Catalytic activation of a single C–F bond in trifluoromethyl arenes

Abstract

Synthetic methods for the direct transformation of ArCF₃ to ArCF₂R would enable efficient diversification of trifluoromethyl arenes and would be of great utility in medicinal chemistry. Unfortunately, the development of such methods has been hampered by the fundamental properties of C–F bonds, which are exceptionally strong and become stronger with increased fluorination of the carbon atom. Here, we describe a method for the catalytic reduction of ArCF₃ to ArCF₂H through a highly selective activation of a single C–F bond. Mechanistic studies reveal separate reaction pathways for the formation of ArCF₂H and ArCH₃ products and point to the formation of an unexpected intermediate as the source of the unusual selectivity for the mono-reduction.