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Development of new bifunctional iridium complexes for hydrogenation and dehydrogenation reactions

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Development of new bifunctional iridium complexes for hydrogenation and dehydrogenation reactions

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Content DEVELOPMENT OF NEW BIFUNCTIONAL IRIDIUM COMPLEXES FOR HYDROGENATION AND DEHYDROGENATION REACTIONS by Ivan Demianets A Dissertation Presented to the FACULTY OF THE USC GRADUATE SCHOOL UNIVERSITY OF SOUTHERN CALIFORNIA in Partial Fulfilment of the Requirements for the Degree DOCTOR OF PHILOSOPHY (CHEMISTRY) May 2019 © Copyrights by Ivan Demianets, 2019. All rights Reserved Dedication To my Mother, Father, and Alona. i ii Acknowledgment I want to thank my advisor, Prof. Travis J. Williams, for his guidance and understanding over the years I have spent at USC. Travis’s door was always open for me, and he was always happy to help. I have learned a lot from you, and I am grateful to have had such a knowledgeable, wise, and kind advisor. I wish you and your family all the best. I would like to express my appreciation to my graduate committee members: Professors G. K. Surya Prakash, Barry C. Thompson, Jahan M. Dawlaty, Ralf Haiges, Shaama Mallikarjun Sharada, and Steven Nutt and thank them for their time and support. To all the Williams group members that I had pleasure working with – Dr. Lily Zhang, Dr. Zhiyao Lu, Dr. Jeff Celaje, Forrest Zhang, Paul Lauridsen, Valery Cherepakhin, Talya Kapenstein, Elyse Kedzie, Lisa Kam, Carlos Navarro, and Anju Nalikezhathu – thank you for being great labmates. Forrest, thank you for introducing me to the life in Williams lab. Paul, I truly appreciate you spending weekends running reactions with me, and I will always remember our SHC stories. Yao and Jeff, thank you for sharing your wisdom. Lily, thank you for being an honest friend and of course, thank you for introducing me to your husband Dr. Benjamin Decato to whom I also extend my appreciation. Thank you, my Happy Monday crew, I truly enjoyed the time we have spent and conversations we have had together, and I am hopeful we will continue this tradition. I also want to thank our collaborators Prof. Jahan M. Dawlaty and Prof. Shaama Mallikarjun Sharada as well as their research groups. In particular, I would like to thank Jonathan R. Hunt from the Dawlaty group for always doing extra work for our projects to succeed. To all the staff of Loker Hydrocarbon Research Institute and the Chemistry Department at USC – David Hunter, Carole Phillips, Jessy May, Dr. Robert Aniszfeld, Michele Dea, Magnolia Benitez, Allan Kershaw, Dr. Frank J. Devlin, and Michael Nonezyan – thank you for your help and advice. Furthermore, I would like to thank the Sonosky foundation for support and generosity. iii Thank you to Dr. Nadia Korovina, Dr. Anastasia Gunina, Dr. Anastasia Kadina, Dr. Betsy Melenbrink, Dr. Cesar De Leon, Dr. Anna and Erik Gerdtsson, Ariel Wein, Joel Patrow, and Sahar Roshandal for all the help and conversations we had. To Kyle McClary, thank you for being a great friend. A special thank you to the families of Luchan, Tretyak, Oliynyk, and Tsupa. I am grateful for your support and friendship. Thank you for having my back all these years. To my chemistry teacher, Vitaliy Basanets, as well as to another great chemist from my hometown Dr. Yuriy Galabura, thank you for helping me to get where I am right now. I also would like to express my appreciation to my undergraduate research advisor Dr. Alexey Kolendo, thank you for being patient with me. To Dr. Tetiana Bezugla, thank you for your support and help when I was going through my hard times. To all my friends and family in Ukraine, to my fellows at Initiative E+ and all the chemists from my hometown, to those who inspired me, I wouldn’t be here without you, thank you. To my loving mom and my sister and her family, thank you for your prayers and your help. I hope I made you proud. Finally, to my fiancé Alona, who deserves the most credit for her unconditional love and constant support she expressed over the last three years, thank you. You make my life complete. iv Abstract Hydrogenation and dehydrogenation are among the most important reactions in catalysis. As demonstrated in Chapter 1, homogeneous catalysts based on bidentate iridium complexes have a special place in the field of hydride transfer reactions, therefore, were the subject of my investigation. Chapter 2 describes Cp*IrCl(2-pyridylmethyl)toluenesulfonamide bidentate complex that effects transfer hydrogenation through a metal-ligand cooperative mechanism through reversibly dearomatized ligand. This complex accesses a mechanism for transfer hydrogenation of ketones with isopropyl alcohol that has not been previously reported. It is the first example of metal-ligand cooperation via reversible ligand dearomatization outside of the pincer scaffold. Besides the transfer hydrogenation, a newly synthesized family of iridium sulfonamide complexes, including the one mentioned above, act as hydrogenation and water oxidation catalysts. This is demonstrated in Chapter 3. Chapter 4 describes the base-pendant ligand-metal bifunctional catalytic scaffold wherein the concept of a photobase, compound that becomes more basic in the excited state (pKa < pKa*), is used to switch the proton acceptor ability on an active site of the catalyst. In this system quinoline is an efficient photobase that preserves its unique properties in the close proximity of an iridium center and the photochemistry of the metal is orthogonal to the photobase system. As a result, deprotonation of an aliphatic alcohol by the new iridium complex became possible. This is the first case of metal-orthogonal optical pKa control in a transition metal complex. The same quinoline-containing complex acts as a catalyst for light-driven formic acid dehydrogenation, as revealed in Chapter 5. However, it was demonstrated that the presence of the quinoline moiety does not affect the reaction. Nevertheless, this catalytic scaffold can operate in neat formic acid, at ambient temperature, and more importantly without added base. v Chapter 6 describes a high-utility technique for the conversion of crude glycerol to value- added lactides based on the oxidative conversion of glycerol to lactate. The process utilizes a structurally novel iridium catalyst and enables unprecedented efficiency, longevity, and conversion in the oxidation of glycerol to lactic acid. This enables a very practical alternative to fermentation, which is the only technology known to be applied on a large scale. Chapter 7 recounts the preliminary data on the synthesis of new gadolinium complexes for the site-specific labeling of proteins that can also be utilized as an MRI contrast agent. vi Table of Contents Dedication Acknowledgment Abstract Preparative Procedures List of Tables List of Figures List of Schemes Chapter 1. Recent Advances in Iridium Catalyzed Homogeneous Hydrogenation and Dehydrogenation Reactions i ii iv x xvii xviii xxviii 1 1.1. Introduction 1.2. Hydrogenation 1.2.1. CO2 Hydrogenation to Methanol 1.2.2. CO2 Hydrogenation to Formic Acid 1.3. Dehydrogenation 1.3.1. Dehydrogenation of Methanol 1.3.2. Dehydrogenation of Formic Acid 1.3.3. Dehydrogenation of Glycerol 1.4. References Chapter 2. A Structurally Unique Metal-Ligand Cooperative Catalyst for Transfer Hydrogenation 1 2 2 3 5 5 6 8 9 16 2.1. Introduction 2.2. Mechanistic Studies 16 18 vii 2.3. Conclusion 2.4. References Chapter 3. Synthesis, Structure, and Reactivity of Novel Amino Sulfonamide Complexes of Iridium(III) 23 24 27 3.1. Introduction 3.2. Design and Synthesis of Iridium(III) Amino Sulfonamide Complexes 3.3. Screen for Reactivity 3.3.1. CO2 Hydrogenation 3.3.2. Transfer Hydrogenation of Ketones 3.3.3. Water Oxidation 3.4. Conclusion 3.5. References Chapter 4. Optical pKa Control in a Bifunctional Iridium(I) Complexes 27 27 29 29 31 32 33 34 36 4.1. Introduction 4.2. Synthesis and Characterization of Complexes 4.1 and 4.2 4.3. Experimental Support for Photobasicity Preservation in Complexes 4.1 and 4.2 4.4. Conclusion 4.5. References Chapter 5. Base and Solvent-free, Light-driven Formic Acid Dehydrogenation by Iridium(I) Complexes 36 38 40 44 44 50 5.1. Introduction 5.2. Studies on Light-Driven Formic Acid Dehydrogenation Using Iridium(I) Complexes 5.3. Synthesis of Iridium(I) Complexes 5.1 – 5.6 50 51 54 viii 5.4. Conclusion 5.5. References Chapter 6. PLA and Lactides Synthesis from Lactic Acid of Post Glycerol Dehydrogenation Process 57 57 60 6.1. Introduction 6.2. Glycerol Dehydrogenation 6.3. PLA and Lactides Syntheses 6.4. Conclusion 6.5. References Chapter 7. Gd(III)DOTA Complexes for MRI Contrast Agents and Labeling of Proteins 60 61 62 63 64 66 7.1. Introduction 7.2. Design and Synthesis of Gd(III) Complexes 7.3. Conclusion 7.4. References Chapter 8. Experimental and Spectral Data 66 68 71 72 74 8.1. General Methods 8.1.1. Reagents 8.1.2. Instrumentations 8.1.3. Experimental Procedures 8.2. Chapter 2 Experimental and Spectral Data 8.2.1. Synthesis Procedures and Characterization Data 8.2.2. Mechanistic Studies 74 74 74 75 77 77 92 ix 8.2.3. Computational Methods 8.3. Chapter 3 Experimental and Spectral Data 8.4. Chapter 4 Experimental and Spectral Data 8.4.1. Synthesis Procedures and Characterization Data 8.4.2. Spectral Data 8.4.3. Discussion of Fluorescence and Inter-System Crossing in Quinoline 8.4.4. Discussion of UV-vis Spectrum of the Methyl Homolog (Complex 4.13) of Complex 4.2. 8.4.5. Quantum Yield Data 8.4.6. Complex 4.1 Decomposition Studies 8.5. Chapter 5 Experimental and Spectral Data 8.5.1. Synthesis Procedures and Characterization Data 8.5.2. Spectral Data 8.6. Chapter 6 Experimental and Spectral Data 8.7. Chapter 7 Experimental and Spectral Data 8.8. X-ray Crystallography Data 8.9. References 104 105 135 135 160 161 165 167 169 171 171 189 190 202 210 274 x Preparative Procedures Complex 2.1 76 Complex 2.2 79 Complex 2.2’ 82 Complex 2.4 86 Complex 3.1 106 Complex 3.3 109 N TsHN 2. [IrCp*Cl 2 ] 2 1. Et 3 N DCM, 3h, 93% 2.1 2.5 N N Ts Ir Cl 2.1 N N Ts Ir N N Ts Ir Cl DCM, 1h KOtBu 2.2 2.1 N N Ts Ir N N Ts Ir Cl DCM, 1h KOtBu 2.2 DCM, 1h hv 2.2’ N N Ir S O O N N Ts Ir 2.2 2.4 N N Ts Ir H DCM, 30 mins 95% HCOOH 2. [IrCp*Cl 2 ] 2 1. Et 3 N H 2 N N Ts Ir Cl 3.1 DCM, 3h, 97% H 2 N TsHN 3.15 2. [IrCp*Cl 2 ] 2 1. KOtBu H 2 N N Ts Ir Cl 3.3 THF, 16h, 99% H 2 N TsHN 3.17 xi Complex 3.4 111 Complex 3.5 115 Complex 3.6 119 Complex 3.7 122 Complex 3.8 125 Complex 3.9 129 N N TsHN 2. [IrCp*Cl 2 ] 2 1. Et 3 N DCM, 3h, 89% 3.4 3.18 N N N Ts Ir Cl H 2 N N Ts Ir Cl 3.5 3.19 2. [IrCp*Cl 2 ] 2 1. KOtBu THF, 16h, 99% TsHN H 2 N 3.1 THF, 2h, 96% AgOTf H 2 N N Ts Ir Cl H 2 N N Ts Ir OTf 3.6 3.2 N N Ts Ir OTf N N Ts Ir Cl THF, 2h, 93% AgOTf 3.7 3.3 THF, 2h, 98% AgOTf H 2 N N Ts Ir Cl H 2 N N Ts Ir OTf 3.8 3.4 N N N Ts Ir OTf N N N Ts Ir Cl THF, 2h, 91% AgOTf 3.9 xii 8-Bromoquinoline 4.4 133 Methyl quinoline-8-carboxylate 4.5 134 8-(Hydroxydi(pyridin-2-yl)methyl)quinoline 4.6 135 8-(Methoxydi(pyridin-2-yl)methyl)quinoline 4.7 138 Complex 4.1 142 Complex 4.2 146 SO 3 Na O 2 N H 2 N Br N Br 4.4 FeSO 4 . 7H 2 O MeSO 3 H, 125 o C, 16 h, 73% HO OH OH N Br 4.4 CO (6 atm.), MeOH Pd(OAc) 2 , DPPF, Et 3 N. THF : MeOH 3:1, 50 o C, 14 days, 98% N O O 4.5 N I , EtMgBr N N 4.6 N OH DCM, 16 h, RT, 86% N O O 4.5 N N 4.6 N N 4.7 N N OH OMe THF, 18 h, RT, 98% CH 3 I, NaH N N 4.6 N OH DCM, RT, 95% 1. [Ir(COD)Cl] 2 , 18h 2. NaOTf, 1h N N OH N Ir OTf 4.1 N N 4.7 N OMe DCM, RT, 96% 1. [Ir(COD)Cl] 2 , 18h 2. NaOTf, 1h N N OMe N Ir OTf 4.2 xiii 8-Acetylquinoline 4.9 150 1-(Pyridin-2-yl)-1-(quinolin-8-yl)ethan-1-ol 4.10 151 Complex 4.11 153 Complex 5.3 168 Complex 5.4 171 SO 3 Na O 2 N H 2 N N 4.9 FeSO 4 . 7H 2 O MeSO 3 H, 125 o C, 16 h, 62% HO OH OH O 4.8 O N 4.9 O N I EtMgBr DCM, 16 h, RT, 68% N 4.10 HO N Et 2 Zn Toluene,16 h, RT, 74% 4.11 N 4.10 HO N N O Zn N O Zn N N N N OH N Ir OTf CO 1atm. N N OH N Ir OC OC OTf 5.1 5.3 DCM, 2 h, RT, 99% N N O N Ir OTf 5.2 N N O N Ir OC OC OTf 5.4 CO 5 atm. DCM, 16 h, RT, 98% xiv Naphthalen-1-yldi(pyridin-2-yl)methanol 5.13 175 2,2'-(Methoxy(naphthalen-1-yl)methylene)dipyridine 5.14 176 Complex 5.5 178 Complex 5.6 181 Complex 6.1 186 N N OH O O 5.12 N I , EtMgBr DCM, 16 h, RT, 40% 5.13 N N OH 5.13 THF, 18 h, RT, 99% CH 3 I, NaH N N O 5.14 N N OH Ir OTf 5.5 N N OH 5.13 DCM, RT, 95% 1. [Ir(COD)Cl] 2 , 18h 2. NaOTf, 1h N N O 5.14 DCM, RT, 97% 1. [Ir(COD)Cl] 2 , 18h 2. NaOTf, 1h N N O Ir OTf 5.6 N Ir N N OTf N N N Ag Cl Cl N N N Ag 1. [Ir(COD)Cl] 2 2. NaOTf DCM, 85% 6.1 xv Complex 6.2 189 Potassium lactate 193 Lactic acid 194 rac-Lactides 195 Compound 7.10 198 Compound 7.13 200 N Ir N N Mes OTf N N N Mes Ag Cl Cl N N N Mes Ag 1. [Ir(COD)Cl] 2 2. NaOTf CH 3 CN, 95% 6.2 HO OH OH 6.1 (20 ppm), KOH Neat, 145 o C 90% HO O OK HO O OK pH extraction HCl aq pH < 1 62% HO O OH 1. ΔT 2. ΔT, SnO 3. Recrustallization 69% O O O O O O O O + HO O OH HO N N N N O O O O O O O HN N N N N O O O O O O O 7.4 7.10 HATU, 25 o C, RT 5 min. in CH 3 CN 95% NH 2 HN N N N N O O O O O O O 7.10 HN N N N N O OH O OH O O HO 7.13 1h, 74 o C, 99% TFA/DCM 1:1 xvi Compound 7.3 202 Compound 7.8 203 Compound 7.11 204 Compound 7.1 204 HN N N N N O O O O O O O 7.3 HN N N N N O OH O OH O O HO 7.13 34h, RT, 81% GdCl 3 . 6H 2 O Gd HO N N N N O O O O O O O NH N N N N O O O O O O O 7.4 7.8 HATU, 50 o C, 24 h. in CH 3 CN 40% NH 2 OTBDMS TBDMSO ; TBDMS = Si NH N N N N O O O O O O O 7.8 TBDMSO 1h, 75 o C, 9 M H 2 SO 4 NH N N N N O OH O OH O O HO 7.11 HO NH N N N N O OH O OH O O HO 7.11 HO 34h, RT, 74% GdCl 3 . 6H 2 O NH N N N N O O O O O O O 7.1 HO Gd xvii List of Tables Table 2.1. Kinetic isotope effect data. 22 Table 3.1. Transfer hydrogenation of ketones by iridium(III) sulfonamide complexes 3.1-3.9. 32 Table 3.2. Water oxidation by iridium(III) sulfonamide complexes 3.1-3.4, 3.6-3.9. 33 Table 4.1. Estimated pKa values of investigated compounds. 42 Table 6.1. Dehydrogenation of neat glycerol to lactate. 62 Table 8.2.1. Kinetic isotope effect data. 97 Table 8.2.2. Data for Eyring analysis. 100 Table 8.4.1. Fluorescence quantum yield of quinoline moiety of complex 4.2. 167 xviii List of Figures Figure 1.1. Iridium complexes for CO2 to formate hydrogenation. 4 Figure 1.2. Interconversion of iridium complexes 1.3, 1.5, and 1.6. 6 Figure 1.3. Novel amino sulfonamide complexes of iridium(III). 7 Figure 1.4. A. Catalytic glycerol dehydrogenation to lactate. B. Glycerol dehydrogenation complexes 1.11 and 1.12. 8 Figure 2.1. Precatalysts and their activity toward metal-ligand cooperative mechanism. 17 Figure 2.2. X-Ray structure of 2.1 (left) and 2.2’ (right). Ellipsoids drawn at the 50% probability level. 20 Figure 2.3. Optimized structures of TS 3 and TS 3’. The proton shuttle was modeled as H2O in place of IPA; Cp* was modeled as Cp; and tosyl sulfonamide was modeled as the triflyl congener. 23 Figure 3.1. Iridium complexes investigated in light-driven formic acid dehydrogenation. 28 Figure 3.2. X-Ray structures of iridium complexes 3.2 (left) and 3.6 (right), triflate counterion omitted for clarity. 29 Figure 3.3. NMR of post reaction mixture of CO2 hydrogenation by 3.2 in 8 m H2SO4 in D2O. 30 Figure 4.1. ORTEP drawings of 4.1, triflate counterion is omitted for clarity. Ellipsoids drawn at the 50% probability level. 40 xix Figure 4.2. Emission spectra of quinoline (A-B) and complex 4.2 (C-D) in various solvents. Spectra B and D are zoomed versions of A and C excluding HFIPA data for clarity. Concentration of 4.2 was 1.4 ´ 10 -4 M and concentration of quinoline was 2.5 ´ 10 -5 M. Spectra collected at room temperature under ambient conditions. 41 Figure 4.3. Absorption and emission spectra of complex 4.2 in HFIPA. 43 Figure 5.1. Iridium complexes investigated in light-driven formic acid dehydrogenation. 52 Figure 5.2. Light-driven formic acid dehydrogenation by 5.1. Left: lamp ON all the time. Right: lamp ON and OFF (shaded areas). 53 Figure 5.3. Left: Light-driven formic acid dehydrogenation by 5.1 and 5.2 in the absence of a base and in the presence of 100 eq. of sodium formate; Right: Light-driven formic acid dehydrogenation by 5.1, complex A, and complex B. 54 Figure 5.4. Left: absorption spectra of 5.1 in selected solvents. Right: light-driven formic acid dehydrogenation profile of 5.1, 5.2, 5.4, and 5.6. 56 Figure 7.1. Structure of gadolinium(III) complexes 7.1, 7.2, and 7.3. 68 Figure 7.2. A. Proposed site-specific labeling of proteins with Gd(III) complexes 7.3 via “Click” reaction. B. Schematic representation of a labeled with two gadolinium chelates protein. 69 Figure 8.2.1. 1 H NMR spectrum of complex 2.1 at 25 °C in CD2Cl2. 79 Figure 8.2.2. 13 C NMR spectrum of complex 2.1 at 25 °C in CD2Cl2. 79 Figure 8.2.3. IR spectrum of complex 2.1. 80 Figure 8.2.4. X-Ray structure of complex 2.1. 80 xx Figure 8.2.5. 1 H NMR spectrum of complex 2.2 at 25 °C in CD2Cl2. 82 Figure 8.2.6. COSY NMR spectrum of complex 2.2 at 25 °C in CD2Cl2. 83 Figure 8.2.7. 13 C NMR spectrum of complex 2.2 at 25 °C in CD2Cl2. 83 Figure 8.2.8. 1 H NMR spectrum of complex 2.2’ at 25 °C in CD2Cl2. 85 Figure 8.2.9. COSY NMR spectrum of complex 2.2’ at 25 °C in CD2Cl2. 86 Figure 8.2.10. 13 C NMR spectrum of complex 2.2’ at 25 °C in CD2Cl2. 86 Figure 8.2.11. IR spectrum of complex 2.2’. 87 Figure 8.2.12. X-Ray structure of complex 2.2’. 87 Figure 8.2.13. 1 H NMR spectrum of complex 2.4 at 25 °C in CD2Cl2. 89 Figure 8.2.14. 13 C NMR spectrum of complex 2.4 at 25 °C in CD2Cl2. 90 Figure 8.2.15. IR spectrum of complex 2.4. 90 Figure 8.2.16. Complex 2.1 initiation in the presence of KOtBu at 25 °C in (CD3)2CHOH. 93 Figure 8.2.17. Complex 2.1 initiation in the presence of KOtBu at 25 °C in (CD3)2CHOH with assigned complex 2.2 (purple) and hydride complex 2.4 (red). 93 Figure 8.2.18. Kinetic studies of acetophenone transfer hydrogenation by 2.1 at 83.1 °C; arrayed 1 H NMR spectra in (CD3)2CHOH. (Peak at 6.1 ppm is a center of the spectra, instrument artifact). 94 xxi Figure 8.2.19. Kinetic Studies of acetophenone transfer hydrogenation by 2.1 in fully protonated (CH3)2CHOH, conc. vs. time. Determined by 1 H NMR of the aliquots in CDCl3. Exponential coefficients represents kobs. 96 Figure 8.2.20. Kinetic Studies of acetophenone transfer hydrogenation by 2.1, conc. vs. time, monitored by 1 H NMR in (CD3)2CHOH (top left), (CD3)2CDOH (top right), (CD3)2CHOD (bottom left), (CD3)2CDOD (buttom right). Exponential coefficients represents kobs. 96 Figure 8.2.21. Eyring plot: ΔH ‡ = 29.1(8) kcal mol -1 , ΔS ‡ = -17(19) eu. 98 Figure 8.2.22. Kinetic Studies of acetophenone transfer hydrogenation by 2.1, conc. vs. time, at different temperatures. 88.2 o C (top left), 83.1 o C (top right), 62.6 o C (bottom left), 53.2 o C (buttom right). Exponential coefficients represents kobs. Monitored by 1 H NMR in (CD3)2CHOH. 99 Figure 8.2.23. Kinetic Studies of acetophenone transfer hydrogenation by 2.1, arrayed 1 H NMR spectra; (CD3)2CHOH (top left), (CD3)2CDOH (top right), (CD3)2CHOD (bottom left), (CD3)2CDOD (buttom right). Figure 8.2.24. Kinetic studies of acetophenone transfer hydrogenation by 2.1, arrayed 1 H NMR spectra in (CD3)2CHOH at 88.2 °C. Additives: none (top left), drop of mercury (top right), one-half molar equivalent of phenanthroline (buttom). 101 Figure 8.3.1. 1 H NMR spectrum of complex 3.1 at 25 °C in CD2Cl2. 108 Figure 8.3.2. 13 C NMR spectrum of complex 3.1 at 25 °C in CD2Cl2. 109 Figure 8.3.3. IR spectrum of complex 3.1. 109 xxii Figure 8.3.4. 1 H NMR spectrum of complex 3.3 at 25 °C in CD2Cl2. 111 Figure 8.3.5. 13 C NMR spectrum of complex 3.3 at 25 °C in CD2Cl2. 112 Figure 8.3.6. IR spectrum of complex 3.3. 112 Figure 8.3.7. 1 H NMR spectrum of complex 3.4 at 25 °C in CD2Cl2. 114 Figure 8.3.8. 13 C NMR spectrum of complex 3.4 at 25 °C in CD2Cl2. 115 Figure 8.3.9. IR spectrum of complex 3.4. 115 Figure 8.3.10. 1 H NMR spectrum of complex 3.5 at 25 °C in CD2Cl2. 117 Figure 8.3.11. 1 H NMR spectrum of complex 3.5 at -20 °C in CD2Cl2. 118 Figure 8.3.12. COSY spectrum of complex 3.5 at -20 °C in CD2Cl2. 118 Figure 8.3.13. 13 C NMR spectrum of complex 3.5 at 25 °C in CD2Cl2. 119 Figure 8.3.14. IR spectrum of complex 3.5. 119 Figure 8.3.15. 1 H NMR spectrum of complex 3.6 at 25 °C in CD2Cl2. 121 Figure 8.3.16. 13 C NMR spectrum of complex 3.6 at 25 °C in CD2Cl2. 122 Figure 8.3.17. 19 F NMR spectrum of complex 3.6 at 25 °C in CD2Cl2. 122 Figure 8.3.18. IR spectrum of complex 3.6. 123 Figure 8.3.19. X-Ray structure of complex 3.6. 123 Figure 8.3.20. 1 H NMR spectrum of complex 3.7 at 25 °C in CD2Cl2. 125 Figure 8.3.21. 13 C NMR spectrum of complex 3.7 at 25 °C in CD2Cl2. 126 Figure 8.3.22. 19 F NMR spectrum of complex 3.7 at 25 °C in CD2Cl2. 126 xxiii Figure 8.3.23. IR spectrum of complex 3.7. 127 Figure 8.3.24. 1 H NMR spectrum of complex 3.8 at 25 °C in CD2Cl2. 129 Figure 8.3.25. 13 C NMR spectrum of complex 3.8 at 25 °C in CD2Cl2. 129 Figure 8.3.26. 19 F NMR spectrum of complex 3.8 at 25 °C in CD2Cl2. 130 Figure 8.3.27. IR spectrum of complex 3.8. 130 Figure 8.3.28. 1 H NMR spectrum of complex 3.9 at 25 °C in CD2Cl2. 132 Figure 8.3.29. 13 C NMR spectrum of complex 3.9 at 25 °C in CD2Cl2. 133 Figure 8.3.30. 19 F NMR spectrum of complex 3.9 at 25 °C in CD2Cl2. 133 Figure 8.3.31. IR spectrum of complex 3.9. 134 Figure 8.4.1. 1 H NMR spectrum of ligand 4.6 at 25 °C in CDCl3. 139 Figure 8.4.2. 13 C NMR spectrum of ligand 4.6 at 25 °C in CDCl3. 139 Figure 8.4.3. IR spectrum of ligand 4.6. 140 Figure 8.4.4. 1 H NMR spectrum of ligand 4.7 at 25 °C in CDCl3. 142 Figure 8.4.5. 13 C NMR spectrum of ligand 4.7 at 25 °C in CDCl3. 142 Figure 8.4.6. IR spectrum of ligand 4.7. 143 Figure 8.4.7. 1 H NMR spectrum of complex 4.1 at 25 °C in CD2Cl2. 145 Figure 8.4.8. 13 C NMR spectrum of complex 4.1 at 25 °C in CD2Cl2. 145 Figure 8.4.9. 19 F NMR spectrum of complex 4.1 at 25 °C in CD2Cl2. 146 Figure 8.4.10. IR spectrum of complex 4.1. 146 xxiv Figure 8.4.11. X-Ray structure of complex 4.1. 147 Figure 8.4.12. 1 H NMR spectrum of complex 4.2 at 25 °C in CD2Cl2. 149 Figure 8.4.13. 13 C NMR spectrum of complex 4.2 at 25 °C in CD2Cl2. 149 Figure 8.4.14. 19 F NMR spectrum of complex 4.2 at 25 °C in CD2Cl2. 150 Figure 8.4.15. IR spectrum of complex 4.2. 150 Figure 8.4.16. 1 H NMR spectrum of 4.10 at 25 °C in CDCl3. 154 Figure 8.4.17. 13 C NMR spectrum of 4.10 at 25 °C in CDCl3. 154 Figure 8.4.18. IR spectrum of ligand 4.10. 155 Figure 8.4.19. 1 H NMR spectrum of 4.11 at 25 °C in CD2Cl2. 157 Figure 8.4.20. 13 C NMR spectrum of 4.11 at 25 °C in CD2Cl2. 157 Figure 8.4.21. IR spectrum of Complex 4.11. 158 Figure 8.4.22. Left: dimeric zinc complex characterized by van Koten et al. Right: structure of decomposition product 4.12. 158 Figure 8.4.23. X-Ray structure of complex 4.12. 159 Figure 8.4.24. Absorption spectra of quinoline in different solvents. 160 Figure 8.4.25. Emission spectra of quinoline in different solvents (310 nm excitation wavelength). 160 Figure 8.4.26. Absorption spectra of complex 4.1 in different solvents. 162 xxv Figure 8.4.27. Emission spectra of complex 4.1 in different solvents (310 nm excitation wavelength). 162 Figure 8.4.28. Absorption spectra of complex 4.2 in different solvents. 163 Figure 8.4.29. Emission spectra of complex 4.2 in different solvents (310 nm excitation wavelength). 163 Figure 8.4.30. Emission and absorption spectra of complex 4.2 in HFIPA. 164 Figure 8.4.31. Emission and absorption spectra of complex 4.2 in HFIPA (absorption region zoomed). 164 Figure 8.4.32. Absorption spectra of complex 4.2, complex 4.13, and quinoline in DCM. 165 Figure 8.4.33. 1 H NMR spectrum of complex 4.13 at 25 °C in CD2Cl2. 166 Figure 8.4.34. COSY spectrum of complex 4.13 at 25 °C in CD2Cl2. 166 Figure 8.4.35. Absorption spectra of complex 4.1 (red) and ligand 4.6 (blue) in HFIPA. 169 Figure 8.4.36. Zoomed absorption spectra of complex 4.1 (red) and ligand 4.6 (blue) in HFIPA. 169 Figure 8.4.37. Emission spectra of complex 4.1 (red) and ligand 4.6 (blue) in HFIPA (310 nm excitation wavelength). 170 Figure 8.4.38. Q-Tof spectra of complex 4.1 in HFIPA. 170 Figure 8.5.1. 1 H NMR spectrum of complex 5.3 at 25 °C in CDCl3. 172 Figure 8.5.2. 13 C NMR spectrum of complex 5.3 at 25 °C in CDCl3. 173 Figure 8.5.3. 19 F NMR spectrum of complex 5.3 at 25 °C in CDCl3. 173 xxvi Figure 8.5.4. IR spectrum of complex 5.3. 174 Figure 8.5.5. 1 H NMR spectrum of complex 5.4 at 25 °C in CDCl3. 176 Figure 8.5.6. 13 C NMR spectrum of complex 5.4 at 25 °C in CDCl3. 176 Figure 8.5.7. 19 F NMR spectrum of complex 5.4 at 25 °C in CDCl3. 177 Figure 8.5.8. IR spectrum of complex 5.4. 177 Figure 8.5.9. 1 H NMR spectrum of ligand 5.13 at 25 °C in CDCl3. 179 Figure 8.5.10. 1 H NMR spectrum of ligand 5.14 at 25 °C in CDCl3. 181 Figure 8.5.11. 1 H NMR spectrum of complex 5.5 at 25 °C in CD2Cl2. 183 Figure 8.5.12. 13 C NMR spectrum of complex 5.5 at 25 °C in CD2Cl2. 183 Figure 8.5.13. 19 F NMR spectrum of complex 5.5 at 25 °C in CD2Cl2. 184 Figure 8.5.14. IR spectrum of complex 5.5. 185 Figure 8.5.15. 1 H NMR spectrum of complex 5.6 at 25 °C in CD2Cl2. 186 Figure 8.5.16. 13 C NMR spectrum of complex 5.6 at 25 °C in CD2Cl2. 187 Figure 8.5.17. 19 F NMR spectrum of complex 5.6 at 25 °C in CD2Cl2. 187 Figure 8.5.18. IR spectrum of complex 5.6. 188 Figure 8.5.19. Absorption spectra of complex 5.2 in different solvents. 189 Figure 8.5.20. Absorption spectra of complex 5.2 and it’s methyl homolog in formic acid. 189 Figure 8.6.1. 1 H NMR spectrum of complex 6.1 at 25 °C in CD2Cl2. 191 xxvii Figure 8.6.2. 13 C NMR spectrum of complex 6.1 at 25 °C in CD2Cl2. 192 Figure 8.6.3. 19 F NMR spectrum of complex 6.1 at 25 °C in CD2Cl2. 192 Figure 8.6.4. 1 H NMR spectrum of complex 6.2 at 25 °C in CD2Cl2. 194 Figure 8.6.5. 13 C NMR spectrum of complex 6.2 at 25 °C in CD2Cl2. 195 Figure 8.6.6. 19 F NMR spectrum of complex 6.2 at 25 °C in CD2Cl2. 195 Figure 8.6.7. 1 H-NMR spectrum of the glycerol isolated from a transesterification product of Wesson soybean oil. 196 Figure 8.6.8. A snapshot of reaction mixture after 3 days. 197 Figure 8.6.9. 1 H NMR of reaction mixture after 7 days, at 90% conversion. The solvent is D2O. 198 Figure 8.6.10. 1 H NMR of isolated lactic acid in D2O. 199 Figure 8.6.11. 1 H NMR of polylactic acid oligomer in DMSO-d6. 200 Figure 8.6.12. 1 H NMR “zoom-in” on "methine" region of the polylactic acid oligomer. 200 Figure 8.6.13. 1 H NMR of rac-lactide in DMSO-d6. 201 Figure 8.7.1. 1 H NMR spectrum of complex 7.10 at 25 °C in CD2Cl2. 203 Figure 8.7.2. 13 C NMR spectrum of complex 7.10 at 25 °C in CD2Cl2. 203 Figure 8.7.3. 1 H NMR spectrum of complex 7.13 at 25 °C in CD2Cl2. 205 Figure 8.7.4. 13 C NMR spectrum of complex 7.13 at 25 °C in CD2Cl2. 205 Figure 8.8.1. X-Ray structure of complex 2.1. 210 xxviii Figure 8.8.2. X-Ray structure of complex 2.2’. 226 Figure 8.8.3. X-Ray structure of complex 3.6. 238 Figure 8.8.4. X-Ray structure of complex 4.1. 250 Figure 8.8.5. X-Ray structure of complex 4.12. 264 List of Schemes Scheme 1.1. CO2 to methanol hydrogenation. 2 Scheme 1.2. Stepwise methanol dehydrogenation process. 5 Scheme 1.3. Formic acid dehydrogenation (left) and dehydration (right). 7 Scheme 2.1. A. Transfer hydrogenation of acetophenone reaction scheme. B. Proposed mechanism for TH by complex 2.1. 19 Scheme 2.2. Formation of 2.2’. 20 Scheme 3.1. Synthesis of iridium(III) complexes 3.1-3.9. 28 Scheme 3.2. Transfer hydrogenation of ketones by complexes 3.1-3.9. 31 Scheme 3.3. Ionic equation of water oxidation processes with ceric ammonium nitrate catalyzed by complexes 3.1-3.4, 3.6-3.9. 33 Scheme 4.1. Light-driven deprotonation of hexafluoroisopropanol by complexes 4.1 and 4.2. 37 Scheme 4.2. Synthesis of quinoline-iridium(I) conjugates 4.1 and 4.2. 39 Scheme 5.1. Light-driven formic acid dehydrogenation by complexes 5.1-5.6. 51 Scheme 5.2. Synthesis of iridium(I) complexes 5.1 – 5.6. 55 Scheme 6.1. Glycerol dehydrogenation by iridium complexes 6.1 and 6.2. 61 Scheme 6.2. Vegetable oil to PLA conversion. 63 Scheme 7.1. Synthesis of gadolinium(III) complexes 7.1, 7.2, and 7.3. 71 xxviii 1 Chapter 1. Recent Advances in Iridium-Catalyzed Homogeneous Hydrogenation and Dehydrogenation Reactions 1.1. Introduction Hydrogenation and dehydrogenation are the key reactions in catalysis that often result in a product of increased value. That is ultimately true for a wide range of processes applied on both small and a large scale. Catalytic hydrogenation of nitrogen, known as the Haber process, is the primary source of nitrogen in agriculture worldwide. As a result, nearly 80% of the total nitrogen atoms in the human body arrive from this process. 1 Dehydrogenation reactions are of the great significance too. Well established dehydrogenation of alkanes to olefins and aromatic compounds, as well as alcohols to aldehydes and ketones, are among examples of such transformations. Hydrogen produced by dehydrogenation is of particular interest since it has found great utilization as an energy carrier and has the potential to replace the fossil fuels. 2–5 Homogeneous and heterogeneous catalysis are both employed to improve existing processes. Homogeneous catalysis, however, proved to be more selective and well-behaved, therefore superior in unveiling previously unknown reactivities. Small molecules of transition metal complexes that participate in homogeneous catalysis provide a convenient handle to catalytic mechanisms investigation due to their well-defined structures. Nevertheless, a current issue in homogeneous catalysis remains the development of new highly robust transition-metal complexes affording high productivity and selectivity in a variety of processes. Moreover, there is also a high demand for catalysts that can operate via non-classical mechanisms. In this context, iridium complexes have shown the ability to catalyze a wide range of reactions following unconventional mechanisms, including hydrogenation and dehydrogenation, therefore have attracted our attention as a subject for detailed research. 2 1.2. Hydrogenation 1.2.1. CO2 Hydrogenation to Methanol Reduction of carbon dioxide with hydrogen to methanol is an appealing approach toward CO2 utilization for several reasons. First, carbon dioxide is one of the major components of greenhouse gas, 6 and its significant amount has an anthropogenic origin. 7 Therefore, utilization of CO2 for methanol production would reduce the effect of human activities on the global environmental changes. 8,9 Second, if carbon dioxide is converted to methanol efficiently, it will serve as a feedstock for organic building blocks 10,11 in chemical synthesis campaigns, as well as provide a useful fuel. 6-12 There is an increasing demand for methanol as both a synthetic building block and as an energy source, 13 hence, a technology that can catalyze the conversion from CO2 to methanol would be of great economic value. 6-14 Indeed, methanol is an excellent alternative fuel and energy source, in general. It can be oxidized with air in a direct methanol fuel cell (DMFC) to generate electricity, 15 used as a classical fuel on its own, 16 and used as an additive to gasoline. 17 The only products of complete methanol combustion or oxidation with air are water and carbon dioxide, so one can envision carbon dioxide as a readily available 2,3,18 (atmospheric CO2), recyclable 6,19 and high-energy 6-13 molecular hydrogen storage carrier that would fasten otherwise dangerous hydrogen gas into well-behaved and relatively safe liquid methanol. Scheme 1.1. CO2 to methanol hydrogenation. Although methanol synthesis from carbon dioxide is not as industrialized as conventional methanol synthesis from carbon monoxide, 20 this alternative CO2 to methanol route has attracted increasing attention of investigators in fields of photocatalysis, 21 electrocatalysis, as well as homogeneous 22,23 and heterogeneous catalysis. 24 A significant number of the reported heterogeneous catalytic systems are based on copper supported by metal oxides, where copper CO 2 HCOOH CH 3 OH + H 2 + 2 H 2 - 2 H 2 O 3 atoms are believed to be active centers of the catalyst. 25 Those systems are known to undergo deactivation easily due to the sensitivity of copper, 26 and that profoundly impacts selectivity and conversion in a negative way. Recent advances in this field include several catalytic systems based on indium oxide 27,28 that have high methanol selectivity (with low conversion, however); as well as the more notable zinc oxide – zirconium oxide catalytical system developed by Li et al., 29 which has both high methanol selectivity and unprecedented CO2 to methanol conversion. Homogeneous catalysis does not provide a great solution for direct CO2 to methanol conversion. The major limiting factor for this transformation is the use of a stoichiometric base. This is key, because base deprotonates formic acid, the first-formed product of CO2 reduction, thus making formate ion, which is difficult to reduce. There are few systems available for the direct carbon dioxide to methanol conversion. 30–32 All of them are based on ruthenium and operate by unconventional mechanisms and in some cases requiring a separate catalyst for each catalytic step. Unfortunately, none of these systems can be applied on a large scale due to the low turnover numbers. 1.2.2. CO2 Hydrogenation to Formic Acid One of the available strategies for carbon dioxide recycling is its reduction to formate or formic acid. Last decade was especially prosperous in this field, and iridium complexes proved to play an unambiguously important role in a mentioned conversion. In 2009, Nozaki et al. reported catalytic hydrogenation of carbon dioxide in aqueous hydroxide solution with isopropyl- substituted PNP-pincer iridium trihydride 1.1 as a catalyst. 33 Resulting formate was obtained with the turnover number up to 3 500 000 and a turnover frequency of 150 000 h −1 . Both TON and TOF are the highest values reported to date. Nozaki’s system operates at elevated temperatures and pressure above 50 atm. Authors used the experimental as well as the computational studies to 4 support their proposed mechanism and suggested that deprotonation of a backbone (dearomatization step) or the hydrogenolysis is the rate-determining steps. Figure 1.1. Iridium complexes for CO2 to formate hydrogenation. Another remarkable iridium catalytical system for CO2 to formate transformations was reported by Peris et al. in 2011 34 . They have demonstrated a high TON of 190 000 on iridium bis- NHC complex 1.2 under the hydrogen pressure of 60 atm. The temperature of the reaction was rather high, up to 200 °C; nonetheless, complex appeared to be thermally stable under those conditions. Both, the reactivity and the thermal stability of the metal complex might be explained by the electron donor character of the chelating NHC ligands. Peris et al. were also the first to introduce isopropanol as the hydrogen source for CO2 hydrogenation. Transfer hydrogenation helped them to overcome inconveniences of using pressurized H2; however, use of a non-H2 hydrogen source resulted in a lower reactivity. In the same year Muckerman, Fujita, and Himeda described series of iridium complexes, which promote the catalytic hydrogenation of CO2 in basic water. 35 Remarkably, reported system operates under atmospheric pressure and at room temperature. The ligand design is of particular interest in these systems. It is based either on bipyridine, like complex 1.3 or pyridyl azole, like complex 1.4. In both cases, ligand contains hydroxy groups. It appeared that proton-responsive substituents enormously increase the catalytic reactivity since they result in secondary coordination sphere interactions. They have demonstrated that hydroxy-containing complexes N P P Ir H H H 1.1 O O Ir I I N N N N SO 3 - - O 3 S K + K + 1.2 N N Ir OH 2 Cp* OH OH 1.3 N N N Ir OH 2 Cp* OH 1.4 (OTf) 2 (OTf) 2 5 were much more efficient than the unsubstituted complexes. Also, incorporation of additional electron-donating hydroxy functionalities into the ligand led to the enhanced reactivity of pyridyl azole-based complexes in comparison to analogous bipyridine compounds. 1.3. Dehydrogenation 1.3.1. Dehydrogenation of Methanol The unsustainability of hydrocarbon-based fuels, as well as the pollution caused by burning them, urges new clean technologies for energy generation to be developed. Hydrogen has a high energy content (120 MJ/kg) and exceeds the one of gasoline by three times (44 MJ/kg), 36 therefore is well suitable for chemical energy storage. It can be burned directly in the internal combustion engine to give heat or catalytically oxidized in a fuel cell to produce electricity. Water is the only by-product in both cases, thus proving the clean nature of the energy stored in hydrogen. Fuel cell electric vehicles are produced by multiple manufacturers and are on a road already. 37–39 They are being served by 33 hydrogen fueling stations in California, 40 with more planned to be open in a close future across the country. 41 Scheme 1.2. Stepwise methanol dehydrogenation process. Large-scale hydrogen utilization as a fuel, however, creates a new challenge, since under ambient condition it is a gas. Absorption, compression, and cryogenic liquefaction are among available hydrogen storage strategies, however, all of them known to be non-cost efficient, low in capacity and involve safety issues. 42 As a result, dehydrogenation of small molecules is an attractive approach toward on-demand hydrogen release. Organic hydrogen carriers like formic acid or methanol have high hydrogen storage density and due to its liquid appearance can be CH 3 OH HCHO OH OH H H HCOOH CO 2 -H 2 -H 2 -H 2 H 2 O 6 distributed by excising fuel infrastructure. Moreover, selective dehydrogenation of these compounds would produce hydrogen and carbon dioxide only. The latter can be recycled by known systems, 43–45 fulfilling a carbon-neutral fuel cycle. Methanol dehydrogenation is possible with few ruthenium and iron complexes. 46 In 2015, Fujita and Yamaguchi reported an efficient iridium-based catalytic system for the production of hydrogen from an aqueous methanol. 46 The catalyst for this transformation is an anionic iridium complex 1.6 that features a functional bipyridonate ligand. Complex 1.6 can be generated via reversible deprotonation of the mentioned above complex 1.3. Catalytic hydrogen evolution by this system yielded in 10,510 TON under mild temperature below 100 °C in a weakly basic solution of sodium hydroxide. The mechanism at which described system operates is not entirely understood; however, ligand-metal cooperative mechanism seems to be critical for this conversion. Figure 1.2. Interconversion of iridium complexes 1.3, 1.5, and 1.6. 1.3.2. Dehydrogenation of Formic Acid Unlike the methanol dehydrogenation case, there are quite a few heterogeneous 47–58 and homogeneous 59–75 systems capable of formic acid dehydrogenation. Heterogeneous catalysts are known to be separable from the reaction mixture bulk, as well as reusable. 57 However, harsh conditions are often required for heterogeneous catalysis and as a result selectivity of the process decreases. Homogeneous catalysts, on the other side, are in general more efficient, selective and robust at milder conditions. Selectivity is a crucial aspect in catalysis since the small amounts of N N Ir OH 2 Cp* OH OH 1.3 2+ N N Ir OH 2 Cp* O O 1.5 N N Ir OH Cp* O O 1.6 - Base Base Acid Acid 7 undesirable by-products is a well-known reason that hinders on scale application. For example, most of the formic acid dehydrogenation systems, both heterogeneous and homogeneous lacking the selectivity and produce carbon monoxide. CO is known to poison fuel cell catalysts and therefore limit the use of formic acid as an organic hydrogen carrier in those cases. Scheme 1.3. Formic acid dehydrogenation (left) and dehydration (right). A great example of an iridium catalyst for the formic dehydrogenation was reported by Reek et al. 76 Their system is based on phosphine-functionalized sulfonamide (bisMETAMORPhos) ligand. The anionic form of this ligand act as an internal base, thus affording base-free formic acid dehydrogenation by its iridium complex 1.7. The system appeared to be highly reactive, TOF of 3270 h –1 , as well as selective, producing only carbon dioxide and hydrogen with no carbon monoxide being detected. It is believed that the mechanism at which dehydrogenation is happening involves direct hydride transfer from formic acid to the metal center rather than the β-hydride elimination. Figure 1.3. Iridium complexes for formic acid dehydrogenation. An interesting approach towards formic acid dehydrogenation was selected by Miller et al. 77 They have demonstrated photochemical formic acid dehydrogenation by iridium(III) bipyridine complex 1.8 under mild conditions. The rate-determining step in this system was found to be light-triggered hydrogen release from a metal hydride intermediate. Unfortunately, the HCOOH CO 2 + H 2 HCOOH CO + H 2 O ; O P P Ph Ph N NH Ir S S R O O R O O N N Ir Cl Cp* Cl Ir P N tBu tBu Ir P N tBu tBu H H solv solv H H 2+ Ir N P tBu tBu OTf 1.7 1.8 1.9 1.10 8 catalyst did not operate with a high turnover frequency nor did it provide a great turnover number due to its decomposition. One of the most robust formic acid dehydrogenation catalysts came out of our research group and was reported by Celaje et al. 66 It is a complex of iridium bearing the 2-((di- tbutylphosphino)methyl)pyridine as a ligand. The complex 1.9 delivers high turnover frequency (3.7 s −1 ) as well as high turnover numbers (2.16 million) at a low loading and a catalytic amount of base. The complex can be reused for more than 50 cycles even after exposure to air. The mechanism through which this system operates appeared to be unique and is based on two-metal intermediates, like 1.10. Besides remarkable reactivity, the described system delivers great selectivity with no carbon monoxide being detected above 10 ppm level. 1.3.3. Dehydrogenation of Glycerol Similarly to formic acid dehydrogenation, glycerol dehydrogenation is another example of a technology that is impractical due to the low selectivity. However, lactate is a major product of this transformation, small percent of a side product glycols is almost unexceptionally formed. That prohibits the formation of long chains, which is crucial in polylactic acid synthesis. With a rapidly growing market for this biodegradable material 78 and low efficiency of current fermentation-based lactic acid manufacturing, the technology based on glycerol would be of great value. Figure 1.4. A. Catalytic glycerol dehydrogenation to lactate. B. Glycerol dehydrogenation complexes 1.11 and 1.12. OH OH HO + H 2 OH O O Base - , Cat. 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Lauridsen who helped in complexes synthesis and Valery Cherepakhin who helped with X-ray data collection. DFT studies performed by our collaborator Prof. Shaama Mallikarjun Sharada. 2.1. Introduction We describe here an iridium complex that effects transfer hydrogenation through a metal- ligand cooperative mechanism through reversibly dearomatized, bidentate ligand. The complex, Cp*IrCl(2-pyridylmethyl)toluenesulfonamide (2.1), accesses a mechanism for transfer hydrogenation of ketones with isopropyl alcohol that has not been previously reported: the system initiates via elimination of HCl from 2.1 with base to give dearomatized 16 e- coordinatively unsaturated complex (2), analogous to the one identified by Milstein. Kinetic evidence and density functional theory (DFT) calculations both indicate that 2.2 proceeds to transfer H2 through a single transition state in which activation of isopropanol’s C–H and O–H bonds is concerted. DFT studies reveal that one solvent molecule is needed to “shuttle” a proton from the alcohol to the ligand. Thus, we characterize for the first time an example of metal-ligand cooperation via reversible ligand dearomatization outside of the pincer scaffold. Substrate activation via dual-site metal-ligand cooperation is a thought-provoking area in catalysis, 2–6 particularly because such mechanisms enable reactivity that is not available to the metal alone. Asymmetric hydrogenation of unsaturated polar bonds demonstrated by Noyori is an excellent example of this. 7 In Noyori’s systems, cooperation between a ruthenium center and its amido ligand results into H2 splitting and delivery of proton and hydride to substrate. Transfer 17 hydrogenation by these systems occurs analogously. 8,9 A different model of cooperative hydrogen transfer was discovered by Milstein, et. al. 10 who show aromatization and dearomatization of pyridine-based pincer complexes. Catalysts of this type are versatile in their applications, with reactivity being heavily dependent on the ligand design. Figure 2.1. Precatalysts and their activity toward metal-ligand cooperative mechanism. The community generally accepts that Milstein’s PNP and PNN pincers operate via a metal-ligand cooperative mechanism; still, the role of the ligand backbone in catalysis is actively being studied for some reactions of the system. 11–14 More broadly, controversy surrounds many bifunctional mechanism proposals, 14–17 and cases are documented of non-cooperative, metal- centered catalysis by complexes in which cooperation was designed or expected. 18–24 Particularly in our lab, bidentate complexes, unlike their pincer congeners, are known not to participate in cooperative catalysis when a reversibly dearomatized ligand is designed into the chelate to serve that purpose. 25–28 For example, in the cases of complexes B and C (Figure 2.1), we showed that the dearomatized complex is not part of the C–H bond cleavage in which the complex participates. N Ir P N Ir N N t Bu t Bu L X N M P t Bu t Bu N N Ts A B C 2.1 Milstein et al. Previous Work Previous Work This Work M = Ir, Ru, Rh etc. X = P t Bu 2 , NEt 2. Cooperative Metal-Centered Formic Acid Dehydrogenation Metal-Centered Alcohol Dehydrogenation Cooperative Transfer Hydrogenation of Ketones Previous Work Metal-Centered Alcohol-Amine Coupling H H H H H H H H Ir Cl OTf OTf N N Ts H H Ru Cl 18 Here we report a bidentate iridium complex, Cp*IrCl(2-pyridylmethyl)toluenesulfonamide (2.1), which enables transfer hydrogenation via metal-ligand cooperation through reversibly dearomatized pyridine moiety of the ligand. The iridium metal center and the (2- pyridylmethyl)sulfonamide ligand of the complex act in concert in C–H and O–H activation via reversible dearomatization of the ligand: this contrasts the NNP Milstein complexes in which chemistry happens more readily on phosphorus side of the pincer and shows instead an example of a picolylamine fragment that effects the chemistry. This is demonstrated on the transfer hydrogenation of ketones with isopropyl alcohol as a hydrogen source. Because the concerted nature of proton/hydride transfer on Milstein-type pincers is still open, 14 and our bidentate complexes that have access to a similar cooperative mechanism don’t use it, we saw fit fully to characterize this present system with experimental and computational data. Kinetic isotope effect data align with the concerted nature of this transformation, and DFT calculations validate ligand dearomatization in the cooperative mechanism. Calculations further show that the measured activation energy is best explained by incorporating a second isopropanol molecule as a proton transfer shuttle in the transition state. 2.2. Mechanistic Studies Complex 2.1 undergoes rapid HCl elimination in dichloromethane solvent when treated with base, quantitatively transforming into complex 2.2. This reaction is accompanied by a color change from yellow to deep purple, which is associated with the dearomatization of the pyridine moiety. This transformation is readily characterized by 1 H NMR. It is similar to dearomatization reactions of the parent pincer complexes. 10 We have observed this process of pyridine dearomatization in our other bidentate P–N (B) and C–N (C), 25,26 even though these do not exploits bifunctional mechanisms for C–H bond cleavage or formation. 19 Scheme 2.1. A. Transfer hydrogenation of acetophenone reaction scheme. B. Proposed mechanism for TH by complex 2.1. Interestingly, complex 2.1 undergoes intramolecular C–H activation if exposed to direct sunlight (Scheme 2). The resulting complex 2.2’ features a bond from the iridium center to the ortho position of its tosyl moiety. Proton transfer from that position results in a backbone protonation and re-aromatization of the pyridine. This conversion is quantitative. Moreover, the intramolecular C–H activation is selective over the intermolecular process, even if conversion is conducted in benzene or toluene as a solvent. Photolysis is essential for the formation of 2.2’, since 2.1 2.2 TS 2.3 H O H O H 2.4 TS 2.5 O OH Ph O Ph OH + Base - HCl OH Ph O + O Ph OH + 2.1, Base A: Transfer hydrogenation (TH) of acetophenone B: TH mechanism with precatalyst 2.1 N N Ts Ir Cl N N Ts Ir Ir H N Ts N Ir N Ts N H O Ph H O H Ir N Ts N 20 heating 2.2 in dichloromethane, benzene, or toluene does not result in any reaction. The exact mechanism of intramolecular C–H activation leading to complex 2.2’ is not yet known. Crystals of 2.2' suitable for X-ray analysis were obtained by layering n-heptane over a concentrated dichloromethane solution of 2.2 (Figure 2.2). The structures show that each complex retains the expected piano stool geometry. Scheme 2.2. Formation of 2.2’. Figure 2.2. X-Ray structure of 2.1 (left) and 2.2’ (right). Ellipsoids drawn at the 50% probability level. When complex 2.1 is treated with a base in isopropyl alcohol, complex 2.2 is formed, the reaction mixture transiently turns from yellow to deep purple only, then rapidly changes to deep red. 1 H NMR studies of this sequence in (CD3)2CHOH solution confirmed the presence of 2.2 and N N Ts Ir Cl 2.2 N N Ir S O O 2.1 2.2’ hv +KOtBu - KCl, tBuOH N N Ts Ir 21 revealed the formation of a single hydride species, 2.4. Heating this mixture does not result in a visible change in the spectra, suggesting that the system is inactive in acceptorless dehydrogenation of a secondary alcohol under the conditions. Complex 2.4 can be independently prepared by reacting 2.2 with formic acid. Introduction of acetophenone as a hydrogen acceptor in an isopropanol solution of 2.1 and base afforded transfer hydrogenation. This reaction proceeds with concerted cleavage of C–H and O–H in a single step via metal-ligand cooperation. A homolog of complex 2.1 containing a (2-pyridyl-ethylenyl)sulfonamide backbone previously reported by O’Connor et al. 29 shows very different reactivity in transfer hydrogenation of ketones with isopropyl alcohol. This complex facilitates base-free transfer hydrogenation, whilst our system is inactive in the absence of a base. While these investigators observe deep purple coloration after adding base, this treatment shuts down reactivity. In contrast, we find a deep purple color is associated with an active catalyst, complex 2.2. We found a binuclear mechanism of transfer hydrogenation by our system by KIE data. KIE studies in four isopropanol isotopologs show that both the C–H and the O–H groups of isopropanol are involved in (or before) the rate-determining transition state. The combined isotope effect (kCHOH/kCDOD = 2.15(3)) matches the product of the average separate O–H and C–H isotope effects 2.16(6). This is consistent with a mechanism in which the transformation of both hydride and proton bonds occurs in a single kinetically relevant step. Secondary KIEs were determined by comparing measured rate constants of (CH3)2CHOH and (CD3)2CHOH, k(CH3)2CHOH/k(CD3)2CHOH = 1.69(18)/1.38(2) = 1.23(13). 22 Table 2.1. Kinetic isotope effect data. Compound k, s -1 KIE observed (CD3)2CHOH 1.38(2) x 10 -4 kCHOH/kCHOD 1.13(2) (CD3)2CDOH 7.63(1) x 10 -5 kCDOH/kCDOD 1.19(2) (CD3)2CHOD 1.22(1) x 10 -4 kCHOH/kCDOH 1.80(4) (CD3)2CDOD 6.40(9) x 10 -5 kCHOD/kCDOD 1.91(4) kCHOH/kCDOD 2.15(3) We find that the catalysis is homogeneous. The physical appearance of the reaction mixture of acetophenone transfer hydrogenation by precatalyst 2.1 is a transparent red solution. All of the kinetic data are cleanly modeled, and the use of a mercury drop, as well as quantitative poisoning experiments further confirmed homogeneous catalysis. 30 A mercury drop in the reaction mixture did not change its rate. When one half equivalent of phenanthroline (relative to iridium) is added, the rate constant of the reaction decreases by only ca. 70%. This is inconsistent with the formation of a reactive iridium nanocluster. 31 Eyring analysis was used to determine the activation parameters of acetophenone transfer hydrogenation. Rate constants were obtained by NMR in (CD3)2CHOH at variable temperatures and resulted in ΔH ‡ = +29.1(8) kcal mol -1 and ΔS ‡ = -17(19) eu. Hybrid, dispersion-corrected DFT and reaction path search methods were employed to determine the transition state of this transformation, TS 2.3. The computed ΔH ‡ = +26.2 kcal mol -1 is in reasonable agreement with the experimentally determined value. It must be noted that the DFT model utilized a sterically less hindered Cp and H2O as models of Cp* and isopropanol, respectively. A transition state TS 2.3’ in D 3 C OH/D CD 3 Ph O + D 3 C O CD 3 Ph OH/D CH 3 /CD 3 + 2.1, KOtBu H/D H/D 85 o C 23 which the activation of the C–H and O–H bonds occurs directly between the metal and the ligand without an intervening proton shuttle gave a high calculated activation enthalpy, ΔH ‡ = +52 kcal mol -1 , which is energetically unrealistic and in discord with experiment. Similar proton shuttles have been invoked in the pincer hydrogenation literature. 32,33 Figure 2.3. Optimized structures of TS 3 and TS 3’. The proton shuttle was modeled as H2O in place of IPA; Cp* was modeled as Cp; and tosyl sulfonamide was modeled as the triflyl congener. 2.3. Conclusion In conclusion, we present the first example of a bidentate transition metal complex that operates via metal-ligand cooperative mechanism previously known only in the pincer scaffold only. 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Organometallics 2005, 24 (8), 1819–1831. (32) Zeng, G.; Guo, Y.; Li, S. H2 activation by a (PNP)Lr(C6H5) Complex via the Dearomatization/Aromatization Process of the PNP Ligand: A Computational Study. Inorg. Chem. 2009, 48 (21), 10257–10263. (33) Iron, M. A.; Ben-Ari, E.; Cohen, R.; Milstein, D. Metal–Ligand Cooperation in the Trans Addition of Dihydrogen to a Pincer Ir(I) Complex: A DFT Study. J. Chem. Soc. Dalton Trans. 2009, 0 (43), 9433–9439. 27 Chapter 3. Synthesis, Structure, and Reactivity of Novel Amino Sulfonamide Complexes of Iridium(III) This chapter contains preliminary unpublished experimental results. I would like to take this opportunity to acknowledge Paul J. Lauridsen who helped in complexes synthesis and reactivity data collection. 3.1. Introduction A new family of Ir(III) complexes with bidentate amino sulfonamide ligand scaffold was synthesized and investigated as hydrogenation, transfer hydrogenation, and water oxidation catalysts. In particular, the presented complexes appear to catalyze base-free CO2 hydrogenation, transfer hydrogenation of ketones, and water oxidation with ceric ammonium nitrate (CAN). Amino sulfonamide complexes of transition metals have a long history of successful catalytic reactivity. 1–5 Asymmetric hydrogenation catalyst developed by Noyori is one of the greatest examples. 6 Iridium(III) sulfonamide complexes have also been reported, 7 however, unlike Noyori’s ruthenium system, the reactivity of iridium compounds was not investigated in depth. It is surprising considering the wide spectrum of unique reactivities characteristic to both Ir(I) and Ir(III) complexes. Moreover, iridium complexes are known to catalyze base-free transformations, 7– 11 a quality that is essential for one of our targeted reaction of carbon dioxide hydrogenation to methanol. 3.2. Design and Synthesis of Iridium(III) Amino Sulfonamide Complexes Complexes 3.1-3.9 were designed to have two reoccurring X-type ligand fragments of sulfonamide and pentamethylcyclopentadienyl. A third X-type chloride ligand is present only in 3.1-3.5 fragments, and in the remaining complexes, 3.6-3.9, it is displaced by the outer sphere 28 triflate anion. However, the major difference among these compounds is an L-type ligand. In complexes 3.1, 3.3, 3.5, 3.6, and 3.8 it is represented by an aliphatic primary amine while in the rest there is an aromatic pyridine or pyrimidine in place. Figure 3.1. Novel amino sulfonamide complexes of iridium(III). As demonstrated in Scheme 3.1, complexes 3.1-3.5 were synthesized in two steps starting from the tosylation of corresponding amines, 3.10-3.14. Deprotonation of the sulfonamides 3.15- 3.19 followed by the addition of pentamethylcyclopentadienyliridium(III) chloride dimer afforded complexes 3.1-3.5. Treatment of 3.1-3.4 with silver triflate resulted in complexes 3.6-3.9. Unfortunately, the same reaction conditions did not facilitate the transformation of 3.5 to its triflate form, leading instead to multiple unidentified products. Scheme 3.1. Synthesis of iridium(III) complexes 3.1-3.9. 3.6 3.7 3.1 3.2 3.3 3.4 3.8 3.9 N N N Ts Ir Cl N N N Ts Ir OTf H 2 N N Ts Ir Cl H 2 N N Ts Ir OTf N N Ts Ir Cl H 2 N N Ts Ir Cl N N Ts Ir OTf H 2 N N Ts Ir OTf H 2 N N Ts Ir Cl 3.5 3.10 R = ethylamine 3.11 R = methylpyridine 3.12 R = cyclohexylamine 3.13 R = methylpyrimidine 3.14 R = propylamine R NH 2 TsCl, Base R NHTs Base, [IrCp*Cl 2 ] 2 3.1-3.5 N N Ir Cl Ts AgOTf N N Ir OTf Ts 3.6-3.9 3.15-3.19 29 The X-Ray structure of 3.6 revealed that it is a 16 e - coordinatively unsaturated complexes. It is unusual for Ir(III) complexes to exist in this particular geometry. It is typical for inner sphere chloride to be displaced by the outer sphere triflate in similar compounds, however, in most cases this results in a fully-coordinated, solvent-supported form of the complex. Moreover, isolation of complexes 3.6-3.9 involves THF, known coordinative solvent, however, even this did not result in the solvento formation. Figure 3.2. X-Ray structures of iridium complexes 3.2 (left) and 3.6 (right), triflate counterion omitted for clarity. 3.3. Screen for Reactivity 3.3.1. CO2 Hydrogenation Iridium(III) complexes 3.1-3.9 were tested for the base-free CO2 hydrogenation. While 3.1- 3.5 were completely inert, 3.6-3.9 catalyzed carbon dioxide to formic acid transformation. Complex 3.6 delivered the highest turnover number among all the complexes reaching a TON of 30 in 24 hours. This particular run was conducted in D2O and required high pressures of both gases pCO2 = 20 atm and pH2 = 60 atm, as well as the temperature of 100 o C. A decrease in the 30 temperature or partial pressure of gases resulted in no reactivity or single digits TON amplifying the importance of the harsh conditions for the reaction to occur. Figure 3.3. NMR of post reaction mixture of CO2 hydrogenation by 3.2 in 8 m H2SO4 in D2O. Interestingly, addition of sulfuric acid to the reaction mixture shut down the carbon dioxide hydrogenation in most cases. However, complex 3.2 appeared to be active in 8 m H2SO4 solution in D2O producing substoichiometric amounts of both formic acid and methanol (Figure 3.3). This is promising since the obtained results demonstrate a possibility of base-free hydrogenation of CO2 to methanol. Unfortunately, conditions optimization did not help to overcome stoichiometric conversion, therefore, catalytic turnover was not achieved. 31 3.3.2. Transfer Hydrogenation of Ketones After we observed promising base-free hydrogenation results with complexes, we proceeded to screen base-free transfer hydrogenation reactivity. This reaction uses safer, non-H2 hydrogen sources, IPA in our case, and therefore is appealing on its own. Complexes 3.1-3.9, however, appeared to be inactive to this reaction, only occasionally delivering few turnovers that were not reproducible if repeated. The situation changed dramatically when a catalytic amount of base was introduced to the reaction mixture. The whole family of complexes expressed the ability to catalyze transfer hydrogenation at those conditions and the results of these reactions are summarized in Table 3.1. Moreover, there is a trend of increased reactivity of aromatic amine- containing complexes toward this reaction. Scheme 3.2. Transfer hydrogenation of ketones by complexes 3.1-3.9. We observed that the appearance of the reaction mixture of acetophenone transfer hydrogenation by pyridine- and pyrimidine-containing complexes was different than in those reactions that utilize the rest of complexes. The reaction mixture with complexes 3.2, 3.4, 3.7, and 3.9 turns purple at the beginning of the reaction and then goes to red while reaction mixture with complexes 3.1, 3.3, 3.5, 3.6, and 3.8 remains orange at any time point of the reaction. This observation, together with the different trends of reactivity, can be explained by different mechanisms at which those two types of complexes operate. As described in Chapter 2, complexes 3.2, 3.4, 3.7, and 3.9 operate via a metal-ligand cooperative mechanism involving dearomatization of the ligand backbone. The rest of the complexes containing primary aliphatic amine cannot operate through the same mechanism due to the absence of dearomatizable moiety in the ligand. O OH [Ir], Base IPA, reflux 32 It is reasonable to assume that complexes 3.1, 3.3, 3.5, 3.6, and 3.8 operate through the Noyori- type mechanism since the ligands are either the same or reminiscent to those used by Noyori. Table 3.1. Transfer hydrogenation of ketones by iridium(III) sulfonamide complexes 3.1-3.9. Entry Catalyst TON 1 h TON 4 h KOtBu KOH KOtBu KOH 1 3.1 64 58 86 84 2 3.2 84 81 98 99 3 3.3 67 53 94 74 4 3.4 62 81 94 98 5 3.5 67 56 93 78 6 3.6 70 57 93 81 7 3.7 75 80 97 98 8 3.8 68 61 86 84 9 3.9 74 64 96 98 Typical reaction conditions are 1 mol% catalyst loading, 10 mol% base loading. Hotplate temperature was set to 85 o C. Mesitylene was used as an internal standard and TON calculated from NMR data. All reactions reached the completion in 8 h. 3.3.3. Water Oxidation These complexes are also capable of catalyzing water oxidation processes with ceric ammonium nitrate (CAN). Our studies revealed that iridium complexes 3.1-3.4 and 3.6-3.9 have comparable reactivity as summarized in Table 3.2, and that modifications of the ligand do not lead to a significant change in the reactivity. Unfortunately, all of the investigated complexes deliver most of the reactivity in the first 10 minutes of the experiment and completely stop after an hour. 33 Increase in the temperature did not result in better reactivity and facilitated even faster deactivation. Scheme 3.3. Ionic equation of water oxidation processes with ceric ammonium nitrate catalyzed by complexes 3.1-3.4, 3.6-3.9. Table 3.2. Water oxidation by iridium(III) sulfonamide complexes 3.1-3.4, 3.6-3.9. Entry Catalyst TON 1 3.1 607 2 3.2 574 3 3.3 540 4 3.4 581 5 3.6 533 6 3.7 530 7 3.8 558 8 3.9 556 9 -- 0 Typical reaction conditions are 0.05 mol% catalyst loading, 1.2 M aqueous CAN at 70 o C. 1 TON calculated per 1 O2 molecule formed. Reaction stops completely after 1h. 3.4. Conclusion In conclusion, we have prepared a general synthetic procedure for the family of Ir(III) amino sulfonamide complexes and conducted the initial reactivity screening for a set of selected reactions. Reported complexes have moderate reactivity toward ketones transfer hydrogenation with isopropyl as well as water oxidation with ceric ammonium nitrate reactions. New iridium 4 Ce 4+ + 2 H 2 O 4 Ce 3+ + 4 H + + O 2 [Ir] 34 complexes also appeared to be active toward base-free hydrogenation of carbon dioxide to formic acid and, more importantly, delivered promising results in carbon dioxide to methanol conversion. 3.5. References (1) Günnaz, S.; Özdemir, N.; Dayan, S.; Dayan, O.; Çetinkaya, B. Synthesis of Ruthenium(II) Complexes Containing Tridentate Triamine (NNN) and Bidentate Diamine Ligands (NN): As Catalysts for Transfer Hydrogenation of Ketones. Organometallics 2011, 30 (15), 4165– 4173. (2) Klingele, M. H.; Moubaraki, B.; Murray, K. S.; Brooker, S. Synthesis and Some First-Row Transition-Metal Complexes of the 1,2,4-Triazole-Based Bis(Terdentate) Ligands TsPMAT and PMAT. Chem. Eur. J. 2005, 11 (23), 6962–6973. (3) Kilpin, K. J.; Jarman, B. P.; Henderson, W.; Nicholson, B. K. Catalytic Activity of Cycloaurated Complexes in the Addition of 2-Methylfuran to Methyl Vinyl Ketone. Appl. Organomet. Chem. 2011, 25 (11), 810–814. (4) Gonzalez-de-Castro, A.; Robertson, C. M.; Xiao, J. Dehydrogenative α-Oxygenation of Ethers with an Iron Catalyst. J. Am. Chem. Soc. 2014, 136 (23), 8350–8360. (5) Trose, M.; Dell’Acqua, M.; Pedrazzini, T.; Pirovano, V.; Gallo, E.; Rossi, E.; Caselli, A.; Abbiati, G. [Silver(I)(Pyridine-Containing Ligand)] Complexes as Unusual Catalysts for A3-Coupling Reactions. J. Org. Chem. 2014, 79 (16), 7311–7320. (6) Noyori, R.; Hashiguchi, S. Asymmetric Transfer Hydrogenation Catalyzed by Chiral Ruthenium Complexes. Acc. Chem. Res. 1997, 30 (2), 97–102. (7) Ruff, A.; Kirby, C.; Chan, B. C.; O’Connor, A. R. Base-Free Transfer Hydrogenation of Ketones Using Cp∗Ir(Pyridinesulfonamide)Cl Precatalysts. Organometallics 2016, 35 (3), 327–335. (8) Dong, Z.-R.; Li, Y.-Y.; Chen, J.-S.; Li, B.-Z.; Xing, Y.; Gao, J.-X. Highly Efficient Iridium Catalyst for Asymmetric Transfer Hydrogenation of Aromatic Ketones under Base-Free Conditions. Org. Lett. 2005, 7 (6), 1043–1045. (9) Soltani, O.; Ariger, M. A.; Vázquez-Villa, H.; Carreira, E. M. Transfer Hydrogenation in Water: Enantioselective, Catalytic Reduction of α-Cyano and α-Nitro Substituted Acetophenones. Org. Lett. 2010, 12 (13), 2893–2895. (10) Corberán, R.; Peris, E. An Unusual Example of Base-Free Catalyzed Reduction of C=O and 35 C=NR Bonds by Transfer Hydrogenation and Some Useful Implications. Organometallics 2008, 27 (8), 1954–1958. (11) Sordakis, K.; Tsurusaki, A.; Iguchi, M.; Kawanami, H.; Himeda, Y.; Laurenczy, G. Carbon Dioxide to Methanol: The Aqueous Catalytic Way at Room Temperature. Chem. Eur. J. 2016, 22 (44), 15605–15608. 36 Chapter 4. Optical pKa Control in a Bifunctional Iridium(I) Complexes This chapter contains published work and is substantially reprinted from the original publication. 1 I would like to take this opportunity to acknowledge my co-author. Jonathan R. Hunt conducted spectral data collection and analysis and contributed to spectral results interpretation. 4.1. Introduction As emphasized in Chapter 1, catalytic methanol dehydrogenation is a holy grail reaction in chemistry. However, today it is not feasible unless stoichiometric amounts of base are present. Use of the base necessarily disqualifies this process from translation to practice, because the base will react with the CO2 product of the reaction and form carbonate. The carbonate salt makes the system inappropriate for re-use. The ultimate goal for us is to substitute the stoichiometric base needed for methanol dehydrogenation with a catalytic photobase. This would prevent the carbonate problem that cripples aqueous methanol as a hydrogen source. Chapter 4 describes the first steps toward this goal, namely the synthesis of iridium complexes that contain a pendant photobase and their ability to deprotonate alcohols. There are few ways to switch catalytic reactivity on or off, or change its selectivity, with external radiation; many of these involve photochemical activation (or deactivation) of a catalyst. In the case of homogeneous late transition metal catalysts, the metal complex itself is frequently the chromophore involved in such reactivity switching, because of low-lying empty orbitals enabling facile d-d or LMCT absorption bands. We have prepared a base-pendant ligand-metal bifunctional catalytic scaffold wherein the concept of a photobase, compound that becomes more basic in the excited state (pKa < pKa*), is used to switch the proton acceptor ability on an active site of the catalyst. So doing requires the design of molecular organometallics in which the photochemistry of the metal is orthogonal to the photobase system. In this chapter we introduce a 37 class of such complexes. While excellent progress has been made in photoacid chemistry, neither a photoacid nor a photobase has been designed into the structure of transition metal catalyst where the metal is not part of the chromophore. We find that quinoline is an efficient photobase that preserves its unique properties in the close proximity of an iridium center. The efficacy of the photobase (9.3 < pKa* < 12.4) in the iridium complex is unhindered relative to the free quinoline. We apply this notion to successful photo-driven deprotonation of an aliphatic alcohol, thus showing the first case of metal-orthogonal optical pKa control in a transition metal complex. Scheme 4.1. Light-driven deprotonation of hexafluoroisopropanol by complexes 4.1 and 4.2. Photoacids and photobases are compounds that change their pKa upon photoexcitation. Photon absorption in a photoacid results in an increased acidity, with an excited state pKa* being lower than the ground state; pKa > pKa*. Compounds with this class of photoreactivity, e.g., 1- naphthol, 1-naphthylamine etc., have been understood since the 1930s. 2 Förster characterized this phenomenon as excited state proton transfer (ESPT), 3 and described the Förster cycle as a strategy to determine pKa*. 4 Photophysical processes in photoacids have been investigated for more than 40 years. 4–17 Applications of these photoacids vary from probes for solvent environment 19–23 and molecular switches 24 to tools for local pH control 25 and markers for protein folding studies. 26 Inorganic photoacids first appeared in 1976. These compounds generally feature ruthenium and a functionalized polypyridine ligand. 27–33 In transition metal-containing photoacids, the metal is part of the chromophore. The supporting ligand tends to contain amines 29 or carboxylates, 30,31 N N O N Ir N N O N + Ir pK a (QH) + ~ 4.8 9.3 < pK a (Complex 4.2 H)* + < 12.4 H + 2+* (CF 3 ) 2 CHOH hv (CF 3 ) 2 CHO - 38 common in photobases; or phenols, 32 these are common in photoacids. Examples of photobases and photoacids containing transition metals; Re(I), 34 Fe(II), 35 Os(II), 36,37 Pt(II), 38 Ir(III), 39 and Rh(III) 40 are known, as are select hetero- and homobimetallic 40 and trimetallic 35 complexes. In fact, Meyer et al. 41 recently demonstrated that in ruthenium polypyridine the same functional group can behave as both photoacid or photobase depending on the ancillary ligands. Photobasicity has been characterized more recently than photoacidity, 5,42–51 and there are fewer applications of this phenomenon in reaction chemistry. Common examples of organic compounds that exhibit photobasicity include aromatic carboxylic acids (1-naphtholate) and azoles (quinoline), with the latter exhibiting relatively high pKa* of 11.5, (DpKa = 6.7). 5 Despite outstanding recent progress in photoredox chemistry based on iridium, ruthenium, and nickel systems, there is a dearth of examples of photoacids and bases in transition metal catalysis, particularly as applied to organic synthesis. 4.2. Synthesis and Characterization of Complexes 4.1 and 4.2 The synthesis and characterization of two iridium complexes that contain a pendant quinoline is presented below. We demonstrate that photobasicity of the quinoline is retained in these complexes and metal-orthogonal optical control over pKa of the photobase is feasible. We also show that one of the newly-synthesized complexes can deprotonate hexafluoroisopropanol (HFIPA) (pKa = 9.3) 52 upon the photoexcitation. This demonstrates for the first time that a photobase can be designed into a late metal complex, where it can effect proton transfers independent of the metal center. 39 Scheme 4.2. Synthesis of quinoline-iridium(I) conjugates 4.1 and 4.2. We designed our ligands (4.6 and 4.7, Scheme 4.2) to avoid a direct conjugation connection between the metal and the photobase. Thus, the quinoline moiety is placed on a carbon intervening the two chelating pyridine rings. Tris-heterocyclic fragments 6 and 7 are readily available in 3 and 4 steps, respectively, from the corresponding bromoaniline, and each participates in facile ligation to cyclooctadiene iridium chloride dimer to afford complexes 4.1 and 4.2 respectively. Crystals of 4.1 suitable for X-ray structure analysis were obtained by layering n-heptane over a concentrated dichloromethane solution of 4.1. An X-ray structure affirmed that the iridapyrimidine ring prefers the expected boat conformation. (Figure 1). Importantly, iridium is not bound to the quinoline moiety of 4.6, which contrasts an analogous a zinc-containing complex (4.12, see Chapter 8). Solution NMR data for both 4.1 and 4.2 are consistent with a dynamic structure in which both the ring flip of the iridapyrimidine ring 53 and rotation of the quinoline- carbinol bond are rapid on the NMR timescale. Thus, while the quinoline nitrogen is not bound to the iridium center, it has access to the space around the metal. 4.3 H 2 N Br N R N N 4.6 R = H N OR [Ir(COD)Cl] 2 NaOTf N N OR N Ir OTf 4.1 R = H 4.2 R = Me glycerol, H + CO, Pd 2-Iodopyridine EtMgBr CH 3 I, NaH 4.6 / 4.7 4.4 R = Br 4.5 R = MeOC(O) 4.7 R = Me 40 Figure 4.1. ORTEP drawings of 4.1, triflate counterion is omitted for clarity. Ellipsoids drawn at the 50% probability level. 4.3. Experimental Support for Photobasicity Preservation in Complexes 4.1 and 4.2 While it is possible to use Forster thermodynamic cycle to measure the excited state pKa* values of molecular quinoline species, 49 analysis of organometallic complexes 4.1 and 4.2 is frustrated by the overlap of broad iridium absorption features with those of the quinoline chromophore. We were thus unable to perform a clean Forster cycle analysis. We have previously used the emission of 5-methoxyquinoline in organic solvents of varying pKa values to bracket its excited state pKa* as an alternative to Forster cycle analysis. 54 Here we will take a similar approach. In this work, we begin by studying the absorption and emission spectra of quinoline in a set of solvents. Previous studies suggest that unsubstituted quinoline displays rapid (< 1 ps) intersystem crossing in the free base form in solution, so it has negligible fluorescence. 47 The protonated form does not undergo intersystem crossing under analogous conditions. Moreover, any quinoline molecule that is protonated in the ground state will emit from the protonated state once excited. Thus, if quinoline is not protonated in the ground state, emission from the protonated 41 form is indicative of excited state proton capture. We find that in each of the solvents that we studied, quinoline absorbs from the unprotonated form (see Chapter 8), as is expected from the solvents’ respective pKa values. The emission of quinoline in dichloromethane and high pKa alcohols appears to be negligible, which is consistent with no proton transfer in the excited state. However, in HFIPA significant emission from protonated quinoline was observed (Figure 4.2A), which indicates that quinoline deprotonates HFIPA after it has been photoexcited. Similar emission from protonated quinoline was observed in 2,2,2-trifluoroethanol (TFE), but with far less intensity (Figure 4.2A-B). The difference in intensity is most probably related to the higher pKa of TFE, as discussed in the Chapter 8. Figure 4.2. Emission spectra of quinoline (A-B) and complex 4.2 (C-D) in various solvents. Spectra B and D are zoomed versions of A and C excluding HFIPA data for clarity. 42 Concentration of 4.2 was 1.4 ´ 10 -4 M and concentration of quinoline was 2.5 ´ 10 -5 M. Spectra collected at room temperature under ambient conditions. We use the method above to approximate the pKa* of the quinoline moiety when imbedded in complex 4.2. The emission behavior of the quinoline moiety is more complicated when it is attached to a transition metal than it is in free quinoline, nevertheless, we observe increased emission from complex 4.2 when it is irradiated in HFIPA solvent (Figure 4.2C). This observation implies that the quinoline moiety in complex 4.2 can deprotonate HFIPA and that quinoline, therefore, retains its photobasicity when it is tethered in complex 4.2. The ability of the tethered quinoline to deprotonate HFIPA means its pKa* is near the pKa of HFIPA (9.3) or higher. However, unlike molecular quinoline, the same was not observed in TFE solvent (pKa 12.4, Figure 2D). This indicates that the pKa* of the quinoline moiety is lower than the pKa of TFE or the pKa* of molecular quinoline. Table 4.1. Estimated pKa values of investigated compounds. Solvent pKa Compound pKa or pKa* IPA 16.5 QuinolineH + 4.8 EtOH 15.9 MeOH 15.5 QuinolineH* + 11.5* TFE 12.4 HFIPA 9.3 Complex 2 H* + > 9.3* The two lowest energy absorption bands of the complex 4.2 can be assigned to dσ-MLCT (472 nm) and dπ*-MLCT to N-heterocycle (530 nm), respectively, by analogy to well- characterized systems in the literature. 55 The emission we observe for complex 4.2 in HFIPA 43 solvent (Figure 4.3) is blue-shifted with respect to both of these MLCT absorption bands. Since emission cannot be higher in energy than its corresponding absorption, the emission we see at 440 nm must be from excitation of the quinoline moiety in complex 4.2. This should not be confused with a small amount of emission at 350 nm that is observed from free quinoline or complex 4.2 in dichloromethane solution. This emission is higher energy than the emission observed from the same chromophores when measured in hydrogen bonding solvents. Figure 4.3. Absorption and emission spectra of complex 4.2 in HFIPA. Complex 4.1 was also studied using the method described above, but we found that it is not stable in HFIPA, TFE, methanol, or ethanol: the absorption features in these solvents were weak or completely absent. Interestingly, emission in HFIPA was strong, but its frequency is blue- shifted with respect to complex 2 and much closer to the emission frequency of free ligand 4.6 (compare 389 nm with 402 nm for free 4.6). Mass spectral studies of complex 4.1 in HFIPA 44 solution reveal a ligand-metal decomplexation decomposition pathway in this solvent (see Chapter 8). We are therefore unable to determine a pKa* for complex 4.1. 4.4. Conclusion In summary, we have synthesized, characterized and studied a new class of a photobase- containing Ir(I) complexes. Photoexcitation of given complexes results in a pKa increase of the quinoline moiety, as a consequence deprotonation of aliphatic low pKa alcohols appeared to be feasible. 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Anthrylmethylamines and Anthrylmethylazamacrocycles as Fluorescent PH Sensors—a Systematic Study of Their Static and Dynamic Properties. J. Chem. Soc. Perkin Trans. 2 2002, 0 (5), 1005–1011. (23) Barrash-Shiftan, N.; Brauer, B.; Pines, E. Solvent Dependence of Pyranine Fluorescence and UV-Visible Absorption Spectra. J. Phys. Org. Chem. 1998, 11 (10), 743–750. (24) Tatum, L. A.; Foy, J. T.; Aprahamian, I. Waste Management of Chemically Activated Switches: Using a Photoacid to Eliminate Accumulation of Side Products. J. Am. Chem. Soc. 2014, 136 (50), 17438–17441. (25) Peretz-Soroka, H.; Pevzner, A.; Davidi, G.; Naddaka, V.; Kwiat, M.; Huppert, D.; Patolsky, F. Manipulating and Monitoring On-Surface Biological Reactions by Light-Triggered Local PH Alterations. Nano Lett. 2015, 15 (7), 4758–4768. (26) Abbruzzetti, S.; Crema, E.; Masino, L.; Vecli, A.; Viappiani, C.; Small, J. R.; Libertini, L. J.; Small, E. W. Fast Events in Protein Folding: Structural Volume Changes Accompanying the Early Events in the N→I Transition of Apomyoglobin Induced by Ultrafast PH Jump. Biophys. J. 2000, 78 (1), 405–415. (27) Vos, J. G. Excited-State Acid-Base Properties of Inorganic Compounds. Polyhedron 1992, 11 (18), 2285–2299. (28) Peterson, S. H.; Demas, J. N. Excited State Acid-Base Reactions of Transition Metal Complexes: Dicyanobis(2,2′-Bipyridine) Ruthenium(III) in Aqueous Acid. J. Am. Chem. Soc. 1976, 98 (24), 7880–7881. (29) Thompson, A. M. W. C.; Smailes, M. C. C.; Je, J. C.; Ward, M. D. Ruthenium Tris- (Bipyridyl) Complexes with Pendant Protonable and Deprotonable Moieties: PH Sensitivity of Electronic Spectral and Luminescence Properties. J. Chem. Soc., Dalton Trans. 1997, No. 5, 737–743. (30) Lay, P. A.; Sasse, W. H. F. Proton Transfer in the Excited State of Carboxylic Acid Derivatives of Tris(2,2’-Bipyridine-N,N’)Ruthenium(II). Inorg. Chem. 1984, 23 (12), 4123–4125. (31) Nazeeruddin, M. K.; Kalyanasundaram, K. Acid-Base Behavior in the Ground and Excited States of Ruthenium(II) Complexes Containing Tetraimines or Dicarboxybipyridines as Protonatable Ligands. Inorg. Chem. 1989, 28 (23), 4251–4259. 47 (32) Giordano, P. J.; Bock, O.; Wrighton, M. S. Excited State Proton Transfer of Ruthenium(II) Complexes of 4,7-Dihydroxy- 1,10-Phenanthroline. Increased Acidity in the Excited State. J. Am. Chem. Soc. 1978, 100 (22), 6960–6965. (33) O’Donnell, R. M.; Sampaio, R. N.; Li, G.; Johansson, P. G.; Ward, C. L.; Meyer, G. J. Photoacidic and Photobasic Behavior of Transition Metal Compounds with Carboxylic Acid Group(S). J. Am. Chem. Soc. 2016, 138 (11), 3891–3903. (34) Leasure, R. M.; Sacksteder, L. A.; Reitz, G. A.; Demas, J. N.; Nesselrodt, D.; DeGraff, B. A. Excited-State Acid-Base Chemistry of (α-Diimine)Cyanotricarbonyl Rhenium(I) Complexes. Inorg. Chem. 1991, 30 (19), 3722–3728. (35) Maity, D.; Mardanya, S.; Karmakar, S.; Baitalik, S. PH-Induced Processes in Wire-like Multichromophoric Homo- and Heterotrimetallic Complexes of Fe(II), Ru(II), and Os(II). Dalton Trans. 2015, 44 (21), 10048–10059. (36) Browne, W. R.; O’Connor, C. M.; Hughes, H. P.; Hage, R.; Walter, O.; Doering, M.; Gallagher, J. F.; Vos, J. G. Ruthenium(II) and Osmium(II) Polypyridyl Complexes of an Asymmetric Pyrazinyl- and Pyridinyl-Containing 1,2,4-Triazole Based Ligand. Connectivity and Physical Properties of Mononuclear ComplexesElectronic Supplementary Information (ESI) Available: 1H NMR . J. Chem. Soc. Dalton Trans. 2002, 0 (21), 4048– 4054. (37) Das, S.; Saha, D.; Mardanya, S.; Baitalik, S. A Combined Experimental and DFT/TDDFT Investigation of Structural, Electronic, and PH-Induced Tuning of Photophysical and Redox Properties of Osmium(Ii) Mixed-Chelates Derived from Imidazole-4,5-Dicarboxylic Acid and 2,2′-Bipyridine. Dalton Trans. 2012, 41 (39), 12296. (38) Cummings, S. D.; Eisenberg, R. Acid-Base Behavior of the Ground and Excited States of Platinum(II) Complexes of Quinoxaline-2,3-Dithiolate. Inorg. Chem. 1995, 34 (13), 3396– 3403. (39) Leavens, B. B. H.; Trindle, C. O.; Sabat, M.; Altun, Z.; Demas, J. N.; DeGraff, B. A. Photophysical and Analyte Sensing Properties of Cyclometalated Ir(III) Complexes. J. Fluoresc. 2012, 22 (1), 163–174. (40) Maity, D.; Bhaumik, C.; Karmakar, S.; Baitalik, S. Photoinduced Electron and Energy Transfer and PH-Induced Modulation of the Photophysical Properties in Homo- and Heterobimetallic Complexes of Ruthenium(II) and Rhodium(III) Based on a Heteroditopic Phenanthroline–Terpyridine Bridge. Inorg. Chem. 2013, 52 (14), 7933–7946. 48 (41) O’Donnell, R. M.; Sampaio, R. N.; Li, G.; Johansson, P. G.; Ward, C. L.; Meyer, G. J. Photoacidic and Photobasic Behavior of Transition Metal Compounds with Carboxylic Acid Group(S). J. Am. Chem. Soc. 2016, 138 (11), 3891–3903. (42) Liu, X.; Karsili, T. N. V.; Sobolewski, A. L.; Domcke, W. Photocatalytic Water Splitting with the Acridine Chromophore: A Computational Study. J. Phys. Chem. B 2015, 119 (33), 10664–10672. (43) Nachliel, E.; Ophir, Z.; Gutman, M. Kinetic Analysis of Fast Alkalinization Transient by Photoexcited Heterocyclic Compounds. POH Jump. J. Am. Chem. Soc. 1987, 109 (5), 1342– 1345. (44) Naik, L. R.; Suresh Kumar, H. M.; Inamdar, S. R.; Math, N. N. Steady-State and Time- Resolved Emission Studies of 6-Methoxy Quinoline. Spectrosc. Lett. 2005, 38 (4–5), 645– 659. (45) Pines, E.; Huppert, D.; Gutman, M.; Nachliel, N.; Fishman, M. The POH Jump: Determination of Deprotonation Rates of Water by 6-Methoxyquinoline and Acridine. J. Phys. Chem. 1986, 90 (23), 6366–6370. (46) Poizat, O.; Bardez, E.; Buntinx, G.; Alain, V. Picosecond Dynamics of the Photoexcited 6- Methoxyquinoline and 6-Hydroxyquinoline Molecules in Solution. J. Phys. Chem. A 2004, 108 (11), 1873–1880. (47) Driscoll, E. W.; Hunt, J. R.; Dawlaty, J. M. Proton Capture Dynamics in Quinoline Photobases: Substituent Effect and Involvement of Triplet States. J. Phys. Chem. A 2017, 121 (38), 7099–7107. (48) Akulov, K.; Simkovitch, R.; Erez, Y.; Gepshtein, R.; Schwartz, T.; Huppert, D. Acid Effect on Photobase Properties of Curcumin. J. Phys. Chem. A 2014, 118 (13), 2470–2479. (49) Driscoll, E. W.; Hunt, J. R.; Dawlaty, J. M. Photobasicity in Quinolines: Origin and Tunability via the Substituents’ Hammett Parameters. J. Phys. Chem. Lett. 2016, 7 (11), 2093–2099. (50) Munitz, N.; Avital, Y.; Pines, D.; Nibbering, E. T. J.; Pines, E. Cation-Enhanced Deprotonation of Water by a Strong Photobase. Isr. J. Chem. 2009, 49 (2), 261–272. (51) Suenobu, T.; Guldi, D. M.; Ogo, S.; Fukuzumi, S. Excited-State Deprotonation and H/D Exchange of an Iridium Hydride Complex. Angew. Chemie - Int. Ed. 2003, 42 (44), 5492– 5495. (52) Middleton, W. J.; Llndsey, R. V. Hydrogen Bonding in Fluoro Alcohols. J. Am. Chem. Soc. 49 1964, 86 (22), 4948–4952. (53) 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. (54) Hunt, J. R.; Dawlaty, J. M. Photodriven Deprotonation of Alcohols by a Quinoline Photobase. J. Phys. Chem. A 2018, 122 (40), 7931–7940. (55) Fordyce, W. A.; Crosby, G. A. Electronic Spectroscopy of N-Heterocyclic Complexes of Rhodium(I) and Iridium(I). Inorg. Chem. 1982, 21 (3), 1023–1026. 50 Chapter 5. Base and Solvent-free, Light-driven Formic Acid Dehydrogenation by Iridium(I) Complexes This chapter contains preliminary unpublished data. I would like to take this opportunity to acknowledge my collaborator Jonathan R. Hunt that collected spectra and eudiometric data and contributed to spectral results interpretation. 5.1. Introduction The Sun is expected to exist for the next 5 billion years, 1 therefore utilizing the sunlight as an energy source is an appealing approach towards a sustainable energy future. Current challenges in conversion and storage of solar energy limit the light utilization, however few of the known approaches are promising. One of them is the light-driven on-demand hydrogen release from organic small molecules. Hydrogen is a classic fuel 2 and can be burned directly in the internal combustion engine to give heat or catalytically oxidized in a fuel cell to produce electricity. Using the light as a driving force in these processes will generate clean energy, where water is the only by-product. Moreover, a system that is initiated by light will be more responsive to turning on and off the reactivity, property that is crucial in the fuel cell field. Organic hydrogen carriers like formic acid have a high hydrogen storage density of 4.3 wt%. It is a liquid so potentially it can be distributed by excising fuel infrastructure. Unlike hydrogen gas itself, formic acid is not associated with high cost and low capacity storage, 3 however, it has its own downside of corrosiveness. Transition metal complex catalyzed formic acid dehydrogenation 4,5,14–20,6–13 is well known and one of the best systems was reported by our group. 19 Unfortunately, catalytical systems that utilize light to promote the dehydrogenation are barely present in the literature. In 1993, King et al. discovered that chromium hexacarbonyl promotes formic acid dehydrogenation under irradiation. 21 However, the reaction was possible 51 only in an aqueous solution of and reaction appeared to be slow with the turnover number TON 18 after the first hour of the experiment. Sixteen years later, Beller et al. reported ruthenium- catalyzed hydrogen generation from formic acid in the presence of sub-stoichiometric amounts of amines. 22 The highest reported turnover number by their system reached TON 2804. In 2015, Miller et al. demonstrated photochemical formic acid dehydrogenation by iridium(III) complexes. 23 Their system also required a base for the dehydrogenation to occur and maximum turnover number above 500 TON was achieved after 30 hours of illumination. This chapter describes for the first time light-driven and base and solvent-free formic acid dehydrogenation catalyzed by iridium(I) complexes. Light is the only energy source required for the catalysis to occur and the reaction is feasible at otherwise ambient conditions. Use of a neat hydrogen carrier with no solvent or other additives makes this system attractive due to the undiluted density of the formic acid. 5.2. Studies on Light-Driven Formic Acid Dehydrogenation Using Iridium(I) Complexes Complexes 5.1 changes its appearance when mixed with neat formic acid from yellow to transparent. Interestingly, we never observed deposition of iridium metal or any other visible decomposition product, therefore we proceeded to screen formic acid dehydrogenation reactivity using 5.1. Scheme 5.1. Light-driven formic acid dehydrogenation by complexes 5.1-5.6. HCOOH CO 2 + H 2 hv, 5.1 - 5.6 52 Figure 5.1. Iridium complexes investigated in light-driven formic acid dehydrogenation. All of the efforts, including addition of a catalytic or stoichiometric amount of base or use of the toluene or water as solvents resulted in no reactivity. Heating any of the systems mentioned above was not beneficial either. Unlike other iridium(I) catalysts previously reported, complex 5.1 appeared to be completely inert to formic acid dehydrogenation. To our surprise, the situation changed dramatically when the solution of complex 5.1 in neat formic acid was exposed to the light produced by 400 W Hg vapor lamp. The system appeared to be reactive and capable of dehydrogenating formic acid on a course of hours. We monitored the system by gas evolution using eudiometry (Figure 5.2, left). A formic acid solution of 5.1 was placed in a quartz tube closed with a stopper. A piece of Tygon tubing with a needle on one end was used to connect it with a reversed graduated burette. Standard reaction mixture contained 0.5 mL of formic acid with 0.02 mol% complex loading. N Ir N OH OTf 5.5 N Ir N O OTf 5.6 N Ir N OH N OTf 5.1 N Ir N O N OTf N Ir N OH N CO CO OTf N Ir N O N CO CO OTf 5.2 5.3 5.4 Ir P N tBu tBu Ir N N N OTf OTf A B 53 Figure 5.2. Light-Driven Formic Acid Dehydrogenation by 5.1. Left: Lamp ON all the time. Right: Lamp ON and OFF (shaded areas). In order to prove the significance of the light in formic acid dehydrogenation by 5.1 few of experiments were conducted. In the first experiments, a quartz tube containing 5.1 formic acid solution was wrapped with an alumina foil and placed under the lamp; however, this resulted in no gas evolved. In the second experiment, sample without the aluminum foil was placed under the lamp for one hour, then the lamp was turned off (Figure 5.2, left). We discovered that the removal of the light source stops the dehydrogenation process completely. By repeating the cycle of the lamp being turned on and turned off two more times we further proved that the light is essential for observed reactivity (Figure 5.2, right). Complex 5.2, which has the methylated hydroxy group of the ligand appeared to have the identical reactivity profile to that of complex 5.1 in light-driven formic acid dehydrogenation (Figure 5.3, left). This suggests that the hydroxy group of 5.1 is not involved in the mechanism of this transformation. Interestingly, when 100 eq. of sodium formate was added to both of them, the reactivity dropped by nearly 50% in both cases. This is unusual, and to our best knowledge is the only system for formic acid dehydrogenation that is inhibited by a base. 54 Figure 5.3. Left: Light-driven formic acid dehydrogenation by 5.1 and 5.2 in the absence of a base and in the presence of 100 eq. of sodium formate; Right: Light-driven formic acid dehydrogenation by 5.1, complex A, and complex B. We also tried complex A and B for this reaction (Figure 5.3, right). Complex A is one of the most reactive catalysts for this process, reaching millions of turnover numbers. 19 Complex B has significantly lower reactivity. Nevertheless, both of them dehydrogenate formic acid at elevated temperature and catalytic amounts of base. Surprisingly, none of them appeared to be as reactive as 5.1 under exposure to light, with complex B being deactivated almost immediately. From the coordinated ligand design point of view complex A and B are reminiscent with 5.1 and 5.2 and differ only by one X-type ligand. However, it seems like replacement of the pyridine moiety to phosphine or carbene does not result in the desired reactivity and points to the importance of the spaced bipyridine scaffold for base-free light-driven formic acid dehydrogenation. 5.3. Synthesis of Iridium(I) Complexes 5.1 – 5.6 To further investigate the impact of other components of complexes 5.1 and 5.2 like pendant quinoline and cyclooctadiene (COD) ligand we designed and synthesized complexes 5.3- 55 5.6. Compounds 5.3 and 5.4 can be directly obtained from the carbon monoxide displacement of COD in 5.1 and 5.2 respectively. Interestingly, the COD displacement in 5.1 was afforded by utilizing a balloon pressure of CO, when the same displacement in 5.2 occurred only with the elevated pressure of carbon monoxide of 5 atm. Naphthalene-containing spaced bipyridine fragments 5.13 and 5.14 are readily available in 1 and 2 steps, respectively, from the methyl naphthoate 5.12, and each participates in facile ligation to cyclooctadiene iridium chloride dimer to afford complexes 5.5 and 5.6 respectively. Scheme 5.2. Synthesis of iridium(I) complexes 5.1 – 5.6. Due to the structural differences it is reasonable to expect at least some change in the reactivities of 5.3-5.6 toward light-driven formic acid dehydrogenation reaction in comparison to 5.1 and 5.2. However, to our great surprise, complexes 5.3-5.6 delivered almost identical results 5.7 H 2 N Br N R N N 5.10 R = H N OR [Ir(COD)Cl] 2 NaOTf N N OR N Ir OTf 5.1 R = H 5.2 R = Me glycerol, H + CO, Pd 2-Iodopyridine EtMgBr CH 3 I, NaH 5.10 / 5.11 5.8 R = Br 5.9 R = MeOC(O) 5.11 R = Me N N 5.13 R = H OR [Ir(COD)Cl] 2 NaOTf N N OR Ir OTf 5.5 R = H 5.6 R = Me 2-Iodopyridine EtMgBr CH 3 I, NaH 5.14 R = Me O O CO N N OR N Ir OC OC OTf 5.3 R = H 5.4 R = Me A B 5.12 56 (Figure 5.4, right). These results suggest that the role of the pendant quinoline is insignificant and it is not involved in the reaction mechanism. Moreover, the fact that the quinoline would be fully protonated, therefore would have a completely different electronic character in comparison to the naphthalene in neat formic acid, suggests that pendant functionality is not part of the reactive chromophore. Figure 5.4. Left: Absorption spectra of 5.1 in selected solvents. Right: Light-driven formic acid dehydrogenation profile of 5.1, 5.2, 5.4, and 5.6. Replacement of the COD with carbon dioxide ligands in 5.1 and 5.2 did not affect the reactivity profile either. It might be explained if the active catalyst is the same in both instances. This can take place if COD or CO ligands are replaced by formic acid or formate under the reaction conditions. We do not have a direct proof of this happening. However, the absorption spectra of 5.1 in formic acid appears to be significantly different to any other spectra taken in a non-protic solvent (Figure 5.4, left). This behavior confirms the structural changes of 5.1 in formic acid, but it is inconclusive if those changes are due to the displacement of an L-type ligands. 57 The dehydrogenation reaction slows down after a couple of hours and the grey metal film can be observed on the walls. The decomposition pathway is not clearly understood, however, metal precipitation has to be due to the aggregation and/or partial or complete deligation of the iridium. 5.4. Conclusion In conclusion, we report here the first iridium(I) based system for light-driven formic acid dehydrogenation. The new catalytic scaffold can operate in neat formic acid, at ambient temperature, and more importantly without the base added, enabling the turnover number of 49 TON after the first four hours of the experiment. Furthermore, experimental work conducted here has yielded new insight into the importance of iridium(I) spaced bipyridines in studied here dehydrogenative process. (Future work in our laboratory regards the investigation of the mechanism for light-driven formic acid dehydrogenation on the reported complexes, conditions optimization, and catalytic system deactivation studies.) – not in a thesis. 5.5. 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Dehydrogenation of Formic Acid by Ir–BisMETAMORPhos Complexes: Experimental and Computational Insight into the Role of a Cooperative Ligand. Chem. Sci. 2015, 6 (2), 1027–1034. (7) Myers, T. W.; Berben, L. A. Aluminium–Ligand Cooperation Promotes Selective Dehydrogenation of Formic Acid to H2 and CO2. Chem. Sci. 2014, 5 (7), 2771–2777. (8) Sponholz, P.; Mellmann, D.; Junge, H.; Beller, M. Towards a Practical Setup for Hydrogen Production from Formic Acid. ChemSusChem 2013, 6 (7), 1172–1176. (9) Bielinski, E. A.; Lagaditis, P. O.; Zhang, Y.; Mercado, B. Q.; Würtele, C.; Bernskoetter, W. H.; Hazari, N.; Schneider, S. Lewis Acid-Assisted Formic Acid Dehydrogenation Using a Pincer-Supported Iron Catalyst. J. Am. Chem. Soc. 2014, 136 (29), 10234–10237. (10) Czaun, M.; Goeppert, A.; Kothandaraman, J.; May, R. B.; Haiges, R.; Prakash, G. K. S.; Olah, G. A. Formic Acid As a Hydrogen Storage Medium: Ruthenium-Catalyzed Generation of Hydrogen from Formic Acid in Emulsions. 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A Prolific Catalyst for Dehydrogenation of Neat Formic Acid. Nat. Commun. 2016, 7, 11308. (20) Gao, Y.; Kuncheria, J.; Yap, G. P. A.; Puddephatt, R. J. An Efficient Binuclear Catalyst for Decomposition of Formic Acid. Chem. Commun. 1998, 2365–2366. (21) Linn, D. E.; King, R. B.; King, A. D. Catalytic Reactions of Formate: Part 1. Photocatalytic Hydrogen Production from Formate with Chromium Hexacarbonyl. J. Mol. Catal. 1993, 80 (2), 151–163. (22) Loges, B.; Boddien, A.; Junge, H.; Noyes, J. R.; Baumann, W.; Beller, M. Hydrogen Generation: Catalytic Acceleration and Control by Light. Chem. Commun. 2009, 4185– 4187. (23) Barrett, S. M.; Slattery, S. A.; Miller, A. J. M. Photochemical Formic Acid Dehydrogenation by Iridium Complexes: Understanding Mechanism and Overcoming Deactivation. ACS Catal. 2015, 5 (11), 6320–6327. 60 Chapter 6. PLA and Lactides Synthesis from Lactic Acid of Post Glycerol Dehydrogenation Process This chapter contains published work 1 . I would like to take this opportunity to acknowledge my co-authors. Zhiyao Lu developed the catalyst, discovered the reactivity and conducted a major body of the experimental work. Rasha Hamze contributed to ligands syntheses and Nicky Terrile contributed to the synthesis of biodiesel. 6.1. Introduction Glycerol is a byproduct of biodiesel production and is associated with the cost of disposal 2 . More than 2.0 billion gallons of glycerol is accumulated each year by the biodiesel industry in the United States only. 3 Moreover, the volume of produced glycerol is projected to grow further in the future. 4 Glycerol constitutes about 10% of the weight of crude biodiesel, therefore its utilization creates an opportunity for new technology. 5 In recent years, multiple technologies based on the catalytic conversion of glycerol to value-added products have been developed. 6 Selective dehydrogenation of glycerol to lactic acid is one of them. It is particularly appealing because lactic acid is a valuable feed-stock for organic synthesis as well as a precursor for polylactic acid (PLA). Polylactic acid has a great potential to replace unsustainable petroleum-based polymers, not only because it has similar physical properties, but also because it is biodegradable. PLA is already widely used instead of polyethylene and polypropylene in packaging and other industries. It has also found application in manufacturing of sophisticated biomedical devices and 3D printing filament. Demand for poly(lactic) acid plastics is already higher than production capacity. 7 This is a consequence of existing lactic acid production technologies inefficiency. Currently, lactic acid is produced by fermentation. Fermentation is the major process applied on industrial scale for lactic acid production and unfortunately results only in diluted and contaminated with other 61 compounds product. 8 In this regards, homogeneous conversion of neat glycerol to lactic acid has shown promising reactivity, selectivity and yield. Moreover, acceptorless dehydrogenation of glycerol would result in readily-separable byproduct H2, which is an energy carrier and has value of its own. This chapter describes the most robust and selective catalyst to date for the conversion of glycerol to lactic acid. Our system enables high conversion as well as great selectivity (> 99%) for this process. Use of crude glycerol isolated from biodiesel production appeared not to compromise the reactivity, selectively resulting in lactate. Lactic acid can be easily isolated from our reaction mixture and then converted to rac- and meso-lactides, the precursors for PLA synthesis. Oligomers of polylactic acid were synthesized as well. 6.2. Glycerol Dehydrogenation Heating KOH and glycerol with compound 6.1 or 6.2 in air results in the selective formation of H2 and lactate with no other products detectable. The robustness of the catalyst is evident from an experiment in which we observe over 1 million turnovers in 8 days. This TON is higher than any other homogeneous system reported to date. Further, our system is robust at higher temperatures: at 180 °C the reaction time is shortened from days to hours (entries 5-9,19). We think that the greater stability and longevity of catalysts 6.1 and 6.2 are due, in part, to the bidentate architecture of the (pyridyl)carbene. This appears to inhibit ligand scrambling processes, which are observed in the Crabtree system. Scheme 6.1. Glycerol dehydrogenation by iridium complexes 6.1 and 6.2. HO OH OH OH O - O Ir, Base - N Ir N N R OTf + H 2 ; Ir = 6.1 R = Me 6.2 R = Mes 62 Table 6.1. Dehydrogenation of neat glycerol to lactate. Typical reaction conditions are 5 mL glycerol, Ir catalyst, and base (NaOH weighed and mixed in air). Reaction progress was monitored by gas evolution. a 9.3 g glycerol isolated from biodiesel transesterification was used. b The reaction started with 7.4 mL of glycerol. 6.3. PLA and Lactides Syntheses Described glycerol dehydrogenation reactions are free of solvent, therefore in most cases reaction mixture comprises mostly lactate salt upon the completion. Lactic acid isolation can be achieved using a simple pH extraction. This is important because key to the value of this contribution is the ability to convert crude output from biodiesel production to value-added material. Along these lines, we have demonstrated the conversion of soybean oil to fatty acid methyl esters (FAMEs, a biodiesel component) and crude glycerol, then further conversion of the resulting crude glycerol to a lactate salt. Thus, we treated 100 mL (93.2 g) of Wesson soybean oil with sodium methoxide and successfully isolated 100 mL of FAMEs and 9.3 g glycerol, the latter with > 95% NMR purity. With no further purification this glycerol was catalytically converted to an isolated aliquot of 5.6 g of lactic acid. Of further importance to the utility of this technology is a facile route to convert the crude lactic acid to rac- and meso-lactide monomers for use in PLA synthesis. Since the glycerol dehydrogenation process catalyzed by 6.1 or 6.2 is highly selective and result in high conversion, Entry Catalyst (ppm) Temp. (°C) Time Base (mol%) TON Conversion 1 20 (6.2) 145 7 d 100 40889 81.7% (55.6%) b 2 a 140 (6.2) 145 7 d 100 45010 90.0% (61.2%) b 3 b 140 (6.1) 180 3 d 100 50006 99.9% 63 prepolymerization of lactic acid would result in PLA oligomers and no other copolymers, like those with starting glycerol or potential side products. Thus, lactic acid can be thermally oligomerized directly from our concentrated extract to yield a prepolymer, which can then be treated with SnO to convert the material to crude rac- and meso-lactide mixture. Recrystallization of the lactide mixture successfully afforded rac-lactide with high purity and a yield of 69% from crude lactic acid, with a small fraction of meso-lactide available from the mother liquor. Since the purity of the lactic acid directly correlates with the yield of valuable final rac-lactide products, our method appeared to be more clean and superior to the one where lactic acid originates from fermentation process. Scheme 6.2. Vegetable oil to PLA conversion. 6.4. Conclusion In conclusion, we present here a high-utility technique for the conversion of crude glycerol to value-added lactides based on the oxidative conversion of glycerol to lactate. This oxidation utilizes a structurally novel iridium catalyst supported by a bidentate (pyridylmethyl)imidazolium carbene ligand. The new catalyst system enables unprecedented efficiency, longevity, and O O O O HO O O O O O O O OH n HO OH OH Base, MeOH -FAMEs Glycerol 6.1 (20 ppm), KOH Neat, 145 o C 90% HO O OK pH extraction HCl aq pH < 1 62% HO O OH Lactate Lactic Acid ΔT ΔT, SnO Polylactic Acid (oligomers) Lactide Recrustallization 69% O O O O O O O O + rac-Lactides 64 conversion in the oxidation of glycerol to lactic acid and thus enables a very practical alternative to fermentation compared to those currently available for lactic acid preparation. The reactive mechanism of this new system is proposed on the basis of experimental evidence: oxidation involves turnover-limiting β-hydride elimination to form dihydroxyacetone, which is converted rapidly to lactate. 6.5. References (1) 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. (2) Anastas, P. T.; Zimmerman, J. B. Innovations in Green Chemistry and Green Engineering, Springer-Verlag New York, 2013. (3) U. S. Monthly Biodiesel Production Report 2013 – 2015: http://www.eia.gov/biofuels/biodiesel/production/. (4) Global Glycerol Market Size, Market Share, Application Analysis, Regional Outlook, Growth, Trends, Competitive Scenario And Forecasts, 2012 to 2020: http://www.hexaresearch.com/research-report/glycerol-industry/. (5) (a)Tan, H.W.; Abdul Aziz, A.R.; Aroua, M.K. Glycerol Production and Its Applications As a Raw Material: A Review. Renew. Sustainable Energy Rev. 2013, 27, 118-127. (b) Quispea, C. A. G.; Coronadoc C. J. R.; Carvalho J. A. Jr. Glycerol: Production, Consumption, Prices, Characterization and New Trends in Combustion. Renew. Sustainable Energy Rev. 2013, 27, 475-493. (6) Pagliaro, M.; Ciriminna, R.; Kimura, H.; Rossi, M.; Pina, C. D. From Glycerol to Value- Added Products. Angew. Chem. Int. Ed. 2007, 46, 4434–4440; (b) Gu, Y.; Azzouzi, A.; Pouilloux, Y.; Jerome, F.; Barrault, J. Heterogeneously Catalyzed Etherification of Glycerol: New Pathways for Transformation of Glycerol to More Valuable Chemicals. Green Chem. 2008, 10, 164–167; (c) Katryniok, B.; Kimura, H; Skrzyńska, E.; Girardon, J.-S.; Fongarland, P.; Capron, M.; Ducoulombier, R.; Mimura, N.; Paul, S. Dumeignil F. Selective Catalytic Oxidation of Glycerol: Perspectives for High Value Chemicals. Green Chem. 2011, 13, 1960– 1979; (d) Dam, J.; Hanefeld, U. Renewable Chemicals: Dehydroxylation of Glycerol and Polyols. ChemSusChem 2011, 4, 1017–1034; (e) Wang, 65 Z.; Wang, L.; Jiang, Y.; Hunger, M.; Huang, J. Cooperativity of Brønsted and Lewis Acid Sites on Zeolite for Glycerol Dehydration. ACS Catal. 2014, 4, 1144–1147; (f) Haidera, M. H. Dummer, N. F.; Zhang, D.; Miedziak, P.; Davies, T. E.; Taylor, S. H.; Willock, D. J.; Knight, D. W.; Chadwick, D.; Hutchings, G. J. Rubidium- and Caesium-Doped Silicotungstic Acid Catalysts Supported on Alumina for the Catalytic Dehydration of Glycerol to Acrolein. J. Catal. 2012, 286, 206–213; (g) Painter, R. M.; Pearson, D. M.; Waymouth, R. M. Selective Catalytic Oxidation of Glycerol to Dihydroxyacetone. Angew. Chem. Int. Ed. 2010, 49, 9456–9459; (h) Chung, K.; Banik, S. M.; De Crisci, A. G.; Pearson, D. M.; Blake, T. R.; Olsson, J. V.; Ingram, A. J.; Zare, R. N.; Waymouth, R. M. Chemoselective Pd-Catalyzed Oxidation of Polyols: Synthetic Scope and Mechanistic Studies. J. Am. Chem. Soc. 2013, 135, 7593–7602; (i) Zhang, Y., Zhang, N., Tangb, Z.-R.; Xu, Y.-J. Identification of Bi2WO6 as a Highly Selective Visible-Light Photocatalyst toward Oxidation of Glycerol to Dihydroxyacetone in Water. Chem. Sci. 2013, 4, 1820– 1824; (j) Villa, A.; Veith, G. M.; Prati, L. Selective Oxidation of Glycerol under Acidic Conditions Using Gold Catalysts. Angew. Chem. Int. Ed. 2011, 49, 4499–4502; (k) Brett, G. L.; He, Q.; Hammond, C.; Miedziak, P. J.; Dimitratos, N.; Sankar, M.; Herzing, A. A.; Conte, M.; Lopez-Sanchez, J. A.; Kiely, C. J.; Knight, D. W.; Taylor, S. H.; Hutchings, G. J. Angew. Chem. Int. Ed. 2011, 50, 10136–10139; (l) Ruiz, V. R.; Velty, A.; Santos, L. L.; Leyva-Pérez, A.; Sabater, M. J.; Iborra, S.; Corma, A. J. Gold Catalysts and Solid Catalysts for Biomass Transformations: Valorization of Glycerol and Glycerol–Water Mixtures Through Formation of Cyclic Acetals. J. Catal. 2010, 271, 351–357; (m) Lao, D. B.; Owens, A. C. E.; Heinekey, D. M.; Goldberg, K. I. Partial Deoxygenation of Glycerol Catalyzed by Iridium Pincer Complexes. ACS Catal., 2013, 3, 2391-2396. (7) U.S. Department of Agriculture, Renewable Chemicals & Materials Opportunity Assessment, Final Report, 2014. (8) Tamburini, F.; Kelly, T.; Weerapana, E.; Byers, J. A. Paper to Plastics: An Interdisciplinary Summer Outreach Project in Sustainability. J. Chem. Educ. 2014, 91 (10), 1574–1579. 66 Chapter 7. Gd(III)DOTA Complexes for MRI Contrast Agents and Labeling of Proteins This chapter describes unpublished preliminary results that were obtained as a part of a collaborative project with groups of Susumu Takahashi and Peter Qin. 7.1. Introduction Magnetic resonance imaging (MRI) is a non-invasive imaging technique, widely used in medicine. High-quality images obtained by use of MRI deepens understanding of anatomy, physiology, and complex processes inside of the human body. 1–4 Three-dimensional results of MRI provide both morphological and functional information and are superior to other imaging techniques, especially in visualizing of soft tissue. 4 MRI became an irreplaceable handle in the detection and treatment of the broad spectrum of diseases, including cancer and other types of tumor. Physics of MRI are analogous to those of nuclear magnetic resonance (NMR) spectroscopy and are based on excitation and detection of the change in the direction of the rotational axis of nuclei with non-zero spin. 3,5 The proton ( 1 H) remains the main targeting isotope in MRI, 6 not only because of its high abundance in the human body but also because of its high gyromagnetic ratio (γ = 42.6 MHz/T). Presence of protons, however, does not always guarantee acquisition of an informative image. The concentration of protons as well as the relaxation properties of the proton- containing tissue are the key factors that impact the success of MRI results. One of the major challenges in the field of MRI is the differentiation of tissues with similar relaxation parameters. This is crucial, especially for the accurate diagnostic imaging of cancer in other soft tissues. In order to provide a solution to this problem, contrast agents have been developed. 1,5,7–9 Contrast agents are chemical compounds that enhance the image contrast between 67 the tissue of interest and surrounding tissues, therefore increasing the visibility of the target on MRI image. Relaxation consists of two simultaneous independent processes T1 and T2 relaxations. The T1 process is associated with the enthalpy of the spin system and T2 with the entropy. Most of the contrast agents are designed for T1 relaxation time constant shortening. 5 Structure of the contrast agent highly depends on the specific targeting tissue. However, most of the available contrast agents in the US are based on gadolinium(III). 10–12 Gadolinium(III) is a highly paramagnetic ion, and this property makes its chelates excellent contrast agents. Gadolinium complexes cannot be seen on MRI image directly. Role of the contrast agent is to promote the rapid relaxation of nuclear spins that are excited during the MRI experiment. Application of an appropriate pulse sequence results in the amplification of signals from aqueous regions that are in close proximity to the gadolinium complex. 13 Gadolinium itself is toxic, however, in the form of a complex its toxicity is reduced. Several of gadolinium-based contrast agents, like Magnevist and Dotarem, are FDA approved for medical diagnostics. Generally, the efficacy of the drug correlates with the relaxivity of the compound. It has been demonstrated that more relaxive drug is also more toxic; 10 therefore discovery of a less toxic yet relaxive product is highly desirable. Factors like decomplexation and short circulation half-live in the human body, further stimulate the development of new contrast agents. Besides application as MRI contrast agents, complexes of gadolinium are employed as spin labels for local dynamics studies and distance determination in proteins. 6,14–16 The site-specific labeling of proteins with Gd(III) complexes allows higher resolution, longer-range measurements, and absence of anisotropy, unlike nitroxide radicals or fluorescent labeling techniques. Double- Electron-Electron Resonance (DEER) measurements are used in the related studies and are based on the dipolar coupling between spatially separated unpaired electrons of the gadolinium. Spin 68 labels based on gadolinium provide the ability to investigate biomolecules with previously not available precision, therefore help to solve problems of biochemistry and biology. 7.2. Design and Synthesis of Gd(III) Complexes Selection of an appropriate ligand scaffold for the gadolinium complex is an important step that would define future properties of the synthesized product. In our case, factors like binding affinity in the complex, as well as, price, time, and complexity of the synthesis played a key role in the design of the ligands. Presented in this chapter gadolinium complexes 7.1, 7.2, and 7.3 (Figure 7.1) have 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid, also known as DOTA, as a core of their ligand design. DOTA is a twelve-membered ring containing four nitrogen atoms and is a good “cage” chelating ligand for the lanthanides like gadolinium 14 . Due to the great stability, Gd-DOTA complex itself is commercially available as Dotarem, and as mentioned above, employed as MRI contrast agent. Figure 7.1. Structure of gadolinium(III) complexes 7.1, 7.2, and 7.3. It is not known for the DOTA or any DOTA-like ligands to perturb the useful properties of the gadolinium. 6 Thus, the installation of various functionalities into the complex via ligand synthesis is possible. One of our ultimate goals is to apply new complexes for site-specific labeling NH N N N N O O O O O O O Gd NH N N N N O O O O O O O Gd NH N N N N O O O O O O O Gd HO 7.1 7.2 7.3 HO 69 of proteins. In order to achieve it the size, the spacial properties, and the reactivity of a pendant functionality have to be taken into consideration. Complexes 7.1, 7.2, and especially 7.3 have relatively short pendant arms. This is beneficial, since the shorter the arm, the higher the precision of the DEER measurement. Doubly labeled representation of protein for DEER measurement is depicted in Figure 7.2B. Complexes 7.1 and 7.2 are isomers with a relatively small difference in distance from the reactive group to the gadolinium center. Despite this fact, 7.1 and 7.2 will have a significantly different rotational profile. Both complexes have the same rigid part that includes Gd-DOTA and an aromatic ring. As a result, the rotation would be possible only around O-C bond to the spacing CH2, and that will shape the rotational behavior of the complex. The absence of multiple spacers, as well as the rigidity of the pending arm, are among important factors that will impact the accuracy of the space- related measurements using DEER. Figure 7.2. A. Proposed site-specific labeling of proteins with Gd(III) complexes 7.3 via “Click” reaction. B. Schematic representation of a labeled with two gadolinium chelates protein. The terminal alkyne of the complex 7.3 introduces the possibility to perform “click” reaction for the labeling of previously azide-functionalized proteins (Figure 7.2A). “Click” chemistry is a class of reactions commonly used in bioconjugation; therefore labeling of proteins N 3 NH N N N N O O O O O O O Gd “Click” reaction + N NH N N N N O O O O O O O Gd N N A B DEER “Gd” “Gd” 70 with the complex 7.3 would be easy for the biochemical community due to the familiarity with the procedure. 17 Primary alcohol functionality of the complexes 7.1 and 7.2 is not readily reactive in comparison to the terminal alkyne. This might be more beneficial if 7.1 and 7.2 are used as contrast agents for MRI. Polar and hydrogen bonding properties of the hydroxyl group, together with the aromaticity of the arm might increase the retention time in the human body. Primary alcohols, however, are capable of multiple conversions, thus, can be used as precursors for protein tags as well. Synthesis of complexes 7.1, 7.2, and 7.3 follows the same steps. (Scheme 7.1). In a first step, commercially available tri-tert-butyl 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetate (DOTA-tri-t-Bu-ester) 7.4 is coupled with an appropriate amine. This reaction is facilitated by (1- [Bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxid hexafluorophosphate coupling agent, also known as HATU. Newly-formed amide products 7.8, 7.9, and 7.10 then undergo deprotection under acidic conditions, resulting in a free acid compounds 7.11, 7.12, and 7.13 respectively. Deprotection reaction of the compound with multiple protection groups might result in a partial liberation of carboxylate, however, in the case of 7.8 and 7.9 it was avoided by use of 9M H2SO4. Terminal alkyl of the amide 7.10 appeared to be reactive at those conditions, therefore 1:1 mixture of DCM and trifluoroacetic acid was used for deprotection purposes. The last step is a ligation with the gadolinium, performed by reaction of 7.11, 7.12, or 7.13 with GdCl3 . 6H2O in water at pH = 6. Detailed experimental procedures can be found in Chapter 8. Experimental and Spectral Data. 71 Scheme 7.1. Synthesis of gadolinium(III) complexes 7.1, 7.2, and 7.3. 7.3. Conclusion This chapter describes preliminary data on the design and synthesis of new gadolinium complexes for the site-specific labeling of proteins as well as for the application as MRI contrast agent. Presence of a reactive pendant group in prepared complexes expands the scope of application of the new compounds even further, for example, to the surface functionalization. Moreover, our gadolinium complexes can be utilized as building blocks for the preparation of sophisticated molecular assemblies like gadolinium-containing dendrimers and polymers. We further envision that application of complexes described above would facilitate problem-solving processes in the fields of chemistry, biology, surface science as well as medicine. HO N N N N O O O O O O O HN N N N N O O O O O O O R HN N N N N O OH O OH O O HO R NH 2 OTBDMS 7.5 7.8 (R-NH 2 = 7.5), 7.4 NH 2 OTBDMS 7.6 H + R-NH 2 NH 2 7.7 GdCl 3 . 6H 2 O 7.9 (R-NH 2 = 7.6), 7.10 (R-NH 2 = 7.7). 7.11 (R-NH 2 = 7.5), 7.12 (R-NH 2 = 7.6), 7.13 (R-NH 2 = 7.7). 7.1 7.2 7.3 ; TBDMS = Si N N N N O N N PF 6 ; HATU = HATU, RT, CH 3 CN H 2 SO 4 or TFA 72 7.4. References (1) Boros, E.; Gale, E. M.; Caravan, P. MR Imaging Probes: Design and Applications. Dalton Transactions. NIH Public Access March 21, 2015, pp 4804–4818. (2) Sim, N.; Parker, D. Critical Design Issues in the Targeted Molecular Imaging of Cell Surface Receptors. Chemical Society Reviews. April 21, 2015, pp 2122–2134. (3) Jellinger, K. A. Magnetic Resonance Imaging, 3rd Edition. David D. Stark and William G. Bradley, Jr (Eds). Volumes I-III. Mosby, St. Louis, MO, USA, 1999. 1936 + =100 Pp. ISBN 0-8151-8518-9; 28607. Eur. J. Neurol. 2001, 8 (1), 96–97. (4) Hollingworth, W.; Todd, C. J.; Bell, M. I.; Arafat, Q.; Girling, S.; Karia, K. R.; Dixon, A. K. The Diagnostic and Therapeutic Impact of MRI: An Observational Multi-Centre Study. Clin. Radiol. 2000, 55 (11), 825–831. (5) Hashemi, R. H.; Bradley, W. G.; Lisanti, C. J. MRI : The Basics; Williams & Wilkins, 2010. (6) Fisher, M. J.; Williamson, D. J.; Burslem, G. M.; Plante, J. P.; Manfield, I. W.; Tiede, C.; Ault, J. R.; Stockley, P. G.; Plein, S.; Maqbool, A.; et al. Trivalent Gd-DOTA Reagents for Modification of Proteins. RSC Adv. 2015, 5 (116), 96194–96200. (7) Li, V.; Chang, A. Y.; Williams, T. J. A Noncovalent, Fluoroalkyl Coating Monomer for Phosphonate-Covered Nanoparticles. Tetrahedron 2013, 69 (36), 7741–7745. (8) Wu, X.; Dawsey, A. C.; Siriwardena-Mahanama, B. N.; Allen, M. J.; Williams, T. J. A (Fluoroalkyl)Guanidine Modulates the Relaxivity of a Phosphonate-Containing T1- Shortening Contrast Agent. J. Fluor. Chem. 2014, 168, 177–183. (9) Li, V.; Ghang, Y. J.; Hooley, R. J.; Williams, T. J. Non-Covalent Self Assembly Controls the Relaxivity of Magnetically Active Guests. Chem. Commun. 2014, 1375–1377. (10) Dawsey, A. C.; Hathaway, K. L.; Kim, S.; Williams, T. J. Introductory Chemistry: A Molar Relaxivity Experiment in the High School Classroom. J. Chem. Educ. 2013, 90 (7), 922– 925. (11) Raymond, K. N.; Pierre, V. C. Next Generation, High Relaxivity Gadolinium MRI Agents. In Bioconjugate Chemistry; 2005; Vol. 16, pp 3–8. (12) Caravan, P.; Ellison, J. J.; McMurry, T. J.; Lauffer, R. B. Gadolinium(III) Chelates as MRI Contrast Agents: Structure, Dynamics, and Applications. Chem. Rev. 1999, 99 (9), 2293– 2352. (13) Geraldes, C. F. G. C.; Laurent, S. Classification and Basic Properties of Contrast Agents for Magnetic Resonance Imaging. Contrast Media Mol. Imaging 2009, 4 (1), 1–23. 73 (14) De León-Rodríguez, L. M.; Kovacs, Z. The Synthesis and Chelation Chemistry of DOTA - Peptide Conjugates. Bioconjugate Chemistry. American Chemical Society February 2008, pp 391–402. (15) Yagi, H.; Banerjee, D.; Graham, B.; Huber, T.; Goldfarb, D.; Otting, G. Gadolinium Tagging for High-Precision Measurements of 6 Nm Distances in Protein Assemblies by EPR. J. Am. Chem. Soc. 2011, 133 (27), 10418–10421. (16) Dalaloyan, A.; Qi, M.; Ruthstein, S.; Vega, S.; Godt, A.; Feintuch, A.; Goldfarb, D. Gd(III)- Gd(III) EPR Distance Measurements-the Range of Accessible Distances and the Impact of Zero Field Splitting. Phys. Chem. Chem. Phys. 2015, 17 (28), 18464–18476. (17) Anseth, K. S.; Klok, H. A. Click Chemistry in Biomaterials, Nanomedicine, and Drug Delivery. Biomacromolecules. American Chemical Society January 11, 2016, pp 1–3. 74 Chapter 8. Experimental and Spectral Data 8.1. General Procedures 8.1.1. Reagents All air and moisture sensitive procedures were carried out in a Vacuum Atmospheres glove box under nitrogen or using standard Schlenk techniques. NMR solvents were purchased from Cambridge Isotopes Laboratories. Dichloromethane-d2 was dried by stirring over CaH2 for 1 day followed by vapor transfer into a dry flask; chloroform-d3 was used as received. Hexanes, ethyl ether, dichloromethane and tetrahydrofuran solvents were purchased from VWR and dried in a J. C. Meyer solvent purification system with alumina/copper(II) oxide columns. Methanol, ethanol, isopropanol, 2,2,2-trifluoethanol and hexafluoroisopropanol were dried by stirring over CaH2 (5% w/v) overnight, followed by vapor transfer into a dry flask. 2,2,2-Trifluoethanol and hexafluoroisopropanol were stirred over Na2CO3 (10% w/v) over 1 hour then separated by a vapor transfer step. Chloro(1,5-cyclooctadiene)iridium(I) dimer (Strem), pentamethylcyclopentadienyl iridium(III) dichloride dimer (Strem), sodium trifluoromethanesulfonate (Sigma-Aldrich), sodium hydride (Sigma-Aldrich) were purged with nitrogen and stored under nitrogen atmosphere. Starting materials as well as reagents were purchased from the following list of vendors: Sigma- Aldrich, Strem Chemicals, TCI, VWR, Oakwood Chemicals, Chem Impex, Alpha Aesar, Combi Blocks, Acros and Ark Pharm. Known compounds were synthesized using literature procedures directly or with slight modification; new compounds syntheses are described in sections below. 8.1.2. Instrumentations NMR spectra were recorded on a Varian 400MR, VNMRS-500, or VNMRS-600 spectrometer and processed using MestreNova. 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 75 singlet, (d) doublet, (t) triplet, (dd) double doublet, etc. 13 C spectra are delimited by carbon peaks, not carbon count. Air-sensitive NMR spectra were taken in J-Young tubes (Wilmad or Norell) with Teflon valve plugs. Mass spectra were obtained on Bruker Autoflex Speed MALDI MS spectrometer using the evaporated drop method on a coated plate or Agilent Q-Tof tandem mass spectrometer. The matrices used for MALDI are 2,5-dihydroxybenzoic acid or anthracene. VWR B1500A-MT Ultrasonic Cleaner was used as a sonicator. 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. CHNS elemental analyses of compounds were collected at Robertson Microlit Laboratories. IR spectra were obtained using Jasco FT/IR-4600 FT-IR Spectrometer. Spectral data were obtained on Perkin-Elmer UV-Vis-NIR and Horiba Fluorimeter. The Concentration of the complexes solutions for absorption and emission studies was 1.4 . 10 -4 M and concentration of quinoline was 2.5 . 10 -5 M. Q-Tof samples were treated with activated carbon (10% w/v) and stirred for 10 minutes, then filtrated through a Teflon syringe filter 8.1.3. Experimental Procedures Procedure 1 (J-Young tube experiments for measuring NMR kinetics) In a typical run, in a glovebox a stock solution of Complex 2.1 in DCM (0.3 mL, 16.7 mM) was transferred to a J-Young tube via syringe. Next, the DCM was evaporated under reduced pressure. KOtBu (3 mg, 0.027 mmol) was added to the tube, followed by the addition of acetophenone (58 μL, 0.5 mmol) and mesitylene internal standard (7 μL, 0.05 mmol) via micropipette. Finally, 0.5 mL respective isotopolog of isopropanol was added via syringe. The tube was sealed, shook well and left for 20 minutes at room temperature before running an NMR experiment. The temperature is mentioned in the experimental description of each individual 76 experiment. The rate constant of each kinetic run is calculated based on the consumption of the ketone substrate. The NMR instrument was pre-lock-and-shimmed before every kinetic study. 77 8.2. Chapter 2 Experimental and Spectral Data 8.2.1. Synthesis Procedures and Characterization Data 4-Methyl-N-(pyridin-2-ylmethyl)benzenesulfonamide 2.5 4-methyl-N-(pyridin-2-ylmethyl)benzenesulfonamide was synthesized following procedure by Prim et al., 1 and isolated in a good yield of 87%. Obtained product matches reported NMR spectra of the given compound. 1 H NMR (400 MHz, Chloroform-d) δ 8.61 (d, J = 5.7 Hz, 1H), 8.31 (t, J = 7.8 Hz, 1H), 7.97 (d, J = 7.8 Hz, 1H), 7.75 (dd, J = 8.4, 1.9 Hz, 3H), 7.36 (t, J = 8.7 Hz, 1H), 7.27 (d, J = 4.6 Hz, 2H), 4.65 (d, J = 6.5 Hz, 2H), 2.39 (s, 3H). 13 C NMR (101 MHz, Chloroform-d) δ 153.56, 145.03, 141.34, 129.83, 127.06, 126.59, 125.18, 43.86, 21.51. Complex 2.1 In the glovebox under nitrogen, in a 8 dram vial with magnetic stir bar, pentamethylcyclopentadienyl iridium (III) dichloride dimer (50.0 mg, 0.063 mmol, 1 equiv.), 4- methyl-N-(pyridin-2-ylmethyl)benzenesulfonamide (33 mg, 0.123 mmol, 2 equiv.) and triethylamine (26 μL, 0.188 mmol, 3 equiv.) were dissolved in 4 mL of DCM and left stirring for 3 hours. After this, DCM was evaporated and the brown solid residue was redissolved in 6 mL of N TsHN 2. [IrCp*Cl 2 ] 2 1. Et 3 N DCM, 3h, 93% 2.1 2.5 N N Ts Ir Cl N TsHN 2. [IrCp*Cl 2 ] 2 1. Et 3 N DCM, 3h, 93% 2.1 2.5 N N Ts Ir Cl 78 THF. After stirring for 30 minutes, the solution was filtered through a Teflon syringe filter to remove the triethylamine hydrochloride byproduct. The solvent was evaporated under reduced pressure and resulting in a yellow-red glassy solid. This solid was dissolved in 0.4 mL of dry DCM, and dropwise added over 20 mL of hexanes, leading to precipitation of Complex 2.1. A yellow crystalline solid was acquired and dried under vacuum (73 mg, 0.117 mmol, 93%). This sample was later determined to be spectroscopically pure under NMR. Layering of hexanes over dichloromethane solution of 1 produced crystals suitable for X-ray crystallography. 1 H NMR (600 MHz, Methylene Chloride-d2) δ 8.52 (dt, J = 5.8, 1.0 Hz, 1H), 7.84 – 7.75 (m, 2H), 7.70 (td, J = 7.7, 1.5 Hz, 1H), 7.27 (td, J = 6.4, 5.7, 1.4 Hz, 1H), 7.24 – 7.20 (m, 1H), 7.14 – 7.09 (m, 2H), 4.81 – 4.47 (m, 2H), 2.31 (s, 3H), 1.70 (s, 15H). 13 C NMR (101 MHz, Methylene Chloride-d2) δ 164.23, 151.13, 140.61, 140.47, 137.86, 128.53, 127.95, 124.51, 120.23, 86.38, 57.66, 31.55, 22.61, 20.96, 13.83, 9.21. FTIR ν 3491.01,3036.37, 2958.27, 2916.32, 2862.81, 2818.94, 1607.86, 1568.81, 1474.31, 1446.83, 1401.51, 1380.3, 1355.23, 1274.72, 1224.58, 1134.42, 1104.05, 1083.8, 1055.84, 1030.77, 1000.87, 961.341, 931.932, 815.742, 768.494, 723.175, 708.712, 660.982, 619.52, 590.593, 556.363, 536.114, 506.223, 485.492, 481.635, 476.813, 468.135, 452.225 MS (MALDI) calculated for [C23H28IrN2O2S] + 589.2, found 589.4. 79 Figure 8.2.1. 1 H NMR spectrum of complex 2.1 at 25 °C in CD2Cl2. Figure 8.2.2. 13 C NMR spectrum of complex 2.1 at 25 °C in CD2Cl2. 0 . 5 1 . 0 1 . 5 2 . 0 2 . 5 3 . 0 3 . 5 4 . 0 4 . 5 5 . 0 5 . 5 6 . 0 6 . 5 7 . 0 7 . 5 8 . 0 8 . 5 9 . 0 9 . 5 f 1 ( p p m ) 1 5 . 1 0 3 . 0 8 2 . 2 0 2 . 0 1 1 . 0 1 1 . 0 3 1 . 0 2 1 . 9 0 1 . 0 0 - 1 0 0 1 0 2 0 3 0 4 0 5 0 6 0 7 0 8 0 9 0 1 0 0 1 1 0 1 2 0 1 3 0 1 4 0 1 5 0 1 6 0 1 7 0 1 8 0 1 9 0 2 0 0 2 1 0 2 2 0 2 3 0 f 1 ( p p m ) 80 Figure 8.2.3. IR spectrum of complex 2.1. Figure 8.2.4. X-Ray structure of complex 2.1. 81 Complex 2.2 In the glovebox under nitrogen, 2.1 (5 mg, 0.008 mmol, 1 equiv.) and potassium tert- butoxide (5 mg, 0.045 mmol, 5.6 equiv.) were dissolved in 0.5 mL CD2Cl2 in a J-Young tube. The tube was sealed and sonicated for 1 hour outside of the glovebox. The sonicator was shielded with thin alumina foil to prevent exposure to light. During this time, the reaction turned from yellow to deep purple. The J-Young tube was placed back into the glovebox and its content was transferred into the syringe. The solution was filtered through a Teflon syringe filter into a clean J-Young tube, affording separation of an unreacted amount of KOtBu and formed KCl. The J-Young tube was carried to the NMR room covered in alumina foil and NMR spectra were collected. Provided characterization data below is based on the obtained spectra of the mixture of 2.2 and tert-butanol and not on an isolated 2.2 sample. Any approach to isolate free Complex 2.2 led to decomposition. Compound 2.2 is well soluble in most common aprotic solvents including n-pentane, hexanes, n- heptane, toluene, benzene, diethyl ether, DCM etc. even at reduced temperatures. Complex 2.2 appeared to be moisture-, air- and light sensitive. 1 H NMR (600 MHz, Methylene Chloride-d2) δ 8.27 – 8.23 (m, 1H), 8.11 (s, 1H), 7.47 – 7.40 (m, 2H), 7.38 (dt, J = 8.9, 1.4 Hz, 1H), 7.20 (d, J = 8.0 Hz, 2H), 6.41 (ddd, J = 9.0, 6.2, 1.2 Hz, 1H), 5.80 (ddd, J = 7.4, 6.2, 1.6 Hz, 1H), 2.38 (s, 3H), 1.78 (s, 15H). 2.1 N N Ts Ir N N Ts Ir Cl DCM, 1h KOtBu 2.2 82 13 C NMR (101 MHz, Methylene Chloride-d2) δ 149.02, 143.06, 129.44, 126.02, 124.18, 122.18, 121.84, 108.46, 86.52, 35.04, 32.01, 28.96, 23.07, 21.57, 14.29, 9.80, 9.24. Figure 8.2.5. 1 H NMR spectrum of complex 2.2 at 25 °C in CD2Cl2. 0 .5 1 . 0 1 . 5 2 . 0 2 . 5 3 . 0 3 . 5 4 . 0 4 . 5 5 . 0 5 . 5 6 . 0 6 . 5 7 . 0 7 . 5 8 . 0 8 . 5 9 . 0 9 . 5 1 0 . 0 f 1 ( p p m ) 1 5 . 3 1 3 . 1 8 1 . 0 0 0 . 9 9 2 . 1 2 1 . 1 1 1 . 9 1 0 . 7 9 1 . 0 8 83 Figure 8.2.6. COSY NMR spectrum of complex 2.2 at 25 °C in CD2Cl2. Figure 8.2.7. 13 C NMR spectrum of complex 2.2 at 25 °C in CD2Cl2. - 0 . 5 0 . 0 0 . 5 1 . 0 1 . 5 2 . 0 2 . 5 3 . 0 3 . 5 4 . 0 4 . 5 5 . 0 5 . 5 6 . 0 6 . 5 7 . 0 7 . 5 8 . 0 8 . 5 9 . 0 f 2 ( p p m ) 0 1 2 3 4 5 6 7 8 9 f 1 ( p p m ) - 1 0 0 1 0 2 0 3 0 4 0 5 0 6 0 7 0 8 0 9 0 1 0 0 1 1 0 1 2 0 1 3 0 1 4 0 1 5 0 1 6 0 1 7 0 1 8 0 1 9 0 2 0 0 2 1 0 2 2 0 2 3 0 f 1 ( p p m ) 84 Complex 2.2’ In the glovebox under nitrogen, in an 8 dram vial with a magnetic stir bar, Complex 2.1 (20.0 mg, 0.032 mmol, 1 equiv.) and potassium tert-butoxide (20 mg, 0.179 mmol, 5.6 equiv.) were dissolved in 6 mL of DCM and sealed with the cap. A layer of black electrical tape was applied to the joint to ensure a good seal. The vial was left stirring for 30 minutes and appearance of the reaction mixture changed from yellow to deep purple. After that, the vial was taken outside and left stirring for another hour under direct sunlight. The reaction mixture went from deep purple to deep red and then to a more transparent red solution. The vial was placed back into the glovebox and an aliquot of the reaction mixture was used to run an NMR experiment in CD2Cl2 to check the conversion of 2.1 and 2.2. After this, in the glovebox, the solution was filtered through a Teflon syringe filter to remove unreacted KOtBu and formed KCl. The solvent was evaporated under reduced pressure which yielded a red glassy solid. This solid was dissolved in 0.3 mL of dry DCM and drop by drop crashed over 10 mL of hexanes, leading to precipitation of Complex 2.2’. A pale pink crystalline solid was acquired and dried under vacuum (15 mg, 0.026 mmol, 80%). This sample was later determined to be spectroscopically pure under NMR. Layering of n-pentane over dichloromethane solution of 2.2’ produced crystals suitable for X-ray crystallography. (Complex 2.2’ can also be prepared in a good yield by the stepwise formation of 2.2, filtration of an excess of KOtBu and then exposure to sunlight.) 2.1 N N Ts Ir N N Ts Ir Cl DCM, 1h KOtBu 2.2 DCM, 1h hv 2.2’ N N Ir S O O 85 1 H NMR (600 MHz, Methylene Chloride-d2) δ 8.27 – 8.23 (m, 1H), 8.11 (s, 1H), 7.47 – 7.40 (m, 2H), 7.38 (dt, J = 8.9, 1.4 Hz, 1H), 7.20 (d, J = 8.0 Hz, 2H), 6.41 (ddd, J = 9.0, 6.2, 1.2 Hz, 1H), 5.80 (ddd, J = 7.4, 6.2, 1.6 Hz, 1H), 2.38 (s, 3H), 1.78 (s, 15H). 13 C NMR (101 MHz, Methylene Chloride-d2) δ 166.92, 149.87, 146.58, 145.59, 139.72, 136.87, 136.00, 124.05 (d, J = 5.7 Hz), 122.02, 119.64, 88.43, 60.57, 53.92, 53.65, 53.38, 53.11, 52.84, 21.03, 8.63. FTIR ν 3033.48, 2950.07, 2914.88, 2865.22, 2362.85, 2336.82, 1604, 1574.11, 1470.46, 1439.12, 1403.44, 1378.37, 1341.73, 1259.29, 1215.42, 1148.4, 1124.78, 1086.69, 1032.21, 996.535, 958.93, 926.628, 895.291, 849.49, 833.098, 802.242, 764.155, 728.961, 683.642, 664.839, 617.109, 601.2, 583.843, 559.738, 541.417, 510.08, 483.081, 464.278, 456.082. MS (MALDI) calculated for [C23H27IrN2O2S] 588.1, found 587.3. Figure 8.2.8. 1 H NMR spectrum of complex 2.2’ at 25 °C in CD2Cl2. 0 . 5 1 . 0 1 .5 2 . 0 2 . 5 3 . 0 3 . 5 4 . 0 4 . 5 5 . 0 5 . 5 6 . 0 6 . 5 7 . 0 7 . 5 8 . 0 8 . 5 9 . 0 9 . 5 f 1 ( p p m ) 1 5 . 0 6 3 . 0 3 1 . 0 2 1 . 0 5 0 . 9 3 1 . 9 2 1 . 0 3 1 . 0 0 1 . 0 5 1 . 0 0 86 Figure 8.2.9. COSY NMR spectrum of complex 2.2’ at 25 °C in CD2Cl2. Figure 8.2.10. 13 C NMR spectrum of complex 2.2’ at 25 °C in CD2Cl2. 1 . 0 1 . 5 2 . 0 2 . 5 3 . 0 3 . 5 4 . 0 4 . 5 5 . 0 5 . 5 6 . 0 6 . 5 7 . 0 7 . 5 8 . 0 8 . 5 f 2 ( p p m ) 1 2 3 4 5 6 7 8 9 f 1 ( p p m ) - 1 0 0 1 0 2 0 3 0 4 0 5 0 6 0 7 0 8 0 9 0 1 0 0 1 1 0 1 2 0 1 3 0 1 4 0 1 5 0 1 6 0 1 7 0 1 8 0 1 9 0 2 0 0 2 1 0 2 2 0 2 3 0 f 1 ( p p m ) 87 Figure 8.2.11. IR spectrum of complex 2.2’. Figure 8.2.12. X-Ray structure of complex 2.2’. 88 Complex 2.4 In the glovebox under nitrogen, in an 8 dram vial with magnetic stir bar, Complex 2.1 (10.0 mg, 0.016 mmol, 1 equiv.) and potassium tert-butoxide (10 mg, 0.089 mmol, 5.6 equiv.) were dissolved in 2 mL of DCM and sealed with the cap. The vial was left stirring for 30 minutes and appearance of the reaction mixture changed from yellow to deep purple (formation of 2.2). After that, the solution was filtered through a Teflon syringe filter to remove unreacted KOtBu and formed KCl. Formic acid (4 μL, 0.106 mmol, 6 equiv.) was added to the filtrate resulting in a rapid color change of the mixture from deep purple to red. The solvent was evaporated under reduced pressure and yielded in a yellow-red glassy solid. This solid was dissolved in 0.3 mL of dry DCM followed by addition of 5 mL of hexanes. Solvent evaporation under reduced pressure led to the formation of Complex 2.4. A pale yellow crystalline solid was acquired and dried under vacuum (9 mg, 0.015 mmol, 95%). This sample was later determined to be spectroscopically pure under NMR. 1 H NMR (600 MHz, Methylene Chloride-d2) δ 8.35 (d, J = 5.9 Hz, 1H), 7.54 (dd, J = 12.1, 7.8 Hz, 3H), 7.20 (d, J = 7.8 Hz, 1H), 6.99 (d, J = 7.9 Hz, 2H), 6.91 (t, J = 6.7 Hz, 1H), 4.76 (d, J = 17.2 Hz, 1H), 4.43 (d, J = 17.2 Hz, 1H), 2.26 (s, 3H), 1.81 (d, J = 1.2 Hz, 15H), -10.40 (s, 1H). 13 C NMR (101 MHz, Methylene Chloride-d2) δ 152.24, 136.03, 128.02, 127.40, 122.98, 119.33, 87.28, 61.16, 20.89, 9.74. N N Ts Ir 2.2 2.4 N N Ts Ir H DCM, 30 mins 95% HCOOH 89 FTIR ν 2955.86, 2910.06, 2866.18, 2050.44, 1599.66, 1444.42, 1378.85, 1275.68, 1134.42, 1087.66, 1034.14, 1000.39, 956.037, 922.771, 862.507, 809,956, 764.637, 729.925, 706.301, 662.911, 617.592, 605.057, 547.685. MS (MALDI) calculated for [C23H29IrN2O2S] 590.2 found 589.3. Figure 8.2.13. 1 H NMR spectrum of complex 2.4 at 25 °C in CD2Cl2. - 1 1 - 1 0 - 9 - 8 - 7 - 6 - 5 - 4 - 3 - 2 - 1 0 1 2 3 4 5 6 7 8 9 f 1 ( p p m ) 1 . 0 3 1 5 . 1 8 3 . 0 2 1 . 0 4 1 . 0 6 1 . 0 2 1 . 9 8 1 . 0 5 3 . 0 0 1 . 0 0 90 Figure 8.2.14. 13 C NMR spectrum of complex 2.4 at 25 °C in CD2Cl2. Figure 8.2.15. IR spectrum of complex 2.4. - 1 0 0 1 0 2 0 3 0 4 0 5 0 6 0 7 0 8 0 9 0 1 0 0 1 1 0 1 2 0 1 3 0 1 4 0 1 5 0 1 6 0 1 7 0 1 8 0 1 9 0 2 0 0 2 1 0 2 2 0 2 3 0 f 1 ( p p m ) 91 Isotopologs of 2-propanol for Kinetic Isotope Effect studies (CD3)2CHOH Following a modified procedure by Kavana et al., 2 acetone-d6 (10 mL, 136 mmol) and 1- Hydroxytetraphenylcyclopentadienyl-(tetraphenyl-2,4-cyclopentadien-1-one)-μ-hydrotetracarbo- nyldiruthenium(II) (Shvo catalyst) (20 mg, 0.0184 mmol) were transferred to 125mL stainless steel Parr aparatus with previously-placed magnetic stirr bar. Parr aparatus was pressurized with 35 atm. of H2 gas and left for 6 hours at 110 °C. After that, apparatus was allowed to reach room temperature and recharged with H2to a pressure of 35 atm. and left for 12 hours at 110 °C. After the reaction completion the resultant (CD3)2CHOH was dried over CaH2 and then vapor transferred into a dry flask. 1 H NMR (400 MHz, Chloroform-d) δ 3.92 (s, 1H), 2.28 (s, 1H). (CD3)2CHOD The glassware used in this procedure went through the three cycles of flame drying and rinsing with D2O to remove protons from the glass surface. NaCl (1.57 g) was dissolved in 4.7 ml of D2O, forming 25 wt% solution. The solution was divided into two equal portions via syringe. First portion was combined with 2 mL of (CD3)2CHOH and was shaken well for a few seconds (Ratio of D2O to IPA is 5:1). After that, two layers were formed with the top layer being IPA and the botom one being brine. IPA layer was collected and poured over second portion of the brine, so the salting out could be conducted againg. Solution was shaked and top layer was separated and placed into the dry 20 mL flask with the stir bar. CaH2 was added to the flask in a small portions to remove remaining D2O and the flask was constantly cooled in liquid nitrogen to avoid any overheating inside. CaH2 was added to the flask until the visible formation of the gas has stopped. After that, (CD3)2CHOD was distilled under vacuum, dried over CaH2 overnight and vapor 92 transferred to the flask at which it was stored (1.22 mL, 61%). The degree of deuteration of the hydroxyl group reached >95%. 1 H NMR (400 MHz, Chloroform-d) δ 3.91 (s, 1H). (CD3)2CDOD d8-Isopropanol was purchased from Sigma-Aldrich. Solvent was dried over CaH2 and then vapour transferred into a dry flask in which it was stored before use. (CD3)2CDOH The glassware used in this procedure was previously flame dried. The brine solution was prepared by mixing 1.57 g of NaCl in 4.7 mL of H2O and divided into two portions. Following the analogous procedure to the (CD3)2CHOD preparation described above lead to the collection of 1.18 mL, 59% of (CD3)2CDOH with the degree of protonation of the hydroxyl group reaching >98%. 1 H NMR (400 MHz, Chloroform-d) δ 1.98 (s, 1H). 8.2.2. Mechanistic Studies Catalyst Initiation In a glovebox, 0.3 mL of the 16.7 mM stock solution of the Complex 2.1 in DCM was transferred into the J-Young tube followed by DCM vaporization under reduced pressure. KOtBu (3 mg, 0.027 mmol) was added to the tube, followed by the addition of 0.5 mL of (CD3)2CHOH. The J-Young tube was sealed and covered in aluminum foil. The tube is then shaken well and left at room temperature for 5 minutes. 1 H NMR is taken after that. 1 H NMR shows the formation of a mixture of 2.2 and 2.4. 93 Figure 8.2.16. Complex 2.1 initiation in the presence of KOtBu at 25 °C in (CD3)2CHOH. Figure 8.2.17. Complex 2.1 initiation in the presence of KOtBu at 25 °C in (CD3)2CHOH with assigned complex 2.2 (purple) and hydride complex 2.4 (red). - 1 4 - 1 3 - 1 2 - 1 1 - 1 0 - 9 - 8 - 7 - 6 - 5 - 4 - 3 - 2 - 1 0 1 2 3 4 5 6 7 8 f 1 ( p p m ) 94 Figure 8.2.18. Kinetic studies of acetophenone transfer hydrogenation by 2.1 at 83.1 °C; arrayed 1 H NMR spectra in (CD3)2CHOH. (Peak at 6.1 ppm is a center of the spectra, instrument artifact). Kinetic Isotope Effect The J-Young tubes used in the experiments with (CD3)2CHOD and (CD3)2CDOD went through the three cycles of rinsing with D2O (to remove protons from the glass surface) each time followed by the flame drying (to remove moisture). The J-Young tubes used in the experiments with (CD3)2CHOH and (CD3)2CDOH were flame dried to remove moisture. For all of the runs Complex 2.1 was transferred into the J-Young tubes from the same DCM stock solution. All of the samples were prepared following the Procedure 1. All of the NMR kinetic runs were conducted at 85 o C. The rate constant of the reaction in a fully protonated IPA (CH3)2CHOH was determined by monitoring the conversion of the acetophenone in 8 parallel samples. Eight samples were prepared in the glovebox in the same manner as described above for other isotopologs. An aliquot 95 from the first tube was analyzed by NMR in CDCl3 right after the samples were prepared. Seven of remaining tubes were placed in an oil bath outside of the glovebox with the temperature set to 85 o C. Each tube was removed from the bath at different times. An aliquot from the tube was analyzed by NMR with CDCl3 as a solvent. A total of eight datapoints were collected. Figure 8.2.19. Kinetic Studies of acetophenone transfer hydrogenation by 2.1 in fully protonated (CH3)2CHOH, conc. vs. time. Determined by 1 H NMR of the aliquots in CDCl3. Exponential coefficient represents kobs. 96 Figure 8.2.20. Kinetic Studies of acetophenone transfer hydrogenation by 2.1, conc. vs. time, monitored by 1 H NMR in (CD3)2CHOH (top left), (CD3)2CDOH (top right), (CD3)2CHOD (bottom left), (CD3)2CDOD (buttom right). Exponential coefficients represent kobs. 97 Table 8.2.1. Kinetic isotope effect data. Compound k, s -1 KIE observed kCHOH 1.38(2) × 10 -4 kCHOH/kCHOD 1.13(2) kCDOH 7.63(1) × 10 -5 kCDOH/kCDOD 1.19(2) kCHOD 1.22(1) × 10 -4 kCHOH/kCDOH 1.80(4) kCDOD 6.40(9) × 10 -5 kCHOD/kCDOD 1.91(4) kCHOH/kCDOD 2.15(3) Comparison of measured rate constants for parallel runs at 85 °C gave kinetic isotope effects of kCHOH/kCHOD = 1.13(2), kCDOH/kCDOD = 1.19(2), kCHOH/kCDOH = 1.80(4), kCHOD/kCDOD = 1.91(4), kCHOH/kCDOD = 2.15(3). Secondary kinetic isotope effect was determined by comparison of measured rate constants of (CH3)2CHOH and (CD3)2CHOH, k(CH3)2CHOH /k(CD3)2CHOH = 1.69(18) / 1.38(2) = 1.23(13). Kinetic Isotope Effect data conclude that both the C–H and O–H groups of 2-propylanol are involved in, or before, the rate-determining transition state. The combined isotope effect (kCHOH/kCDOD = 2.15(3)) is comparable to the product of the average separate O–H and C–H isotope effects 2.16(6). This is consistent with a mechanism in which the transformation of both hydride and proton bonds occurs in a single kinetically relevant step. 98 Eyring Plot In a typical run, the sample was prepared following the Procedure 1. Complex 2.1 was distributed from the same DCM stock solution. (CD3)2CHOH was used for all of the experiments. The temperature was calibrated using propyl glycol VT calibration standart. Four experiments at 88.2 o C, 83.1 o C, 62.6 o C and 53.2 o C were conducted. The NMR instrument was pre-lock-and- shimmed before every kinetic study. The rate constant of each kinetic run is calculated based on the consumption of the ketone substrate. Figure 8.2.21. Eyring plot: ΔH ‡ = 29.1(8) kcal mol -1 , ΔS ‡ = -17(19) eu. 99 Figure 8.2.22. Kinetic Studies of acetophenone transfer hydrogenation by 2.1, conc. vs. time, at different temperatures. 88.2 o C (top left), 83.1 o C (top right), 62.6 o C (bottom left), 53.2 o C (buttom right). Exponential coefficients represent kobs. Monitored by 1 H NMR in (CD3)2CHOH. 100 Table 8.2.2. Data for Eyring analysis. T, K 1000/T k, s -1 Error Rln(k/T)- Rln(kb/h) Error d(ΔH ‡ ), kcal/mol d(ΔS ‡ ), eu 361.4 2.77 1.06 × 10 -4 2.22 × 10 -6 -76.99 4.16 × 10 -2 0.75 10.41 356.2 2.81 6.76 × 10 -5 1.39 × 10 -6 -77.85 4.10 × 10 -2 0.76 10.28 335.7 2.98 1.40 × 10 -5 6.61 × 10 -7 -79.77 3.67× 10 -1 0.81 23.16 326.0 3.07 6.96 × 10 -6 4.57 × 10 -7 -82.20 1.12 × 10 -1 0.84 32.06 <d(ΔH‡)> <d(ΔS‡)> 0.79 18.98 101 Proton-Hydride Fidelity Proton-hydride fidelity can be observed during the experiments conducted for KIE studies. In cases of (CD3)2CHOH and (CD3)2CHOD, 1-phenyl ethanol is formed with selectively protonated C-H bond (C6H5)CH(OH)CH3. In cases of (CD3)2CDOD and (CD3)2CDOH, 1-phenyl ethanol is selectively formed with deuterium instead, producing (C6H5)CD(OH)CH3. O-H, as well as C-H bonds of CH3, undergo H/D exchange if the base is present. Figure 8.2.23. Kinetic Studies of acetophenone transfer hydrogenation by 2.1, arrayed 1 H NMR spectra; (CD3)2CHOH (top left), (CD3)2CDOH (top right), (CD3)2CHOD (bottom left), (CD3)2CDOD (buttom right). 102 Homogeneity Tests Visual Appearance and Well-Behaved Kinetics The reaction mixture is a translucent pale red solution, with no precipitation of any kind occurring during the catalysis. The reaction follows well-behaved catalysis kinetics through the pseudo-first order (see KIE, Eyring plot studies). Mercury Drop Test The sample for mercury drop test was prepared in an analogous way as described in Procedure 1, however a drop of mercury was added to the solution before the NMR experiment. The rate of transfer hydrogenation was then measured to be 1.47(3) × 10 -4 mol s -1 at 88.2 °C, which is comparable to the measured rate of transfer hydrogenation in the absence of mercury (1.43(2) × 10 -4 mol s -1 ). Quantitative Poisoning Phenanthroline was selected as a catalytic poison. Phenanthroline (0.45 mg, 0.0025 mmol), one-half mole equivalent relative to the iridium catalyst, was transferred in 0.2 mL of DCM to the J-Young tube. DCM was then removed under reduced pressure and the tube was used to prepare the sample as described in Procedure 1. The rate of transfer hydrogenation was then measured to be 1.06(1) × 10 -4 mol s -1 at 88.2 °C, which is 72% to the measured rate of transfer hydrogenation in the absence of phenanthroline (1.47(3) × 10 -4 mol s -1 ). 103 Figure 8.2.24. Kinetic studies of acetophenone transfer hydrogenation by 2.1, arrayed 1 H NMR spectra in (CD3)2CHOH at 88.2 °C. Additives: none (top left), drop of mercury (top right), one- half molar equivalent of phenanthroline (buttom). 104 8.2.3. Computational Methods The model system consists of the Ir catalyst with Cp instead of Cp*, an isopropanol molecule as the substrate, and a water molecule as the proton shuttle. All simulations were carried out using Version 5.0.2 of Q-Chem, 3 an ab initio quantum chemistry software. The B3LYP 4,5 hybrid density functional along with Grimme’s D3 dispersion correction using the Becke-Johnson damping (D3-BJ) function, 6,7 were chosen as the level of theory. The Ir atom was represented using the Stuttgart small-core ‘srsc’ effective core potential, 8,9 and all remaining atoms were represented using the double-ζ 6-31G* basis set. The role of isopropanol solvent was incorporated using the implicit conductor-like polarizable continuum model (C-PCM) 10-12 with a dielectric constant of 18.23. Transition state guesses for pathways with and without the proton shuttle were generated using the double-ended freezing string method (FSM), 13-15 and refined using the partitioned- rational function optimization (P-RFO) method. The reactant and transition states were verified using vibrational analysis. Intrinsic reaction coordinate (IRC) 16-19 calculations confirmed that, upon perturbation, the transition state follows the reaction path to the initial unreacted isopropanol- catalyst system on one side and the concerted reaction product on the other. The reported enthalpies of activation are zero-point corrected and calculated at 350 K and 1 atm. 105 8.3. Chapter 3 Experimental and Spectral Data N-(2-Aminoethyl)-4-methylbenzenesulfonamide 3.15 N-(2-Aminoethyl)-4-methylbenzenesulfonamide was synthesized following procedure by Andna and Miesch, 20 and isolated in a good yield of 77%. Obtained product matches reported NMR spectra of the given compound. 1 H NMR (400 MHz, Chloroform-d) δ 7.75 (dd, J = 8.2, 1.2 Hz, 2H), 7.32 – 7.24 (m, 3H), 3.00 (td, J = 6.2, 5.6, 2.1 Hz, 2H), 2.93 – 2.85 (m, 2H), 2.40 (s, 3H). 13 C NMR (101 MHz, Chloroform-d) δ 143.31, 136.84, 129.69, 127.06, 40.76, 21.48. Synthesis procedure for 4-Methyl-N-(pyridin-2-ylmethyl)benzenesulfonamide 3.16, is described above in Chapter 8.2 N-((1R,2R)-2-Aminocyclohexyl)-4-methylbenzenesulfonamide 3.17 N-((1R,2R)-2-Aminocyclohexyl)-4-methylbenzenesulfonamide was synthesized following procedure by Walsh et al., 21 and isolated in a good yield of 93%. Obtained product matches reported NMR spectra of the given compound. 1 H NMR (400 MHz, Methylene Chloride-d2) δ 7.81 – 7.69 (m, 2H), 7.38 – 7.29 (m, 2H), 2.56 – 2.49 (m, 1H), 2.44 (h, J = 0.4 Hz, 3H), 2.31 (ddd, J = 11.0, 9.8, 4.1 Hz, 1H), 1.94 – 1.84 (m, 2H), 1.66 – 1.59 (m, 2H), 1.31 – 0.97 (m, 6H). 13 C NMR (101 MHz, Chloroform-d) δ 137.97, 129.64, 127.03, 60.17, 32.54, 24.92, 24.73, 21.51. 2. [IrCp*Cl 2 ] 2 1. Et 3 N H 2 N N Ts Ir Cl 3.1 DCM, 3h, 97% H 2 N TsHN 3.15 H 2 N TsHN 3.17 106 4-Methyl-N-(pyrimidin-2-ylmethyl)benzenesulfonamide 3.18 4-Methyl-N-(pyrimidin-2-ylmethyl)benzenesulfonamide was synthesized by following modified procedure for synthesis of 4-Methyl-N-(pyridin-2- ylmethyl)benzenesulfonamide by Prim et al., 1 and isolated in a good yield of 67%. 1 H NMR (400 MHz, Methylene Chloride-d2) δ 8.59 (d, J = 4.9 Hz, 1H), 7.75 – 7.65 (m, 2H), 7.27 – 7.22 (m, 2H), 7.15 (tt, J = 4.9, 0.7 Hz, 1H), 5.85 (s, 1H), 4.36 (dd, J = 5.2, 0.7 Hz, 2H), 2.36 (d, J = 0.7 Hz, 3H). N-(2-Aminopropyl)-4-methylbenzenesulfonamide 3.19 N-(2-Aminopropyl)-4-methylbenzenesulfonamide was synthesized following procedure by Andna and Miesch, 20 and isolated in a good yield of 77%. Obtained product matches reported NMR spectra of the given compound. 1 H NMR (400 MHz, Methylene Chloride-d2) δ 7.82 – 7.64 (m, 2H), 7.35 (d, J = 7.9 Hz, 2H), 3.04 (t, J = 6.1 Hz, 2H), 2.76 (s, 2H), 2.44 (s, 3H), 1.58 – 1.50 (m, 2H). 13 C NMR (101 MHz, Chloroform-d) δ 143.09, 137.09, 129.61, 127.02, 42.80, 21.48. N N TsHN 2. [IrCp*Cl 2 ] 2 1. Et 3 N DCM, 3h, 89% 3.4 3.18 N N N Ts Ir Cl H 2 N N Ts Ir Cl 3.5 3.19 2. [IrCp*Cl 2 ] 2 1. KOtBu THF, 16h, 99% TsHN H 2 N 107 Complex 3.1 In the glovebox under nitrogen, in a 8 dram vial with magnetic stir bar, pentamethylcyclopentadienyl iridium (III) dichloride dimer (50.0 mg, 0.063 mmol, 1 equiv.), N- (2-aminoethyl)-4 methylbenzenesulfonamide 3.15 (27 mg, 0.123 mmol, 2 equiv.) and triethylamine (26 μL, 0.188 mmol, 3 equiv.) were dissolved in 4 mL of DCM and left stirring for 3 hours. After this, DCM was evaporated, and the yellow-red solid residue was redissolved in 6 mL of THF. After stirring for 30 minutes, the solution was filtered through a Teflon syringe filter to remove the triethylamine hydrochloride byproduct. The solvent was evaporated under reduced pressure and resulting in a red glassy solid. This solid was dissolved in 0.3 mL of dry DCM and dropwise crashed over 25 mL of hexanes, leading to precipitation of Complex 3.1. A yellow crystalline solid was acquired and dried under vacuum (69 mg, 0.119 mmol, 97%). This sample was later determined to be spectroscopically pure under NMR. 1 H NMR (600 MHz, Methylene Chloride-d2) δ 7.74 – 7.66 (m, 2H), 7.20 – 7.09 (m, 2H), 3.72 – 3.68 (m, 2H), 2.64 (d, J = 3.0 Hz, 4H), 2.35 (s, 3H), 1.71 (s, 15H). 13 C NMR (101 MHz, Methylene Chloride-d2) δ 141.10, 140.23, 128.41, 127.77, 85.26, 50.60, 48.51, 45.88, 21.02, 9.09. FTIR ν 3496.79, 3230.18, 3145.33, 3034.92, 2956.34, 2915.36, 2858.47, 2667.55, 1594.84, 1490.22, 1451.17, 1380.3, 1327.75, 1263.15, 1198.06, 1157.56, 1127.19, 1095.37, 1079.94, 2. [IrCp*Cl 2 ] 2 1. Et 3 N H 2 N N Ts Ir Cl 3.1 DCM, 3h, 97% H 2 N TsHN 3.15 108 1033.18, 980.625, 912.165, 837.437, 814.295, 708.712, 656.161, 616.627, 592.039, 547.685, 509.115, 485.974, 469.1, 464.278 MS (MALDI) calculated for [C23H28IrN2O2S] + 576.12, 541.15 found 542.14. Figure 8.3.1. 1 H NMR spectrum of complex 3.1 at 25 °C in CD2Cl2. 0 . 5 1 . 0 1 . 5 2 . 0 2 . 5 3 . 0 3 . 5 4 . 0 4 . 5 5 . 0 5 . 5 6 . 0 6 . 5 7 . 0 7 . 5 8 . 0 8 . 5 9 . 0 9 . 5 1 0 . 0 1 0 . 5 f 1 ( p p m ) 1 5 . 1 2 3 . 1 0 4 . 0 0 2 . 1 9 2 . 0 0 2 . 0 2 109 Figure 8.3.2. 13 C NMR spectrum of complex 3.1 at 25 °C in CD2Cl2. Figure 8.3.3. IR spectrum of complex 3.1. - 1 0 0 1 0 2 0 3 0 4 0 5 0 6 0 7 0 8 0 9 0 1 0 0 1 1 0 1 2 0 1 3 0 1 4 0 1 5 0 1 6 0 1 7 0 1 8 0 1 9 0 2 0 0 2 1 0 2 2 0 2 3 0 f 1 ( p p m ) 110 Synthesis procedure for 3.2, is described above in Chapter 8.2 Complex 3.3 In the glovebox under nitrogen, in an 8 dram vial with a magnetic stir bar, N-((1R,2R)-2- Aminocyclohexyl)-4-methylbenzenesulfonamide 3.17 (33 mg, 0.123 mmol, 1 equiv.) and potassium tert-butoxide (14 mg, 0.123 mmol, 1 equiv.) were dissolved in 5 mL of THF and left stirring for 14 hours. After this, pentamethylcyclopentadienyl iridium (III) dichloride dimer (50.0 mg, 0.063 mmol, 0.5 equiv.) was added to the reaction mixture, followed by 1 mL of THF. After stirring for 2 hours, THF was evaporated, and the brown solid residue was redissolved in 3 mL of DCM. The solution was filtered through a Teflon syringe filter to remove the potassium chloride byproduct. The solvent was evaporated under reduced pressure resulting in a yellow-red glassy solid. This solid was dissolved in 0.4 mL of dry DCM and 5 mL of hexanes were added next. The resulting heterogeneous mixture was sonicated for 30 minutes and then solvents were evaporated. The remaining solid was then sonicated with 5 mL of hexanes for 1 hour. A yellow crystalline solid of 3.3 was acquired and dried under vacuum (77 mg, 0.123 mmol, 99%). This sample was later determined to be spectroscopically pure under NMR. 2. [IrCp*Cl 2 ] 2 1. KOtBu H 2 N N Ts Ir Cl 3.3 THF, 16h, 99% H 2 N TsHN 3.17 111 1 H NMR (400 MHz, Methylene Chloride-d2) δ 7.84 (s, 2H), 7.19 (d, J = 8.0 Hz, 2H), 3.76 (s, 1H), 3.54 (s, 1H), 2.57 (d, J = 11.4 Hz, 1H), 2.38 (s, 3H), 2.29 (s, 2H), 1.96 (d, J = 12.4 Hz, 1H), 1.68 (s, 15H), 1.37 (dd, J = 29.5, 10.5 Hz, 2H), 1.35 – 1.23 (m, 3H), 1.24 – 1.00 (m, 2H). 13 C NMR (101 MHz, Methylene Chloride-d2) δ 140.03, 128.39, 127.42, 85.16, 24.83, 20.98. FTIR ν 3506.44, 3264.41, 3217.65, 3143.88, 2924.04, 2857.99, 1590.02, 1489.26, 1446.83, 1380.3, 1313.29, 1259.77, 1185.53, 1120.92, 1086.21, 1041.37, 961.823, 944.949, 895.291, 838.883, 811.885, 710.64, 661.946, 573.719, 550.095, 515.865, 466.689 MS (MALDI) calculated for [C23H28IrN2O2S] + 595.20 found 595.03. Figure 8.3.4. 1 H NMR spectrum of complex 3.3 at 25 °C in CD2Cl2. 0 . 5 1 . 0 1 . 5 2 . 0 2 . 5 3 . 0 3 . 5 4 . 0 4 . 5 5 . 0 5 . 5 6 . 0 6 . 5 7 . 0 7 . 5 8 . 0 8 . 5 9 . 0 9 . 5 1 0 . 0 1 0 . 5 f 1 ( p p m ) 1 . 9 9 2 . 5 2 2 . 0 4 1 5 . 4 7 1 . 1 2 1 . 9 9 2 . 9 8 1 . 0 3 0 . 8 8 0 . 9 1 2 . 0 0 1 . 9 2 112 Figure 8.3.5. 13 C NMR spectrum of complex 3.3 at 25 °C in CD2Cl2. Figure 8.3.6. IR spectrum of complex 3.3. - 1 0 0 1 0 2 0 3 0 4 0 5 0 6 0 7 0 8 0 9 0 1 0 0 1 1 0 1 2 0 1 3 0 1 4 0 1 5 0 1 6 0 1 7 0 1 8 0 1 9 0 2 0 0 2 1 0 2 2 0 2 3 0 f 1 ( p p m ) 113 Complex 3.4 In the glovebox under nitrogen, in an 8 dram vial with a magnetic stir bar, pentamethylcyclopentadienyl iridium(III) dichloride dimer (50.0 mg, 0.063 mmol, 1 equiv.), 4- methyl-N-(pyrimidin-2-ylmethyl)benzenesulfonamide 3.18 (33 mg, 0.123 mmol, 2 equiv.) and triethylamine (26 μL, 0.188 mmol, 3 equiv.) were dissolved in 4 mL of DCM and left stirring for 3 hours. After this, DCM was evaporated and the brown solid residue was redissolved in 6 mL of THF. After stirring for 30 minutes, the solution was filtered through a Teflon syringe filter to remove the triethylamine hydrochloride byproduct. The solvent was evaporated under reduced pressure and resulting in a brown glassy solid. This solid was dissolved in 0.3 mL of dry DCM, and dropwise crashed over 20 mL of hexanes, leading to precipitation of Complex 3.4. A brown crystalline solid was acquired and dried under vacuum (68 mg, 0.110 mmol, 89%). This sample was later determined to be spectroscopically pure under NMR. 1 H NMR (400 MHz, Methylene Chloride-d2) δ 8.72 – 8.64 (m, 2H), 7.85 – 7.80 (m, 2H), 7.31 (tq, J = 5.0, 0.8 Hz, 1H), 7.13 (ddq, J = 7.9, 1.3, 0.6 Hz, 2H), 5.00 – 4.61 (m, 2H), 2.33 (s, 3H), 1.71 (d, J = 1.1 Hz, 15H). 13 C NMR (101 MHz, Methylene Chloride-d2) δ 174.00, 158.06 (d, J = 21.3 Hz), 140.67, 140.13, 128.60, 128.08, 86.80, 9.24. N N TsHN 2. [IrCp*Cl 2 ] 2 1. Et 3 N DCM, 3h, 89% 3.4 3.18 N N N Ts Ir Cl 114 FTIR ν 3729.66, 3705.55, 3625.52, 3596.11, 3563.32, 3498.72, 3048.91, 2963.57, 2917.29, 2861.36, 2360.93, 2338.75, 1649.8, 1586.65, 1560.13, 1544.7, 1491.67, 1454.55, 1419.83, 1382.23, 1343.18, 1275.68, 1183.6, 1135.87, 1109.83, 1085.73, 1031.73, 991.232, 937.717, 817.188, 732.335, 665.321, 619.52, 563.594, 540.935 MS (MALDI) calculated for [C22H27IrN3O2S] + , 590.15 found 590.00. Figure 8.3.7. 1 H NMR spectrum of complex 3.4 at 25 °C in CD2Cl2. 0 . 5 1 . 0 1 . 5 2 . 0 2 . 5 3 . 0 3 . 5 4 . 0 4 . 5 5 . 0 5 . 5 6 . 0 6 . 5 7 . 0 7 . 5 8 . 0 8 . 5 9 . 0 9 . 5 1 0 . 0 1 0 . 5 f 1 ( p p m ) 1 5 . 2 8 3 . 1 5 2 . 2 2 2 . 0 4 1 . 0 9 2 . 0 0 1 . 9 8 115 Figure 8.3.8. 13 C NMR spectrum of complex 3.4 at 25 °C in CD2Cl2. Figure 8.3.9. IR spectrum of complex 3.4. - 1 0 0 1 0 2 0 3 0 4 0 5 0 6 0 7 0 8 0 9 0 1 0 0 1 1 0 1 2 0 1 3 0 1 4 0 1 5 0 1 6 0 1 7 0 1 8 0 1 9 0 2 0 0 2 1 0 2 2 0 2 3 0 f 1 ( p p m ) 116 Complex 3.5 In the glovebox under nitrogen, in an 8 dram vial with a magnetic stir bar, N-(2- aminopropyl)-4-methylbenzenesulfonamide 3.19 (33 mg, 0.123 mmol, 1 equiv.) and potassium tert-butoxide (14 mg, 0.123 mmol, 1 equiv.) were dissolved in 5 mL of THF and left stirring for 14 hours. After this, pentamethylcyclopentadienyl iridium (III) dichloride dimer (50.0 mg, 0.063 mmol, 0.5 equiv.) was added to the reaction mixture, followed by 1 ml of THF. After stirring for 2 hours, THF was evaporated, and the brown solid residue was redissolved in 3 mL of DCM. The solution was filtered through a Teflon syringe filter to remove the potassium chloride byproduct. The solvent was evaporated under reduced pressure resulting in a yellow-red glassy solid. This solid was dissolved in 0.4 mL of dry DCM and 5 mL of hexanes were added next. The resulting heterogeneous mixture was sonicated for 30 minutes and then solvents were evaporated. The remaining solid was then sonicated with 5 mL of hexanes for 1 hour. A yellow crystalline solid of 3.5 was acquired and dried under vacuum (72 mg, 0.123 mmol, 99%). This sample was later determined to be spectroscopically pure under NMR. 1 H NMR (600 MHz, Methylene Chloride-d2) δ 7.85 – 7.82 (m, 2H), 7.14 (d, J = 8.0 Hz, 2H), 3.74 (s, 1H), 3.53 (s, 1H), 3.46 (d, J = 14.5 Hz, 1H), 3.16 (d, J = 12.0 Hz, 1H), 2.87 (t, J = 13.0 Hz, 1H), 2.52 (d, J = 12.9 Hz, 1H), 2.33 (s, 3H), 1.69 (s, 1H), 1.66 (s, 16H), 1.05 (d, J = 14.0 Hz, 1H). H 2 N N Ts Ir Cl 3.5 3.19 2. [IrCp*Cl 2 ] 2 1. KOtBu THF, 16h, 99% TsHN H 2 N 117 13 C NMR (101 MHz, Methylene Chloride-d2) δ 128.39, 127.41, 127.09, 85.16, 45.70, 24.82, 9.13, 8.80. FTIR ν 3544.52, 3478.95, 3263.93, 3224.88, 3142.44, 2927.41, 2859.43, 2658.39, 2486.76, 1581.83, 1489.74, 1446.35, 1400.55, 1380.78, 1319.55, 1259.77, 1183.6, 1159.01, 1122.85, 1086.21, 1035.59, 962.305, 944.467, 895.773, 838.883, 815.259, 710.158, 661.946, 617.109, 572.273, 550.095, 525.507, 520.204, 501.401, 494.652, 469.1, 460.421, 454.154 MS (MALDI) calculated for [C23H28IrN2O2S] + 555.17, found 554.97. Figure 8.3.10. 1 H NMR spectrum of complex 3.5 at 25 °C in CD2Cl2. 0 . 5 1 . 0 1 . 5 2 . 0 2 . 5 3 . 0 3 . 5 4 . 0 4 . 5 5 . 0 5 . 5 6 . 0 6 . 5 7 . 0 7 . 5 8 . 0 8 . 5 9 . 0 9 . 5 1 0 . 0 f 1 ( p p m ) 1 5 . 2 9 3 . 0 9 2 . 0 1 2 . 0 0 1 . 9 7 118 Figure 8.3.11. 1 H NMR spectrum of complex 3.5 at -20 °C in CD2Cl2. Figure 8.3.12. COSY spectrum of complex 3.5 at -20 °C in CD2Cl2. 0 . 5 1 . 0 1 . 5 2 . 0 2 . 5 3 . 0 3 . 5 4 . 0 4 . 5 5 . 0 5 . 5 6 . 0 6 . 5 7 . 0 7 . 5 8 . 0 8 . 5 9 . 0 9 . 5 1 0 . 0 1 0 . 5 f 1 ( p p m ) 1 . 2 1 1 5 . 6 9 0 . 9 8 3 . 0 9 0 . 9 5 0 . 9 9 1 . 0 0 1 . 1 3 0 . 9 6 0 . 9 0 2 . 1 1 2 . 0 6 1 . 0 1 . 5 2 . 0 2 . 5 3 . 0 3 . 5 4 . 0 4 . 5 5 . 0 5 . 5 6 . 0 6 . 5 7 . 0 7 . 5 8 . 0 8 . 5 f 2 ( p p m ) 0 1 2 3 4 5 6 7 8 f 1 ( p p m ) 119 Figure 8.3.13. 13 C NMR spectrum of complex 3.5 at 25 °C in CD2Cl2. Figure 8.3.14. IR spectrum of complex 3.5. 0 1 0 2 0 3 0 4 0 5 0 6 0 7 0 8 0 9 0 1 0 0 1 1 0 1 2 0 1 3 0 1 4 0 1 5 0 1 6 0 1 7 0 f 1 ( p p m ) 120 Complex 3.6 In the glovebox under nitrogen, in an 8 dram vial with a magnetic stir bar, Complex 3.1 (50 mg, 0.088 mmol, 1 equiv.) and silver triflate (27 mg, 0.104 mmol, 1.2 equiv.) were dissolved in 5 mL of THF and left stirring for 2 hours. The solution was filtered through a Teflon syringe filter to remove the silver chloride byproduct. After this, THF was evaporated, and the deep-red solid residue was redissolved in 0.4 mL of DCM and filtered through a Teflon syringe filter to remove the remaining 0.2 equiv. of silver triflate. The DCM solution was then dropwise crashed over 25 mL of hexanes, leading to precipitation of Complex 3.6. A red crystalline solid was acquired and dried under vacuum (58 mg, 0.85 mmol, 96%). This sample was later determined to be spectroscopically pure under NMR. Layering of n-pentane over THF solution of 3.6 produced crystals suitable for X-ray crystallography. 1 H NMR (600 MHz, Methylene Chloride-d2) δ 7.68 – 7.62 (m, 2H), 7.37 – 7.31 (m, 2H), 5.43 (s, 2H), 3.02 (t, J = 6.2 Hz, 2H), 2.66 (p, J = 6.1 Hz, 2H), 2.43 (s, 3H), 1.82 (s, 15H). 13 C NMR 13 C NMR (101 MHz, Methylene Chloride-d2) δ 141.00, 127.13, 125.53, 121.91, 92.49, 63.60, 21.24, 10.15. 19 F NMR (376 MHz, Methylene Chloride-d2) δ -78.41. FTIR ν 3473.17, 3230.18, 3110.14, 2983.82, 2956.82, 2922.59, 2878.72, 2359.96, 2338.75, 2056.71, 1599.66, 1495.04, 1455.03, 1387.53, 1340.28, 1282.43, 1241.45, 1224.09, 1139.24, 3.1 THF, 2h, 96% AgOTf H 2 N N Ts Ir Cl H 2 N N Ts Ir OTf 3.6 121 1087.66, 1024.02, 957.484, 917.468, 823.455, 757.405, 707.747, 670.142, 633.019, 597.825, 571.79, 549.131, 515.383, 500.437, 472.957 MS (MALDI) calculated for [C19H28IrN2O2S] + 541.15, found 542.14. Figure 8.3.15. 1 H NMR spectrum of complex 3.6 at 25 °C in CD2Cl2. - 2 - 1 0 1 2 3 4 5 6 7 8 9 1 0 1 1 1 2 1 3 1 4 f 1 ( p p m ) 1 5 . 2 8 3 . 0 8 2 . 0 9 2 . 0 9 2 . 0 1 2 . 0 2 2 . 0 0 122 Figure 8.3.16. 13 C NMR spectrum of complex 3.6 at 25 °C in CD2Cl2. Figure 8.3.17. 19 F NMR spectrum of complex 3.6 at 25 °C in CD2Cl2. - 1 0 0 1 0 2 0 3 0 4 0 5 0 6 0 7 0 8 0 9 0 1 0 0 1 1 0 1 2 0 1 3 0 1 4 0 1 5 0 1 6 0 1 7 0 1 8 0 1 9 0 2 0 0 2 1 0 2 2 0 2 3 0 f 1 ( p p m ) - 1 6 0 - 1 5 0 - 1 4 0 - 1 3 0 - 1 2 0 - 1 1 0 - 1 0 0 - 9 0 - 8 0 - 7 0 - 6 0 - 5 0 - 4 0 - 3 0 - 2 0 - 1 0 0 1 0 2 0 3 0 f 1 ( p p m ) 123 Figure 8.3.18. IR spectrum of complex 3.6. Figure 8.3.19. X-Ray structure of complex 3.6. 124 Complex 3.7 In the glovebox under nitrogen, in an 8 dram vial with a magnetic stir bar, Complex 3.2 (50 mg, 0.080 mmol, 1 equiv.) and silver triflate (25 mg, 0.096 mmol, 1.2 equiv.) were dissolved in 5 mL of THF and left stirring for 2 hours. The solution was filtered through a Teflon syringe filter to remove the silver chloride byproduct. After this, THF was evaporated, and the deep-red solid residue was redissolved in 0.4 mL of DCM and filtered through a Teflon syringe filter to remove the remaining 0.2 equiv. of silver triflate. The DCM solution was then dropwise crashed over 25 mL of hexanes, leading to precipitation of Complex 3.7. A red crystalline solid was acquired and dried under vacuum (55 mg, 0.074 mmol, 93%). This sample was later determined to be spectroscopically pure under NMR. 1 H NMR (600 MHz, Methylene Chloride-d2) δ 9.12 (dd, J = 6.1, 1.2 Hz, 1H), 8.08 (td, J = 7.8, 1.5 Hz, 1H), 7.74 – 7.72 (m, 2H), 7.72 – 7.68 (m, 2H), 7.41 – 7.36 (m, 2H), 4.09 (s, 2H), 2.44 (s, 3H), 1.85 (s, 15H). 13 C NMR (101 MHz, Methylene Chloride-d2) δ 166.21, 150.96, 144.17, 140.98, 127.10, 125.58, 121.88, 92.42, 63.45, 31.54, 21.22, 13.83, 10.10. 19 F NMR (376 MHz, Methylene Chloride-d2) δ -78.47. 3.2 N N Ts Ir OTf N N Ts Ir Cl THF, 2h, 93% AgOTf 3.7 125 FTIR ν 3479.92, 3225.84, 3140.51, 3058.07, 2958.75, 2925, 2870.04, 1615.57, 1598.22, 1486.37, 1450.69, 1381.75, 1257.84, 1222.65, 1146.47 1086.21, 1025.46, 914.093, 847.561, 822.009, 766.566, 710.158, 666.285, 633.019, 551.542, 514.419, 470.546 MS (MALDI) calculated for [C23H28IrN2O2S] + 589.15, found 589.01. Figure 8.3.20. 1 H NMR spectrum of complex 3.7 at 25 °C in CD2Cl2. 0 . 5 1 . 0 1 . 5 2 . 0 2 . 5 3 . 0 3 . 5 4 . 0 4 . 5 5 . 0 5 . 5 6 . 0 6 . 5 7 . 0 7 . 5 8 . 0 8 . 5 9 . 0 9 . 5 1 0 . 0 1 0 . 5 f 1 ( p p m ) 1 5 . 1 8 3 . 3 3 2 . 0 6 2 . 0 0 1 . 9 5 2 . 0 4 1 . 0 6 1 . 0 7 126 Figure 8.3.21. 13 C NMR spectrum of complex 3.7 at 25 °C in CD2Cl2. Figure 8.3.22. 19 F NMR spectrum of complex 3.7 at 25 °C in CD2Cl2. - 1 0 0 1 0 2 0 3 0 4 0 5 0 6 0 7 0 8 0 9 0 1 0 0 1 1 0 1 2 0 1 3 0 1 4 0 1 5 0 1 6 0 1 7 0 1 8 0 1 9 0 2 0 0 2 1 0 2 2 0 2 3 0 f 1 ( p p m ) - 2 0 0 - 1 9 0 - 1 8 0 - 1 7 0 - 1 6 0 - 1 5 0 - 1 4 0 - 1 3 0 - 1 2 0 - 1 1 0 - 1 0 0 - 9 0 - 8 0 - 7 0 - 6 0 - 5 0 - 4 0 - 3 0 - 2 0 - 1 0 0 1 0 2 0 3 0 f 1 ( p p m ) 127 Figure 8.3.23. IR spectrum of complex 3.7. Complex 3.8 In the glovebox under nitrogen, in an 8 dram vial with a magnetic stir bar, Complex 3.3 (50 mg, 0.079 mmol, 1 equiv.) and silver triflate (25 mg, 0.095 mmol, 1.2 equiv.) were dissolved in 5 mL of THF and left stirring for 2 hours. The solution was filtered through a Teflon syringe filter to remove the silver chloride byproduct. After this, THF was evaporated, and the deep-red solid residue was redissolved in 0.4 mL of DCM and filtered through a Teflon syringe filter to remove the remaining 0.2 equiv. of silver triflate. The DCM solution was then added to 5 mL of hexanes. The resulting heterogeneous mixture was sonicated for 30 minutes and then solvents were 3.3 THF, 2h, 98% AgOTf H 2 N N Ts Ir Cl H 2 N N Ts Ir OTf 3.8 128 evaporated. The remaining solid was then sonicated with 5 mL of hexanes for 1 hour. A red crystalline solid of 3.8 was acquired and dried under vacuum (57 mg, 0.077 mmol, 98%). This sample was later determined to be spectroscopically pure under NMR. 1 H NMR (400 MHz, Methylene Chloride-d2) δ 7.65 (d, J = 8.0 Hz, 2H), 7.33 (d, J = 8.0 Hz, 2H), 5.97 (s, 1H), 4.27 (s, 1H), 2.88 (td, J = 10.8, 3.4 Hz, 1H), 2.44 (s, 3H), 2.21 (dd, J = 16.1, 9.9 Hz, 2H), 1.80 (d, J = 0.9 Hz, 15H), 1.44 – 1.38 (m, 2H), 1.12 – 0.85 (m, 4H), 0.74 (dd, J = 11.6, 3.4 Hz, 1H). 13 C NMR (101 MHz, Methylene Chloride-d2) δ 142.77, 140.22, 129.65, 91.15, 70.40, 64.45, 32.76, 24.87, 24.54, 21.14, 10.10. 19 F NMR (376 MHz, Methylene Chloride-d2) δ -78.68. FTIR ν 3474.62, 3204.15, 3105.31, 2931.75, 2862.33, 1598.22, 1496.01, 1451.17, 1382.23, 1278.57, 1086.69, 957.966, 937.717, 883.238, 829.723, 758.37, 708.712, 663.393, 552.506, 515.865, 469.1 MS (MALDI) calculated for [C23H34IrN2O2S] + 595.20, found 592.88. 129 Figure 8.3.24. 1 H NMR spectrum of complex 3.8 at 25 °C in CD2Cl2. Figure 8.3.25. 13 C NMR spectrum of complex 3.8 at 25 °C in CD2Cl2. 0 . 5 1 . 0 1 . 5 2 . 0 2 . 5 3 . 0 3 . 5 4 . 0 4 . 5 5 . 0 5 . 5 6 . 0 6 . 5 7 . 0 7 . 5 8 . 0 8 . 5 9 . 0 9 . 5 1 0 . 0 1 0 . 5 f 1 ( p p m ) 1 . 1 3 4 . 0 9 2 . 0 9 1 5 . 0 6 2 . 2 3 2 . 9 9 1 . 1 8 1 . 0 7 1 . 0 2 2 . 0 0 2 . 0 1 - 1 0 0 1 0 2 0 3 0 4 0 5 0 6 0 7 0 8 0 9 0 1 0 0 1 1 0 1 2 0 1 3 0 1 4 0 1 5 0 1 6 0 1 7 0 1 8 0 1 9 0 2 0 0 2 1 0 2 2 0 2 3 0 f 1 ( p p m ) 130 Figure 8.3.26. 19 F NMR spectrum of complex 3.8 at 25 °C in CD2Cl2. Figure 8.3.27. IR spectrum of complex 3.8. - 2 0 0 - 1 9 0 - 1 8 0 - 1 7 0 - 1 6 0 - 1 5 0 - 1 4 0 - 1 3 0 - 1 2 0 - 1 1 0 - 1 0 0 - 9 0 - 8 0 - 7 0 - 6 0 - 5 0 - 4 0 - 3 0 - 2 0 - 1 0 0 1 0 2 0 3 0 f 1 ( p p m ) 131 Complex 3.9 In the glovebox under nitrogen, in an 8 dram vial with a magnetic stir bar, complex 3.4 (50 mg, 0.080 mmol, 1 equiv.) and silver triflate (25 mg, 0.096 mmol, 1.2 equiv.) were dissolved in 5 mL of THF and left stirring for 2 hours. The solution was filtered through a Teflon syringe filter to remove the silver chloride byproduct. After this, THF was evaporated, and the deep-red solid residue was redissolved in 0.4 mL of DCM and filtered through a Teflon syringe filter to remove the remaining 0.2 equiv. of silver triflate. The DCM solution was then dropwise crashed over 25 mL of hexanes, leading to precipitation of Complex 3.9. A red crystalline solid was acquired and dried under vacuum (54 mg, 0.073 mmol, 91%). This sample was later determined to be spectroscopically pure under NMR. 1 H NMR (600 MHz, Methylene Chloride-d2) δ 9.43 (dd, J = 6.2, 2.1 Hz, 1H), 9.05 (dd, J = 4.8, 2.1 Hz, 1H), 7.84 (t, J = 5.4 Hz, 1H), 7.74 (d, J = 8.3 Hz, 2H), 7.38 (d, J = 8.0 Hz, 2H), 4.13 (s, 2H), 2.44 (s, 3H), 1.87 (s, 15H). 13 C NMR (101 MHz, Methylene Chloride-d2) δ 161.03, 158.63, 129.92, 122.07, 70.47, 61.85, 46.84, 26.55, 10.10, 9.52, 8.47. 19 F NMR (376 MHz, Methylene Chloride-d2) δ -78.82. FTIR ν 3444.72, 3229.7, 3088.92, 2928.86, 2886.92, 2290.05, 2073.58, 2021.03, 2003.2, 1995, 1626.18, 1594.36, 1565.43, 1451.65, 1396.21, 1275.2, 1223.13, 1156.6, 1089.58, 1024.98, 3.4 N N N Ts Ir OTf N N N Ts Ir Cl THF, 2h, 91% AgOTf 3.9 132 950.252, 871.185, 814.777, 759.816, 730.889, 706.301, 665.321, 633.019, 570.344, 551.059, 513.454, 478.742, 457.047, 451.261 MS (MALDI) calculated for [C22H27IrN3O2S] + 590.15, found 590.03. Figure 8.3.28. 1 H NMR spectrum of complex 3.9 at 25 °C in CD2Cl2. 0 . 5 1 . 0 1 . 5 2 . 0 2 . 5 3 . 0 3 . 5 4 . 0 4 . 5 5 . 0 5 . 5 6 . 0 6 . 5 7 . 0 7 . 5 8 . 0 8 . 5 9 . 0 9 . 5 1 0 . 0 1 0 . 5 1 1 . 0 f 1 ( p p m ) 1 5 . 4 6 3 . 2 6 2 . 2 3 1 . 9 9 2 . 0 0 1 . 0 9 1 . 0 1 1 . 0 9 133 Figure 8.3.29. 13 C NMR spectrum of complex 3.9 at 25 °C in CD2Cl2. Figure 8.3.30. 19 F NMR spectrum of complex 3.9 at 25 °C in CD2Cl2. - 1 0 0 1 0 2 0 3 0 4 0 5 0 6 0 7 0 8 0 9 0 1 0 0 1 1 0 1 2 0 1 3 0 1 4 0 1 5 0 1 6 0 1 7 0 1 8 0 1 9 0 2 0 0 2 1 0 2 2 0 2 3 0 f 1 ( p p m ) - 1 6 0 - 1 5 0 - 1 4 0 - 1 3 0 - 1 2 0 - 1 1 0 - 1 0 0 - 9 0 - 8 0 - 7 0 - 6 0 - 5 0 - 4 0 - 3 0 - 2 0 - 1 0 0 f 1 ( p p m ) 134 Figure 8.3.31. IR spectrum of complex 3.9. 135 8.4. Chapter 4 Experimental and Spectral Data 8.4.1. Synthesis Procedures and Characterization Data 8-Bromoquinoline 4.4 Following a modified procedure by Douglas et al., 22 8-bromoquinoline was synthesized by adding 15 mL of methane sulfonic acid to a 100 mL 3-neck round bottom flask with magnetic stir bar inside. The flask was heated to 125 o C and 2-bromoaniline (4.0 g, 0.0233 mol, 1 equiv.) was added portionwise over the course of 10 minutes, followed by sodium 3-nitrobenzenesulfonate (3.3 g, 0.0147 mol, 0.63 equiv.) and FeSO4•7H2O (0.2 g, 0.719 mmol, 0.03 equiv.). Glycerol (5.1 mL, 0.0698 mol, 3 equiv.) was added in three portions (3 ´ 1.7 mL) using an addition funnel in 2- hour intervals. After the addition of the last portion of glycerol, the flask was left for 12 hours at 125 o C. The flask was cooled down to room temperature and the brown contents were transferred to a 500 mL beaker with the help of 100 mL of water. The content of the beaker was placed in an ice bath and treated with 50% w/v NaOH until pH reached 14. The heterogeneous mixture was extracted three times with diethyl ether (3 ´ 50 mL). Layer separation appeared to be slow, in some cases over an hour. Combined organic layers were washed with brine, dried with MgSO4, filtered through the Celite pad and evaporated. The obtained brown oil was distilled under vacuum yielding SO 3 Na O 2 N H 2 N Br N Br 4.4 FeSO 4 . 7H 2 O MeSO 3 H, 125 o C, 16 h, 73% HO OH OH 136 a high viscosity yellow oil (3.5 g, 0.0168 mol, 73%). The obtained product matched reported NMR spectra for 8-bromoquinoline. 22 1 H NMR (600 MHz, Chloroform-d) δ 9.06 (dd, J = 4.2, 1.7 Hz, 1H), 8.18 (dd, J = 8.2, 1.7 Hz, 1H), 8.07 (dd, J = 7.5, 1.3 Hz, 1H), 7.80 (dd, J = 8.2, 1.3 Hz, 1H), 7.48 (dd, J = 8.2, 4.2 Hz, 1H), 7.41 (t, J = 7.8 Hz, 1H). 13 C NMR (101 MHz, Chloroform-d) δ 151.28, 151.26, 145.31, 136.62, 133.20, 129.58, 127.80, 127.76, 127.04, 127.02, 126.98, 124.80, 121.97, 121.96, 121.94, 121.89. Methyl quinoline-8-carboxylate 4.5 8-Bromoquinoline (2.77 g, 13.3 mmol, 1 equiv) was transferred to a 125 mL high pressure Parr apparatus, followed by the addition of 1,1’-Ferrocenediyl-bis(diphenylphosphine) (DPPF) (0.59 g, 1.06 mmol, 8 mol %), palladium(II) acetate (0.12g, 0.53 mmol, 4 mol %) and Et3N (5.56 mL, 39.9 mmol, 3 equiv.). Dry methanol (9 mL) and dry THF (3 mL) were added thereafter. The Parr apparatus was charged with 6 atm. of carbon monoxide and left at 50 o C for 7 days. After allowing the apparatus to cool down to room temperature, gas from inside of it was released completely and then repeatedly charged with 6 atm. of carbon monoxide and left at 50 o C for 7 days again. The Parr apparatus was cooled to room temperature, the gas was released, and the reaction mixture was filtrated through the silica pad and later evaporated. The resulting brown oil underwent purification on a flash purification system (Hex, EtOAc solvents gradient) and the N Br 4.4 CO (6 atm.), MeOH Pd(OAc) 2 , DPPF, Et 3 N. THF : MeOH 3:1, 50 o C, 14 days, 98% N O O 4.5 137 collected combined fractions were evaporated. Yellow oil (2.43g, 13.0 mmol, 98%) was acquired and analyzed by NMR. The results matched previously reported spectra for the assigned compound. 23 1 H NMR (400 MHz, Chloroform-d) δ 9.06 (dt, J = 4.2, 1.6 Hz, 1H), 8.20 (dt, J = 8.3, 1.5 Hz, 1H), 8.04 (dt, J = 7.2, 1.4 Hz, 1H), 7.96 (dt, J = 8.2, 1.4 Hz, 1H), 7.58 (ddd, J = 8.2, 7.2, 1.1 Hz, 1H), 7.47 (ddd, J = 8.3, 4.2, 1.2 Hz, 1H), 4.12 – 4.00 (m, 3H). 13 C NMR (101 MHz, Chloroform-d) δ 167.94, 151.00, 145.02, 135.94, 131.32, 130.99, 129.88, 127.96, 125.22, 121.29, 52.24. 8-(Hydroxydi(pyridin-2-yl)methyl)quinoline 4.6 2-Iodopyridine (0.5 mL, 3.84 mmol, 2.4 equiv.) was added to a previously flame dried 250 mL flask with a magnetic stir bar inside of the glove box, followed by the addition of 60 mL of dry DCM. The flask was sealed with a rubber stopper and taken outside of the glove box, later to be connected to the nitrogen line. A 3M solution of EtMgBr in diethyl ester (1.3 mL, 3.84 mmol, 2.4 equiv.) in a syringe with a needle was added dropwise to the stirring DCM solution of 2- iodopyridine through the rubber stopper and left for 45 minutes. A solution of methyl quinoline- 8-carboxylate (300 mg, 1.60 mmol, 1 equiv.) in 5 mL of dry DCM was added dropwise in the same way and left for 16 hours. The reaction solution was washed with saturated NaHCO3 solution of N I , EtMgBr N N 4.6 N OH DCM, 16 h, RT, 86% N O O 4.5 138 30 mL, which was then extracted twice with DCM (2 ´ 15 mL). Combined DCM fractions were dried over MgSO4, treated with activated charcoal, filtered through Celite pad and evaporated. Obtained yellow oil underwent recrystallization from boiling diethyl ether resulting in white crystals (431 mg, 1.38 mmol, 86%) that were further analyzed by NMR and proved to be spectroscopically pure. 1 H NMR (400 MHz, Chloroform-d) δ 8.96 (s, 1H), 8.67 – 8.62 (m, 1H), 8.53 (ddt, J = 4.8, 2.0, 1.0 Hz, 2H), 8.22 – 8.15 (m, 1H), 7.77 – 7.65 (m, 5H), 7.44 (ddd, J = 8.2, 7.2, 0.9 Hz, 1H), 7.35 (ddd, J = 8.3, 4.3, 0.9 Hz, 1H), 7.28 (t, J = 1.2 Hz, 1H), 7.16 – 7.11 (m, 2H). 13 C NMR (101 MHz, Chloroform-d) δ 164.83, 148.20, 148.15, 147.74, 147.69, 146.69, 141.75, 137.27, 136.25, 136.21, 130.43, 129.04, 127.70, 126.01, 122.52, 122.49, 122.47, 121.72, 121.67, 120.50, 120.43, 84.10. FTIR ν 3087.48, 3047.94, 3006.96, 2360.93, 2338.75, 2080.82, 2022.96, 1992.59, 1956.43, 1905.33, 1853.74, 1786.24, 1735.14, 1611.23, 1585.2, 1565.43, 1496.01, 1462.74, 1427.07, 1365.35, 1311.84, 1287.25, 1242.9, 1211.08, 1164.79, 1147.44, 1103.57, 1042.82, 988.821, 937.717, 920.843, 894.809, 826.348, 779.101, 762.709, 727.514, 700.516, 676.41, 635.912, 615.663, 540.453, 496.098, 462.832 MS (MALDI) calculated for C20H15N3O 313.12, found 314.03. 139 Figure 8.4.1. 1 H NMR spectrum of ligand 4.6 at 25 °C in CDCl3. Figure 8.4.2. 13 C NMR spectrum of ligand 4.6 at 25 °C in CDCl3. 0 . 0 0 . 5 1 . 0 1 . 5 2 . 0 2 . 5 3 . 0 3 . 5 4 . 0 4 . 5 5 . 0 5 . 5 6 . 0 6 . 5 7 . 0 7 . 5 8 . 0 8 . 5 9 . 0 9 . 5 1 0 . 0 f 1 ( p p m ) 2 . 0 1 1 . 0 7 1 . 0 3 1 . 0 6 5 . 1 8 1 . 0 6 2 . 0 1 1 . 0 2 1 . 0 0 7 . 0 7 . 2 7 . 4 7 . 6 7 . 8 8 . 0 8 . 2 8 . 4 8 . 6 8 . 8 9 . 0 f 1 ( p p m ) - 1 0 0 1 0 2 0 3 0 4 0 5 0 6 0 7 0 8 0 9 0 1 0 0 1 1 0 1 2 0 1 3 0 1 4 0 1 5 0 1 6 0 1 7 0 1 8 0 1 9 0 2 0 0 2 1 0 2 2 0 2 3 0 f 1 ( p p m ) 140 Figure 8.4.3. IR spectrum of ligand 4.6. 8-(Methoxydi(pyridin-2-yl)methyl)quinoline 4.7 In the glovebox under nitrogen, 8-(hydroxydi(pyridin-2-yl)methyl)quinoline 4.6 (50 mg, 0.16 mmol, 1 equiv) and sodium hydride (15 mg, 0.64 mmol, 4 equiv) were mixed together in an 8 dram vial with a previously-placed magnetic stir bar. CH3I (40 µL, 0.64 mmol, 4 equiv.) was added to 3 mL of THF and this solution was transferred to the vial. The stirring solution was left for 18 hours and then slowly quenched with 20 mL of saturated NaHCO3 outside of the glove box. N N 4.6 N N 4.7 N N OH OMe THF, 18 h, RT, 98% CH 3 I, NaH 141 The resulting solution was extracted with DCM (3 ´ 15 mL) and fractions were combined, dried over MgSO4 and evaporated. Resulting grey powder (52 mg, 0.16 mmol, 98%) appeared to be spectroscopically pure under NMR. 1 H NMR (400 MHz, Chloroform-d) δ 8.54 – 8.49 (m, 2H), 8.49 – 8.46 (m, 1H), 8.12 (dd, J = 7.4, 1.4 Hz, 1H), 8.09 – 8.02 (m, 1H), 7.83 (dt, J = 8.1, 1.1 Hz, 2H), 7.79 (dd, J = 8.2, 1.4 Hz, 1H), 7.62 – 7.53 (m, 3H), 7.22 – 7.16 (m, 1H), 7.06 (dddd, J = 7.5, 4.8, 1.2, 0.5 Hz, 2H), 3.26 (d, J = 0.6 Hz, 3H). 13 C NMR (101 MHz, Chloroform-d) δ 162.53, 147.99, 147.90, 139.87, 135.90, 131.03, 128.83, 121.17, 120.18, 87.44, 52.91. FTIR ν 3051.8, 3003.11, 2935.13, 2831.47, 1585.68, 1568.81, 1496.01, 1462.74, 1429.48, 1382.23, 1309.91, 1240, 1198.06, 1156.12, 1132.97, 1105.01, 1080.91, 1047.64, 993.643, 965.198, 946.395, 910.236, 887.577, 828.759, 790.671, 764.155, 744.388, 709.194, 673.035, 635.43, 616.627, 582.397, 558.773, 533.703, 503.33, 486.456, 458.975. MS (MALDI) calculated for C21H17N3O 327.14, found 327.91. 142 Figure 8.4.4. 1 H NMR spectrum of ligand 4.7 at 25 °C in CDCl3. Figure 8.4.5. 13 C NMR spectrum of ligand 4.7 at 25 °C in CDCl3. 0 . 0 0 . 5 1 . 0 1 . 5 2 . 0 2 . 5 3 . 0 3 . 5 4 . 0 4 . 5 5 . 0 5 . 5 6 . 0 6 . 5 7 . 0 7 . 5 8 . 0 8 . 5 9 . 0 9 . 5 1 0 . 0 f 1 ( p p m ) 3 . 0 0 2 . 0 5 1 . 0 8 3 . 1 4 1 . 0 6 1 . 9 9 1 . 0 2 0 . 9 8 1 . 0 0 1 . 9 2 7 . 0 7 . 2 7 . 4 7 . 6 7 . 8 8 . 0 8 . 2 8 . 4 8 . 6 f 1 ( p p m ) - 1 0 0 1 0 2 0 3 0 4 0 5 0 6 0 7 0 8 0 9 0 1 0 0 1 1 0 1 2 0 1 3 0 1 4 0 1 5 0 1 6 0 1 7 0 1 8 0 1 9 0 2 0 0 2 1 0 2 2 0 2 3 0 f 1 ( p p m ) 143 Figure 8.4.6. IR spectrum of ligand 4.7. Complex 4.1 In the glovebox under nitrogen, in a 8 dram vial with a magnetic stir bar, chloro(1,5- cyclooctadiene)iridium(I) dimer (50.0 mg, 0.074 mmol, 1 equiv.) and 8-(hydroxydi(pyridin-2- yl)methyl)quinoline 4.6 (47 mg, 0.148 mmol, 2 equiv.) were dissolved in 3 mL of DCM and left stirring for 18 hours. After this, sodium trifluoromethanesulfonate (28 mg, 0.163 mmol, 2.2 equiv.) was also added to the mixture and left for 1 hour more. After stirring for 1 hour, the solution was filtered through a Teflon syringe filter to remove the sodium chloride byproduct. The solvent was N N 4.6 N OH DCM, RT, 95% 1. [Ir(COD)Cl] 2 , 18h 2. NaOTf, 1h N N OH N Ir OTf 4.1 144 evaporated under reduced pressure and yielded a yellow glassy solid. This yellow solid was dissolved in 0.4 mL of dry DCM, then slowly added, to 20 mL of hexanes, leading to precipitation of 4.1. A yellow crystalline solid was acquired and dried under vacuum (107 mg, 0.140 mmol, 95%). This sample was later determined to be spectroscopically pure under NMR. Layering of n- heptane over dichloromethane solution of 4.1 produced crystals suitable for X-ray crystallography. 1 H NMR (600 MHz, Methylene Chloride-d2) δ 8.52 (d, J = 5.7 Hz, 2H), 8.40 (dd, J = 4.3, 1.7 Hz, 1H), 8.32 (d, J = 8.1 Hz, 2H), 8.16 (dd, J = 8.2, 1.7 Hz, 1H), 8.09 (td, J = 7.9, 1.4 Hz, 2H), 7.98 (d, J = 8.5 Hz, 1H), 7.49 (dd, J = 8.5, 7.0 Hz, 1H), 7.43 (t, J = 6.7 Hz, 2H), 7.37 (dd, J = 8.2, 4.4 Hz, 1H), 6.89 (d, J = 7.0 Hz, 1H), 5.52 (s, 1H), 3.75 (d, J = 7.4 Hz, 2H), 2.63 – 2.34 (m, 4H), 1.84 (q, J = 8.0 Hz, 2H), 1.63 (s, 2H), 1.47 (d, J = 8.6 Hz, 2H). 13 C NMR (101 MHz, Methylene Chloride-d2) δ 149.16, 148.82, 140.14, 136.18, 129.29, 128.93, 128.19, 124.59, 124.18, 123.97, 122.22, 109.76, 31.01 (d, J = 10.7 Hz). 19 F NMR (376 MHz, Methylene Chloride-d2) δ -78.94. FTIR ν 3359.87, 2912.95, 2884.99, 2840.63, 2357.55, 1604, 1494.08, 1465.15, 1437.67, 1380.78, 1274.72, 1252.06, 1226.02, 1204.33, 1151.78, 1069.82,1027.87, 985.447, 897.219, 828.759, 796.457, 762.709, 696.177, 663.393, 632.537, 571.79, 516.347, 487.902. MS (MALDI) calculated for [C28H27IrN3O] + 614.18, found 613.80. Anal. Calcd for C29H27F3IrN3O4S: C, 45.66; H, 3.57; N, 5.51; S, 4.20 Found: C, 45.51; H, 3.67; N, 5.35; S, 4.22. 145 Figure 8.4.7. 1 H NMR spectrum of complex 4.1 at 25 °C in CD2Cl2. Figure 8.4.8. 13 C NMR spectrum of complex 4.1 at 25 °C in CD2Cl2. 0 . 0 0 . 5 1 . 0 1 . 5 2 . 0 2 . 5 3 . 0 3 . 5 4 . 0 4 . 5 5 . 0 5 . 5 6 . 0 6 . 5 7 . 0 7 . 5 8 . 0 8 . 5 9 . 0 9 . 5 1 0 . 0 1 0 . 5 f 1 ( p p m ) 2 . 3 6 2 . 1 4 2 . 2 5 4 . 1 7 2 . 1 8 0 . 9 8 0 . 9 4 1 . 0 0 2 . 0 5 1 . 1 5 0 . 9 9 2 . 0 0 1 . 0 4 1 . 9 9 1 . 0 0 2 . 0 9 - 1 0 0 1 0 2 0 3 0 4 0 5 0 6 0 7 0 8 0 9 0 1 0 0 1 1 0 1 2 0 1 3 0 1 4 0 1 5 0 1 6 0 1 7 0 1 8 0 1 9 0 2 0 0 2 1 0 2 2 0 2 3 0 f 1 ( p p m ) 146 Figure 8.4.9. 19 F NMR spectrum of complex 4.1 at 25 °C in CD2Cl2. Figure 8.4.10. IR spectrum of complex 4.1. - 2 0 0 - 1 9 0 - 1 8 0 - 1 7 0 - 1 6 0 - 1 5 0 - 1 4 0 - 1 3 0 - 1 2 0 - 1 1 0 - 1 0 0 - 9 0 - 8 0 - 7 0 - 6 0 - 5 0 - 4 0 - 3 0 - 2 0 - 1 0 0 1 0 2 0 3 0 f 1 ( p p m ) - 7 8 . 9 4 147 Figure 8.4.11. X-Ray structure of complex 4.1. Complex 4.2 Complex 4.2 was prepared by following an analogous procedure to that described above for complex 1. In the glovebox under nitrogen, in a 8 dram vial with a magnetic stir bar, chloro(1,5- N N 4.7 N OMe DCM, RT, 96% 1. [Ir(COD)Cl] 2 , 18h 2. NaOTf, 1h N N OMe N Ir OTf 4.2 148 cyclooctadiene)Iridium(I) dimer (50.0 mg, 0.074 mmol, 1 equiv.) and 8-(methoxydi(pyridin-2- yl)methyl)quinoline 4.7 (48 mg, 0.148 mmol, 2 equiv.) were dissolved in 3 mL of DCM and left stirring for 18 hours. Sodium trifluoromethanesulfonate (28 mg, 0.163 mmol, 2.2 equiv.) was later added to the mixture and left for 1 hour. After stirring, the solution was filtered through a Teflon syringe filter to remove the sodium chloride byproduct. The solvent was evaporated under reduced pressure and yielded in a yellow glassy solid. This yellow solid was dissolved in 0.4 mL of dry DCM, then added slowly, dropwise, to 20 mL of hexanes, leading to precipitation of 4.2. A yellow crystalline solid was acquired and dried under vacuum (110 mg, 0.142 mmol, 96%). This sample was later determined to be spectroscopically pure under NMR. 1 H NMR (500 MHz, Methylene Chloride-d2) δ 8.74 – 8.70 (m, 1H), 8.40 (d, J = 5.7 Hz, 1H), 8.34 (dt, J = 4.4, 1.5 Hz, 1H), 8.18 – 8.10 (m, 3H), 8.07 – 7.99 (m, 3H), 7.53 (ddt, J = 7.3, 5.8, 1.5 Hz, 1H), 7.49 (ddd, J = 8.2, 6.8, 1.1 Hz, 1H), 7.39 – 7.35 (m, 1H), 7.35 – 7.31 (m, 1H), 6.75 (dt, J = 6.9, 1.2 Hz, 1H), 3.86 (s, 1H), 3.79 (t, J = 7.6 Hz, 1H), 3.52 (s, 1H), 2.94 (d, J = 1.2 Hz, 3H), 2.47 (d, J = 7.3 Hz, 2H), 1.95 (q, J = 8.7, 6.4 Hz, 2H), 1.83 (s, 2H), 1.40 (q, J = 9.6, 7.7 Hz, 1H), 1.28 (d, J = 6.6 Hz, 2H). 13 C NMR (101 MHz, Methylene Chloride-d2) δ 150.19, 149.00, 148.18, 147.06, 141.10, 139.35, 135.62, 129.74, 128.23, 127.96, 125.28, 124.79, 123.42, 123.01, 122.18, 107.26, 81.05, 77.80, 66.35, 33.65, 32.52, 29.45. 19 F NMR (376 MHz, Methylene Chloride-d2) δ -78.94. FTIR ν 2948.63, 2837.74, 1603.04, 1462.26, 1445.39, 1387.53, 1260.25, 1221.68, 1148.4, 1087.17, 1028.35, 990.75, 895.773, 832.133, 796.457, 768.012, 677.856, 655.197, 632.537, 570.344, 516.347, 484.045. MS (MALDI) calculated for [C29H29IrN3O] + 628.19, found 627.86. 149 Anal. Calcd for C29H27F3IrN3O4S: C, 46.38; H, 3.76; N, 5.41; S, 4.13 Found: C, 46.45; H, 3.85; N, 5.38; S, 4.11. Figure 8.4.12. 1 H NMR spectrum of complex 4.2 at 25 °C in CD2Cl2. Figure 8.4.13. 13 C NMR spectrum of complex 4.2 at 25 °C in CD2Cl2. 0 . 5 1 . 0 1 . 5 2 . 0 2 . 5 3 . 0 3 . 5 4 . 0 4 . 5 5 . 0 5 . 5 6 . 0 6 . 5 7 . 0 7 . 5 8 . 0 8 . 5 9 . 0 9 . 5 1 0 . 0 f 1 ( p p m ) 2 . 1 6 1 . 2 8 2 . 3 2 2 . 1 3 2 . 3 2 3 . 3 3 1 . 1 6 1 . 1 8 1 . 1 9 1 . 0 0 0 . 9 8 0 . 9 9 1 . 1 1 1 . 0 6 2 . 9 6 3 . 1 1 0 . 9 3 1 . 1 5 1 . 1 1 - 1 0 0 1 0 2 0 3 0 4 0 5 0 6 0 7 0 8 0 9 0 1 0 0 1 1 0 1 2 0 1 3 0 1 4 0 1 5 0 1 6 0 1 7 0 1 8 0 1 9 0 2 0 0 2 1 0 2 2 0 2 3 0 f 1 ( p p m ) 150 Figure 8.4.14. 19 F NMR spectrum of complex 4.2 at 25 °C in CD2Cl2. Figure 8.4.15. IR spectrum of complex 4.2. - 2 0 0 - 1 9 0 - 1 8 0 - 1 7 0 - 1 6 0 - 1 5 0 - 1 4 0 - 1 3 0 - 1 2 0 - 1 1 0 - 1 0 0 - 9 0 - 8 0 - 7 0 - 6 0 - 5 0 - 4 0 - 3 0 - 2 0 - 1 0 0 1 0 2 0 3 0 f 1 ( p p m ) - 7 8 . 9 4 151 8-Acetylquinoline 4.9 Following a similar procedure to synthesis of 8-bromoquinoline (4.4) described above, 8- acetylquinoline was synthesized by adding 11 mL of methane sulfonic acid to 100 mL 3-neck round bottom flask with a magnetic stir bar inside. The flask was heated to 125 o C and 2’- aminoacetophenone 4.8 (2.70 g, 20.0 mmol, 1 equiv.) was added portionwise over the course of 10 minutes, followed by sodium 3-nitrobenzenesulfonate (2.84 g, 12.6 mmol, 0.63 equiv.) and FeSO4•7H2O (0.167 g, 0.6 mmol, 0.03 equiv.). Glycerol (3.6 mL, 60.0 mmol, 3 equiv.) was added in two portions (2 ´ 1.8 mL) using an addition funnel, with 2 hours intervals. After the addition of the second portion of glycerol, the flask was left for 18 hours at 125 o C. The flask was cooled down to room temperature and the brown contents of it were transferred to a 500 mL beaker with the help of 50 mL of water. The content of the beaker was placed in an ice bath and treated with 50% w/v NaOH until pH reached 14. The heterogeneous mixture was extracted three times with diethyl ether (3 ´ 100 mL). Layer separation appeared to be slow, in some cases over an hour. Combined organic layers were washed with brine, dried with MgSO4, filtered through the Celite pad and evaporated. The obtained brown oil was distilled under vacuum yielding a high viscosity yellow oil (2.12 g, 12.4 mmol, 62%). Obtained product matched reported NMR spectra for 8- acetylquinoline. 24 SO 3 Na O 2 N H 2 N N 4.9 FeSO 4 . 7H 2 O MeSO 3 H, 125 o C, 16 h, 62% HO OH OH O 4.8 O 152 1 H NMR (400 MHz, Chloroform-d) δ 8.98 (ddt, J = 3.5, 1.8, 0.9 Hz, 1H), 8.22 – 8.16 (m, 1H), 8.02 – 7.87 (m, 2H), 7.59 (ddt, J = 8.2, 7.1, 0.8 Hz, 1H), 7.46 (ddt, J = 8.3, 4.2, 0.9 Hz, 1H), 2.95 (d, J = 0.7 Hz, 3H). 13 C NMR (101 MHz, Chloroform-d) δ 150.35, 136.19, 131.25, 129.12, 125.89, 121.34, 32.68. 1-(Pyridin-2-yl)-1-(quinolin-8-yl)ethan-1-ol 4.10 2-Iodopyridine (0.46 mL, 3.56 mmol, 1.5 equiv.) was added to a previously flame dried 250 mL flask with a magnetic stir bar inside of the glove box, followed by the addition of 50 mL of dry DCM. The flask was sealed with the rubber stopper and taken outside of the glove box, later to be connected to the nitrogen line. A 3M solution of EtMgBr in diethyl ester (1.2 mL, 3.56 mmol, 1.5 equiv.) in a syringe with a needle was added dropwise to the stirring DCM solution of 2- iodopyridine through the rubber stopper and left for 45 minutes. A solution of 8-acetylquinoline (406 mg, 2.37 mmol, 1 equiv.) in 10 mL of dry DCM was added dropwise in the same way and left for 16 hours. The reaction solution was washed with saturated NaHCO3 solution of 30 mL, which was then extracted twice with DCM (2 ´ 20 mL). Combined DCM fractions were dried over MgSO4, treated with activated charcoal, filtered through Celite pad and evaporated. The obtained N 4.9 O N I EtMgBr DCM, 16 h, RT, 68% N 4.10 HO N 153 yellow oil underwent recrystallization from boiling diethyl ether resulting in white crystals (403 mg, 1.61 mmol, 68%) that were further analyzed by NMR and proved to be spectroscopically pure. 1 H NMR (400 MHz, Chloroform-d) δ 8.71 (dt, J = 4.4, 1.6 Hz, 2H), 8.41 (dtd, J = 4.9, 1.7, 0.9 Hz, 1H), 8.16 (dt, J = 8.3, 1.5 Hz, 1H), 7.99 (dq, J = 8.0, 1.2 Hz, 1H), 7.86 (dt, J = 7.3, 1.3 Hz, 1H), 7.74 (dq, J = 8.3, 1.3 Hz, 1H), 7.66 (dddd, J = 8.8, 7.9, 2.2, 1.1 Hz, 1H), 7.56 (ddd, J = 8.4, 7.3, 1.2 Hz, 1H), 7.36 (ddt, J = 8.3, 4.3, 1.2 Hz, 1H), 7.04 (ddt, J = 7.5, 4.8, 1.3 Hz, 1H), 2.12 (d, J = 1.2 Hz, 3H). 13 C NMR (101 MHz, Chloroform-d) δ 167.64, 148.08, 147.50 (d, J = 6.5 Hz), 146.12, 142.61, 137.36, 136.15, 128.83, 128.14, 127.34, 126.94 – 126.05 (m), 121.12 (d, J = 5.7 Hz), 120.52 (d, J = 8.7 Hz), 119.91, 79.02, 29.40 (d, J = 4.6 Hz). FTIR ν 3226.33, 3218.61, 3083.62, 3051.32, 2987.68, 2935.13, 2870.04, 2361.41, 2346.46, 2339.23, 1966.07, 1936.18, 1905.33, 1880.74, 1855.67, 1832.53, 1780.94, 1754.9, 1582.79, 1496.97, 1460.33, 1424.65, 1360.05, 1313.29, 1284.36, 1258.81, 1240.97, 1220.24, 1176.36, 1139.72, 1127.67, 1111.28, 1087.66, 1061.62, 991.714, 957.966, 930.485, 869.256, 832.133, 792.118, 786.815, 748.727, 696.659, 620.002, 590.111, 528.882, 496.098, 470.064, 462.35, 1230.84, 1220.24, 1185.53, 1176.85, 1139.72, 1134.42, 1127.67, 1122.85, 1111.28, 1099.23, 1087.66, 1073.67, 1061.62, 991.714, 957.966, 930.485, 869.256, 832.133, 792.6, 789.707, 786.815, 761.262, 748.727, 734.264, 696.659, 634.466, 620.002, 603.61, 590.111, 528.882, 496.098, 470.546, 467.171, 462.832 MS (MALDI) calculated for C16H14N2O 250.11, found 250.97. 154 Figure 8.4.16. 1 H NMR spectrum of 4.10 at 25 °C in CDCl3. Figure 8.4.17. 13 C NMR spectrum of 4.10 at 25 °C in CDCl3. 0 . 0 0 . 5 1 . 0 1 . 5 2 . 0 2 . 5 3 . 0 3 . 5 4 . 0 4 . 5 5 . 0 5 . 5 6 . 0 6 . 5 7 . 0 7 . 5 8 . 0 8 . 5 9 . 0 9 . 5 1 0 . 0 f 1 ( p p m ) 3 . 0 0 0 . 9 9 1 . 0 0 1 . 0 0 1 . 0 3 1 . 0 0 1 . 0 0 1 . 0 1 0 . 9 8 0 . 9 4 1 . 8 3 - 1 0 0 1 0 2 0 3 0 4 0 5 0 6 0 7 0 8 0 9 0 1 0 0 1 1 0 1 2 0 1 3 0 1 4 0 1 5 0 1 6 0 1 7 0 1 8 0 1 9 0 2 0 0 2 1 0 2 2 0 2 3 0 f 1 ( p p m ) 155 Figure 8.4.18. IR spectrum of ligand 4.10. Complex 4.11. In the glovebox under nitrogen, in an 8 dram vial with a magnetic stir bar, to solid 1- (pyridin-2-yl)-1-(quinolin-8-yl)ethan-1-ol (4.10) (100 mg, 0.4 mmol, 1 equiv.) was added 0.8 mL toluene solution of diethylzinc (45 µL, 0.4 mmol, 1 equiv.). After this, another 0.4 mL of toluene was added to the mixture and left until white solid precipitated. (Solid precipitation differed from run to run, on average being in between 15-30 minutes.). The obtained solid was washed with toluene on a filter paper and dried under vacuum (203 mg, 0.296 mmol, 74%). The white Et 2 Zn Toluene,16 h, RT, 74% 4.11 N 4.10 HO N N O Zn N O Zn N N 156 crystalline solid appeared to be 92% spectroscopically pure under NMR. The remaining impurities may be assigned to the trimeric structure, since both the trimeric and dimeric zinc complexes of similar structure have been previously reported by van Koten et al., 25 with the dimer being characterized by X-ray crystallography. Layering of n-pentane over benzene solution of 4.11 produced crystals suitable for X-ray crystallography, however, those appeared to be the decomposition product 4.12. White crystalline powder of 4.11 appeared to be relatively air stable over short periods of time, however not tolerant to moisture. If dissolved in organic solvents, 4.11 appeared to be relatively stable over short periods of time, however unstable if the solution is exposed to air, moisture or light. 1 H NMR (400 MHz, Methylene Chloride-d2) δ 8.72 (dd, J = 4.5, 1.9 Hz, 1H), 8.50 (ddd, J = 5.1, 1.7, 1.0 Hz, 1H), 8.24 (ddd, J = 8.3, 1.9, 0.4 Hz, 1H), 8.08 (dd, J = 7.3, 1.5 Hz, 1H), 7.74 (dd, J = 8.2, 1.4 Hz, 1H), 7.67 – 7.55 (m, 2H), 7.46 – 7.38 (m, 2H), 7.18 (ddd, J = 7.4, 5.1, 1.1 Hz, 1H), 2.16 (s, 3H), 1.49 (t, J = 8.1 Hz, 3H), 0.54 (dd, J = 8.0, 3.5 Hz, 2H). 13 C NMR (101 MHz, Methylene Chloride-d2) δ 148.52, 145.73, 137.98, 127.72, 126.96 (d, J = 7.7 Hz), 126.76, 121.91, 121.61, 120.58 – 119.63 (m), 31.35, 13.15, -4.60. FTIR ν 2977.55, 2925.97, 2885.47, 2849.31, 1597.73, 1566.88, 1494.56, 1463.71, 1430.92, 1358.6, 1294.48, 1233.25, 1166.72, 1130.08, 1098.74, 1082.35, 1054.39, 1017.75, 994.607, 933.378, 916.022, 861.06, 830.205, 788.261, 753.548, 690.391, 638.805, 597.825, 541.417, 507.669, 468.617, 462.832. MS (MALDI) calculated for C36H36N4O2Zn2 684.14, found 685.35. 157 Figure 8.4.19. 1 H NMR spectrum of 4.11 at 25 °C in CD2Cl2. Figure 8.4.20. 13 C NMR spectrum of 4.11 at 25 °C in CD2Cl2. - 0 . 5 0 . 0 0 . 5 1 . 0 1 . 5 2 . 0 2 . 5 3 . 0 3 . 5 4 . 0 4 . 5 5 . 0 5 . 5 6 . 0 6 . 5 7 . 0 7 . 5 8 . 0 8 . 5 9 . 0 9 . 5 1 0 . 0 f 1 ( p p m ) 2 . 0 8 2 . 8 7 3 . 0 1 1 . 0 0 2 . 0 8 2 . 0 1 0 . 9 4 1 . 0 7 0 . 9 8 0 . 8 7 1 . 0 0 - 1 0 0 1 0 2 0 3 0 4 0 5 0 6 0 7 0 8 0 9 0 1 0 0 1 1 0 1 2 0 1 3 0 1 4 0 1 5 0 1 6 0 1 7 0 1 8 0 1 9 0 2 0 0 2 1 0 2 2 0 2 3 0 f 1 ( p p m ) 158 Figure 8.4.21. IR spectrum of Complex 4.11. Figure 8.4.22. Left: dimeric zinc complex characterized by van Koten et al. Right: structure of decomposition product 4.12. Zn N N O O N N 12 N O Zn N O Zn Si Si Zn N N O O N N 4.12 159 Figure 8.4.23. X-Ray structure of complex 4.12. 160 8.4.2. Spectral Data Figure 8.4.24. Absorption spectra of quinoline in different solvents. Figure 8.4.25. Emission spectra of quinoline in different solvents (310 nm excitation wavelength). 260 280 300 320 340 0 0.2 0.4 0.6 0.8 1 Wavelength / nm Absorbance HFIPA TFE MeOH EtOH IPA DCM 350 400 450 500 550 0 5 10 15 x 10 6 Wavelength / nm Emission / CPS HFIPA TFE MeOH EtOH IPA DCM 161 8.4.3. Discussion of Fluorescence and Inter-System Crossing in Quinoline In general, quinoline displays rapid (< 1 ps) intersystem crossing in the free base form in solution, so it has negligible fluorescence. The protonated form does not undergo intersystem crossing under the same conditions and therefore emits much more strongly. Any quinoline molecule that captures a proton before intersystem crossing occurs will emit from the protonated state. If quinoline is not protonated in the ground state, emission from the protonated form is indicative of excited state proton capture (photobasicity). According to the figures above, quinoline appears to deprotonate both HFIPA and TFE in the excited state. However, emission intensity in HFIPA is significantly stronger than it is in TFE. Free energy relationships (correlations between the thermodynamics of a reaction and the kinetics of the reaction) have been described throughout the excited state proton transfer community. Generally, proton transfer reactions with greater thermodynamic drive tend to happen more quickly than proton transfer reactions with lower thermodynamic drives. This trend has been well-described in the literature using Marcus free energy relations for proton transfer. 26,27 According to this logic, proton transfer in TFE (pKa = 12.4) should be slower than in HFIPA (pKa = 9.3) when the same excited state proton acceptor is utilized because of the smaller thermodynamic drive for protonation in TFE. We find that quinoline undergoes rapid ISC that prevents emission, and the only emission we observe comes from quinoline molecules that are protonated before ISC occurs. Therefore, if the excited state proton transfer occurs more quickly, more quinoline get protonated before ISC occurs and there is more emission. Therefore, the greater emission intensity in HFIPA than in TFE is completely consistent with their relative pKa values and the Marcus free energy relations for proton transfer used in the proton transfer literature. 162 Figure 8.4.26. Absorption spectra of complex 4.1 in different solvents. Figure 8.4.27. Emission spectra of complex 4.1 in different solvents (310 nm excitation wavelength). 300 350 400 450 500 550 0 0.2 0.4 0.6 0.8 1 Wavelength / nm Absorbance HFIPA TFE MeOH EtOH IPA DCM 350 400 450 500 550 0 1 2 3 4 x 10 5 Wavelength / nm Emission / CPS HFIPA TFE MeOH EtOH IPA DCM 163 Figure 8.4.28. Absorption spectra of complex 4.2 in different solvents. Figure 8.4.29. Emission spectra of complex 4.2 in different solvents (310 nm excitation wavelength). 300 350 400 450 500 550 600 0 0.2 0.4 0.6 0.8 1 Wavelength / nm Absorbance HFIPA TFE MeOH EtOH IPA DCM 350 400 450 500 550 0 1 2 3 4 5 6 7 x 10 5 Wavelength / nm Emission / CPS HFIPA TFE MeOH EtOH IPA DCM 164 Figure 8.4.30. Emission and absorption spectra of complex 4.2 in HFIPA. Figure 8.4.31. Emission and absorption spectra of complex 4.2 in HFIPA (absorption region zoomed). 165 8.4.4. Discussion of UV-vis Spectrum of the Methyl Homolog (Complex 4.13) of Complex 4.2. We have tried to synthesize the methyl homolog of complex 4.2 by following an analogous synthetic route to 4.2, however were not able to isolate clean complex 4.13. The reaction is frustrated by a ca. 10 mol% impurity (Figure 8.4.32). Even though we were not able to separate 4.13 from the impurities, the UV-vis spectra of the mixture allowed us to make the following conclusion. The presence of quinoline red-shifts the absorption of complex 4.2. However, the emission spectra of 4.2 nearly match that of molecular quinoline and show a trend based on solvent pKa values. Therefore, while quinoline may have a polarizing influence on the MLCT and d-d transitions resulting in their red shift, the deprotonation effect seems to be localized on the quinoline moiety. Figure 8.4.32. Absorption spectra of complex 4.2, complex 4.13, and quinoline in DCM. 166 Figure 8.4.33. 1 H NMR spectrum of complex 4.13 at 25 °C in CD2Cl2. Figure 8.4.34. COSY spectrum of complex 4.13 at 25 °C in CD2Cl2. 0 . 0 0 . 5 1 . 0 1 . 5 2 . 0 2 . 5 3 . 0 3 . 5 4 . 0 4 . 5 5 . 0 5 . 5 6 . 0 6 . 5 7 . 0 7 . 5 8 . 0 8 . 5 9 . 0 9 . 5 1 0 . 0 1 0 . 5 f 1 ( p p m ) 4 . 3 4 3 . 3 0 4 . 1 2 3 . 0 8 3 . 9 9 1 . 6 5 2 . 0 0 1 . 7 4 2 . 0 0 - 1 . 0 - 0 . 5 0 . 0 0 . 5 1 . 0 1 . 5 2 . 0 2 . 5 3 . 0 3 . 5 4 . 0 4 . 5 5 . 0 5 . 5 6 . 0 6 . 5 7 . 0 7 . 5 8 . 0 8 . 5 9 . 0 9 . 5 1 0 . 0 f 2 ( p p m ) - 1 0 1 2 3 4 5 6 7 8 9 1 0 f 1 ( p p m ) 167 8.4.5. Quantum Yield Data. Table 8.4.1. Fluorescence quantum yield of quinoline moiety of complex 4.2. Solvent Fluorescence Quantum Yield of Quinoline Moiety of Complex 4.2 HFIPA 2.8 x 10 -3 TFE 3.2 x 10 -4 MeOH 2.0 x 10 -4 EtOH 1.8 x 10 -4 IPA 2.3 x 10 -4 DCM 6.2 x 10 -4 Fluorescence quantum yields were determined for the quinoline moiety of complex 2 (1.4 x 10 -4 M) in various solvents with respect to anthracene (5 x 10 -5 M) in ethanol using the equation Φ= Φ % ∗ 𝐼𝑛𝑡 𝐼𝑛𝑡 % ∗ (1−10 -. / ) (1−10 -. ) ∗ 𝑛 1 𝑛 % 1 where Φ is the fluorescence quantum yield, Int is the integrated emission intensity, A is the absorbance at the excitation wavelength (310 nm in all cases), and n is the refractive index of the solvent. The subscript “R” indicates that the values are for the reference chromophore (in this case Φ % = 0.270 5 and 𝑛 % = 1.361 for anthracene in ethanol). Emission spectra were integrated numerically using Simpson’s rule. The absorbance values used for estimation of quantum yield are the absorbance values of complex 2 at 310 nm. Because we know that the absorption at 310 nm may not be entirely due to absorption of the quinoline moiety, the fluorescence quantum yields listed above should be 168 considered as lower bounds for the true quantum yields of the quinoline moiety of complex 2 in the given solvent. Additionally, due to the overlap of quinoline moiety emission and absorption from LMCT, there is likely to be some re-absorption of emitted photons. Re-absorption of emitted photons would similarly result in an underestimated fluorescence quantum yield. 169 8.4.6. Complex 4.1 Decomposition Studies Figure 8.4.35. Absorption spectra of complex 4.1 (red) and ligand 4.6 (blue) in HFIPA. Figure 8.4.36. Zoomed absorption spectra of complex 4.1 (red) and ligand 4.6 (blue) in HFIPA. 300 350 400 450 500 550 0 0.5 1 1.5 2 2.5 3 Wavelength / nm Absorbance OH complex in HFIPA Ligand in HFIPA 300 350 400 450 500 550 0 0.2 0.4 0.6 0.8 1 Wavelength / nm Absorbance OH complex in HFIPA Ligand in HFIPA 170 Figure 8.4.37. Emission spectra of complex 4.1 (red) and ligand 4.6 (blue) in HFIPA (310 nm excitation wavelength). Figure 8.4.38. Q-Tof spectra of complex 4.1 in HFIPA. 350 400 450 500 550 0 1 2 3 4 x 10 5 Wavelength / nm Emission / CPS OH complex in HFIPA Ligand in HFIPA Sample Name ID Ir NNOH Position P3-E1 Instrument Name LC-QTOF1 User Name Inj Vol 1 InjPosition Sample Type Sample IRM Calibration Status Success Data Filename Id Ir NNOH4.d ACQ Method demianet M4 pos A2B2.m Comment Acquired Time 9/21/2018 1:31:29 PM (UTC-07:00) 6 x10 0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 1.9 2 2.1 2.2 2.3 2.4 2.5 2.6 2.7 2.8 2.9 3 3.1 3.2 3.3 3.4 Counts vs. Mass-to-Charge (m/z) 200 250 300 350 400 450 500 550 600 650 700 750 800 850 900 950 1000 1050 1100 +ESI Scan (rt: 0.664 min) Frag=155.0V Id Ir NNOH4.d 630.1710 314.1278 646.1655 428.0965 235.0856 473.1179 612.1596 171 8.5. Chapter 5 Experimental and Spectral Data 8.5.1. Synthesis Procedures and Characterization Data Synthesis procedures for 5.1, 5.2, and 5.8-5.11 are described above in Chapter 8.4 Complex 5.3 Complex 5.1 (26 mg, 0.034 mmol) was transferred to an 8 dram vial followed by the addition of 2 mL of dry methylene chloride in a glovebox. The vial was closed with the rubber septum and removed from the glovebox. A balloon charged with carbon monoxide was attached to the vial and left at room temperature for 2 hours. After the gas was released, the reaction mixture was placed back inside the glovebox and later evaporated. The resulting orange glassy product was redissolved in 2 mL of DCM and evaporated again to remove all of the cyclooctadiene. The remaining glassy product was dissolved in 0.2 mL of dry DCM, then slowly added to 10 mL of hexanes, leading to precipitation of 5.3. A yellow crystalline solid was acquired and dried under vacuum (24 mg, 0.034 mmol, 99%). This sample was later determined to be spectroscopically pure under NMR. N N OH N Ir OTf CO 1atm. N N OH N Ir OC OC OTf 5.1 5.3 DCM, 2 h, RT, 99% 172 1 H NMR (400 MHz, Methanol-d4) δ 8.75 – 8.65 (m, 3H), 8.49 – 8.39 (m, 1H), 8.26 (t, J = 7.8 Hz, 3H), 8.05 (dd, J = 8.2, 1.3 Hz, 1H), 7.62 – 7.47 (m, 3H), 7.46 – 7.38 (m, 1H), 7.23 (d, J = 7.4 Hz, 1H), 6.40 (s, 1H). 13 C NMR (101 MHz, Methanol-d4) δ 168.25, 147.56, 135.02, 129.86, 129.07, 127.35, 124.21, 123.81, 119.77. 19 F NMR (376 MHz, Methylene Chloride-d2) δ -81.00. FTIR ν 3271.16, 3115.44, 3091.33, 2957.3, 2926.45, 2860.88, 2077.44, 2007.53, 1606.41, 1509.51, 1468.53, 1442.98, 1392.84, 1277.13, 1242.9, 1225.06, 1157.56, 1091.51, 1075.12, 1027.39, 919.397, 896.255, 862.507, 803.689, 773.315, 700.516, 674.481, 669.178, 633.019, 572.273, 553.47, 535.15, 515.383, 498.509, 461.868 MS (MALDI) calculated for [C22H15IrN3O3] + 562.07, found 561.84. Figure 8.5.1. 1 H NMR spectrum of complex 5.3 at 25 °C in CDCl3. 0 . 5 1 . 0 1 . 5 2 . 0 2 . 5 3 . 0 3 . 5 4 . 0 4 . 5 5 . 0 5 . 5 6 . 0 6 . 5 7 . 0 7 . 5 8 . 0 8 . 5 9 . 0 9 . 5 1 0 . 0 1 0 . 5 f 1 ( p p m ) 1 . 0 3 1 . 0 7 1 . 1 5 3 . 0 6 1 . 0 4 2 . 9 5 1 . 0 0 3 . 0 9 173 Figure 8.5.2. 13 C NMR spectrum of complex 5.3 at 25 °C in CDCl3. Figure 8.5.3. 19 F NMR spectrum of complex 5.3 at 25 °C in CDCl3. - 1 0 0 1 0 2 0 3 0 4 0 5 0 6 0 7 0 8 0 9 0 1 0 0 1 1 0 1 2 0 1 3 0 1 4 0 1 5 0 1 6 0 1 7 0 1 8 0 1 9 0 2 0 0 2 1 0 2 2 0 2 3 0 f 1 ( p p m ) - 2 0 0 - 1 9 0 - 1 8 0 - 1 7 0 - 1 6 0 - 1 5 0 - 1 4 0 - 1 3 0 - 1 2 0 - 1 1 0 - 1 0 0 - 9 0 - 8 0 - 7 0 - 6 0 - 5 0 - 4 0 - 3 0 - 2 0 - 1 0 0 1 0 2 0 3 0 f 1 ( p p m ) 174 Figure 8.5.4. IR spectrum of complex 5.3. Complex 5.4 Complex 5.2 (26 mg, 0.034 mmol) was transferred to a 125 mL high pressure Parr apparatus, followed by the addition of 2 mL of dry methylene chloride in a glovebox. The Parr apparatus was removed from the glovebox and charged with 5 atm. of carbon monoxide and left at room temperature for 16 hours. After that gas was released, and the reaction mixture was transferred into 8 dram vial and later evaporated. The resulting orange glassy product was N N O N Ir OTf 5.2 N N O N Ir OC OC OTf 5.4 CO 5 atm. DCM, 16 h, RT, 98% 175 redissolved in 2 mL of DCM and evaporated again to remove all of the cyclooctadiene. The remaining glassy product was dissolved in 0.2 mL of dry DCM, then slowly added to 10 mL of hexanes, leading to precipitation of 5.4. An orange crystalline solid was acquired and dried under vacuum (24 mg, 0.034 mmol, 98%). This sample was later determined to be spectroscopically pure under NMR. 1 H NMR (400 MHz, Methanol-d4) δ 8.81 (s, 2H), 8.48 (s, 2H), 8.37 (dd, J = 4.2, 1.8 Hz, 1H), 8.34 – 8.20 (m, 3H), 8.14 (dd, J = 8.2, 1.4 Hz, 1H), 7.63 (dd, J = 8.2, 7.4 Hz, 3H), 7.41 (dd, J = 8.3, 4.2 Hz, 1H), 7.12 (dd, J = 7.4, 1.3 Hz, 1H), 3.37 (s, 3H). 13 C NMR (101 MHz, Methanol-d4) δ 147.85, 140.08, 134.97, 132.14, 129.97, 127.25, 124.16, 122.89, 119.65, 52.14. 19 F NMR (376 MHz, Methylene Chloride-d2) δ -80.90. FTIR ν 3108.21, 3061.92, 3012.75, 2942.84, 2834.85, 2360.93, 2338.75, 2073.1, 2007.05, 1603.52, 1507.1, 1461.78, 1442.49, 1254.95, 1220.24, 1145.51, 1084.76, 1056.32, 1025.94, 981.59, 943.985, 902.04, 806.581, 775.726, 693.284, 674.481, 654.715, 631.573, 570.344, 536.596, 513.936, 480.67, 465.243 MS (MALDI) calculated for [C23H17IrN3O3] + 576.09, found 575.68. 176 Figure 8.5.5. 1 H NMR spectrum of complex 5.4 at 25 °C in CDCl3. Figure 8.5.6. 13 C NMR spectrum of complex 5.4 at 25 °C in CDCl3. 0 . 5 1 . 0 1 . 5 2 . 0 2 . 5 3 . 0 3 . 5 4 . 0 4 . 5 5 . 0 5 . 5 6 . 0 6 . 5 7 . 0 7 . 5 8 . 0 8 . 5 9 . 0 9 . 5 1 0 . 0 1 0 . 5 1 1 . 0 1 1 . 5 f 1 ( p p m ) 3 . 0 9 1 . 0 0 0 . 9 6 3 . 3 3 1 . 1 2 2 . 9 9 1 . 0 4 2 . 2 4 1 . 9 7 - 1 0 0 1 0 2 0 3 0 4 0 5 0 6 0 7 0 8 0 9 0 1 0 0 1 1 0 1 2 0 1 3 0 1 4 0 1 5 0 1 6 0 1 7 0 1 8 0 1 9 0 2 0 0 2 1 0 2 2 0 2 3 0 f 1 ( p p m ) 177 Figure 8.5.7. 19 F NMR spectrum of complex 5.4 at 25 °C in CDCl3. Figure 8.5.8. IR spectrum of complex 5.4. - 2 0 0 - 1 9 0 - 1 8 0 - 1 7 0 - 1 6 0 - 1 5 0 - 1 4 0 - 1 3 0 - 1 2 0 - 1 1 0 - 1 0 0 - 9 0 - 8 0 - 7 0 - 6 0 - 5 0 - 4 0 - 3 0 - 2 0 - 1 0 0 1 0 2 0 3 0 f 1 ( p p m ) 178 Naphthalen-1-yldi(pyridin-2-yl)methanol 5.13 2-Iodopyridine (0.4 mL, 3.07 mmol, 2.4 equiv.) was added to a previously flame dried 250 mL flask with a magnetic stir bar inside of the glove box, followed by the addition of 60 mL of dry DCM. The flask was sealed with a rubber stopper and taken outside of the glove box, later to be connected to the nitrogen line. A 3 M solution of EtMgBr in diethyl ether (1.03 mL, 3.07 mmol, 2.4 equiv.) in a syringe with a needle was added dropwise to the stirring DCM solution of 2- iodopyridine through the rubber stopper and left for 45 minutes. A solution of methyl 1-naphthoate (239 mg, 1.28 mmol, 1 equiv.) in 5 mL of dry DCM was added dropwise in the same way and left for 16 hours. The reaction solution was washed with saturated NaHCO3 solution of 30 mL, which was then extracted twice with DCM (2 ´ 15 mL). Combined DCM fractions were dried over MgSO4, treated with activated charcoal, filtered through Celite pad and evaporated. Obtained yellow oil underwent recrystallization from boiling diethyl ether resulting in white crystals (162 mg, 0.512 mmol, 40%) that were analyzed by NMR and proved to be spectroscopically pure. Due to the limited stability 5.13 was characterized only by 1 H NMR and used for the preparation of 5.14 and 5.5 right after the recrystallization. N N OH O O 5.12 N I , EtMgBr DCM, 16 h, RT, 40% 5.13 179 1 H NMR (400 MHz, Chloroform-d) δ 8.56 (ddd, J = 4.9, 1.8, 1.0 Hz, 2H), 7.88 (dq, J = 8.7, 0.9 Hz, 1H), 7.82 – 7.76 (m, 2H), 7.74 – 7.66 (m, 4H), 7.35 (ddd, J = 8.1, 6.8, 1.2 Hz, 1H), 7.25 (d, J = 0.9 Hz, 1H), 7.23 – 7.19 (m, 3H), 6.99 (d, J = 1.1 Hz, 1H), 6.75 (dd, J = 7.3, 1.2 Hz, 1H). Figure 8.5.9. 1 H NMR spectrum of ligand 5.13 at 25 °C in CDCl3. 2,2'-(Methoxy(naphthalen-1-yl)methylene)dipyridine 5.14 0 . 5 1 . 0 1 . 5 2 . 0 2 . 5 3 . 0 3 . 5 4 . 0 4 . 5 5 . 0 5 . 5 6 . 0 6 . 5 7 . 0 7 . 5 8 . 0 8 . 5 9 . 0 9 . 5 f 1 ( p p m ) P R O T O N _ 0 1 I D _ 1 6 4 _ p o s t _ r e c r y s t 1 . 0 3 1 . 0 0 3 . 1 9 1 . 1 9 1 . 0 3 4 . 1 4 2 . 0 5 1 . 0 3 2 . 0 0 N N OH 5.13 THF, 18 h, RT, 99% CH 3 I, NaH N N O 5.14 180 In the glovebox under nitrogen, naphthalen-1-yldi(pyridin-2-yl)methanol 5.13 (50 mg, 0.16 mmol, 1 equiv) and sodium hydride (15 mg, 0.64 mmol, 4 equiv) were mixed together in an 8 dram vial with a previously-placed magnetic stir bar. CH3I (40 µL, 0.64 mmol, 4 equiv.) was added to 3 mL of THF and this solution was transferred to the vial. The stirring solution was left for 18 hours and then slowly quenched with 20 mL of saturated NaHCO3 outside of the glove box. The resulting solution was extracted with DCM (3 ´ 15 mL) and fractions were combined, dried over MgSO4 and evaporated. Resulting grey powder (52 mg, 0.16 mmol, 99%) appeared to be spectroscopically pure under NMR. Due to the limited stability 5.14 was characterized only by 1 H NMR and used for the preparation of 5.6 right after the isolation. 1 H NMR (400 MHz, Chloroform-d) δ 8.56 (ddt, J = 4.8, 1.8, 0.9 Hz, 2H), 7.93 (dt, J = 8.8, 0.9 Hz, 1H), 7.86 – 7.79 (m, 2H), 7.68 – 7.57 (m, 5H), 7.41 (ddd, J = 8.1, 7.2, 0.7 Hz, 1H), 7.38 – 7.31 (m, 1H), 7.21 – 7.14 (m, 1H), 7.09 (dddd, J = 7.2, 4.9, 1.5, 0.8 Hz, 2H), 3.29 (d, J = 0.7 Hz, 3H). 181 Figure 8.5.10. 1 H NMR spectrum of ligand 5.14 at 25 °C in CDCl3. Complex 5.5 In the glovebox under nitrogen, in a 8 dram vial with a magnetic stir bar, chloro(1,5- cyclooctadiene)iridium(I) dimer (20.0 mg, 0.030 mmol, 1 equiv.) and naphthalen-1-yldi(pyridin- 2-yl)methanol 5.13 (20 mg, 0.064 mmol, 2.1 equiv.) were dissolved in 2 mL of DCM and left 0 . 0 0 . 5 1 . 0 1 . 5 2 . 0 2 . 5 3 . 0 3 . 5 4 . 0 4 . 5 5 . 0 5 . 5 6 . 0 6 . 5 7 . 0 7 . 5 8 . 0 8 . 5 9 . 0 9 . 5 1 0 . 0 f 1 ( p p m ) P R O T O N _ 0 1 I D _ 1 6 7 3 . 1 4 2 . 0 8 1 . 0 8 1 . 0 7 1 . 0 9 5 . 1 7 2 . 1 5 1 . 0 1 2 . 0 0 1 . 8 5 3 . 7 4 N N OH Ir OTf 5.5 N N OH 5.13 DCM, RT, 95% 1. [Ir(COD)Cl] 2 , 18h 2. NaOTf, 1h 182 stirring for 18 hours. After this, sodium trifluoromethanesulfonate (15 mg, 0.087 mmol, 2.9 equiv.) was also added to the mixture and left for 1 hour more. After stirring for 1 hour, the solution was filtered through a Teflon syringe filter to remove the sodium chloride byproduct. The solvent was evaporated under reduced pressure and yielded a yellow glassy solid. This yellow solid was dissolved in 0.4 mL of dry DCM, then slowly added, to 20 mL of hexanes, leading to precipitation of 5.5. A yellow crystalline solid was acquired and dried under vacuum (44 mg, 0.058 mmol, 95%). This sample was later determined to be spectroscopically pure under NMR. 1 H NMR (500 MHz, Methylene Chloride-d2) δ 8.94 (s, 1H), 8.47 (s, 1H), 8.40 (s, 1H), 8.25 (s, 1H), 8.14 (t, J = 7.9 Hz, 2H), 8.02 (d, J = 8.5 Hz, 1H), 7.88 – 7.79 (m, 1H), 7.53 – 7.36 (m, 4H), 7.31 – 7.19 (m, 2H), 6.75 (dt, J = 7.0, 0.9 Hz, 1H), 5.87 (s, 1H), 3.80 (s, 1H), 3.55 (d, J = 42.4 Hz, 2H), 2.42 (s, 2H), 2.13 (d, J = 46.4 Hz, 1H), 1.82 (s, 4H), 1.54 (d, J = 2.7 Hz, 1H), 1.25 – 1.12 (m, 1H). 13 C NMR (101 MHz, Methylene Chloride-d2) δ 146.82, 140.93, 134.62, 130.96, 130.51, 128.88, 127.21, 126.93, 126.52, 125.92, 124.02, 121.54, 109.37, 85.42, 80.76, 63.39, 33.36, 31.55, 29.21, 22.62, 13.84. 19 F NMR (376 MHz, Methylene Chloride-d2) δ -78.94. FTIR ν 3280.32, 2950.07, 2913.91, 2869.56, 2840.63, 1602.07, 1506.13, 1462.26, 1442.98, 1397.17, 1326.79, 1246.27, 1222.65, 1154.19, 1087.66, 1069.33, 1027.87, 912.647, 896.737, 835.508, 801.76, 771.387, 701.48, 666.767, 633.019, 571.79, 550.095, 515.383, 493.205, 487.42, 470.546 MS (MALDI) calculated for [C29H28IrN2O] + 613.18, found 612.61. 183 Figure 8.5.11. 1 H NMR spectrum of complex 5.5 at 25 °C in CD2Cl2. Figure 8.5.12. 13 C NMR spectrum of complex 5.5 at 25 °C in CD2Cl2. 0 . 0 0 . 5 1 . 0 1 . 5 2 . 0 2 . 5 3 . 0 3 . 5 4 . 0 4 . 5 5 . 0 5 . 5 6 . 0 6 . 5 7 . 0 7 . 5 8 . 0 8 . 5 9 . 0 9 . 5 f 1 ( p p m ) P R O T O N _ 0 1 I D _ 1 6 8 1 . 2 5 1 . 0 7 3 . 7 3 1 . 0 5 2 . 1 1 1 . 9 4 0 . 9 0 0 . 9 4 0 . 9 7 2 . 1 6 4 . 0 0 1 . 0 6 1 . 0 6 2 . 0 4 0 . 9 0 1 . 0 3 1 . 0 3 0 . 8 7 1 0 2 0 3 0 4 0 5 0 6 0 7 0 8 0 9 0 1 0 0 1 1 0 1 2 0 1 3 0 1 4 0 1 5 0 1 6 0 1 7 0 f 1 ( p p m ) 184 Figure 8.5.13. 19 F NMR spectrum of complex 5.5 at 25 °C in CD2Cl2. Figure 8.5.14. IR spectrum of complex 5.5. - 2 0 0 - 1 9 0 - 1 8 0 - 1 7 0 - 1 6 0 - 1 5 0 - 1 4 0 - 1 3 0 - 1 2 0 - 1 1 0 - 1 0 0 - 9 0 - 8 0 - 7 0 - 6 0 - 5 0 - 4 0 - 3 0 - 2 0 - 1 0 0 1 0 2 0 3 0 f 1 ( p p m ) - 7 8 . 9 4 185 Complex 5.6 Complex 5.6 was prepared by following an analogous procedure to that described above for complex 5.5. In the glovebox under nitrogen, in a 8 dram vial with magnetic stir bar, chloro(1,5- cyclooctadiene)Iridium(I) dimer (19.0 mg, 0.028 mmol, 1 equiv.) and 2,2'-(methoxy(naphthalen- 1-yl)methylene)dipyridine 5.14 (20 mg, 0.061 mmol, 2.2 equiv.) were dissolved in 2 mL of DCM and left stirring for 18 hours. Sodium trifluoromethanesulfonate (15 mg, 0.087 mmol, 2.9 equiv.) was later added to the mixture and left for 1 hour. After stirring, the solution was filtered through a Teflon syringe filter to remove the sodium chloride byproduct. The solvent was evaporated under reduced pressure and yielded in a yellow glassy solid. This yellow solid was dissolved in 0.4 mL of dry DCM, then added slowly, dropwise, to 20 mL of hexanes, leading to precipitation of 5.6. A yellow crystalline solid was acquired and dried under vacuum (42 mg, 0.054 mmol, 97%). This sample was later determined to be spectroscopically pure under NMR. 1 H NMR (600 MHz, Methylene Chloride-d2) δ 9.06 (d, J = 5.4 Hz, 1H), 8.21 (d, J = 5.8 Hz, 1H), 8.12 (q, J = 8.8, 7.7 Hz, 3H), 7.99 (d, J = 8.7 Hz, 1H), 7.95 (d, J = 8.1 Hz, 1H), 7.77 (dd, J = 8.1, 1.0 Hz, 1H), 7.47 (d, J = 6.6 Hz, 2H), 7.41 (ddd, J = 8.1, 6.5, 1.6 Hz, 1H), 7.34 (dd, J = 8.7, 6.7 Hz, 1H), 7.25 – 7.18 (m, 2H), 6.44 (dd, J = 6.6, 0.9 Hz, 1H), 3.91 (s, 1H), 3.75 (s, 1H), 3.46 (s, N N O 5.14 DCM, RT, 97% 1. [Ir(COD)Cl] 2 , 18h 2. NaOTf, 1h N N O Ir OTf 5.6 186 1H), 2.88 (s, 3H), 2.51 (d, J = 8.7 Hz, 1H), 2.45 (s, 1H), 2.34 (s, 1H), 2.11 (d, J = 11.6 Hz, 1H), 1.98 (d, J = 15.3 Hz, 1H), 1.92 (s, 2H), 1.32 (dt, J = 12.6, 6.8 Hz, 2H). 13 C NMR (101 MHz, Methylene Chloride-d2) δ 152.45, 147.15, 133.70, 131.02, 130.60, 128.73, 127.80, 127.43, 127.15, 124.99, 124.43, 123.76, 123.32, 104.88, 96.52, 61.51, 52.01, 33.80, 31.54, 28.96, 22.61, 13.83. 19 F NMR (376 MHz, Methylene Chloride-d2) δ -78.94. FTIR ν 3847.29, 3578.27, 3496.31, 3082.65, 2951.04, 2871.49, 2838.22, 1601.59, 1458.89, 1445.87, 1259.29, 1221.2, 1145.99, 1086.21, 1053.91, 1027.87, 988.821, 891.916, 805.135, 768.494, 632.055, 574.683, 549.131, 514.901, 485.492 MS (MALDI) calculated for [C30H30IrN2O] + 627.20, found 626.79. Figure 8.5.15. 1 H NMR spectrum of complex 5.6 at 25 °C in CD2Cl2. 0 . 5 1 .0 1 .5 2 .0 2 . 5 3 . 0 3 . 5 4 . 0 4 . 5 5 . 0 5 . 5 6 . 0 6 . 5 7 . 0 7 . 5 8 . 0 8 . 5 9 . 0 9 . 5 1 0 . 0 1 0 . 5 f 1 ( p p m ) 2 . 2 6 2 . 0 9 1 . 1 8 1 . 0 9 1 . 1 8 1 . 2 9 1 . 1 7 3 . 3 2 1 . 0 4 1 . 0 8 1 . 0 5 1 . 0 0 2 . 0 8 1 . 1 6 0 . 9 9 1 . 9 3 1 . 0 4 0 . 9 8 1 . 1 2 3 . 0 0 1 . 1 0 1 . 1 3 187 Figure 8.5.16. 13 C NMR spectrum of complex 5.6 at 25 °C in CD2Cl2. Figure 8.5.17. 19 F NMR spectrum of complex 5.6 at 25 °C in CD2Cl2. 1 0 2 0 3 0 4 0 5 0 6 0 7 0 8 0 9 0 1 0 0 1 1 0 1 2 0 1 3 0 1 4 0 1 5 0 1 6 0 1 7 0 1 8 0 1 9 0 2 0 0 2 1 0 f 1 ( p p m ) - 2 0 0 - 1 9 0 - 1 8 0 - 1 7 0 - 1 6 0 - 1 5 0 - 1 4 0 - 1 3 0 - 1 2 0 - 1 1 0 - 1 0 0 - 9 0 - 8 0 - 7 0 - 6 0 - 5 0 - 4 0 - 3 0 - 2 0 - 1 0 0 1 0 2 0 3 0 f 1 ( p p m ) - 7 8 . 9 4 188 Figure 8.5.18. IR spectrum of complex 5.6. 189 8.5.2. Spectral Data Figure 8.5.19. Absorption spectra of complex 5.2 in different solvents. Figure 8.5.20. Absorption spectra of complex 5.2 and it’s methyl homolog in formic acid. 190 8.6. Chapter 6 Experimental and Spectral Data 8.6.1. Synthesis Procedures and Characterization Data Complex 6.1 In the glovebox under nitrogen, in a 100 mL in a Schlenk flask, dichloro-di(1-methyl-3-(2- picolyl)-imidazol-2-ylidene)-disilver(I) (89.5 mg, 0.141 mmol) was added in small portions to a stirring solution of chloro(1,5-cyclooctadiene)Iridium(I) dimer (95.0 mg, 0.141 mmol) in 20 mL dry dichloromethane. After 30 minutes, sodium trifluoromethanesulfonate (49 mg, 0.285 mmol) was also added to the mixture. After stirring for another 30 minutes, the solution was filtered through a dry pad of celite to remove the sodium chloride byproduct. The solvent was evaporated under reduced pressure to yield a red glassy solid. This red solid was dissolved in 5 mL dry dichloromethane, and 10 mL dry hexanes was slowly added to the solution to facilitate a precipitation. A red crystalline solid was acquired and dried under vacuum (150 mg, 85%). This sample was later determined to be spectroscopically pure under NMR. Slow recrystallization from dichloromethane and hexanes produced crystals suitable for X-ray crystallography. 6.1 is mildly air-sensitive and is stored under N2. N Ir N N OTf N N N Ag Cl Cl N N N Ag 1. [Ir(COD)Cl] 2 2. NaOTf DCM, 85% 6.1 191 1 H NMR (600 MHz, methylene chloride-d2) δ 8.55 (d, J = 5.2 Hz, py 1H), 7.79 (t, J = 7.7 Hz, py 1H), 7.64 (d, J = 7.9 Hz, py 1H), 7.33 (t, J = 6.4 Hz, py 1H), 7.14 (d, J = 2.0 Hz, imi 1H), 6.89 (d, J = 2.0 Hz, imi 1H), 5.74 (d, J = 15.0 Hz, methylene 1H), 5.56 (d, J = 14.8 Hz, methylene 1H), 4.48 (s, COD sp 2 1H), 4.28 (s, COD sp 2 1H), 3.89 (s, imi-methyl 3H), 3.48 (s, COD sp 2 1H), 3.29 (s, COD sp 2 1H), 2.33 (s, COD sp 3 2H), 2.14 (s, COD sp 3 2H), 1.81 (s, COD sp 3 3H), 1.61 (s, COD sp 3 1H). 13 C NMR (151 MHz, methylene chloride-d2) δ 174.54, 153.26, 151.42, 140.12, 137.58, 126.40, 123.16, 122.31, 79.57, 75.42, 65.59, 58.86, 55.30, 37.87, 33.38, 33.24, 30.14, 29.77. 19 F NMR (470 MHz, methylene chloride-d2) δ -79.41. MS (MALDI) calc’d for [C18H23IrN3] + 474.2, found 473.9. Figure 8.6.1. 1 H NMR spectrum of complex 6.1 at 25 °C in CD2Cl2. 192 Figure 8.6.2. 13 C NMR spectrum of complex 6.1 at 25 °C in CD2Cl2. Figure 8.6.3. 19 F NMR spectrum of complex 6.1 at 25 °C in CD2Cl2. 193 Complex 6.2 In the glovebox under nitrogen, in a 100 mL in a Schlenk flask, dichloro-di(1-(2,4,6- trimethylphenyl)-3-(2-picolyl)-imidazol-2-ylidene)-disilver(I) 28 (251 mg, 0.298 mmol) was added in small portions to a stirring solution of chloro(1,5-cyclooctadiene)Iridium(I) dimer (200.0 mg, 0.298 mmol) in 20 mL dry acetonitrile. After 30 minutes, sodium trifluoromethanesulfonate (102.5 mg, 0.596 mmol) was also added to the mixture. After stirring for another 30 minutes, the solution was filtered through a dry pad of celite to remove the sodium chloride byproduct. The solvent was evaporated under reduced pressure to yield a red glassy solid. This red solid was dissolved in 10 mL dry dichloromethane, and 20 mL dry hexanes was added to the solution to facilitate a precipitation. A red crystalline solid was acquired and dried under vacuum (400 mg, 93%). This sample was later determined to be spectroscopically pure under NMR. Slow recrystallization from dichloromethane and hexanes produced crystals suitable for X-ray crystallography. 1 H NMR (600 MHz, methylene chloride-d2) δ 8.50 (ddd, J = 7.7, 1.6, 0.8 Hz, py 1H), 8.08 (ddd, J = 7.8, 1.6, 0.7 Hz, py 1H), 8.01 (td, J = 7.7, 1.5 Hz, py 1H), 7.70 (d, J = 1.9 Hz, imi 1H), 7.48 (ddd, J = 7.4, 5.6, 1.5 Hz, py 1H), 7.04 (s, mesityl-ar 1H), 7.00 (s, mesityl-ar 1H), 6.88 (d, J = 1.9 Hz, imi 1H), 5.77 (s, methylene 1H), 5.74 (s, methylene 1H), 4.15 (s, COD sp 2 1H), 4.07 (s, COD sp 2 1H), 3.92 (s, COD sp 2 1H), 3.21 (s, COD sp 2 1H), 2.37 (s, mesityl-para-methyl 3H), 2.25-1.85 N Ir N N Mes OTf N N N Mes Ag Cl Cl N N N Mes Ag 1. [Ir(COD)Cl] 2 2. NaOTf CH 3 CN, 95% 6.2 194 (m, COD sp 3 6H), 2.06 (s, mesityl-ortho-methyl 3H), 1.90 (s, mesityl-ortho-methyl 3H), 1.63 (s, COD sp 3 1H) 1.47 (s, COD sp 3 1H). 13 C NMR (151 MHz, methylene chloride-d2) δ 174.64, 153.38, 151.40, 140.51, 140.16, 135.32, 129.68, 129.46, 126.88, 126,74, 123.51, 122.54, 86.04, 82.80, 66.08, 64.43, 55,34, 34.99, 31.89, 31.44, 28.17, 21.23, 19.13, 17.94. 19 F NMR (470 MHz, methylene chloride-d2) δ -79.43. Elemental Analysis (CHNS) calc’d for C27H31F3IrN3O3S: C, 44.62; H, 4.30; N, 5.78; S, 4.41. Found: C, 44.55; H, 4.24; N, 5.84; S, 4.24. IR (thin film/cm -1 ) ν 3584, 3441, 2918, 2849, 2362, 1734, 1608, 1444, 1411, 1263, 1223, 1070, 1030, 853, 804, 636, 628. MS (MALDI) calc’d for [C26H31IrN3] + 578.2, found 577.9. Figure 8.6.4. 1 H NMR spectrum of complex 6.2 at 25 °C in CD2Cl2. 195 Figure 8.6.5. 13 C NMR spectrum of complex 6.2 at 25 °C in CD2Cl2. Figure 8.6.6. 19 F NMR spectrum of complex 6.2 at 25 °C in CD2Cl2. 196 From soybean oil to FAMEs and glycerol In a typical reaction soybean oil (100 mL, 93 g) is added to a stirring solution of dilute NaOMe (20 mg) in dry methanol (100 mL) under nitrogen. The mixture is heated in a water bath set to 50 °C for 5 hours. After stirring is stopped and the mixture is returned to room temperature, the reaction mixture settles to two layers. On the top is the SoyFAME layer, in it ca. 100 mL of biodiesel material. The bottom is a methanol solution of glycerol, which was subsequently concentrated by rotary evaporation, then dried on a lyophilizer overnight, and finally on a high- vacuum Schlenk line to afford 9.3 g of NMR pure (> 95%) glycerol. We believe that the glycerol is mostly free of methanol or water. Figure 8.6.7. 1 H-NMR spectrum of the glycerol isolated from a transesterification product of Wesson soybean oil. 197 From glycerol to lactic acid Iridium catalyst 9 (5.8 mg, 140 ppm to glycerol) and NaOH (4.0 g, 1.0 eq. to glycerol), are weighed in air and added to a round bottom flask equipped with a magnetic stir bar. Glycerol (9.3 g from soybean oil, above) is added to the same flask. The flask then is connected to a short path distilling head, which has an 8 mm Tygon tubing gas outlet put in a water eudiometer. The flask is then placed in an oil bath set to 145 °C, and the reaction progress is monitored by eudiometry and 1 H-NMR. A snapshot of the reaction mixture is taken in 1 H-NMR, which shows well-controlled selectivity for lactate. Figure 8.6.8. A snapshot of reaction mixture after 3 days. H2O (solvent) glycerol lactate } 198 After 7 days, eudiometry shows that the reaction has ca. 90% conversion. The reaction flask was cooled to room temperature. 1 H NMR shows only lactate product and a small amount of glycerol. Figure 8.6.9. 1 H NMR of reaction mixture after 7 days, at 90% conversion. The solvent is D2O. We find that using NaOH instead of KOH yielded much more soluble solid at the end of the reaction, which enabled a much facile isolation of lactic acid. Accordingly, conc. hydrochloric acid (1 M, 70 mL) was added the reaction flask until the pH was < 1, then the solution was extracted with ethyl acetate (25 mL × 5). The organic solvent was evaporated under a constant flow of air, a colorless liquid left at the bottom of the flask was identified as NMR pure lactic acid (5.6 g, 61.5%). lactate } glycerol 199 Figure 8.6.10. 1 H NMR of isolated lactic acid in D2O. Lactide synthesis The reactions for lactic acid to lactide conversion are based on known procedures. 29,30 From lactic acid to polylactic acid oligomers In a typical run, 2.50 g of lactic acid obtained from the previously described extractions is weighed in air and added to a round bottom flask equipped with a magnetic stirring bar. The flask is connected to a Dean-Stark trap with the condenser on top of it. The flask is then placed in a wax bath set to 210 °C. The reaction is carried out under nitrogen for 6 hours. 200 Figure 8.6.11. 1 H NMR of polylactic acid oligomer in DMSO-d6. Figure 8.6.12. 1 H NMR “zoom-in” on "methine" region of the polylactic acid oligomer. 201 Lactide formation In a typical run, 1.0 wt % of SnO (25 mg, 0.186 mmol) is added to the flask containing our synthetic lactic acid oligomers (2.5 g). The flask is equipped with distillation apparatus, and the receiving flask is placed into an oil bath set to 80 °C. The reaction flask is placed in a wax bath set to 210 °C and is stirred for 3 hours. During this time, lactide mixture condensed in the receiving flask. This lactide mixture is dissolved in ethyl acetate (3 mL) and washed with 2 × 3 mL ethyl acetate, then transferred into a 50 mL beaker. The beaker is stored at -15 °C for 72 h. White crystals of rac-lactide recrystallized from the solution is filtrated, dried, weighted and analyzed by 1 H- NMR (0.69 g, 69% yield). The rac-lactide is > 90% pure by 1 H-NMR. Figure 8.6.13. 1 H NMR of rac-lactide in DMSO-d6. 202 8.7. Chapter 7 Experimental and Spectral Data Compound 7.10 Tri-tert-butyl 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetate (DOTA-tri-t-Bu-ester) (100 mg, 0.175 mmol) and 1-[Bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxid hexafluorophosphate (HATU) (73 mg, 0.192 mmol) were dissolved in 1.5 mL of CH3CN. Propargyl amine (15 mg, 0.272 mmol) was added after. After stirring for 5 minutes at room temperature white solid precipitated (apparently HOAt) and reaction reached full conversion (monitored by MALDI). Acetonitrile was removed by rotoevaporation and 10 mL of DCM were added to the residue and then washed five times with 7 mL of water each time. The organic layer was dried over MgSO4 and solvent was evaporated to yield a yellow viscous oil (101 mg, 95%). This sample appeared to be spectroscopically clean based on NMR. The results matched previously reported spectra for the assigned compound. 31 1 H NMR (600 MHz, Methylene Chloride-d2) δ 7.15 (s, 1H), 4.01 (s, 2H), 3.63 (s, 4H), 3.48 (s, 4H), 3.05 (s, 8H), 2.96 (s, 8H), 2.76 (s, 8H), 2.26 (s, 1H), 1.47 (d, J = 7.2 Hz, 27H). 13 C NMR (151 MHz, Methylene Chloride-d2) δ 169.37, 82.70, 82.40, 71.00, 56.22, 55.73, 52.13, 51.93, 38.33, 31.52, 28.85, 27.77, 27.75, 13.82. MS (MALDI) calc’d for [C31H55N5O7] 609.4, found 609.7. HO N N N N O O O O O O O HN N N N N O O O O O O O 7.4 7.10 HATU, 25 o C, RT 5 min. in CH 3 CN 95% NH 2 203 Figure 8.7.1. 1 H NMR spectrum of complex 7.10 at 25 °C in CD2Cl2. Figure 8.7.2. 13 C NMR spectrum of complex 7.10 at 25 °C in CD2Cl2. 0 . 5 1 . 0 1 . 5 2 . 0 2 . 5 3 . 0 3 . 5 4 . 0 4 . 5 5 . 0 5 . 5 6 . 0 6 . 5 7 . 0 7 . 5 8 . 0 8 . 5 9 . 0 9 . 5 f 1 ( p p m ) 2 7 . 0 6 0 . 8 9 8 . 1 9 8 . 1 2 8 . 2 6 4 . 0 9 4 . 0 7 2 . 3 0 1 . 0 0 1 . 4 6 1 . 4 8 2 . 2 6 2 . 7 6 2 . 9 6 3 . 0 5 3 . 4 8 3 . 6 3 4 . 0 1 5 . 3 3 7 . 1 5 - 1 0 0 1 0 2 0 3 0 4 0 5 0 6 0 7 0 8 0 9 0 1 0 0 1 1 0 1 2 0 1 3 0 1 4 0 1 5 0 1 6 0 1 7 0 1 8 0 1 9 0 2 0 0 2 1 0 2 2 0 2 3 0 f 1 ( p p m ) 204 Compound 7.13 Propargyl DOTA-tri-ester 7.10 (101 mg, 0.166 mmol) was dissolved in 2.0 mL of 1:1 DCM/TFA mixture and refluxed at 74 °C for 1 hour. TFA and remaining DCM were removed under reduced pressure using a Shlenk line with a liquid nitrogen trap. Resulting brown viscous oil (72 mg, 0.163 mmol, 99%) was analyzed by MALDI and appeared to be fully a deprotected product. This sample appeared to be spectroscopically clean based on NMR. The results matched previously reported spectra for the assigned compound. 31 1 H NMR (600 MHz, Methylene Chloride-d2) δ 4.49 – 3.21 (m, 25H), 3.08 (s, 6H). 13 C NMR (151 MHz, Methylene Chloride-d2) δ 169.55, 169.12, 82.34, 56.08 (d, J = 61.8 Hz), 51.90, 50.27, 38.33, 28.86, 27.78. MS (MALDI) calc’d for [C19H31N5O7] 441.2, found 442.3. HN N N N N O O O O O O O 7.10 HN N N N N O OH O OH O O HO 7.13 1h, 74 o C, 99% TFA/DCM 1:1 205 Figure 8.7.3. 1 H NMR spectrum of complex 7.13 at 25 °C in CD2Cl2. Figure 8.7.4. 13 C NMR spectrum of complex 7.13 at 25 °C in CD2Cl2. - 2 - 1 0 1 2 3 4 5 6 7 8 9 1 0 1 1 1 2 1 3 1 4 f 1 ( p p m ) 6 . 0 0 2 5 . 3 9 - 1 0 0 1 0 2 0 3 0 4 0 5 0 6 0 7 0 8 0 9 0 1 0 0 1 1 0 1 2 0 1 3 0 1 4 0 1 5 0 1 6 0 1 7 0 1 8 0 1 9 0 2 0 0 2 1 0 2 2 0 2 3 0 f 1 ( p p m ) 206 Compound 7.3. 5 mL of water were added to propargyl DOTA 7.11 (72 mg, 0.163 mmol) and stirred for 30 minutes. Gadolinium(III) chloride hexahydrate (73 mg, 0.196 mmol) was dissolved in 2.0 mL of water and added to previously made propargyl DOTA solution. pH was adjusted to 6.16 and mixture was stirred for 6h at 70 °C. After this, the mixture was cooled down to room temperature with the following pH adjustment to 11.00. Solid particles were filtrated using VWR sterile syringe filter (0.45 µm PES) and solution of 10 mL was transferred into cellulose ester membrane tube (Mw cutoff 500 D, Spectra/Por dialysis membrane Biotech CE) and placed in 2 L beaker filled with DI water, which was changed 5 times every two hours and then left overnight. The solution from the tube was lyophilized resulting to (79 mg, 0.132 mmol, 81%). The result matched previously reported mass spectra for the assigned compound. 31 MS (MALDI) calc’d for [C19H28GdN5O7] 596.1, found 596.9. HN N N N N O O O O O O O 7.3 HN N N N N O OH O OH O O HO 7.13 34h, RT, 81% GdCl 3 . 6H 2 O Gd 207 Compound 7.8 Tri-tert-butyl 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetate (DOTA-tri-t-Bu-ester) (100 mg, 0.175 mmol) and 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxid hexafluorophosphate (HATU) (73 mg, 0.192 mmol) were dissolved in 1.5 mL of CH3CN. 4-(((Tert-butyldimethylsilyl)oxy)methyl)aniline (65 mg, 0.272 mmol) was added after. After stirring for 24 hours at 50 o C white solid of HOAt precipitated and reaction reached full conversion (monitored by MALDI). Acetonitrile was removed by rotoevaporation and 10 mL of DCM were added to the residue and then washed five times with 7 mL of water each time. The organic layer was dried over MgSO4 and solvent was evaporated to yield a yellow viscous oil which was further purified by reversed phase chromatography with H2O/MeOH solvents system (61 mg, 0.077 mmol, 40%). Due to the instability 7.8 was analyzed by MALDI only and used for the preparation of 7.11 right after the isolation. MS (MALDI) calc’d for [C41H73N5O8Si] 791.5, found 792.2. HO N N N N O O O O O O O NH N N N N O O O O O O O 7.4 7.8 HATU, 50 o C, 24 h. in CH 3 CN 40% NH 2 OTBDMS TBDMSO ; TBDMS = Si 208 Compound 7.11 To compound 7.8 (61 mg, 0.077 mmol) was added 2.0 mL 9M H2SO4 and heated at 75 °C for 1 hour. After this, the reaction mixture was analyzed by MALDI and appeared to contain fully a deprotected product. pH was adjusted to 6.16 and mixture was used in the next step without any further purification. MS (MALDI) calc’d for [C23H35N5O8] 509.3, found 510.1. Compound 7.1 NH N N N N O O O O O O O 7.8 TBDMSO 1h, 75 o C, 9 M H 2 SO 4 NH N N N N O OH O OH O O HO 7.11 HO NH N N N N O OH O OH O O HO 7.11 HO 34h, RT, 74% GdCl 3 . 6H 2 O NH N N N N O O O O O O O 7.1 HO Gd 209 3 mL of water was added to the solution from the previous step containing 0.077 mmol of 7.11. Gadolinium(III) chloride hexahydrate (34 mg, 0.092 mmol) was dissolved in 2.0 mL of water and added to 7.11 solution. pH was readjusted to 6.16 and the mixture was stirred for 6h at 70°C. After this, the mixture was cooled down to room temperature with thefollowing pH adjustment to 11.00. Solid particles were filtrated using VWR sterile syringe filter (0.45 µm PES) and solution of 10 mL was transferred into cellulose ester membrane tube (Mw cutoff 500 D, Spectra/Por dialysis membrane Biotech CE) and placed in 2 L beaker filled with DI waster, which was changed 5 times every two hours and then left overnight. The solution from the tube was lyophilized resulting to (38 mg, 0.057 mmol, 74%). Due to the instability and paramagnetic nature 7.1 was analyzed by MALDI only. MS (MALDI) calc’d for [C23H34GdN5O8] 2+ 666.1, found 666.5. Compound 7.2. Compound 7.2 was synthesized in an analogous manner to its isomer Compound 7.1 delivering comparable conversion and was only monitored by MALDI. Compound 7.2 was not isolated by the dialysis procedure. 210 8.8. X-ray Crystallography Data We gratefully acknowledge Prof. Ralf Haiges for helping us with X-ray data acquisition and solving the solid-state structures. CDCC #1895674 (2.1), # 1895677 (2.2’), # 1895676 (3.6), #1875215 (4.1), and #1875216 (4.12), contain supplementary crystallographic data for this thesis. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif. Crystal structure of 2.1 Figure 8.8.1. X-Ray structure of complex 2.1. 211 A orange prism-like specimen of C23H28ClIrN2O2S, approximate dimensions 0.138 mm x 0.220 mm x 0.421 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). The total exposure time was 1.40 hours. The frames were integrated with the Bruker SAINT software package using a SAINT V8.38A (Bruker AXS, 2013) algorithm. The integration of the data using an orthorhombic unit cell yielded a total of 105011 reflections to a maximum θ angle of 30.60° (0.70 Å resolution), of which 6852 were independent (average redundancy 15.326, completeness = 99.7%, Rint = 5.69%, Rsig = 2.28%) and 5325 (77.71%) were greater than 2σ(F 2 ). The final cell constants of a = 8.5457(15) Å, b = 19.012(5) Å, c = 27.515(6) Å, volume = 4470.4(17) Å 3 , are based upon the refinement of the XYZ-centroids of 9970 reflections above 20 σ(I) with 4.527° < 2θ < 60.90°. Data were corrected for absorption effects using the multi-scan method (SADABS). The ratio of minimum to maximum apparent transmission was 0.653. The calculated minimum and maximum transmission coefficients (based on crystal size) are 0.4875 and 0.7461. The structure was solved and refined using the Bruker SHELXTL Software Package, using the space group P b c a, with Z = 8 for the formula unit, C23H28ClIrN2O2S. The final anisotropic full-matrix least-squares refinement on F 2 with 277 variables converged at R1 = 2.62%, for the observed data and wR2 = 5.62% for all data. The goodness-of-fit was 1.099. The largest peak in the final difference electron density synthesis was 1.384 e - /Å 3 and the largest hole was -1.406 e - /Å 3 with an RMS deviation of 0.122 e - /Å 3 . On the basis of the final model, the calculated density was 1.855g/cm 3 and F(000), 2448 e - . 212 Table 1. Sample and crystal data for Complex 2.1. Identification code Complex 2.1 Chemical formula C23H28ClIrN2O2S Formula weight 624.18 g/mol Temperature 100(2) K Wavelength 0.71073 Å Crystal size 0.138 x 0.220 x 0.421 mm Crystal habit orange prism Crystal system orthorhombic Space group P b c a Unit cell dimensions a = 8.5457(15) Å α = 90° b = 19.012(5) Å β = 90° c = 27.515(6) Å γ = 90° Volume 4470.4(17) Å 3 Z 8 Density (calculated) 1.855 g/cm 3 Absorption coefficient 6.209 mm -1 F(000) 2448 Table 2. Data collection and structure refinement for Complex 2.1. Diffractometer Bruker APEX DUO Radiation source fine-focus tube, MoKα Theta range for data collection 1.48 to 30.60° Index ranges -12<=h<=12, -26<=k<=27, -39<=l<=39 Reflections collected 105011 Independent reflections 6852 [R(int) = 0.0569] 213 Coverage of independent reflections 99.7% Absorption correction multi-scan Max. and min. transmission 0.7461 and 0.4875 Structure solution technique direct methods Structure solution program SHELXTL XT 2014/5 (Bruker AXS, 2014) Refinement method Full-matrix least-squares on F 2 Refinement program SHELXL-2016/6 (Sheldrick, 2016) Function minimized Σ w(Fo 2 - Fc 2 ) 2 Data / restraints / parameters 6852 / 0 / 277 Goodness-of-fit on F 2 1.099 Δ/σmax 0.002 Final R indices 5325 data; I>2σ(I) R1 = 0.0262, wR2 = 0.0515 all data R1 = 0.0389, wR2 = 0.0562 Weighting scheme w=1/[σ 2 (Fo 2 )+(0.0159P) 2 +10.6787P] where P=(Fo 2 +2Fc 2 )/3 Largest diff. peak and hole 1.384 and -1.406 eÅ -3 R.M.S. deviation from mean 0.122 eÅ -3 214 Table 3. Atomic coordinates and equivalent isotropic atomic displacement parameters (Å 2 ) for Complex 2.1. U(eq) is defined as one third of the trace of the orthogonalized Uij tensor. x/a y/b z/c U(eq) C1 0.6841(3) 0.12124(14) 0.06437(10) 0.0140(5) C2 0.6256(3) 0.08323(15) 0.02579(10) 0.0169(6) C3 0.5284(3) 0.11655(16) 0.99271(10) 0.0176(6) C4 0.4949(3) 0.18725(16) 0.99922(10) 0.0185(6) C5 0.5610(3) 0.22350(15) 0.03809(10) 0.0139(5) C6 0.5331(4) 0.30037(15) 0.04674(10) 0.0166(6) C7 0.4864(3) 0.44531(14) 0.10414(10) 0.0138(5) C8 0.3816(3) 0.47977(15) 0.07369(11) 0.0175(6) C9 0.2477(3) 0.51048(14) 0.09342(12) 0.0177(6) C10 0.2182(3) 0.50814(14) 0.14306(12) 0.0162(6) C11 0.3253(4) 0.47297(15) 0.17303(11) 0.0179(6) C12 0.4580(3) 0.44119(15) 0.15398(11) 0.0178(6) C13 0.0741(4) 0.54177(16) 0.16424(12) 0.0228(6) C14 0.9608(3) 0.28393(14) 0.15335(10) 0.0128(5) C15 0.8502(3) 0.29587(15) 0.19248(10) 0.0143(5) C16 0.7896(3) 0.22858(17) 0.20681(10) 0.0157(5) C17 0.8555(3) 0.17565(15) 0.17586(10) 0.0153(5) C18 0.9615(3) 0.21026(15) 0.14238(10) 0.0140(5) C19 0.0722(3) 0.33666(16) 0.13275(12) 0.0206(6) C20 0.8276(4) 0.36311(17) 0.21951(11) 0.0240(7) C21 0.6787(4) 0.2150(2) 0.24776(11) 0.0282(7) C22 0.8373(4) 0.09776(16) 0.18296(12) 0.0271(7) 215 x/a y/b z/c U(eq) C23 0.0661(4) 0.17502(18) 0.10647(11) 0.0233(6) Cl1 0.45117(7) 0.24652(4) 0.15378(2) 0.01771(12) Ir1 0.72557(2) 0.25043(2) 0.13198(2) 0.00961(3) N1 0.6529(3) 0.19069(12) 0.07066(8) 0.0124(4) N2 0.6548(3) 0.32643(11) 0.08003(8) 0.0122(4) O1 0.7870(2) 0.43242(11) 0.11246(8) 0.0194(4) O2 0.6700(3) 0.43647(11) 0.03058(8) 0.0213(4) S1 0.66332(8) 0.41020(3) 0.08004(2) 0.01372(12) Table 4. Bond lengths (Å) for Complex 1. C1-N1 1.358(3) C1-C2 1.378(4) C1-H1 0.95 C2-C3 1.386(4) C2-H2 0.95 C3-C4 1.386(4) C3-H3 0.95 C4-C5 1.392(4) C4-H4 0.95 C5-N1 1.345(3) C5-C6 1.500(4) C6-N2 1.472(4) C6-H6A 0.99 C6-H6B 0.99 C7-C8 1.390(4) C7-C12 1.395(4) C7-S1 1.781(3) C8-C9 1.395(4) C8-H8 0.95 C9-C10 1.390(5) C9-H9 0.95 C10-C11 1.402(4) C10-C13 1.505(4) C11-C12 1.388(4) C11-H11 0.95 C12-H12 0.95 C13-H13A 0.98 C13-H13B 0.98 C13-H13C 0.98 C14-C18 1.433(4) C14-C15 1.451(4) C14-C19 1.494(4) C14-Ir1 2.189(3) C15-C16 1.435(4) 216 C15-C20 1.492(4) C15-Ir1 2.157(3) C16-C17 1.434(4) C16-C21 1.495(4) C16-Ir1 2.170(3) C17-C18 1.450(4) C17-C22 1.502(4) C17-Ir1 2.171(3) C18-C23 1.491(4) C18-Ir1 2.175(3) 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-H21A 0.98 C21-H21B 0.98 C21-H21C 0.98 C22-H22A 0.98 C22-H22B 0.98 C22-H22C 0.98 C23-H23A 0.98 C23-H23B 0.98 C23-H23C 0.98 Cl1-Ir1 2.4216(8) Ir1-N2 2.121(2) Ir1-N1 2.127(2) N2-S1 1.594(2) O1-S1 1.446(2) O2-S1 1.451(2) Table 5. Bond angles (°) for Complex 2.1. N1-C1-C2 122.5(3) N1-C1-H1 118.8 C2-C1-H1 118.8 C1-C2-C3 118.9(3) C1-C2-H2 120.5 C3-C2-H2 120.5 C2-C3-C4 118.8(3) C2-C3-H3 120.6 C4-C3-H3 120.6 C3-C4-C5 119.7(3) C3-C4-H4 120.1 C5-C4-H4 120.1 N1-C5-C4 121.3(3) N1-C5-C6 116.0(2) C4-C5-C6 122.7(3) N2-C6-C5 108.3(2) N2-C6-H6A 110.0 C5-C6-H6A 110.0 N2-C6-H6B 110.0 C5-C6-H6B 110.0 217 H6A-C6-H6B 108.4 C8-C7-C12 120.5(3) C8-C7-S1 119.9(2) C12-C7-S1 119.5(2) C7-C8-C9 119.4(3) C7-C8-H8 120.3 C9-C8-H8 120.3 C10-C9-C8 121.2(3) C10-C9-H9 119.4 C8-C9-H9 119.4 C9-C10-C11 118.4(3) C9-C10-C13 121.0(3) C11-C10-C13 120.6(3) C12-C11-C10 121.3(3) C12-C11-H11 119.4 C10-C11-H11 119.4 C11-C12-C7 119.3(3) C11-C12-H12 120.4 C7-C12-H12 120.4 C10-C13-H13A 109.5 C10-C13-H13B 109.5 H13A-C13- H13B 109.5 C10-C13-H13C 109.5 H13A-C13- H13C 109.5 H13B-C13- H13C 109.5 C18-C14-C15 108.2(2) C18-C14-C19 125.0(3) C15-C14-C19 126.3(3) C18-C14-Ir1 70.29(15) C15-C14-Ir1 69.29(15) C19-C14-Ir1 132.7(2) C16-C15-C14 107.4(2) C16-C15-C20 125.5(3) C14-C15-C20 126.0(3) C16-C15-Ir1 71.14(15) C14-C15-Ir1 71.72(15) C20-C15-Ir1 131.6(2) C17-C16-C15 108.7(2) C17-C16-C21 125.1(3) C15-C16-C21 126.2(3) C17-C16-Ir1 70.73(16) C15-C16-Ir1 70.12(15) C21-C16-Ir1 126.0(2) C16-C17-C18 107.7(2) C16-C17-C22 125.1(3) C18-C17-C22 126.5(3) C16-C17-Ir1 70.70(16) C18-C17-Ir1 70.67(15) C22-C17-Ir1 131.7(2) C14-C18-C17 107.9(2) 218 C14-C18-C23 125.5(3) C17-C18-C23 126.3(3) C14-C18-Ir1 71.38(15) C17-C18-Ir1 70.35(15) C23-C18-Ir1 128.8(2) C14-C19-H19A 109.5 C14-C19-H19B 109.5 H19A-C19- H19B 109.5 C14-C19-H19C 109.5 H19A-C19- H19C 109.5 H19B-C19- H19C 109.5 C15-C20-H20A 109.5 C15-C20-H20B 109.5 H20A-C20- H20B 109.5 C15-C20-H20C 109.5 H20A-C20- H20C 109.5 H20B-C20- H20C 109.5 C16-C21-H21A 109.5 C16-C21-H21B 109.5 H21A-C21- H21B 109.5 C16-C21-H21C 109.5 H21A-C21- H21C 109.5 H21B-C21- H21C 109.5 C17-C22-H22A 109.5 C17-C22-H22B 109.5 H22A-C22- H22B 109.5 C17-C22-H22C 109.5 H22A-C22- H22C 109.5 H22B-C22- H22C 109.5 C18-C23-H23A 109.5 C18-C23-H23B 109.5 H23A-C23- H23B 109.5 219 C18-C23-H23C 109.5 H23A-C23- H23C 109.5 H23B-C23- H23C 109.5 N2-Ir1-N1 75.27(9) N2-Ir1-C15 112.84(10) N1-Ir1-C15 166.06(10) N2-Ir1-C16 147.32(10) N1-Ir1-C16 136.39(10) C15-Ir1-C16 38.74(11) N2-Ir1-C17 165.26(10) N1-Ir1-C17 103.94(10) C15-Ir1-C17 65.19(11) C16-Ir1-C17 38.57(11) N2-Ir1-C18 126.33(10) N1-Ir1-C18 100.82(9) C15-Ir1-C18 65.25(10) C16-Ir1-C18 64.81(11) C17-Ir1-C18 38.98(11) N2-Ir1-C14 104.17(10) N1-Ir1-C14 129.54(10) C15-Ir1-C14 38.99(10) C16-Ir1-C14 64.50(10) C17-Ir1-C14 64.62(10) C18-Ir1-C14 38.33(10) N2-Ir1-Cl1 84.93(7) N1-Ir1-Cl1 84.11(7) C15-Ir1-Cl1 107.41(8) C16-Ir1-Cl1 90.18(8) C17-Ir1-Cl1 109.73(8) C18-Ir1-Cl1 148.69(8) C14-Ir1-Cl1 146.26(7) C5-N1-C1 118.7(2) C5-N1-Ir1 116.84(18) C1-N1-Ir1 124.25(18) C6-N2-S1 111.65(18) C6-N2-Ir1 113.06(16) S1-N2-Ir1 131.87(13) O1-S1-O2 116.68(13) O1-S1-N2 109.00(12) O2-S1-N2 110.21(13) O1-S1-C7 106.35(13) O2-S1-C7 104.70(13) N2-S1-C7 109.61(13) Table 6. Torsion angles (°) for Complex 2.1. N1-C1-C2-C3 -1.5(4) C1-C2-C3-C4 0.8(4) C2-C3-C4-C5 1.0(4) C3-C4-C5-N1 -2.3(4) 220 C3-C4-C5-C6 178.5(3) N1-C5-C6-N2 18.4(3) C4-C5-C6-N2 -162.4(3) C12-C7-C8-C9 0.2(4) S1-C7-C8-C9 -176.4(2) C7-C8-C9-C10 0.9(4) C8-C9-C10- C11 -1.1(4) C8-C9-C10- C13 179.6(3) C9-C10-C11- C12 0.1(4) C13-C10-C11- C12 179.4(3) C10-C11-C12- C7 1.0(4) C8-C7-C12- C11 -1.1(4) S1-C7-C12-C11 175.5(2) C18-C14-C15- C16 2.8(3) C19-C14-C15- C16 -169.0(3) Ir1-C14-C15- C16 62.58(18) C18-C14-C15- C20 171.6(3) C19-C14-C15- C20 -0.2(4) Ir1-C14-C15- C20 -128.7(3) C18-C14-C15- Ir1 -59.76(18) C19-C14-C15- Ir1 128.5(3) C14-C15-C16- C17 -2.5(3) C20-C15-C16- C17 -171.3(3) Ir1-C15-C16- C17 60.47(19) C14-C15-C16- C21 176.3(3) C20-C15-C16- C21 7.5(5) Ir1-C15-C16- C21 -120.7(3) C14-C15-C16- Ir1 -62.96(18) C20-C15-C16- Ir1 128.2(3) C15-C16-C17- C18 1.2(3) C21-C16-C17- C18 -177.6(3) Ir1-C16-C17- C18 61.31(18) 221 C15-C16-C17- C22 171.9(3) C21-C16-C17- C22 -6.9(4) Ir1-C16-C17- C22 -128.0(3) C15-C16-C17- Ir1 -60.08(19) C21-C16-C17- Ir1 121.1(3) C15-C14-C18- C17 -2.1(3) C19-C14-C18- C17 169.8(3) Ir1-C14-C18- C17 -61.21(18) C15-C14-C18- C23 -176.0(3) C19-C14-C18- C23 -4.1(4) Ir1-C14-C18- C23 124.8(3) C15-C14-C18- Ir1 59.13(18) C19-C14-C18- Ir1 -129.0(3) C16-C17-C18- C14 0.5(3) C22-C17-C18- C14 -170.0(3) Ir1-C17-C18- C14 61.87(18) C16-C17-C18- C23 174.4(3) C22-C17-C18- C23 3.9(5) Ir1-C17-C18- C23 -124.2(3) C16-C17-C18- Ir1 -61.33(19) C22-C17-C18- Ir1 128.1(3) C4-C5-N1-C1 1.7(4) C6-C5-N1-C1 -179.1(2) C4-C5-N1-Ir1 -173.8(2) C6-C5-N1-Ir1 5.4(3) C2-C1-N1-C5 0.3(4) C2-C1-N1-Ir1 175.3(2) C5-C6-N2-S1 164.49(19) C5-C6-N2-Ir1 -33.8(3) C6-N2-S1-O1 - 178.67(19) Ir1-N2-S1-O1 24.2(2) C6-N2-S1-O2 -49.4(2) Ir1-N2-S1-O2 153.42(17) C6-N2-S1-C7 65.3(2) 222 Ir1-N2-S1-C7 -91.86(19) C8-C7-S1-O1 132.7(2) C12-C7-S1-O1 -43.9(3) C8-C7-S1-O2 8.6(3) C12-C7-S1-O2 -168.0(2) C8-C7-S1-N2 -109.6(2) C12-C7-S1-N2 73.8(2) Table 7. Anisotropic atomic displacement parameters (Å 2 ) for Complex 2.1. 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 0.0176(13) 0.0110(12) 0.0134(12) 0.0007(10) -0.0031(10) -0.0003(10) C2 0.0216(14) 0.0112(13) 0.0178(13) -0.0033(10) -0.0025(11) -0.0015(10) C3 0.0199(14) 0.0186(14) 0.0142(13) -0.0028(10) -0.0054(11) -0.0052(11) C4 0.0183(14) 0.0198(15) 0.0174(13) -0.0001(11) -0.0076(11) 0.0004(11) C5 0.0152(13) 0.0139(12) 0.0128(12) 0.0011(10) -0.0013(10) 0.0004(10) C6 0.0228(15) 0.0122(13) 0.0149(13) -0.0002(10) -0.0044(11) 0.0026(11) C7 0.0153(13) 0.0078(12) 0.0183(13) 0.0003(10) -0.0003(10) 0.0002(9) C8 0.0202(14) 0.0162(13) 0.0162(13) 0.0010(11) -0.0031(11) 0.0021(11) C9 0.0210(13) 0.0100(14) 0.0222(14) -0.0001(10) -0.0033(12) 0.0035(11) 223 U11 U22 U33 U23 U13 U12 C10 0.0138(13) 0.0077(12) 0.0270(15) -0.0018(11) 0.0010(10) 0.0002(10) C11 0.0192(14) 0.0174(14) 0.0173(13) 0.0023(10) 0.0014(11) 0.0039(11) C12 0.0161(13) 0.0172(14) 0.0203(14) 0.0041(11) -0.0004(11) 0.0034(11) C13 0.0203(15) 0.0164(14) 0.0318(17) -0.0024(12) 0.0008(13) 0.0047(12) C14 0.0105(12) 0.0143(13) 0.0136(13) -0.0024(10) -0.0038(10) 0.0024(10) C15 0.0131(13) 0.0172(13) 0.0125(12) -0.0051(10) -0.0046(10) 0.0003(10) C16 0.0129(13) 0.0237(14) 0.0105(12) -0.0004(10) -0.0038(9) 0.0001(10) C17 0.0153(13) 0.0156(13) 0.0149(12) 0.0004(10) -0.0073(10) 0.0000(10) C18 0.0104(12) 0.0191(14) 0.0124(12) -0.0032(10) -0.0052(10) 0.0058(10) C19 0.0109(13) 0.0203(15) 0.0304(16) 0.0030(12) -0.0017(11) -0.0029(11) C20 0.0237(15) 0.0261(16) 0.0223(15) -0.0141(12) -0.0078(13) 0.0058(13) C21 0.0203(15) 0.053(2) 0.0117(13) 0.0065(14) -0.0003(12) -0.0046(15) C22 0.0347(18) 0.0138(14) 0.0327(17) 0.0068(13) -0.0186(15) -0.0049(13) C23 0.0203(15) 0.0283(16) 0.0212(15) -0.0082(13) -0.0015(12) 0.0112(13) Cl1 0.0106(3) 0.0224(3) 0.0202(3) 0.0024(3) 0.0008(2) 0.0001(3) 224 U11 U22 U33 U23 U13 U12 Ir1 0.00878(5) 0.01057(5) 0.00947(5) -0.00118(4) -0.00129(3) 0.00064(4) N1 0.0133(11) 0.0109(10) 0.0131(10) -0.0007(8) -0.0032(8) 0.0000(8) N2 0.0151(11) 0.0073(10) 0.0142(10) -0.0005(8) -0.0032(9) 0.0021(8) O1 0.0157(10) 0.0134(10) 0.0290(12) -0.0013(8) -0.0021(8) -0.0035(8) O2 0.0248(11) 0.0178(10) 0.0215(10) 0.0096(8) 0.0073(9) 0.0011(9) S1 0.0132(3) 0.0103(3) 0.0177(3) 0.0018(2) 0.0015(2) 0.0000(2) Table 8. Hydrogen atomic coordinates and isotropic atomic displacement parameters (Å 2 ) for Complex 2.1. x/a y/b z/c U(eq) H1 0.7486 0.0980 0.0874 0.017 H2 0.6515 0.0350 0.0219 0.02 H3 0.4854 0.0914 -0.0340 0.021 H4 0.4272 0.2109 -0.0227 0.022 H6A 0.5378 0.3264 0.0156 0.02 H6B 0.4283 0.3076 0.0612 0.02 H8 0.4011 0.4824 0.0397 0.021 H9 0.1753 0.5334 0.0725 0.021 H11 0.3067 0.4709 0.2070 0.022 H12 0.5288 0.4169 0.1747 0.021 H13A 0.0774 0.5926 0.1585 0.034 H13B 0.0702 0.5326 0.1993 0.034 H13C -0.0192 0.5219 0.1487 0.034 H19A 1.1000 0.3232 0.0995 0.031 H19B 1.1669 0.3383 0.1528 0.031 225 x/a y/b z/c U(eq) H19C 1.0227 0.3832 0.1325 0.031 H20A 0.8432 0.4029 0.1974 0.036 H20B 0.9036 0.3659 0.2461 0.036 H20C 0.7213 0.3648 0.2328 0.036 H21A 0.6101 0.2558 0.2521 0.042 H21B 0.7380 0.2068 0.2777 0.042 H21C 0.6153 0.1734 0.2403 0.042 H22A 0.8718 0.0731 0.1536 0.041 H22B 0.7272 0.0867 0.1893 0.041 H22C 0.9012 0.0826 0.2106 0.041 H23A 1.0159 0.1319 0.0946 0.035 H23B 1.1657 0.1632 0.1221 0.035 H23C 1.0853 0.2068 0.0791 0.035 226 Crystal structure of 2.2’ Figure 8.8.2. X-Ray structure of complex 2.2’. A orange prism-like specimen of C23H27IrN2O2S, approximate dimensions 0.081 mm x 0.323 mm x 0.619 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). 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 triclinic unit cell 227 yielded a total of 19752 reflections to a maximum θ angle of 27.47° (0.77 Å resolution), of which 4863 were independent (average redundancy 4.062, completeness = 99.8%, Rint = 5.52%, Rsig = 4.93%) and 4289 (88.20%) were greater than 2σ(F 2 ). The final cell constants of a = 8.163(6) Å, b = 9.868(7) Å, c = 14.028(10) Å, α = 72.304(10)°, β = 83.079(10)°, γ = 82.565(10)°, volume = 1063.5(13) Å 3 , are based upon the refinement of the XYZ-centroids of reflections above 20 σ(I). Data were corrected for absorption effects using the multi-scan method (SADABS). The structure was solved and refined using the Bruker SHELXTL Software Package, using the space group P -1, with Z = 2 for the formula unit, C23H27IrN2O2S. The final anisotropic full- matrix least-squares refinement on F 2 with 268 variables converged at R1 = 4.88%, for the observed data and wR2 = 12.86% for all data. The goodness-of-fit was 1.006. The largest peak in the final difference electron density synthesis was 9.057 e - /Å 3 and the largest hole was -2.562 e - /Å 3 with an RMS deviation of 0.263 e - /Å 3 . On the basis of the final model, the calculated density was 1.835 g/cm 3 and F(000), 576 e - . Table 1. Sample and crystal data for Complex 2.2’. Identification code Complex 2.2’ Chemical formula C23H27IrN2O2S Formula weight 587.72 g/mol Temperature 100(2) K Wavelength 0.71073 Å Crystal size 0.081 x 0.323 x 0.619 mm Crystal habit orange prism Crystal system triclinic 228 Space group P -1 Unit cell dimensions a = 8.163(6) Å α = 72.304(10)° b = 9.868(7) Å β = 83.079(10)° c = 14.028(10) Å γ = 82.565(10)° Volume 1063.5(13) Å 3 Z 2 Density (calculated) 1.835 g/cm 3 Absorption coefficient 6.397 mm -1 F(000) 576 Table 2. Data collection and structure refinement for Complex 2.2’. Diffractometer Bruker APEX DUO Radiation source fine-focus tube, MoKα Theta range for data collection 1.53 to 27.47° Index ranges -10<=h<=10, -12<=k<=12, -18<=l<=18 Reflections collected 19752 Independent reflections 4863 [R(int) = 0.0552] Absorption correction multi-scan Structure solution technique direct methods Structure solution program SHELXTL XT 2014/4 (Bruker AXS, 2014) Refinement method Full-matrix least-squares on F 2 Refinement program SHELXTL XL 2014/7 (Bruker AXS, 2014) Function minimized Σ w(Fo 2 - Fc 2 ) 2 229 Data / restraints / parameters 4863 / 0 / 268 Goodness-of-fit on F 2 1.006 Final R indices 4289 data; I>2σ(I) R1 = 0.0488, wR2 = 0.1247 all data R1 = 0.0562, wR2 = 0.1286 Weighting scheme w=1/[σ 2 (Fo 2 )+(0.0731P) 2 +13.4360P] where P=(Fo 2 +2Fc 2 )/3 Largest diff. peak and hole 9.057 and -2.562 eÅ -3 R.M.S. deviation from mean 0.263 eÅ -3 Table 3. Atomic coordinates and equivalent isotropic atomic displacement parameters (Å 2 ) for Complex 2.2’. U(eq) is defined as one third of the trace of the orthogonalized Uij tensor. x/a y/b z/c U(eq) C1 0.9451(10) 0.3426(8) 0.4065(7) 0.0218(16) C2 0.8598(11) 0.3411(9) 0.4981(7) 0.0257(18) C3 0.9492(11) 0.3273(8) 0.5793(6) 0.0245(17) C4 0.1198(11) 0.3196(8) 0.5664(6) 0.0239(17) C5 0.1994(10) 0.3225(8) 0.4722(6) 0.0211(16) C6 0.3839(11) 0.3144(9) 0.4512(6) 0.0230(17) C7 0.3473(10) 0.5975(8) 0.2217(6) 0.0191(15) C8 0.2174(10) 0.5226(9) 0.2134(6) 0.0198(15) C9 0.0746(10) 0.6078(8) 0.1741(6) 0.0209(16) 230 x/a y/b z/c U(eq) C10 0.0632(11) 0.7570(9) 0.1438(6) 0.0250(17) C11 0.1984(12) 0.8257(9) 0.1489(7) 0.0268(18) C12 0.3435(11) 0.7482(9) 0.1869(7) 0.0246(17) C13 0.9045(13) 0.8427(10) 0.1095(8) 0.033(2) C14 0.3015(11) 0.0744(9) 0.2741(7) 0.0243(17) C15 0.1336(11) 0.1181(9) 0.2568(6) 0.0243(17) C16 0.1227(10) 0.2311(8) 0.1636(6) 0.0189(15) C17 0.2913(10) 0.2566(9) 0.1228(6) 0.0216(16) C18 0.3993(11) 0.1623(10) 0.1908(8) 0.0290(19) C19 0.3664(15) 0.9603(11) 0.3620(9) 0.042(3) C20 0.9839(13) 0.0561(11) 0.3224(8) 0.034(2) C21 0.9695(11) 0.2970(11) 0.1121(8) 0.0300(19) C22 0.3415(13) 0.3600(11) 0.0233(7) 0.035(2) C23 0.5845(12) 0.1456(13) 0.1780(10) 0.045(3) Ir1 0.24812(4) 0.30420(3) 0.26528(2) 0.01715(11) N1 0.1124(9) 0.3288(7) 0.3950(5) 0.0203(13) N2 0.4339(8) 0.3440(7) 0.3427(5) 0.0202(13) O1 0.6438(8) 0.4642(7) 0.2127(5) 0.0287(13) O2 0.5613(8) 0.5590(7) 0.3554(5) 0.0285(13) S1 0.5135(2) 0.4911(2) 0.28543(15) 0.0202(4) Table 4. Bond lengths (Å) for Complex 2.2’. C1-N1 1.350(11) C1-C2 1.382(12) C1-H1 0.95 C2-C3 1.390(13) C2-H2 0.95 C3-C4 1.377(13) C3-H3 0.95 C4-C5 1.394(12) C4-H4 0.95 C5-N1 1.347(11) 231 C5-C6 1.496(12) C6-N2 1.477(11) C6-H6A 0.99 C6-H6B 0.99 C7-C8 1.403(12) C7-C12 1.415(11) C7-S1 1.759(8) C8-C9 1.410(11) C8-Ir1 2.046(8) C9-C10 1.397(12) C9-H9 0.95 C10-C11 1.387(13) C10-C13 1.498(13) C11-C12 1.394(13) C11-H11 0.95 C12-H12 0.95 C13-H13A 0.98 C13-H13B 0.98 C13-H13C 0.98 C14-C15 1.409(13) C14-C18 1.447(14) C14-C19 1.492(13) C14-Ir1 2.222(8) C15-C16 1.441(12) C15-C20 1.515(13) C15-Ir1 2.206(8) C16-C17 1.448(11) C16-C21 1.494(12) C16-Ir1 2.184(8) C17-C18 1.415(13) C17-C22 1.504(13) C17-Ir1 2.168(8) C18-C23 1.494(13) C18-Ir1 2.170(8) 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-H21A 0.98 C21-H21B 0.98 C21-H21C 0.98 C22-H22A 0.98 C22-H22B 0.98 C22-H22C 0.98 C23-H23A 0.98 C23-H23B 0.98 C23-H23C 0.98 Ir1-N1 2.076(7) Ir1-N2 2.108(7) N2-S1 1.608(7) O1-S1 1.440(6) O2-S1 1.458(6) 232 Table 5. Bond angles (°) for Complex 2.2’. N1-C1-C2 121.5(8) N1-C1-H1 119.2 C2-C1-H1 119.2 C1-C2-C3 118.9(8) C1-C2-H2 120.6 C3-C2-H2 120.6 C4-C3-C2 119.6(8) C4-C3-H3 120.2 C2-C3-H3 120.2 C3-C4-C5 119.1(8) C3-C4-H4 120.5 C5-C4-H4 120.5 N1-C5-C4 121.0(8) N1-C5-C6 116.1(7) C4-C5-C6 122.9(7) N2-C6-C5 111.6(7) N2-C6-H6A 109.3 C5-C6-H6A 109.3 N2-C6-H6B 109.3 C5-C6-H6B 109.3 H6A-C6-H6B 108.0 C8-C7-C12 123.3(8) C8-C7-S1 115.2(6) C12-C7-S1 121.4(6) C9-C8-C7 115.6(7) C9-C8-Ir1 126.7(6) C7-C8-Ir1 117.6(6) C8-C9-C10 122.5(8) C8-C9-H9 118.7 C10-C9-H9 118.7 C11-C10-C9 119.5(8) C11-C10-C13 120.0(8) C9-C10-C13 120.4(8) C10-C11-C12 121.0(8) C10-C11-H11 119.5 C12-C11-H11 119.5 C11-C12-C7 117.8(8) C11-C12-H12 121.1 C7-C12-H12 121.1 C10-C13-H13A 109.5 C10-C13-H13B 109.5 H13A-C13-H13B 109.5 C10-C13-H13C 109.5 H13A-C13-H13C 109.5 H13B-C13-H13C 109.5 C15-C14-C18 106.9(8) C15-C14-C19 126.7(9) C18-C14-C19 126.4(9) C15-C14-Ir1 70.8(5) C18-C14-Ir1 68.8(5) C19-C14-Ir1 124.9(6) C16-C15-C14 109.6(8) C16-C15-C20 123.6(8) C14-C15-C20 126.8(8) 233 C16-C15-Ir1 70.0(4) C14-C15-Ir1 72.1(5) C20-C15-Ir1 125.6(6) C15-C16-C17 106.7(7) C15-C16-C21 127.0(8) C17-C16-C21 126.0(8) C15-C16-Ir1 71.6(5) C17-C16-Ir1 69.9(4) C21-C16-Ir1 129.0(6) C18-C17-C16 107.8(7) C18-C17-C22 126.4(8) C16-C17-C22 125.7(8) C18-C17-Ir1 71.1(5) C16-C17-Ir1 71.2(4) C22-C17-Ir1 125.6(6) C17-C18-C14 109.0(8) C17-C18-C23 127.0(10) C14-C18-C23 123.9(10) C17-C18-Ir1 70.9(5) C14-C18-Ir1 72.7(5) C23-C18-Ir1 125.7(6) C14-C19-H19A 109.5 C14-C19-H19B 109.5 H19A-C19-H19B 109.5 C14-C19-H19C 109.5 H19A-C19-H19C 109.5 H19B-C19-H19C 109.5 C15-C20-H20A 109.5 C15-C20-H20B 109.5 H20A-C20-H20B 109.5 C15-C20-H20C 109.5 H20A-C20-H20C 109.5 H20B-C20-H20C 109.5 C16-C21-H21A 109.5 C16-C21-H21B 109.5 H21A-C21-H21B 109.5 C16-C21-H21C 109.5 H21A-C21-H21C 109.5 H21B-C21-H21C 109.5 C17-C22-H22A 109.5 C17-C22-H22B 109.5 H22A-C22-H22B 109.5 C17-C22-H22C 109.5 H22A-C22-H22C 109.5 H22B-C22-H22C 109.5 C18-C23-H23A 109.5 C18-C23-H23B 109.5 H23A-C23-H23B 109.5 C18-C23-H23C 109.5 H23A-C23-H23C 109.5 H23B-C23-H23C 109.5 C8-Ir1-N1 85.4(3) C8-Ir1-N2 82.8(3) N1-Ir1-N2 78.6(3) C8-Ir1-C18 126.3(4) N1-Ir1-C18 147.8(3) 234 N2-Ir1-C18 98.1(3) C8-Ir1-C17 99.2(3) N1-Ir1-C17 156.5(3) N2-Ir1-C17 124.8(3) C18-Ir1-C17 38.1(3) C8-Ir1-C16 105.1(3) N1-Ir1-C16 117.6(3) N2-Ir1-C16 162.1(3) C18-Ir1-C16 64.2(3) C17-Ir1-C16 38.9(3) C8-Ir1-C15 139.3(3) N1-Ir1-C15 97.6(3) N2-Ir1-C15 137.7(3) C18-Ir1-C15 63.3(3) C17-Ir1-C15 64.0(3) C16-Ir1-C15 38.3(3) C8-Ir1-C14 163.2(3) N1-Ir1-C14 110.8(3) N2-Ir1-C14 104.5(3) C18-Ir1-C14 38.5(4) C17-Ir1-C14 64.1(3) C16-Ir1-C14 63.8(3) C15-Ir1-C14 37.1(3) C1-N1-C5 119.7(7) C1-N1-Ir1 123.4(6) C5-N1-Ir1 116.7(6) C6-N2-S1 117.9(6) C6-N2-Ir1 111.7(5) S1-N2-Ir1 113.0(4) O1-S1-O2 115.2(4) O1-S1-N2 108.5(4) O2-S1-N2 111.9(4) O1-S1-C7 108.9(4) O2-S1-C7 109.1(4) N2-S1-C7 102.3(4) Table 6. Anisotropic atomic displacement parameters (Å 2 ) for Complex 2.2’. 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 0.024(4) 0.015(4) 0.027(4) -0.005(3) -0.006(3) -0.003(3) C2 0.028(4) 0.019(4) 0.029(5) -0.004(3) 0.002(3) -0.005(3) C3 0.036(5) 0.015(4) 0.019(4) -0.003(3) 0.006(3) -0.004(3) C4 0.037(5) 0.014(4) 0.021(4) -0.001(3) -0.009(3) -0.006(3) 235 U11 U22 U33 U23 U13 U12 C5 0.028(4) 0.016(4) 0.016(4) 0.001(3) -0.003(3) -0.006(3) C6 0.029(4) 0.025(4) 0.014(4) -0.002(3) -0.007(3) -0.003(3) C7 0.023(4) 0.017(4) 0.017(4) -0.004(3) -0.001(3) -0.001(3) C8 0.028(4) 0.019(4) 0.011(3) -0.004(3) -0.003(3) 0.002(3) C9 0.024(4) 0.017(4) 0.020(4) -0.004(3) -0.005(3) 0.001(3) C10 0.036(5) 0.022(4) 0.017(4) -0.006(3) -0.003(3) -0.001(3) C11 0.041(5) 0.016(4) 0.023(4) -0.003(3) 0.000(4) -0.008(3) C12 0.031(4) 0.019(4) 0.025(4) -0.010(3) 0.005(3) -0.006(3) C13 0.044(6) 0.021(4) 0.033(5) -0.008(4) -0.010(4) 0.008(4) C14 0.034(5) 0.020(4) 0.022(4) -0.007(3) -0.010(3) -0.003(3) C15 0.038(5) 0.020(4) 0.018(4) -0.008(3) -0.004(3) -0.009(3) C16 0.022(4) 0.017(4) 0.019(4) -0.009(3) -0.002(3) 0.000(3) C17 0.025(4) 0.023(4) 0.020(4) -0.012(3) 0.003(3) -0.005(3) C18 0.026(4) 0.026(4) 0.044(6) -0.025(4) -0.002(4) 0.000(3) C19 0.052(7) 0.031(5) 0.044(6) -0.011(5) -0.022(5) 0.005(5) C20 0.045(6) 0.031(5) 0.028(5) -0.006(4) 0.003(4) -0.019(4) C21 0.024(4) 0.036(5) 0.034(5) -0.017(4) -0.008(4) 0.002(4) C22 0.045(6) 0.038(5) 0.025(5) -0.016(4) 0.010(4) -0.017(4) C23 0.020(5) 0.055(7) 0.073(8) -0.042(6) -0.003(5) 0.005(4) Ir1 0.02046(17) 0.01446(16) 0.01625(17) -0.00396(11) -0.00336(10) -0.00036(10) N1 0.027(4) 0.016(3) 0.016(3) -0.003(3) -0.002(3) -0.002(3) N2 0.021(3) 0.019(3) 0.021(3) -0.007(3) -0.003(3) -0.003(3) O1 0.023(3) 0.031(3) 0.029(3) -0.007(3) 0.002(2) 0.002(2) O2 0.032(3) 0.028(3) 0.030(3) -0.012(3) -0.009(3) -0.007(3) S1 0.0204(9) 0.0210(9) 0.0196(10) -0.0062(8) -0.0019(7) -0.0027(7) 236 x/a y/b z/c U(eq) H1 -0.1154 0.3536 0.3505 0.026 H2 -0.2579 0.3493 0.5053 0.031 H3 -0.1069 0.3233 0.6434 0.029 H4 0.1823 0.3123 0.6210 0.029 H6A 0.4277 0.3845 0.4767 0.028 H6B 0.4328 0.2178 0.4873 0.028 H9 -0.0174 0.5619 0.1681 0.025 H11 0.1920 0.9271 0.1261 0.032 H12 0.4369 0.7950 0.1894 0.03 H13A -0.0924 0.9418 0.1091 0.05 H13B -0.1889 0.8019 0.1554 0.05 H13C -0.1092 0.8404 0.0416 0.05 H19A 0.2817 -0.0535 0.4190 0.063 H19B 0.4661 -0.0113 0.3803 0.063 H19C 0.3940 -0.1293 0.3444 0.063 H20A -0.1110 0.1292 0.3135 0.051 H20B 0.0085 0.0245 0.3929 0.051 H20C -0.0426 -0.0256 0.3032 0.051 H21A -0.0715 0.2279 0.0854 0.045 H21B -0.0050 0.3821 0.0568 0.045 H21C -0.1157 0.3243 0.1602 0.045 H22A 0.4540 0.3843 0.0239 0.052 H22B 0.2643 0.4470 0.0117 0.052 H22C 0.3390 0.3160 -0.0304 0.052 Table 7. Hydrogen atomic coordinates and isotropic atomic displacement parameters (Å 2 ) for Complex 2.2’. 237 x/a y/b z/c U(eq) H23A 0.6223 0.0620 0.1544 0.068 H23B 0.6284 0.1325 0.2426 0.068 H23C 0.6241 0.2314 0.1287 0.068 238 Crystal structure of 3.6 Figure 8.8.3. X-Ray structure of complex 3.6. A clear red prism-like specimen of C20H20IrN2S, approximate dimensions 0.060 mm x 0.120 mm x 0.326 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 3.50 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 239 of 35238 reflections to a maximum θ angle of 31.50° (0.68 Å resolution), of which 7574 were independent (average redundancy 4.652, completeness = 94.4%, Rint = 3.68%, Rsig = 2.93%) and 6540 (86.35%) were greater than 2σ(F 2 ). The final cell constants of a = 12.646(10) Å, b = 11.595(9) Å, c = 17.732(15) Å, β = 110.15(2)°, volume = 2441.(6) Å 3 , are based upon the refinement of the XYZ-centroids of 120 reflections above 20 σ(I) with 7.686° < 2θ < 54.35°. Data were corrected for absorption effects using the multi-scan method (SADABS). The ratio of minimum to maximum apparent transmission was 0.706. The structure was solved and refined using the Bruker SHELXTL Software Package, with Z = 4 for the formula unit, C20H20IrN2S. The final anisotropic full-matrix least-squares refinement on F 2 with 312 variables converged at R1 = 2.03%, for the observed data and wR2 = 3.92% for all data. The goodness-of-fit was 1.316. The largest peak in the final difference electron density synthesis was 1.160 e - /Å 3 and the largest hole was -1.000 e - /Å 3 with an RMS deviation of 0.116 e - /Å 3 . On the basis of the final model, the calculated density was 1.898 g/cm 3 and F(000), 1352 e - . Table 1. Sample and crystal data for Complex 3.6. Identification code Complex 3.6 Chemical formula C20H20IrN2S Formula weight 512.67 g/mol Temperature 100(2) K Wavelength 0.71073 Å Crystal size 0.060 x 0.120 x 0.326 mm Crystal habit clear red prism Crystal system monoclinic Unit cell dimensions a = 12.646(10) Å α = 90° b = 11.595(9) Å β = 110.15(2)° 240 c = 17.732(15) Å γ = 90° Volume 2441.(6) Å 3 Z 4 Density (calculated) 1.898 g/cm 3 Absorption coefficient 5.761 mm -1 F(000) 1352 Table 2. Data collection and structure refinement for Complex 3.6. Diffractometer Bruker APEX DUO Radiation source fine-focus tube, MoKα Theta range for data collection 1.72 to 31.50° Index ranges -17<=h<=18, -16<=k<=16, -25<=l<=25 Reflections collected 35238 Independent reflections 7574 [R(int) = 0.0368] Coverage of independent reflections 94.4% Absorption correction multi-scan Structure solution technique direct methods Structure solution program SHELXTL XT 2014/4 (Bruker AXS, 2014) Refinement method Full-matrix least-squares on F 2 Refinement program SHELXTL XL 2014/7 (Bruker AXS, 2014) Function minimized Σ w(Fo 2 - Fc 2 ) 2 Data / restraints / parameters 7574 / 1 / 312 Goodness-of-fit on F 2 1.316 Δ/σmax 0.003 241 Final R indices 6540 data; I>2σ(I) R1 = 0.0203, wR2 = 0.0379 all data R1 = 0.0280, wR2 = 0.0392 Weighting scheme w=1/[σ 2 (Fo 2 )] where P=(Fo 2 +2Fc 2 )/3 Largest diff. peak and hole 1.160 and -1.000 eÅ -3 R.M.S. deviation from mean 0.116 eÅ -3 Table 3. Atomic coordinates and equivalent isotropic atomic displacement parameters (Å 2 ) for Complex 3.6. U(eq) is defined as one third of the trace of the orthogonalized Uij tensor. x/a y/b z/c U(eq) C1 0.99958(17) 0.4128(2) 0.31990(12) 0.0181(4) C2 0.06707(17) 0.31888(19) 0.37445(12) 0.0169(4) C3 0.28383(16) 0.12651(17) 0.44437(11) 0.0127(4) C4 0.31701(17) 0.02102(18) 0.48379(12) 0.0160(4) C5 0.41021(18) 0.01864(19) 0.55480(12) 0.0182(4) C6 0.47040(18) 0.11972(18) 0.58669(12) 0.0171(4) C7 0.43479(17) 0.22356(18) 0.54598(12) 0.0164(4) C8 0.34227(17) 0.22770(18) 0.47473(12) 0.0154(4) C9 0.57313(19) 0.1171(2) 0.66328(13) 0.0248(5) C10 0.35308(16) 0.42669(19) 0.26567(12) 0.0156(4) C11 0.34888(17) 0.30336(18) 0.24756(12) 0.0143(4) C12 0.25653(17) 0.28417(18) 0.17481(12) 0.0148(4) C13 0.20385(17) 0.39689(19) 0.14657(11) 0.0155(4) 242 x/a y/b z/c U(eq) C14 0.26650(17) 0.48409(18) 0.20102(12) 0.0159(4) C15 0.43703(18) 0.4846(2) 0.33731(13) 0.0216(5) C16 0.43169(18) 0.21484(19) 0.29557(13) 0.0203(5) C17 0.22037(19) 0.17238(19) 0.13155(13) 0.0213(5) C18 0.10415(18) 0.4160(2) 0.07154(11) 0.0222(5) C19 0.2426(2) 0.61139(18) 0.19492(14) 0.0226(5) C20 0.1714(2) 0.6489(2) 0.52519(15) 0.0281(5) F1 0.21278(15) 0.62634(13) 0.60382(9) 0.0399(4) F2 0.13428(14) 0.75842(14) 0.51689(9) 0.0452(4) F3 0.08115(13) 0.58055(18) 0.49263(11) 0.0578(5) Ir1 0.19278(2) 0.36302(2) 0.26290(2) 0.01078(2) N1 0.07967(16) 0.47656(16) 0.28881(11) 0.0155(4) N2 0.13360(14) 0.26151(15) 0.32998(9) 0.0130(3) O1 0.20376(12) 0.07780(13) 0.29055(8) 0.0169(3) O2 0.07476(12) 0.06824(13) 0.36733(8) 0.0172(3) O3 0.21578(16) 0.65582(15) 0.39377(10) 0.0330(4) O4 0.30335(16) 0.50614(15) 0.49110(11) 0.0373(4) O5 0.36412(14) 0.70671(16) 0.51948(10) 0.0341(4) S1 0.16769(4) 0.12684(4) 0.35238(3) 0.01269(9) S2 0.27682(5) 0.62704(5) 0.47730(3) 0.02025(11) Table 4. Bond lengths (Å) for Complex 3.6. C1-N1 1.499(3) C1-C2 1.504(3) C1-H1A 0.99 C1-H1B 0.99 C2-N2 1.489(3) C2-H2A 0.99 C2-H2B 0.99 C3-C8 1.386(3) 243 C3-C4 1.393(3) C3-S1 1.7720(19) C4-C5 1.391(3) C4-H4 0.95 C5-C6 1.399(3) C5-H5 0.95 C6-C7 1.390(3) C6-C9 1.516(3) C7-C8 1.390(3) C7-H7 0.95 C8-H8 0.95 C9-H9A 0.98 C9-H9B 0.98 C9-H9C 0.98 C10-C14 1.440(3) C10-C11 1.456(3) C10-C15 1.498(3) C10-Ir1 2.134(2) C11-C12 1.422(3) C11-C16 1.497(3) C11-Ir1 2.188(2) C12-C13 1.467(3) C12-C17 1.489(3) C12-Ir1 2.184(2) C13-C14 1.427(3) C13-C18 1.495(3) C13-Ir1 2.1461(19) C14-C19 1.496(3) C14-Ir1 2.172(2) C15-H15A 0.98 C15-H15B 0.98 C15-H15C 0.98 C16-H16A 0.98 C16-H16B 0.98 C16-H16C 0.98 C17-H17A 0.98 C17-H17B 0.98 C17-H17C 0.98 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-F1 1.331(3) C20-F2 1.338(3) C20-F3 1.339(3) C20-S2 1.824(3) Ir1-N2 1.9875(16) Ir1-N1 2.1007(18) N1-H1N 0.89(2) N1-H2N 0.92(3) N2-S1 1.6247(18) O1-S1 1.4380(15) O2-S1 1.4540(15) O3-S2 1.4484(17) 244 O4-S2 1.4360(19) O5-S2 1.4297(17) Table 5. Bond angles (°) for Complex 3.6. N1-C1-C2 106.64(16) N1-C1-H1A 110.4 C2-C1-H1A 110.4 N1-C1-H1B 110.4 C2-C1-H1B 110.4 H1A-C1-H1B 108.6 N2-C2-C1 106.16(16) N2-C2-H2A 110.5 C1-C2-H2A 110.5 N2-C2-H2B 110.5 C1-C2-H2B 110.5 H2A-C2-H2B 108.7 C8-C3-C4 121.02(18) C8-C3-S1 120.86(15) C4-C3-S1 118.08(15) C5-C4-C3 118.83(19) C5-C4-H4 120.6 C3-C4-H4 120.6 C4-C5-C6 121.17(19) C4-C5-H5 119.4 C6-C5-H5 119.4 C7-C6-C5 118.51(19) C7-C6-C9 120.16(19) C5-C6-C9 121.32(19) C8-C7-C6 121.21(19) C8-C7-H7 119.4 C6-C7-H7 119.4 C3-C8-C7 119.25(19) C3-C8-H8 120.4 C7-C8-H8 120.4 C6-C9-H9A 109.5 C6-C9-H9B 109.5 H9A-C9-H9B 109.5 C6-C9-H9C 109.5 H9A-C9-H9C 109.5 H9B-C9-H9C 109.5 C14-C10-C11 108.38(17) C14-C10-C15 125.86(19) C11-C10-C15 125.69(18) C14-C10-Ir1 71.90(12) C11-C10-Ir1 72.32(11) C15-C10-Ir1 123.96(15) C12-C11-C10 107.90(17) C12-C11-C16 126.76(19) C10-C11-C16 125.27(18) C12-C11-Ir1 70.85(12) C10-C11-Ir1 68.33(11) C16-C11-Ir1 128.65(14) C11-C12-C13 107.57(18) C11-C12-C17 127.52(19) 245 C13-C12-C17 124.86(18) C11-C12-Ir1 71.19(11) C13-C12-Ir1 68.81(11) C17-C12-Ir1 127.24(15) C14-C13-C12 108.43(17) C14-C13-C18 126.4(2) C12-C13-C18 125.12(19) C14-C13-Ir1 71.69(11) C12-C13-Ir1 71.58(11) C18-C13-Ir1 124.36(14) C13-C14-C10 107.54(18) C13-C14-C19 126.39(19) C10-C14-C19 125.97(19) C13-C14-Ir1 69.71(11) C10-C14-Ir1 69.06(11) C19-C14-Ir1 123.89(15) C10-C15-H15A 109.5 C10-C15-H15B 109.5 H15A-C15- H15B 109.5 C10-C15-H15C 109.5 H15A-C15- H15C 109.5 H15B-C15- H15C 109.5 C11-C16-H16A 109.5 C11-C16-H16B 109.5 H16A-C16- H16B 109.5 C11-C16-H16C 109.5 H16A-C16- H16C 109.5 H16B-C16- H16C 109.5 C12-C17-H17A 109.5 C12-C17-H17B 109.5 H17A-C17- H17B 109.5 C12-C17-H17C 109.5 H17A-C17- H17C 109.5 H17B-C17- H17C 109.5 C13-C18-H18A 109.5 C13-C18-H18B 109.5 H18A-C18- H18B 109.5 C13-C18-H18C 109.5 H18A-C18- H18C 109.5 H18B-C18- H18C 109.5 C14-C19-H19A 109.5 C14-C19-H19B 109.5 246 H19A-C19- H19B 109.5 C14-C19-H19C 109.5 H19A-C19- H19C 109.5 H19B-C19- H19C 109.5 F1-C20-F2 107.16(19) F1-C20-F3 107.5(2) F2-C20-F3 107.3(2) F1-C20-S2 111.91(17) F2-C20-S2 111.27(18) F3-C20-S2 111.44(16) N2-Ir1-N1 79.28(7) N2-Ir1-C10 137.50(7) N1-Ir1-C10 119.26(8) N2-Ir1-C13 147.39(7) N1-Ir1-C13 111.72(7) C10-Ir1-C13 65.41(7) N2-Ir1-C14 174.00(7) N1-Ir1-C14 98.61(8) C10-Ir1-C14 39.05(7) C13-Ir1-C14 38.60(8) N2-Ir1-C12 119.16(8) N1-Ir1-C12 149.42(7) C10-Ir1-C12 65.20(8) C13-Ir1-C12 39.61(8) C14-Ir1-C12 65.25(8) N2-Ir1-C11 115.34(7) N1-Ir1-C11 158.54(8) C10-Ir1-C11 39.34(8) C13-Ir1-C11 65.07(7) C14-Ir1-C11 65.17(8) C12-Ir1-C11 37.96(7) C1-N1-Ir1 111.59(13) C1-N1-H1N 109.5(14) Ir1-N1-H1N 109.5(14) C1-N1-H2N 110.4(19) Ir1-N1-H2N 111.6(19) H1N-N1-H2N 104.(2) C2-N2-S1 116.50(13) C2-N2-Ir1 116.73(13) S1-N2-Ir1 125.97(10) O1-S1-O2 116.24(9) O1-S1-N2 108.52(8) O2-S1-N2 109.14(9) O1-S1-C3 108.63(9) O2-S1-C3 107.04(9) N2-S1-C3 106.89(9) O5-S2-O4 116.39(11) O5-S2-O3 115.19(11) O4-S2-O3 113.98(11) O5-S2-C20 102.79(11) O4-S2-C20 102.69(12) O3-S2-C20 103.13(12) 247 Table 6. Anisotropic atomic displacement parameters (Å 2 ) for Complex 3.6. 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 0.0147(10) 0.0221(11) 0.0194(10) 0.0022(9) 0.0083(8) 0.0034(9) C2 0.0170(10) 0.0203(11) 0.0154(9) 0.0000(8) 0.0082(8) 0.0012(9) C3 0.0126(9) 0.0135(10) 0.0122(8) -0.0003(7) 0.0046(7) -0.0001(8) C4 0.0165(10) 0.0140(11) 0.0179(9) 0.0007(8) 0.0066(8) -0.0003(8) C5 0.0204(11) 0.0154(11) 0.0184(10) 0.0024(8) 0.0062(9) 0.0047(9) C6 0.0166(10) 0.0209(12) 0.0151(9) -0.0020(8) 0.0071(8) 0.0050(8) C7 0.0158(10) 0.0167(11) 0.0170(9) -0.0025(8) 0.0060(8) -0.0014(8) C8 0.0168(10) 0.0131(10) 0.0171(9) 0.0018(8) 0.0067(8) -0.0005(8) C9 0.0204(11) 0.0267(13) 0.0209(10) -0.0026(9) -0.0009(9) 0.0064(10) C10 0.0115(9) 0.0187(11) 0.0167(9) 0.0015(8) 0.0053(8) -0.0007(8) C11 0.0122(9) 0.0156(11) 0.0166(9) 0.0018(8) 0.0071(8) 0.0003(8) C12 0.0153(10) 0.0183(11) 0.0138(9) -0.0001(8) 0.0086(8) -0.0007(8) C13 0.0133(9) 0.0237(11) 0.0113(9) 0.0034(8) 0.0066(8) 0.0006(8) C14 0.0146(10) 0.0166(11) 0.0180(10) 0.0042(8) 0.0076(8) 0.0003(8) C15 0.0167(11) 0.0218(12) 0.0227(11) -0.0026(9) 0.0024(9) -0.0046(9) C16 0.0164(10) 0.0181(11) 0.0277(11) 0.0053(9) 0.0092(9) 0.0045(9) C17 0.0259(12) 0.0223(12) 0.0187(10) -0.0060(8) 0.0119(9) -0.0052(10) C18 0.0188(11) 0.0366(14) 0.0109(9) 0.0021(9) 0.0047(8) 0.0011(10) C19 0.0230(11) 0.0155(12) 0.0291(12) 0.0064(9) 0.0089(10) 0.0033(9) C20 0.0240(12) 0.0277(14) 0.0335(13) -0.0105(10) 0.0111(10) -0.0044(10) F1 0.0608(11) 0.0371(9) 0.0313(8) -0.0030(6) 0.0278(8) -0.0042(8) F2 0.0430(10) 0.0427(10) 0.0460(9) -0.0098(8) 0.0106(8) 0.0206(8) 248 U11 U22 U33 U23 U13 U12 F3 0.0330(9) 0.0796(14) 0.0702(12) -0.0385(11) 0.0297(9) -0.0321(9) Ir1 0.01080(4) 0.01216(4) 0.00910(3) 0.00099(3) 0.00309(3) 0.00051(3) N1 0.0153(9) 0.0165(9) 0.0141(8) 0.0017(7) 0.0043(7) 0.0032(8) N2 0.0155(8) 0.0134(9) 0.0114(7) 0.0024(6) 0.0062(6) 0.0021(7) O1 0.0221(8) 0.0146(8) 0.0152(6) -0.0016(6) 0.0080(6) -0.0008(6) O2 0.0157(7) 0.0193(8) 0.0158(7) 0.0001(6) 0.0045(6) -0.0067(6) O3 0.0436(11) 0.0320(11) 0.0204(8) -0.0018(7) 0.0072(8) -0.0048(8) O4 0.0499(12) 0.0218(9) 0.0464(11) 0.0020(8) 0.0245(9) 0.0111(8) O5 0.0254(9) 0.0405(11) 0.0339(10) -0.0016(8) 0.0069(8) -0.0145(8) S1 0.0137(2) 0.0128(2) 0.0114(2) 0.00031(17) 0.00407(18) - 0.00180(19) S2 0.0200(3) 0.0195(3) 0.0226(3) -0.0014(2) 0.0092(2) -0.0014(2) Table 7. Hydrogen atomic coordinates and isotropic atomic displacement parameters (Å 2 ) for Complex 3.6. x/a y/b z/c U(eq) H1A -0.0631 0.3788 0.2747 0.022 H1B -0.0328 0.4661 0.3501 0.022 H2A 0.1181 0.3523 0.4257 0.02 H2B 0.0162 0.2624 0.3868 0.02 H4 0.2767 -0.0481 0.4626 0.019 H5 0.4334 -0.0529 0.5821 0.022 H7 0.4744 0.2930 0.5673 0.02 H8 0.3194 0.2991 0.4471 0.019 H9A 0.6141 0.1907 0.6692 0.037 H9B 0.6229 0.0533 0.6605 0.037 249 x/a y/b z/c U(eq) H9C 0.5488 0.1058 0.7097 0.037 H15A 0.5045 0.5054 0.3249 0.032 H15B 0.4582 0.4314 0.3834 0.032 H15C 0.4033 0.5547 0.3506 0.032 H16A 0.3935 0.1400 0.2917 0.03 H16B 0.4622 0.2392 0.3521 0.03 H16C 0.4936 0.2074 0.2743 0.03 H17A 0.2527 0.1654 0.0887 0.032 H17B 0.1376 0.1701 0.1079 0.032 H17C 0.2469 0.1080 0.1696 0.032 H18A 0.0649 0.4871 0.0770 0.033 H18B 0.0523 0.3501 0.0629 0.033 H18C 0.1298 0.4234 0.0254 0.033 H19A 0.2909 0.6496 0.1693 0.034 H19B 0.2583 0.6435 0.2490 0.034 H19C 0.1630 0.6245 0.1625 0.034 H1N 0.0407(18) 0.5154(19) 0.2447(13) 0.014(6) H2N 0.117(3) 0.533(3) 0.3245(18) 0.056(10) 250 Crystal structure of 4.1. Figure 8.8.4. X-Ray structure of complex 4.1. A clear red Block-like specimen of C29H27F3IrN3O4S, approximate dimensions 0.142 mm x 0.203 mm x 0.302 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 0.70 hours. The frames were integrated with the Bruker SAINT software package using a SAINT V8.34A (Bruker AXS, 251 2013) algorithm. The integration of the data using a monoclinic unit cell yielded a total of 65072 reflections to a maximum θ angle of 30.46° (0.70 Å resolution), of which 8003 were independent (average redundancy 8.131, completeness = 99.6%, Rint = 7.23%, Rsig = 4.07%) and 6740 (84.22%) were greater than 2σ(F 2 ). The final cell constants of a = 9.7042(13) Å, b = 14.975(2) Å, c = 18.313(2) Å, β = 96.560(2)°, volume = 2643.8(6) Å 3 , are based upon the refinement of the XYZ-centroids of 9464 reflections above 20 σ(I) with 4.477° < 2θ < 60.78°. Data were corrected for absorption effects using the multi-scan method (SADABS). The ratio of minimum to maximum apparent transmission was 0.784. The calculated minimum and maximum transmission coefficients (based on crystal size) are 0.3030 and 0.5260. 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, C29H27F3IrN3O4S. The final anisotropic full-matrix least-squares refinement on F 2 with 385 variables converged at R1 = 2.39%, for the observed data and wR2 = 5.07% for all data. The goodness-of-fit was 1.038. The largest peak in the final difference electron density synthesis was 0.729 e - /Å 3 and the largest hole was -0.635 e - /Å 3 with an RMS deviation of 0.129 e - /Å 3 . On the basis of the final model, the calculated density was 1.916g/cm 3 and F(000), 1496 e - . Table 2. Sample and crystal data for Complex 4.1. Identification code Complex 4.1 Chemical formula C29H27F3IrN3O4S Formula weight 762.79 g/mol Temperature 100(2) K Wavelength 0.71073 Å Crystal size 0.142 x 0.203 x 0.302 mm Crystal habit clear red Block Crystal system monoclinic Space group P 1 21/c 1 252 Unit cell dimensions a = 9.7042(13) Å α = 90° b = 14.975(2) Å β = 96.560(2)° c = 18.313(2) Å γ = 90° Volume 2643.8(6) Å 3 Z 4 Density (calculated) 1.916 g/cm 3 Absorption coefficient 5.193 mm -1 F(000) 1496 Table 3. Data collection and structure refinement for Complex 4.1. Diffractometer Bruker APEX DUO Radiation source fine-focus tube, MoKα Theta range for data collection 1.76 to 30.46° Index ranges -13<=h<=13, -21<=k<=21, -26<=l<=26 Reflections collected 65072 Independent reflections 8003 [R(int) = 0.0723] Coverage of independent reflections 99.6% Absorption correction multi-scan Max. and min. transmission 0.5260 and 0.3030 Structure solution technique direct methods Structure solution program SHELXTL XT 2014/4 (Bruker AXS, 2014) Refinement method Full-matrix least-squares on F 2 Refinement program SHELXTL XL 2014/7 (Bruker AXS, 2014) 253 Function minimized Σ w(Fo 2 - Fc 2 ) 2 Data / restraints / parameters 8003 / 6 / 385 Goodness-of-fit on F 2 1.038 Δ/σmax 0.002 Final R indices 6740 data; I>2σ(I) R1 = 0.0239, wR2 = 0.0481 all data R1 = 0.0329, wR2 = 0.0507 Weighting scheme w=1/[σ 2 (Fo 2 )+(0.0161P) 2 +0.1290P] where P=(Fo 2 +2Fc 2 )/3 Largest diff. peak and hole 0.729 and -0.635 eÅ -3 R.M.S. deviation from mean 0.129 eÅ -3 Table 4. Atomic coordinates and equivalent isotropic atomic displacement parameters (Å 2 ) for Complex 4.1. U(eq) is defined as one third of the trace of the orthogonalized Uij tensor. x/a y/b z/c U(eq) C1 0.1592(3) 0.47819(17) 0.78632(14) 0.0163(5) C2 0.1312(3) 0.39476(18) 0.75216(15) 0.0205(6) C3 0.1337(3) 0.38871(18) 0.67781(15) 0.0201(6) C4 0.1654(2) 0.46462(16) 0.63770(14) 0.0139(5) C5 0.1937(2) 0.54607(15) 0.67677(12) 0.0103(4) C6 0.1688(3) 0.46279(18) 0.56049(14) 0.0188(5) C7 0.1999(3) 0.53838(18) 0.52414(14) 0.0191(6) C8 0.2296(3) 0.61839(17) 0.56296(13) 0.0145(5) 254 x/a y/b z/c U(eq) C9 0.2281(2) 0.62451(15) 0.63800(13) 0.0101(4) C10 0.2336(2) 0.71738(16) 0.67347(12) 0.0096(4) C11 0.2870(2) 0.72109(15) 0.75569(12) 0.0094(4) C12 0.2039(2) 0.75396(15) 0.80635(13) 0.0117(5) C13 0.2558(3) 0.75886(16) 0.87960(13) 0.0144(5) C14 0.3921(3) 0.73265(17) 0.90064(13) 0.0154(5) C15 0.4708(3) 0.70249(16) 0.84766(13) 0.0143(5) C16 0.3276(2) 0.78220(15) 0.63584(12) 0.0098(4) C17 0.2772(3) 0.86233(16) 0.60513(13) 0.0128(5) C18 0.3672(3) 0.92064(17) 0.57572(13) 0.0162(5) C19 0.5069(3) 0.89823(16) 0.57924(13) 0.0158(5) C20 0.5509(3) 0.81776(17) 0.61098(13) 0.0141(5) C21 0.5438(3) 0.51903(17) 0.75065(14) 0.0147(5) C22 0.6718(3) 0.56236(18) 0.76649(14) 0.0168(5) C23 0.8014(3) 0.53301(19) 0.73237(15) 0.0216(6) C24 0.8226(3) 0.59037(19) 0.66520(16) 0.0229(6) C25 0.6872(3) 0.61745(18) 0.62270(15) 0.0187(5) C26 0.5714(3) 0.56117(18) 0.60489(13) 0.0154(5) C27 0.5671(3) 0.46216(17) 0.62201(15) 0.0196(6) C28 0.5214(3) 0.44122(17) 0.69811(14) 0.0177(5) C29 0.9570(3) 0.87935(16) 0.43601(13) 0.0138(5) F1 0.89322(17) 0.95716(10) 0.42018(9) 0.0237(4) F2 0.08938(15) 0.89766(11) 0.46057(8) 0.0238(4) F3 0.95757(16) 0.83450(10) 0.37246(8) 0.0216(3) Ir1 0.53401(2) 0.64427(2) 0.69513(2) 0.00992(3) N1 0.1888(2) 0.55153(14) 0.75136(11) 0.0137(4) N2 0.4194(2) 0.69587(13) 0.77606(11) 0.0102(4) 255 x/a y/b z/c U(eq) N3 0.4631(2) 0.75951(13) 0.63766(10) 0.0105(4) O1 0.09613(17) 0.75189(12) 0.66717(9) 0.0117(3) O2 0.8625(2) 0.87661(13) 0.56203(10) 0.0259(5) O3 0.74142(19) 0.79013(15) 0.46130(11) 0.0278(5) O4 0.96681(19) 0.74131(12) 0.51983(10) 0.0210(4) S1 0.87143(6) 0.81504(4) 0.50227(3) 0.01455(12) Table 5. Bond lengths (Å) for Complex 4.1. C1-N1 1.319(3) C1-C2 1.410(4) C1-H1A 0.95 C2-C3 1.368(4) C2-H2 0.95 C3-C4 1.406(4) C3-H3 0.95 C4-C6 1.418(3) C4-C5 1.425(3) C5-N1 1.375(3) C5-C9 1.432(3) C6-C7 1.364(4) C6-H6 0.95 C7-C8 1.406(3) C7-H7 0.95 C8-C9 1.379(3) C8-H8 0.95 C9-C10 1.533(3) C10-O1 1.423(3) C10-C11 1.536(3) C10-C16 1.547(3) C11-N2 1.350(3) C11-C12 1.387(3) C12-C13 1.380(3) C12-H12 0.95 C13-C14 1.391(3) C13-H13 0.95 C14-C15 1.378(3) C14-H14 0.95 C15-N2 1.352(3) C15-H15 0.95 C16-N3 1.355(3) C16-C17 1.390(3) C17-C18 1.387(3) C17-H17 0.95 C18-C19 1.391(4) 256 C18-H18 0.95 C19-C20 1.384(3) C19-H19 0.95 C20-N3 1.349(3) C20-H20 0.95 C21-C22 1.402(4) C21-C28 1.511(4) C21-Ir1 2.130(2) C21-H21 0.983(18) C22-C23 1.531(4) C22-Ir1 2.145(2) C22-H22 0.968(18) C23-C24 1.533(4) C23-H23A 0.99 C23-H23B 0.99 C24-C25 1.504(4) C24-H24A 0.99 C24-H24B 0.99 C25-C26 1.413(4) C25-Ir1 2.141(2) C25-H25 0.975(18) C26-C27 1.517(4) C26-Ir1 2.133(2) C26-H26 0.962(18) C27-C28 1.542(4) C27-H27A 0.99 C27-H27B 0.99 C28-H28A 0.99 C28-H28B 0.99 C29-F1 1.336(3) C29-F2 1.340(3) C29-F3 1.344(3) C29-S1 1.822(3) Ir1-N3 2.096(2) Ir1-N2 2.099(2) O1-H1O 0.76(3) O2-S1 1.4410(19) O3-S1 1.4414(19) O4-S1 1.4530(19) Table 6. Bond angles (°) for Complex 4.1. N1-C1-C2 124.3(2) N1-C1-H1A 117.8 C2-C1-H1A 117.8 C3-C2-C1 118.4(2) C3-C2-H2 120.8 C1-C2-H2 120.8 C2-C3-C4 119.8(2) C2-C3-H3 120.1 C4-C3-H3 120.1 C3-C4-C6 122.5(2) 257 C3-C4-C5 118.1(2) C6-C4-C5 119.5(2) N1-C5-C4 121.6(2) N1-C5-C9 118.7(2) C4-C5-C9 119.7(2) C7-C6-C4 120.1(2) C7-C6-H6 119.9 C4-C6-H6 119.9 C6-C7-C8 120.3(2) C6-C7-H7 119.9 C8-C7-H7 119.9 C9-C8-C7 122.4(2) C9-C8-H8 118.8 C7-C8-H8 118.8 C8-C9-C5 118.0(2) C8-C9-C10 118.6(2) C5-C9-C10 122.2(2) O1-C10-C9 107.93(18) O1-C10-C11 105.90(18) C9-C10-C11 116.08(19) O1-C10-C16 109.34(18) C9-C10-C16 111.99(18) C11-C10-C16 105.32(18) N2-C11-C12 121.5(2) N2-C11-C10 117.6(2) C12-C11-C10 120.8(2) C13-C12-C11 119.6(2) C13-C12-H12 120.2 C11-C12-H12 120.2 C12-C13-C14 118.9(2) C12-C13-H13 120.5 C14-C13-H13 120.5 C15-C14-C13 118.9(2) C15-C14-H14 120.5 C13-C14-H14 120.5 N2-C15-C14 122.3(2) N2-C15-H15 118.9 C14-C15-H15 118.9 N3-C16-C17 121.5(2) N3-C16-C10 116.9(2) C17-C16-C10 121.6(2) C18-C17-C16 119.5(2) C18-C17-H17 120.3 C16-C17-H17 120.3 C17-C18-C19 118.9(2) C17-C18-H18 120.5 C19-C18-H18 120.5 C20-C19-C18 118.8(2) C20-C19-H19 120.6 C18-C19-H19 120.6 N3-C20-C19 122.5(2) N3-C20-H20 118.7 C19-C20-H20 118.7 C22-C21-C28 123.3(2) 258 C22-C21-Ir1 71.42(15) C28-C21-Ir1 112.31(16) C22-C21-H21 117.2(16) C28-C21-H21 114.2(17) Ir1-C21-H21 109.2(17) C21-C22-C23 122.2(2) C21-C22-Ir1 70.30(14) C23-C22-Ir1 113.54(17) C21-C22-H22 120.4(17) C23-C22-H22 112.5(17) Ir1-C22-H22 108.8(17) C22-C23-C24 111.0(2) C22-C23-H23A 109.4 C24-C23-H23A 109.4 C22-C23-H23B 109.4 C24-C23-H23B 109.4 H23A-C23-H23B 108.0 C25-C24-C23 112.1(2) C25-C24-H24A 109.2 C23-C24-H24A 109.2 C25-C24-H24B 109.2 C23-C24-H24B 109.2 H24A-C24-H24B 107.9 C26-C25-C24 125.7(2) C26-C25-Ir1 70.39(14) C24-C25-Ir1 110.94(18) C26-C25-H25 115.1(17) C24-C25-H25 113.8(17) Ir1-C25-H25 111.8(17) C25-C26-C27 125.1(2) C25-C26-Ir1 71.00(15) C27-C26-Ir1 113.51(17) C25-C26-H26 113.8(17) C27-C26-H26 116.0(17) Ir1-C26-H26 106.9(16) C26-C27-C28 113.8(2) C26-C27-H27A 108.8 C28-C27-H27A 108.8 C26-C27-H27B 108.8 C28-C27-H27B 108.8 259 H27A-C27-H27B 107.7 C21-C28-C27 112.5(2) C21-C28-H28A 109.1 C27-C28-H28A 109.1 C21-C28-H28B 109.1 C27-C28-H28B 109.1 H28A-C28-H28B 107.8 F1-C29-F2 107.3(2) F1-C29-F3 107.19(19) F2-C29-F3 107.1(2) F1-C29-S1 111.75(17) F2-C29-S1 112.15(16) F3-C29-S1 111.09(17) N3-Ir1-N2 83.20(7) N3-Ir1-C21 163.47(9) N2-Ir1-C21 89.16(9) N3-Ir1-C26 99.58(9) N2-Ir1-C26 155.87(9) C21-Ir1-C26 81.60(10) N3-Ir1-C25 93.14(9) N2-Ir1-C25 165.48(9) C21-Ir1-C25 97.71(10) C26-Ir1-C25 38.61(10) N3-Ir1-C22 157.33(9) N2-Ir1-C22 97.13(9) C21-Ir1-C22 38.28(10) C26-Ir1-C22 89.37(10) C25-Ir1-C22 80.87(10) C1-N1-C5 117.8(2) C11-N2-C15 118.8(2) C11-N2-Ir1 118.17(15) C15-N2-Ir1 123.01(16) C20-N3-C16 118.7(2) C20-N3-Ir1 121.97(16) C16-N3-Ir1 118.74(15) C10-O1-H1O 108.(2) O2-S1-O3 115.85(13) O2-S1-O4 114.21(12) O3-S1-O4 114.59(12) O2-S1-C29 103.82(12) O3-S1-C29 103.20(11) O4-S1-C29 102.81(11) 260 Table 7. Anisotropic atomic displacement parameters (Å 2 ) for Complex 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 0.0128(12) 0.0183(13) 0.0180(12) 0.0039(10) 0.0023(10) -0.0015(10) C2 0.0178(13) 0.0148(13) 0.0295(15) 0.0068(11) 0.0048(11) -0.0046(11) C3 0.0173(13) 0.0128(12) 0.0300(15) -0.0020(11) 0.0017(11) -0.0060(10) C4 0.0086(11) 0.0135(12) 0.0194(12) -0.0012(10) 0.0009(9) -0.0002(9) C5 0.0068(11) 0.0114(11) 0.0122(11) -0.0003(9) -0.0011(8) 0.0012(9) C6 0.0182(13) 0.0185(13) 0.0194(13) -0.0082(10) 0.0013(10) -0.0042(10) C7 0.0207(14) 0.0241(14) 0.0127(12) -0.0060(10) 0.0027(10) -0.0036(11) C8 0.0157(12) 0.0163(12) 0.0111(11) -0.0001(9) 0.0004(9) -0.0008(10) C9 0.0075(11) 0.0112(11) 0.0111(11) 0.0004(8) -0.0013(8) -0.0012(8) C10 0.0092(11) 0.0107(11) 0.0087(10) -0.0001(9) -0.0001(8) 0.0014(9) C11 0.0116(11) 0.0061(10) 0.0103(11) 0.0009(8) 0.0005(9) -0.0001(9) C12 0.0118(11) 0.0095(11) 0.0143(11) -0.0012(9) 0.0028(9) -0.0009(9) C13 0.0197(13) 0.0126(12) 0.0117(11) -0.0013(9) 0.0055(9) -0.0029(10) C14 0.0202(13) 0.0162(12) 0.0086(11) 0.0018(9) -0.0039(9) -0.0013(10) C15 0.0164(12) 0.0126(12) 0.0130(12) -0.0001(9) -0.0023(9) 0.0005(10) C16 0.0130(11) 0.0088(11) 0.0077(10) -0.0005(8) 0.0011(8) -0.0023(9) 261 U11 U22 U33 U23 U13 U12 C17 0.0142(12) 0.0136(12) 0.0105(11) 0.0016(9) 0.0013(9) 0.0018(9) C18 0.0223(13) 0.0119(12) 0.0146(12) 0.0039(10) 0.0030(10) 0.0018(10) C19 0.0219(13) 0.0113(12) 0.0150(12) 0.0002(10) 0.0057(10) -0.0040(10) C20 0.0134(12) 0.0157(12) 0.0139(11) -0.0012(10) 0.0046(9) -0.0017(10) C21 0.0149(12) 0.0146(12) 0.0148(12) 0.0055(10) 0.0028(9) 0.0043(10) C22 0.0166(13) 0.0168(13) 0.0158(12) 0.0002(10) -0.0037(10) 0.0083(10) C23 0.0112(12) 0.0269(15) 0.0255(14) -0.0046(12) -0.0026(10) 0.0078(11) C24 0.0156(13) 0.0229(15) 0.0315(15) -0.0108(12) 0.0083(11) -0.0001(11) C25 0.0222(14) 0.0148(12) 0.0213(13) -0.0010(10) 0.0118(11) 0.0038(11) C26 0.0162(12) 0.0179(13) 0.0124(11) 0.0001(10) 0.0029(9) 0.0056(10) C27 0.0198(14) 0.0132(13) 0.0256(14) -0.0049(10) 0.0028(11) -0.0001(10) C28 0.0147(12) 0.0098(11) 0.0292(14) 0.0017(11) 0.0054(10) 0.0011(10) C29 0.0154(12) 0.0133(12) 0.0124(11) -0.0015(9) -0.0004(9) 0.0031(9) F1 0.0322(9) 0.0138(8) 0.0246(8) 0.0025(6) 0.0005(7) 0.0074(7) F2 0.0148(8) 0.0319(9) 0.0239(8) 0.0030(7) -0.0012(6) -0.0041(7) F3 0.0276(9) 0.0241(9) 0.0135(7) -0.0042(6) 0.0048(6) 0.0045(7) Ir1 0.00886(5) 0.00990(5) 0.01112(5) 0.00078(4) 0.00162(3) 0.00105(4) N1 0.0117(10) 0.0157(11) 0.0138(10) 0.0036(8) 0.0027(8) -0.0002(8) N2 0.0087(9) 0.0105(10) 0.0112(9) 0.0014(8) -0.0003(8) -0.0008(8) N3 0.0121(10) 0.0108(10) 0.0085(9) -0.0010(7) 0.0008(7) -0.0010(8) O1 0.0074(8) 0.0164(9) 0.0109(8) 0.0014(7) -0.0006(6) 0.0026(7) 262 U11 U22 U33 U23 U13 U12 O2 0.0324(12) 0.0294(11) 0.0172(10) -0.0073(8) 0.0084(8) 0.0010(9) O3 0.0150(10) 0.0436(13) 0.0232(10) 0.0044(9) -0.0049(8) -0.0079(9) O4 0.0240(10) 0.0168(10) 0.0202(10) 0.0023(7) -0.0059(8) 0.0005(8) S1 0.0128(3) 0.0191(3) 0.0114(3) -0.0001(2) -0.0003(2) -0.0004(2) Table 8. Hydrogen atomic coordinates and isotropic atomic displacement parameters (Å 2 ) for Complex 4.1. x/a y/b z/c U(eq) H1A 0.1567 0.4818 0.8379 0.02 H2 0.1110 0.3439 0.7801 0.025 H3 0.1142 0.3334 0.6534 0.024 H6 0.1494 0.4088 0.5340 0.023 H7 0.2016 0.5369 0.4724 0.023 H8 0.2515 0.6701 0.5365 0.017 H12 0.1119 0.7730 0.7907 0.014 H13 0.1993 0.7798 0.9151 0.017 H14 0.4302 0.7355 0.9507 0.018 H15 0.5645 0.6858 0.8619 0.017 H17 0.1818 0.8770 0.6043 0.015 H18 0.3340 0.9750 0.5535 0.019 H19 0.5709 0.9375 0.5602 0.019 H20 0.6466 0.8030 0.6141 0.017 H21 0.480(2) 0.5201(19) 0.7889(12) 0.018 H22 0.694(3) 0.5932(17) 0.8128(11) 0.02 H23A 0.7918 0.4696 0.7174 0.026 H23B 0.8837 0.5384 0.7694 0.026 263 x/a y/b z/c U(eq) H24A 0.8756 0.6446 0.6816 0.028 H24B 0.8780 0.5564 0.6325 0.028 H25 0.696(3) 0.6665(15) 0.5885(14) 0.022 H26 0.510(2) 0.5811(18) 0.5631(12) 0.019 H27A 0.6605 0.4365 0.6195 0.023 H27B 0.5024 0.4325 0.5838 0.023 H28A 0.4218 0.4251 0.6921 0.021 H28B 0.5742 0.3890 0.7194 0.021 H1O 0.064(3) 0.7449(18) 0.6275(15) 0.014 264 Crystal structure of 4.12. Figure 8.8.5. X-Ray structure of complex 4.12. A clear colourless blades-like specimen of C32H26N4O2Zn, approximate dimensions 0.080 mm x 0.130 mm x 0.320 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 21.00 hours. The frames were integrated with the Bruker SAINT software package using a SAINT V8.37A (Bruker AXS, 2013) algorithm. The integration of the data using a monoclinic unit cell yielded a total of 35490 reflections to a maximum θ angle of 30.82° (0.69 Å resolution), of which 4522 were 265 independent (average redundancy 7.848, completeness = 98.4%, Rint = 6.47%, Rsig = 4.25%) and 3487 (77.11%) were greater than 2σ(F 2 ). The final cell constants of a = 22.909(6) Å, b = 8.141(2) Å, c = 16.097(5) Å, β = 102.406(5)°, volume = 2932.0(14) Å 3 , are based upon the refinement of the XYZ-centroids of reflections above 20 σ(I). Data were corrected for absorption effects using the multi-scan method (SADABS). The calculated minimum and maximum transmission coefficients (based on crystal size) are 0.7650 and 0.9330. The structure was solved and refined using the Bruker SHELXTL Software Package, using the space group C 1 2/c 1, with Z = 4 for the formula unit, C32H26N4O2Zn. The final anisotropic full-matrix least-squares refinement on F 2 with 206 variables converged at R1 = 4.03%, for the observed data and wR2 = 9.87% for all data. The goodness-of-fit was 1.049. The largest peak in the final difference electron density synthesis was 0.892 e - /Å 3 and the largest hole was -0.791 e - /Å 3 with an RMS deviation of 0.086 e - /Å 3 . On the basis of the final model, the calculated density was 1.441g/cm 3 and F(000), 1328 e - . Table 2. Sample and crystal data for Complex 4.12. Identification code Complex 4.12 Chemical formula C32H26N4O2Zn Formula weight 636.04 g/mol Temperature 100(2) K Wavelength 0.71073 Å Crystal size 0.080 x 0.130 x 0.320 mm Crystal habit clear colourless blades Crystal system monoclinic Space group C 1 2/c 1 266 Unit cell dimensions a = 22.909(6) Å α = 90° b = 8.141(2) Å β = 102.406(5)° c = 16.097(5) Å γ = 90° Volume 2932.0(14) Å 3 Z 4 Density (calculated) 1.441 g/cm 3 Absorption coefficient 0.883 mm -1 F(000) 1328 Table 3. Data collection and structure refinement for Complex 4.12. Diffractometer Bruker APEX DUO Radiation source fine-focus tube, MoKα Theta range for data collection 1.82 to 30.82° Index ranges -31<=h<=32, -11<=k<=11, -23<=l<=22 Reflections collected 35490 Independent reflections 4522 [R(int) = 0.0647] Absorption correction multi-scan Max. and min. transmission 0.9330 and 0.7650 Structure solution technique direct methods Structure solution program SHELXTL XT 2014/5 (Bruker AXS, 2014) Refinement method Full-matrix least-squares on F 2 Refinement program SHELXTL XL 2014/7 (Bruker AXS, 2014) 267 Function minimized Σ w(Fo 2 - Fc 2 ) 2 Data / restraints / parameters 4522 / 7 / 206 Goodness-of-fit on F 2 1.049 Final R indices 3487 data; I>2σ(I) R1 = 0.0403, wR2 = 0.0903 all data R1 = 0.0625, wR2 = 0.0987 Weighting scheme w=1/[σ 2 (Fo 2 )+(0.0425P) 2 +4.9624P] where P=(Fo 2 +2Fc 2 )/3 Largest diff. peak and hole 0.892 and -0.791 eÅ -3 R.M.S. deviation from mean 0.086 eÅ -3 Table 4. Atomic coordinates and equivalent isotropic atomic displacement parameters (Å 2 ) for Complex 4.12. U(eq) is defined as one third of the trace of the orthogonalized Uij tensor. x/a y/b z/c U(eq) C1 0.30907(8) 0.6048(2) 0.52824(12) 0.0144(3) C2 0.35172(9) 0.7179(2) 0.51660(13) 0.0177(4) C3 0.40365(9) 0.6567(2) 0.49608(14) 0.0201(4) C4 0.41141(8) 0.4881(2) 0.49005(13) 0.0171(4) C5 0.36672(8) 0.3828(2) 0.50450(11) 0.0114(3) C6 0.37137(7) 0.1921(2) 0.50362(11) 0.0108(3) C7 0.43048(8) 0.1471(2) 0.56580(12) 0.0154(4) C8 0.37144(8) 0.1416(2) 0.41127(12) 0.0128(3) 268 x/a y/b z/c U(eq) C9 0.42163(8) 0.0793(2) 0.38788(13) 0.0183(4) C10 0.42244(9) 0.0336(3) 0.30345(14) 0.0248(4) C11 0.37263(10) 0.0523(3) 0.24052(13) 0.0224(4) C12 0.31913(9) 0.1131(2) 0.26039(12) 0.0164(4) C13 0.31816(8) 0.1577(2) 0.34588(12) 0.0127(3) C14 0.26585(10) 0.1271(2) 0.19754(13) 0.0214(4) C15 0.21488(10) 0.1815(3) 0.21940(13) 0.0228(4) C16 0.21740(9) 0.2232(2) 0.30521(13) 0.0186(4) N1 0.31608(7) 0.44190(18) 0.52119(10) 0.0121(3) N2 0.26619(7) 0.21436(18) 0.36608(10) 0.0135(3) O1 0.32476(5) 0.11796(15) 0.53255(8) 0.0111(2) Zn1 0.25 0.25 0.5 0.01023(8) C17 0.5435(3) 0.6150(8) 0.2101(4) 0.0502(8) C18 0.5663(3) 0.4610(7) 0.2552(5) 0.0502(8) C19 0.5121(3) 0.3810(7) 0.2714(4) 0.0502(8) C20 0.4710(3) 0.5180(8) 0.2775(5) 0.0502(8) O2 0.5015(5) 0.6673(5) 0.2524(8) 0.0575(13) Table 5. Bond lengths (Å) for Complex 4.12. C1-N1 1.344(2) C1-C2 1.384(3) C1-H1 0.95 C2-C3 1.394(3) C2-H2 0.95 C3-C4 1.390(3) C3-H3 0.95 C4-C5 1.393(2) C4-H4 0.95 C5-N1 1.335(2) C5-C6 1.556(3) C6-O1 1.391(2) C6-C8 1.543(3) C6-C7 1.545(2) C7-H7A 0.98 C7-H7B 0.98 269 C7-H7C 0.98 C8-C9 1.381(2) C8-C13 1.436(3) C9-C10 1.413(3) C9-H9 0.95 C10-C11 1.362(3) C10-H10 0.95 C11-C12 1.421(3) C11-H11 0.95 C12-C14 1.413(3) C12-C13 1.428(3) C13-N2 1.379(2) C14-C15 1.364(3) C14-H14 0.95 C15-C16 1.411(3) C15-H15 0.95 C16-N2 1.320(2) C16-H16 0.95 N1-Zn1 2.1510(15) N2-Zn1 2.2830(17) O1-Zn1 1.9944(13) Zn1-O1 1.9944(13) Zn1-N1 2.1510(15) Zn1-N2 2.2830(17) C17-O2 1.360(10) C17-C18 1.486(9) C17-H17A 0.99 C17-H17B 0.99 C18-C19 1.473(9) C18-H18A 0.99 C18-H18B 0.99 C19-C20 1.477(9) C19-H19A 0.99 C19-H19B 0.99 C20-O2 1.501(7) C20-H20A 0.99 C20-H20B 0.99 Table 6. Bond angles (°) for Complex 4.12. N1-C1-C2 122.98(17) N1-C1-H1 118.5 C2-C1-H1 118.5 C1-C2-C3 117.24(16) C1-C2-H2 121.4 C3-C2-H2 121.4 C4-C3-C2 119.87(17) C4-C3-H3 120.1 C2-C3-H3 120.1 C3-C4-C5 119.12(17) C3-C4-H4 120.4 C5-C4-H4 120.4 N1-C5-C4 120.89(16) N1-C5-C6 115.17(15) 270 C4-C5-C6 123.94(15) O1-C6-C8 111.50(14) O1-C6-C7 108.00(14) C8-C6-C7 112.27(14) O1-C6-C5 111.77(14) C8-C6-C5 106.80(14) C7-C6-C5 106.43(14) C6-C7-H7A 109.5 C6-C7-H7B 109.5 H7A-C7-H7B 109.5 C6-C7-H7C 109.5 H7A-C7-H7C 109.5 H7B-C7-H7C 109.5 C9-C8-C13 117.38(17) C9-C8-C6 122.27(17) C13-C8-C6 120.35(15) C8-C9-C10 122.87(19) C8-C9-H9 118.6 C10-C9-H9 118.6 C11-C10-C9 120.25(18) C11-C10-H10 119.9 C9-C10-H10 119.9 C10-C11-C12 119.81(19) C10-C11-H11 120.1 C12-C11-H11 120.1 C14-C12-C11 121.43(18) C14-C12-C13 118.67(17) C11-C12-C13 119.89(18) N2-C13-C12 120.33(17) N2-C13-C8 119.90(16) C12-C13-C8 119.77(16) C15-C14-C12 119.83(18) C15-C14-H14 120.1 C12-C14-H14 120.1 C14-C15-C16 118.24(19) C14-C15-H15 120.9 C16-C15-H15 120.9 N2-C16-C15 124.28(18) N2-C16-H16 117.9 C15-C16-H16 117.9 C5-N1-C1 119.82(16) C5-N1-Zn1 108.59(11) C1-N1-Zn1 129.60(12) C16-N2-C13 118.63(16) C16-N2-Zn1 114.24(13) C13-N2-Zn1 126.06(12) C6-O1-Zn1 110.84(10) O1-Zn1-O1 180.00(6) O1-Zn1-N1 79.31(6) O1-Zn1-N1 100.69(6) O1-Zn1-N1 100.70(6) O1-Zn1-N1 79.30(6) N1-Zn1-N1 180.0 O1-Zn1-N2 97.18(5) O1-Zn1-N2 82.82(5) N1-Zn1-N2 90.54(6) 271 N1-Zn1-N2 89.45(6) O1-Zn1-N2 82.82(5) O1-Zn1-N2 97.18(5) N1-Zn1-N2 89.45(6) N1-Zn1-N2 90.55(6) N2-Zn1-N2 180.0 O2-C17-C18 103.4(6) O2-C17-H17A 111.1 C18-C17- H17A 111.1 O2-C17-H17B 111.1 C18-C17- H17B 111.1 H17A-C17- H17B 109.1 C19-C18-C17 103.8(5) C19-C18-H18A 111.0 C17-C18- H18A 111.0 C19-C18-H18B 111.0 C17-C18- H18B 111.0 H18A-C18- H18B 109.0 C18-C19-C20 104.6(5) C18-C19-H19A 110.8 C20-C19- H19A 110.8 C18-C19-H19B 110.8 C20-C19- H19B 110.8 H19A-C19- H19B 108.9 C19-C20-O2 104.6(6) C19-C20-H20A 110.8 O2-C20-H20A 110.8 C19-C20-H20B 110.8 O2-C20-H20B 110.8 H20A-C20- H20B 108.9 C17-O2-C20 107.6(6) Table 7. Anisotropic atomic displacement parameters (Å 2 ) for Complex 4.12. 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 0.0146(8) 0.0123(8) 0.0165(9) -0.0007(7) 0.0037(7) 0.0015(6) 272 U11 U22 U33 U23 U13 U12 C2 0.0195(9) 0.0112(9) 0.0219(10) -0.0013(6) 0.0034(7) -0.0021(6) C3 0.0191(9) 0.0143(9) 0.0282(11) -0.0010(7) 0.0078(8) -0.0059(7) C4 0.0135(8) 0.0161(8) 0.0234(10) -0.0012(7) 0.0075(7) -0.0015(7) C5 0.0109(8) 0.0123(8) 0.0109(8) -0.0004(6) 0.0024(6) -0.0001(6) C6 0.0085(7) 0.0098(7) 0.0146(8) -0.0007(6) 0.0035(6) 0.0003(6) C7 0.0111(8) 0.0162(8) 0.0186(9) 0.0015(7) 0.0023(7) 0.0013(6) C8 0.0137(8) 0.0096(7) 0.0165(9) -0.0010(6) 0.0067(7) -0.0001(6) C9 0.0146(9) 0.0200(9) 0.0219(10) -0.0029(7) 0.0074(7) 0.0017(7) C10 0.0216(10) 0.0285(11) 0.0283(11) -0.0081(9) 0.0148(9) 0.0020(8) C11 0.0271(11) 0.0237(10) 0.0205(10) -0.0076(8) 0.0139(8) -0.0016(8) C12 0.0208(9) 0.0149(8) 0.0154(9) -0.0023(7) 0.0080(7) -0.0029(7) C13 0.0154(8) 0.0094(7) 0.0149(8) -0.0004(6) 0.0070(7) -0.0007(6) C14 0.0300(11) 0.0210(9) 0.0133(9) -0.0019(7) 0.0046(8) -0.0029(8) C15 0.0234(10) 0.0272(10) 0.0155(10) 0.0009(8) -0.0009(8) 0.0000(8) C16 0.0172(9) 0.0207(10) 0.0177(9) 0.0014(7) 0.0031(7) 0.0038(7) N1 0.0119(7) 0.0105(7) 0.0137(7) 0.0001(5) 0.0027(6) 0.0010(5) N2 0.0139(7) 0.0123(7) 0.0148(7) 0.0004(5) 0.0040(6) 0.0018(5) O1 0.0087(6) 0.0102(5) 0.0152(6) 0.0018(5) 0.0042(5) 0.0000(4) Zn1 0.00811(13) 0.00946(13) 0.01354(14) 0.00048(11) 0.00328(9) 0.00051(10) C17 0.054(2) 0.0387(16) 0.061(2) 0.0011(14) 0.0212(16) -0.0007(14) C18 0.054(2) 0.0387(16) 0.061(2) 0.0011(14) 0.0212(16) -0.0007(14) C19 0.054(2) 0.0387(16) 0.061(2) 0.0011(14) 0.0212(16) -0.0007(14) C20 0.054(2) 0.0387(16) 0.061(2) 0.0011(14) 0.0212(16) -0.0007(14) O2 0.080(3) 0.057(2) 0.0385(19) -0.002(4) 0.018(2) -0.049(4) Table 8. Hydrogen atomic coordinates and isotropic atomic displacement parameters (Å 2 ) for Complex 4.12. 273 x/a y/b z/c U(eq) H1 0.2732 0.6442 0.5418 0.017 H2 0.3458 0.8325 0.5224 0.021 H3 0.4337 0.7301 0.4862 0.024 H4 0.4467 0.4453 0.4762 0.021 H7A 0.4358 0.0277 0.5665 0.023 H7B 0.4291 0.1854 0.6231 0.023 H7C 0.4640 0.1997 0.5472 0.023 H9 0.4572 0.0667 0.4304 0.022 H10 0.4579 -0.0104 0.2905 0.03 H11 0.3737 0.0248 0.1835 0.027 H14 0.2655 0.0987 0.1402 0.026 H15 0.1786 0.1911 0.1780 0.027 H16 0.1817 0.2600 0.3201 0.022 H17A 0.5758 -0.3030 0.2138 0.06 H17B 0.5255 -0.4065 0.1495 0.06 H18A 0.5861 -0.6092 0.2192 0.06 H18B 0.5950 -0.5149 0.3091 0.06 H19A 0.5214 -0.6825 0.3251 0.06 H19B 0.4945 -0.6939 0.2242 0.06 H20A 0.4648 -0.4711 0.3363 0.06 H20B 0.4318 -0.4993 0.2385 0.06 274 8.9. References (1) Perato, S.; Large, B.; Lu, Q.; Gaucher, A.; Prim, D. Pyridylmethylamine–Palladium Catalytic Systems: A Selective Alternative in the C−H Arylation of Indole. ChemCatChem 2017, 9 (3), 389–392. 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Abstract (if available)

Abstract Hydrogenation and dehydrogenation are among the most important reactions in catalysis. As demonstrated in Chapter 1, homogeneous catalysts based on bidentate iridium complexes have a special place in the field of hydride transfer reactions, therefore, were the subject of my investigation. ❧ Chapter 2 describes Cp ⃰ IrCl(2-pyridylmethyl)toluenesulfonamide bidentate complex that effects transfer hydrogenation through a metal-ligand cooperative mechanism through reversibly dearomatized ligand. This complex accesses a mechanism for transfer hydrogenation of ketones with isopropyl alcohol that has not been previously reported. It is the first example of metal-ligand cooperation via reversible ligand dearomatization outside of the pincer scaffold. ❧ Besides the transfer hydrogenation, a newly synthesized family of iridium sulfonamide complexes, including the one mentioned above, act as hydrogenation and water oxidation catalysts. This is demonstrated in Chapter 3. ❧ Chapter 4 describes the base-pendant ligand-metal bifunctional catalytic scaffold wherein the concept of a photobase, compound that becomes more basic in the excited state (pKₐ < pKₐ ⃰ ), is used to switch the proton acceptor ability on an active site of the catalyst. In this system quinoline is an efficient photobase that preserves its unique properties in the close proximity of an iridium center and the photochemistry of the metal is orthogonal to the photobase system. As a result, deprotonation of an aliphatic alcohol by the new iridium complex became possible. This is the first case of metal-orthogonal optical pKₐ control in a transition metal complex. ❧ The same quinoline-containing complex acts as a catalyst for light-driven formic acid dehydrogenation, as revealed in Chapter 5. However, it was demonstrated that the presence of the quinoline moiety does not affect the reaction. Nevertheless, this catalytic scaffold can operate in neat formic acid, at ambient temperature, and more importantly without added base. ❧ Chapter 6 describes a high-utility technique for the conversion of crude glycerol to value-added lactides based on the oxidative conversion of glycerol to lactate. The process utilizes a structurally novel iridium catalyst and enables unprecedented efficiency, longevity, and conversion in the oxidation of glycerol to lactic acid. This enables a very practical alternative to fermentation, which is the only technology known to be applied on a large scale. ❧ Chapter 7 recounts the preliminary data on the synthesis of new gadolinium complexes for the site-specific labeling of proteins that can also be utilized as an MRI contrast agent.

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Creator Demianets, Ivan (author)

Core Title Development of new bifunctional iridium complexes for hydrogenation and dehydrogenation reactions

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Degree Doctor of Philosophy

Degree Program Chemistry

Publication Date 03/08/2019

Defense Date 02/28/2019

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Advisor Williams, Travis (committee chair), Prakash, Surya (committee member), Sharada, Shaama (committee member)

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