Applications of Proton-Coupled Electron Transfer in Organic Synthesis: Strategies for C(sp3)–H Bond Activation and Improved Reaction Quantum Efficiency

Abstract

Proton-coupled electron transfer, or PCET, is a process described by the transfer of both a proton and an electron. This type of reactivity is established in biology as a fundamental method of accomplishing proton transfer, electron transfer, and radical transfer in proteins. A subclass of PCET reactions, known as concerted, multi-site PCETs, advantageously alters the thermodynamics and kinetics of bond homolysis, enabling the generation of open-shell intermediates under mild conditions. This dissertation describes two distinct applications of concerted, multi-site PCET in organic synthesis to yield highly reactive radical intermediates and to improve the lifetime of these intermediates in photoredox catalysis. In Chapter 2, a method for the homolysis of strong, C(sp3)–H bonds is described in the context of an intermolecular C–H alkylation, catalyzed by a cationic iridium(III) photocatalyst and anionic Brønsted base. In-depth mechanistic studies of the reaction demonstrate that ground state ion-pairing between the photo-oxidant and base enables the concerted activation of the C–H bond via multi-site PCET. In this case, ion-pairing is essential for lowering the kinetic barrier of the concerted activation step. In Chapter 3, redox relays built into the ligand framework of an iridium(III) photocatalyst are described and utilized to improve the quantum yield of a preparative scale photoredox reaction. These ligands are shown to undergo reversible PCET upon excitation of the catalyst, which enables long-lived charge separation and subsequently alters the thermodynamics and kinetics of charge recombination, leading to the observed improvement in reaction efficiency.