Difluorocarbene-Mediated Direct Primary Amidation of Carboxylic Acids Using Bromodifluoroacetamide as a Bifunctional Reagent.

We report a difluorocarbene-mediated direct primary amidation of carboxylic acids using bromodifluoroacetamide as a dual-function reagent that supplies both activation and ammonia. This catalyst-free, air-compatible protocol converts aromatic, heterocyclic, unsaturated, and aliphatic acids into primary amides and enables late-stage drug modification, cascade cyclization to isoindolinones, and one-pot nitrile formation. Mechanistic studies confirm a deoxygenative pathway.