Methods for C–C and C–N Bond Formation via Metallaphotoredox Catalysis

Abstract

In the field of synthetic organic chemistry, photocatalysis has emerged as a powerful visible light-driven platform for enabling the synthesis of complex molecular scaffolds. These molecules have a wide variety of important applications, spanning pharmaceuticals, agrochemicals, fragrances, and polymers. Through the merger of photoredox and transition metal catalysis, our group has shown over the last decade that numerous attractive bond disconnections can be accessed via photocatalytic generation of alkyl radicals and activated transition metal catalysts. Moreover, due to the facile nature of visible-light activation and its unique reactivity, metallaphotoredox catalysis has witnessed broad utility in radiochemical and biological applications, among others. Described herein are methods and applications of this metallaphotoredox platform. The second chapter of this thesis details a collaboration with Merck and the University of Pennsylvania for the development of a metallaphotoredox-catalyzed radiolabeling strategy. This unified and general approach allows for the installation of (radio)isotope-bearing methyl groups for applications in PET radioligand discovery. In the third chapter, a dual copper photoredox-catalyzed deoxygenative amination strategy is disclosed, effectively harnessing native and abundant alcohols as diverse alkylating reagents for C(sp3)–N bond formation. Chapter four outlines the ongoing collaboration with Janssen, delineating the late-stage peptide functionalization of alcohol-containing amino acid residues via deoxygenative C–C bond formation. Lastly, following a serendipitous discovery from the study detailed in chapter four, a mild and weakly basic dual nickel photoredox-catalyzed arylation of N-heterocycles was examined and is described in chapter five.