Copper-Catalyzed Hydroamination of gem-Difluoroalkenes Access to Diversified α-Difluoromethyl Amines

Abstract

The difluoromethyl group (CF2H) 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-CF2H transition-metal intermediate. This new reaction proceeds through Cu-H insertion to gem-difluoroalkenes and gives valuable alkyl-CF2H-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.