Organophotoredox-Driven Three-Component Synthesis of β-Trifluoromethyl β-Amino Ketones†

Abstract

In this work, we present a photoredox three-component reaction that enables the synthesis of medicinally relevant β-trifluoromethyl β-amino ketones from a N-trifluoroethylhydroxylamine derivative, styrenes and DMSO. Remarkably, fluoromethyl, difluoromethyl and pentafluoroethyl analogues are also accessed using the same reaction conditions. The mechanistic investigations, including radical trapping experiments, cyclic voltammetry, Stern-Volmer quenching studies and isotope labelling experiments support the photoinduced radical/polar crossover and Kornblum-type oxidation mechanisms. Finally, the applicability of the accessed organic skeletons is showcased by notable derivatization reactions.