Synergistic Organophotoredox and Copper Catalysis Enabling the Difluoromethylation of Alkyl Bromides

Abstract

The difluoromethyl (-CF 2 H) group enhances metabolic stability and druglike properties, yet existing alkyl difluoromethylation methods often suffer from harsh conditions or complex reagents. We report a mild, late-stage dehalogenative difluoromethylation of unactivated alkyl bromides via photoredox and copper dual catalysis. This operationally simple protocol uses commercially available, non-ozone-depleting reagents and proceeds through silyl-mediated halogen abstraction and copper-mediated radical capture, enabling efficient C(sp 3 )–CF 2 H bond formation with a broad scope and reduced reaction times.

Topics & Concepts