Bond Activation by Unconventional Lewis Pairs by Jacob Geri A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy (Chemistry) in the University of Michigan 2018 Doctoral Committee: Associate Professor Nathaniel Szymczak, Chair Professor Richard Laine Professor Melanie Sanford Professor John Wolfe Jacob B. Geri [email protected] ORCID iD: 0000-0002-9215-5610 © Jacob B. Geri 2018 Dedication This thesis is dedicated to my family: inherited, given, and chosen. But most importantly, my mother. ii Acknowledgements Nathaniel Szymczak has been an ideal PhD supervisor. He provides a high degree of freedom to his students, which forces them to take responsibility for the success or failure of fundamental project hypotheses from their first days in the lab. With Nate as a guide, I learned essential scientific skills: how to formulate testable hypotheses, how to recognize and escape from intractable approaches to chemical problems, and how to design robust experiments which provide definitive yes/no answers. In other words, Nate taught me a language in which one can ask Nature questions and get answers back. He also made me a better scientific communicator, and I tried to follow his example when mentoring undergraduate and graduate students later in my graduate career. He put an extraordinary amount of effort into my training; I estimate that he has spent between five and seven hundred hours teaching me how to be a good scientist. He always supported my work, always believed in my projects and dreams, never gave me an order, and never told me “no”. His integrity, intelligence, sensitivity, and idealism will inspire me for the rest of my life. I appreciate the helpful advice and suggestions of PhD committee members Richard Laine, John Wolf, and Melanie Sanford. I am especially thankful to Melanie Sanford, who gave me very insightful professional advice and excellent training while I worked in her lab during a first-year lab rotation. I also need to thank Vincent Pecoraro, who gave me my first lab experiences in graduate school while I was an entirely inexperienced synthetic chemist, and Nicolai Lehnert, who was very patient with my questions in his Advanced Inorganic Spectroscopy course. Corinna Schindler also provided essential experimental assistance. Much of my PhD work would not have been possible without the tireless work of Jeff Kampf, who provided crystal data for numerous difficult and unstable molecules. I would also like to thank Paul Lennon, James Windak, Eugenio Alvarado, and Chris Kojiro, who provided instrumental support and training, and Gunther Kellner for his help with equipment. The members of the Szymczak Lab have been wonderful comrades and friends. I am grateful for their patience with my idiosyncrasies and excesses over the last five years; without iii their support, scientific conversations, and frequent rebuttals to my crazier ideas I think I would still be deep in the scientific wilderness. Eric Dahl was an especially helpful; we worked well together and helped each other reach many crucial realizations and invent new research directions. Grayson Ritch has been a close personal friend, and has never hesitated to call me out on my excesses. Lily Hale’s piercing intelligence, indefatigable work ethic, idealism, and illuminating scientific conversations have always inspired me to be better and never accept failure. James Shanahan has been a close collaborator and friend, and his careful work and depth of vision have provided much needed perspective at crucial junctures. The five of us have been close, and I look forward to seeing what new directions our lives will take. In my early years in the lab, I was still quite inexperienced in the lab and benefited greatly from the mentorship of Dr. Cameron Moore at an important and precarious time. Oscar Tutusaus and Laura Essex also provided important support and validation at this time. Tyler Carter, another early Szymczak lab member, unknowingly enabled most of my later work by leaving behind a very consequential vial full of extra hexamethylborazine when he graduated. I had the pleasure of working with three very talented undergraduate students: Justin Wang, Tyler Lopez, and Joanna Ciatti. Tyler and Joanna were amazingly hard-working members of the lab, and impressed me with their drive and ambition. I am especially happy that I was able to see Joanna develop into an independent scientist over the course of her long tenure in the Szymczak lab, transitioning from working on an established project to leading a new effort, and am excited to see how her bright future unfolds. I have enjoyed watching Michael Wade Wolfe’s synthetic skills, knowledge, and scientific thinking develop over the past two years while pursuing independent work relating to our borazine fluoroalkylation reagents. I am especially happy that unfinished aspects of my project can continue in the hands of such an excellent colleague. Lastly, I need to thank all of my wonderful friends and family members for their love and support. Matthew Wolfe, Isaac Roles, Martin Hurtado, Claire Radigan, Julian Hurtado, Philip and Vicki Kiser, Jefferson Clayton, Raymond Rivera, Justin Straughan, Robert Campana, Alonso Arguelles, Aaron Proctor, Michael Robo, Michael Carnegie, Roland Philbin, Ethan Preston, Ryan Pool, and Noah Allington are wonderful friends who gave me perspective on life beyond the laboratory. I thank my family, but especially Lisa Geri, Barry Stipe, Carol Cushing, and Monica Stipe. Most importantly, I need to thank Jihkai Yeh for all of the love, energy, and happiness he has given me in our time together. iv Table of Contents Dedication ii Acknowledgements iii List of Figures viii Abstract xii Chapter 1. Introduction 1 1.1 The Frustrated Lewis Pair (FLP) Concept 1 1.2 Intermolecular Transition-Metal Based FLPs 3 1.3 Intramolecular Transition-Metal Based FLPs 5 1.4 FLPs Using Reduced Transition Metals as Lewis Bases 9 1.5 Organic electronically frustrated Lewis pairs 12 Chapter 2. A Proton-Switchable Nitrile Hydroboration Catalyst 15 2.1 Abstract 15 2.2 Introduction 15 2.3 Synthesis, Characterization, and Structural Features of Designed Complexes 17 2.4 E-H Heterolysis: Reactions and Kinetics 19 2.5 Catalytic Hydroboration of Polar Bonds 21 2.6 Mechanistic Analysis 23 2.7 Conclusions 26 2.8 Experimental Details 27 Chapter 3. Charge Effects Regulate Reversible CO 2 Reduction Catalysis 40 3.1 Abstract 40 3.2 Introduction 40 3.3 Reaction Optimization 41 3.4 Effect of Ligand Design Parameters on Catalytic Activity 42 3.5 Preliminary Mechanistic Analysis 44 v 3.6 Conclusions 46 3.7 Experimental Details 46 Chapter 4. Testing the Push-Pull Hypothesis: Lewis-Acid Augmented N 2 Activation 53 4.1 Abstract 53 4.2 Introduction 53 4.3 Preparation and Characterization of Fe-N2-LA Adducts 55 4.4 Computational Analysis of Fe-N2-LA Adducts 56 4.5 Electrochemical Characterization of Fe-N2-LA Adducts 58 4.6 Selective -N Protonation of N 2 59 4.7 Synthesis of Push-Pull Bimetallic N 2 Complexes 60 4.8 Conclusions 61 4.9 Experimental Details 61 Chapter 5. Recyclable Trifluoromethylation Reagents from Fluoroform 73 5.1 Abstract 73 5.2 Introduction 73 5.3 Computational Selection of Lewis Acids for Experimental Investigation 75 5.4 Experimental Screening of Lewis Acids 75 - 5.5 Synthesis and Characterization of Borazine-CF 3 Adducts 76 - 5.6 Preliminary Investigation of CF 3 Transfer to Organic Electrophiles 78 - + 5.7 Synthesis of Existing CF 3 , CF 3•, and CF 3 Reagents 79 5.8 Conclusions 80 5.9 Experimental Details 81 Chapter 6. Room-Temperature, Rapid, and Broad Scope Trifluoromethylation of Organic and - Inorganic Electrophiles with Borazine-CF 3 Adducts 93 6.1 Abstract 93 6.2 Introduction 93 6.3 Trifluoromethylation of Transition Metal Electrophiles 94 6.4 Trifluoromethylation of Main Group Inorganic Electrophiles 95 6.5 Comparison with Previously Reported Reagents 96 6.6 Raid Synthesis of Togni I from HCF 3 and its In-Situ Use 96 - 6.7 Addition of CF 3 to Carbonyl and Imine-Containing Compounds 97 vi - 6.8 Nucleophilic Aromatic Substitution and Heteroaromatic Addition with CF 3 97 6.9 Selective C-H Trifluoromethylation Reactions with Unsubstituted Quinolines 97 6.10 Conclusions 99 6.11 Experimental Details 99 Chapter 7. The Difluoromethyl Group as a Masked Nucleophile 122 7.1 Abstract 122 7.2 Introduction 122 - 7.3 Deprotonation of PhCF 2H and Capture of PhCF 2 Anion 126 7.4 Difluorobenzylation of Organic Electrophiles 127 7.5 K(iPr) 2 as a Base for PhCF 2H Deprotonation 128 - 7.6 Broad-Scope Preparation of Nucleophilic ArCF 2 Reagents 129 7.7 Conclusions 131 7.8 Difluoromethyl anion transfer reagents generated from difluoromethane 132 7.9 Experimental Details 135 Chapter 8. Summary and Future Outlook 148 8.1 Summary 148 8.2 Future Outlook 150 Bibliography 153 vii List of Figures Figure 1-1 Polar bond heterolysis ................................................................................................... 2 Figure 1-2 The FLP concept ........................................................................................................... 2 Figure 1-3 Example systems used in Chapters 2-7 ......................................................................... 3 Figure 1-4 Intermolecular transition metal-based FLPs ................................................................. 4 Figure 1-5 Intramolecular transition-metal based FLPs with primary coordination-sphere bound bases ...............................................................................................................................................