 254 31 P NMR spectrum of complex 1.18 at 25 °C in CD3CN. 11 B NMR spectrum of complex 1.18 at 25 °C in CD3CN. 255 IR spectrum of complex 1.18-d6. 256 Ruthenium 5.3 Complex 5.3 was synthesized using the procedure used for the synthesis of complex 3.1 (see Section 6.3.1). 2-((Di-tert-butylphosphino)methyl)pyridine 1 (74.7 mg, 0.31 mmol), tricarbonyldichlororuthenium(II) dimer, (80.6 mg, 0.16 mmol), and sodium trifluoromethanesulfonate (81.2 mg, 0.47 mmol) were used. Pure product was isolated as an yellow solid (112.7 mg, 78% yield). 1 H NMR (500 MHz, Methylene Chloride-d2) δ 9.47 – 9.37 (m, 1H), 7.92 – 7.83 (m, 1H), 7.58 (d, J = 7.9 Hz, 1H), 7.42 (t, J = 6.7 Hz, 1H), 4.07 (dd, J = 16.6, 10.4 Hz, 1H), 3.50 (dd, J = 16.6, 10.7 Hz, 1H), 1.44 (d, J = 14.5 Hz, 9H), 1.31 (d, J = 13.9 Hz, 8H). 13 C NMR (126 MHz, Methylene Chloride-d2) δ 161.35, 151.97, 139.67, 123.94, 123.87, 123.75, 38.73, 38.60, 37.84, 37.68, 35.43, 35.26, 30.04, 30.03, 29.68, 29.66. 31 P NMR (202 MHz, Methylene Chloride-d2) δ 95.75. HRMS (ESI/APCI): m/z = 430.0265 g/mol, calc’d. for C16H24RuClNO2P + [M-CO] + : 430.0271 g/mol. FT-IR (thin film/cm -1 ) ν = 3107, 3028, 2996, 2954, 2907, 2877, 2122, 2053, 1989, 1607, 1566, 1478, 1444, 1394, 1374, 1314, 1267, 1224, 1180, 1161, 1106, 1061, 1030, 936, 896, 834, 808. 1 H NMR spectrum of complex 5.3 at 25 °C in CD2Cl2. 257 13 C NMR spectrum of complex 5.3 at 25 °C in CD2Cl2. 31 P NMR spectrum of complex 5.3 at 25 °C in CD2Cl2. 258 IR spectrum of complex 5.3. 259 Iridium 5.4 Complex 5.4 was synthesized using the procedure used for the synthesis of complex 3.1 (see Section 6.3.1). 2-((Di-tert-butylphosphino)methyl)pyridine 1 (24.0 mg, 93 µmol), pentamethylcyclopentadienyliridium(III) chloride dimer (44.0 mg, 55 µmol), and sodium trifluoromethanesulfonate (33.0 mg, 0.19 mmol) were used. Pure product was isolated as a yellow solid (50 mg, 72% yield). Crystals suitable for X-ray crystallography was obtained by Dr. Jessica Herron from a dichloromethane/ethyl ether solution. 1 H NMR (600 MHz, Methylene Chloride-d2) δ 8.45 (d, J = 5.9 Hz, 1H), 7.92 (t, J = 7.5 Hz, 1H), 7.70 (d, J = 7.9 Hz, 1H), 7.33 (t, J = 6.7 Hz, 1H), 4.15 (dd, J = 16.4, 9.1 Hz, 1H), 3.92 (dd, J = 16.4, 11.4 Hz, 1H), 1.77 (d, J = 1.8 Hz, 15H), 1.50 (d, J = 14.6 Hz, 9H), 1.14 (d, J = 13.8 Hz, 9H). 13 C NMR (151 MHz, Methylene Chloride-d2) 164.13, 152.52, 140.31, 125.51, 124.64 (d, J = 7.6 Hz), 94.99 (d, J = 2.2 Hz), 37.90 (d, J = 21.0 Hz), 37.59 (d, J = 19.8 Hz), 35.76 (d, J = 28.5 Hz), 30.71 (d, J = 2.4 Hz), 29.30 (d, J = 3.0 Hz), 10.42. 31 P NMR (243 MHz, Methylene Chloride-d2) δ 59.86. HRMS (ESI/APCI): m/z = 600.2148 g/mol, calc’d. for C24H39ClIrNP + [M] + : 600.2133 g/mol. FT-IR (thin film/cm -1 ) ν = 3138, 2970, 2920, 2875, 2428, 2298, 1607, 1565, 1540, 1475, 1375, 1269, 1223, 1150, 1109, 1075, 1031, 940, 896, 827, 810. 260 1 H NMR spectrum of complex 5.4 at 25 °C in CD2Cl2. 13 C NMR spectrum of complex 5.4 at 25 °C in CD2Cl2. 261 31 P NMR spectrum of complex 5.4 at 25 °C in CD2Cl2. IR spectrum of iridium 5.4. 262 Rhodium 5.5 Complex 5.5 was synthesized using the procedure used for the synthesis of complex 3.1 (see Section 6.3.1). 2-((Di-tert-butylphosphino)methyl)pyridine 1 (24.5 mg, 103 µmol), chloro(1,5- cyclooctadiene)rhodium(I) dimer (23.4 mg, 48 µmol), and sodium trifluoromethanesulfonate (25.0 mg, 0.14 mmol) were used. Pure product was isolated as a light yellow solid (35 mg, 62% yield). 1 H NMR (600 MHz, Methylene Chloride-d2) δ 7.98 (t, J = 7.7 Hz, 1H), 7.92 (d, J = 5.8 Hz, 1H), 7.79 (d, J = 7.9 Hz, 1H), 7.41 (t, J = 6.6 Hz, 1H), 5.23 (s, 2H), 4.82 – 4.71 (m, 2H), 3.56 (d, J = 9.5 Hz, 2H), 2.59 – 2.41 (m, 4H), 2.35 (dt, J = 13.3, 6.3 Hz, 2H), 2.24 – 2.14 (m, 2H), 1.31 (d, J = 13.5 Hz, 18H). 13 C NMR (151 MHz, Methylene Chloride-d2) δ 164.09 (d, J = 6.0 Hz), 148.90, 140.80, 124.83 (d, J = 9.1 Hz), 123.93, 102.44 (d, J = 9.1 Hz), 102.39 (d, J = 9.1 Hz), 76.48 (d, J = 12.1 Hz), 36.58 (dd, J = 13.6 and 1.5 Hz), 33.86 (d, J = 19.6 Hz), 32.50 (d, J = 3.0 Hz), 29.89 (d, J = 3 Hz), 27.84. 31 P NMR (243 MHz, Methylene Chloride-d2) δ 68.23 (d, J = 100.3 Hz) HRMS (ESI/APCI): m/z = 432.1313 g/mol, calc’d. for C21H32RhNP + [M] + : 432.1322 g/mol. FT-IR (thin film/cm -1 ) ν = 3036, 2954, 2888, 2836, 1605, 1565, 1474, 1445, 1431, 1390, 1369, 1336, 1318, 1272, 1223, 1148, 1105, 1078, 1031, 996, 892, 874, 822. 1 H NMR spectrum of complex 5.5 at 25 °C in CD2Cl2. 263 13 C NMR spectrum of complex 5.5 at 25 °C in CD2Cl2. 31 P NMR spectrum of complex 5.5 at 25 °C in CD2Cl2. 264 IR spectrum of complex 5.5. 265 Rhodium 5.6 Complex 5.6 was synthesized using the procedure used for the synthesis of complex 3.1 (see Section 6.3.1). 2-((Di-tert-butylphosphino)methyl)pyridine 1 (20.9 mg, 88 µmol), chloro(norbornadiene)rhodium(I) dimer (20.2 mg, 44 µmol), and sodium trifluoromethanesulfonate (30 mg, 0.17 mmol) were used. Pure product was isolated as an orange solid (34 mg, 66% yield). 1 H NMR (500 MHz, Methylene Chloride-d2) δ 7.96 (tt, J = 7.7, 1.3 Hz, 1H), 7.75 (d, J = 7.9 Hz, 1H), 7.61 (d, J = 5.7 Hz, 1H), 7.39 (t, J = 6.7 Hz, 1H), 5.21 (t, J = 2.8 Hz, 2H), 4.71 (t, J = 2.7 Hz, 2H), 4.10 (dq, J = 4.5, 2.1 Hz, 2H), 3.45 (d, J = 9.2 Hz, 2H), 1.79 – 1.72 (m, 1H), 1.28 (d, J = 14.0 Hz, 18H). 13 C NMR (126 MHz, Methylene Chloride-d2) δ 164.58, 164.56, 164.53, 164.51, 148.64, 140.81, 124.46, 124.45, 124.39, 124.38, 123.67, 86.52, 86.47, 86.44, 86.39, 66.93, 66.92, 66.89, 66.88, 63.06, 62.98, 52.99, 52.98, 52.97, 36.12, 36.10, 36.00, 35.98, 33.30, 33.15, 29.49, 29.45. 31 P NMR (243 MHz, Methylene Chloride-d2) δ 64.95 (d, J = 143.4 Hz) HRMS (ESI/APCI): m/z = 448.1620 g/mol, calc’d. for C22H36RhNP + [M] + : 448.1635 g/mol. FT-IR (thin film/cm -1 ) ν = 2963, 2926, 2753, 166, 1475, 1443, 1401, 1371, 1312, 1271, 1223, 1180, 1149, 1106, 1064, 1031, 957, 892, 867. 266 1 H NMR spectrum of complex 5.6 at 25 °C in CD2Cl2. 13 C NMR spectrum of complex 5.6 at 25 °C in CD2Cl2. 267 31 P NMR spectrum of complex 5.6 at 25 °C in CD2Cl2. IR spectrum of complex 5.6. 268 Rhodium 5.7 Complex 5.7 was synthesized using the procedure used for the synthesis of complex 3.1 (see Section 6.3.1). 2-((Di-tert-butylphosphino)methyl)pyridine 1 (18.6 mg, 78 µmol), chloro(dicarbonyl)rhodium(I) dimer (15.2 mg, 39 µmol), and sodium trifluoromethanesulfonate (30 mg, 0.17 mmol) were used. Pure product was isolated as a light yellow solid (23 mg, 54% yield). 1 H NMR (600 MHz, Methylene Chloride-d2) δ 9.50 (s, 1H), 7.79 (t, J = 7.9 Hz, 1H), 7.50 (d, J = 7.9 Hz, 1H), 7.29 (s, 1H), 3.49 (dd, J = 9.8, 2.5 Hz, 2H), 1.34 (dd, J = 14.3, 2.7 Hz, 18H). 13 C NMR (151 MHz, Methylene Chloride-d2) δ 162.98, 151.39, 139.17, 122.61, 122.54, 122.41, 35.88, 35.72, 34.17, 34.04, 29.02, 28.99. 31 P NMR (243 MHz, Methylene Chloride-d2) δ 100.20 (d, J = 167.7 Hz) HRMS (ESI/APCI): m/z = 368.0628 g/mol, calc’d. for C15H24RhNOP + [M-CO] + : 368.0645 g/mol. FT-IR (thin film / cm -1 ) ν = 3934, 3104, 3066, 3030, 2948, 2893, 2495, 2074, 1970, 1934, 1606, 1563, 1475, 1441, 1391, 1370, 1314, 1266, 1183, 1157, 1101, 1061, 1022, 937, 894, 832, 813. 1 H NMR spectrum of complex 5.7 at 25 °C in CD2Cl2. 269 13 C NMR spectrum of complex 5.7 at 25 °C in CD2Cl2. 270 31 P NMR spectrum of complex 5.7 at 25 °C in CD2Cl2. IR spectrum of complex 5.7. 271 6.5.3. Studies on CO2 Hydrogenation Hydrogen-deuterium exchange on the ligand arm of complex 1.18 In the drybox, complex 1.18 (2 mg, 2.6 µmol) was dissolved in 0.6 mL of CD3CN in a J- Young tube. Potassium tert-butoxide (0.5 mg) was added. The protons for the methylene arm, the O‒H, and the acetonitrile methyl all disappear, indicating H‒D exchanged on the methylene arm and O‒H and substitution of deuterated acetonitrile. All the non-exchangeable peaks remain the same (cf. Figures 6.5.2 and 6.5.3 in Section 6.5.2). Heating the deuterated complex in CH3CN to 110 °C for 12 hours leads to H‒D exchange and reappearance of the hydrogens on the methylene arm, the O‒H, and the acetonitrile methyl. Hydrogenation of CO2 using complex 1.18 In the drybox, an 8-dram vial was charged with complex 1.18 (4.0 mg, 5.2 µmol), KOtBu (0.6 mg, 53 µmol), and 2 mL of toluene. The vial was placed in a 600 mL Parr apparatus, which was then pressurized to 1000 psi with 1:1 H2/CO2 gas. The mixture was heated to 105 °C for 90 hours and then allowed to cool to room temperature. The pressure was released and analysis of the crude reaction mixture by NMR showed that methanol was not formed and only a trace amount of formic acid was present. 272 6.5.4. Acceptorless Dehydrogenation Studies Conversion of glycerol to lactate using ruthenium 5.3 In the drybox, a 25 mL round bottom flask was charged with 5.3 (10.1 mg, 16.6 µmol) and KOH (1.5 g, 26.7 mmol). The flask was taken out of the drybox and glycerol (2.0 mL, 27.3 mmol) was added. The flask was fitted with a vent line connected to a 1 L euditometer filled with water. The mixture was heated to 145 °C overnight producing 940 mL of gas. The 1 H NMR of the crude reaction mixture showed clean conversion to lactic acid. The ratio of glycerol to lactic acid was 1:1 (vide infra). Since ca. 680 mL of H2 would have been produced if one equivalent of H2 was produced, the production of 940 mL of gas indicates that gases other than H2 (perhaps CO or CO2) might be forming. Figure 6.5.4. 1 H NMR spectrum of the crude reaction mixture showing glycerol and lactate. 273 The Guerbet reaction of iridium 5.4 These procedures were provided by Xingyue Zhang and are discussed in her thesis. 35 Coupling of 1-butanol to form 5.13 1.0 mol% of 5.4 (5.8 mg, 7.7 µmol), 10 mol% KOH (4.4 mg, 77 µmol), and 1-octanol (4.10, 0.125 mL, 0.79 mmol) were added to a 2 mL Schlenk bomb in a glove box. The reaction was sealed and removed from the glove box and placed into a 130 °C oil bath for 48 hours under positive N2 pressure. After 48 hours, an aliquot from the solution was dissolved in CDCl 3 (0.6 mL), and a 1 H NMR spectrum was taken to determine conversion. The reaction mixture was extracted with hexanes and run through the GC-MS to confirm the identity of 5.13. Coupling of EtOH to 1-butanol 0.20 mol% of 5.4 (2.6 mg, 3.5 µmol), 10 mol% KOH (9.6 mg, 35 µmol), and ethanol (0.1 mL, 1.7 mmol) were added to a 2 mL Schlenk bomb in a glove box. The reaction was sealed and removed from the glove box and into a 150 °C oil bath for 90 hours. After 90 hours, an aliquot from the solution was dissolved in CDCl3 (0.6 mL), and a 1 H NMR spectrum was taken to determine conversion. 274 6.5.5. NMR Studies to Observe Formation of Complexes 5.17 – 5.21 NMR studies were performed to observe and characterize complexes 5.17 – 5.21. In the drybox, the pyridylphosphine complex (ca. 5 mg) is dissolved in CD2Cl2 in a J-Young tube. KOtBu is then added and reaction progress is followed by NMR. When the reaction is complete, the solution is filtered to remove excess KOtBu. The solvent is evaporated in vacuo to remove tert- butanol. The residue is then redissolved in CD2Cl2 and the resulting deprotonated complex is characterized by NMR. Iridium 5.17 1 H NMR (500 MHz, Methylene Chloride-d2) δ 6.68 (d, J = 6.6 Hz, 1H), 6.39 – 6.27 (m, 2H), 5.08 (s, 1H), 4.44 – 4.34 (m, 2H), 4.12 – 4.03 (m, 2H), 3.42 (d, J = 2.7 Hz, 1H), 2.30 – 2.20 (m, 2H), 2.15 – 2.04 (m, 2H), 1.86 (dt, J = 14.1, 6.9 Hz, 2H), 1.65 – 1.55 (m, 2H), 1.28 (dd, J = 13.1, 2.6 Hz, 18H). 13 C NMR (126 MHz, Methylene Chloride-d2) δ 144.17, 131.48, 117.68, 117.55, 100.75, 82.02, 81.92, 67.06, 66.59, 56.43, 37.33, 37.12, 33.59, 29.59, 29.56, 28.67. 31 P NMR (202 MHz, Methylene Chloride-d2) δ 46.07 For the 1 H NMR spectrum of complex 5.17, see Figure 5.7. Complex 5.17 is unstable to air and moisture and IR and MALDI data were not obtained. 275 13 C NMR spectrum of complex 5.17 at 25 °C in CD2Cl2. 31 P NMR spectrum of complex 5.17 at 25 °C in CD2Cl2. 276 Iridium 5.18 1 H NMR (600 MHz, Methylene Chloride-d2) δ 6.77 (d, J = 6.6 Hz, 1H), 6.46 – 6.30 (m, 2H), 5.16 (td, J = 6.3, 1.8 Hz, 1H), 4.52 (q, J = 3.2 Hz, 2H), 3.70 (q, J = 2.8 Hz, 2H), 3.17 (d, J = 3.6 Hz, 1H), 2.23 (dddd, J = 13.5, 10.0, 7.4, 5.9 Hz, 2H), 2.19 – 2.07 (m, 4H), 1.90 (dd, J = 14.2, 7.0 Hz, 2H), 1.74 – 1.64 (m, 2H), 1.19 – 1.08 (m, 12H). 13 C NMR (151 MHz, Methylene Chloride-d2) δ 176.64, 176.52, 144.97, 131.85, 117.41, 117.29, 101.11, 85.73, 85.65, 62.08, 61.66, 55.28, 33.59, 33.57, 30.95, 28.73, 28.72, 25.48, 25.26, 17.74, 17.72, 17.42. 31 P NMR (243 MHz, Methylene Chloride-d2) δ 35.49. Complex 5.18 is unstable to air and moisture and IR and MALDI data were not obtained. 1 H NMR spectrum of complex 5.18 at 25 °C in CD2Cl2. 277 13 C NMR spectrum of complex 5.18 at 25 °C in CD2Cl2. 31 P NMR spectrum of complex 5.18 at 25 °C in CD2Cl2. 278 Rhodium 5.20 1 H NMR (500 MHz, Benzene-d6) δ 6.52 (d, J = 6.5 Hz, 1H), 6.47 (d, J = 8.8 Hz, 1H), 6.41 (ddd, J = 8.8, 6.4, 2.6 Hz, 1H), 5.30 (t, J = 6.2 Hz, 1H), 4.66 (d, J = 5.2 Hz, 2H), 4.34 (dd, J = 5.1, 2.6 Hz, 2H), 3.22 (d, J = 3.2 Hz, 1H), 2.22 – 2.10 (m, 2H), 2.01 – 1.89 (m, 2H), 1.78 (dt, J = 14.4, 7.2 Hz, 2H), 1.57 – 1.48 (m, 2H), 1.25 (dd, J = 12.4, 2.5 Hz, 15H). 13 C NMR (126 MHz, Benzene-d6) δ 145.33, 132.29, 117.72, 117.58, 101.14, 96.03, 95.95, 95.88, 70.86, 70.77, 62.30, 61.87, 36.86, 36.84, 36.71, 36.70, 32.96, 32.94, 29.91, 29.87, 28.33. 31 P NMR (202 MHz, Benzene-d6) δ 54.73 (d, J = 145.4 Hz). Complex 5.20 is unstable to air and moisture and IR and MALDI data were not obtained. 1 H NMR spectrum of complex 5.20 at 25 °C in CD2Cl2. 279 13 C NMR spectrum of complex 5.20 at 25 °C in CD2Cl2. 31 P NMR spectrum of complex 5.20 at 25 °C in CD2Cl2. 280 Rhodium 5.21 1 H NMR (600 MHz, methylene chloride-d2) δ 6.33 – 6.27 (m, 1H), 6.13 (d, J = 8.9 Hz, 1H), 6.08 (d, J = 6.2 Hz, 1H), 5.05 (td, J = 6.2, 1.5 Hz, 1H), 4.64 (td, J = 2.9, 1.5 Hz, 2H), 4.16 (td, J = 3.0, 1.5 Hz, 2H), 3.89 (tp, J = 3.5, 1.8 Hz, 2H), 3.04 (s, 1H), 1.54 (dq, J = 8.2, 1.6 Hz, 1H), 1.43 (dt, J = 8.2, 1.6 Hz, 1H), 1.27 – 1.22 (m, 18H). 13 C NMR (151 MHz, Methylene Chloride-d2) δ 144.90, 131.98, 115.86, 115.75, 99.42, 79.37, 79.33, 79.31, 79.26, 65.17, 65.16, 65.14, 65.13, 62.44, 62.09, 55.21, 55.15, 52.06, 36.14, 36.12, 36.00, 35.99, 30.95, 29.47, 29.44, 29.22, 29.18. 31 P NMR (243 MHz, Methylene Chloride-d2) δ 58.65 (d, J = 165.2 Hz). Complex 5.21 is unstable to air and moisture and IR and MALDI data were not obtained. 1 H NMR spectrum of complex 5.21 at 25 °C in CD2Cl2. 281 13 C NMR spectrum of complex 5.21 at 25 °C in CD2Cl2. NMR spectrum of complex 5.21 at 25 °C in CD2Cl2. 282 6.6. X-ray Crystallography Data We gratefully acknowledge Prof. Ralf Haiges for helping us with X-ray data acquisition and solving the solid state structures of complexes 3.1, 4.1, and 5.4. 6.6.1. Crystal Structure Data for Iridium 3.1 Figure 6.6.1. ORTEP diagram of iridium 3.1. Ellipsoids are drawn at the 50% probability level. A clear orange plate-like specimen of C25H39ClF3IrNO3PS, approximate dimensions 0.111 mm x 0.165 mm x 0.211 mm, was used for the X-ray crystallographic analysis. The X-ray intensity data were measured on a Bruker APEX DUO system equipped with a TRIUMPH curved-crystal monochromator and a MoKα fine-focus tube (λ = 0.71073 Å). A total of 2520 frames were collected. The total exposure time was 7.00 hours. The frames were integrated with the Bruker SAINT software package using a SAINT V8.34A (Bruker AXS, 2013) algorithm. The integration of the data using a monoclinic unit cell yielded a total of 68655 283 reflections to a maximum θ angle of 30.66° (0.70 Å resolution), of which 8609 were independent (average redundancy 7.975, completeness = 98.5%, Rint = 6.47%, Rsig = 3.89%) and 7161 (83.18%) were greater than 2σ(F 2 ). The final cell constants of a = 8.1455(8) Å, b = 16.5588(16) Å, c = 20.962(2) Å, β = 94.132(2)°, volume = 2820.0(5) Å 3 , are based upon the refinement of the XYZ- centroids of 9400 reflections above 20 σ(I) with 4.92° < 2θ < 61.25°. Data were corrected for absorption effects using the multi-scan method (SADABS). The ratio of minimum to maximum apparent transmission was 0.642. The calculated minimum and maximum transmission coefficients (based on crystal size) are 0.4180 and 0.6060. The structure was solved and refined using the Bruker SHELXTL Software Package, using the space group P 1 21/c 1, with Z = 4 for the formula unit, C 25H39ClF3IrNO3PS. The final anisotropic full-matrix least-squares refinement on F 2 with 336 variables converged at R1 = 3.38%, for the observed data and wR2 = 7.42% for all data. The goodness-of-fit was 1.039. The largest peak in the final difference electron density synthesis was 2.425 e - /Å 3 and the largest hole was - 1.196 e - /Å 3 with an RMS deviation of 0.173 e - /Å 3 . On the basis of the final model, the calculated density was 1.765 g/cm 3 and F(000), 1488 e - . 284 Sample and crystal data for iridium 4.1. Identification code Jessica Chemical formula C25H39ClF3IrNO3PS Formula weight 749.25 Temperature 100(2) K Wavelength 0.71073 Å Crystal size 0.111 x 0.165 x 0.211 mm Crystal habit clear orange plate Crystal system monoclinic Space group P 1 21/c 1 Unit cell dimensions a = 8.1455(8) Å α = 90° b = 16.5588(16) Å β = 94.132(2)° c = 20.962(2) Å γ = 90° Volume 2820.0(5) Å 3 Z 4 Density (calculated) 1.765 g/cm 3 Absorption coefficient 5.007 mm -1 F(000) 1488 285 Data collection and structure refinement for iridium 3.1. Diffractometer Bruker APEX DUO Radiation source fine-focus tube, MoKα Theta range for data collection 1.57 to 30.66° Index ranges -11<=h<=11, -23<=k<=23, -30<=l<=29 Reflections collected 68655 Independent reflections 8609 [R(int) = 0.0647] Coverage of independent reflections 98.5% Absorption correction multi-scan Max. and min. transmission 0.6060 and 0.4180 Structure solution technique direct methods Structure solution program SHELXTL XT 2013/6 (Sheldrick, 2013) Refinement method Full-matrix least-squares on F 2 Refinement program SHELXTL XLMP 2014/1 (Bruker AXS, 2013) Function minimized Σ w(Fo 2 - Fc 2 ) 2 Data / restraints / parameters 8609 / 0 / 336 Goodness-of-fit on F 2 1.039 Δ/σmax 0.001 Final R indices 7161 data; I>2σ(I) R1 = 0.0338, wR2 = 0.0697 all data R1 = 0.0475, wR2 = 0.0742 Weighting scheme w=1/[σ 2 (Fo 2 )+(0.0202P) 2 +14.0820P] where P=(Fo 2 +2Fc 2 )/3 Largest diff. peak and hole 2.425 and -1.196 eÅ -3 R.M.S. deviation from mean 0.173 eÅ -3 286 Atomic coordinates and equivalent isotropic atomic displacement parameters (Å 2 ) for iridium 3.1. U(eq) is defined as one third of the trace of the orthogonalized Uij tensor. x/a y/b z/c U(eq) C1 0.6194(5) 0.0263(2) 0.37115(18) 0.0161(7) C2 0.5910(5) 0.9407(2) 0.36121(19) 0.0172(7) C3 0.4406(5) 0.9203(2) 0.38770(19) 0.0172(7) C4 0.3733(5) 0.9930(2) 0.41537(18) 0.0168(7) C5 0.4855(5) 0.0570(2) 0.40540(18) 0.0161(7) C6 0.7775(5) 0.0711(3) 0.3651(2) 0.0230(8) C7 0.7101(6) 0.8804(3) 0.3379(2) 0.0265(9) C8 0.3681(6) 0.8372(2) 0.3907(2) 0.0243(9) C9 0.2201(5) 0.9966(3) 0.45131(18) 0.0200(8) C10 0.4805(6) 0.1416(3) 0.4305(2) 0.0252(9) C11 0.1759(5) 0.1585(2) 0.3206(2) 0.0198(8) C12 0.0771(5) 0.2236(2) 0.3024(2) 0.0232(9) C13 0.0458(5) 0.2401(2) 0.2383(2) 0.0244(9) C14 0.1085(5) 0.1881(2) 0.1942(2) 0.0224(8) C15 0.2028(5) 0.1217(2) 0.21508(19) 0.0162(7) C16 0.2562(5) 0.0597(2) 0.16908(19) 0.0183(8) C17 0.4411(6) 0.9100(3) 0.1528(2) 0.0234(9) C18 0.3223(7) 0.8496(3) 0.1795(2) 0.0321(11) C19 0.6127(6) 0.8729(3) 0.1542(3) 0.0389(13) C20 0.3804(7) 0.9259(3) 0.0821(2) 0.0382(12) C21 0.6138(5) 0.0748(3) 0.17956(19) 0.0202(8) C22 0.7811(5) 0.0388(3) 0.2041(2) 0.0279(9) C23 0.6169(6) 0.0927(3) 0.1078(2) 0.0320(11) C24 0.5900(5) 0.1554(2) 0.2144(2) 0.0237(9) C25 0.0621(7) 0.3481(3) 0.4916(2) 0.0332(11) Cl1 0.12181(12) 0.94466(6) 0.28736(5) 0.01814(18) F1 0.2217(4) 0.3526(3) 0.51074(18) 0.0557(10) F2 0.0440(4) 0.3768(2) 0.43187(15) 0.0458(8) F3 0.9828(4) 0.39791(18) 0.52904(17) 0.0458(8) Ir01 0.38599(2) 0.00731(2) 0.31072(2) 0.01079(4) N1 0.2420(4) 0.10888(18) 0.27825(16) 0.0148(6) O1 0.0901(6) 0.2009(3) 0.4563(2) 0.0545(12) 287 x/a y/b z/c U(eq) O2 0.8174(5) 0.2503(2) 0.4716(2) 0.0446(10) O3 0.0075(5) 0.2261(2) 0.56247(17) 0.0400(9) P1 0.44129(11) 0.00631(6) 0.20159(4) 0.01277(17) S1 0.98597(15) 0.24390(7) 0.49608(5) 0.0247(2) Bond lengths (Å) for iridium 3.1. C1-C5 1.440(6) C1-C2 1.449(6) C1-C6 1.499(5) C1-Ir01 2.230(4) C2-C3 1.422(6) C2-C7 1.499(6) C2-Ir01 2.207(4) C3-C4 1.461(5) C3-C8 1.499(6) C3-Ir01 2.185(4) C4-C5 1.424(5) C4-C9 1.505(5) C4-Ir01 2.216(4) C5-C10 1.499(5) C5-Ir01 2.245(4) C11-N1 1.349(5) C11-C12 1.382(6) C12-C13 1.379(6) C13-C14 1.387(6) C14-C15 1.393(5) C15-N1 1.356(5) C15-C16 1.495(6) C16-P1 1.836(4) C17-C19 1.526(7) C17-C18 1.526(6) C17-C20 1.550(7) C17-P1 1.895(4) C21-C23 1.536(6) C21-C22 1.542(6) C21-C24 1.540(6) C21-P1 1.889(4) C25-F3 1.337(6) C25-F1 1.335(6) C25-F2 1.338(6) C25-S1 1.838(5) Cl1-Ir01 2.4073(9) Ir01-N1 2.134(3) Ir01-P1 2.3634(10) O1-S1 1.423(4) O2-S1 1.435(4) O3-S1 1.421(4) 288 Bond angles (°) for iridium 3.1. C5-C1-C2 107.3(3) C5-C1-C6 123.6(4) C2-C1-C6 126.9(4) C5-C1-Ir01 71.8(2) C2-C1-Ir01 70.1(2) C6-C1-Ir01 136.4(3) C3-C2-C1 108.1(3) C3-C2-C7 124.4(4) C1-C2-C7 126.8(4) C3-C2-Ir01 70.3(2) C1-C2-Ir01 71.8(2) C7-C2-Ir01 131.5(3) C2-C3-C4 108.5(3) C2-C3-C8 126.0(4) C4-C3-C8 125.4(4) C2-C3-Ir01 71.9(2) C4-C3-Ir01 71.8(2) C8-C3-Ir01 125.1(3) C5-C4-C3 107.0(3) C5-C4-C9 127.5(4) C3-C4-C9 125.4(4) C5-C4-Ir01 72.5(2) C3-C4-Ir01 69.5(2) C9-C4-Ir01 126.2(3) C4-C5-C1 109.2(3) C4-C5-C10 127.6(4) C1-C5-C10 123.0(4) C4-C5-Ir01 70.3(2) C1-C5-Ir01 70.6(2) C10-C5-Ir01 129.4(3) N1-C11-C12 123.1(4) C13-C12-C11 119.1(4) C12-C13-C14 118.4(4) C13-C14-C15 120.2(4) N1-C15-C14 121.0(4) N1-C15-C16 117.6(3) C14-C15-C16 121.3(4) C15-C16-P1 111.1(3) C19-C17-C18 109.5(4) C19-C17-C20 108.4(4) C18-C17-C20 107.2(4) C19-C17-P1 111.3(3) C18-C17-P1 109.2(3) C20-C17-P1 111.1(3) C23-C21-C22 108.9(4) C23-C21-C24 108.0(4) C22-C21-C24 108.4(4) C23-C21-P1 114.9(3) C22-C21-P1 109.9(3) C24-C21-P1 106.5(3) F3-C25-F1 106.8(4) F3-C25-F2 107.8(5) F1-C25-F2 107.5(4) F3-C25-S1 111.7(3) F1-C25-S1 111.3(4) F2-C25-S1 111.5(3) N1-Ir01-C3 146.45(14) N1-Ir01-C2 157.89(14) C3-Ir01-C2 37.77(15) N1-Ir01-C4 109.65(13) C3-Ir01-C4 38.76(14) C2-Ir01-C4 63.87(14) N1-Ir01-C1 119.77(13) C3-Ir01-C1 63.50(15) C2-Ir01-C1 38.13(15) C4-Ir01-C1 63.35(14) N1-Ir01-C5 98.56(13) C3-Ir01-C5 63.09(14) C2-Ir01-C5 63.02(14) C4-Ir01-C5 37.22(14) 289 C1-Ir01-C5 37.55(14) N1-Ir01-P1 80.53(9) C3-Ir01-P1 131.85(11) C2-Ir01-P1 105.68(11) C4-Ir01-P1 169.46(10) C1-Ir01-P1 109.67(10) C5-Ir01-P1 140.93(11) N1-Ir01-Cl1 79.16(9) C3-Ir01-Cl1 89.85(11) C2-Ir01-Cl1 121.11(11) C4-Ir01-Cl1 92.90(10) C1-Ir01-Cl1 152.83(10) C5-Ir01-Cl1 126.75(11) P1-Ir01-Cl1 91.72(3) C11-N1-C15 118.0(3) C11-N1-Ir01 120.4(3) C15-N1-Ir01 121.3(3) C16-P1-C21 103.03(19) C16-P1-C17 103.6(2) C21-P1-C17 110.21(19) C16-P1-Ir01 98.47(13) C21-P1-Ir01 115.43(13) C17-P1-Ir01 122.39(14) O3-S1-O1 115.7(3) O3-S1-O2 114.4(3) O1-S1-O2 115.0(3) O3-S1-C25 103.1(2) O1-S1-C25 102.9(3) O2-S1-C25 103.3(2) Anisotropic atomic displacement parameters (Å 2 ) for iridium 3.1. The anisotropic atomic displacement factor exponent takes the form: -2π 2 [ h 2 a *2 U11 + ... + 2 h k a * b * U12 ] U11 U22 U33 U23 U13 U12 C1 0.0121(16) 0.0208(18) 0.0147(17) 0.0031(14) -0.0038(13) 0.0008(13) C2 0.0147(18) 0.0205(18) 0.0160(18) 0.0025(14) -0.0020(14) 0.0051(14) C3 0.023(2) 0.0145(17) 0.0144(18) 0.0032(13) 0.0014(15) 0.0028(14) C4 0.0179(17) 0.0184(18) 0.0139(16) 0.0006(14) 0.0003(13) 0.0027(14) C5 0.0194(19) 0.0170(17) 0.0108(17) -0.0018(13) -0.0058(14) 0.0001(14) C6 0.0160(19) 0.029(2) 0.024(2) -0.0012(17) -0.0028(16) -0.0058(16) C7 0.024(2) 0.022(2) 0.034(2) 0.0033(18) 0.0052(18) 0.0096(17) C8 0.032(2) 0.0162(19) 0.024(2) 0.0042(16) 0.0025(18) -0.0003(16) C9 0.0206(18) 0.026(2) 0.0143(17) 0.0020(15) 0.0035(14) 0.0008(16) C10 0.029(2) 0.020(2) 0.025(2) -0.0082(16) -0.0020(18) -0.0023(17) C11 0.020(2) 0.0185(18) 0.021(2) -0.0004(15) 0.0000(15) 0.0000(15) C12 0.021(2) 0.0149(18) 0.034(2) -0.0047(16) 0.0008(17) 0.0020(15) C13 0.018(2) 0.0143(18) 0.040(3) 0.0071(17) -0.0043(17) 0.0011(14) C14 0.0178(19) 0.0214(19) 0.027(2) 0.0101(17) -0.0023(16) -0.0015(16) C15 0.0132(17) 0.0179(18) 0.0175(18) 0.0036(14) 0.0008(14) -0.0018(13) C16 0.0164(18) 0.0236(19) 0.0146(18) 0.0025(14) -0.0016(14) 0.0015(15) 290 U11 U22 U33 U23 U13 U12 C17 0.027(2) 0.021(2) 0.023(2) -0.0075(16) 0.0070(17) -0.0020(16) C18 0.046(3) 0.020(2) 0.031(3) -0.0085(18) 0.011(2) -0.0069(19) C19 0.033(3) 0.034(3) 0.050(3) -0.020(2) 0.003(2) 0.007(2) C20 0.054(3) 0.038(3) 0.023(2) -0.009(2) 0.003(2) -0.011(2) C21 0.0180(19) 0.0240(19) 0.019(2) 0.0047(15) 0.0018(15) -0.0017(16) C22 0.019(2) 0.028(2) 0.037(3) 0.0012(19) 0.0032(18) -0.0023(17) C23 0.036(3) 0.038(3) 0.023(2) 0.0096(19) 0.010(2) -0.007(2) C24 0.021(2) 0.0166(19) 0.033(2) 0.0042(17) 0.0022(17) -0.0043(15) C25 0.030(3) 0.044(3) 0.025(2) -0.004(2) 0.0019(19) -0.008(2) Cl1 0.0159(4) 0.0167(4) 0.0218(5) -0.0001(3) 0.0011(3) -0.0028(3) F1 0.0321(18) 0.081(3) 0.053(2) -0.0077(19) -0.0037(16) -0.0222(18) F2 0.052(2) 0.054(2) 0.0322(17) 0.0097(15) 0.0037(15) -0.0128(16) F3 0.059(2) 0.0287(16) 0.051(2) -0.0066(14) 0.0140(17) -0.0036(14) Ir01 0.01103(6) 0.01005(6) 0.01122(6) -0.00013(5) 0.00038(4) 0.00010(5) N1 0.0151(15) 0.0119(14) 0.0170(16) 0.0021(11) -0.0024(12) 0.0011(11) O1 0.066(3) 0.052(3) 0.048(3) -0.016(2) 0.022(2) 0.014(2) O2 0.036(2) 0.037(2) 0.057(3) 0.0117(18) -0.0185(19) -0.0072(16) O3 0.056(2) 0.038(2) 0.0249(18) -0.0017(15) -0.0054(17) -0.0063(18) P1 0.0130(4) 0.0127(4) 0.0125(4) -0.0001(3) 0.0005(3) -0.0007(3) S1 0.0283(6) 0.0257(5) 0.0199(5) -0.0052(4) -0.0008(4) 0.0030(4) Hydrogen atomic coordinates and isotropic atomic displacement parameters (Å 2 ) for iridium 3.1. x/a y/b z/c U(eq) H6A 0.7549 0.1217 0.3419 0.035 H6B 0.8523 0.0378 0.3416 0.035 H6C 0.8286 0.0830 0.4078 0.035 H7A 0.7848 -0.0926 0.3101 0.04 H7B 0.6495 -0.1622 0.3138 0.04 H7C 0.7740 -0.1435 0.3746 0.04 H8A 0.4267 -0.1934 0.4252 0.036 H8B 0.3786 -0.1905 0.3499 0.036 H8C 0.2514 -0.1586 0.3989 0.036 H9A 0.2447 -0.0231 0.4950 0.03 H9B 0.1345 -0.0373 0.4297 0.03 291 x/a y/b z/c U(eq) H9C 0.1811 0.0525 0.4526 0.03 H10A 0.3759 0.1506 0.4497 0.038 H10B 0.4904 0.1798 0.3952 0.038 H10C 0.5719 0.1498 0.4628 0.038 H11 0.1984 0.1482 0.3649 0.024 H12 0.0314 0.2565 0.3338 0.028 H13 -0.0172 0.2860 0.2246 0.029 H14 0.0870 0.1977 0.1497 0.027 H16A 0.2793 0.0863 0.1284 0.022 H16B 0.1662 0.0203 0.1599 0.022 H18A 0.3610 -0.1648 0.2234 0.048 H18B 0.3170 -0.1991 0.1529 0.048 H18C 0.2125 -0.1262 0.1794 0.048 H19A 0.6877 -0.0895 0.1349 0.058 H19B 0.6080 -0.1778 0.1300 0.058 H19C 0.6527 -0.1380 0.1986 0.058 H20A 0.2676 -0.0531 0.0802 0.057 H20B 0.3825 -0.1247 0.0579 0.057 H20C 0.4526 -0.0345 0.0636 0.057 H22A 0.8636 0.0818 0.2085 0.042 H22B 0.8154 -0.0016 0.1735 0.042 H22C 0.7707 0.0131 0.2457 0.042 H23A 0.5084 0.1119 0.0911 0.048 H23B 0.6448 0.0433 0.0852 0.048 H23C 0.6997 0.1343 0.1012 0.048 H24A 0.5770 0.1449 0.2598 0.036 H24B 0.4915 0.1827 0.1954 0.036 H24C 0.6864 0.1899 0.2102 0.036 292 6.6.2. Crystal Structure Data for Ruthenium 4.1 Figure 6.6.2. ORTEP diagram of ruthenium 4.1. Ellipsoids are drawn at the 50% probability level. A clear orange plate-like specimen of C 25.50 H 39 Cl 2 F 3 NO 3 PRuS, approximate dimensions 0.037 mm x 0.130 mm x 0.159 mm, was used for the X-ray crystallographic analysis. The X-ray intensity data were measured on a Bruker APEX DUO system equipped with a TRIUMPH curved- crystal monochromator and a MoKα fine-focus tube (λ = 0.71073 Å). A total of 3429 frames were collected. The total exposure time was 16.69 hours. The frames were integrated with the Bruker SAINT software package using a SAINT V8.30C (Bruker AXS, 2013) algorithm. The integration of the data using a monoclinic unit cell yielded a total of 99186 293 reflections to a maximum θ angle of 30.58° (0.70 Å resolution), of which 17308 were independent (average redundancy 5.731, completeness = 99.4%, Rint = 5.25%) and 15885 (91.78%) were greater than 2σ(F 2 ). The final cell constants of a = 8.674(14) Å, b = 24.77(4) Å, c = 13.71(2) Å, β = 102.912(17)°, volume = 2871.(8) Å 3 , are based upon the refinement of the XYZ-centroids of 9586 reflections above 20 σ(I) with 4.478° < 2θ < 60.99°. Data were corrected for absorption effects using the multi-scan method (SADABS). The ratio of minimum to maximum apparent transmission was 0.893. The calculated minimum and maximum transmission coefficients (based on crystal size) are 0.8690 and 0.9670. The structure was solved and refined using the Bruker SHELXTL Software Package, using the space group P 1 21 1, with Z = 4 for the formula unit, C25.50H39Cl2F3NO3PRuS. The final anisotropic full-matrix least-squares refinement on F 2 with 695 variables converged at R1 = 3.84%, for the observed data and wR2 = 9.04% for all data. The goodness-of-fit was 1.045. The largest peak in the final difference electron density synthesis was 1.729 e - /Å 3 and the largest hole was - 1.250 e - /Å 3 with an RMS deviation of 0.115 e - /Å 3 . On the basis of the final model, the calculated density was 1.619 g/cm -3 and F (000), 1436 e - . 294 Sample and crystal data for ruthenium 4.1. Identification code Jeff051913 Chemical formula C25.50H39Cl2F3NO3PRuS Formula weight 699.57 Wavelength 0.71073 Å Crystal size 0.037 x 0.130 x 0.159 mm Crystal habit clear orange plate Crystal system monoclinic Space group P 1 21 1 Unit cell dimensions a = 8.674(14) Å α = 90° b = 24.77(4) Å β = 102.912(17)° c = 13.71(2) Å γ = 90° Volume 2871.(8) Å 3 Z 4 Density (calculated) 1.619 g/cm 3 Absorption coefficient 0.909 mm -1 F(000) 1436 295 Data collection and structure refinement for ruthenium 4.1. Diffractometer Bruker APEX DUO Radiation source fine-focus tube, MoKα Theta range for data collection 1.64 to 30.58° Index ranges -12<=h<=12, -35<=k<=35, -19<=l<=19 Reflections collected 99186 Independent reflections 17308 [R(int) = 0.0525] Coverage of independent reflections 99.4% Absorption correction multi-scan Max. and min. transmission 0.9670 and 0.8690 Structure solution technique direct methods Structure solution program SHELXTL XT 2013/1 (Sheldrick, 2013) Refinement method Full-matrix least-squares on F 2 Refinement program SHELXTL XL 2013/2 (Bruker AXS, 2013) Function minimized Σ w(Fo 2 - Fc 2 ) 2 Data / restraints / parameters 17308 / 2 / 695 Goodness-of-fit on F 2 1.045 Δ/σmax 0.001 Final R indices 15885 data; I>2σ(I) R1 = 0.0384, wR2 = 0.0875 all data R1 = 0.0451, wR2 = 0.0904 Weighting scheme w=1/[σ 2 (Fo 2 )+(0.0437P) 2 +4.3600P] where P=(Fo 2 +2Fc 2 )/3 Absolute structure parameter 0.5(0) Largest diff. peak and hole 1.729 and -1.250 eÅ -3 R.M.S. deviation from mean 0.115 eÅ -3 296 Atomic coordinates and equivalent isotropic atomic displacement parameters (Å 2 ) for ruthenium 4.1. U(eq) is defined as one third of the trace of the orthogonalized U ij tensor. x/a y/b z/c U(eq) C1 0.9054(6) 0.5895(2) 0.0740(4) 0.0119(9) C2 0.0582(6) 0.57232(19) 0.1271(4) 0.0117(9) C3 0.0785(6) 0.5429(2) 0.2159(4) 0.0126(9) C4 0.9460(6) 0.52867(18) 0.2553(4) 0.0114(9) C5 0.7952(6) 0.54695(19) 0.2066(4) 0.0123(9) C6 0.7752(6) 0.5766(2) 0.1155(4) 0.0123(9) C7 0.8811(6) 0.6245(2) 0.9803(4) 0.0157(10) C8 0.8400(7) 0.6821(2) 0.0082(5) 0.0241(11) C9 0.0222(7) 0.6257(2) 0.9314(4) 0.0232(12) C10 0.9659(6) 0.4968(2) 0.3510(3) 0.0154(9) C11 0.0938(6) 0.4089(2) 0.2093(4) 0.0146(9) C12 0.1444(6) 0.3565(2) 0.2358(4) 0.0164(10) C13 0.0702(7) 0.3139(2) 0.1791(5) 0.0235(12) C14 0.9419(7) 0.3243(2) 0.1018(5) 0.0205(11) C15 0.8931(6) 0.3775(2) 0.0806(4) 0.0139(9) C16 0.7558(6) 0.3894(2) 0.9957(4) 0.0143(9) C17 0.5472(6) 0.4735(2) 0.8869(4) 0.0146(10) C18 0.6607(6) 0.4985(3) 0.8282(4) 0.0187(9) C19 0.4223(7) 0.5157(2) 0.8948(4) 0.0236(12) C20 0.4705(7) 0.4241(3) 0.8264(4) 0.0264(13) C21 0.5236(6) 0.4364(2) 0.0989(4) 0.0139(9) C22 0.6232(7) 0.4116(2) 0.1960(4) 0.0169(10) C23 0.4356(6) 0.4864(2) 0.1263(4) 0.0173(11) C24 0.4004(6) 0.3938(2) 0.0499(5) 0.0207(11) C25 0.0403(5) 0.58672(19) 0.5583(4) 0.0107(8) C26 0.1723(6) 0.59918(18) 0.5183(4) 0.0108(9) C27 0.1562(6) 0.62891(19) 0.4285(4) 0.0121(9) C28 0.0070(6) 0.64771(19) 0.3769(4) 0.0117(9) C29 0.8720(5) 0.63338(19) 0.4152(4) 0.0106(8) C30 0.8882(6) 0.60359(18) 0.5034(4) 0.0110(8) C31 0.0623(7) 0.5530(2) 0.6528(4) 0.0168(10) C32 0.1072(7) 0.4953(2) 0.6296(4) 0.0215(11) C33 0.9186(7) 0.5523(2) 0.6995(4) 0.0214(11) C34 0.9920(6) 0.6810(2) 0.2834(4) 0.0161(9) 297 x/a y/b z/c U(eq) C35 0.8515(6) 0.7670(2) 0.4245(4) 0.0142(9) C36 0.7894(6) 0.8180(2) 0.4048(4) 0.0177(10) C37 0.8661(7) 0.8610(2) 0.4601(5) 0.0225(11) C38 0.9980(6) 0.85055(19) 0.5330(4) 0.0162(10) C39 0.0546(6) 0.7978(2) 0.5526(4) 0.0126(9) C40 0.1931(6) 0.78615(18) 0.6364(4) 0.0123(9) C41 0.4281(6) 0.7382(2) 0.5376(4) 0.0124(9) C42 0.3332(6) 0.7656(2) 0.4427(4) 0.0164(10) C43 0.5551(6) 0.7780(2) 0.5898(4) 0.0172(10) C44 0.5110(6) 0.6870(2) 0.5090(4) 0.0155(10) C45 0.3965(6) 0.7013(2) 0.7476(4) 0.0145(9) C46 0.4772(7) 0.7502(2) 0.8080(4) 0.0222(11) C47 0.5211(7) 0.6584(2) 0.7406(4) 0.0215(11) C48 0.2829(6) 0.6778(2) 0.8066(4) 0.0166(9) C49 0.5840(8) 0.4364(3) 0.5098(5) 0.0275(13) C50 0.3877(8) 0.7354(3) 0.1303(5) 0.0264(12) C51 0.9381(9) 0.8639(3) 0.1875(7) 0.047(2) Cl1 0.01951(13) 0.47848(5) 0.96010(9) 0.0125(2) Cl2 0.92689(13) 0.69742(4) 0.67094(9) 0.0116(2) Cl3 0.1211(3) 0.85203(13) 0.25346(17) 0.0691(8) Cl4 0.8229(3) 0.80552(7) 0.14207(17) 0.0595(7) F1 0.7229(5) 0.44451(18) 0.5715(4) 0.0556(14) F2 0.6096(8) 0.40167(18) 0.4415(4) 0.0663(17) F3 0.4952(6) 0.4125(3) 0.5622(4) 0.0653(17) F4 0.4632(7) 0.75035(19) 0.0604(3) 0.0485(12) F5 0.2341(5) 0.73648(19) 0.0890(4) 0.0510(13) F6 0.4181(6) 0.77262(18) 0.2010(3) 0.0431(11) N1 0.9671(5) 0.41959(16) 0.1345(3) 0.0114(8) N2 0.9804(5) 0.75627(17) 0.4970(3) 0.0104(8) O1 0.4927(9) 0.5327(3) 0.5360(4) 0.066(2) O2 0.6102(6) 0.5167(2) 0.3959(4) 0.0408(12) O3 0.3506(6) 0.4816(3) 0.3913(5) 0.068(2) O4 0.6112(5) 0.6774(3) 0.2288(4) 0.0389(11) O5 0.4253(6) 0.6351(2) 0.0919(4) 0.0322(10) O6 0.3454(6) 0.6577(2) 0.2457(4) 0.0370(11) P1 0.66400(14) 0.45412(5) 0.01614(9) 0.0098(2) P2 0.28419(14) 0.72105(5) 0.61768(9) 0.0088(2) 298 x/a y/b z/c U(eq) Ru1 0.89657(4) 0.50044(2) 0.09656(2) 0.00767(7) Ru2 0.05183(4) 0.67549(2) 0.53556(2) 0.00708(7) S1 0.49890(16) 0.49927(8) 0.45138(11) 0.0268(3) S2 0.44897(15) 0.66852(6) 0.18003(10) 0.0198(3) Bond lengths (Å) for ruthenium 4.1. C1-C6 1.410(7) C1-C2 1.427(7) C1-C7 1.525(7) C1-Ru1 2.232(6) C2-C3 1.395(7) C2-Ru1 2.247(5) C2-H2 1.0 C3-C4 1.420(7) C3-Ru1 2.263(5) C3-H3 1.0 C4-C5 1.404(7) C4-C10 1.507(7) C4-Ru1 2.234(6) C5-C6 1.425(7) C5-Ru1 2.229(5) C5-H5 1.0 C6-Ru1 2.204(5) C6-H6 1.0 C7-C9 1.521(8) C7-C8 1.540(8) C7-H7 1.0 C8-H8A 0.98 C8-H8B 0.98 C8-H8C 0.98 C9-H9A 0.98 C9-H9B 0.98 C9-H9C 0.98 C10-H10A 0.98 C10-H10B 0.98 C10-H10C 0.98 C11-N1 1.351(7) C11-C12 1.390(7) C11-H11 0.95 C12-C13 1.382(9) C12-H12 0.95 C13-C14 1.379(9) C13-H13 0.95 C14-C15 1.394(8) C14-H14 0.95 C15-N1 1.355(7) C15-C16 1.497(7) C16-P1 1.838(6) C16-H16A 0.99 C16-H16B 0.99 C17-C19 1.525(8) C17-C18 1.534(7) C17-C20 1.543(8) C17-P1 1.896(6) C18-H18A 0.98 C18-H18B 0.98 C18-H18C 0.98 C19-H19A 0.98 C19-H19B 0.98 C19-H19C 0.98 C20-H20A 0.98 C20-H20B 0.98 C20-H20C 0.98 C21-C22 1.542(7) C21-C23 1.544(8) C21-C24 1.545(8) 299 C21-P1 1.892(5) C22-H22A 0.98 C22-H22B 0.98 C22-H22C 0.98 C23-H23A 0.98 C23-H23B 0.98 C23-H23C 0.98 C24-H24A 0.98 C24-H24B 0.98 C24-H24C 0.98 C25-C26 1.410(7) C25-C30 1.428(7) C25-C31 1.517(7) C25-Ru2 2.226(6) C26-C27 1.413(7) C26-Ru2 2.198(5) C26-H26 1.0 C27-C28 1.408(7) C27-Ru2 2.213(5) C27-H27 1.0 C28-C29 1.431(7) C28-C34 1.505(7) C28-Ru2 2.230(6) C29-C30 1.396(7) C29-Ru2 2.256(5) C29-H29 1.0 C30-Ru2 2.259(5) C30-H30 1.0 C31-C33 1.523(8) C31-C32 1.535(8) C31-H31 1.0 C32-H32A 0.98 C32-H32B 0.98 C32-H32C 0.98 C33-H33A 0.98 C33-H33B 0.98 C33-H33C 0.98 C34-H34A 0.98 C34-H34B 0.98 C34-H34C 0.98 C35-N2 1.346(6) C35-C36 1.377(7) C35-H35 0.95 C36-C37 1.387(8) C36-H36 0.95 C37-C38 1.365(8) C37-H37 0.95 C38-C39 1.401(7) C38-H38 0.95 C39-N2 1.354(7) C39-C40 1.494(7) C40-P2 1.839(5) C40-H40A 0.99 C40-H40B 0.99 C41-C43 1.530(7) C41-C42 1.533(7) C41-C44 1.553(7) C41-P2 1.885(5) C42-H42A 0.98 C42-H42B 0.98 C42-H42C 0.98 C43-H43A 0.98 C43-H43B 0.98 C43-H43C 0.98 C44-H44A 0.98 C44-H44B 0.98 C44-H44C 0.98 C45-C48 1.523(7) C45-C47 1.534(8) C45-C46 1.544(8) C45-P2 1.893(6) C46-H46A 0.98 C46-H46B 0.98 C46-H46C 0.98 C47-H47A 0.98 C47-H47B 0.98 300 C47-H47C 0.98 C48-H48A 0.98 C48-H48B 0.98 C48-H48C 0.98 C49-F3 1.307(8) C49-F1 1.324(8) C49-F2 1.326(8) C49-S1 1.831(7) C50-F6 1.321(8) C50-F5 1.326(8) C50-F4 1.329(8) C50-S2 1.825(7) C51-Cl3 1.668(8) C51-Cl4 1.790(8) C51-H51A 0.99 C51-H51B 0.99 Cl1-Ru1 2.413(3) Cl2-Ru2 2.411(3) N1-Ru1 2.125(5) N2-Ru2 2.127(5) O1-S1 1.436(6) O2-S1 1.423(5) O3-S1 1.432(6) O4-S2 1.434(5) O5-S2 1.440(5) O6-S2 1.431(5) P1-Ru1 2.368(3) P2-Ru2 2.364(3) Bond angles (°) for ruthenium 4.1. C6-C1-C2 117.6(5) C6-C1-C7 119.7(4) C2-C1-C7 122.5(4) C6-C1-Ru1 70.4(3) C2-C1-Ru1 72.0(3) C7-C1-Ru1 132.6(3) C3-C2-C1 121.5(5) C3-C2-Ru1 72.6(3) C1-C2-Ru1 70.8(3) C3-C2-H2 118.6 C1-C2-H2 118.6 Ru1-C2-H2 118.6 C2-C3-C4 120.4(5) C2-C3-Ru1 71.4(3) C4-C3-Ru1 70.5(3) C2-C3-H3 119.1 C4-C3-H3 119.1 Ru1-C3-H3 119.1 C5-C4-C3 119.1(5) C5-C4-C10 119.8(4) C3-C4-C10 121.1(4) C5-C4-Ru1 71.5(3) C3-C4-Ru1 72.7(3) C10-C4-Ru1 130.0(3) C4-C5-C6 120.1(4) C4-C5-Ru1 71.9(3) C6-C5-Ru1 70.3(3) C4-C5-H5 119.3 C6-C5-H5 119.3 Ru1-C5-H5 119.3 C1-C6-C5 121.2(4) C1-C6-Ru1 72.5(3) C5-C6-Ru1 72.2(3) C1-C6-H6 119.0 C5-C6-H6 119.0 Ru1-C6-H6 119.0 C9-C7-C1 114.1(4) C9-C7-C8 110.2(4) C1-C7-C8 108.4(4) C9-C7-H7 108.0 C1-C7-H7 108.0 C8-C7-H7 108.0 C7-C8-H8A 109.5 C7-C8-H8B 109.5 301 H8A-C8-H8B 109.5 C7-C8-H8C 109.5 H8A-C8-H8C 109.5 H8B-C8-H8C 109.5 C7-C9-H9A 109.5 C7-C9-H9B 109.5 H9A-C9-H9B 109.5 C7-C9-H9C 109.5 H9A-C9-H9C 109.5 H9B-C9-H9C 109.5 C4-C10-H10A 109.5 C4-C10-H10B 109.5 H10A-C10-H10B 109.5 C4-C10-H10C 109.5 H10A-C10-H10C 109.5 H10B-C10-H10C 109.5 N1-C11-C12 122.5(5) N1-C11-H11 118.8 C12-C11-H11 118.8 C13-C12-C11 119.1(5) C13-C12-H12 120.5 C11-C12-H12 120.5 C14-C13-C12 118.9(5) C14-C13-H13 120.6 C12-C13-H13 120.6 C13-C14-C15 119.5(5) C13-C14-H14 120.3 C15-C14-H14 120.3 N1-C15-C14 122.0(5) N1-C15-C16 117.9(5) C14-C15-C16 120.1(5) C15-C16-P1 110.5(4) C15-C16-H16A 109.5 P1-C16-H16A 109.5 C15-C16-H16B 109.5 P1-C16-H16B 109.5 H16A-C16-H16B 108.1 C19-C17-C18 108.1(5) C19-C17-C20 110.7(5) C18-C17-C20 106.7(5) C19-C17-P1 110.3(4) C18-C17-P1 108.7(3) C20-C17-P1 112.1(4) C17-C18-H18A 109.5 C17-C18-H18B 109.5 H18A-C18-H18B 109.5 C17-C18-H18C 109.5 H18A-C18-H18C 109.5 H18B-C18-H18C 109.5 C17-C19-H19A 109.5 C17-C19-H19B 109.5 H19A-C19-H19B 109.5 C17-C19-H19C 109.5 H19A-C19-H19C 109.5 H19B-C19-H19C 109.5 C17-C20-H20A 109.5 C17-C20-H20B 109.5 H20A-C20-H20B 109.5 C17-C20-H20C 109.5 H20A-C20-H20C 109.5 H20B-C20-H20C 109.5 C22-C21-C23 108.7(4) C22-C21-C24 107.6(4) C23-C21-C24 108.8(4) C22-C21-P1 107.3(4) C23-C21-P1 112.3(4) C24-C21-P1 111.9(4) C21-C22-H22A 109.5 C21-C22-H22B 109.5 H22A-C22-H22B 109.5 C21-C22-H22C 109.5 H22A-C22-H22C 109.5 H22B-C22-H22C 109.5 C21-C23-H23A 109.5 C21-C23-H23B 109.5 H23A-C23-H23B 109.5 302 C21-C23-H23C 109.5 H23A-C23-H23C 109.5 H23B-C23-H23C 109.5 C21-C24-H24A 109.5 C21-C24-H24B 109.5 H24A-C24-H24B 109.5 C21-C24-H24C 109.5 H24A-C24-H24C 109.5 H24B-C24-H24C 109.5 C26-C25-C30 117.8(5) C26-C25-C31 119.6(4) C30-C25-C31 122.4(5) C26-C25-Ru2 70.3(3) C30-C25-Ru2 72.7(3) C31-C25-Ru2 131.5(3) C25-C26-C27 121.4(4) C25-C26-Ru2 72.5(3) C27-C26-Ru2 71.9(3) C25-C26-H26 118.8 C27-C26-H26 118.8 Ru2-C26-H26 118.8 C28-C27-C26 120.7(4) C28-C27-Ru2 72.2(3) C26-C27-Ru2 70.8(3) C28-C27-H27 119.0 C26-C27-H27 119.0 Ru2-C27-H27 119.0 C27-C28-C29 118.0(5) C27-C28-C34 120.3(4) C29-C28-C34 121.8(4) C27-C28-Ru2 70.8(3) C29-C28-Ru2 72.4(3) C34-C28-Ru2 128.6(4) C30-C29-C28 121.1(4) C30-C29-Ru2 72.1(3) C28-C29-Ru2 70.4(3) C30-C29-H29 118.7 C28-C29-H29 118.7 Ru2-C29-H29 118.7 C29-C30-C25 120.9(5) C29-C30-Ru2 71.9(3) C25-C30-Ru2 70.2(3) C29-C30-H30 118.8 C25-C30-H30 118.8 Ru2-C30-H30 118.8 C25-C31-C33 114.0(4) C25-C31-C32 109.0(4) C33-C31-C32 110.2(4) C25-C31-H31 107.8 C33-C31-H31 107.8 C32-C31-H31 107.8 C31-C32-H32A 109.5 C31-C32-H32B 109.5 H32A-C32-H32B 109.5 C31-C32-H32C 109.5 H32A-C32-H32C 109.5 H32B-C32-H32C 109.5 C31-C33-H33A 109.5 C31-C33-H33B 109.5 H33A-C33-H33B 109.5 C31-C33-H33C 109.5 H33A-C33-H33C 109.5 H33B-C33-H33C 109.5 C28-C34-H34A 109.5 C28-C34-H34B 109.5 H34A-C34-H34B 109.5 C28-C34-H34C 109.5 H34A-C34-H34C 109.5 H34B-C34-H34C 109.5 N2-C35-C36 123.4(5) N2-C35-H35 118.3 C36-C35-H35 118.3 C35-C36-C37 118.5(5) C35-C36-H36 120.7 C37-C36-H36 120.7 C38-C37-C36 118.4(5) 303 C38-C37-H37 120.8 C36-C37-H37 120.8 C37-C38-C39 121.1(5) C37-C38-H38 119.4 C39-C38-H38 119.4 N2-C39-C38 120.0(5) N2-C39-C40 119.0(4) C38-C39-C40 120.9(5) C39-C40-P2 111.0(3) C39-C40-H40A 109.4 P2-C40-H40A 109.4 C39-C40-H40B 109.4 P2-C40-H40B 109.4 H40A-C40-H40B 108.0 C43-C41-C42 107.9(4) C43-C41-C44 108.6(4) C42-C41-C44 109.7(4) C43-C41-P2 112.0(4) C42-C41-P2 107.1(3) C44-C41-P2 111.5(3) C41-C42-H42A 109.5 C41-C42-H42B 109.5 H42A-C42-H42B 109.5 C41-C42-H42C 109.5 H42A-C42-H42C 109.5 H42B-C42-H42C 109.5 C41-C43-H43A 109.5 C41-C43-H43B 109.5 H43A-C43-H43B 109.5 C41-C43-H43C 109.5 H43A-C43-H43C 109.5 H43B-C43-H43C 109.5 C41-C44-H44A 109.5 C41-C44-H44B 109.5 H44A-C44-H44B 109.5 C41-C44-H44C 109.5 H44A-C44-H44C 109.5 H44B-C44-H44C 109.5 C48-C45-C47 108.4(5) C48-C45-C46 106.5(5) C47-C45-C46 109.7(5) C48-C45-P2 109.9(3) C47-C45-P2 110.0(4) C46-C45-P2 112.2(4) C45-C46-H46A 109.5 C45-C46-H46B 109.5 H46A-C46-H46B 109.5 C45-C46-H46C 109.5 H46A-C46-H46C 109.5 H46B-C46-H46C 109.5 C45-C47-H47A 109.5 C45-C47-H47B 109.5 H47A-C47-H47B 109.5 C45-C47-H47C 109.5 H47A-C47-H47C 109.5 H47B-C47-H47C 109.5 C45-C48-H48A 109.5 C45-C48-H48B 109.5 H48A-C48-H48B 109.5 C45-C48-H48C 109.5 H48A-C48-H48C 109.5 H48B-C48-H48C 109.5 F3-C49-F1 106.4(6) F3-C49-F2 107.9(6) F1-C49-F2 106.1(6) F3-C49-S1 113.4(5) F1-C49-S1 111.7(4) F2-C49-S1 111.0(5) F6-C50-F5 108.4(6) F6-C50-F4 106.6(6) F5-C50-F4 107.2(6) F6-C50-S2 111.5(5) F5-C50-S2 111.0(5) F4-C50-S2 111.9(5) Cl3-C51-Cl4 115.8(5) Cl3-C51-H51A 108.3 304 Cl4-C51-H51A 108.3 Cl3-C51-H51B 108.3 Cl4-C51-H51B 108.3 H51A-C51-H51B 107.4 C11-N1-C15 117.9(4) C11-N1-Ru1 120.8(3) C15-N1-Ru1 121.2(3) C35-N2-C39 118.5(4) C35-N2-Ru2 121.2(3) C39-N2-Ru2 120.0(3) C16-P1-C21 104.3(2) C16-P1-C17 103.8(2) C21-P1-C17 109.7(3) C16-P1-Ru1 98.06(19) C21-P1-Ru1 115.40(19) C17-P1-Ru1 122.27(17) C40-P2-C41 104.1(2) C40-P2-C45 104.0(2) C41-P2-C45 109.7(3) C40-P2-Ru2 97.93(19) C41-P2-Ru2 115.83(19) C45-P2-Ru2 121.97(17) N1-Ru1-C6 153.78(18) N1-Ru1-C5 117.21(18) C6-Ru1-C5 37.50(18) N1-Ru1-C1 161.62(17) C6-Ru1-C1 37.06(19) C5-Ru1-C1 67.25(19) N1-Ru1-C4 94.27(18) C6-Ru1-C4 67.05(18) C5-Ru1-C4 36.68(18) C1-Ru1-C4 79.64(18) N1-Ru1-C2 124.6(2) C6-Ru1-C2 66.1(2) C5-Ru1-C2 77.8(2) C1-Ru1-C2 37.15(18) C4-Ru1-C2 66.07(18) N1-Ru1-C3 98.35(19) C6-Ru1-C3 77.9(2) C5-Ru1-C3 65.6(2) C1-Ru1-C3 66.44(18) C4-Ru1-C3 36.80(18) C2-Ru1-C3 36.04(18) N1-Ru1-P1 79.98(14) C6-Ru1-P1 95.16(16) C5-Ru1-P1 98.14(16) C1-Ru1-P1 117.82(13) C4-Ru1-P1 124.27(13) C2-Ru1-P1 154.40(13) C3-Ru1-P1 161.06(13) N1-Ru1-Cl1 79.89(13) C6-Ru1-Cl1 126.14(14) C5-Ru1-Cl1 161.89(13) C1-Ru1-Cl1 94.64(14) C4-Ru1-Cl1 143.49(15) C2-Ru1-Cl1 87.58(15) C3-Ru1-Cl1 107.91(17) P1-Ru1-Cl1 90.46(11) N2-Ru2-C26 154.37(18) N2-Ru2-C27 117.75(19) C26-Ru2-C27 37.37(18) N2-Ru2-C25 160.85(17) C26-Ru2-C25 37.16(19) C27-Ru2-C25 67.39(19) N2-Ru2-C28 94.04(18) C26-Ru2-C28 67.24(18) C27-Ru2-C28 36.95(18) C25-Ru2-C28 80.11(18) N2-Ru2-C29 97.93(19) C26-Ru2-C29 77.96(19) C27-Ru2-C29 66.0(2) C25-Ru2-C29 66.45(18) C28-Ru2-C29 37.19(18) N2-Ru2-C30 123.93(19) C26-Ru2-C30 66.1(2) C27-Ru2-C30 78.0(2) 305 C25-Ru2-C30 37.12(18) C28-Ru2-C30 66.51(18) C29-Ru2-C30 36.02(18) N2-Ru2-P2 80.73(14) C26-Ru2-P2 94.96(16) C27-Ru2-P2 97.64(16) C25-Ru2-P2 117.72(13) C28-Ru2-P2 123.75(14) C29-Ru2-P2 160.94(13) C30-Ru2-P2 154.31(13) N2-Ru2-Cl2 79.80(13) C26-Ru2-Cl2 125.68(14) C27-Ru2-Cl2 161.57(13) C25-Ru2-Cl2 94.19(14) C28-Ru2-Cl2 144.05(15) C29-Ru2-Cl2 108.10(17) C30-Ru2-Cl2 87.54(15) P2-Ru2-Cl2 90.46(11) O2-S1-O3 114.5(4) O2-S1-O1 114.2(5) O3-S1-O1 116.7(5) O2-S1-C49 103.7(3) O3-S1-C49 102.4(4) O1-S1-C49 102.8(3) O6-S2-O4 115.1(3) O6-S2-O5 115.3(3) O4-S2-O5 114.9(3) O6-S2-C50 103.5(3) O4-S2-C50 102.0(3) O5-S2-C50 103.5(3) Anisotropic atomic displacement parameters (Å 2 ) for ruthenium 4.1. The anisotropic atomic displacement factor exponent takes the form: -2π 2 [ h 2 a *2 U11 + ... + 2 h k a * b * U12 ] U11 U22 U33 U23 U13 U12 C1 0.012(2) 0.011(2) 0.013(2) 0.0002(18) 0.0009(17) -0.0015(16) C2 0.011(2) 0.012(2) 0.011(2) 0.0004(17) 0.0007(17) -0.0042(16) C3 0.012(2) 0.012(2) 0.013(2) -0.0010(17) 0.0023(17) 0.0007(16) C4 0.015(2) 0.0079(19) 0.011(2) -0.0028(16) 0.0027(17) 0.0001(16) C5 0.013(2) 0.010(2) 0.015(2) -0.0014(17) 0.0049(17) -0.0001(16) C6 0.008(2) 0.013(2) 0.015(2) -0.0037(17) 0.0011(17) 0.0005(16) C7 0.017(2) 0.016(2) 0.012(2) 0.0037(18) -0.0017(18) -0.0052(18) C8 0.027(3) 0.016(3) 0.028(3) 0.007(2) 0.005(2) 0.002(2) C9 0.033(3) 0.023(3) 0.015(3) 0.002(2) 0.008(2) -0.009(2) C10 0.026(2) 0.011(2) 0.0085(19) -0.0039(18) 0.0045(17) -0.002(2) C11 0.014(2) 0.014(2) 0.016(2) 0.0016(18) 0.0027(18) 0.0025(17) C12 0.015(2) 0.018(2) 0.019(2) 0.0107(19) 0.0085(19) 0.0097(19) C13 0.026(3) 0.014(2) 0.033(3) 0.014(2) 0.011(2) 0.012(2) C14 0.022(3) 0.016(2) 0.023(3) -0.004(2) 0.003(2) 0.000(2) C15 0.017(2) 0.014(2) 0.013(2) 0.0000(18) 0.0058(18) -0.0011(17) C16 0.013(2) 0.016(2) 0.014(2) -0.0035(18) 0.0024(18) -0.0028(17) C17 0.011(2) 0.018(2) 0.014(2) 0.0022(19) -0.0011(18) -0.0036(18) C18 0.017(2) 0.026(2) 0.013(2) 0.002(2) 0.0011(17) 0.000(2) 306 U11 U22 U33 U23 U13 U12 C19 0.017(3) 0.032(3) 0.019(3) 0.005(2) 0.000(2) 0.009(2) C20 0.027(3) 0.033(3) 0.015(3) 0.000(2) -0.004(2) -0.012(2) C21 0.012(2) 0.018(2) 0.013(2) 0.0011(18) 0.0039(17) -0.0018(17) C22 0.017(2) 0.021(2) 0.014(2) 0.003(2) 0.0069(19) -0.0007(19) C23 0.007(2) 0.026(3) 0.018(2) -0.003(2) -0.0002(19) -0.0013(18) C24 0.016(2) 0.022(3) 0.027(3) -0.002(2) 0.008(2) -0.006(2) C25 0.012(2) 0.0070(19) 0.011(2) -0.0014(17) -0.0004(17) -0.0014(16) C26 0.010(2) 0.0055(18) 0.015(2) -0.0028(16) -0.0009(17) 0.0015(15) C27 0.012(2) 0.0089(19) 0.016(2) -0.0033(17) 0.0049(17) -0.0008(16) C28 0.014(2) 0.010(2) 0.011(2) -0.0039(16) 0.0012(17) -0.0007(16) C29 0.010(2) 0.010(2) 0.011(2) -0.0045(16) 0.0004(16) -0.0007(16) C30 0.008(2) 0.0087(19) 0.015(2) -0.0027(17) 0.0004(17) -0.0008(15) C31 0.022(3) 0.011(2) 0.014(2) 0.0017(18) -0.0030(19) -0.0039(18) C32 0.028(3) 0.010(2) 0.023(3) 0.009(2) 0.000(2) 0.003(2) C33 0.034(3) 0.016(2) 0.016(3) 0.003(2) 0.009(2) -0.004(2) C34 0.020(2) 0.017(2) 0.013(2) 0.0064(19) 0.0058(17) 0.0038(19) C35 0.011(2) 0.017(2) 0.014(2) 0.0045(18) 0.0029(18) 0.0034(18) C36 0.015(2) 0.017(2) 0.021(3) 0.010(2) 0.0049(19) 0.0053(18) C37 0.023(3) 0.015(2) 0.029(3) 0.003(2) 0.006(2) 0.000(2) C38 0.019(2) 0.0036(19) 0.028(3) 0.0041(18) 0.009(2) 0.0035(17) C39 0.010(2) 0.012(2) 0.018(2) 0.0033(18) 0.0053(18) 0.0028(16) C40 0.015(2) 0.0051(18) 0.018(2) -0.0016(17) 0.0062(19) 0.0006(16) C41 0.009(2) 0.014(2) 0.016(2) 0.0005(18) 0.0060(17) -0.0020(16) C42 0.014(2) 0.019(2) 0.016(2) 0.0057(19) 0.0042(19) -0.0023(18) C43 0.014(2) 0.016(2) 0.022(3) -0.002(2) 0.0045(19) -0.0079(18) C44 0.016(2) 0.016(3) 0.017(2) -0.0042(18) 0.009(2) -0.0004(17) C45 0.012(2) 0.017(2) 0.012(2) 0.0004(18) -0.0020(17) -0.0010(18) C46 0.020(3) 0.024(3) 0.017(3) -0.001(2) -0.005(2) -0.008(2) C47 0.016(2) 0.024(3) 0.022(3) 0.008(2) -0.002(2) 0.006(2) C48 0.017(2) 0.018(2) 0.014(2) 0.002(2) 0.0010(17) -0.004(2) C49 0.028(3) 0.026(3) 0.028(3) -0.006(2) 0.004(3) -0.009(2) C50 0.026(3) 0.031(3) 0.021(3) 0.000(2) 0.002(2) 0.003(2) C51 0.039(4) 0.039(4) 0.060(5) 0.013(4) 0.004(4) 0.006(3) Cl1 0.0105(5) 0.0162(5) 0.0116(5) 0.0002(4) 0.0044(4) 0.0006(4) Cl2 0.0111(5) 0.0119(5) 0.0127(5) -0.0008(4) 0.0046(4) 0.0000(4) Cl3 0.0654(15) 0.0936(19) 0.0414(11) 0.0274(12) -0.0025(10) -0.0242(14) Cl4 0.0864(16) 0.0261(8) 0.0476(11) -0.0024(8) -0.0238(11) 0.0108(9) 307 U11 U22 U33 U23 U13 U12 F1 0.032(2) 0.032(2) 0.084(4) 0.000(2) -0.027(2) 0.0086(18) F2 0.133(5) 0.023(2) 0.045(3) -0.0106(19) 0.025(3) -0.002(3) F3 0.044(3) 0.101(5) 0.051(3) 0.037(3) 0.011(2) -0.013(3) F4 0.077(3) 0.044(2) 0.030(2) 0.0116(19) 0.021(2) -0.003(2) F5 0.030(2) 0.039(2) 0.072(3) 0.008(2) -0.013(2) 0.0119(18) F6 0.062(3) 0.032(2) 0.034(2) -0.0100(18) 0.009(2) -0.005(2) N1 0.0110(18) 0.0108(18) 0.0122(19) 0.0023(15) 0.0024(15) 0.0026(14) N2 0.0084(19) 0.0114(18) 0.0114(18) 0.0033(14) 0.0024(15) 0.0023(14) O1 0.079(5) 0.079(5) 0.038(3) -0.008(3) 0.007(3) 0.062(4) O2 0.038(3) 0.035(3) 0.055(3) 0.004(2) 0.021(2) -0.004(2) O3 0.025(3) 0.118(6) 0.048(3) 0.036(4) -0.022(2) -0.018(3) O4 0.018(2) 0.054(3) 0.040(3) 0.016(3) -0.0045(18) -0.002(2) O5 0.031(2) 0.034(2) 0.030(2) -0.0085(19) 0.0064(19) 0.0063(19) O6 0.038(3) 0.043(3) 0.035(3) 0.005(2) 0.020(2) -0.003(2) P1 0.0076(5) 0.0118(5) 0.0094(5) 0.0007(4) 0.0007(4) -0.0003(4) P2 0.0077(5) 0.0086(5) 0.0099(5) -0.0003(4) 0.0017(4) -0.0007(4) Ru1 0.00587(14) 0.00878(14) 0.00807(15) 0.00076(12) 0.00091(11) 0.00044(12) Ru2 0.00616(14) 0.00635(14) 0.00849(15) -0.00006(12) 0.00117(11) 0.00015(12) S1 0.0151(6) 0.0418(8) 0.0232(6) -0.0001(7) 0.0036(5) 0.0072(6) S2 0.0128(5) 0.0268(7) 0.0191(6) 0.0026(5) 0.0022(4) 0.0023(5) Hydrogen atomic coordinates and isotropic atomic displacement parameters (Å 2 ) for ruthenium 4.1. x/a y/b z/c U(eq) H2 1.1484 0.5746 0.0929 0.014 H3 1.1823 0.5249 0.2431 0.015 H5 0.6999 0.5327 0.2277 0.015 H6 0.6658 0.5828 0.0746 0.015 H7 0.7883 0.6099 -0.0696 0.019 H8A 0.9289 0.6971 0.0578 0.036 H8B 0.7457 0.6811 0.0364 0.036 H8C 0.8192 0.7049 -0.0519 0.036 H9A 1.1145 0.6402 -0.0211 0.035 H9B 0.9978 0.6486 -0.1283 0.035 H9C 1.0452 0.5889 -0.0878 0.035 H10A 0.8926 0.5105 0.3902 0.023 H10B 1.0748 0.5005 0.3899 0.023 308 x/a y/b z/c U(eq) H10C 0.9432 0.4586 0.3350 0.023 H11 1.1504 0.4382 0.2451 0.017 H12 1.2287 0.3502 0.2920 0.02 H13 1.1071 0.2780 0.1931 0.028 H14 0.8871 0.2955 0.0633 0.025 H16A 0.6766 0.3602 -0.0101 0.017 H16B 0.7924 0.3910 -0.0677 0.017 H18A 0.6002 0.5125 -0.2358 0.028 H18B 0.7350 0.4709 -0.1842 0.028 H18C 0.7196 0.5281 -0.1329 0.028 H19A 0.4727 0.5462 -0.0650 0.035 H19B 0.3429 0.4995 -0.0732 0.035 H19C 0.3709 0.5283 -0.1723 0.035 H20A 0.4012 0.4057 -0.1367 0.04 H20B 0.5534 0.3993 -0.1837 0.04 H20C 0.4082 0.4361 -0.2387 0.04 H22A 0.7074 0.4368 0.2263 0.025 H22B 0.6703 0.3776 0.1803 0.025 H22C 0.5553 0.4047 0.2429 0.025 H23A 0.4187 0.4822 0.1942 0.026 H23B 0.3332 0.4898 0.0789 0.026 H23C 0.4990 0.5188 0.1231 0.026 H24A 0.3444 0.3803 0.0996 0.031 H24B 0.4543 0.3637 0.0250 0.031 H24C 0.3245 0.4102 -0.0059 0.031 H26 0.2808 0.5928 0.5604 0.013 H27 0.2533 0.6430 0.4093 0.014 H29 -0.2309 0.6518 0.3873 0.013 H30 -0.2035 0.6015 0.5363 0.013 H31 0.1530 0.5686 0.7031 0.02 H32A 0.0208 0.4792 0.5795 0.032 H32B 0.1258 0.4736 0.6910 0.032 H32C 0.2036 0.4960 0.6036 0.032 H33A -0.1155 0.5895 0.7076 0.032 H33B -0.0536 0.5347 0.7651 0.032 H33C -0.1676 0.5324 0.6558 0.032 H34A -0.0314 0.7185 0.2975 0.024 309 x/a y/b z/c U(eq) H34B -0.0938 0.6666 0.2309 0.024 H34C 0.0915 0.6795 0.2609 0.024 H35 -0.1992 0.7379 0.3849 0.017 H36 -0.3041 0.8237 0.3545 0.021 H37 -0.1722 0.8968 0.4475 0.027 H38 0.0524 0.8796 0.5712 0.019 H40A 0.1582 0.7854 0.7004 0.015 H40B 0.2724 0.8153 0.6406 0.015 H42A 0.2863 0.7990 0.4608 0.025 H42B 0.2491 0.7412 0.4087 0.025 H42C 0.4036 0.7739 0.3979 0.025 H43A 0.6155 0.7908 0.5420 0.026 H43B 0.6264 0.7598 0.6457 0.026 H43C 0.5046 0.8087 0.6152 0.026 H44A 0.5058 0.6871 0.4368 0.023 H44B 0.4576 0.6547 0.5265 0.023 H44C 0.6219 0.6867 0.5454 0.023 H46A 0.3983 0.7784 0.8091 0.033 H46B 0.5598 0.7644 0.7766 0.033 H46C 0.5246 0.7389 0.8767 0.033 H47A 0.5616 0.6425 0.8068 0.032 H47B 0.6083 0.6752 0.7170 0.032 H47C 0.4729 0.6302 0.6935 0.032 H48A 0.2362 0.6445 0.7743 0.025 H48B 0.1989 0.7039 0.8084 0.025 H48C 0.3406 0.6698 0.8750 0.025 H51A 0.9451 0.8869 0.1295 0.056 H51B 0.8810 0.8849 0.2299 0.056 310 6.6.3. Crystal Structure Data for Iridium 5.4 Figure 6.6.3. ORTEP diagram of iridium 5.4. Ellipsoids are drawn at the 50% probability level. I carried out the synthesis of iridium 5.4. Dr. Jessica Herron grew crystals suitable for X- ray analysis. A clear orange plate-like specimen of C25H39ClF3IrNO3PS, approximate dimensions 0.111 mm x 0.165 mm x 0.211 mm, was used for the X-ray crystallographic analysis. The X-ray intensity data were measured on a Bruker APEX DUO system equipped with a TRIUMPH curved-crystal monochromator and a MoKα fine-focus tube (λ = 0.71073 Å). 311 A total of 2520 frames were collected. The total exposure time was 7.00 hours. The frames were integrated with the Bruker SAINT software package using a SAINT V8.34A (Bruker AXS, 2013) algorithm. The integration of the data using a monoclinic unit cell yielded a total of 68655 reflections to a maximum θ angle of 30.66° (0.70 Å resolution), of which 8609 were independent (average redundancy 7.975, completeness = 98.5%, Rint = 6.47%, Rsig = 3.89%) and 7161 (83.18%) were greater than 2σ(F 2 ). The final cell constants of a = 8.1455(8) Å, b = 16.5588(16) Å, c = 20.962(2) Å, β = 94.132(2)°, volume = 2820.0(5) Å 3 , are based upon the refinement of the XYZ- centroids of 9400 reflections above 20 σ(I) with 4.92° < 2θ < 61.25°. Data were corrected for absorption effects using the multi-scan method (SADABS). The ratio of minimum to maximum apparent transmission was 0.642. The calculated minimum and maximum transmission coefficients (based on crystal size) are 0.4180 and 0.6060. The structure was solved and refined using the Bruker SHELXTL Software Package, using the space group P 1 21/c 1, with Z = 4 for the formula unit, C 25H39ClF3IrNO3PS. The final anisotropic full-matrix least-squares refinement on F 2 with 336 variables converged at R1 = 3.38%, for the observed data and wR2 = 7.42% for all data. The goodness-of-fit was 1.039. The largest peak in the final difference electron density synthesis was 2.425 e - /Å 3 and the largest hole was - 1.196 e - /Å 3 with an RMS deviation of 0.173 e - /Å 3 . On the basis of the final model, the calculated density was 1.765 g/cm 3 and F(000), 1488 e - . 312 Sample and crystal data for iridium 5.4. Identification code Jessica 36 Chemical formula C25H39ClF3IrNO3PS Formula weight 749.25 Temperature 100(2) K Wavelength 0.71073 Å Crystal size 0.111 x 0.165 x 0.211 mm Crystal habit clear orange plate Crystal system monoclinic Space group P 1 21/c 1 Unit cell dimensions a = 8.1455(8) Å α = 90° b = 16.5588(16) Å β = 94.132(2)° c = 20.962(2) Å γ = 90° Volume 2820.0(5) Å 3 Z 4 Density (calculated) 1.765 g/cm 3 Absorption coefficient 5.007 mm -1 F(000) 1488 313 Data collection and structure refinement for iridium 5.4. Diffractometer Bruker APEX DUO Radiation source fine-focus tube, MoKα Theta range for data collection 1.57 to 30.66° Index ranges -11<=h<=11, -23<=k<=23, -30<=l<=29 Reflections collected 68655 Independent reflections 8609 [R(int) = 0.0647] Coverage of independent reflections 98.5% Absorption correction multi-scan Max. and min. transmission 0.6060 and 0.4180 Structure solution technique direct methods Structure solution program SHELXTL XT 2013/6 (Sheldrick, 2013) Refinement method Full-matrix least-squares on F 2 Refinement program SHELXTL XLMP 2014/1 (Bruker AXS, 2013) Function minimized Σ w(Fo 2 - Fc 2 ) 2 Data / restraints / parameters 8609 / 0 / 336 Goodness-of-fit on F 2 1.039 Δ/σmax 0.001 Final R indices 7161 data; I>2σ(I) R1 = 0.0338, wR2 = 0.0697 all data R1 = 0.0475, wR2 = 0.0742 Weighting scheme w=1/[σ 2 (Fo 2 )+(0.0202P) 2 +14.0820P] where P=(Fo 2 +2Fc 2 )/3 Largest diff. peak and hole 2.425 and -1.196 eÅ -3 R.M.S. deviation from mean 0.173 eÅ -3 314 Atomic coordinates and equivalent isotropic atomic displacement parameters (Å 2 ) for iridium 5.4. U(eq) is defined as one third of the trace of the orthogonalized Uij tensor. x/a y/b z/c U(eq) C1 0.6194(5) 0.0263(2) 0.37115(18) 0.0161(7) C2 0.5910(5) 0.9407(2) 0.36121(19) 0.0172(7) C3 0.4406(5) 0.9203(2) 0.38770(19) 0.0172(7) C4 0.3733(5) 0.9930(2) 0.41537(18) 0.0168(7) C5 0.4855(5) 0.0570(2) 0.40540(18) 0.0161(7) C6 0.7775(5) 0.0711(3) 0.3651(2) 0.0230(8) C7 0.7101(6) 0.8804(3) 0.3379(2) 0.0265(9) C8 0.3681(6) 0.8372(2) 0.3907(2) 0.0243(9) C9 0.2201(5) 0.9966(3) 0.45131(18) 0.0200(8) C10 0.4805(6) 0.1416(3) 0.4305(2) 0.0252(9) C11 0.1759(5) 0.1585(2) 0.3206(2) 0.0198(8) C12 0.0771(5) 0.2236(2) 0.3024(2) 0.0232(9) C13 0.0458(5) 0.2401(2) 0.2383(2) 0.0244(9) C14 0.1085(5) 0.1881(2) 0.1942(2) 0.0224(8) C15 0.2028(5) 0.1217(2) 0.21508(19) 0.0162(7) C16 0.2562(5) 0.0597(2) 0.16908(19) 0.0183(8) C17 0.4411(6) 0.9100(3) 0.1528(2) 0.0234(9) C18 0.3223(7) 0.8496(3) 0.1795(2) 0.0321(11) C19 0.6127(6) 0.8729(3) 0.1542(3) 0.0389(13) C20 0.3804(7) 0.9259(3) 0.0821(2) 0.0382(12) C21 0.6138(5) 0.0748(3) 0.17956(19) 0.0202(8) C22 0.7811(5) 0.0388(3) 0.2041(2) 0.0279(9) C23 0.6169(6) 0.0927(3) 0.1078(2) 0.0320(11) C24 0.5900(5) 0.1554(2) 0.2144(2) 0.0237(9) C25 0.0621(7) 0.3481(3) 0.4916(2) 0.0332(11) Cl1 0.12181(12) 0.94466(6) 0.28736(5) 0.01814(18) F1 0.2217(4) 0.3526(3) 0.51074(18) 0.0557(10) F2 0.0440(4) 0.3768(2) 0.43187(15) 0.0458(8) F3 0.9828(4) 0.39791(18) 0.52904(17) 0.0458(8) Ir01 0.38599(2) 0.00731(2) 0.31072(2) 0.01079(4) N1 0.2420(4) 0.10888(18) 0.27825(16) 0.0148(6) O1 0.0901(6) 0.2009(3) 0.4563(2) 0.0545(12) O2 0.8174(5) 0.2503(2) 0.4716(2) 0.0446(10) O3 0.0075(5) 0.2261(2) 0.56247(17) 0.0400(9) 315 x/a y/b z/c U(eq) P1 0.44129(11) 0.00631(6) 0.20159(4) 0.01277(17) S1 0.98597(15) 0.24390(7) 0.49608(5) 0.0247(2) Bond lengths (Å) for iridium 5.4. C1-C5 1.440(6) C1-C2 1.449(6) C1-C6 1.499(5) C1-Ir01 2.230(4) C2-C3 1.422(6) C2-C7 1.499(6) C2-Ir01 2.207(4) C3-C4 1.461(5) C3-C8 1.499(6) C3-Ir01 2.185(4) C4-C5 1.424(5) C4-C9 1.505(5) C4-Ir01 2.216(4) C5-C10 1.499(5) C5-Ir01 2.245(4) C11-N1 1.349(5) C11-C12 1.382(6) C12-C13 1.379(6) C13-C14 1.387(6) C14-C15 1.393(5) C15-N1 1.356(5) C15-C16 1.495(6) C16-P1 1.836(4) C17-C19 1.526(7) C17-C18 1.526(6) C17-C20 1.550(7) C17-P1 1.895(4) C21-C23 1.536(6) C21-C22 1.542(6) C21-C24 1.540(6) C21-P1 1.889(4) C25-F3 1.337(6) C25-F1 1.335(6) C25-F2 1.338(6) C25-S1 1.838(5) Cl1-Ir01 2.4073(9) Ir01-N1 2.134(3) Ir01-P1 2.3634(10) O1-S1 1.423(4) O2-S1 1.435(4) O3-S1 1.421(4) Bond angles (°) for iridium 5.4. C5-C1-C2 107.3(3) C5-C1-C6 123.6(4) C2-C1-C6 126.9(4) C5-C1-Ir01 71.8(2) C2-C1-Ir01 70.1(2) C6-C1-Ir01 136.4(3) C3-C2-C1 108.1(3) C3-C2-C7 124.4(4) C1-C2-C7 126.8(4) C3-C2-Ir01 70.3(2) C1-C2-Ir01 71.8(2) C7-C2-Ir01 131.5(3) C2-C3-C4 108.5(3) C2-C3-C8 126.0(4) C4-C3-C8 125.4(4) C2-C3-Ir01 71.9(2) C4-C3-Ir01 71.8(2) C8-C3-Ir01 125.1(3) 316 C5-C4-C3 107.0(3) C5-C4-C9 127.5(4) C3-C4-C9 125.4(4) C5-C4-Ir01 72.5(2) C3-C4-Ir01 69.5(2) C9-C4-Ir01 126.2(3) C4-C5-C1 109.2(3) C4-C5-C10 127.6(4) C1-C5-C10 123.0(4) C4-C5-Ir01 70.3(2) C1-C5-Ir01 70.6(2) C10-C5-Ir01 129.4(3) N1-C11-C12 123.1(4) C13-C12-C11 119.1(4) C12-C13-C14 118.4(4) C13-C14-C15 120.2(4) N1-C15-C14 121.0(4) N1-C15-C16 117.6(3) C14-C15-C16 121.3(4) C15-C16-P1 111.1(3) C19-C17-C18 109.5(4) C19-C17-C20 108.4(4) C18-C17-C20 107.2(4) C19-C17-P1 111.3(3) C18-C17-P1 109.2(3) C20-C17-P1 111.1(3) C23-C21-C22 108.9(4) C23-C21-C24 108.0(4) C22-C21-C24 108.4(4) C23-C21-P1 114.9(3) C22-C21-P1 109.9(3) C24-C21-P1 106.5(3) F3-C25-F1 106.8(4) F3-C25-F2 107.8(5) F1-C25-F2 107.5(4) F3-C25-S1 111.7(3) F1-C25-S1 111.3(4) F2-C25-S1 111.5(3) N1-Ir01-C3 146.45(14) N1-Ir01-C2 157.89(14) C3-Ir01-C2 37.77(15) N1-Ir01-C4 109.65(13) C3-Ir01-C4 38.76(14) C2-Ir01-C4 63.87(14) N1-Ir01-C1 119.77(13) C3-Ir01-C1 63.50(15) C2-Ir01-C1 38.13(15) C4-Ir01-C1 63.35(14) N1-Ir01-C5 98.56(13) C3-Ir01-C5 63.09(14) C2-Ir01-C5 63.02(14) C4-Ir01-C5 37.22(14) C1-Ir01-C5 37.55(14) N1-Ir01-P1 80.53(9) C3-Ir01-P1 131.85(11) C2-Ir01-P1 105.68(11) C4-Ir01-P1 169.46(10) C1-Ir01-P1 109.67(10) C5-Ir01-P1 140.93(11) N1-Ir01-Cl1 79.16(9) C3-Ir01-Cl1 89.85(11) C2-Ir01-Cl1 121.11(11) C4-Ir01-Cl1 92.90(10) C1-Ir01-Cl1 152.83(10) C5-Ir01-Cl1 126.75(11) P1-Ir01-Cl1 91.72(3) C11-N1-C15 118.0(3) C11-N1-Ir01 120.4(3) C15-N1-Ir01 121.3(3) C16-P1-C21 103.03(19) C16-P1-C17 103.6(2) C21-P1-C17 110.21(19) C16-P1-Ir01 98.47(13) C21-P1-Ir01 115.43(13) C17-P1-Ir01 122.39(14) O3-S1-O1 115.7(3) 317 O3-S1-O2 114.4(3) O1-S1-O2 115.0(3) O3-S1-C25 103.1(2) O1-S1-C25 102.9(3) O2-S1-C25 103.3(2) Anisotropic atomic displacement parameters (Å 2 ) for iridium 5.4. The anisotropic atomic displacement factor exponent takes the form: -2π 2 [ h 2 a *2 U11 + ... + 2 h k a * b * U12 ] U11 U22 U33 U23 U13 U12 C1 0.0121(16) 0.0208(18) 0.0147(17) 0.0031(14) -0.0038(13) 0.0008(13) C2 0.0147(18) 0.0205(18) 0.0160(18) 0.0025(14) -0.0020(14) 0.0051(14) C3 0.023(2) 0.0145(17) 0.0144(18) 0.0032(13) 0.0014(15) 0.0028(14) C4 0.0179(17) 0.0184(18) 0.0139(16) 0.0006(14) 0.0003(13) 0.0027(14) C5 0.0194(19) 0.0170(17) 0.0108(17) -0.0018(13) -0.0058(14) 0.0001(14) C6 0.0160(19) 0.029(2) 0.024(2) -0.0012(17) -0.0028(16) -0.0058(16) C7 0.024(2) 0.022(2) 0.034(2) 0.0033(18) 0.0052(18) 0.0096(17) C8 0.032(2) 0.0162(19) 0.024(2) 0.0042(16) 0.0025(18) -0.0003(16) C9 0.0206(18) 0.026(2) 0.0143(17) 0.0020(15) 0.0035(14) 0.0008(16) C10 0.029(2) 0.020(2) 0.025(2) -0.0082(16) -0.0020(18) -0.0023(17) C11 0.020(2) 0.0185(18) 0.021(2) -0.0004(15) 0.0000(15) 0.0000(15) C12 0.021(2) 0.0149(18) 0.034(2) -0.0047(16) 0.0008(17) 0.0020(15) C13 0.018(2) 0.0143(18) 0.040(3) 0.0071(17) -0.0043(17) 0.0011(14) C14 0.0178(19) 0.0214(19) 0.027(2) 0.0101(17) -0.0023(16) -0.0015(16) C15 0.0132(17) 0.0179(18) 0.0175(18) 0.0036(14) 0.0008(14) -0.0018(13) C16 0.0164(18) 0.0236(19) 0.0146(18) 0.0025(14) -0.0016(14) 0.0015(15) C17 0.027(2) 0.021(2) 0.023(2) -0.0075(16) 0.0070(17) -0.0020(16) C18 0.046(3) 0.020(2) 0.031(3) -0.0085(18) 0.011(2) -0.0069(19) C19 0.033(3) 0.034(3) 0.050(3) -0.020(2) 0.003(2) 0.007(2) C20 0.054(3) 0.038(3) 0.023(2) -0.009(2) 0.003(2) -0.011(2) C21 0.0180(19) 0.0240(19) 0.019(2) 0.0047(15) 0.0018(15) -0.0017(16) C22 0.019(2) 0.028(2) 0.037(3) 0.0012(19) 0.0032(18) -0.0023(17) C23 0.036(3) 0.038(3) 0.023(2) 0.0096(19) 0.010(2) -0.007(2) C24 0.021(2) 0.0166(19) 0.033(2) 0.0042(17) 0.0022(17) -0.0043(15) C25 0.030(3) 0.044(3) 0.025(2) -0.004(2) 0.0019(19) -0.008(2) Cl1 0.0159(4) 0.0167(4) 0.0218(5) -0.0001(3) 0.0011(3) -0.0028(3) F1 0.0321(18) 0.081(3) 0.053(2) -0.0077(19) -0.0037(16) -0.0222(18) F2 0.052(2) 0.054(2) 0.0322(17) 0.0097(15) 0.0037(15) -0.0128(16) F3 0.059(2) 0.0287(16) 0.051(2) -0.0066(14) 0.0140(17) -0.0036(14) 318 U11 U22 U33 U23 U13 U12 Ir01 0.01103(6) 0.01005(6) 0.01122(6) -0.00013(5) 0.00038(4) 0.00010(5) N1 0.0151(15) 0.0119(14) 0.0170(16) 0.0021(11) -0.0024(12) 0.0011(11) O1 0.066(3) 0.052(3) 0.048(3) -0.016(2) 0.022(2) 0.014(2) O2 0.036(2) 0.037(2) 0.057(3) 0.0117(18) -0.0185(19) -0.0072(16) O3 0.056(2) 0.038(2) 0.0249(18) -0.0017(15) -0.0054(17) -0.0063(18) P1 0.0130(4) 0.0127(4) 0.0125(4) -0.0001(3) 0.0005(3) -0.0007(3) S1 0.0283(6) 0.0257(5) 0.0199(5) -0.0052(4) -0.0008(4) 0.0030(4) Hydrogen atomic coordinates and isotropic atomic displacement parameters (Å 2 ) for iridium 5.4. x/a y/b z/c U(eq) H6A 0.7549 0.1217 0.3419 0.035 H6B 0.8523 0.0378 0.3416 0.035 H6C 0.8286 0.0830 0.4078 0.035 H7A 0.7848 -0.0926 0.3101 0.04 H7B 0.6495 -0.1622 0.3138 0.04 H7C 0.7740 -0.1435 0.3746 0.04 H8A 0.4267 -0.1934 0.4252 0.036 H8B 0.3786 -0.1905 0.3499 0.036 H8C 0.2514 -0.1586 0.3989 0.036 H9A 0.2447 -0.0231 0.4950 0.03 H9B 0.1345 -0.0373 0.4297 0.03 H9C 0.1811 0.0525 0.4526 0.03 H10A 0.3759 0.1506 0.4497 0.038 H10B 0.4904 0.1798 0.3952 0.038 H10C 0.5719 0.1498 0.4628 0.038 H11 0.1984 0.1482 0.3649 0.024 H12 0.0314 0.2565 0.3338 0.028 H13 -0.0172 0.2860 0.2246 0.029 H14 0.0870 0.1977 0.1497 0.027 H16A 0.2793 0.0863 0.1284 0.022 H16B 0.1662 0.0203 0.1599 0.022 H18A 0.3610 -0.1648 0.2234 0.048 H18B 0.3170 -0.1991 0.1529 0.048 H18C 0.2125 -0.1262 0.1794 0.048 H19A 0.6877 -0.0895 0.1349 0.058 H19B 0.6080 -0.1778 0.1300 0.058 319 x/a y/b z/c U(eq) H19C 0.6527 -0.1380 0.1986 0.058 H20A 0.2676 -0.0531 0.0802 0.057 H20B 0.3825 -0.1247 0.0579 0.057 H20C 0.4526 -0.0345 0.0636 0.057 H22A 0.8636 0.0818 0.2085 0.042 H22B 0.8154 -0.0016 0.1735 0.042 H22C 0.7707 0.0131 0.2457 0.042 H23A 0.5084 0.1119 0.0911 0.048 H23B 0.6448 0.0433 0.0852 0.048 H23C 0.6997 0.1343 0.1012 0.048 H24A 0.5770 0.1449 0.2598 0.036 H24B 0.4915 0.1827 0.1954 0.036 H24C 0.6864 0.1899 0.2102 0.036 320 6.7. 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Abstract (if available)

Abstract Research presented in this work describes the syntheses, characterization, and reactivity studies of transition metal complexes of two classes of bidentate ligands, namely (1) dipyridylborate and (2) pyridylphosphine. These ligands are proposed to work via cooperative catalysis, wherein the ligand and metal work together to effect catalytic transformations. ❧ Our group initially investigated the dipyridylborate ligand to develop catalysts with a pendant Lewis acid, specifically boron, which can function to direct substrates to transition metal centers. Here, the syntheses and solution dynamics of novel nickel complexes supported by this ligand are reported. Using one of these complexes, the first experimental proof for the viability of a square-planar to square-planar rotation around a nickel(II) center is provided. NMR inversion recovery kinetics experiments were used to determine the rates as well as the activation parameters (∆H, and ∆S,) of this process. ❧ The development of the pyridylphosphine ligand was inspired by Milstein’s PNP and PNN pincer complexes, which function via a metal-ligand cooperation mechanism. These pincer complexes have proven to be very versatile and useful catalysts, exhibiting excellent reactivity in a wide range of reactions from hydrogenation of esters and amides to acceptorless dehydrogenation reactions to water splitting. Whereas pincer ligands are tridentate, the pyridylphosphine is a bidentate ligand which we hypothesized to be capable of functioning via a metal-ligand cooperation mechanism. We reasoned that the use of a bidentate instead of a tridentate ligand might be advantageous because of a) more facile ligand synthesis and b) flexibility in the synthesis and electronic tuning of possible catalysts. ❧ Our initial motivation for developing complexes with a pyridylphosphine ligand was to investigate its reactivity in CO₂ activation. Although we have not found the desired reactivity in this regard, we have discovered an iridium pyridylphosphine complex with excellent reactivity toward formic acid dehydrogenation. This reaction is important because the hydrogen gas that is released can be used in fuel cells to generate electricity cleanly, producing only water as a byproduct. The iridium catalyst is robust (affording millions of turnovers), stable to air and water, and selective, producing less than 10 ppm carbon monoxide, a fuel cell poison. The mechanism of catalysis, which was studied in great detail, is discussed. Furthermore, we have also discovered a ruthenium pyridylphosphine complex that has great reactivity in the dehydrative coupling of amines with benzylic alcohols. This reaction is of great significance in organic synthesis because alkylated amines are intermediates in a wide range of useful compounds such as polymers, agrochemicals, and pharmaceuticals

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Asset Metadata

Creator Celaje, Jeff Joseph A. (author)

Core Title Transition metal complexes of pyridylphosphine and dipyridylborate ligands in dehydrogenation reactions

School College of Letters, Arts and Sciences

Degree Doctor of Philosophy

Degree Program Chemistry

Publication Date 11/10/2017

Defense Date 11/10/2016

Publisher University of Southern California (original), University of Southern California. Libraries (digital)

Tag cooperative catalysis,dipyridylborate,formic acid dehydrogenation,OAI-PMH Harvest,organometallic chemistry,pyridylphosphine

Format application/pdf (imt)

Language English

Contributor Electronically uploaded by the author (provenance)

Advisor Williams, Travis J. (committee chair), Christe, Karl O. (committee member), Petruska, John A. (committee member)

Creator Email celaje@usc.edu,jcelaje3@gmail.com

Permanent Link (DOI) https://doi.org/10.25549/usctheses-c40-319905

Unique identifier UC11213718

Identifier etd-CelajeJeff-4914.pdf (filename),usctheses-c40-319905 (legacy record id)

Legacy Identifier etd-CelajeJeff-4914.pdf

Dmrecord 319905

Document Type Dissertation

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Rights Celaje, Jeff Joseph A.

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Source University of Southern California (contributing entity), University of Southern California Dissertations and Theses (collection)

Access Conditions The author retains rights to his/her dissertation, thesis or other graduate work according to U.S. copyright law. Electronic access is being provided by the USC Libraries in agreement with the a...

Repository Name University of Southern California Digital Library

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