DIVERSIFYING THE SYNTHETIC TOOLBOX VIA PHOTOREDOX REACTION DEVELOPMENT AND GENERALIZATION

Abstract

The efficient formation of carbon–carbon bonds remains one of the foremost aims of contemporary organic chemistry. Over the past century, the field has seen the rise of transition metal-mediated cross-coupling as a valuable strategy to forge these coveted bonds. Cross-coupling reactions have fundamentally reshaped retrosynthetic logic and established themselves as indispensable tools for the preparation of complex organic molecules. However, notable deficiencies remain for efficiently integrating C(sp3)-fragments in a modular manner, underscoring the urgent requirement for the development of adequate synthetic methods.This dissertation aims to further diversifying the synthetic chemist’s toolbox through metallaphotoredox catalysis, with a focus on enabling efficient formation of C(sp3)-enriched products. This was done through two main approaches: developing new organic methods enabling previously inaccessible disconnections and enhancing existing reactions recalcitrant to traditional generalization approaches. Chapter two introduces a deoxydifluoromethylation reaction, merging benzoxazolium-mediated alcohol activation and copper-mediated bond formation to replace aliphatic alcohols with their difluoromethyl bioisosteres, thereby facilitating the exploration of bioisostere chemical space. Chapter three expounds a novel approach towards the generalization of complex chemical reactions via additive mapping, increasing the utility of the metallaphotoredox decarboxylative arylation while revealing fundamental mechanistic insight into nickel-mediated cross-coupling processes. Chapter four focuses on the expansion of available C(sp2) coupling partners for C(sp2)–C(sp3) bond formation, successfully coupling aryl carboxylic acids with various underexplored C(sp3) coupling partners.