Silyl-mediated photoredox-catalyzed Giese reaction: addition of non-activated alkyl bromides

Chem Sci. 2018 Jul 11;9(32):6639-6646. doi: 10.1039/c8sc02253d. eCollection 2018 Aug 28.

Abstract

The emergence of photoredox catalysis has enabled the discovery of mild and efficient conditions for the generation of a variety of radical reaction platforms. Herein is disclosed the development of a conjugate addition reaction of non-activated alkyl bromides to Michael acceptors under visible-light photoredox catalysis. Optimization of the reaction was achieved using high-throughput experimentation (HTE) tools to enable the identification of mild, general and practical reaction conditions. A diverse set of alkyl bromides was successfully added to cyclic or acyclic α,β-unsaturated esters and amides. The features of this transformation allowed also access to a key intermediate of Vorinostat®, an HDAC inhibitor used to fight cancer and HIV.