New and efficient approaches to functionalization via metal catalyzed and photo induced transformations

NEW AND EFFICIENT APPROACHES TO FUNCTIONALIZATION VIA METALCATALYZED AND PHOTO-INDUCED TRANSFORMATIONS by VU TRAN NGUYEN, M Eng DISSERTATION Presented to the Graduate Faculty of The University of Texas at San Antonio in Partial Fulfillment of the Requirements for the Degree of DOCTOR OF PHILOSOPHY IN CHEMISTRY COMMITTEE MEMBERS: Oleg V Larionov, Ph.D., Chair Francis K Yoshimoto, Ph.D Hyunsoo Han, Ph.D John C.-G Zhao, Ph.D THE UNIVERSITY OF TEXAS AT SAN ANTONIO College of Science Department of Chemistry December 2020 DEDICATION To my wife and my dear daughter who always believe in me To my parents who provide me with constant inspiration ACKNOWLEDGEMENTS First and foremost, I have to thank my family who has supported me not only through graduate school but through life thus far Their concern and encouragement are what kept me going every moment in my life I owe my deepest gratitude to my wife for her silent sacrifice to my little family I owe my mother, who inspired me and let me know about the beautiful world of chemistry Secondly, I need to thank Dr Oleg V Larionov for his constant encouragement and support to push me to become better Without him motivating me, I would never have the achievement today I learned from him the way of thinking and developing a project I hope that I can continue to grow and advance as I finish my career at UTSA I want to also acknowledge my committee members, Dr Hyunsoo Han, Dr Francis Yoshimoto, and Dr John C.-G Zhao, for all the time and effort you all have made to help me become a well-rounded chemist You all have been key to my professional development by always being ready to question me to help me achieve all the critical milestones of graduate school Thank you for always encouraging me to better I would like to thank the Department of Chemistry at the University of Texas at San Antonio for the constant support and continued dedication to providing opportunities for success There is not one faculty member who I have not interacted with, asked advice, or been evaluated by I would also like to thank all the professors that took part in teaching me during my education at UTSA I would like to thank my lab members for all the years we have spent together Without your support, I know that I also would not have been nearly successful as today Special thanks to Anh Vo, who gave me an opportunity to join the group of Dr Larionov and begun my career here at UTSA All are owed thanks (not limited too or in any specific order): David Stephens, Bhuwan Chhetri, Johant Lakey-Beitia, John Doyle, Jessica Burch, Victoria Soto, Adelphe Mfuh, Shengfei Jin, Xianwei Sui, Graham Haug, Brett Schneider, Oscar Garcia, Carsten Flores-Hansen, Dat Nguyen, Hang Dang, Viet Nguyen, Ngan Vuong, Hoang Pham, Trang Le, Dat Le, Tiffany Nguyen, Tu Ho I want to thank various agencies and foundations for supporting our work at the lab of Dr Larionov: the Max and Minnie Tomerlin Voelcker Fund, the Welch Foundation, the National Institute of General Medical Sciences, and the University of Texas at San Antonio I also want to iv thank Dr Judith Walmsley for her generous donation to my awards at UTSA: Abrams and Walmsley awards These awards helped me focus on science and get some achievements so far “This Master’s Thesis/Recital Document or Doctoral Dissertation was produced in accordance with guidelines which permit the inclusion as part of the Master’s Thesis/Recital Document or Doctoral Dissertation the text of an original paper, or papers, submitted for publication The Master’s Thesis/Recital Document or Doctoral Dissertation must still conform to all other requirements explained in the “Guide for the Preparation of a Master’s Thesis/Recital Document or Doctoral Dissertation at The University of Texas at San Antonio.” It must include a comprehensive abstract, a full introduction and literature review, and a final overall conclusion Additional material (procedural and design data as well as descriptions of equipment) must be provided in sufficient detail to allow a clear and precise judgment to be made of the importance and originality of the research reported It is acceptable for this Master’s Thesis/Recital Document or Doctoral Dissertation to include as chapters authentic copies of papers already published, provided these meet type size, margin, and legibility requirements In such cases, connecting texts, which provide logical bridges between different manuscripts, are mandatory Where the student is not the sole author of a manuscript, the student is required to make an explicit statement in the introductory material to that manuscript describing the student’s contribution to the work and acknowledging the contribution of the other author(s) The approvals of the Supervising Committee which precede all other material in the Master’s Thesis/Recital Document or Doctoral Dissertation attest to the accuracy of this statement.” December 2020 v NEW AND EFFICIENT APPROACHES TO FUNCTIONALIZATION VIA METALCATALYZED AND PHOTO-INDUCED TRANSFORMATIONS Vu Tran Nguyen, Ph.D The University of Texas at San Antonio, 2020 Supervising Professor: Oleg V Larionov, Ph.D Functionalization has emerged as an attractive strategy for the diversification of compounds especially in drug development and materials science The recent emerging trend in chemical functionalization is not only to access challenging and valuable compounds using abundant and inexpensive materials but also to consider environmental aspects of new methodologies New methodologies in the fields of photocatalysis, transition metal catalysis, radical chemistry, and redox chemistry have found applications in functionalization Herein, new and efficient approaches to functionalization of common aryl halides, abundant carboxylic acids, and readily available alkenes via metal-catalyzed or photoinduced transformations will be discussed Specifically, the focus will be on the following transformations: conversion of aryl halides to borylated compounds and corresponding sulfones, as well as conversion of carboxylic acids to amines, alkenes, and other important compounds Alkenes take part in discrete carboborative ring contractions or challenging dienes syntheses In some cases, discussion of the mechanistic investigations and density functional theory calculations will be included to provide insights into the reaction details Some ongoing works with preliminary results in decarboxylation and dienylation will be briefly discussed vi TABLE OF CONTENTS ACKNOWLEDGEMENTS iv ABSTRACT vi TABLE OF CONTENTS vii LIST OF FIGURES xiii CHAPTER I INTRODUCTION CHAPTER II PHOTO-INDUCED RING CONTRACTION INTRODUCTION EXPERIMENTAL DESIGN RESULTS AND DISCUSSIONS 12 MECHANISTIC INVESTIGATION 15 CONCLUSION 21 GENERAL PROCEDURES AND CHARACTERIZATION OF PRODUCTS 21 CHAPTER III SULFOLENE SYNTHESIS AND TRANSITION METAL – CATALYZED DIENYLATION USING SULFOLENE 49 CHAPTER III.1 SULFOLENE SYNTHESIS 50 INTRODUCTION 50 EXPERIMENTAL DESIGN 51 RESULTS AND DISCUSSIONS 53 CONCLUSION 54 GENERAL PROCEDURES AND CHARACTERIZATION OF PRODUCTS 54 vii CHAPTER III.2 PALLADIUM-CATALYZED DIENYLATION 58 INTRODUCTION 58 EXPERIMENTAL DESIGN 60 RESULTS AND DISCUSSIONS 61 CONCLUSION 66 GENERAL PROCEDURES AND CHARACTERIZATION OF PRODUCTS 66 CHAPTER III.3 NICKEL-CATALYZED DIENYLATION 85 INTRODUCTION 85 EXPERIMENTAL DESIGN 85 RESULTS AND DISCUSSIONS 87 CONCLUSION 88 GENERAL PROCEDURES AND CHARACTERIZATION OF PRODUCTS 88 CHAPTER IV ACRIDINE-CATALYZED DECARBOXYLATION AND FUNCTIONALIZATION OF CARBOXYLIC ACIDS 92 CHAPTER IV.1 DECARBOXYLATIVE OLEFINATION 93 INTRODUCTION 93 EXPERIMENTAL DESIGN 96 RESULTS AND DISCUSSIONS 99 CONCLUSION 116 GENERAL PROCEDURES AND CHARACTERIZATION OF PRODUCTS 116 viii CHAPTER IV.2 DECARBOXYLATIVE AMINATION 165 INTRODUCTION 165 EXPERIMENTAL DESIGN 167 RESULTS AND DISCUSSIONS 169 CONCLUSION 178 GENERAL PROCEDURES AND CHARACTERIZATION OF PRODUCTS 178 CHAPTER IV.3 DECARBOXYLATIVE SULFONYLATION 234 INTRODUCTION 234 EXPERIMENTAL DESIGN 234 CHAPTER V FUNCTIONALIZATION OF ARYL HALIDES 236 CHAPTER V.1 BORYLATION OF ARYL HALIDES 237 INTRODUCTION 237 EXPERIMENTAL DESIGN 238 RESULTS AND DISCUSSIONS 239 CONCLUSION 244 GENERAL PROCEDURES AND CHARACTERIZATION OF PRODUCTS 244 CHAPTER V.2 SULFONE SYNTHESIS 257 INTRODUCTION 257 EXPERIMENTAL DESIGN 259 RESULTS AND DISCUSSIONS 260 ix CONCLUSION 268 GENERAL PROCEDURES AND CHARACTERIZATION OF PRODUCTS 268 CHAPTER VI DIMERIZATION OF QUINOLINES 286 INTRODUCTION 287 EXPERIMENTAL DESIGN 287 RESULTS AND DISCUSSIONS 288 CONCLUSION 293 GENERAL PROCEDURES AND CHARACTERIZATION OF PRODUCTS 293 APPENDIX A Copyright Clearance 301 APPENDIX B Copies of 1H and 13CNMR Spectra for Chapter II 307 APPENDIX C Copies of 1H and 13CNMR Spectra for Chapter III 365 APPENDIX D Copies of 1H and 13CNMR Spectra for Chapter IV.1 422 APPENDIX E Copies of 1H and 13CNMR Spectra for Chapter IV.2 533 APPENDIX F Copies of 1H and 13CNMR Spectra for Chapter V.1 666 APPENDIX H Copies of 1H and 13CNMR Spectra for Chapter VI 729 APPENDIX G Copies of 1H and 13CNMR Spectra for Chapter V.2 758 REFERENCES 797 VITA x LIST OF TABLES Chapter II Table II.1.Optimization for photoinduced carboborative ring contraction 10 Table II.2 Photoinduced carboborative ring contraction in the presence of different photosensitizers 11 Table II.3 Scope of the Photoinduced Carboborative Ring Contraction 12 Table II.4 Scope of the Photoinduced Carboborative Ring Contraction of Terpenoids 14 Chapter III Table III.1 Optimization of the 3-sulfolene synthesis from 1,3-dienes 52 Table III.2 Synthesis of 3-sulfolenes from 1,3-dienes 53 Table III.3 Optimization of Reaction Conditions 61 Table III.4 Scope of the Reaction with Sulfolene 62 Table III Scope of the Reaction with Substituted Sulfolenes 64 Table III.6 Optimization tables for Ni-catalyzed dienylation 86 Chapter IV Table IV.1 Reaction conditions for dehydrodecarboxylation 97 Table IV.2 Reaction conditions for cooperative chemoenzymatic LACo process 98 Table 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Guin, J Chem Eur J 2015, 21, 17618–17622 831 (18) Grainger, R.; Nikmal, A.; Cornella, J.; Larrosa, I Org Biomol Chem 2012, 10, 3172– 3174 832 VITA Vu Nguyen was born in Quang Tri Province, Central Vietnam He graduated from Ho Chi Minh University of Technology with a B.E in Chemical Engineering before being a researcher in the Department of Chemical Engineering there He joined the laboratory of Dr Oleg V Larionov as a post-baccalaureate researcher at the University of Texas at San Antonio in summer 2015 after he obtained his M.E in Chemical Engineering from Ho Chi Minh University of Technology In the fall of 2016, he became a doctoral student working in the lab laboratory of Dr Oleg Larionov developing new and efficient methodologies for functionalization In the spring of 2021, he will join the Department of Chemical Engineering, Ho Chi Minh University of Technology as a lecturer ... Document or Doctoral Dissertation attest to the accuracy of this statement.” December 2020 v NEW AND EFFICIENT APPROACHES TO FUNCTIONALIZATION VIA METALCATALYZED AND PHOTO- INDUCED TRANSFORMATIONS. .. the fields of photocatalysis, transition metal catalysis, radical chemistry, and redox chemistry have found applications in functionalization Herein, new and efficient approaches to functionalization. .. abundant carboxylic acids, and readily available alkenes via metal- catalyzed or photoinduced transformations will be discussed Specifically, the focus will be on the following transformations: conversion