Electrophilic ‘Umpolung’ Cyclizations of Alkynes in the Synthesis of Polycyclic Aromatic Hydrocarbons by Liam Britt A thesis presented to the University of Waterloo in fulfillment of the thesis requirements for the degree of Master of Science in Chemistry Waterloo, Ontario, Canada, 2021 © Liam Britt 2021 Author’s Declaration I hereby declare that I am the sole author of this thesis. This is a true copy of the thesis, including any required final revisions, as accepted by my examiners. I understand that my thesis may be made electronically available to the public. ii Abstract Polycyclic aromatic hydrocarbons (PAHs), such as acenes and phenacenes, are important structural motifs which have found great utility in the future of electronics as organic semi- conducting materials. Reliable methods of synthesizing PAHs, particularly the phenacene type, are limited; and modern techniques employ expensive transition metal catalysts. A less explored but potentially superior strategy involves utilizing hypervalent iodine methodology, avoiding the need for transition metal catalysts. In recent studies, a reaction was developed that could couple ortho-biphenylstyrenes intramolecularly in the synthesis of phenanthrenes using only a catalytic amount of iodotoluene, and m-CPBA as an oxidant. In this thesis, we investigate the mechanism of the rearrangement observed in this recently uncovered reaction, and further apply what we have learned toward a novel strategy for electrophilic ‘umpolung’ cyclizations of alkynes in the synthesis of fluorinated PAHs. iii Acknowledgements I would first like to extend my deepest gratitude to my supervisor, Dr. Graham Murphy, for all of his guidance and support, as well as patience and understanding throughout my time in Waterloo. His love for chemistry, creative spirit, and willingness to foster that in others has kept the fire burning in my spirit. I would like to thank my committee members, Dr. Mike Chong and Dr. Eric Fillion for their continued guidance and commitment to excellence within the field. I would like to further extend my gratitude to Dr. Mike Chong who helped me find my path toward excellence, with lessons I will continue to learn for the rest of my life. I would also like to thank my fellow colleagues in the Murphy lab, both past and present, from whom I have learned so much through endless discussions of chemistry and all else. In particular, I would like to thank those for the continued support in the writing, reviewing, and editing of my thesis: Avery To, Tristan Chidley, and Islam Jameel. A special thanks to Dr. Zhensheng Zhao for his early work1 and assistance in the lab during my first year on campus. I would also like to acknowledge the important work and assistance provided by Jalil Assoud with my X-ray crystallography samples. Furthermore, I would like to extend my sincere gratitude to Janet Venne for all her assistance at the NMR. Lastly, I want to express my sincerest thanks and gratitude to the entire University of Waterloo and its Department of Chemistry for granting me the opportunity to complete my graduate studies, and for all their support and resources provided to me over the past few years. iv Table of Contents Author’s Declaration ...................................................................................................................... ii Abstract .......................................................................................................................................... iii Acknowledgements ........................................................................................................................ iv List of Figures ............................................................................................................................... vii List of Tables ............................................................................................................................... viii List of Abbreviations ..................................................................................................................... ix List of Schemes ................................................................................................................................x Chapter 1: Introduction ................................................................................................................... 1 1.1 Polycyclic Aromatic Hydrocarbons ................................................................................. 1 1.2 Hypervalent Iodine ........................................................................................................... 2 1.3 Iodonium Salts.................................................................................................................. 7 1.4 Catalytic Synthesis of Phenanthrene using Hypervalent Iodine Reagents ..................... 10 Chapter 2: Mechanistic Studies .................................................................................................... 13 2.1 Background: Vinylene Phenonium Cation ..................................................................... 13 2.2 Mechanistic Studies of the HVI Catalyzed Reaction ..................................................... 16 2.3 Synthesis of Styrenes and Epoxide Control Reactions .................................................. 24 2.4 Synthesis of cis- and trans-β-methyl Styrene Isomers. ................................................. 27 2.5 Vinyl (aryl)iodonium Salts ............................................................................................. 30 2.6 Discussion ...................................................................................................................... 35 2.7 Experimental Procedures for Chapter 2 ......................................................................... 41 2.7.1 Synthesis of 2-(4-methylphenyl)benzaldehyde (46) ............................................... 42 2.7.2 Synthesis of 4'-methyl-2-(prop-1-en-1-yl)-1,1'-biphenyl ....................................... 43 2.7.3 Synthesis of epoxide: 2-methyl-3-(4'-methyl-[1,1'-biphenyl]-2-yl)oxirane ........... 44 2.7.4 Synthesis of 2-ethynyl-4'-methyl-1,1'-biphenyl (49) .............................................. 45 2.7.5 Alternate synthesis of 2-ethynyl-4'-methyl-1,1'-biphenyl (49) ............................... 46 2.7.6 General procedure for phenanthrene synthesis ....................................................... 47 2.7.7 General procedure for control reactions with epoxide ............................................ 48 2.7.8 Synthesis of cis-4'-methyl-2-(prop-1-en-1-yl)-1,1'-biphenyl .................................. 48 2.7.9 Synthesis of trans-4'-methyl-2-(prop-1-en-1-yl)-1,1'-biphenyl .............................. 50 2.7.10 Synthesis of 2-bromo-4'-methyl-1,1'-biphenyl ....................................................... 50 2.7.11 Synthesis of (Z)-4,4,5,5-tetramethyl-2-(2-(4'-methyl-[1,1'-biphenyl]-2-yl)prop-1- en-1-yl)-1,3,2-dioxaborolane (Z-53) ...................................................................................... 51 2.7.12 Synthesis of (E)-4,4,5,5-tetramethyl-2-(2-(4'-methyl-[1,1'-biphenyl]-2-yl)prop-1- en-1-yl)-1,3,2-dioxaborolane ................................................................................................. 52 2.7.13 General procedure for preparation and reaction of E- and Z- iodonium salts ........ 53 2..14 Synthesis of (E)-(2-(4’-methyl-[1,1'-biphenyl]-2-yl)vinyl-1-D)(p-tolyl)iodonium tetrafluoroborate (E-33) ......................................................................................................... 54 Chapter 3: Umpolung Electrophilic Cyclizations ......................................................................... 57 3.1 Background: Phenacenes................................................................................................ 57 3.2 Fluorovinyl (aryl)iodonium salts .................................................................................... 60 3.3 Results ............................................................................................................................ 64 3.4 Discussion ...................................................................................................................... 75 3.5 Future directions ............................................................................................................. 81 3.6 Experimental Procedures for Chapter 3 ......................................................................... 86 3.6.1 Synthesis of (2-bromophenyl)ethynyl) trimethylsilane .......................................... 86 3.6.2 Synthesis of (4'-methyl-[1,1'-biphenyl]-2-yl)ethynyl) trimethylsilane ................... 87 3.6.3 Synthesis of alkynyl trifluoroborate (88) ................................................................ 88 3.6.4 General procedure for synthesis of (Z)-(2-fluoro-2-(4'-methyl-[1,1'-biphenyl]-2- yl)vinyl)-(p-tolyl) iodonium tetrafluoroborate (Z-90) from alkynyl trifluoroborate (88) ..... 89 3.6.5 General procedure for conversion of vinyl iodonium salt to phenanthrene (91a).. 90 3.6.6 Synthesis of (4'-methyl-[1,1'-biphenyl]-2-yl)ethynyl)(p-tolyl)iodonium tetrafluoroborate (89) ............................................................................................................. 91 References ..................................................................................................................................... 93 Appendix I – X Ray Crystal Structures .......................................................................................