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

Abstract

Synthetic methods for the direct transformation of ArCF 3 to ArCF 2 R 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 ArCF 3 to ArCF 2 H through a highly selective activation of a single C-F bond. Mechanistic studies reveal separate reaction pathways for the formation of ArCF 2 H and ArCH 3 products and point to the formation of an unexpected intermediate as the source of the unusual selectivity for the mono-reduction.