Intercepting Photochemically Generated Aminoalkyl and Aryl Radical Intermediates to Access Complexity Quickly Open Access
Pratt, Cameron (Summer 2021)
Abstract
By using radicals generated by photoredox catalysts, three carbon to carbon bond forming reactions have been developed. These methods are robust and operate under mild conditions. The first method showcases a simple and scalable approach to synthesizing a large range of unnatural amino acids which could modulate cell permeability and in vivo stability. A key discovery in this process was the significant effect amine loading had on restricting product formation to the desired mono-functionalized products. This method was also shown to work in increasingly complex amines including on the active ingredient of cough medicine: dextromethorphan. Using a similar redox neutral mechanistic pathway, the second method showcases a unique way to install cyclobutanes on a carbon alpha to the nitrogen in tertiary anilines. These cyclobutanes, which are often difficult to install, can act as phenyl ring isosteres. In this case, a breakthrough was made with the electrophilic strain- releasing coupling partner. It was found that electron poor rings in the phenyl sulfone led to the desired reactivity. The final chapter highlights how spirocyclic compounds can be formed via a radical hydroarylation pathway that is a metal-free alternative to existing radical methods. Access to these types of scaffolds is already valuable thanks to their presence in a wide selection of biologically relevant molecules. Overcoming the need for a metal photoredox catalyst was achieved by using a cyanoarene catalyst.
Table of Contents
Light: A Historic Reagent 1
Light and Life 2
Brief History of Photochemistry 3
Introduction to Photoredox Catalysis 5
Photoredox Catalysis for Synthesis 8
Chapter One References 9
Synthesis of Unnatural Amino Acids and Peptides using Aminoalkyl Radicals 11
Introduction 12
Results and Discussion 14
Conclusion 21
Supporting Information 21
Chapter Two References 74
Radical α (alpha) C‒H Cyclobutylation of Aniline Derivatives 77
Introduction 78
Results and Discussion 79
Conclusion 83
Supporting Information 84
Chapter Three References 104
Synthesis of Spirocyclic Piperidines by Radical Hydroarylation 107
Introduction 108
Results and Discussion 111
Conclusion 114
Supporting Information 114
Chapter Three References 135
About this Dissertation
| School | |
|---|---|
| Department | |
| Degree | |
| Submission | |
| Language |
|
| Research Field | |
| Keyword | |
| Committee Chair / Thesis Advisor | |
| Committee Members |
Primary PDF
| Thumbnail | Title | Date Uploaded | Actions |
|---|---|---|---|
|
|
Intercepting Photochemically Generated Aminoalkyl and Aryl Radical Intermediates to Access Complexity Quickly () | 2021-06-24 17:47:44 -0400 |
|
Supplemental Files
| Thumbnail | Title | Date Uploaded | Actions |
|---|