Copper-Catalyzed Hydroamination of <i>gem</i>-Difluoroalkenes Access to Diversified α-Difluoromethyl Amines

Abstract

The difluoromethyl group (CF 2 H) is of great importance in medicinal chemistry. We report herein an efficient method for the synthesis of diversified α-difluoromethyl amines through copper-catalyzed hydroamination of gem -difluoroalkenes, where the C–N bond formed via a α-CF 2 H transition-metal intermediate. This new reaction proceeds through Cu–H insertion to gem -difluoroalkenes and gives valuable alkyl–CF 2 H-containing compounds, which overcome the much more challenged β-F elimination from α-fluoroalkyl organocopper species. The reaction exhibits broad substrate scope with readily available starting materials and commercial catalysis.

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