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Selective functionalizations of arylboronic acids and studies on cationic intermediates

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Selective functionalizations of arylboronic acids and studies on cationic intermediates

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Content INFORMATION TO USERS This m a n u s c rip t ha s b e e n rep ro d u c e d fr o m the m ic r o f i l m mas ter. UMI film s the text d irectl y fr o m the orig in a l or c o p y s u b m it te d . T h u s , s o m e thesis and d is s ertatio n co p ies are in typewriter face, w h ile o th e rs m a y be fr o m any type of co m p u te r prin te r. The quality of this reproduction is dependent upon the quality of the copy submitted. B r o k e n or in d is ti n ct p rin t, c o lo re d or p o o r quality illustratio ns a n d p h o to g r a p h s , p rin t bleed th ro u g h , s u b s ta n d a rd m a r g in s , a n d im p ro p e r a lig nm ent c a n adversely affect r e p ro d u c tio n . In the u n lik e ly event that the author d id n o t s e n d U M I a c om ple te m an uscript a n d there are m is s in g pages, these w ill b e no ted . A ls o , if un au th o rize d c o p y rig h t m aterial h a d to be rem o ved , a no te w ill in d ic a te th e deletion. 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SELECTIVE FUNCTIONALIZATIONS OF ARYLBORONIC ACIDS AND STUDIES ON CATIONIC INTERMEDIATES by Stefan Salzbrunn A Dissertation Presented to the FACULTY OF THE GRADUATE SCHOOL UNIVERSITY OF SOUTHERN CALIFORNIA In Partial Fulfillment of the Requirements for the Degree DOCTOR OF PHILOSOPHY (Chemistry) December 2000 Copyright 2000 Stefan Salzbrunn Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. UMI Number: 3041516 ______ (f t UMI UMI Microform 3041516 Copyright 2002 by ProQuest Information and Learning Company. All rights reserved. This microform edition is protected against unauthorized copying under Title 17, United States Code. ProQuest Information and Learning Company 300 North Zeeb Road P.O. Box 1346 Ann Arbor, Ml 48106-1346 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. UNIVERSITY OF SOUTHERN CALIFORNIA The Graduate School University Park LO S ANGELES, CALIFORNIA 90089 1 6 9 5 Thi s di ssertati on, w ritten by Stefan Salzbrunn Under the di recti on o f A_ia. Di ssertati on Commi ttee, and approved by a ll its member s, has been presented to and accept ed by The Graduate School , in p a rtia l fu lfillm en t o f requi rements fo r the degree o f DOCTOR O F PHI LOSOPHY Dean o f Graduate Studies Date December 18, 2000 DI SSER TA H O N C O M M ITTEE Reproduced with permission of the copyright owner. Further reproduction prohibited without permission Stefan Salzbrunn Prof. Dr. G. K. Surya Prakash ABSTRACT SELECTIVE FUNCTIONALIZATIONS OF ARYLBORONIC ACIDS AND STUDIES ON CATIONIC INTERMEDIATES Selective functionalizations of arylboronic acids were carried out to obtain the psosubstituted products in all cases. Arylboronic acids were converted to aryl iodides and subsequently coupled to form symmetrical biaryls in one pot in good yields. Additionally, arylboronic acids were selectively converted to phenols. This methodology allows subsequent coupling to afford symmetrical diaryl ethers in one pot under mild conditions in good to excellent yields. Furthermore, arylboronic acids were nitrated using Crivello’s reagent. The reaction gave mononitro- and dinitro-products at -35°C in acetonitrile for a variety of electronically and sterically different substrates in good yields. Quantum chemical ab initio and Density Functional calculations were performed on trimethylsilyl-substituted norbomyl cations. For the substituted 2-norbomyl cation, the 3-exo-trimethylsilyl-2-norbornyl cation is the global minimum. This cation has a classical structure due to extensive stabilization by the f)-silyl substituent. Transition states for the interconversion of the isomeric cations and the corresponding activation barriers were also computed. Additionally, higher-coordinated singlet X IV and X IV (X=B, Al and Ga) were calculated by Density Functional and Coupled Cluster methods. Their structures and energetics as well as their stabilities for deprotonation and dehydrogenation were also computed. Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Fur meine Eltern ii Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. ACKNOWLEDGMENTS I am extremely grateful to Professor G. K. Surya Prakash and Professor George A. Olah. Their support, guidance and encouragement have significantly influenced the time I have spent at the Loker Hydrocarbon Research Institute. It has been very enjoyable to work in their research group and carry out the research presented in this dissertation. I would like to also thank my close friend Dr. Jurgen Simon. Without his help and support the research presented in Chapter One would not have been possible. I am also thankful to all of the fellow students, postdocs and staff at the USC Chemistry department. Judson Partin, Victor Vilchiz, Dr. Yuk Yin Sham, Dr. Jens Joschek, Dr. Thorsten Schroer, Dr. Stefan Schneider, Dr. Akihisa Saitoh, Michele Dea, David Hunter and Dr. Robert Aniszfeld have been more than helpful and supportive. I am thankful for friendship and camaraderie of all of my colleagues at USC. Specifically, Professor Golam Rasul helped in carrying out the computational studies; Professor Nicos A. Petasis and his research group collaborated on the arylboronic acid chemistry. Margo Bolten has been extremely valuable in the preparation of this dissertation. I want to thank her very much for her professional proofreading and editing. iii Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. My close family—both in Germany and the US—has been very kind and encouraging throughout these years. Most importantly, I want to thank my mother Elisabeth and my father Hermann for all their love, help and support. Words fall short to express all my feelings. I also want to thank Dr. and Mrs. Oschmann for being like parents. They have provided much more than a second ‘Zuhause.’ Moreover, I want to thank Sven Slazenger for helping me throughout the stay in the US. He has taken great toll on himself by managing most customer-relations by himself. Thank you Sven and let’s have many more successful years. Finally, I want to thank my beautiful wife Molly Ann for all the love she has shown and all the time she has committed to help me finish this dissertation. Thank you Gato. I love you very much. Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. TABLE OF CONTENTS Dedication ii Acknowledgments iii List of Figures ix List of Schemes xii List of Tables xv 1 Selective Functionalizations of Arylboronic Acids 1 1.1 Introduction 2 1.1.1 Arylboronic Acids 2 1.1.2 Preparation of Arylboronic Acids 3 1.1.3 Applications of Arylboronic Acids 5 1.1.4 Functionalizations of Arylboronic Acids 6 1.1.4.1 Ipso-Substitutions of Arylboronic Acids 7 with AAHalosuccinimides 1.1.5 Biaryls 9 1.1.5.1 Overview 9 1.1.5.2 Cross-Coupling Reactions 12 1.1.5.3 The Suzuki Cross-Coupling Reaction 14 1.1.6 Phenols 15 1.1.6.1 Overview 15 1.1.6.2 Manufacture and Use 16 1.1.6.3 Chemical Properties 17 v Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 1.1.6.4 Synthesis from Arylboronic Acids 18 1.1.7 Diaryl Ethers 19 1.1.7.1 Overview 19 1.1.7.2 Synthetic Approaches 20 1.2 Results and Discussion 27 1.2.1 One-Pot Synthesis of Symmetrical Biaryls 28 1.2.2 Conversion of Arylboronic Acids to Phenols 33 1.2.3 One-Pot Synthesis of Symmetrical Diaryl Ethers 35 1.2.4 Regioselective Nitration of Arylboronic Acids 40 1.3 Conclusion 46 1.4 Experimental Part 48 1.4.1 General 48 1.4.2 One-Pot Synthesis of Symmetrical Biaryls 49 1.4.3 Conversion of Arylboronic Acids to Phenols 52 1.4.4 One-Pot Synthesis of Symmetrical Diaryl Ethers 55 1.4.5 Regioselective Nitration of Arylboronic Acids 58 1.5 References 65 2 Studies on Cationic Intermediates 77 2.1 Introduction 78 2.1.1 Theoretical Background 78 2.1.1.1 The Schrodinger Equation 79 2.1.1.2 Separation of Nuclear Motion 80 2.1.1.3 Molecular Orbital Theory 81 2.1.1.4 Hartree-Fock Theory 83 2.1.1.5 Closed-Shell Systems 83 vi Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 2.1.1.6 Open-Shell Systems 84 2.1.1.7 Electron Correlation 85 2.1.1.8 Configuration Interaction 85 2.1.1.9 Moller-Plesset Perturbation Theory 87 2.1.1.10 Density Functional Theory 88 2.1.2 Computational Chemistry 90 2.1.2.1 Molecular Mechanics 90 2.1.2.2 Electronic Structure Theory 91 2.1.2.3 Semi-Empirical Methods 92 2.1.2.4 Ab Initio Methods 92 2.1.2.5 Density Functional Methods 93 2.1.2.6 Quantum Chemical Models 93 2.1.2.7 Basis Sets 94 2.1.3 Electron Deficient Intermediates 98 2.1.4 The 2-Norbomyl Cation 99 2.1.4.1 The 2-Norbomyl Cation as an Intermediate 100 in Solvolysis 2.1.4.2 The Stable Nonclassical 2-Norbomyl Cation 102 2.1.5 Silyl Effects in Carbocations 107 2.2 Theoretical Investigations of 113 Trimethylsilyl-Substituted Norbomyl Cations 2.2.1 Trimethylsilyl-Substituted 2-Norbomyl Cations 113 2.2.1.1 Minimum Energy Structures 115 2.2.1.2 Transition States 124 2.2.1.3 Energetics 130 2.2.1.4 Unstable Structures 136 2.2.2 Trimethylsilyl-Substituted 1- and 7-Norbomyl Cations 137 2.2.3 Isodesmic Reactions 143 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 2.2.4 Summary 147 2.3 Higher-Coordinated Boron, Aluminum 149 and Gallium Cations 2.3.1 Structures and Energetics of XH4 + 151 and XH6 * (X=B, Al and Ga) Cations 2.4 Conclusion 160 2.5 Computational Methods 162 2.6 References 163 Bibliography 172 Appendix 189 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. LIST OF FIGURES Figure 1.1 Figure 1.2 Figure 2.1 Figure 2.2 Figure 2.3 Figure 2.4 Figure 2.5 Figure 2.6 Examples of molecules containing biaryl subunits 1 1 Examples of diaryl ether building blocks 19 in natural products and synthetic polymers Geometry of the 2-norbomyl cation (2.1) at the 106 B3LYP/6-3lG(d) level (from reference 86) Geometry of 3-exo-trimethylsilyl-2-norbomyl cation 116 (2.25) at the B3LYP/6-31G(d) level In the bottom structure, the hydrogen atoms are omitted for clarity (distances are indicated in A) Geometry of 5-exo-trimethylsilyl-2-norbornyl cation 117 (2.26) at the B3LYP/6-31G(d) level In the bottom structure, the hydrogen atoms are omitted for clarity (distances are indicated in A) Geometry of 6-exo-trimethylsilyl-2-norbornyl cation 118 (2.27) at the B3LYP/6-31G(d) level In the bottom structure, the hydrogen atoms are omitted for clarity (distances are indicated in A) Geometry of 2-trimethylsilyl-2-norbomyl cation 119 (2.28) at the B3LYP/6-31G(d) level In the bottom structure, the hydrogen atoms are omitted for clarity (distances are indicated in A) Geometry of 3-endo-trimethylsityl-2-norbomyl cation 120 (2.32) at the B3LYP/6-31G(d) level In the bottom structure, the hydrogens are omitted for clarity (distances are indicated in A) ix Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Figure 2.7 Figure 2.8 Figure 2.9 Figure 2.10 Figure 2.11 Figure 2.12 Figure 2.13 Geometry of 4-trimethylsilyl-2-norbomyl cation 121 (2.33) at the B3LYP/6-31G(d) level In the bottom structure, the hydrogens are omitted for clarity (distances are indicated in A) Geometry of the transition state (2.35) at the 125 B3LYP/6-31G(d) level In the bottom structure, most hydrogen atoms are omitted for clarity (distances are indicated in A) Geometry of the transition state (2.36) at the 126 B3LYP/6-31G(d) level In the bottom structure, most hydrogen atoms are omitted for clarity (distances are indicated in A) Geometry of the transition state (2.37) at the 127 B3LYP/6-31G(d) level In the bottom structure, most hydrogen atoms are omitted for clarity (distances are indicated in A) Geometry of the transition state (2.38) at the 128 B3LYP/6-31G(d) level In the bottom structure, most hydrogen atoms are omitted for clarity (distances are indicated in A) Geometry of the transition state (2.39) at the 129 B3LYP/6-31G(d) level In the bottom structure, most hydrogen atoms are omitted for clarity (distances are indicated in A) Geometry of 2-exo-trimethylsilyl-1 -norbomyl cation 139 (2.42) at the B3LYP/6-31G(d) level In the bottom structure, the hydrogen atoms are omitted for clarity (distances are indicated in A) Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Figure 2.14 Figure 2.15 Figure 2.16 Figure 2.17 Figure 2.18 Figure 2.19 Figure 2.20 Figure 2.21 Geometry of 7-trimethylsilyl-7-norbomyl cation 140 (2.43) at the B3LYP/6-31G(d) level In the bottom structure, the hydrogen atoms are omitted for clarity (distances are indicated in A) Geometry of the transition state (2.44) at the 142 B3LYP/6-31G(d) level In the bottom structure, most hydrogen atoms are omitted for clarity (distances are indicated in A) Geometry of 2-exo-trimethylsilyl norbomane (2.34) at 146 the B3LYP/6-31G(d) level In the bottom structure, the hydrogen atoms are omitted for clarity (distances are indicated in A) Relative enthalpy diagram of the minimum energy 148 structures and the transition states for their interconversions The preferred Cs symmetrical structure of CH5 * 150 The structures of BH2 * and AIH2 + 151 Geometries from B3LYP/6-311 ++G(3df,2pd) and 153 MP2/6-311 ++G(3df,2pd) (values in parentheses) of XhV (distances are in A) Geometries from B3LYP/6-311 ++G(3df,2pd) and 154 MP2/6-311 ++G(3df,2pd) (values in parentheses) of XH6 + (distances are in A) Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. LIST OF SCHEMES Scheme 1.1 Boroxine formation 3 Scheme 1.2 Synthetic routes to arylboronic acids 4 Scheme 1.3 Multicomponent synthesis of a-arylglycines 5 Scheme 1.4 General catalytic cycle for cross-coupling reactions 12 Scheme 1.5 Suzuki cross-coupling reaction 14 Scheme 1.6 Two-step diaryl ether synthesis with TKNOah 21 Scheme 1.7 Activation of the aryl halide by an 22 orfho-nitro substituent Scheme 1.8 Activation of the aryl halide by a triazene substituent 23 Scheme 1.9 Activation of the phenoxide with cesium carbonate 24 and copper(l) triflate Scheme 1.10 Copper(ll)-promoted coupling of arylbomic acids 25 and phenols Scheme 1.11 Assumed pathway of the copper(ll)-promoted 26 diaryl ether formation Scheme 1.12 Electrophilic jpso-substitution of arylboronic acids 27 Scheme 1.13 Strategy for symmetrical biaryls from 28 arylboronic acids in one pot Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Scheme 1.14 Reaction of arylboronic acids with hydrogen peroxide 33 Scheme 1.15 Strategy for the one-pot synthesis of diaryl ethers 36 from arylboronic acids Scheme 1.16 Regioselective nitration of arylboronic acids 40 Scheme 1.17 Suggested mechanism for the nitration 44 of arylboronic acids Scheme 2.1 The 2-norbomyl cation 99 Scheme 2.2 Solvolysis studies on 2-norbomyl arenesulfonates 100 Scheme 2.3 Suggested pathway for the solvolysis of 2-norbomyl 101 derivatives Scheme 2.4 Preparation of the 2-norbomyl cation 103 under stable ion conditions Scheme 2.5 Degenerate shifts in the 2-norbomyl cation 104 Scheme 2.6 Hyperconjugation in carbocations 108 Scheme 2.7 2,6-Disubstituted norbomyl derivatives 109 Scheme 2.8 Silyl-substituted bicyclobutonium ions 111 Scheme 2.9 The 6,6-dimethyl-5-neopentyl-6-sila-2-norbomyl cation 112 Scheme 2.10 Interconversion of trimethylsilyl-2-norbomyl derivatives 114 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Scheme 2.11 Comparison of the exo- and endo- transition states for 135 the 3,2-hydride shift in (2.27) Scheme 2.12 Systems for which no minimum on the PES was found 136 and the obtained analogues Scheme 2.13 Isodesmic Reaction to compute the siiyi effect 143 xiv Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. LIST OF TABLES Table 1.1 I pso-iodination of arylboronic acids 8 Table 1.2 Synthesis of symmetrical biaryls 30 from arylboronic acids Table 1.3 Conversion of arylboronic acids to phenols 34 with hydrogen peroxide Table 1.4 Effect of the HzOz/arylboronic acid ratio 37 on product yield Table 1.5 One-pot synthesis of diaryl ethers 39 from arylboronic acids Table 1.6 Nitration of arylboronic acids 41 Table 2.1 Basis Sets 97 Table 2.2 Absolute energies 131 Table 2.3 Relative energies 132 Table 2.4 Enthalpy changes for the Isodesmic Reactions 144 Table 2.5 Energies for the singlet X IV and X IV cations 156 Table 2.6 Deprotonation and dehydrogenation enthalpies 158 xv Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Chapter One Selective Functionalizations of Arylboronic Acids Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 1.1 INTRODUCTION 1.1.1 ARYLBORONIC ACIDS The chemistry of arylboronic acids1 continues to be the focus of numerous research endeavors. Michaelis and Becker first prepared phenylboronic acid in 1880,2 which was expected to have mild antiseptic activity similar to boric acid. In the 1930s, it was shown that various arylboronic acids are toxic towards microorganisms while being relatively harmless towards higher animals.3 Since they are comparatively stable compounds, they have a wide range of applications in organic synthesis. Arylboronic acids are increasingly used in the industrial production of pharmaceuticals and novel organic materials.4 Convenience in handling and their commercial availability5 make them especially attractive to large-scale synthesis. Almost all arylboronic acids are high-melting, crystalline compounds that are convenient to handle due to their relatively low toxicity and stability to air and water. They are characterized quite easily by NMR-spectroscopy, and their 1 1 B-NMR spectrum especially distinguishes them from other boron- containing compounds. 2 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Formation of cyclic trimeric anhydrides (triaryl boroxines)6 ,7 is characteristic for arylboronic acids (Scheme 1.1). This dehydration equilibrium means that traces of anhydride are always present in the boronic acids. Since theses triaryl boroxines react very similar to arylboronic acids, this does not seem to be a problem for most applications. However, the calculation of yields is subject to some uncertainty because of the differing molecular weights. Since water is being liberated in the triaryl boroxine formation, applications that require anhydrous conditions can easily be carried out by addition of powdered molecular sieves to the solvent. Ar / O — B - 3 H20 / \ Ar— B(OH), „ Ar B 0 \ / + 3H 20 \ / \ Ar 1.1 1.2 Scheme 1.1 Boroxine formation 1.1.2 PREPARATION OF ARYLBORONIC ACIDS The first preparation of phenylboronic acid was earned out by hydrolysis of phenylborondichloride obtained from the reaction of diphenylmercury and 3 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. boron trichloride.2 For most synthetic purposes, there are several facile routes to arylboronic acids (Scheme 1.2).8 '9 (Ar)3B 1.4 1. PdCI2(dppf) KOAc/ DMSO 2. H30 * 1. Mg / Et20 or BuLi / EtjO 2. BY3 3. HjO" Ar—X 1.3 Ar—B(OH)2 1.1 A r-B Y ; 1.6 Scheme 1.2 Synthetic routes to arylboronic acids Reaction of trialkylborates with arylmagnesium or aryllithium reagents has become the most important source for arylboronic acids. Aryllithium compounds can easily be prepared either by halogen-metal exchange from aryl halides (1.3) and n-butyllithium or by direct metallation of substituted aromatics with f-butyllithium.1 0 The palladium-catalyzed coupling between aryl 4 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. halides (1.3) and alkoxydiboron derivatives (1.5) is another convenient method.1 1 1.1.3 APPLICATIONS OF ARYLBORONIC ACIDS Phenylboronic acid has been used to protect diols and in stereocontrolled Diels-Alder reactions.1 2 , 1 3 Recently, arylboronic acids have attracted increasing attention for their novel molecular recognition properties.1 4 They also play important roles in cross-coupling reactions to form biaryls or diaryl ethers. These important structural units and the role of arylboronic acids in their syntheses will be described later. Petasis and Zavialov have reported an efficient one-step, three- component synthesis of p,y-unsaturated a-amino acids from alkenylboronic acids, amines and a-ketoacids.1 5 They have also reported a conceptually related boronic acid Mannich reaction between an arylboronic acid, an amine and an a-keto acid (Scheme 1.3).1 6 Ar-B(OH)z ♦ R OH CHjClj or toluene RT OH 1.1 1.7 1.8 1.9 Scheme 1.3 Multicomponent synthesis of a-arylgiycines 5 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. This new, one-step, three-component approach produces a- arylglycines in very good yields. The reaction is practical and experimentally convenient, often occurring by simply stirring the three components in aqueous solution at room temperature over several hours. If certain chiral amine auxiliaries are used, optically active arylglycine derivatives in up to 99%de can be obtained. 1.1.4 FUNCTIONALIZATION OF ARYLBORONIC ACIDS Aromatic substitution reactions have been investigated extensively.1 7 '1 9 Directing effects of various substituents and the classification of activated and deactivated aromatic compounds are well known. To describe different positions relative to a substituent on aromatic systems, ortho, meta and para are generally used. When an electrophile attacks a substituted aromatic ring directly at the position bearing the substituent, the attack is termed to occur at the ipso-position.1 7 , 2 0 , 2 1 The better a substituent stabilizes a positive charge, the easier it gets replaced. This characteristic decides whether the existing substituent or the attacking electrophile is separated off in the rearomatization of the G-complex to produce product or yield back the starting material. Several applications of /pso-substitution of arylboronic acids have been reported. Aryl azides can be prepared indirectly from arylboronic acids by in 6 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. situ conversion into aryl-lead triazetates and reaction with sodium azide.2 2 The preparation of fluoroarenes by reaction with cesium fluoroxysulphate is not a direct substitution either, but rather a two-step process involving the formation of an activated boronic acid complex and a subsequent /pso-substitution of the complex.2 3 1.1.4.1 Ipso-Substitution of Arylboronic Acids with A/-Halosuccinimides Petasis and Zavialov have reported the conversion of alkenyl boronic acids to alkenyl halides by reaction with /V-halosuccinimides.2 4 Our research group has then applied this methodology to arylboronic acids.2 5 ,2 6 A/-halosuccinimides react with arylboronic acids under mild conditions to form the corresponding aryl halides in good to excellent yields. Table 1.1 illustrates this reaction for the iodination with A/-iodosuccinimide (NIS) in acetonitrile. Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Table 1.1 /pso-iodination of arylboronic acids B(OH)2 MeCN v y 1.10 Substrate NIS [equiv.] Temp. [°C] Product Yield [%]* 1.1.1 1.1.2 1.1.3 1.1.4 1.1.5 1. 1.6 1.1.7 1.1.8 1.1.9 1.1.10 1.1.11 1.1.12 1.1.13 1.1.14 1.1.15 1.1.16 R = H R = 2-Me R = 2-OMe R = 3-CI R = 3-Br R = 3-OMe R = 3-N02 R = 4-CI R = 4-Br R = 4-OMe R = 4-CHO R = 4-CH=CH2 R = 2,6-OMe ,B(OH)2 b(0h> 2 1.5 1.5 1.0 1.5 1.5 1.0 2.0 1.5 1.5 1.5 1.2 1.0 1.0 1.0 1.0 1.0 81 1.10.1 61 81 1.10.2 72 25 1.10.3 89 81 1.10.4 76 81 1.10.5 77 25 1.10.6 46 81 1.10.7 25 81 1.10.8 90 81 1.10.9 88 81 1.10.10 90 81 1.10.11 94 81 1.10.12 78 25 1.10.13 84 25 1.10.14 72 25 1.10.15 71 25 1.10.16 83 isolated, unoptimized yield 8 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. A great variety of substrates were reacted with NIS to afford the iodoarenes (1.10) in good to excellent yields. The reaction avoids harsh reaction conditions, strong oxidizing reagents to activate the halogens2 7 and highly toxic aromatic mercury2 8 and thallium2 9 compounds, which are often needed for this conversion by other methods. It is therefore well suited for a great variety of targets. Furthermore, the reagent NIS can also be generated in situ by reacting sodium iodide with N-chlorosuccinimide. Since Na1 2 5 l is the most common source for radioactive iodine, the latter can be incorporated into aromatics by this procedure. Since the reaction tolerates a variety of substituents, this step can be utilized as one of the last steps in synthesis of complex molecules. 1.1.5 BIARYLS 1.1.5.1 Overview Biaryls and their higher homologues (teraryls, oligoaryls, polyaryls) are of great importance in science. They are an important class of compounds that is of current interest to a broad spectrum of research.3 0 Various natural products, polymers, advanced materials, pharmaceuticals, liquid crystals, 9 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. ligands and other molecules of biological or medicinal interest contain biaryl units. Examples are ferrocene derivatives (1.11),3 1 saddle-shaped host compounds (1.12),3 2 novel anti-HIV agents such as michellamines (1.13)3 3 and ligands for enantioselective organic reactions such as the group of 1,1 ’-bi(2-naphtol) (BINOL) (1.14)3 4 (Figure 1.1). They are also found in rigid-rod polymers such as poly(p-phenylene) derivatives (1.15)3 5 (Figure 1.1), which play important roles in a number of diverse technologies including high-performance engineering materials,3 6 conducting polymers3 7 and nonlinear optical materials.3 8 Traditional methods for their synthesis include the Grignard reaction,3 9 the Gomberg-Bachmann reaction4 0 and the Ullmann coupling 4 1 ,4 2 However, these methods give inconsistent and unsatisfying results for almost all complex molecules. It is therefore not surprising that many new methods for their synthesis have been developed over the last decades. 10 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Me Me HN' OH Me’ Me OMe OH OMe OH OH Me OH HO. ,Me NH OH Me 1.13 1.14 COOH HOOC n 1.15 Figure 1.1 Examples of molecules containing biaryl subunits 11 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 1.1.5.2 Cross*Coupling Reactions Cross-coupling reactions provide a convenient method for one of the essentials in synthetic organic chemistry: the formation of carbon-carbon bonds. There are four important (new) catalytic methods for the preparation of biaryls: the Kharasch, Negishi, Stille and Suzuki reactions.1 0 '4 3 " 4 6 All off them are cross-coupling reactions using either nickel or palladium catalysts. A general catalytic cycle for the cross-coupling reactions is depicted in Scheme 1.4. r 2-r ' 1.18 Pd(0) R -X 1.3 R -Pd(ll)-R 1.17 R -Pd(ll)-X 1.16 M-X R -M Scheme 1.4 General catalytic cycle for cross-coupling reactions 12 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. The cycle involves oxidative addition, transmetallation and reductive elimination sequences, all of which can be broken up into further knotty processes including ligand exchanges. However, there is no doubt about the presence of the intermediates (1.16) and (1.17), which have been isolated and/or characterized by spectroscopic techniques.4 7 '5 3 Oxidative addition of the aryl (or alkenyl, alkynyl, allyl, benzyl) halide to the palladium(O) complex affords the stable trans-a-palladium(ll) complex (1.16). This is often the rate-determining step in the catalytic cycle. Transmetallation affords (1.17), which undergoes reductive elimination to form the product (1.18) and reproduces the palladium(O) complex. The Kharasch reaction5 4 "5 9 began to achieve importance in the late 1970’s. An aryl Grignard reagent is reacted with an aryl halide in the presence of a nickel catalyst to yield the biaryl. Other functionalized aryls, such as phenolic triflates, mesylates and ethers, have been used as well. However, the polar nature of the Grignard reagent precludes the use of several types of functional groups. This is not the case in the Negishi reaction.6 0 "6 3 Aryl zinc reagents and aryl halides or triflates are coupled to the biaryls in a palladium- catalyzed sequence. Functional groups such as aldehydes, ketones, esters, amines and nitro groups are tolerated in the non-zinc containing coupling partner. Aryllithium compounds, however, are not generally used in either reaction due to their highly polar and basic nature. 13 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Stille published his original manuscript in 1978 and the reaction soon gained increasing attention due to its immense versatility.6 4 "6 6 An organotin compound (arylstannane) and an aryl halide or triflate are reacted under neutral conditions under palladium(O) catalysis. The reaction tolerates a great variety of substituents on either coupling partner, thus providing a method for substrates not compatible with the Kharasch and Negishi reactions. However, the toxicity of the organotin reagents is the major disadvantage of this important method. 1.1.5.3 The Suzuki Cross-Coupling Reaction The Suzuki reaction has proven to be extremely versatile and has found extensive use in organic synthesis.6 7 This palladium(O) catalyzed reaction is probably the most widely used application of arylboronic acids. It is mostly used to form symmetrical or asymmetrical biaryls from arylboronic acids and aryl halides (Scheme 1.5).6 6 There are several related cross-coupling reactions of similar type that involve 1-alkenyl, 1-alkynyl, allyl or benzyl halides. B(OH)2 - x- 1.1 1.3 1.18 Scheme 1.5 Suzuki cross-coupling reaction 14 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. In most cases, Pd(PPh3)4 is used as a catalyst, sometimes in combination with PdCl2(PPh3 )2, aqueous Na2 C03 as a base and dimethoxyethane (DME) as a solvent.6 7 '7 0 Although phosphine-based catalysts are generally used since they are stable on prolonged heating, catalysts such as Pd(OAc)2, [(n3 -C3Hs)PdCI]2 and Pd2 (dba)3 C6 H 6 have been successfully employed also.7 1 '7 3 The coupling can also be carried out in water by using a water-soluble phosphine ligand such as (m-Na03 SC6H4PPh2).7 4 Various other bases or combinations thereof are routinely used. The selection includes Et3 N,7 5 NaHC03 ,6 9 Cs2 C03 ,7 6 TI2 C03 7 7 and K3 P04 7 8 with or without Bu4 NCI7 9 and 18-crown-6.7 6 1.1.6 PHENOLS 1.1.6.1 Overview Prior to World War I, the only source for phenol8 0 was coal tar. The first synthetic phenol was produced by sulfonation of benzene and subsequent hydrolysis. Today, essentially all phenol produced is synthetic. Phenol is an important industrial intermediate. Estimated annual phenol production is in 15 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. excess of 7 million metric tons annually—almost twice as much as in 1978— and is expected to grow at an annual rate of roughly 4% through 2002.8 1 1.1.6.2 Manufacture and Use Phenol is mainly produced by the Cumene Peroxidation Route, a process that isopropylates benzene to cumene that is oxidized to cumene hydroperoxide and then cleaved to phenol and acetone.8 2 The Toluene- Benzoic Acid Process,8 0 8 3 a two-step process, has also been used extensively. The conversion of toluene to benzoic acid is achieved by liquid- phase, free-radical oxidation. After purification, the benzoic acid is oxydecarboxylated to phenol. Most phenol produced is further utilized in other processes to make a variety of synthetic products. The three most significant commercial products are 2,2-bis-(4-hydroxyphenyl)propane (bisphenol A), phenolic resins (from condensation of phenol and formaldehyde) and caprolactam. Bisphenol A is produced by the reaction of phenol and acetone in the presence of an acid catalyst. It is mostly used for polycarbonate resins, largely used in the telecommunications and computer industries and for epoxy resins. Phenolic resins are the condensation product of a substituted or unsubstituted phenol and an aldehyde, mostly formaldehyde (formaldehyde- phenol combinations account for over 95% of all phenolic resins). They are 16 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. mostly used in the construction industry as plywood, oriented standardboard and insulation material, and in the automotive industry in underbody parts. The third major market for phenol is the production of caprolactam. To obtain this cyclic amide, phenol is catalytically hydrated to cyclohexanone, then converted to cyclohexanone oxime and finally quantitatively rearranged in the presence of oleum (Beckmann rearrangement). The major portion of caprolactam is consumed for the production of nylon-6 fibers for carpet and rug yarn and for plastics. 1.1.6.3 Chemical Properties The aromatic ring and the hydroxyl group—as well as the influences of the two moieties upon each other—characterize phenol. There are a great variety of laboratory reactions involving phenols.8 4 Due to the activation by the hydroxy-group, phenols are amongst the most reactive aromatics. Phenols are weak Branstedt acids.8 5 Their corresponding base, the phenolate anion, however, is much more activated than phenol itself. Phenols readily undergo electrophilic aromatic substitution that often proceeds to form di- or trisubstituted products. 17 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 1.1.6.4 Synthesis from Arylboronic Acids A great variety of phenols are available commercially, and laboratory syntheses involving phenols are routine endeavors for organic chemists. But there are only a few methods to convert arylboronic acids to phenols available today. Hawthorne reported the conversion of phenylmagnesium bromide to phenol in 1957.8 6 In this procedure, the Grignard compound was transformed to phenylboronic acid with methyl borate and subsequently converted to phenol with hydrogen peroxide in one pot. Webb and coworkers reacted arylboronic acids with Oxone®8 7 in 10 to 15% aqueous acetone buffered with sodium bicarbonate.8 8 They obtained a few corresponding phenols in good to excellent yields. Bank and Longley successfully employed 1 7 oxygen labeled potassium hydroperoxide (KOOH) to form 1 7 oxygen-enriched phenols in modest yields.8 9 Researchers from Chisso Corporation in Japan have patented procedures for the oxidation of various fluorine substituted arylboronic acids with hydroperoxides to form the corresponding phenols as intermediates for drugs, agrochemicals and liquid crystals in moderate to good yields.9 0 18 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 1.1.7 DIARYL ETHERS 1.1.7.1 Overview Diaryl ethers9 1 are important structural building blocks found in natural products such as perrottetines (1.19)9 2 and their cyclic analogues riccardin B (1.20)9 3 (Figure 1.2). OH HO 1.19 OH HOOC? 1.21 ■ O H HO' 1.20 — - O - Y = S02, c=o 1.22 Figure 1.2 Examples of diaryl ether building blocks in natural products and synthetic polymers 19 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Many more complex molecules containing sensitive functional groups and stereogenic centers9 4 also contain diaryl ether building blocks. Examples are the cyclic peptide K13 (1.21) or the vancomycin group of antibiotics.9 5 "9 7 Vancomycin contains multiple diaryl ether building blocks and has found clinical use for more than 40 years. Mostly the Evans and Nicolaou research groups have performed extensive research on its synthesis.9 8 "1 0 2 In addition to that, poly(aryl ethers) (1.22) (Figure 1.2) are important commercial polymers used as engineering thermoplastics.1 0 3 The large-scale preparation of these polymers remains a challenging task, partly because of difficulties in creating the diaryl ether segments. 1.1.7.2 Synthetic Approaches Over the last decade there have been numerous attempts to develop new methods for the preparation of diaryl ethers. Previously, the classical Ullmann ether synthesis1 0 4 -1 0 5 has been the only suitable method to achieve this task, using copper powder or copper salts. Due to the poor nucleophilicity of the phenoxide and the low reactivity of the aryl halides involved, harsh conditions have to be used. These include extended reaction times and elevated reaction temperatures of 120-250°C (by using high boiling solvents or neat reagents). Simple diaryl ethers—such as (1.20)—not containing functional groups have been successfully synthesized by using copper 20 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. phenoxide and aryl bromide in refluxing pyridine for twenty hours. Poly(aryl ethers) have also been modeled with activated haloarenes and phenols.1 0 6 First attempts in providing milder methods have been made by Yamamura et al. in 1981.1 0 7 They used Thallium(lll) nitrate to couple 2,6- dihalophenols (1.23) to form a 2-substituted quinone (1.24), which subsequently is reduced to the corresponding diaryl ether (1.25) in poor to moderate yields (Scheme 1.6). COOMe COOMe N 1 I MeOH. -35'C X OH 1.24 1.23 Zn / AcOH HO. MeOOC. COOMe OH 1.25 Scheme 1.6 Two-step diaryl ether synthesis with TI(N03 )3 21 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Evans and coworkers employed this procedure in their synthesis of the orienticin C aglycone.1 0 8 Even though this procedure is carried out under mild conditions, it has several disadvantages: it is a two-step procedure, it requires a specific type of substituted phenol and it uses a highly toxic thallium compound. It is therefore not considered to be a general, user-friendly method. Several researchers successfully introduced activating groups to be able to carry out the Ullmann diaryl ether synthesis under milder conditions. By introducing an activating ortho-nitro substituent into the aryl halide, Eicher and Walter could modify the reaction conditions to 125°C or less for one hour to perform their syntheses of the previously described perrottetines (Scheme 1,7).9 2 '9 3 Similar activation was also used by Evans in synthetic approaches toward vancomycin.9 8 '9 9 One drawback of this approach is the necessity to introduce the ortho-nitro substituent and subsequent reduction and deamination, unless the functional group is contained in the target molecule. NO, X HO. 1.26 1.27 NO, X=CI: NaH, DMF, 125”C X=F: Na,C03 or CsF. DMF, 25” C 1.28 Scheme 1.7 Activation of the aryl halide by an ortbo-nitro substituent 22 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Nicoiaou et al. have also activated the aryl halides. By using ortho- triazene substituents, they were able to react the aryl halide smoothly with phenols in the presence of CuBr • SMe2 and K2CO3 at 80°C and obtained the diaryl ethers in good yields (Scheme 1.8).1 0 9 However, the triazene subunit has to be introduced and subsequently transformed and/or removed after the coupling. MeCN/pyr. 80"C 1.31 Scheme 1.8 Activation of the aryl halide by a triazene substituent 23 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Activation of the phenoxide with cesium carbonate as a base and catalytic amounts of copper(l) trifiate and ethyl acetate has also been demonstrated by Buchwald and coworkers (Scheme 1.9).1 1 0 They assume the formation of a cuprate-like intermediate, which readily undergoes reaction with the aryl halide to form the diaryl ethers in high yields. In certain cases, addition of stoichiometric quantities of 1-naphthoic acid increases the reactivity of less activated phenoxides. HOv v\ 1.27 (CuOTf)2 • PhH, EtOAc Cs2C 0 3, toluene, 80”C A r ° \ 0 „© Cu Cs ArO / 1.32 1.3 1.33 Scheme 1.9 Activation of the phenoxide with cesium carbonate and copper(l) trifiate 24 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. In 1998, researchers at DuPont and David A. Evans independently found the remarkably simple solution.1 1 1 ,1 1 2 In the presence of copper(ll) acetate and a base, arylboronic acids and phenols react at room temperature to form diaryl ethers in good to excellent yields (Scheme 1.10). A great variety of substituents are tolerated on both the arylboronic acid as well as on the phenol. Addition of powdered 4A molecular sieves (MS) to seemingly anhydrous reaction conditions increases yields, which indicates possible triaryl boroxine formation (see Scheme 1.1, page 3). 1.3 (H 0 )3 B 'n ^ N 1.1 C u(OAc> 2, N E lj CH2CI2, 4A MS. 25"C 1.33 Scheme 1.10 Copper(ll)-promoted coupling of arylboronic acids and phenols The assumed pathway of this reaction is shown in Scheme 1.11. The initial step is the transmetallation of the arylboronic acid (1.1) with the copper(ll) salt, followed by a ligand exchange and reductive elimination. The unresolved issue is the oxidation state of the intermediate [(1.35) or (1.36)] before breakdown to diaryl ether product. 25 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Ar— B(OH)2 1.1 X -C u "-X reductive reductive 1. reductive elimination reductive elimination Ar—O -A r 1 1.33 Scheme 1.11 Assumed pathway of the copper(ll)-promoted diaryl ether formation This discovery marks a clear breakthrough in the synthesis of diaryl ethers. A great variety of commercially available arylboronic acids and phenols can easily be coupled. A big step toward the syntheses of various natural products has been made. Furthermore, the reaction is carried out under mild conditions and does not use highly toxic materials. Additionally, with this methodology one can also achieve A/-arylation of different types of N-nucleophiles.1 1 1 26 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 1.2 RESULTS AND DISCUSSION To take full advantage of the increasing commercial availability of a great variety of arylboronic acids,5 new methodologies to convert them to other useful synthons for organic synthesis are desirable. We were interested in the regioselective conversion of arylboronic acids as illustrated in Scheme 1.12. These conversions can be considered electrophilic /pso-substitutions of arylboronic acids. B(OH)a 1.1 1.37 E = N 0 2, NO, OH. F, Cl. Br, I, etc. Scheme 1.12 Electrophilic /pso-substitution of arylboronic acids 27 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 1.2.1 ONE-POT SYNTHESIS OF SYMMETRICAL BIARYLS Since our research group has developed a method to convert arylboronic acids into aryl halides (see page 7), both components for the Suzuki cross-coupling reaction (see page 14), we developed a strategy to combine the two reactions to generate symmetrical biaryls in one pot, as shown in Scheme 1.13. N — I R 1.1 1.10 Pd(0) / base 1.38 Scheme 1.13 Strategy for symmetrical biaryls from arylboronic acids in one pot By converting only half of the arylboronic acid employed to the corresponding iodoarene, a 1 -to-1 mixture of the two is created, which, in turn, 28 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. can be coupled to the biaryl. Simple addition of the catalyst and base should perform this task, if all other parameters are compatible with either reaction. Acetonitrile had been used as a solvent in the conversion of arylboronic acids to aryl halides (see page 7), but turned out to be unsuitable for the cross-coupling reaction. We therefore investigated the use of other solvents for the /pso-iodination reaction. The reaction in dichloromethane turned out to afford similar yields as previously obtained in acetonitrile, while providing a suitable medium for the coupling. In an early experiment, we reacted 4-chlorophenylboronic acid with a half molar equivalent of NIS to afford a one-to-one mixture of the arylboronic acid and the corresponding iodobenzene. After a few hours, tetrakis(triphenylphosphine) palladium and sodium carbonate were added. The corresponding biaryl was formed in very good yield after column chromatographic purification. Further investigation showed that to increase the yields for electron deficient substrates the reaction temperature had to be increased. We investigated the use of a Pressure Schlenk Tube (PST), or a higher boiling solvent. Both options gave satisfying results. We therefore used 1,2- dichloroethane in those cases. This solvent is similar to dichloromethane (b.p. 40°C), yet its boiling point is 84°C. We successfully employed this methodology to convert a variety of arylboronic acids to the corresponding biaryls as summarized in Table 1.2. 29 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Table 1.2 Synthesis of symmetrical biaryls from arylboronic acids B(OH)2 1)0.5 equiv. NIS solvent / A 1.1 2) Pd(PPh3)4 Na2C 03 / H20 1.38 Substrate Solvent Temp. [°C] Product Yield Mg' B(Oh)2 1.1.17 MeO 1.1.10 MeO^ ^,B(OH)j 1.1.6 1.1.7 1.1.18 CH2 CI2 40 CH2 CI2 40 CH2 CI2 40 CICH2 CH2 CI 84 CICH2 CH2 CI 84 MO' \ / V / 1.38.17 -M e 93 MeO \ / V / 1.38.10 MeO OMe OMe 95 1.38.6 89 OjN NO- 1.38.7 70 75 1.38.18 isolated yield continued 30 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Table 1.2 (continued) Synthesis of Symmetrical Diaryls from Arylboronic Acids Substrate Solvent Temp. [°C] Product Yield [•/.]' B(OHh cich^hjCi B r— y y — ^ y — B r 73 1.38.9 HOOC' CICH2 CH2 CI 84 HOOC \ r \ / 1.38.19 COOH 59 1.1.19 B(OH)j c ic h2 c h 2 ci 84 F 65 1.1.20 1.38.20 isolated yield The reaction turned out to proceed smoothly at the conditions indicated and a variety of electronically and structurally different substrates can be converted to the corresponding symmetrical biaryls (1.34). For activated substrates the yields are very good. For less activated or deactivated substrates yields tend to be lower, yet the electronically and sterically challenging 2,4-difluorophenylboronic acid (1.1.20) produces the respective biaryl (1.38.20) in 65% yield. This is remarkable, since there is no other convenient method in the literature to obtain these fluorinated biaryls in good 31 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. yield and selectivity, yet they are significant for liquid crystal technology. To substitute fluorine into an existing biaryl, the Balz-Schiemann reaction is often the only choice.1 1 3 This method is expensive and often uses highly toxic reagents, which greatly diminishes its synthetic potential. Additionally, the overall yield for this reaction is in some cases higher than the yield for the conversion to iodoarenes reported earlier (see paragraph 1.1.4.1, page 7). This is somewhat surprising on first thought, since this conversion is the initial step in this method. However, in the present case the reaction temperature was increased by using either a pressure tube or a higher boiling solvent. This will have affected the reaction equilibrium and is therefore the most probable reason for the increased yields. Furthermore, the reaction might have changed its pathway in this solvent, which can influence product yields. This is known for the somewhat-related bromination reaction with NBS.1 1 4 This has, however, not been studied in detail and is subject to speculation at this point. We were unable to perform this coupling sequence using a polyvinylpyridine-based palladium (PVP-Pd) catalyst.1 1 5 The development of this catalyst, however, is still ongoing and further investigations on this topic are necessary. 32 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 1.2.2 CONVERSION OF ARYLBORONIC ACIDS TO PHENOLS Only few reactions for the conversion of arylboronic acids to phenols are known, even though useful precursors for a variety of targets are obtained in this reaction. For the conversion to phenols, a suitable “electrophile" has to be found. As other researchers have demonstrated,8 6 "9 0 peroxides can serve as suitable reagent for this purpose. One has to keep in mind, however, that this reaction probably does not proceed like a typical electrophilic aromatic substitution reaction.1 7 By simply reacting arylboronic acids with an aqueous hydrogen peroxide solution, we obtained the corresponding phenols (1.27) in good to excellent yields (Scheme 1.14). The desired regioselectivity, the ipso- substituted products, were obtained in all cases. 1.1 1.27 Scheme 1.14 Reaction of arylboronic acids with hydrogen peroxide 33 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Table 1.3 Conversion of arylboronic acids to phenols with hydrogen peroxide Substrate Product Yield [%]' Me MeO 1.1.17 1.1.10 e to 1.1.21 o 2 n^ 1.1.7 ^ % / 0 < O H ) 2 1.1.18 cr 1.1.8 1.1.20 ,O H Me 1.27.17 ,0 H MeO 1.27.10 „OH ElO 1.27.21 OjN^ ^OH 1.27.7 ,OH 1.27.18 ,OH C l' 1.27.8 F ■OH 85 72 88 76 63 71 60 1 isolated yield 34 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. A great variety of activating and deactivating substituents are tolerated on the aromatic substrate. Strongly activated aromatic systems, such as 4- tolylboronic acid (1.1.17) and 4-ethoxyphenylboronic acid (1.1.21) react fast and give high product yields. Even deactivated aromatics, such as 3- nitrophenylboronic acid (1.1.7) can be converted with this methodology smoothly to the corresponding phenols at ambient temperature. This is of significant importance, since many natural products and other synthetic target molecules often contain a great variety of electronically and structurally diverse substituents. The reaction is carried out in water and does not use any chemicals that are difficult to handle or pose significant hazards. Other solvents can be employed as well. Usually one would not gain any significant advantage by employing other solvents, since aqueous hydrogen peroxide is used as a reagent. 1.2.3 ONE-POT SYNTHESIS OF SYMMETRICAL DIARYL ETHERS The new methodology introduced by Evans and Chan (see page 25)1 1 1 ,1 1 2 opens many new possibilities in diaryl ether synthesis. Since both an arylboronic acid and a phenol are employed, our plan was to develop a one- pot synthesis of symmetrical diaryl ethers, similar to our one-pot synthesis of symmetrical biaryls. Our plan was to use the method described previously to 35 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. convert part of the arylboronic acid to the phenol and then couple the mixture to form the diaryl ethers (Scheme 1.15). R ■OH 1.1 1.27 1.39 Scheme 1.15 Strategy for the one-pot synthesis of diaryl ethers from arylboronic acids Previous approaches and information found in the respective publications1 1 1 '1 1 2 indicated that water is not a suitable medium for the reaction. The other researchers used dichloromethane to perform the coupling sequence. We therefore tested the conversion of arylboronic acids to phenols in dichloromethane and obtained satisfying results. In order to absorb the water from the added aqueous hydrogen peroxide solution used as a reagent in the first step, we added powdered 4A molecular sieves (MS) to the reaction. This has been described to be advantageous to absorb water that is produced from triaryl boroxine formation, also. 36 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Furthermore, we have found the ratio of the hydrogen peroxide to the arylboronic acid to be critical for the outcome of the reaction. We used the reaction of 4-tolylboronic acid as a model reaction to optimize product yields. Table 1.4 demonstrates the different reaction conditions employed and the corresponding product yields. Since hydrogen peroxide is the limiting reagent in the reaction, yields were calculated on the basis of the hydrogen peroxide employed. Table 1.4 Effect of the H2 0 2 /arylboronic acid ratio on product yield 1) H20 2 (30%) ch2 ci2 — O M e Me V \ it ■ ■ '0(0 1 1 )2 2) 4AMS Me j j 1.1.17 CufO A cfc / NEtj 1.39.17 H2 0 2 -equivalents Solvent Yield [%]* 0.40 H2 0 / no MS - 0.15 CH2 CI2/M S 65 0.25 CH2 CI2 / MS 90 0.31 CH2 CI2 / MS 61 0.40 CH2 CI2 / MS 45 0.45 CH2 CI2 / MS 28 3 isolated yield, based on H2 0 2 37 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. It is evident that a ratio of 0.25 affords best product yields. This is not surprising, since Evans had indicated excess arylboronic acid usage (up to 3 equivalents).1 1 2 One can argue the calculation of product yields, even though they are based on the limiting reagent. It is very easy to convert product yields to reflect the amount of arylboronic acid employed in the reaction. One simply has to divide the mentioned product yields by two, keeping in mind that 50% is the theoretical limit.1 1 6 We then carried out the reaction with a variety of arylboronic acids. They were reacted with the hydrogen peroxide solution in dichloromethane. Molecular sieves were than added to the reaction. Upon addition of the copper(ll) catalyst, the amine base was introduced and the corresponding symmetrical diaryl ethers were formed in the same reaction flask without isolation of the intermediates. This one-pot synthesis was easily carried out under mild conditions and tolerates a variety of substituents (Table 1.5). The reaction produces best results for electron-rich substrates. This is not surprising, since activated aromatics undergo both the conversion to phenols as well as the coupling to diaryl ethers easily and in higher yields. Deactivated substrates such as (1.1.7) and (1.1.22) produce moderate yields, yet this methodology can be important for molecules containing a variety of functional groups, since they are tolerated under the reaction conditions. 38 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Table 1.5 One-pot synthesis of diaryl ethers from arylboronic acids Substrate Product Yield [%]' Me 1.1.17 B(OHh MeO' 1.1.10 0 2N ^ .BtOH), 1.1.7 1.1.18 ,B(OHh cr Br" 1.1.8 ^ ^ . B ( ° H h 1.1.22 1.1.9 1.39.17 MeO \ / ° \ / OMe 1.39.10 o 2n H O z \ // 1.39.7 1.39.18 1.39.8 1.39.22 Br \ / “ u v / 0r 1.39.9 90 79 55 84 85 58 77 isolated yield, based on H2 0 2 39 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 1.2.4 REGIOSELECTIVE NITRATION OF ARYLBORONIC ACIDS We have published preliminary results of this investigation before,1 1 7 but were further interested in this methodology, especially in the mechanistic aspects of the formation of mononitro and dinitro products. Since the nitration of aromatic compounds is one of the most widely studied reactions and an immensely important industrial process, there are several well-established reagents for the nitration of aromatics available.1 1 8 "1 2 1 The most common ones are mixtures of nitric and sulfuric acid,1 2 2 nitronium tetrafluoroborate1 2 3 '1 2 5 and acetyl nitrate.1 2 6 Crivello introduced mixtures of ammonium nitrate and trifluoroacetic anhydride, to nitrate a variety of aromatic compounds at room temperature in good yield.1 2 7 We used this reagent1 2 8 in our methodology to nitrate arylboronic acids under very mild conditions (Scheme 1.16). B{OHh NO, 1.1 NH4NO3 / (CFjCOfeO CHjCN. -35*C NO, /C ^\ 1.40 R NOj 1.41 Scheme 1.16 Regioselective nitration of arylboronic acids 40 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Table 1.6 Nitration of arylboronic acids Substrate Methodb “N02 *” [equiv.] Products Yield [•/•]* 1.1.1 A B B 1.1 2.5 5.0 1.40.1 1.41.1 45 47 .NO, MeO MeO MeO 1.1.10 A B B 1.1 2.5 5.0 1.40.10 63 10 <5 1.41.10 12 49 68 c r 1.1.8 A B B 1.1 2.5 5.0 ci' -NO, 1.40.8 65 45 32 1.41.8 25 46 A / B (0 H b B r ' 1.1.9 A B 1.1 3.5 B r ' , n o 2 1.40.9 57 37 1.41.9 42 a isolated yields b for description of Method A and B see text and pages 58f continued 41 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Table 1.6 (continued) Nitration of Arylboronic Acids Substrate Methodb “N02 *” [equiv.] Products Yield (%]* Bfv ,B(OHh 1.1.5 A 1.1 B r > ,N 0 2 1.40.5 52 ^ . 0 (O H h , n o 2 o2 n^ , n o 2 1.1.22 A B 1.1 2.5 1.40.22 58 30 1.41.22 30 ,B(OH)2 1.1.23 B 2.5 ,N O , 1.40.23 56 ,NO, 1.40.22 12 B(OH)j 1.1.14 3.0 n NO, 1.40.14 23 NO, S 1.41.14 30 n o2 a isolated yields ” for description of Method A and B see text and pages 58f Several substrates were conveniently nitrated to the mononitro- and dinitro products at -35°C. In Method A, the concentration of the nitrating agent 42 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. is kept low, favoring formation of the mononitro product. In Method B, excess nitrating agent is employed at once, resulting in increased formation of dinitro products. The formation of dinitro products gives rise to speculation about the potential mechanism of the reaction. We can rule out the ipso-nitration of the arylboronic acid, followed by a second nitration of the resulting nitrobenzene. Crivello found that nitrobenzene does not react to dinitrobenzene under the conditions employed.1 2 7 We also performed a control experiment: 1-chloro-4- nitrobenzene was reacted with the reagent mixture in a freezer at -25°C for several days and then warmed to room temperature. We could not detect any dinitro products in this reaction. We believe that there is a competition between nitration at the ipso- position and at other ring positions of the activated arylboronic acid (Scheme 1.17). Most likely, the “boronate" complex is surrounded by the NCV- counterion in (1.42). The N02+ -ion is in close vicinity of the /pso-carbon, which can eventually undergo an electrophilic substitution at that position. 43 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. N u (ROhB NOj r> 1.43 n o 2 1.40 N O ® Nu-” B(ORh N C $ NO® Nu— B(OR)j 1.42 % ,'v^\ 1.44 x ’ n o 2 N02 v O J X ^ ' - ' N O j 1.40* x ^ n o 2 1.41 Scheme 1.17 Suggested mechanism for the nitration of arylboronic acids If the concentration of the nitrating agent in the reaction is kept low (method A), collapse of (1.42) to produce the mononitro compound (1.40) is favored. Since most of the nitrating agent is close to the “boronate" complex, ring nitration at other positions does not occur readily. The competing reaction, the nitration at other ring positions to form complex (1.44), is favored if there is excess nitrating agent present (Method B). The directing effects of the substituents (including the “boronate” complex") present will determine the ring position for this substitution. Another NCV-ion is still in close vicinity of the ipso-carbon in (1.44) that can collapse to the dinitro product (1.41). 44 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. In some cases, protiodeboronation1 7 of (1.44) was also observed. Instead of being substituted by NO2*, the “boronate” gets replaced by a proton. In most cases, the product (1.40*) formed by this process is undistinguishable from the product (1.40) formed by the other pathway. But in the nitration of (1.1.23), this leads to the unexpected formation of (1.40.22). Since dinitrated products can be obtained for both activated and deactivated substrates under very mild conditions, the reaction is a significant new method for this important field of organic chemistry. It demonstrates the ability for arylboronic acids to serve as important synthons and/or precursors for a great variety of compounds. Since 1 5 N labeled ammonium nitrate is commercially available, this method can be employed to prepare 1 5 N-enriched nitroarenes. Since the reaction tolerates a great variety of functional groups and occurs readily under mild conditions, it can be employed in the final steps of a multi-step synthesis. 45 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 1.3 CONCLUSION Selective functionalizations of useful synthetic building blocks are of great demand in organic synthesis. Arylboronic acids have become important synthons for a great variety of targets and are routinely employed in numerous synthetic procedures. New methodologies should provide access to regioselectively functionaiized products, while tolerating a variety of substrates under mild reaction conditions. We have demonstrated methods to perform these selective functionalizations of arylboronic acids under mild conditions. The conversion of arylboronic acids to phenols is a convenient and practical reaction at ambient temperature and can be carried out both in aqueous media as well as in organic solvents such as dichloromethane. It gives good yields for a variety of electronically and structurally different substrates. The nitration of arylboronic acids has been particularly intriguing to us. We did not expect the formation of dinitroaryls at low temperatures. More detailed studies revealed the pathway for the reaction and allowed us to direct the reaction toward formation of /pso-substituted mononitroaryls or toward formation of dinitroproducts. Since the nitro-functionality serves as the starting point to many substituted nitrogen-containing compounds, this method opens 46 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. many possibilities. Furthermore, polynitro compounds are of high interest for high energetic materials and fuels. By combining our methods with well-known cross-coupling reactions, we have illustrated simple procedures to obtain symmetrical biaryls and diaryl ethers in one pot. These reactions allow preparation of these important structural units in good to excellent yields, while tolerating a great variety of substrates. Even deactivated substituents readily undergo the reactions. Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 1.4 EXPERIMENTAL PART 1.4.1 GENERAL All starting materials were purchased from Aldrich Chemical Company, Inc., Frontier Scientific, Inc., and Stem Chemicals, Inc. and used without further purification. Solvents were purified/dried with an A2-alumina solvent system (Anhydrous Engineering, Gardena Hills, CA). Thin layer chromatography was performed on precoated TLC plates (silica gel 60 F254) and flash column chromatography using silica gel 60 (particle size 0.040-0.063 nm, 230-400 mesh). Chromatographical separations were also performed on a Cyclograph Centrifugal Chromatography System (Analtech, Inc., Newark, DE). NMR spectra were recorded on Varian Unity 200, Varian Unity 300 and Bruker AC 250 MHz instruments. GC-MS Spectra were recorded on a HP Series II 5890 spectrometer. 48 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 1.4.2 ONE-POT SYNTHESIS OF SYMMETRICAL BIARYLS 4,4’•dimethyl-1,1 ’-biphenyl (1.38.17) (CAS RN 613-33-2) Me- Me 7.0 mmol (1.0 equivalent) of p-tolylboronic acid were dissolved under an inert atmosphere in about 40ml of CH2CI2. 0.5 equivalents of NIS were added. The reaction mixture was heated to reflux for about 6 hours. Having cooled down, a solution of about one equivalent of Na2C0 3 in 10 ml of H 2O and subsequently 0.07 mmol (2 mol%) of tetrakis(triphenylphosphine) palladium were introduced. The flask was heated for 18 h to reflux. The resulting mixture was filtered and the layers were separated. The aqueous layer was washed with CH2CI2 and the combined organic layers were washed with H2 0 and brine. The solvent was removed under reduced pressure and the product recrystallized from CH2 Cl2:hexanes (5:1). Yield: 93%. NMR agrees with published data.1 2 9 ,1 3 0 49 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 4,4’-dimethoxy-1,1 ’-biphenyl (1.38.10) (CAS RN 2132-80-1) MeO- ■OMe Analogous to (1.38.17), except reflux for 2h and 18h. Yield 95%. NMR agrees with published data.1 3 0 ,1 3 1 S.S’-dimetoxy-I.I’-biphenyl (1.38.6) (CAS RN 6161-50-8) MeO OMe Analogous to (1.38.17), except reflux for 2h and 18h. Yield 95%. NMR agrees with published data.1 3 2 ,1 3 3 3,3’-dinitro-1,1 ’-biphenyl (1.38.7) (CAS RN 958-96-3) Analogous to (1.38.17), except in CICH2CH2CI or in a Pressure Schlenk Tube. Yield: 70%. NMR agrees with published data.1 3 4 50 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 4,4’-diacetyl-1,1’-biphenyl (1.38.18) (CAS RN 787-69-9) Analogous to (1.38.7). Yield 75%. NMR agrees with published data.1 3 5 '1 3 6 2,2\4,4’-tetrafluoro-1,1’-biphenyl (1.38.20) (CAS RN 6965-45-3) F Analogous to (1.38.7), Yield 75%. NMR agrees with published data.1 3 7 4,4’-dibromo*1,1 ’-biphenyl (1.38.9) (CAS RN 92-86-4) Analogous to (1.38.7). Yield 75%. NMR agrees with published data.1 3 8 -1 3 9 51 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 1,1 ’-biphenyl-4,4’-dicarboxytic acid (1.38.19) (CAS RN 787-70-2) HOOC •COOH Analogous to (1.38.7), except: The aqueous portion was acidified with hydrochloric acid, the precipitate was filtered off and dissolved in NaOH- solution and again filtered. Hydrochloric acid was added to the filtrate to re precipitate the product, which was filtered off and dried under reduced pressure. Yield 59%. NMR agrees with published data.1 4 0 1.4.3 CONVERSION OF ARYLBORONIC ACIDS TO PHENOLS 4-methylphenol (1.27.17) (p-cresol) (CAS RN 106-44-5) A reaction flask was charged with about 3 mmol (1.0 equivalent), of p- tolylboronic acid, 1.0 equivalents of H2O2 (30% solution) and additional 10ml H2 0 and stirred at room temperature for several hours. 40ml of CH2CI2 were 52 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. added and the layers separated. The aqueous layer was washed with 20ml CH2CI2 and the combined organics were washed with H2O and brine. The solvent was removed under reduced pressure and the compound was purified by flash chromatography and Kugelrohr distillation (if necessary, about 3 mmHg at 80°C). Yield: 85%. NMR agrees with published data.1 4 1 ,1 4 2 4-methoxyphenol (1.27.10) (CAS RN 150-76-5) Analogous to (1.27.17), except Kugelrohr distillation at 3 mmHg and 125° C. Yield 72%. NMR agrees with published data.1 4 2 ,1 4 3 4-ethoxyphenol (1.27.21) (CAS RN 622-62-8) Analogous to (1.27.17), except Kugelrohr distillation at 3 mmHg and 130° C. Yield 88%. NMR agrees with published data.1 4 4 -1 4 5 53 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 3-nitrophenol (1.27.7) (CAS RN 554-84-7) 02 N __OH 1.27.7 Analogous to (1.27.17) except Kugelrohr distillation at 3 mmHg and 175° C. Yield 76%. NMR agrees with published data.1 4 6 ,1 4 7 4’-hydroxyacetophenone (1.27.18) (CAS RN 99-93-4) o Analogous to (1.27.17) except Kugelrohr distillation at 3 mmHg and 200° C. Yield 63%. NMR agrees with published data.1 4 8 4-chlorophenol (1.27.8) (CAS RN 106-48-9) Analogous to (1.27.17). Yield 71%. NMR agrees with published data.1 4 2 1 4 9 54 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 2,4-difluorophenol (1.27.20) (CAS RN 367-27-1) Analogous to (1.27.17), except Kugelrohr distillation at 3 mmHg and 60° C. Yield 60%. NMR agrees with published data.1 5 0 ,1 5 1 1.4.4 ONE-POT SYNTHESIS OF SYMMETRICAL DIARYL ETHERS Bis(4-methylphenyl) ether (1.39.17) (p-tolyl ether) (CAS RN 1579-40-4) Me- ■ M e A reaction flask is charged with about 3 mmol (1.0 equivalents) of p- tolylboronic acid. 20 ml of CH2CI2 and 0.25 equivalents of H 2O2 (30% solution) and allowed to stir at room temperature for several hours. To this mixture powdered 4A molecular sieves, 0.5 equivalents of Cu(OAc)2 and 3.0 equivalents of NEfe are added. The resulting colored reaction mixture is stirred overnight and the diaryl ether is isolated by direct column chromatography of 55 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. the crude mixture with preabsorption on silica gel. Yield: 90%. NMR agrees with published data.1 5 2 -1 5 3 Bis(4-methoxyphenyl) ether (1.39.10) (CAS RN 1655-74-9) MeO OMe Analogous to (1.39.17). Yield 79%. NMR agrees with published data.1 5 4 Bis(3-nitrophenyl) ether (1.39.7) (CAS RN 38490-83-4) o2 n n o 2 Analogous to (1.39.17). Yield 55%. NMR agrees with published data.1 5 5 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Bis(4-acetylphenyl) ether (1.39.18) (CAS RN 2615-11-4) Analogous to (1.39.17). Yield 84%. NMR agrees with published data.1 5 6 1 5 7 Bis(4-chlorophenyl) ether (1.39.8) (CAS RN 2444-89-5) Analogous to (1.39.17). Yield 85%. NMR agrees with published data.1 5 8 Bis(4*fluorophenyl) ether (1.39.22) (CAS RN 330-93-8) Analogous to (1.39.17). Yield 58%. NMR agrees with published data.1 5 9 57 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Bis(4-bromophenyl) ether (1.39.9) (CAS RN 2050-47-7) Analogous to (1.39.17). Yield 77%. NMR agrees with published data.1 6 0 1.4.5 REGIOSELECTIVE NITRATION OF ARYLBORONIC ACIDS Nitrobenzene (1.40.1) (CAS RN 98-95-3) Method A: 1 mmol (1 equivalent) of phenylboronic acid was dissolved under inert conditions in 30 ml acetonitrile and the solution cooled to -35°C. With rapid stirring, 1 ml of trifluoroacetic anhydride was introduced. In a separate flask, 1.1 equivalents of ammonium nitrate and 10 ml acetonitrile were mixed and the mixture cooled. With rapid stirring, trifluoroacetic anhydride was carefully and slowly added until all solids had dissolved. Subsequently, the prepared nitrating agent was dropwise introduced into the 58 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. reaction flask containing the boronic acid. The reaction was allowed to proceed while maintained at -35°C by use of a cooling bath. After 4 hours, the cooling bath was removed and the reaction mixture was allowed to warm to room temperature. Volatile solvents were removed under reduced pressure and the residue dissolved in diethyl ether and purified by passing it over a 5 cm long silica gel flash column (diameter 2 cm). Further purification was carried out by chromatography on a Cyclograph (4mm silica gel, 1000 rpm, 8 ml/min, hexanes/ether). Yield: 78%. NMR agrees with published data.1 6 1 1,3-Dinitrobenzene (1.41.1) (CAS RN 99-65-0) o 2n , n o 2 Method B: 1 mmol (1 equivalent) of phenylboronic acid was dissolved under inert conditions in 30 ml acetonitrile and the solution cooled to -35°C. With rapid stirring, 1 ml of trifluoroacetic anhydride was introduced. In a separate flask, 5.0 equivalents of ammonium nitrate and 5-10 ml acetonitrile were mixed and the mixture cooled. With rapid stirring, trifluoroacetic anhydride was carefully and slowly added until all solids had dissolved. Subsequently, the prepared nitrating agent was introduced into the reaction flask containing the boronic acid at once. The reaction was allowed to proceed 59 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. while maintained at -35°C by use of a cooling bath. After 6 hours, the cooling bath was removed and the reaction mixture was allowed to warm to room temperature. Volatile solvents were removed under reduced pressure and the residue dissolved in diethyl ether and purified by passing it over a 5 cm long silica gel flash column (diameter 2 cm). Further purification and separation from other products was earned out by chromatography on a Cyclograph (4mm silica gel, 1000 rpm, 8 ml/min, hexanes/ether). Yield: 47%. NMR agrees with published data.1 6 2 1-methoxy-4-nitro-benzene (1.40.10) (4-nitroanisole) (CAS RN 100-17-4) Analogous to (1.40.1), except reaction time 2 hours. Yield 63%. NMR agrees with published data.1 6 3 MeO 60 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 1-methoxy-2,4-dinitro-benzene (1.41.10) (2,4-dinitroanisole) (CAS RN 119-27-7) Analogous to (1.41.1), except reaction time 3 hours. Yield 68%. NMR agrees with published data.1 6 4 ,1 6 5 1-chloro-4-nitro-benzene (1.40.8) (CAS RN 100-00-5) Analogous to (1.40.1), except reaction time 5 hours. Yield 65%. NMR agrees with published data.1 6 6 1-chloro-2,4-dinitro*benzene (1.41.8) (CAS RN 97-00-7) Analogous to (1.41.1). Yield 46%. NMR agrees with published data. 167 61 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 1-bromo-4-nitro-benzene (1.40.9) (CAS RN 586-78-7) Analogous to (1.40.1), except reaction time 6 hours. Yield 57%. NMR agrees with published data.1 6 8 1-bromo-2,4-dinitro*benzene (1.41.9) (CAS RN 584-48-5) Analogous to (1.41.1), except 3.5 equivalents of ammonium nitrate and reaction time 5 hours. Yield 42%. NMR agrees with published data.1 6 9 1 -fluoro-4-nitro-benzene (1.40.22) (CAS RN 350-46-9) Analogous to (1.40.1), except reaction time 5 hours. Yield 58%. NMR agrees with published data.1 7 0 62 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 1-fluoro-2,4-dinitro-benzene (1.41.23) (CAS RN 70-34-8) Analogous to (1.40.1), except 3.5 equivalents of ammonium nitrate and reaction time 6 hours. Yield 30%. NMR agrees with published data.1 7 1 1 -bromo-3-nitro-benzene (1.40.5) (CAS RN 585-79-5) Br\ n o2 Analogous to (1.40.1), except reaction time 5 hours. Yield 52%. NMR agrees with published data.1 7 2 ,1 7 3 1-fluoro-3-nitro-benzene (1.40.23) (CAS RN 402-67-5) Analogous to (1.41.1), except 2.5 equivalents of ammonium nitrate and reaction time 5 hours. Yield 56%. NMR agrees with published data.1 7 4 63 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 2-nitro-thiophene (1.40.14) (CAS RN 609-40-5) n o 2 Analogous to (1.40.1), except 3.0 equivalents of ammonium nitrate and reaction time 4 hours. Yield 23% (with 30% mixtures of dinitrothiophenes). NMR agrees with published data.1 7 5 64 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 1.5 REFERENCES (1) Negishi, E. Compreh. Organomet. Chem. 1983, 7, 323. (2) Michaelis, A.; Becker, P. Ber. 1880, 13, 58. (3) Seaman, W.; Johnson, J. R. J. Am. Chem. Soc. 1931, 53, 711. (4) Tour, J. M. Chem. Rev. 1996, 96, 537. (5) Over the last few years a growing number of arylboronic acids have become commercially available from traditional vendors such as Aldrich Chemical Co. Inc., Milwaukee, Wl, but vendors specializing in this field such as Frontier Scientific Inc., Logan, UT provide an extensive variety of substituted substrates. (6) Michaelis, A.; Becker, P. Ber. 1882, 15,182. (7) Santucci, L.; Triboulet, C. J. Chem. Soc. (A) 1969, 392. (8) Koster, R. in Methoden der organischen Chemie (Houben-Weyl), 4th ed., Vol. 13/3a, Koster, R., ed.; Thieme: Stuttgart, 1982, 617. (9) Matteson, D. S. in Chemistry of the Metal Carbon Bond, Vol. 4, Hartley, F. R., ed.; Wiley: Chichester, 1987, 307. (10) Snieckus, V. Chem. Rev. 1990, 90, 879. (11) Ishiyama, T.; Murata, M.; Miyaura, N. J. Org. Chem. 1995, 60, 7508. (12) Suguhara, J. M.; Bowman, C. M. J. Am. Chem. Soc. 1958, 80, 2443. (13) Narasaka, K; Shimada, S.; Osoda, K.; Iwasawa, N. Synthesis 1991, 1171. (14) Suenaga, H.; Yamamoto, H.; Shinkai, S. Pure Appl. 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I., Ed.; Wiley: New York, 1985; Vol. 7. (37) Elsenbaumer, R. L.; Shacklette, L. W. In Handbook of Conducting Polymers', Skotheim, T. A., Ed.; Dekker: New York, 1986; Vol. 1. (38) Williams, D. J., Ed. Nonlinear Optical Properties of Organic and Polymeric Materials’ , ACS Symposium Series 233; American Chemical Society: Washington, DC, 1983. (39) Grignard, V. C. R. Acad. Sci. 1900, 130,1322. (40) Gomberg, M.; Bachmann, W. E. J. Am. Chem. Soc. 1924, 46, 2339. (41) Fanta, P. E. Synthesis 1974, 9. (42) Fanta, P. E. Chem. Rev. 1964, 64, 613. (43) Knight, D. W. In Comprehensive Organic Synthesis, Trost, B. M., Fleming, I., Pattenden, G., Eds.; Pergamon: New York, 1991 (44) Jolly, P. W. In Comprehensive Organometallic Chemistry, Wilkinson, G., Stone, F. G. A., Abel, E. W., Eds.; Pergamon: Oxford, 1982, Vol. 8. (45) Trost, B. M.; Verhoeven, T. R. In Comprehensive Organometallic Chemistry, Wilkinson, G., Stone, F. G. A., Abel, E. W., Eds.; Pergamon: Oxford, 1982, Vol. 8. (46) Stanforth, S. E. 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(67) Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457. (68) Miyaura, N.; Yanagi, T.; Suzuki, A. Synth. Commun. 1981, 11, 513. (69) Gronowitz, S.; Bobosik, V.; Lawitz, K. Chem. Scr. 1984, 23, 120. (70) Alo, B. I.; Kandil, A.; Patil, P. A.; Sharp, M. J.; Siddiqui, M. A.; Snieckus, V. J. Org. Chem. 1991, 56, 3763. (71) Wallow, T. I.; Novak, B. M. J. Org. Chem. 1994, 59, 5034. (72) Bumagin, N. A.; Bykov, V. V.; Beletskaya, I. P. Dok. Akad. Nauk SSSR 1990, 315,1133. (73) Marck, G.; Villiger, A.; Buchecker, R. Tetrahedron Lett. 1994, 35, 3277. (74) Casalnuovo, A. L.; Calabrese, J. C. J. Am. Chem. Soc. 1990, 112, 4324. (75) Muller, W.; Lowe, D. A.; Neijt, H.; Urwyler, S.; Herding, P.; Blaser, D.; Seebach, D. Helv. Chim. Acta 1992, 75, 855. (76) Katz, H. E. J. Org. Chem. 1987, 52, 3932. (77) Hoshino, Y.; Miyaura, N.; Suzuki, A. Bull. Chem. Soc. Jpn. 1988, 61, 3008. (78) Coleman, R. S.; Grant, E. B. Tetrahedron Lett. 1993, 34, 2225. (79) Ishikura, M.; Kamada, M.; Terashima, M. Synthesis 1984, 936. (80) Thurman, C. In Encyclopedia of Chemical Technology, Third Ed., Vol. 17, Mark, H. F., Othmer, D. F., Overberger, C. G., Seaborg, G. T., Eds.; Wiley: New York, Chichester, 1982, 373. (81) Greiner, E. CEH Report on Phenol-, SRI Consulting: Menlo Park, CA, 1999, 686.5000. (82) There are numerous patented modifications of the process. See references 80 and 81. 69 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. (83) Hay, J. M.; Weaver, C. W.; Sterling, D. W. Oil Gas J. 1966, 64, 83. (84) Wedemayer, K. F. In Methoden der organischen Chemie (Houben- Weyl), 4th ed., Vol. 6/1c, Muller, E., ed.; Thieme: Stuttgart, 1982. (85) Branstedt, J. N. Rec. Trav. Chim. 1923, 42, 718. (86) Hawthorne, M. F. J. Org. Chem. 1957, 22, 1001. (87) Oxone® is commercially available from DuPont or Degussa-Huls, respectively, and has the approximate empirical formula 2 KHSOs • KHS04 • K2SO4 (88) Webb, K. S.; Levy, D. Tetrahedron Lett. 1995, 36, 5117. (89) Bank, S.; Longley, K. L. J. Labelled Compd. Radiopharm. 1 990, 28,41. (90) Matsui, S.; Takeuchi, H.; Miyasawa, K.; Goto. Y. JP10025261, 1998. (91) For a recent review see: Theil, F. Angew. Chem. 1999, 111, 2493; Angew. Chem. Int. Ed. 1999, 38, 2345. (92) Eicher, T.; Walter, M. Synthesis 1991,469. (93) Eicher, T.; Frey, S.; Puhl, W.; Buchel, E.; Speicher, A. Eur. J. Org. Chem. 1998, 877. (94) Zhu, J. Synlett W 97,133. (95) For a review see; Rama Rao, A. V.; Gurjar, M. K.; Reddy, K. L.; Rao, A. S. Chem. Rev. 1995, 95,2135. (96) Atkinson, B. A. In Antibiotics in Laboratory Medicine, Lorian, V., Ed.; Williams and Wilkins: Baltimore, 1986, 995. (97) Glycopeptide Antibiotics, Drugs and the Pharmaceutical Sciences-, Nagarajan, R., Ed.; Decker New York, 1994; Vol. 63. (98) Evans, D. A.; Wood, M. R.; Trotter, B. W.; Richardson, T. I.; Barrow, J. C.; Katz, J. L. Angew. Chem. 1998, 110, 2864; Angew. Chem. Int. Ed. 1998, 37, 2700. 70 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. (99) Evans, D. A.; Dinsmore, C. J.; Watson, P. S.; Wood, M. R.; Richardson, T. I.; Trotter, B. W.; Katz, J. L. Angew. Chem. 1998, 110, 2868; Angew. Chem. Int. Ed. 1998, 37, 2704. (100) Nicolaou, K. C.; Natarajan, S.; Li, H.; Jain, N. F.; Hughes, R.; Solomon, M. E.; Ramanjulu, J. M.; Boddy, C. N. C.; Takayanagi, M. Angew. Chem. 1998,110, 2872; Angew. Chem. Int. Ed. 1998, 37, 2708. (101) Nicolaou, K. C.; Jain, N. F.; Natarajan, S.; Hughes, R.; Solomon, M. E.; Li, H.; Ramanjulu, J. M.; Takayanagi, M.; Koumbis, A. E.; Bando, T. Angew. Chem. 1998, 110, 2879; Angew. Chem. Int. Ed. 1998, 37, 2714. (102) Nicolaou, K. C.; Takayanagi, M.; Jain, N. F.; Natarajan, S.; Koumbis, A. E.; Bando, T.; Ramanjulu, J. M. Angew. Chem. 1998, 110, 2881; Angew. Chem. Int. Ed. 1998, 37, 2717. (103) Labadie, J. W.; Hedrick, J. L.; Ueda, M. Am. Chem. Soc. Symp. Ser. 1996, 624, 210. (104) Ullmann, F. Chem. Ber. 1904, 37, 853. (105) Lindley J. Tetrahedron 1984, 40,1433. (106) Jonsson, H.; Hedrick, J. L;Labadie, J. W. Polym. Prepr. Am. Chem. Soc. Div. Polym. Chem. 1992, 33, 394. (107) Noda, H.; Niwa, M.; Yamamura, S. Tetrahedron Lett. 1981, 34, 3247. (108) Evans, D. A.; Barrow, J. C.; Watson, P. S.; Ratz, A. M.; Dinsmore, C. J.; Evrard, D. A.; DeVries, K. M.; Ellmann, J. A.; Rychnovsky, S. D.; Lacour, J. J. Am. Chem. Soc. 1997, 119, 3419. (109) Nicolaou, K. C.; Boddy, C. N. C.; Natarajan, S.; Yue, T.-Y.; Li, H.; Brase, S.; Ramanjulu, J. M. J. Am. Chem. Soc. 1997, 119, 3421. (110) Marcoux, J.-F.; Doye, S.; Buchwald, S. L. J. Am. Chem. Soc. 1997, 119,10539. (111) Chan, D. M. T.; Monaco, K. L.; Wang, R.-P.; Winters, M. P. Tetrahedron Lett. 1998, 39, 2933. (112) Evans, D. A.; Katz, J. L.; West, T. R. Tetrahedron Lett. 1998, 39, 2937. 71 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. (113) Balz, G.; Schiemann, G. Ber. Dtsch. Chem. Ges. 1927, 60,1186. (114) Carey, F. C; Sundberg, R. J. Advanced Organic Chemistry, 3rd Ed.; Plenum Press: New York, 1990, Part A, 692. (115) Pathak, S.; Greci, M. T.; Kwong, R. C.; Mercado, K.; Prakash, G. K. S.; Olah, G. A.; Thompson, M. E. Chem. Mater. 2000, 12, 1985. (116) Since one equivalent of arylboronic acid can theoretically be converted into 0.25 equivalents of phenol, there is at least a 3-fold excess of arylboronic acid present before the coupling. 0.25 equivalents of diaryl ether are therefore the maximum that one can obtain. If one wants to base the calculation on arylboronic acid, the hypothetical maximum becomes 0.50 equivalents, twice as much as one can obtain. (117) Salzbrunn, S. M. S. Thesis; University of Southern California: Los Angeles, 1999. (118) Olah, G. A.; Kuhn, S. J. In Friedei-Crafts and Related Reactions, Olah, G. A., Ed.; Wiley-lnterscience: New York, 1964, Vol. 2, 1393. (119) Olah, G. A. American Chemical Society Symposium Series, Albright, F. A., Ed.; Washington, D. C., 1976, Vol. 22. (120) Olah, G. A.; Malhorta, R.; Narang, S. C. Nitration - Methods and Mechanism-, VCH: New York, 1989. (121) Schofield, K. Aromatic Nitration-, University Press: Cambridge, 1980. (122) Parker, K. A.; Ledeboer, M. W. In Encyclopedia of Reagents for Organic Synthesis, Paquette, L. A., Ed.; Wiley: Chichester, 1995, Vol. 6, 3714. (123) Kuhn, S. J.; Olah, G. A. J. Am. Chem. Soc. 1 961, 83, 4564. (124) Olah, G. A.; Kuhn, S. J. J. Am. Chem. Soc. 1 962, 84, 3684. (125) Olah, G. A.; Prakash, G. K. S.; Wang Q.; Li, X. In Encyclopedia of Reagents for Organic Synthesis, Paquette, L. A., Ed.; Wiley: Chichester, 1995, Vol. 6,3747. (126) Louw, R. In Encyclopedia of Reagents for Organic Synthesis, Paquette, L. A., Ed.; Wiley: Chichester, 1995, Vol. 1, 70. 72 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. (127) Crivello, J. V. J. Org. Chem. 1981, 46, 3056. (128) Even, C.; Fauquenoit, C.; Claes, P. Bull. Soc. Chim. Belg. 1980, 89, 559. (129) Pouchert, C. J.; Behnke, J. The Aldrich Library of 1 3 C and 1 H FT NMR Spectra; Aldrich Chemical Co.: Milwaukee, 1993, Vol. 2, 34C. (130) Courtois, V.; Bardhadi, R.; Troupel, M.;Perichon, J. Tetrahedron 1997, 53,11569. (131) Pouchert, C. J.; Behnke, J. The Aldrich Library of 1 3 C and 1 H FT NMR Spectra-, Aldrich Chemical Co.: Milwaukee, 1993, Vol. 2, 216C. (132) Pouchert, C. J.; Behnke, J. The Aldrich Library of 1 3 C and 1 H FT NMR Spectra', Aldrich Chemical Co.: Milwaukee, 1993, Vol. 2, 216B. (133) Ono, M.; Yoshida, N.; Akita, H. Chem. Pharm. Bull. 1997, 45,1745. (134) Cho, C. S.; Ohe, T.; Uemura, S. J. Organomet. Chem. 1995, 496, 221. (135) Percec, V.; Bae, J.-Y.; Zhao, M.; Hill, D. H. J. Org. Chem. 1995, 60, 176. (136) Chippendale, A. M.; Aujla, R. S.; Harris, R. K.; Packer, K. J.; Purser, S. Magn. Reson. Chem. 1986, 24, 81. (137) Dickerson, D. R.; Finger, G. C.; Shiley, R. H. J. Fluorine Chem. 1973, 3, 113. (138) Pouchert, C. J.; Behnke, J. The Aldrich Library of 1 3 C and 1 H FT NMR Spectra-, Aldrich Chemical Co.: Milwaukee, 1993, Vol. 2 ,158C. (139) Sovocool, G. W.; Wilson, N. K. J. Org. Chem. 1982, 47,4032. (140) Schneider, H.-J.; Wang, M. J. Org. Chem. 1994, 59, 7464. (141) Brycki, B.; Brzezinski, B.; Zundel, G.; Keil, T. Magn. Reson. Chem. 1992, 30, 507. (142) Highet, R. J.; Highet, P. F. J. Org. Chem. 1965, 30, 902. 73 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. (143) Pouchert, C. J.; Behnke, J. The Aldrich Library of 1 3 C and 1 H FT NMR Spectra; Aldrich Chemical Co.: Milwaukee, 1993, Vol. 2, 254B. (144) Pouchert, C. J.; Behnke, J. The Aldrich Library of 1 3 C and 1 H FT NMR Spectra; Aldrich Chemical Co.: Milwaukee, 1993, Vol. 2, 255A. (145) Capparelli, M. P.; Swenton, J. S. J. Org. Chem. 1987, 52, 5360. (146) Pouchert, C. J.; Behnke, J. The Aldrich Library of 1 3 C and 1 H FT NMR Spectra; Aldrich Chemical Co.: Milwaukee, 1993, Vol. 2, 690B. (147) Guillaume, F.; Seguin, J. P.; Nadjo, L.; Uzan, R.; Membrey, F.; Doucet, J. P. J. Chem. Soc. Perkin Trans. 2 1984, 7,1139. (148) Pouchert, C. J.; Behnke, J. The Aldrich Library of 1 3 C and 1 H FT NMR Spectra', Aldrich Chemical Co.: Milwaukee, 1993, Vol. 2, 861B. (149) Pouchert, C. J.; Behnke, J. The Aldrich Library of 1 3 C and 1 H FT NMR Spectra', Aldrich Chemical Co.: Milwaukee, 1993, Vol. 2, 253B. (150) Pouchert, C. J.; Behnke, J. The Aldrich Library of 1 3 C and 1 H FT NMR Spectra-, Aldrich Chemical Co.: Milwaukee, 1993, Vol. 2, 271B. (151) Fifolt, M. J.; Sojka, S. A.; Wolfe, R. A.; Hojnicki, D. S.; Bieron, J. F.; Dinan, F. J. J. Org. Chem. 1989, 54, 3019. (152) Pouchert, C. J.; Behnke, J. The Aldrich Library of 1 3 C and 1 H FT NMR Spectra', Aldrich Chemical Co.: Milwaukee, 1993, Vol. 2, 211C. (153) Beever, W. H.; Stille, J. K. Macromolecules 1979, 12, 1033. (154) Wang, L.; Xi, H.; Sun, X.; Shen, Y.; Yang, Y.; Pan, Y.; Hu, H. Synth. Comm. 2000, 30, 227. (155) Minato, M.; Lahti, P. M. J. Org. Phys. Chem. 1994, 4, 495. (156) Gruetzmacher, H.-F.; Mehdizadeh, A.; Muelverstedt, A. Chem. Ber. 1994, 127,1163. (157) Wolfe, J. F.; Stille, J. K Macromolecules 1976, 9,489. (158) Dawson, B. A.; Chu, I.; Viau, A. Magn. Reson. Chem. 1990, 28, 735. 74 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. (159) Schaefer, T.; Penner, G. H.; Takeuchi, C.; Tseki, P. Can. J. Chem. 1988, 66, 1647. (160) Pouchert, C. J.; Behnke, J. The Aldrich Library of 1 3 C and 1 H FT NMR Spectra-, Aldrich Chemical Co.: Milwaukee, 1993, Vol. 2, 213B. (161) Pouchert, C. J.; Behnke, J. The Aldrich Library of 1 3 C and 1 H FT NMR Spectra-, Aldrich Chemical Co.: Milwaukee, 1993, Vol. 2, 678A. (162) Pouchert, C. J.; Behnke, J. The Aldrich Library of 1 3 C and 1 H FT NMR Spectra-, Aldrich Chemical Co.: Milwaukee, 1993, Vol. 2, 692A. (163) Pouchert, C. J.; Behnke, J. The Aldrich Library of 1 3 C and 1 H FT NMR Spectra-, Aldrich Chemical Co.: Milwaukee, 1993, Vol. 2, 969A. (164) Nudelman, N. S.; Cerdeira, S. B. Magn. Reson.Chem. 1986, 24, 507. (165) Stephens, M. D.; Reinheimer, J. D.; Kappelman, A. H. Can. J. Chem. 1971,49, 3759. (166) Pouchert, C. J.; Behnke, J. The Aldrich Library of ,3C and 1 H FT NMR Spectra-, Aldrich Chemical Co.: Milwaukee, 1993, Vol. 2, 695A. (167) Bacaloglu, R.; Blasko, A.; Bunton, C.; Dorwin, E.; Ortega, F.; Zucco, C. J. Amer. Chem. Soc. 1991, 113, 238. (168) Pouchert, C. J.; Behnke, J. The Aldrich Library of 1 3 C and 1 H FT NMR Spectra-, Aldrich Chemical Co.: Milwaukee, 1993, Vol. 2, 965B. (169) Katritzky, A. R.; Li, J.; Stevens, C. V.; Ager, D. J. Org. Prep. Proced. Int. 1994, 26, 439. (170) Pouchert, C. J.; Behnke, J. The Aldrich Library of 1 3 C and 1 H FT NMR Spectra- Aldrich Chemical Co.: Milwaukee, 1993, Vol. 2, 694C. (171) Pouchert, C. J.; Behnke, J. The Aldrich Library of 1 3 C and 1 H FT NMR Spectra-, Aldrich Chemical Co.: Milwaukee, 1993, Vol. 2, 749C. (172) Batts, B. D.; Pallos, G. Org. Magn. Reson. 1980, 13, 349. (173) Domalewski, W.; Stefaniak, L.; Webb, G. A. J. Mol .Struct. 1993, 295, 19. Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. (174) Pouchert, C. J.; Behnke, J. The Aldrich Library of 1 3 C and 1 H FT NMR Spectra-, Aldrich Chemical Co.: Milwaukee, 1993, Vol. 2, 688C. (175) Pouchert, C. J.; Behnke, J. The Aldn'ch Library o f1 3 C and 1 H FT NMR Spectra-, Aldrich Chemical Co.: Milwaukee, 1993, Vol. 3, 52C. 76 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Chapter Two Studies on Cationic Intermediates Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 2.1 INTRODUCTION Scientists have used models for many centuries. Some philosophers may even argue that chemistry itself is a model discipline to describe nature’s processes. Over the last four decades or so, the use of theoretical models as a research tool in all areas of chemistry has become increasingly important. Today, computational chemistry is routinely used as a tool in chemical research. It has established its presence throughout the field and is no longer restricted to few dedicated theoreticians. To describe and characterize electron-deficient species, computational chemistry has been proven to provide significant insights. A great variety of calculations can be performed to obtain further information about structure, energetics, kinetics, spectroscopic data, and other valuable details. 2.1.1 THEORETICAL BACKGROUND In the 1920s and 1930s, theoretical physics provided the fundamentals for quantum mechanics,1 '6 which explains how entities like electrons have both particle-like and wave-like characteristics. It became possible to extend the orbital theory introduced by Bohr to polyatomic situations and develop further methods to describe the atomic particles.7 '9 78 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 2.1.1.1 The Schrddinger Equation Schrddinger’s basic nonrelativistic equation1 describes the wavefunction ¥ of a particle, or of a collection of particles like a molecule.1 0 For the problems chemists are interested in, the time-dependent equation can be separated into two parts, one of which depends on the position of the particles independent of time and the other of which is a function of time alone. The time-independent equation is focused on in this context: HT =ET Equation 2.1 Time-independent Schrddinger Equation It is a partial differential eigenvalue equation for the energy E and the wavefunction ¥ of a particular state. I-I is the Hamiltonian operator and *P depends on the Cartesian and spin coordinates of the component particles. The solutions have to be restricted to the correct symmetry (antisymmetric for fermions such as electrons and symmetric for bosons) to be physically acceptable. The Schrddinger equation has many solutions for a molecule, corresponding to different stationary states. Most researchers are interested in the ground state, i.e. the state with the lowest energy E. Since the Schrddinger equation is nonrelativistic, it is not valid when the particles approach the speed of light. For the treatment of most computational studies, the relativistic effect 79 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. can be neglected, unless calculations involve the core electrons in large nuclei.1 1 ,1 2 The Schrddinger equation can easily be solved for the hydrogen atom and gives almost perfect agreement to experimental spectroscopic data, if Dirac’s relativistic corrections are included. For more complex systems, however, the equation cannot be solved exactly. Although the theory had been established by the 1920s, solutions for most systems could not be obtained. This led to a famous quote by P. A. M. Dirac in 1929 that describes the situation that researchers faced in this period: The underlying physical laws necessary for the mathematical theory of a large part of physics and the whole of chemistry are thus completely known, and the difficulty lies only in the fact that application of these laws leads to equations that are much too complex to be solved. 2.1.1.2 Separation of Nuclear Motion In the 1930s, physicists and mathematicians developed a series of mathematical approaches and assumptions to simplify the equation and obtain approximate solutions. The first major step is the separation of nuclear and electronic motions. This is frequently called the Born-Oppenheimer approximation.1 3 Since nuclear masses are much greater than those of the electrons, they move much more slowly. The distribution of electrons only 80 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. depends on the position of the nuclei and not on their velocities. The Schrodinger equation can be split into two parts, which can be solved independently. If the electronic wavefunction is solved, one can obtain the effective nuclear potential energy function, or the potential surface of the molecule. The lowest-energy solution of the electronic Schrodinger equation corresponds to the ground-state potential energy surface (PES) of the molecule, which is particularly interesting to chemists. 2.1.1.3 Molecular Orbital Theory Molecular Orbital Theory treats the electrons as moving in independent orbitals. This means, the n electrons of a closed shell molecule are assigned to a set of n molecular orbitals < l> j (i=1,2,..n). ¥ is decomposed into a combination of these one-electron molecular orbital wavefunctions. A series of requirements (symmetry and spin) of these wavefunctions and the corresponding n-electron wavefunction 4* leads to a determinal wavefunction: T = ( n ! r 2det[(<()1 a)(<i>ip)(«i,2a)...] Equation 2.2 Slater determinal wavefunction 81 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. The molecular orbital wavefunctions ^ are taken to be orthonormal and a and p are spin functions. This determinant is commonly called the Slater determinant.1 4 ,1 5 The next approximation expresses the molecular orbitals as linear combinations (LC) of a pre-defined set of three dimensional one-electron basis functions. Any set of appropriately defined functions X ^ can be used to define the individual molecular orbitals as:1 6 N <t>i = Z C u, XM H = 1 Equation 2.3 Basis set expansion The coefficients cw are known as the molecular orbital expansion coefficients and the basis functions Xi...Xn are also chosen to be normalized. These basis functions are usually centered on the atomic nuclei and therefore bear some resemblance to atomic orbitals, although from a mathematical standpoint any appropriately defined functions may be used for a basis expansion. Simple qualitative versions of the molecular orbital theory often use constituent atoms as basis functions. This is described as Linear Combination of Atomic Orbital (LCAO) theory. 82 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 2.1.1.4 Hartree-Fock Theory In order to obtain the expansion coefficients for the basis functions used in the basis set expansion the Hartree-Fock theory can be used. Since ^ is an antisymmetric normalized function of the electronic coordinates, its expectation value for the energy can be calculated according to: s, = jV H ^ dt = ( < t > j |H j< > ;) Equation 2.4 Expectation value for the energy According to the Variational Principle,3 s * is greater than the energy E of the exact wavefunction ¥ from the Schrodinger equation. The coefficients C m of the basis functions used have to be optimized to minimize the expectation value of the energy e,. The resulting e , will be as close to the exact energy E as possible with the limitations imposed by the single- determinant wavefunction and the basis set employed. This method leads to a series of coupled three-dimensional differential equations. 2.1.1.5 Closed-Shell Systems The set of algebraic equations for c^ was derived for the closed-shell wavefunction by Roothaan and Hall in 1951:1 7 ,1 8 83 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. N K F ^ S ^ =0 v=1 Equation 2.5 Roothann-Hall equations S„v are the elements of an N x N matrix called the overlap matrix and F^are the elements of another NxNmatrix called the Fock matrix. Since the Roothaan-Hall equations are not linear, their solution involves an iterative process. This is frequently called Self-Consistent Field (SCF) theory, since the resulting molecular orbitals are derived from their own effective potential. At convergence, the energy is at minimum and the orbitals generate a field which produces the same orbitals. The solution gives a set of occupied and unoccupied (virtual) orbitals of the same size as the basis functions employed. 2.1.1.6 Open-Shell Systems The methods described so far are incapable of treating unpaired electrons. Since these electrons are in different orbitals, two sets of molecular expansion coefficients c“ and c^ are needed.1 9 This results in two sets of Fock matrices and their associated density matrices. The solution produces two sets of orbitals, which are somewhat problematic: Even though their characteristics are similar to open-shell systems, their eigenfunctions are not 84 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. pure spin states, but contain some amount of spin contamination from higher states. 2.1.1.7 Electron Correlation The Hartree-Fock theory does not account for the correlation between the motions of electrons within a molecular system, since electrons are assigned to one-electron orbitals. More importantly, the correlation arising between electrons of opposite spin is inadequate. The two main methods used are the Moller-Plesset Perturbation theory and Configuration Interaction approaches. 2.1.1.8 Configuration Interaction The Hartree-Fock theory assumes to express the exact wavefunction as a single determinant (Equation 2.2). Configuration Interaction (Cl) uses linear combinations of Slater determinants, each of which represents an individual electron configuration. This is done by replacing occupied orbitals within the Hartree-Fock determinant with a virtual orbital. v j/Q is the single-determinant wavefunction obtained from the Hartree- Fock problem. The substituted wavefunctions iys are now constructed from v j/g by replacing occupied orbitals with virtual orbitals. In the Full Cl method, all 85 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. possible substituted determinants \\is and the Hartree-Fock determinant \\i0 are combined to the new wavefunction 'F: ^=b0 V o + S bs H ,s s>0 Equation 2.6 Full Cl wavefunction The coefficients b have to be solved for, again by minimizing the energy of the resultant wavefunction. All of the possible electronic states of the molecule are being mixed. According to quantum mechanics, they all have some probability of being attained. With the Full Cl method it is therefore possible to obtain the most complete non-relativistic treatment of the molecular system. The only limitation is the basis set employed, but one could theoretically obtain the exact solution to the Schrodinger equation if an infinite basis set would be employed. Although the Full Cl method is well defined, size-consistent and variational, it is not a practical system to use for most cases. Due to the multiple determinants involved, the method becomes very expensive and time- consuming for all but very small systems. Even though efficient algorithms for the computational challenge have been—and still are being—developed, 86 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Limited Cl methods are routinely used to reduce the length of the Cl expansion. Only a limited number of substitutions are included, truncating Equation 2.6 at some level of substitution. For example, the CIS method only adds single excitations to the Hartree-Fock determinant, the CID adds double excitations, CISD adds singles and doubles, etc. There are, however, difficulties with this approach: The Limited Cl method is not size-consistent any more. To correct this deficiency, the QCISD method—closely related to coupled cluster theory2 0 '2 2 with singles and doubles (CCSD)—adds terms to CISD to restore size-consistency. To obtain even greater accuracy, QCISD(T) adds triple substitutions to QCISD, and QCISD(TQ) adds both triples and quadruples. 2.1.1.9 Meller-Plesset Perturbation Theory This theory2 3 is closely related to the many-body perturbation theory and is another approach to overcome the lack of electron correlation in SCF calculations. The Hamiltonian is divided into two parts, the second being a perturbation on the first: H, =H0 +XV =H0 +X(H-H0) Equation 2.7 Perturbation of the Hamiltonian 87 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. H is the correct Hamiltonian and X is a dimensionless parameter. H0 is taken to be the sum of the one-electron Fock operators, or the Fock Hamiltonian. Hx coincides with H0 if A.=0 and with H if A.=1. The perturbation procedure used expands the computed energy according to Rayleigh-Schrodinger perturbation theory:2 4 '2 6 Ex=E0+XE1+A.2 E2+/l 3 E3+... Equation 2.8 Energy expansion The series is now cut at some level and X is put at 1. The method is referred to by the highest energy term allowed, i.e. truncation after second order is MP2, after third-order is MP3, etc. This theory is size-consistent if the computations are carried out completely at any given order. The terms become very complicated at higher orders and therefore very expensive. 2.1.1.10 Density Functional Theory Density Functional Theory (DFT)2 7 '2 9 follows an entirely different approach than the previously described methods. Instead of starting from the “correct” quantum mechanical description and then approximating the solution, 88 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. an “idealized” problem is solved directly. Hartree-Fock theory approximates the true many-electron solution by a composite of one-electron solutions, yet DFT directly solves the (idealized) many-electron problem. Electron Correlation is therefore taken into account in DFT methods. The results should be comparable to correlated methods such as MP2, yet the cost is comparable to HF. The DFT approach is based on modeling electron correlation via general functionals3 0 of the electron density. The Hohenberg-Kohn theorem was published in 1964. It demonstrates the existence of a unique functional that demonstrates the existence of the ground state energy and density exactly, but the form of this functional is not provided.3 1 Shortly thereafter, Kohn and Sham extended this result and proved the existence of an exact HFD-type method. They also gave a variational procedure to solve the resulting equations.3 2 A computational scheme for the calculation of the exact ground state density and energy was, in principle, set up. Several approximate functionals have been introduced over the last 20 years.3 3 *3 6 Introduction of empirical parameters in these functionals have improved the method to give very accurate results for systems that can contain up to several hundred atoms. A significant drawback of DFT is that the method cannot systematically be improved, as opposed to ab initio computations. There is no clear convergence to the exact answer of the Schrodinger equation. This area is 89 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. subject to significant research, and dialog and interaction between the groups of theoretical chemists “is a hopeful direction for further progress." (John A. Pople, Nobel Lecture, 1998).9 2.1.2 COMPUTATIONAL CHEMISTRY Chemists make use of the theoretical models, which are well-defined mathematical procedures of simulation. The computational difficulties in these models have become less significant with the ever-increasing power of computers. Today, computers are routinely used in the field to perform a variety of calculations on chemical systems. Computational chemistry distinguishes between two broad areas: molecular mechanics and electronic structure theory. 2.1.2.1 Molecular Mechanics The laws of classical physics form the basis for Molecular Mechanics simulations. The basis for all of the methods is a unique force field that defines how the potential energy of a molecule varies with the location of its components. The components are mainly characterized by the nuclei involved; yet the chemical context of the environment such as hybridization, bonding, charge and neighboring nuclei influence the characteristics of the components. 90 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. The various force constants are partly derived from experimental data to relate these characteristics to observables such as bond lengths, bond angles and energies. The effects of the electrons are implicitly included in the force field and the characteristics of the components, since the electrons are not explicitly treated. Molecular Mechanics calculations are well suited to perform inexpensive and fast calculations for systems with up to several thousand atoms. Individual force fields are parameterized to achieve good results for specific systems. This means that no force field can be used for all molecular systems of interest. Since the effect of electrons is greatly neglected, great caution is necessary for systems where electronic effects predominate. Many computer programs for Molecular Mechanics calculations have been developed, including MM3, HyperChem,3 7 Sybyl and Alchemy. Many research groups—especially theoretical biochemists—have developed individual packages to treat specific systems.3 8 2.1.2.2 Electronic Structure Theory Electronic Structure Theory is based on the laws of quantum mechanics (briefly described earlier)—rather than classical physics—for the computational approach. Since exact solutions to the Schrodinger equation are not computationally practical, different approximations are implemented in 91 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. the main classes of Electronic Structure Theory: Semi-empirical methods, ab initio methods and Density Functional Theory.3 9 2.1.2.3 Semi-Empirical Methods To simplify the computational challenges, this method uses parameters derived from experimental data. Similar to Molecular Mechanics methods, different parameter sets are the basis for different approaches to solve the Schrodinger equation. The three main methods are AM1, MINDO/3 and PM3. They are implemented in programs like AMPAC, HyperChem, MOPAC and Gaussian.4 0 2.1.2.4 Ab Initio Methods These methods are solely based on the laws of quantum mechanics. This “first principles” approach is illustrated in the name ab initio. No experimental parameters—as opposed to molecular mechanics or semi- empirical methods—are used, except the necessary physical constants. In paragraph 2.1.1 (page 78), the theoretical background for these methods was explained, and the various approximations to solve the Schrodinger equation were illustrated. There are numerous software implementations of ab initio methods. Among the more popular ones are Spartan,4 1 Jaguar4 2 and HyperChem. The 92 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. most widely used and—arguably—most sophisticated program suite is Gaussian, which has been used for more than thirty years and provides very extensive ab initio functionality. 2.1.2.5 Density Functional Methods This class of electronic structure methods has been implemented in software packages in the late 1980s, and has led to a “second revolution” in computational chemistry. Although the cost of these calculations sizes at the same power as Hartree-Fock calculations do, the results are comparable to post-SCF methods such as MP2. The methods have been briefly described in paragraph 2.1.1.10 (page 88). 2.1.2.6 Quantum Chemical Models In order to apply the methods to chemical systems, a theoretical model has to be selected. There are many different theoretical models in the available software packages. Each model has to meet certain criteria in order to be applicable to chemical problems: It needs to be uniquely defined, so no other parameters than a specific molecular structure are needed to solve the approximation to the Schrodinger equation. A theoretical model should not rely on presumptions about molecular structure or chemical processes, which would limit its applicability to certain classes of systems. 93 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. After the theoretical model has been defined and implemented, it needs to be verified. The model can be tested against known chemical facts to determine whether the target requirements have been met. After verification, the model can be used to predict answers to chemical problems that are unknown or in dispute. The most commonly used model chemistries refer directly to the different levels of theory (the approximation method) they use. Programs such as Gaussian implement the Hartree-Fock SCF method (keyword HF); the 2n d order Moller-Plesset perturbation theory (MP2); the 4th order Moller-Plesset perturbation theory (MP4); the Becke-style 3-paramter DFT using the Lee- Yang-Parr correlation functional (B3LYP); Quadratic Cl with singles, doubles and triples (QCISD(T)); and coupled cluster methods with singles, doubles and triples (CCSD(T)). 2.1.2.7 Basis Sets Basis set expansions are an essential step in the approximation of the Schrodinger equation (see page 83). To provide basis sets that are well defined for any nuclear configuration, particular sets of basis functions are associated with each nucleus. They depend only on the charge of that nucleus and are therefore useful for theoretical models. In most cases, they have the symmetry properties of atomic orbitals and are classified as s-, p-, d-, f-types. 94 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Two types of atomic basis functions are generally used. The Slater type atomic orbitals (STO) have exponential radial parts, are labeled like hydrogen atomic orbitals and have the (normalized) form:4 3 ^ and < ;2 are constants that determine the size of the orbitals. Atomic orbitals are reasonably represented, but numerical work with these functions is complicated. This has limited their use in model chemistries to some extent. Gaussian-type atomic functions are widely used.4 4 They were introduced by Boys4 5 and have the general form: <t>,s= — expK,r) 7 t Equation 2.9 Slater-type atomic orbitals g(a, x, y,z) = c x n ym z1 e Equation 2.10 Gaussian-type atomic functions 95 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. a is a constant determining the radial extent of the function, x, y and z are the coordinates, c is the normalization constant, thus it depends on a, I, m and n. The actual basis functions for the basis set expansion are obtained through linear combinations of these primitive gaussians. Basis sets can be classified by the number and type of basis functions they contain. Minimal basis sets contain the minimum number of basis functions needed for each atom (1s for H; 1s, 2s, 2px, 2py and 2pz for C; etc.). Split valence basis sets represent each valence orbital by two or more basis functions. Orbitals in these basis sets can change their size, but not their shape. Polarized basis sets add orbitals with angular momentum beyond what is required for the ground state (p functions for hydrogen, d functions for carbon and f functions for transition metals) to remove this limitation. To allow orbitals to occupy larger regions of space, large versions of s- and p-type diffuse functions are included in some basis sets. This is important for systems where electrons can be relatively far from nuclei, such as molecules with lone pairs or significant negative charge. Typical basis sets that are frequently used in computations and their descriptions are illustrated in Table 2.1. 96 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Table 2.1 Basis Sets3 Basis Set Description Number of Basis Functions 15 1 Row Hydrogen Atoms Atoms STO-3Gb Minimal basis set 5 1 3-21G Split valence basis set with 2 sets of functions 9 2 6-31 G(d) Adds polarization functions to heavy atoms 15 2 6-31 G(d.p) Adds polarization to hydrogens 15 5 6-31+G(d) Adds diffuse functions 19 2 6-31+G(d,p) Adds diffuse functions to hydrogens 19 5 6-311+G(d,p) Triple zeta basis set, adds extra valence functions 22 6 6-311+G(2df,2p) Puts 2 d functions and 1 f functions plus diffuse functions on heavy atoms and 2 p functions on hydrogen atoms 34 9 6-311++G(3df,2pd) Puts 3 d and 1 f functions on heavy atoms and 2 p and 1 d functions hydrogen atoms plus diffuse functions on both 39 15 a from Reference 8 b Slater orbitals are approximated with Gaussian functions for performance 97 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 2.1.3 ELECTRON DEFICIENT INTERMEDIATES The chemistry of electron-deficient species has been of great interest in chemistry. The pioneering work of George Olah in the fields of carbocations,4 6 -5 0 superacids,5 1 superelectrophiles5 2 and many related areas has made it possible to prepare and observe many electron-deficient species and obtain detailed knowledge about the processes involved in this fascinating area of chemistry. He was awarded the 1994 Nobel Prize in Chemistry,5 3 “for his contributions to carbocation chemistry" (Citation of the 1994 Nobel Prize in Chemistry).5 4 Computational Chemistry has become an essential tool in the field of electron deficient intermediates. Due to the inherent instability of many species, thermodynamic stabilities are often hard to obtain by experimental studies. Since some properties—such as their chemical shifts—can be obtained, calculation and comparison of these parameters has proven to be extremely helpful in this area of research. 98 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 2.1.4 THE 2-NORBORNYL CATION The 2-norbornyl cation is probably the most extensively studied system in organic chemistry. For more than thirty years, the system has been subject to intense controversy, the so-called “classical-nonclassical ion controversy”.5 5 "5 7 The center of this debate was the structure of the 2- norbornyl cation: Is it correctly depicted as the static symmetrically bridged structure (2.1), or as a rapidly equilibrating pair (2.2.1) and (2.2.2)? 2.1 2.2.1 2.2.2 Scheme 2.1 The 2-norbomyl cation The ion (2.1) is a hyper-coordinated species, containing penta- coordinated carbon. By definition, this has a nonclassical carbocationic structure, or a carbonium ion.5 8 (2.2.1) and (2.2.2) are characterized by classical trivalent carbon and are therefore carbenium ions. 99 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 2.1.4.1 The 2-Norbornyl Cation as an Intermediate in Solvoiysis The heated debate about this problem arose from Winstein and Trifan’s pioneering studies on the solvoiysis behavior of 2-exo- (2.3) and 2-endo- norbornyl brosylates (2.4) (Scheme 2.2).5 9 '6 1 They found that the titrimetric rate for (2.3) in acetic acid is 350 times faster than that of (2.4). Both (2.3) and (2.4) give exclusively (>99.9%) exo product (2.5). Furthermore, starting with optically active (2.3), the polarimetric rate exceeds the titrimetric rate by a factor >104 and produces racemic (2.5), whereas the polarimetric and titrimetric rates of (2.4) are equal but some chirality is preserved. To explain this behavior, Winstein and Trifan suggested a symmetrically bridged intermediate (2.1). Such intermediates had been suggested by Wilson 100 H 0S 02 Ar 2.4 Scheme 2.2 Solvoiysis studies on 2-norbomyl arenesulfonates Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. and coworkers in 1939,6 2 based on the ionic nature of the camphene hydrochloride-isobomyl chloride rearrangement originally recognized by Meerwein and van Emster in 1922.6 3 Winstein and Trifan ascribed the accelerated rate of the exo isomer to the neighboring group participation of the C1-C6 bonding electrons (Scheme 2.3). This anchimeric assistance leads to fast formation of the (nonclassical) transition structure (2.6) and then to (2.1) (or the ion pair). The endo rate was described as normal, thus it is in agreement to that of other secondary substrates without neighboring group participation. Formation of the (classical) transition structure (2.7) is the rate- determining step. Subsequently (2.7) collapses to the same intermediate. Products 2.4 2.7 Scheme 2.3 Suggested pathway for the solvoiysis of 2- norbomyl derivatives 101 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Opponents of this theory—of whom H. C. Brown has been the major and most distinguished advocate—believed that the postulation of a symmetrically bridged 2-norbornyl cation intermediate (2.1) is an incorrect and unnecessary explanation of the facts.5 5 ,6 4 "6 8 Brown suggested a different model, which attributes the rate difference and the exclusive formation of exo product to steric effects. The exo rate should therefore be normal, whereas the endo rate is lowered. Bentley and coworkers dearly showed in the early 1980s that Brown’s interpretation is incorrect.6 9 They compared the solvoiysis rate of secondary substrates in low-nucleophilicity solvents and showed that the observed solvoiysis rate for the 2-exo-norbornyl system is clearly exceptional. Many more experimental and theoretical studies on the solvoiysis behavior have been published to support the existence of (2.1 ).7 0 '7 2 In a detailed theoretical study7 3 at the B3LYP/6-311+G# //B3LYP/6-31G* level, Schreiner, Schleyer and Schaeffer have shown that Winstein and Trifan’s explanations have to be somewhat amended, but Brown’s arguments are incorrect. 2.1.4.2 The Stable Nonclassical 2-Norbornyl Cation Often mixed into interpretations of the solvoiysis experiments—though quite different in origin and characterization—is the observation of (2.1) under long-lived stable ion conditions. The methods developed by Olah in the early 102 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 1960s to generate and observe stable carbocations in low nucleophilicity solutions7 4 "7 6 allowed the direct observation of (2.1). x 2.8 Scheme 2.4 Preparation of the 2-norbornyl cation under stable ion conditions The ion (2.1) can be prepared by the “o route" from 2-norbornyl halides (2.8), by the “n route" from cyclopentenylethyl halides (2.9) and by protonation of nortricyclene (2.10). The best resolved NMR spectra can be obtained from 2-exo-fluoronorbornane in SbFs/S02 or SO2CIF (with or without SO2F2) solutions. The structure of the ion became part of the controversy. Scheme 2.5 shows the degenerate shifts in the 2-norbomyl cation. To understand the data and equilibration processes, the (hypothetical) classical situation is also illustrated. 103 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Nondassical Ion Formulation 6.1.2-hydride shift 3.2-hydride shift L Classical Ion Formulation 6.2-hydnde shift Wagner-Meerwein shift 3,2-hydnde shift Scheme 2.5 Degenerate shifts in the 2-norbornyl cation (from reference 49, page 159) The 395 MHz 1 H NMR spectrum at room temperature shows a single peak. This means that the 6,1,2- and 3,2-hydride shifts are occurring much faster than the NMR timescale. At -158°C the spectrum shows five distinct peaks, with H1 being equivalent to H2 (strongly deshielded at 8 6.75) and H3 being equivalent to H7. This means that both the 6,1,2- and the 3,2-hydride shifts are completely frozen. One observes the symmetrically bridged static (2.1). Opponents argued that there is a rapidly occurring Wagner-Meerwein shift, and one is observing the transition state of this process. This argument 104 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. was proven incorrect when Yannoni and coworkers obtained the solid state 1 3 C NMR spectra of (2.1) at -268°C.7 7 '7 9 In this remarkable achievement, no dynamic equilibrium corresponding to (2.2.1) and (2.2.2) could be frozen out. This means that the hypothetical activation barrier for that process would be less than 0.2 kcal/mol. This is clearly too low for the extensive bond-to-bond rearrangement that has to occur when interconverting (2.2.1) and (2.2.2). Although the geometry of (2.1) is still not known experimentally, the structure of (2.1) has been unambiguously established. A wealth of other data, such as isotopic perturbation of degeneracy,8 0 ESCA8 1 '8 4 and even—to some extent—crystal structures of derivatives,8 5 has contributed to the nonclassical structure. Additionally, high-level ab initio calculations have concluded that (2.2) is not even a minimum on the potential energy surface of the 2-norbornyl cation. Schleyer and coworkers have demonstrated that the symmetrically bridged structure (Cs symmetry, illustrated in Figure 2.1) is the minimum on the potential energy hypersurface, and its calculated chemical shifts coincide with the experimental data.8 6 105 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 1.548 1.545 ,1.512 1.395 1.528 1.892 Figure 2.1 Geometry of the 2-norbornyl cation (2.1) at the B3LYP/6-31G(d) level (from reference 86) The classical structure corresponds to a transition state for the rearrangement of the 2 -norbornyl cation to the bridged 2 -norpinyl cation.87 88 Furthermore, the classical structure is not preferred in high-polar media— which had often been speculated—as a combined ab initio-Monte Carlo study showed.89 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 2.1.5 SILYL EFFECTS IN CARBOCATIONS The interaction of silicon with electron deficient intermediates has long been known. Whitmore and coworkers described the effects of silyl substituents on positively charged carbon in 1946.9 0 There are numerous studies (theory, solvolysis, gas-phase and stable-ion conditions) on silyl- substituted carbocations in the literature.91,92 Important synthetic applications have been developed, based on the ability of silicon to influence the reactivity at electron deficient carbon.93 The effects of silyl substituents are generally classified by the position of the silyl substituent relative to the carbocation (a-,p-,y-, etc. -effect). An a-silyl substituent is generally destabilizing with respect to alkyl-substituents, yet stabilizing with respect to hydrogen. This is slightly different for dicoordinated cations: an a-silyl group stabilizes a vinyl cation approximately the same as a methyl group.94 A few a-silyl substituted carbocations have been observed under stable ion conditions. The diphenyl(trimethylsilyl)-methyl cation (C6H5) 2C+ Si(Me)3 shows slightly shielded chemical shifts for the para- position of the aromatic rings compared to the methyl and hydrogen analogues (C6H5)2C+ Me and (C6H5)2C+ H.95 This could imply a smaller delocalization of the positive charge in the silyl-substituted carbocation. However, due to possible non-planarity of the phenyl rings, a conclusive comparison between the three cations is not possible. 107 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. In contrast, p-silyl substitution is far more stabilizing. At the MP3/6-31 G(d)//MP3/3-21 G(d) level, the H3 SiCH2 CH2 + cation is 38 kcal/mol more stable than the ethyl cation and 10 kcal/mol more stable than the 1-propyl cation.9 6 Vinyl cations are also stabilized. At the same computational level, the H3 SiC=CH+ cation is 28.6 kcal/mol more stable than the parent vinyl cation H2 C=CH+ and 20.5 kcal/mol less in energy than the 1-propenyl cation CH3CH=CH+ .9 6 Lambert and coworkers recently reported the observation of (C6H5 )2 C+ CH2 Si(Et)3 and concluded that this p-silyl cation is not significantly more stabilized (compared to the parent (C6 H5)2 C*CH3 ) by the silyl substituent, since the parent cation is already stabilized by the two phenyl rings.9 7 But Siehl and coworkers have demonstrated the effects of p-silyl substituents on vinyl cations.9 8 -1 0 0 The effect of silyl substituents on allyl cations was also investigated.1 0 1 The stabilizing effect of the p-silyl group is explained by several factors. Silicon has a greater (electron-donating) +l-inductive effect than carbon or hydrogen. Additionally, hyperconjugation (illustrated in Scheme 2.6) of silicon was suggested as early as 1948, and has been extensively studied.1 0 2 '1 0 5 2.11 2.12 Scheme 2.6 Hyperconjugation in carbocations 108 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. This hyperconjugation is one type of vertical stabilization, which means that no change in geometry and atom-atom distances are involved.1 0 6 For a p-silyl substituent (R=SiR’3), a C=C double bond is formed with a positively charged silicon. This is clearly more stabilizing than for an alkyl (R=CH3 ) or hydrogen (R=H) substituent, where a CH3 + or a hf would be formed. However, vertical stabilization is not advantageous for a-silyl substituents, since the unstable C=Si double bond would be formed. Solvolytic studies on 2,6-disubstituted norbornyl systems showed a y-silicon effect. Bentley, Kirmse and coworkers showed in a series of papers,1 0 7 '1 0 9 that the 6-exo-trimethylsilyl substituent in (2.13) causes a rate acceleration of 33,000 relative to hydrogen (Scheme 2.7). 2.13 2.14 2.15 BsO SiMe3 OMs 2.17 2.16 Scheme 2.7 2,6-Disubstituted norbomyl derivatives 109 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. The 6-endo-trimethylsilyl compound (2.14) solvolyzes only 48 times faster than the (unsubstituted) reference compound (2.15). The rate of solvolysis for the corresponding 6-endo compound (2.16), in contrast, is only accelerated by a factor of 2-4, and (2.17) even shows rate retardation. This large kinetic affect was attributed to the interaction of the -/-silicon group with the initial empty 2p(C+ ) orbital in the transition state for the solvolysis. In addition, the strong orientational preference of the W-like geometry for this effect was demonstrated. In an elegant study of silyl-substituted bicyclobutonium ions,1 1 0 ,1 1 1 Siehl and coworkers were able to characterize the 1-(trimethylsilyl)bicyclobutonium ion (2.19) under stable ion conditions (Scheme 2.8). They found different energy surfaces compared to the parent bicyclobutonium and methyl- substituted bicyclobutonium ions, and they supported their findings with ab initio and chemical shift calculations at the MP2/6-31G(d) and the GIAO- MP2//tzp/dz levels. This cation undergoes a fast threefold degenerate methylene rearrangement leading to averaged NMR signals for the exo methylene protons, the endo-methylene protons and the methylene carbon atoms, whereas the isomeric (T-(trimethylsilyi)cyclopropyl)methyl cation does not contribute to NMR chemical shifts. 110 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. e x ch2oh SbF5 SiMe3 S02CIF/S02F2 -130°C 2.18 SiMe3 H' - H H 2.19 , ch2oh SbF5 SiMej'Bu SO2CIF/SO2F2 -130°C 2.20 SiMe2'Bu H H 2.21 -115°C SiMe2'Bu H H 2.22 Scheme 2.8 Silyl-substituted bicyclobutonium ions Moreover, they obtained the S-endo-^butyldimethylsilyObicyclobutonium ion (2.22) by rearrangement from l-fbutyldimethylsilyObicyclobutonium ion (2.21) at -115°C. (2.22) is the first static bicyclobutonium ion on the NMR timescale, due to efficient stabilization of the positive charge by the y - trialkylsilyl substituent. 2-dimensional CH-COSY and HH-COSY NMR spectra fully support the findings and the computed chemical shifts (Scheme 2.8). 111 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. The first silicon-substituted norbornyl cation (2.24) was prepared as a tetrakis(pentafluorophenyl)borate salt by hydride transfer reaction (Scheme 2.9).1 1 2 The resulting 6,6-dimethyl-5-neopentyl-6-sila-2-norbornyl cation (2.24) shows significant deshielding of the C1 and C2 carbons in the 1 3 C-NMR. This and comparison of quantum chemical calculations at the B3LYP/6-31G(d) level provide strong evidence for the n-complexation of the positively charged silicon. Me3CH2C. Me3CH2C. Ph3C*[B(C6F5) 4] 2.23 2.24 Scheme 2.9 The 6,6-dimethyl-5-neopentyl-6-sila-2-norbomyl cation 112 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 2.2 THEORETICAL INVESTIGATIONS OF TRIMETHYLSILYL- SUBSTITUTED NORBORNYL CATIONS Trimethylsilyl-substituted norbornyl cations have not been observed under stable ion conditions. Furthermore, no computational studies have been published on these systems. Since there is evidence for silyl-stabilization from solvolytic studies (see page 109), we were encouraged to investigate the effects of trimethylsilyl-substituents on the norbornyl cations. We were particularly interested in the effects of the trimethylsilyl substituent on the geometry of the cations. In order to gain insight into potential synthetic strategies for precursors to observe these species under stable ion conditions, we were also interested in the nature of the potential energy surface of the systems. We also wanted to obtain information about thermodynamic and kinetic barriers for the interconversion of the isomeric trimethylsilyl-substituted cations. 2.2.1 TRIMETHYLSILYL-SUBSTITUTED 2-NORBORNYL CATIONS The interconversion of trimethylsily-2-norbornyl cations is illustrated in Scheme 2.10. For simplicity, the classical valence structures of the systems 113 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. are shown. 3,2-Hydride (3,2H), 6,2-hydride (6,2H) and (potentially) Wagner- Meerwein (WM) shifts would lead to the cations (2.25)-(2.31). Me3Si- Scheme 2.10 Interconversion of trimethylsilyl-2-norbornyl derivatives As our calculations indicate, the cations (2.29)-(2.31) illustrated in parentheses—as well as a few other ones that mainly occur from 114 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. interconversion of enantiomers—do not correspond to minima on the potential energy surface. Attempts in optimizing the geometries of (2.28)-(2.31) always resulted in other structures or failed. As we show later, this can easily be explained by the stabilizing effects of the trimethylsilyi-substituent, depending on its position in relation to the positive charge. 2.2.1.1 Minimum Energy Structures We were, however, successful in obtaining structures that correspond to minimum energies at the B3LYP/6-31G(d) level for (2.25)-(2.28) and other isomers. This level has been shown to be a “standard level for geometry optimizations of carbon bridged species with reduced computational cost compared to MP2/6-31GV’1 1 3 The optimized geometries are illustrated in Figures 2.4-2.9. Additionally, each structure is displayed with the hydrogen atoms omitted for clarity. Relevant distances are indicated in the figures. 115 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 2.349 Figure 2.2 Geometry of 3-exo-trimethylsilyl-2-norbomyl cation (2.25) at the B3LYP/6-31G(d) level In the bottom structure, the hydrogen atoms are omitted for clarity (distances are indicated in A) 116 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 1.860 Figure 2.3 Geometry of 5-exo-trimethylsilyl-2-norbomyl cation (2.26) at the B3LYP/6-31G(d) level In the bottom structure, the hydrogen atoms are omitted for clarity (distances are indicated in A) 117 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Figure 2.4 Geometry of 6-exo-trimethylsilyl-2-norbornyl cation (2.27) at the B3LYP/6-31G(d) level In the bottom structure, the hydrogen atoms are omitted for clarity (distances are indicated in A) Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Figure 2.5 Geometry of 2-trimethylsilyl-2-norbomyl cation (2.28) at the B3LYP/6-31G(d) level In the bottom structure, the hydrogen atoms are omitted for clarity (distances are indicated in A) 119 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 1.586- 2.134 Figure 2.6 Geometry of 3-encfo-trimethylsilyl-2-norbornyl cation (2.32) at the B3LYP/6-31G(d) level In the bottom structure, the hydrogens are omitted for clarity (distances are indicated in A) 120 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Figure 2.7 Geometry of 4-trimethylsilyl-2-norbomyl cation (2.33) at the B3LYP/6-31G(d) level In the bottom structure, the hydrogens are omitted for clarity (distances are indicated in A ) 121 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Comparison of the geometries reveals intriguing details: the molecules have significantly altered geometries from the parent 2-norbornyl cation (2.1). Especially the degree of bridging—that is the distance between C2 and C6— indicates the nonclassical or classical character of the species. If the cation is bridged, the C2-C6 and the C1-C2 distances are shortened (compared to the neutral species) and the C1-C6 distance is increased. For comparison, see the neutral 2-exo-trimethylsilyl norbornane (2.34) illustrated in Figure 2.16 (page 146) and the 2-norbornyl cation (Figure 2.1, page 106). The 3-exo system (2.25) appears to be essentially unbridged (C2- C6=2.349A). The distance between C1-C6 is only slightly longer than that of C5-C4. However, the C2-C3 distance is significantly shortened and the C3-Si distance is increased. This is indicative of extensive stabilization due to hyperconjugation of the p-silyl substituent and delocalization of the positive charge onto silicon. The 5-exo system (2.26), in contrast, shows extensive bridging. C1-C6 is only slightly shortened and C2-C6 lengthened by less than 0.1 A compared to (2.1). The other bond lengths are also comparable to (2.1). This illustrates the nonclassical character of this cation. Apparently, the silyl substituent is too far from the positive charge to provide any significant stabilization. Similar geometry of the norbomyl-framework is seen in the 6-exo substituted cation (2.27). The structure is extensively bridged, the C2-C6 distance is even 0.1A shorter than in (2.1). From this geometry it appears that 122 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. the silyl substituent participates in weak (through space) hyperconjugation, which shortens the C2-C6 distance and lengthens the C6-Si bond. The a-silyl substituted cation (2.28) shows a decreased amount of bridging. Apparently, the silyl substituent provides increased stability to this system, more than one would expect from an a-silyl effect. The C2-Si bond is just slightly shortened, but that is no indication for stabilization. The C1-C2 bond length, however, is in between the fully bridged structure (2.1) and the neutral structure (2.34). An interesting effect is seen for the 3-endo-trimethylsilyl cation (2.32). The structure is unbridged and the C2-C6 distance is even longer than in the 3-exo analogue. However, the C3-Si distance is slightly longer than in the exo- isomer, therefore increased vertical stabilization of the p-e/ido silyl substituent (compared to the (3-exo substituent) is unlikely. The cation might be unbridged because of steric reasons, not because of a strong silyl-effect. A somewhat different system with the trimethylsilyl substituent at the 4- bridgehead carbon is the 4-trimethylsily-2-norbomyl cation (2.33). The geometry is only slightly altered from the 2-norbornyl cation (2.1). The C2-C6 and the C1-C2 bond lengths are equivalent, the cation is therefore symmetrically bridged. The system has Cs symmetry, indication for no significant stabilization of the positive charge by the y-silyl substituent. 123 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 2.2.1.2 Transition States We were also interested in the transition states for the conversions of the four stable minima (2.25)-(2.28). We were able to locate these transition states by transition state geometry optimizations combined with frequency calculations at the HF/3-21G, HF/6-31G(d) and B3LYP/6-31G(d) levels. It is worth noting that the 3,2-hydride shift in the conversion of (2.26) to (2.27) can occur by the exo- or enc/o-hydrogen. We were able to obtain both transition structures (2.36) and (2.37) that correspond to the exo and endo shift. We will show later that the exo transition state (2.36) is lower in energy. The structures of the transition states are illustrated in Figures 2.10- 2.14. In the bottom structure of each Figure, the hydrogen atoms—except the ones involved in the conversion—have been omitted for clarity. 124 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Figure 2.8 Geometry of the transition state (2.35) at the B3LYP/6-31G(d) level In the bottom structure, most hydrogen atoms are omitted for clarity (distances are indicated in A ) 125 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Figure 2.9 Geometry of the transition state (2.36) at the B3LYP/6-31 G(d) level In the bottom structure, most hydrogen atoms are omitted for clarity (distances are indicated in A) 126 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Figure 2.10 Geometry of the transition state (2.37) at the B3LYP/6-31G(d) level In the bottom structure, most hydrogen atoms are omitted for clarity (distances are indicated in A) 127 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Figure 2.11 Geometry of the transition state (2.38) at the B3LYP/6-31G(d) level In the bottom structure, most hydrogen atoms are omitted for clarity (distances are indicated in A) 128 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Figure 2.12 Geometry of the transition state (2.39) at the B3LYP/6-3lG(d) level In the bottom structure, most hydrogen atoms are omitted for clarity (distances are indicated in A ) 129 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 2.2.1.3 Energetics Frequency calculations at the same level as the geometry optimizations (B3LYP/6-31G(d)) confirmed the stationary points on the potential energy surface: The energy minima corresponding to the cations (2.25)-(2.28) and (2.32)-(2.33) are characterized by an absence of imaginary frequencies (Nlmag=0). The transition states (2.35)-(2.39) correspond to first-order saddle points. The number of imaginary frequencies obtained from the calculations was equal to one in all cases. Additionally, the normal mode corresponding to the imaginary frequencies confirmed that the transition states connect the correct local minimum structures. The Zero Point Energies (ZPE) were also obtained from the frequency calculations at this level. The ZPE is a correction to the electronic energy of the molecule to account for the effects of molecular vibrations (which persist even at 0 K). Single point energy calculations at the B3LYP/6-311+G(3df,2pd) level were then performed on the geometries obtained at the B3LYP/6-31G(d) level. All the computed absolute energies in atomic units (Hartrees) and the ZPE corrections are summarized in Table 2.2. The 3-exo-trimethylsilyl-2-norbornyl cation (2.25) is the global minimum at both the B3LYP/6-31G(d) and B3LYP/6- 311+G(3df,2pd) computational level. This is not surprising, since extensive p-silyl stabilization leads to a nonclassical structure. 130 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Table 2.2 Absolute energies3 2-Norbornyl Cation Absolute Energy B3LYP/6-31G(d) [au] Zero Point Energy" [au] Absolute Energy B3LYP/6-311 +G(3df, 2pd) [au] (2.25) 3-exo-TMS -681.674519 0.267781 -681.927205 (2.26) 5-exo-TMS -681.740475 0.266363 -681.904996 (2.27) 6-exo-TMS -681.759103 0.267175 -681.922215 (2.28) 2-TMS -681.758697 0.266605 -681.920766 (2.32) 3-encfo-TMS -681.751991 0.267208 -681.915352 (2.33) 4-TMS -681.742760 0.266000 -681.906493 (2.35) [(2.25H-M2.26)]* -681.726839 0.264897 -681.892377 (2.36) exo [(2.26)<->(2.27)]* -681.718285 0.263968 -681.883764 (2.37) endo [(2.26)«-M2.27)]* -681.706466 0.263827 -681.872385 (2.38) [(2.27)0(2.28)]* -681.744105 0.264786 -681.908562 (2.39) [(2.25)0(2.28)]* -681.729061 0.264065 -681.893628 3 geometries from the B3LYP/6-31G(d) level " unsealed To compare the energies of the other cations and the transition states for their interconversions, the global minimum (2.25) was used a reference and set to zero. The Zero Point Energies were scaled with a factor of 0.96 to correct for known systematic errors and added to the absolute energies.1 1 4 "1 1 6 The relative energies were then obtained and converted to kcal/mol, as illustrated in Table 2.3. Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Table 2.3 Relative energies3 2-Norbornyl Cation Relative Energy B3LYP/6-31 G(d)b [kcal/mol] Relative Energy B3LYP/6-311 +G(3df, 2pd)b [kcal/mol] (2.25) 3-exo-TMS 0.0 0.0 (2.26) 5-exo-TMS 14.2 13.1 (2.27) 6-exo-TMS 3.0 2.8 (2.28) 2-TMS 2.9 3.3 (2.32) 3-encfo-TMS 7.5 7.1 (2.33) 4-TMS 12.6 11.9 (2.35) [(2.25K+(2.26)]t 21.9 20.1 (2.36) exo [(2.26)«->(2.27)]* 26.7 25.0 (2.37) endo [(2.26)++(2.27)]1 34.0 32.0 (2.38) [(2.27^(2.28)]* 11.0 9.9 (2.39) [(2.25)«-*(2.28)]1 20.0 18.8 3 geometries from the B3LYP/6-31G(d) level 0 includes zero point energy (scaled with 0.96) at B3LYP/6-31G(d) The energy differences from the two computational levels are less than 2.0 kcal/mol for all cases. Even though this is no measure for the accuracy of the methods, it does rule out obvious shortcomings of one single basis set to adequately describe the situation. All cations with the silyl substituent in a-, p- or y-position relative to the positive charge are significantly stabilized. The relative energies coincide with the amount of bridging seen in the geometry of the cations. The more a cation is bridged, the more it resembles the 132 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. nonclassical 2-norbomyl cation and the less it is stabilized by the silyl- substituent. The relative stabilization of the substituents is equivalent to the relative stability of the respective cation. This means, that the a- and y-trimethylsilyl substituents in (2.28) and (2.27) are both equally stabilizing. The p-trimethylsilysilyl group stabilizes (2.25) only by an additional 3 kcal/mol more. However, this is no indication for the total stabilizing effect of the silyl- group. This can be obtained from isodesmic reactions, discussed later in the chapter. Interestingly, the trimethylsilyl group in (2.26) provides little or no stabilizing effect. As seen in the geometry, the system is almost fully bridged. The 3-endo-trimethylsilyl system (2.32) is 7.1 kcal/mol less stable than the exo-isomer (2.25). It is known that endo-compounds are thermodynamically less stable than exo-compounds in norbornyl systems. However, in the process of obtaining the energies of the neutral species (for the isodesmic reactions), it turned out that 2-endo-trimethylsilylnorbomane is only 1.1 kcal/mol less stable than its 2-exo analogue (at B3LYP/6-31G(d)). The extra stabilization to account for the energy difference must therefore be accounted to the greater silyl-effect in the exo-isomer. This is also in agreement with the interpretation of the structures of the two cations. The relative energies of the transition states allow assessing the kinetic barrier between the cations. It is clear that interconversion between systems 133 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. that are similar in geometry is much more feasible than those hydride shifts requiring extensive bond-to-bond rearrangement. (2.27) and (2.28) are equivalent in energy. They both resemble nonclassical, bridged structures. The 6,2-hydride shift has a low barrier of less than 8 kcal/mol. In contrast, the strong stabilization of the p-silyl substituent on (2.25) and its resulting classical structure inhibit the 3,2-hydride shift to form the nonclassical (2.28). This activation barrier is around 19 kcal/mol, even though the energy difference between the two minima is only 3 kcal/mol. Similar bond- to-bond rearrangements have to occur for the conversion of (2.25) to the nonclassical (2.26). In this 6,2-hydride shift, the energy difference between the transition state and (2.25) is around 20 kcal/mol, yet (2.28) is 14 kcal/mol higher in energy than (2.25). The transition state is bridged, therefore more closely resembles (2.28). This is in agreement with the Hammond-postulate.1 1 7 Conversion of the nonclassical (2.27) to the less stable (2.26) also involves bond-to-bond rearrangements. As indicated, two transition states were found corresponding to the exo- and encfo-hydride shift. From the geometry, it is not apparent whether the transition state is similar to the starting material or the product. The energy difference of 22 kcal/mol (or 29 kcal/mol) between (2.36) (or (2.37)) and (2.27) demonstrates that the stabilizing effect of the silyl-group has to be overcome. Interestingly, the endo- transition state is 7 kcal/mol higher in energy than the exo-transition state. This can be explained by looking at the orbital overlap as indicated in Scheme 134 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 2.11. The formalism depicted does not reflect the electron densities of the various molecular orbitals obtained from the calculations, but isolates the individual atoms. This is useful to get a qualitative overview. We also looked at the electron densities by plotting the HOMO and LUMO in a graphical visualization program and found similar results. In (2.36), the alignment of the orbitals still allows some overlap in the transition state, whereas in (2.37) the orbitals are not aligned correctly to provide this stability. endo-TS 2.37 Scheme 2.11 Comparison of the exo- and endo- transition states for the 3,2-hydride shift in (2.27) 135 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 2.2.1.4 Unstable Structures As previously mentioned, we did not find any minima for several structures in our geometry optimizations. The calculations either failed or systems with significantly different geometries resembling other minima were obtained (Scheme 2.12). 2.30 S « M e 3 - K Me-jS 2.31 K 2.29 MfrjSi \ Jt? 2.27 S ' / Me3Si J.28 2.32' SlMei SiMei \ 2.40 r S.Me, 2.36 MejS. 2.25' N 2.26* Scheme 2.12 Systems for which no minimum on the PES was found and the obtained analogues We did not find a minimum for the 6-encfo-trimethylsilyl-2-norbomyl cation (2.30), all attempts resulted in (2.27). Attempts to localize 1-trimethylsilyl-2-norbomyl cation (2.31) led to (2.28). Even though (2.31) is a p-silyl substituted carbocation, the rigid structure of the bridgehead carbon does not allow the silyl substituent to participate in hyperconjugation and this 136 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. substitution imposes strain on the system. The resulting a-silyi substituted carbocation is also significantly stabilized (compared to the 2-norbomyl cation). The 7-trimethylsilyl substituted analogues rearrange to the 3-substituted cations. Surprisingly, we did not find a minimum structure corresponding to the 5-endo-trimethylsilyl-2-norbornyl cation (2.41). All attempts led to the 5-exo isomer (2.31’). 2.2.2 TRIMETHYLSILYL-SUBSTITUTED 1- AND 7-NORBORNYL CATIONS In the same context, we calculated the structures and energies for two other trimethylsilyl-substituted norbornyl cations. The 2-exo-trimethylsilyl-1 - norbomyl cation (2.42) is a bridgehead carbocation. We were interested in the effect of the p-silyl substituent on the geometry and energetics of this inherently unstable carbocation. The 7-norbornyl cation has not been observed under stable ion conditions. Recently, the system has been observed by low temperature IR; ab initio calculations at the MP4(sdq,fc)/6-31G*7/MP2(full)/6-31G* level were also performed.8 7 Several stationary points were found and computed in the isomerisation reaction to form the 2-norbomyl cation. 137 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. We wanted to see whether an a-siiyl substituent would stabilize the 7-trimethylsilyl-7-norbornyl cation (2.43) and raise the kinetic barrier for its rearrangement to the 2-norbomyl cation. Geometry optimizations found minima corresponding to the structures shown in Figures 2.14 and 2.15 for the 2-exo-trimethylsilyl-1 -norbomyl cation (2.42) and the 7-trimethylsily-7-norbornyl cation (2.43). The absolute energy of (2.42) is -681.728506 au (-681.738592 au for (2.43)) at the B3LYP/6-31G(d) level. The ZPE computed at this level is 0.267134 au (0.266890 au for (2.43)). The absolute energy at the B3LYP/6-311+G(3df,2pd) level is -681.891230 au (-681.899292 au for (2.43)). This means the cation (2.42) is 22.2 kcal/mol higher in energy than (2.25) at either level. (2.43) is 17.0 kcal/mol higher in energy than (2.25) at our highest level of theory, and 15.7 kcal/mol less stable at B3LYP/6-31G(d). 138 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Figure 2.13 Geometry of 2-exo-trimethylsilyl-1-norbomyl cation (2.42) at the B3LYP/6-31G(d) level In the bottom structure, the hydrogen atoms are omitted for clarity (distances are indicated in A) 139 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 1.551 1.583 Figure 2.14 Geometry of 7-trimethylsilyl-7-norbomyl cation (2.43) at the B3LYP/6-31G(d) level In the bottom structure, the hydrogen atoms are omitted for clarity (distances are indicated in A) 140 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. The barrier for the 2,7-hydride shift in the 7-norbomyl cation has been calculated to be between 13-15 kcal/mol, depending on the computational level (13.5 kcal/mol at the MP4(sdq,fc)/6-31 G**//MP2(full)/6-31 G* level).8 7 The resulting transition state leads to the 2-norpinyl cation as an intermediate, which rearranges instantly to form the more stable 2-norbomyl cation. We were able to locate the transition state (2.44) for the 2,7 hydride shift in the 7-trimethylsilyl-7-norbornyl cation. This transition state is characterized by one imaginary frequency. The normal mode of this frequency corresponds to the correct hydride transfer. The ion (2.44) is 12.7 kcal/mol higher in energy than (2.43) at the B3LYP/6-311+G(3df,2pd)//B3LYP/6-31G(d) level. This transition state is shown in Figure 2.15. The calculations indicate that the kinetic barrier for the 2,7-hydride shift is even slightly decreased compared to its parent analogue, which was not anticipated. Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 1.561 1.555 Figure 2.15 Geometry of the transition state (2.44) at the B3LYP/6-31G(d) level In the bottom structure, most hydrogen atoms are omitted for clarity (distances are indicated in A) 142 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 2.2.3 ISODESMIC REACTIONS To get a quantitative measure of the silyl-effect in the computed systems, the enthalpy change of an isodesmic reaction can be used. In an isodesmic reaction, the number of electron pairs is held constant and formal chemical bond types are conserved.1 1 8 The formal hydride transfer reaction illustrated in Scheme 2.13 was chosen: K R \ c . CT7* c — ci?- c 2.45 2.46 2.1 2.47 Scheme 2.13 Isodesmic Reaction to compute the silyl effect Comparison of the reaction enthalpy for the various trimethylsilyl- substituted cations (R=TMS) to the 2-norbomyl system (R=H) or methyl- substituted norbomyl systems (R=CH3 ) allows quantification of the silyl effects. We carried out a series of further geometry optimizations and energy calculations to obtain the absolute energies of the molecules necessary to compute the reaction enthalpies. Additionally, the geometries of the neutral species can be compared to the ones of the cations to see the effects of the 143 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. substituents on the system. As an example, the computed structure of 2-exo- trimethylsilyl norbomane is shown in Figure 2.16. The reaction enthalpies for the various substituents are illustrated in Table 2.4. It is not necessary to list the values for all cations discussed earlier, since their relative energies have already been discussed.1 1 9 Table 2.4 Enthalpy changes for the Isodesmic Reactions 2*Norbornyl cation Substituent 6-31 G(d) AH Reaction1 [kcal/mol] 6*311 +G(3df ,2pd)b (2.25) 3-exo-TMS 18.6 17.3 (2.48) 3-exo-Me 0.5 0.8 (2.27) 6-exo-TMS 15.6 14.6 (2.49) 6-exo-Me 1.9 1.9 (2.28) 2-TMS 15.7 14.0 a includes zero point energy (scaled with 0.96) at B3LYP/6-31G(d) b geometries from the B3LYP/6-31G(d) level The results are in agreement with the analysis of the geometries. The (3-silyl substituent stabilizes the positive charge by approximately 17 kcal/mol (compared to hydrogen), whereas a methyl substituent in this position does not add significant stabilization (less than 1 kcal/mol). The inductive effect is much less significant than the vertical stabilization, which is the origin for this strong p-silyl effect. 144 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. It is intriguing, however, that both the a-trimethylsilyl (in (2.28)) and the y-trimethylsilyl substituent (in (2.27)) provide 14-15 kcal/mol stabilization. The a- and y-silyl effects usually significantly differ from each other and are much smaller than the p-silyl effect. It has been noted that the magnitude of the silyl effect depends on the stability of the (parent) carbocation in question. In this system, the 2-norbomyl cation is already stabilized by the delocalization of the positive charge, which leads to its nonclassical structure. The a-silyl substituted cation (2.28) has the nonclassical, bridged structure. In the p-silyl substituted analogue (2.25), however, some of the nonclassical stabilization energy is lost since the cation is essentially unbridged. Apparently, the energy gain by vertical stabilization is much greater than that by delocalization of the positive charge. The latter has been quantified by various techniques and amounts to 10-14 kcal/mol. If this value is added to the enthalpy difference from the isodesmic reaction, the magnitude of the p-silyl effect is around 30 kcal/mol. Comparison with the methyl-substituted analogues shows that inductive effects cannot be the only source of stabilization. This strongly supports the concept of vertical stabilization. 145 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 1.565 Figure 2.16 Geometry of 2-exo-trimethylsilyl norbomane (2.34) at the B3LYP/6-31G(d) level In the bottom structure, the hydrogen atoms are omitted for clarity (distances are indicated in A ) 146 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 2.2.4 SUMMARY An excerpt of the potential energy surface of the trimethylsilyl substituted 2-norbomyl cations is illustrated in Figure 2.17. The stationary points and their corresponding energies are indicated. The 3-exo-trimethylsilyl- 2-norbornyl cation (2.25) is the global minimum. Additionally, (2.25) is also located in a “potential well." Its barriers for interconversion to (2.28) and (2.26) are 18.1 and 20.0 kcal/mol, respectively. It should therefore be possible to observe (2.25) under long-lived stable ion conditions, if proper precursors for the ionization can be synthesized. 147 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. MejSi 2 148 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Figure 2 .17 Relative enthalpy d iag ra m o f t h e m in im u m energy structures a n d t h e transition states fo r their interconversions 2.3 HIGHER-COORDINATED BORON, ALUMINUM AND GALLIUM CATIONS Higher coordinated compounds involving main group elements are of both experimental and theoretical interest.1 2 0 , 1 2 1 A variety of higher coordinated boron, carbon, nitrogen, oxygen and other gold-ligated complexes have been prepared by Schmidbauer and coworkers.1 2 2 '1 2 6 They obtained the crystal structures of these compounds by X-ray crystallography. The “isolobal” anlogues of CH5 + and CH6 2 + have been prepared as the trigonal bipyramidal [(C6 H5 )3 PAu]5 C+ and octahedral [(CeHsbPAukC2 * compounds. The parent five-coordinated CH5 + has also gained great theoretical and practical interest.1 2 7 '1 2 9 Its calculated preferred structure is the Cs symmetrical cation (Figure 2.18), with one three-center two-electron (3c-2e) bond. Ready bond-to-bond (isotopal) proton migration have low barriers and make it a very fluxional molecule.1 3 0 Recently, Oka and coworkers were able to obtain the gas phase infrared spectrum of CH5V3 1 However, the spectrum could not be fully resolved due to the fluctionality of the molecule. Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Figure 2.18 The preferred Cs symmetrical structure of CH5 * An ab initio investigation of SiH2 2 + showed, that there are two minima on the potential energy surface.1 3 2 The D o o h structure, however, is significantly less stable than the C2v symmetrical structure. The structures and energetics of singlet XH2 + (X=B, Al, Ga) have also been investigated at very high theoretical levels.1 3 3 As in the SiH2 2 + case, there are two minima corresponding to the D o c h and the C2 v symmetrical structures for each cation. For BH2 + , the D o o h structure (2.51.1) is the global minimum (Figure 2.19). In the AIH2 + and GaH2 + case however, the C2 v symmetrical structures ((2.52.2) for AIH2 + ) are significantly more stable by 13.1 and 21.5 kcal/mol, respectively (at the CCSD(T)/cc-pVTZ//MP2/6-311 ++G(3df,2pd) level). 150 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. oO-o bh 2 + bh 2 + (2.51.1) (2.51.2) a ih 2 * a ih 2 " (2.52.1) (2.52.2) Figure 2.19 The structures of BH2' and AIH2 ' 2.3.1 STRUCTURES AND ENERGETICS OF XH4 * AND XH6 + (X=B, AL AND GA) CATIONS We extended the previous studies on XH2* (X=B, Al and Ga) cations to the XH4 + and XH6 + analogues. Additionally, we were interested in the effects of different theoretical models on the structures and energetics, specifically whether Density Functional methods would give results similar to other electron correlated methods such as MP2 and CCSD(T). 151 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. We carried out a series of geometry optimizations at the B3LYP/6-311 ++G(3df,2pd) and the MP2/6-311++G(3df,2pd) levels. We were able to obtain the C2V symmetrical structures with one 3c-2e bond and the C2 symmetrical structures with two 3c-2e bonds for the X H / cations in each case (Figure 2.20). The same computations were used for the XH6 + cations and obtained the C2 v and C3 symmetrical structures (2.56)-(2.58) illustrated in Figure 2.21. For the hexacoordinated boronium ion, the C2V symmetrical (2.56.1) was found to be the only stable minimum. Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 152 2.182 (2.299) 1.175(1.172) ' v - 0.824 (0.810) 1.418(1.428) B H / (2.53.1) 0.765 (0.750) 2.018 (2.280) BH4 + (2.53.2) 2.923 (3.039) 1.547(1.540) 0.763 (0.758) 2.116(2.092) A IH / (2.54.1) „ 1.526(1.533) 0.758 (0.752) 2.277 (2.284) 0.763 (0.741) ' 2.920 (3.034) a ih 4 * (2.54.2) < 2.839 (2.977) > - -^ .-0 .7 4 8 (0.741) 2.838 (2.974) G a H / GaH4 + (2.55.1) (2.55.2) Figure 2.20 Geometries from B3LYP/6-311++G(3df,2pd) and MP2/6-311++G(3df,2pd) (values in parentheses) of XH4 * (distances are in A ) 153 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 1.182(1.180) 1.370(1.372) 0.830 (0.819) BH6 - (2.56.1) 1.546(1.541) 0-762 (0.757) 2.101 (2.077) AIH 6 * (2.57.1) (2.57.2) 1.526 (1.534) I- 0.758 (0.752) - 2.257 (2.256) 2.849 (2.964) .______ 2.847 (2.955) 0.748 (0.741) GaH6 + (2.58.1) Figure 2.21 Geometries from B3LYP/6-311++G(3df,2pd) and MP2/6-311 ++G(3df,2pd) (values in parentheses) of XH6* (distances are in A) GaH6 * (2.58.2) 154 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. All structures were characterized as minima by frequency calculations at the same level as the geometry optimizations (Nlmag=0). Zero point vibrational energies were also obtained from the frequency calculations. To compare and calibrate our results, we also earned out geometry optimizations at the CCSD(T)/cc-pVTZ level for (2.53)and (2.54). The obtained geometries are in agreement to the geometries obtained at the other levels. The total energies, scaled zero point vibrational energies (0.96 for B3LYP, 0.93 for MP2) 114*116 and relative energies for the XH4+ and XhV cations are illustrated in Table 2.5. 155 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Reproduced with permission o f th e copyright owner. Further reproduction prohibited without permission. Table 2.5 Energies for the singlet XH4* and XH6* cations Cation Sym B3LYP/6-311 ++G(3df,2pd) MP2/6-311 ++G(3df ,2pd) CCSDT/cc-pVTZ Tot. E [au] ZPE* [kcal/ mol] Rel. Eb [kcal/ mol] Tot. E [au] ZPEC [kcal/ mol] Rel. Ed [kcal/ mol] Tot. E [au] Rel. Ed [kcal / mol] BH4 * (2.53.1) C2V -26.852824 21.3 0.0 -26.742014 21.2 0.0 -26.767170 0.0 BH4 * (2.53.2) C2 -26.724134 14.4 73.8 -26.613439 14.2 73.7 AIH / (2.54.1) C2 v -244.520351 16.0 8.9 -244.023851 16.0 6.6 -244.052881 8.5 AIH4 * (2.54.2) C2 -244.530828 13.6 0.0 -244.030302 13.5 0.0 -244.062416 0.0 GaH4* (2.55.1) C2 v -1926.936811 15.8 22.9 -1925.313991 15.7 19.0 GaH4f (2.55.1) c 2 -1926.969613 13.5 0.0 -1925.340961 13.7 0.0 BH6 * (2.56.1) C2 v -28.070198 33.3 0.0 -27.943668 33.2 0.0 AlHfl* (2.57.1) C2 v -245.713095 25.1 4.6 -245.202312 25.2 1.6 AIH6‘ (2.57.2) C3 -245.713351 20.7 0.0 -245.197693 20.7 0.0 GaH4* (2.58.1) C2 v -1928.125719 24.3 20.3 -1926.487854 24.2 16.5 GaH4 * (2.58.2) C3 -1926.152586 20.8 0.0 -1926.508620 20.8 0.0 a scaled with 0.96 b includes ZPE from B3LYP c scaled with 0.93 d includes ZPE from MP2 u i o > The computations show the same qualitative results at either level of theory, but quantitative results differ. For the XH4 * cations, the C2V symmetrical structure is more stable than the C2 symmetrical structure by approximately 74 kcal/mol at both levels. For the higher-row analogues, however, the stability reverses, similar to the previously reported X fV systems. Localization of lone pair electrons is favored and the C2 symmetrical structures become more stable. For A llV , this energy difference is 8.9 kcal/mol in the DFT and 6 . 6 kcal/mol in the MP2 calculations. The C2 symmetrical GaH4 + (2.55.2) is 22.9 kcal/mol more stable than the C2 V symmetrical (2.55.1) in the DFT calculations (19.0 at MP2). These differences are too large (35% and 21%) to make a definite decision. From the coupled cluster calculations, however, we obtained an energy difference of 8.5 kcal/mol for the AIH4 + cations, which supports the results obtained in the DFT calculations. Similar results are obtained for the higher-coordinated analogues. The C2V symmetrical structure is the only minimum for the hexacoordinated boronium ion, yet two minima were found for the aluminum and gallium analogues. The C3 symmetrical structures are more stable than the ones of C2V symmetry. This difference, however, seems to have decreased in the aluminum case but is essentially unchanged for the gallium cations. Since the geometries indicate that the cations can be interpreted as donor-acceptor complexes of the metal cations and two or three hydrogen 157 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. molecules, we computed the reaction enthalpies for the dissociations into XH(n-2)+ and H2, as well as for the deprotonation reactions (Table 2.6). Table 2.6 Dehydrogenation and deprotonation enthalpies Reaction AH0 [kcal/mol]1 B3LYP/ MP2/ 6-311 ++G(3df, 2pd) 6-311 ++G(3df, 2pd) BH4+ (2.53.1) —» b h3 + H+ 138.4 137.9 BH4 + (2.53.1) —> BH,+ + h2 16.5 14.0 AIH4 + (2.54.2) — > a ih3 + H+ 185.0 180.9 AIH4+ (2.54.2) —» a ih2 + + h2 0.8 0.8 GaH4+ (2.55.2) — ► GaH3 + H+ 202.8 200.2 GaH4+ (2.55.2) — > GaH2 + h2 1.2 0.8 BH6+ (2.56.1) — > b h5 H+ 156.0 159.6 BH6+ (2.56.1) — > BH4+ (2.53.1) h2 17.5 17.3 AIH6+ (2.57.2) -> a ih5 H+ 186.9 182.8 AIH6+ (2.57.2) - > AIH4+ (2.54.2) + h2 0.6 0.5 GaHa+ (2.58.2) — > GaH5 H+ 205.0 200.9 GaH6 + (2.58.2) — > GaH4 + (2.55.2) + h2 0.7 0.8 3 includes zero point vibrational energies (corrected by 0.96 for DFT and 0.93 for MP2) 158 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. The reaction enthalpies show that deprotonation of the cations is strongly disfavored. The lower energy structures corresponding to AIH4\ AIH6+ , GaH4 + and GafV are weak donor-acceptor complexes. The enthalpies for dehydrogenation are less than one kcal/mol. The nature of the interaction between donor and acceptor of the complexes depends on the relative electron transfer ability of the cth- h to the empty p-orbital at X. Therefore, the stability of the bent structures depends on the size as well as the electronegativity of the X. Localization of lone pair electrons thus readily takes place at the heavier atoms (inert pair effect) . 134 159 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 2.4 CONCLUSION Computational methods were used to investigate trimethylsilyl- substituted norbornyl cations. Several structures corresponding to local minima were found on the potential energy hypersurface. The global minimum corresponds to the 3-exo-trimethylsilyl-2-norbornyl cation. This cation does not show the nonclassical structure of the 2 -norbornyl cation, but is stabilized by a strong p-silyl effect. Vertical stabilization of the positive charge by the silicon substituent causes this cation to be more than 17 kcal/mol more stable than the parent 2-norbornyl cation. In addition to that, the transition states interconnecting the different minima were localized and their energetics were obtained and discussed. Since the 3-exo-trimethylsilyl-2-norbornyl cation is located in a ‘potential well,” it is suggested to be a good synthetic target to observe the trimethyl-silyl substituted 2 -norbornyl systems under stable ion conditions. Higher-coordinated singlet XH4 " and XH6 * (X=B, Al and Ga) cations were also investigated with ab initio and Density Functional methods. In the boron case, the C2V symmetrical structures are the most stable structures. In the aluminum and gallium cases, however, the C2 and C3 symmetrical structures become significantly more stable for the XH4 + and XH6* cations, respectively. In addition to that, deprotonation is not energetically favorable for 160 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. all XH4* and XhV cations. The higher-coordinated aluminum and gallium cations, however, can be interpreted as weak donor acceptor complexes between hydrogen and the lower-coordinated analogues. 161 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 2.5 COMPUTATIONAL METHODS Calculations were performed using the Gaussian 94 and 981 3 5 as well as the Spartan 5.x4 1 software packages on IBM RS/6000, IBM RS/6000 SMP and IRIX systems with 2GB RAM. Geometry optimizations were performed with the methyl groups replaced by hydrogens on the silyl substituents until reasonable geometries were obtained. The final geometry optimizations were performed with the trimethylsilyl substituents. Geometry constraints were not imposed on the molecules in the optimization process. In general, low-level calculations at the HF/3-21G were used to obtain starting geometries, which were further optimized at HF/6-31G(d) and finally at B3LYP/6-31G(d). Parallel processing was routinely used to speed up the computations. To localize transition structures, transition state optimizations at the HF/3-21G level were performed, followed by frequency calculations at the same level. The obtained force constants were used in the HF/6-31G(d) optimization via the ‘readfc’ keyword. Similarly, the frequency calculations at the HF/6-31G(d) level provided the force constants for the B3LYP/6-31G(d) optimizations. This time-consuming and costly procedure had to be employed, as all other transition state optimizations failed. Furthermore, replacement of the methyl groups on the silyl substituent by hydrogens did not seem to provide any significant increase in speed. 162 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 2.6 REFERENCES (1) Schrodinger, E. Ann. Phys. 1926, 79, 361. (2) Schiff, L. I. Quantum Mechanics’ , McGraw-Hill: New York, 1968. (3) Levine, I. N. Quantum Chemistry, 4th ed.; Prentice Hall: Englewood Cliffs, 1991. (4) Kemble, E. C. Fundamental Principles of Quantum Mechanics’ , McGraw-Hill: New York, 1965. (5) Pilar, F. L. Elementary Quantum Chemistry, McGraw-Hill: New York, 1968. (6) Hinchliffe, A. Computational Quantum Chemistry, Wiley: New York, 1988. (7) Hehre, W. J; Radom, L.; v. R. Schleyer, P.; Pople, J. A. Ab Initio Molecular Orbital Theory, Wiley: New York, 1986. (8) Forseman, J. B.; Frisch, /E. Exploring Chemistry with Electronic Structure Methods, 2nd Ed.; Gaussian: Pittsburgh, PA, 1996. (9) Pople, J. A. Angew. 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FINAL GEOMETRIES IN CARTESIAN COORDINATES 3-exo-trimethylsilyl-2-norbornyl cation (2.25) B3LYP/6-31G(d) Si -1.7302 0.0265 0.0056 C 1.4375 0.1235 -1.3179 C 1.7491 -1.1055 -0.4299 C 2.6245 0.9847 0.5748 C 1.2370 1.0938 -0.1362 C 0.6959 -1.0416 0.6048 C 2.9787 -0.5182 0.4190 C 0.2765 0.2790 0.7521 C -2.0216 1.7047 -0.7774 C -2.6641 -0.2554 1.6067 C -1.9376 -1.4056 -1.1917 H 2.2804 0.3939 -1.9592 H 2.5859 1.3073 1.6186 H 0.5520 -0.0133 -1.9450 H 3.8737 -0.6813 -0.1887 H 0.4065 -1.8741 1.2434 H 3.3516 1.6185 0.0592 H -0.0465 0.6419 1.7308 H 3.1274 -1.0397 1.3680 H 1.9491 -2.0708 -0.8929 H 0.9171 2.1091 -0.3689 H -1.3297 -1.3163 -2.0969 H -2.9884 -1.4187 -1.5110 H -1.7333 -2.3776 -0.7303 H -1.8312 2.5278 -0.0816 H -3.0786 1.7573 -1.0718 H -1.4215 1.8604 -1.6792 H -2.5730 0.5897 2.2972 H -2.3446 -1.1643 2.1288 H -3.7302 -0.3769 1.3753 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 5-exo-trimethylsilyl-2-norbornyl cation (2.26) B3LYP/6-31G(d) Si 1.6871 0.0097 -0.0223 C -0.1625 0.0607 -0.6389 C -0.9605 -1.2282 -0.4835 C -2.2616 -0.7772 0.7668 C -1.1466 1.0937 -0.0181 C -2.4371 0.9217 -0.8670 C -2.8040 -0.4823 -0.4828 C -1.5910 0.4650 1.3222 C 2.3661 1.7552 -0.2262 C 2.5688 -1.2128 -1.1562 C 1.8097 -0.5691 1.7747 H -1.2467 -1.7662 -1.3921 H -0.6055 -1.9824 0.2255 H -0.0779 0.2811 -1.7114 H -0.7815 0.2461 2.0189 H -0.7788 2.1179 0.0427 H -2.5279 -1.6543 1.3487 H -3.2438 1.5835 -0.5147 H -2.3424 1.0752 1.8407 H -3.4615 -1.1423 -1.0409 H -2.3150 1.0760 -1.9421 H 1.8757 2.4773 0.4370 H 3.4357 1.7723 0.0140 H 2.2605 2.1164 -1.2560 H 2.1745 -2.2323 -1.0639 H 2.4978 -0.9200 -2.2103 H 3.6350 -1.2596 -0.9049 H 2.8647 -0.7462 2.0172 H 1.4456 0.1760 2.4911 H 1.2855 -1.5140 1.9657 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 6-exo-trimethylsilyl-2-norbornyl cation (2.27) B3LYP/6-31G(d) Si 1.6702 -0.0004 -0.0084 C -0.2600 0.0104 -0.5700 C -1.0378 -1.3217 -0.5025 C -2.3374 -0.8642 0.1894 C -0.9992 0.9824 0.5640 C -1.7142 1.2061 -0.6426 C -2.8646 0.2457 -0.7481 C -1.8014 -0.0362 1.3794 C 2.3304 1.7342 -0.3009 C 2.4298 -1.2595 -1.1781 C 1.7813 -0.5309 1.7901 H -1.2091 -1.7465 -1.4954 H -0.5099 -2.0682 0.0986 H -0.0800 0.3953 -1.5836 H -1.1877 -0.6107 2.0763 H -0.3663 1.7391 1.0152 H -3.0513 -1.6503 0.4349 H -3.7597 0.7371 -0.3382 H -2.5933 0.4707 1.9422 H -3.0878 -0.0737 -1.7698 H -1.5202 2.0302 -1.3221 H 2.8413 -0.6176 2.0605 H 1.3268 -1.5113 1.9704 H 1.3341 0.1911 2.4818 H 3.4067 1.7431 -0.0880 H 1.8757 2.4918 0.3472 H 2.2096 2.0557 -1.3418 H 3.5014 -1.3518 -0.9605 H 2.3362 -0.9602 -2.2281 H 1.9897 -2.2561 -1.0654 192 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 2-trimethylsilyl-2-norbornyl cation (2.28) B3LYP/6-31G(d) Si -1.7422 0.0169 0.0281 C 2.3361 -0.3863 -1.2231 C 2.4552 -0.8136 0.2504 C 1.5275 1.3978 0.2838 C 1.0676 0.4667 -1.0405 C 1.0017 -1.2723 0.5337 C 2.6075 0.5436 0.9709 C 0.1728 -0.2463 -0.1743 C -2.1337 -0.0557 1.8652 C -2.4296 -1.4643 -0.9209 C -2.1990 1.6576 -0.7643 H 3.1870 0.1967 -1.5851 H 0.7114 1.7093 0.9427 H 2.1613 -1.2205 -1.9114 H 0.7996 -2.2200 -0.0002 H 3.6029 0.9632 0.7992 H 0.7288 -1.4351 1.5813 H 1.8804 2.3005 -0.2240 H 2.4522 0.4708 2.0504 H 3.2160 -1.5583 0.4852 H 0.6749 1.0876 -1.8424 H -1.7285 2.5138 -0.2677 H -3.2836 1.8032 -0.6904 H -1.9442 1.6939 -1.8295 H -1.6580 0.7548 2.4289 H -1.8364 -1.0089 2.3162 H -3.2163 0.0459 2.0084 H -2.1435 -2.4203 -0.4697 H -2.1253 -1.4700 -1.9730 H -3.5252 -1.4063 -0.8988 193 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 3-endo-trimethylsilyl-2-norbornyl cation (2.32) B3LYP/6-31G(d) Si -1.6570 0.0412 0.0353 C 2.5896 -0.4351 -0.9302 C 2.1687 -0.9191 0.4989 C 1.5251 1.4295 0.1136 C 1.3439 0.4739 -1.1028 C 0.8013 -1.3939 0.1776 C 2.0293 0.4789 1.2341 C 0.2291 -0.5458 -0.7730 C -1.5749 0.4880 1.8552 C -2.7103 -1.4821 -0.2628 C -2.0770 1.4810 -1.0904 H 3.5411 0.1052 -0.9215 H 0.6112 1.9627 0.3845 H 2.6448 -1.2464 -1.6625 H -0.3476 -1.0007 -1.5861 H 3.0238 0.7530 1.5956 H 0.3280 -2.2741 0.6102 H 2.2759 2.1868 -0.1273 H 1.3688 0.4251 2.1021 H 2.7993 -1.6333 1.0283 H 1.2279 0.9741 -2.0645 H -1.2446 -0.3468 2.4827 H -2.5942 0.7431 2.1755 H -0.9460 1.3570 2.0677 H -1.3811 2.3196 -0.9920 H -3.0749 1.8491 -0.8168 H -2.1134 1.1816 -2.1431 H -2.3630 -2.3596 0.2942 H -2.7739 -1.7508 -1.3230 H -3.7321 -1.2747 0.0801 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 4-trimethylsilyl-2-norbornyl cation (2.33) B3LYP/6-31G(d) Si 1.6101 0.0012 -0.0000 C -1.0424 0.6742 -1.1965 c -2.4702 0.6649 -0.6970 c -1.0107 -1.4196 0.0005 c -0.3282 -0.0208 -0.0000 c -2.4701 0.6655 0.6966 c -2.5011 -1.0786 0.0003 c -1.0423 0.6751 1.1960 c 2.1701 1.8042 -0.0003 c 2.1965 -0.8862 -1.5583 c 2.1964 -0.8856 1.5587 H -3.0906 -1.3740 0.8733 H -3.3542 0.8318 -1.3056 H -0.7358 1.7242 1.3135 H -0.9154 0.1722 -2.1592 H -0.7481 -2.0035 0.8866 H -0.7359 1.7232 -1.3150 H -3.0906 -1.3746 -0.8724 H -3.3541 0.8328 1.3052 H -0.7481 -2.0042 -0.8852 H -0.9152 0.1739 2.1591 H 1.8308 2.3520 -0.8877 H 1.8305 2.3523 0.8867 H 3.2657 1.8493 -0.0001 H 3.2924 -0.8848 -1.5961 H 1.8781 -1.9349 -1.5910 H 1.8458 -0.3967 -2.4747 H 1.8781 -1.9343 1.5917 H 3.2923 -0.8842 1.5965 H 1.8457 -0.3957 2.4749 195 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Transition State (2.35) B3LYP/6-31G(d) Si 1.6702 0.0083 -0.0322 C -0.1892 0.0696 -0.6552 C -1.0134 -1.1726 -0.3601 C -1.9647 -0.8285 0.8097 C -1.1757 1.1247 -0.0748 C -2.5195 0.8668 -0.8246 C -2.7438 -0.5822 -0.4378 C -1.5149 0.5459 1.3147 C 2.3252 1.7650 -0.2048 C 2.5313 -1.1798 -1.2171 C 1.8291 -0.6223 1.7418 H -1.8207 -1.2120 -1.2952 H -0.6986 -2.2141 -0.4380 H -0.0702 0.2021 -1.7394 H -0.6616 0.4799 1.9899 H -0.8348 2.1587 -0.1081 H -2.2596 -1.6341 1.4749 H -3.3354 1.4584 -0.3904 H -2.3249 1.0789 1.8216 H -3.5638 -1.2227 -0.7592 H -2.5016 1.0424 -1.9039 H 1.8302 2.4650 0.4782 H 3.3958 1.7867 0.0313 H 2.2104 2.1481 -1.2254 H 2.1368 -2.2015 -1.1525 H 2.4511 -0.8539 -2.2607 H 3.5999 -1.2375 -0.9779 H 2.8891 -0.8144 1.9497 H 1.4892 0.1014 2.4906 H 1.2996 -1.5671 1.9139 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Transition State (2.36) B3LYP/6-31G(d) Si 1.7046 0.0302 -0.0315 C -0.1695 0.0695 -0.5681 c -0.9318 -1.2839 -0.5422 c -2.2528 -0.9748 0.2963 c -1.0982 0.9960 0.3252 c -2.2734 1.1741 -0.6050 c -2.9682 -0.0512 -0.6283 c -1.6735 -0.0029 1.3512 c 2.5664 -1.1235 -1.2480 c 2.3571 1.7932 -0.1794 c 1.8712 -0.6088 1.7388 H -1.1425 -1.6872 -1.5368 H -0.4085 -2.0654 0.0181 H -0.1368 0.4641 -1.5935 H -0.9077 -0.4707 1.9700 H -0.6504 1.9156 0.6980 H -2.8021 -1.8515 0.6349 H -3.3744 1.0774 0.0583 H -2.4412 0.4348 2 .0 0 1 1 H -3.7624 -0.2980 -1.3298 H -2.4159 1.9695 -1.3342 H 2.4584 -0.7821 -2.2841 H 2.1866 -2.1503 -1.1906 H 3.6404 -1.1642 -1.0303 H 1.4275 0.0674 2.4791 H 2.9349 -0.6981 1.9908 H 1.4306 -1.6038 1.8752 H 1.8787 2.4845 0.5247 H 2.2255 2.1954 -1.1909 H 3.4318 1.8124 0.0369 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Transition State (2.37) B3LYP/6-31G(d) Si 1.7074 0.0356 -0.0327 C -0.1636 0.0798 -0.5688 C -0.9185 -1.2875 -0.5524 C -2.2294 -0.9888 0.2742 C -1.1071 0.9882 0.3210 C -2.3621 1.2098 -0.5057 C -3.0545 -0.0131 -0.5250 C -1.6632 -0.0271 1.3567 C 2.3586 1.8015 -0.1577 C 2.5729 -1.1012 -1.2631 C 1.8788 -0.6270 1.7285 H -1.1299 -1.6875 -1.5490 H -0.3745 -2.0636 -0.0064 H -0.1273 0.4884 -1.5892 H -0.8903 -0.4870 1.9735 H -0.6615 1.9110 0.6907 H -2.7761 -1.8767 0.5910 H -2.7133 2.1508 -0.9277 H -2.4366 0.3973 2.0055 H -4.0083 -0.1998 -1.0162 H -2.3219 0.4653 -1.5589 H 1.8753 2.4837 0.5519 H 3.4323 1.8213 0.0636 H 2.2302 2.2147 -1.1652 H 2.1951 -2.1294 -1.2197 H 2.4665 -0.7469 -2.2951 H 3.6466 -1.1433 -1.0444 H 2.9433 -0.7202 1.9759 H 1.4375 0.0388 2.4796 H 1.4380 -1.6236 1.8525 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Transition State (2.38) B3LYP/6-31G(d) Si -1.7338 -0.0089 0.0122 C 2.3073 -0.3822 -1.2291 C 2.5034 -0.7548 0.2542 C 1.3916 1.2923 0.2861 C 1.1073 0.5473 -1.0095 C 1.0795 -1.2324 0.6301 C 2.6211 0.6418 0.9097 C 0.2286 -0.0893 0.0531 C -2.3368 -0.4521 1.7351 C -2.1894 -1.2941 -1.2821 C -2.2020 1.7416 -0.4903 H 3.1624 0.1431 -1.6640 H 0.4189 0.8580 0.9783 H 2.0604 -1.2371 -1.8652 H 0.8134 -2.1509 0.0937 H 3.5161 1.1741 0.5692 H 0.9137 -1.4014 1.6980 H 1.1110 2.3424 0.3634 H 2.6118 0.6413 2.0031 H 3.3083 -1.4513 0.4870 H 0.6439 1.0915 -1.8264 H -3.2946 1.8128 -0.5564 H -1.8063 2.0248 -1.4722 H -1.8836 2.4939 0.2412 H -3.4332 -0.4671 1.7510 H -2.0162 0.2728 2.4928 H -1.9972 -1.4457 2.0486 H -3.2805 -1.3162 -1.3945 H -1.8742 -2.3038 -0.9969 H -1.7655 -1.0655 -2.2660 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Transition State (2.39) B3LYP/6-31G(d) Si 1.8241 0.0276 -0.0310 C -2.0851 -0.2600 1.3415 C -2.3480 -1.0333 0.0209 C -2.0483 1.3473 -0.4552 C -1.1298 0.7640 0.6728 C -0.9146 -1.2796 -0.4005 C -2.8977 0.1160 -0.8944 C -0.1223 -0.1871 0.0094 C 2.1629 1.7281 -0.7537 C 2.5087 -1.3682 -1.0868 C 2.2990 -0.1103 1.7839 H -2.9855 0.1963 1.7609 H -1.4745 1.7975 -1.2710 H -1.6013 -0.8691 2.1121 H -3.9584 0.2614 -0.6762 H -0.5365 -2.1808 -0.8830 H -2.6752 2.1353 -0.0310 H -0.4659 -0.3744 -1.2461 H -2.8145 -0.1194 -1.9594 H -2.9671 -1.9297 0.0523 H -0.6663 1.5196 1.3071 H 3.6028 -1.2955 -1.1151 H 2.1647 -1.3226 -2.1271 H 2.2680 -2.3590 -0.6845 H 3.2408 1.9283 -0.7255 H 1.6713 2.5274 -0.1881 H 1.8482 1.8055 -1.8006 H 3.3860 0.0080 1.8744 H 2.0402 -1.0859 2.2094 H 1.8362 0.6692 2.3988 200 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 2-exo-trimethylsilyl-1-norbornyl cation (2.42) B3LYP/6-31G(d) Si 1.7564 0.0726 -0.0027 C -1.6389 -0.2573 1.3496 C -2.1997 -1.0473 0.1198 C -2.2576 1.4937 -0.2489 C -1.1581 0.6983 0.2957 C -0.8722 -1.3139 -0.6554 C -3.0312 0.0959 -0.5867 C 2.5852 -0.9113 -1.3735 C 1.9211 -0.7704 1.6726 C 2.3324 1.8622 0.0495 C -0.1484 0.1191 -0.5608 H -2.4035 0.1435 2.0161 H -2.0232 2.0685 -1.1439 H -0.1304 0.6227 -1.5330 H -0.8598 -0.7862 1.8961 H -0.2944 -2.1092 -0.1769 H -4.0281 0.1675 -0.1475 H -1.0211 -1.5728 -1.7066 H -2.8227 2.0810 0.4755 H -3.1081 -0.0365 -1.6672 H -2.7966 -1.9316 0.3526 H 2.9885 -0.8698 1.9071 H 2.1716 2.3747 -0.9058 H 3.4082 1.9009 0.2590 H 1.8298 2.4395 0.8345 H 2.4565 -0.4390 -2.3540 H 2.2113 -1.9392 -1.4386 H 3.6633 -0.9702 -1.1801 H 1.5020 -1.7831 1.6918 H 1.4713 -0.1920 2.4875 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. 7-trimethylsilyl-7-norbornyl cation (2.43) B3LYP/6-31G(d) Si -0.6701 -1.5344 0.0000 C -0.1352 2.5336 0.7815 C 1.9296 1.0377 0.7877 C 0.3904 1.1216 1.1493 C 0.3904 1.1216 -1.1493 C 1.9296 1.0377 -0.7877 C 0.0140 0.2652 0.0000 C -0.1352 -2.4027 -1.5752 C -2.5153 -1.0789 0.0000 C -0.1352 -2.4027 1.5752 C -0.1352 2.5336 -0.7815 H 0.1601 0.7586 -2.1503 H 0.5025 3.3097 1.2130 H 2.3942 0.1363 1.1937 H -1.1424 2.6808 1.1810 H 2.4322 1.9036 -1.2277 H -3.0676 -2.0284 0.0000 H 2.4322 1.9036 1.2277 H 2.3942 0.1363 -1.1937 H -1.1424 2.6808 -1.1810 H 0.1601 0.7586 2.1503 H 0.9473 -2.5680 1.6106 H -0.6124 -3.3891 1.6230 H -0.4314 -1.8553 2.4765 H 0.9473 -2.5680 -1.6106 H -0.4314 -1.8553 -2.4765 H -0.6124 -3.3891 -1.6230 H -2.8192 -0.5212 -0.8912 H -2.8192 -0.5212 0.8912 H 0.5025 3.3097 -1.2130 202 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. Transition State (2.44) B3LYP/6-31G(d) Si -1.6749 0.0588 -0.0341 C 2.2587 1.0936 0.7965 C 1.4140 -1.3745 0.7432 C 1.1866 0.0718 1.2025 C 1.3531 -0.1090 -1.1016 c 2.1564 -1.3494 -0.5982 c 0.2679 -0.1736 0.0339 c 2.1207 1.1766 -0.7500 c -1.8207 1.8773 -0.5000 c -2.3467 -0.3271 1.6770 c -2.3351 -1.0969 -1.3585 H 0.2854 -1.5742 0.2674 H 0.9837 -0.1714 -2.1254 H 3.2542 0.7739 1.1174 H 3.0838 1.2160 -1.2665 H 2.0600 2.0534 1.2797 H 3.2364 -1.2036 -0.5112 H 1.4023 -2.1691 1.4953 H 1.9689 -2.2499 -1.1878 H 1.5504 2.0636 -1.0459 H 0.7416 0.1557 2.1919 H -1.3650 2.1000 -1.4709 H -2.8850 2.1334 -0.5761 H -1.3796 2.5397 0.2524 H -2.1884 -1.3715 1.9705 H -1.9189 0.3181 2.4523 H -3.4307 -0.1594 1.6825 H -1.8708 -0.9192 -2.3350 H -2.1948 -2.1532 -1.1001 H -3.4135 -0.9395 -1.4810 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. BH4 + (2.53.1) B3LYP/6-311++G(3df,2pd) B 0.0000 0.0000 0.2129 H 0.0000 1.1049 0.6113 H 0.0000 -0.4122 -1.1436 H 0.0000 -1.1049 0.6113 H 0.0000 0.4122 -1.1436 BH4 + (2.53.2) B3LYP/6-311 ++G(3df,2pd) B 0.0000 0.0000 0.6992 H 0.0000 1.5703 -0.5687 H - 0.0000 -1.1097 -1.1792 H 0.0000 1.1097 -1.1792 H 0.0000 -1.5703 -0.5687 AIH4 + (2.54.1) B3LYP/6-311++G(3df,2pd) A l 0.0000 0.2189 0.0000 H 1.5310 0.4384 0.0000 H -1.5309 0.4393 0.0000 H -0.3815 -1.8621 0.0000 H 0.3813 -1.8612 0.0000 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. AIH4 + (2.54.2) B3LYP/6-311++G(3df,2pd) Al 0.0000 0.0000 0.5482 H 0.0000 1.9578 -1.6177 H -0.4478 -1.4567 -1.9455 H 0.4478 1.4567 -1.9455 H 0.0000 -1.9578 -1.6177 GaH4 + (2.55.1) B3LYP/6-311++G(3df,2pd) Ga 0.0000 0.0000 0.1208 H 0.0000 1.5204 0.2511 H 0.0000 -0.3791 -2.1239 H 0.0000 -1.5204 0.2511 H 0.0000 0.3791 -2.1239 GaH4 + (2.55.2) B3LYP/6-311++G(3df,2pd) Ga 0.0000 0.0000 0.2498 H 0.0000 1.9930 -1.7708 H -0.4749 -1.5188 -2.1014 H 0.4749 1.5188 -2.1014 H 0.0000 -1.9930 -1.7708 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. BH6 + (2.56.1) B3LYP/6-311 ++G(3df,2pd) B -0.0000 -0.1954 0.0006 H 0.0000 -0.7728 1.0330 H -0.0000 -0.7852 -1.0234 H -1.0080 0.6357 0.4119 H -1.0083 0.6318 -0.4182 H 1.0080 0.6357 0.4119 H 1.0083 0.6318 -0.4182 AIH6 + (2.57.1) B3LYP/6-311 ++G(3df,2pd) Al -0.2892 -0.0000 0.0000 H -0.5920 0.0000 1.5160 H -0.5921 -0.0001 -1.5160 H 1.2360 1.3933 0.3810 H 1.2360 1.3933 -0.3811 H 1.2362 -1.3931 0.3811 H 1.2361 -1.3932 -0.3811 AIH6 + (2.57.2) B3LYP/6-311++G(3df,2pd) AI -0.6608 0.0039 0.0019 H 1.5897 -1.6979 -0.7296 H 1.2325 -1.7167 -1.3861 H 1.2573 2.0475 -0.8103 H 1.6310 1.4592 -1.0809 H 1.2522 -0.3375 2.1744 H 1.6283 0.1946 1.8078 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. GaH6 + (2.58.1) B3LYP/6-311 ++G(3df,2pd) Ga -0.1696 - 0.0000 0.0000 H -0.3650 - 0.0000 1.5131 H -0.3651 0.0000 -1.5131 H 1.4967 1.4750 0.3790 H 1.4966 1.4751 -0.3789 H 1.4966 -1.4751 0.3789 H 1.4967 -1.4750 -0.3790 G a H 6+ (2.58.2) B3LYP/6-311 ++G(3df,2pd) Ga 0.3146 -0.0004 0.0025 H -1.8084 -1.0491 -1.5814 H -1.4113 -1.6798 -1.5165 H -1.4487 -0.4803 2.1929 H -1.8526 -0.8274 1.6677 H -1.4199 2.1472 -0.7143 H -1.8110 1.9017 -0.1259 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission.

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Creator Salzbrunn, Stefan (author)

Core Title Selective functionalizations of arylboronic acids and studies on cationic intermediates

Degree Doctor of Philosophy

Degree Program Chemistry

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

Tag chemistry, organic,OAI-PMH Harvest

Language English

Contributor Digitized by ProQuest (provenance)

Permanent Link (DOI) https://doi.org/10.25549/usctheses-c16-134510

Unique identifier UC11334521

Identifier 3041516.pdf (filename),usctheses-c16-134510 (legacy record id)

Legacy Identifier 3041516-0.pdf

Dmrecord 134510

Document Type Dissertation

Rights Salzbrunn, Stefan

Type texts

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

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

Repository Name University of Southern California Digital Library

Repository Location USC Digital Library, University of Southern California, University Park Campus, Los Angeles, California 90089, USA