REACTION DEVELOPMENT AND MECHANISTIC ANALYSIS IN NICKEL/PHOTOREDOX CATALYSIS

Abstract

Transition metal-catalyzed cross-coupling has had a significant impact onpharmaceutical, agrochemical, and materials science research. This broad class of synthetic reactions has dramatically streamlined the synthesis of molecules at the center of research in these areas and others. The development of cross-coupling reactions for such applications continues to occupy a central role in the synthetic organic chemistry community. The advent of photoredox catalysis and its merger with transition metal catalysis has further elevated this broader reaction platform by expanding the scope of accessible bond-forming and bond-breaking events. These advances in cross-coupling technology have seen widespread adoption in academic and industrial settings, but we are just beginning to understand how these processes function on a mechanistic level. This thesis describes the discovery of new reactivity within the broader context of nickel/photoredox dual-catalysis as well as studies into the mechanisms underlying multiple cross-coupling reactions within this regime. Chapter 2 details the discovery of a stereoselective approach to alkyne radical addition using carboxylic acids to effect an overall alkyne hydroalkylation process. In chapter 3, a nickel C–O reductive elimination process is studied in detail using transient absorption spectroscopy and stoichiometric organometallic experiments. Chapter 4 covers the use of multiple spectroscopic, kinetic, and organometallic studies to uncover the mechanism of a Ni/photoredox aryl amination reaction. Finally, the use of pulse radiolysis and spectroelectrochemistry to generate and study short-lived Ni(I) intermediates relevant to Ni/photoredox cross-coupling is disclosed in chapter 5.