Exploring the Synthesis and Reactivity of Electrophilic Phosphonium Salts by Meera Mehta A thesis submitted in conformity with the requirements for the degree of Doctor of Philosophy Department of Chemistry University of Toronto © Copyright by Meera Mehta 2017 Exploring the Synthesis and Reactivity of Electrophilic Phosphonium Salts Meera Mehta Doctor of Philosophy Department of Chemistry University of Toronto 2017 Abstract Phosphorus compounds have a rich chemical history as Lewis donor ligands in transition metal and organometallic chemistry. In this chemistry, they have typically played auxiliary roles, permitting critical breakthroughs in catalysis centred at transition metal active sites. Phosphorus based Lewis acids, which can themselves serve as a primary locus of activity, have been studied to a lesser extent. Previously, the Stephan Group reported the preparation and Lewis acidity and + + consequent reactivity of the fluorophosphonium cations [(C6F5)2PhPF] and [(C6F5)3PF] . This reactivity has been attributed to their energetically accessible σ*(P-F) acceptor orbitals. This original system requires strongly electron-withdrawing perfluoroaryl substituents, thus limiting potential structural variations. The present work focuses on maintaining potent Lewis acidity at a fluorophosphonium centre while avoiding perfluoroarenes. In this dissertation, the preparation of several dicationic phosphonium salts is discussed. In addition, the versatility of this synthetic approach is investigated. To this end, phosphenium cations supported with triazole, chiral, and cAAC- carbenes were prepared. These dicationic phosphonium salts exhibit remarkable Lewis acidity in stoichiometric reactions and act as effective Lewis acid catalysts. These systems effect the ii hydrodefluorination of fluoroalkanes, hydrosilylation of olefins, deoxygenation of ketones, and the reduction of phosphine oxides and amides. Attempts to perform the Michaelis-Arbuzov rearrangements and subsequent reductions led to the catalytic generation of PH3, as well as primary and secondary phosphines from air stable phosphoethers and phosphoesters. Finally, the preparation of tricationic and tetracationic phosphonium salts was investigated. Three synthetic strategies were explored, viz. preparation of a phosphenium dication, a 4,5- phosphinoimidazolium cation, as well as two linked carbene stabilized phosphenium cations. Subsequent oxidation of these species led to unexpected results, which are further discussed in Chapter 5. iii Acknowledgments First and foremost, I would like to thank my supervisor, Professor Doug Stephan. Thank you for always having an open door; all of our insightful discussions about chemistry and politics have made me a better scientist. Thank you for giving me the freedom to explore my curiosities and venture into new areas of chemistry. You have made the lab an exciting place to be and have always encouraged a healthy discussion of ideas. I would also like to thank my committee members, Professor Bob Morris and Professor Datong Song, for their guidance and support. Finally, I would like to acknowledge Professor David Emslie and Professor Mike Brook, both of whom gave me the opportunity to work in their respective labs as an undergraduate. Professor Brook introduced me to the life of a researcher and paired me with a very talented graduate student, Dr. Amanda Grande. Professor Emslie taught me Schlenk handling of air sensitive compounds and inspired me to be an inorganic chemist. I got my first X-ray crystal structure while working with him! All the Stephan group members, both past and present, have been instrumental in my training. Their discussions and friendship have fostered a great learning environment. In particular, I would like to thank Dr. Michael Holthausen for acting as a mentor in the lab and for his contribution on the phosphonium dication project, which is central to my dissertation. Thank you to Dr. Manual Pérez, his extensive background in organic chemistry helped me explore new catalytic applications for my system. He has been a source of laughter and calm in my more stressful hours. I would also like to thank Dr. Timothy Johnstone, soon to be Professor Johnstone, for teaching me X-ray crystallography and always making the time to address my many questions. He has been a source of inspiration, reminding me to branch out and learn as many different techniques as I can. My work here would not be possible without the departmental support team. Thanks to Dr. Darcy Burns, Dmitry Pichugian, Jack Sheng, and Dr. Sergiy Nokhrin for your help with my NMR concerns. In addition, thanks to Shanna Pritchard, Dr. Alan Lough, Anna-Liza Villavelez, Rose Balazs, Ken Greaves and John Ford. Last but not least, I would like to thank my family. Thanks to Vivek, Vishal, Mom, and Dad for your support and understanding while I underwent this process. Finally, I would like to acknowledge my iv partner, Matt Rubel, for his thoughtful support, his endurance of chemistry related discussions at home and at parties, as well as for being my voice of reason. v Table of Contents Abstract ii Acknowledgments iv Table of Contents vi List of Tables ix List of Schemes x List of Figures xi List of Symbols and Abbreviations xiv Chapter 1 Introduction 1 1.1 Phosphorus – the Element 1 1.2 History of Lewis Acid / Lewis Base Chemistry 2 1.2.1 Lewis Base Catalysis 3 1.2.2 Lewis Acid Catalysis 5 1.2.2.1 Boron-Based Lewis Acids 5 1.2.2.2 Aluminium-Based Lewis Acids 9 1.2.2.3 Carbon-Based Lewis Acids 10 1.2.2.4 Silicon-Based Lewis Acids 11 1.2.2.5 Phosphorus-Based Lewis Acids 13 1.2.3 Frustrated Lewis Pair Chemistry and Small Molecule Activation 16 1.3 Dative Bonding in Main Group Compounds 18 1.4 Scope of Thesis 20 1.5 References 23 Chapter 2 Preparation of Lewis Acidic Phosphorus Cations 36 2.1 Introduction 36 2.1.1 Phosphenium Cations 36 vi 2.2 Results and Discussion 37 2.2.1 Synthesis of Phosphonium Dication 37 2.2.2 Lewis Acidity and Fluorophilicity Tests 42 2.2.3 Catalytic Hydrodefluorination 47 2.2.4 Exploring Phosphonium Cation Derivatives 49 2.3 Conclusion 63 2.4 Experimental Details 65 2.5 References 99 Chapter 3 Hydrosilylation of Olefins, Carbonyls & Amides 103 3.1 Introduction 103 3.1.1 History of Catalytic Hydrosilylation 103 3.2 Results and Discussion 104 3.2.1 Hydrosilylation of Olefins 104 3.2.2 Deoxygenation of Ketones 106 3.2.3 Reduction of Amides 115 3.3 Conclusion 121 3.4 Experimental Details 123 3.5 References 152 Chapter 4 Reduction of Phosphine Oxides and Reactivity with Phosphoethers 157 4.1 Introduction 157 4.1.1 Synthesis of Phosphines 157 4.2 Results and Discussion 158 4.2.1 Catalytic Reduction of Phosphine Oxides 158 4.2.2 Reactivity with Phosphoethers 169 4.2.3 Catalytic Generation of PH3, Primary and Secondary Phosphine 173 4.3 Conclusion 176 4.4 Experimental Details 178 4.5 References 195 Chapter 5 Towards Tricationic and Tetracationic Electrophilic Phosphonium Salts 199 vii 5.1 Introduction 199 5.1.1 Polycationic Phosphorus Cations 199 5.2 Results and Discussion 200 5.2.1 Two Carbenes One Phosphorus Centre 200 5.2.2 One Carbene Multiple Phosphorus Centres 202 5.2.3 Two Carbenes Two Phosphorus Centres 211 5.3 Conclusion 213 5.4 Experimental Details 214 5.5 References 222 Chapter 6 Conclusion 224 6.1 Summary of This Work 224 6.1.1 Preparation of Dicationic Phosphonium Salts 224 6.1.2 Lewis Acid Catalysis 224 6.1.3 Towards Polycationic Phosphonium Salts 225 6.2 Future Work 226 6.3 References 227 viii List of Tables Table 2-1 Catalytic Hydrodefluorination of Fluoroalkanes Using Catalyst 2-5 48 Table 3-1 Catalytic Hydrosilylation of Olefins and Alkynes 105 Table 3-2 Deoxygenation / Hydrosilylation of Benzophenone and 2-methylpentan-3-one 108 Table 3-3 Silane Screening for Deoxygenation of Benzophenone using 2-5 109 Table 3-4 Catalytic Deoxygenation of Aryl-substituted Ketones 111 Table 3-5 Catalytic Deoxygenation of Alkyl-substituted Ketones 112 Table 3-6 Reduction of N,N-dimethylbenzamide with Catalyst 2-1, 2-2, 2-5 116 Table 3-7 Amide Reductions Using Catalysts 2-2 and 2-3 118 Table 4-1 Catalytic Reduction of Triphenylphosphine Oxide to Triphenylphosphine 158 Table 4-2 Catalytic Reduction of Phosphine Oxides to Phosphines 163 Table 4-3 Michaelis-Arbuzov Rearrangement Mediated by 2-2 171 Table 4-4 Catalytic Generation of PH3, PhPH2, and Ph2PH 174 ix List of Schemes Scheme 2-1 Preparation of 2-3 38 Scheme 2-2 Preparation of 2-5 39 Scheme 2-3 Reaction of 2-5 with OPEt3 43 Scheme 2-4 Preparation of 2-10 50 Scheme 2-5 Preparation of 2-13 51 Scheme 2-6 Preparation of 2-14 52 Scheme 2-7 Attempted Preparation of 2-16 53 Scheme 2-8 Preparation of 2-17 54 Scheme 2-9 Preparation of 2-19 55 Scheme 2-10 Preparation of 2-20 58 Scheme 2-11 Preparation of 2-21 59 Scheme 2-12 Preparation of 2-24 60 Scheme 2-13 Preparation of 2-26 61 Scheme 2-14 Preparation of 2-29 63 Scheme 4-1 Tandem Michaelis-Arbuzov Rearrangement and Reduction of Methyl Diphenylphosphonite and Ethyl Diphenylphosphonite 172 Scheme 4-2 Synthesis of PH3 Adducts with Lewis Acids 175 Scheme 5-1 Preparation of 5-2 201 Scheme 5-2 Preparation of 5-3 202 Scheme 5-3 Preparation of 5-6 206 Scheme 5-4 Preparation of 5-8 208 Scheme 5-5 Preparation of 5-10 211 x List of Figures Figure 1-1 Lewis Acid/Base Adduct Formation 3 Figure 1-2 General Mechanism for Lewis Base Catalyzed Acylation of Alcohols 4 Figure 1-3 Mechanism for Hydrosilylation of Carbonyls Employing B(C6F5)3 as the Catalyst 6 Figure 1-4 Types of Boron Cations 7 Figure 1-5 Methods for Preparing Borenium Cations 8 Figure 1-6 Aluminium-Based Catalysts 10 Figure 1-7 Methods for Generating Silicon Cations 11 Figure 1-8 Examples of Organic Transformations Facilitated by Silicon Catalysts 13 Figure 1-9 Gabbaï’s Fluoride Ion Senors 14 Figure 1-10 Examples of Phosphonium Salts Tested in Diels-Alder Catalysis 15 Figure 1-11 Catalytic Transfer Hydrogenation of Diazobenzene 16 Figure 1-12 Hydrogenation of Aromatic Bonds 17 Figure 1-13 FLP Reactivity with Carbon Monoxide 18 + Figure 1-14 Bonding Descriptions of [LPPh2] 20 Figure 2-1 POV-ray Depiction of 2-3.