General radical difluoromethylation using difluoroacetic anhydride via photoredox catalysis

Abstract

CF₂H-containing molecules play pivotal roles in diverse fields from medicinal chemistry to materials science. However, the application of existing CF₂H reagents as a source of CF₂H radical is limited by their reactivity and preparation. Herein, we develop a simple and general visible-light-catalyzed radical difluoromethylation reaction of alkenes, dienes, and heteroaromatics using commercially available, easy-to-handle, and low-cost difluoroacetic anhydride as the CF₂H reagent. This scalable protocol enables the convenient synthesis of a range of CF₂H-containing compounds under mild conditions, exhibiting a broad substrate scope and functional group tolerance. Potential applications are further demonstrated by gram-scale synthesis, sunlight experiments, derivatization experiments as well as the synthesis of bioactive molecules.