Highly Selective (Deuterated) Defluorinative Hydrogenation of Trifluoroacetamides

Abstract

The (deuterium-labeled) difluoromethyl (-CF₂H) and monofluoromethyl (-CFH₂) groups play an important role in numerous pharmaceuticals and pesticides due to their unique properties. Achieving highly selective (deuterated) hydrodefluorination of inexpensive and readily available trifluoromethyl compounds to synthesize fluorinated methyl moieties remains challenging. Herein, we report a magnesium-mediated boron-reagent activation strategy for the controllable (deuterated) hydrodefluorination of trifluoroacetamide derivatives. This method features mild reaction conditions, operational simplicity, and excellent tolerance to various functional groups.. Moreover, its synthetic utility is demonstrated through a scaled-up reaction (25 g) and subsequent derivatization. Mechanistic studies suggest that the transformation proceeds via a radical process.