Phosphorus ligand-coupling reactions for the functionalization of pyridine and other azines
Date
2021
Authors
Nottingham, Kyle G., author
McNally, Andrew, advisor
Paton, Robert, committee member
Henry, Chuck, committee member
Cohen, Robert, committee member
Journal Title
Journal ISSN
Volume Title
Abstract
Pyridines and related azines are ubiquitous in pharmaceuticals, agrochemicals, and materials. The discovery and development of new purpose-built molecules is contingent on our ability to modify these motifs. Described herein are the development of methods that selectively functionalize pyridine and diazine scaffolds through phosphorus ligand-coupling. Novel phosphine reagents were designed and leveraged to construct C–C, C–O, and C–N bonds on azines from their C–H precursors. Chapter one introduces the history of phosphorus ligand-coupling and defines the reactivity explored throughout this thesis. Both seminal and contemporary examples of phosphorus ligand-coupling reactions are also discussed to provide context for this work. Chapter two focuses on a method to incorporate fluoroalkyl groups onto azines and pharmaceuticals using phosphorus ligand-coupling. This method offers a complementary alternative to widely used radical addition approaches which often produce regiomeric product mixtures on azines. Chapter three presents the investigation of a phosphorus-mediated alkenylation reaction on pyridines and quinolines. Examination of the reaction of pyridylphosphines with alkyne acceptors uncovered divergent reaction pathways from alkenylphosphonium salts. Mechanistic studies provide an explanation for the origin of selectivity obtained in these reactions. Lastly, chapter four expands upon one of these reaction pathways and describes the development of a method for the direct conversion of pyridines into pyridones and aminopyridines.
Description
Rights Access
Subject
fluoroalkylation
phosphorus
pyridone
ligand-coupling
azines
pyridine