Proton-Coupled Electron Transfer: Expanding the Substrate Scope of the Aza-Pinacol Coupling Reaction

Abstract

Multi-site PCET has enabled enantioselective reductive coupling of ketones and hydrazones to form cyclic vicinal amino alcohols. While prior work in the field has demonstrated successful aza-pinacol coupling of aryl ketones, this study aimed to expand the substrate scope to include alkyl ketones and to study the oxidative quenching of the excited Ir\(^{III}\)(ppy)\(_{3}\)* photocatalyst. Out of the five substrates tested, only one demonstrated cyclization. The results of this study suggested that the mechanism of PCET-driven azapinacol coupling proceeds through a ketyl intermediate and that Ir\(^{III}\)(ppy)\(_{3}\)* quenching requires the use of strong irreversible reducing agents. Future work includes further investigation into the mechanism and screening for Ir\(^{III}\)(ppy)\(_{3}\)* quenching. Approaching these challenges experimentally will help to expand the substrate scope and lead to broader applications of PCET in catalytic organic synthesis.