Difluoromethylation of Aryl Halides via Palladium-Catalyzed Redox-Neutral Deacylation

A novel difluoromethylating reagent was developed via the dehydration condensation between 1,1-difluoroacetone and N'-methylpicolinohydrazonamide (MPHA). This reagent is suitable for palladium-catalyzed coupling reactions, offering a broad substrate scope (43 examples) and excellent scalability (gram-scale synthesis), and can be efficiently employed for the modification of drug molecules to enable the facile synthesis of difluoromethylated (hetero)arenes. Mechanistic studies indicate that the successful release of the difluoromethyl radical results from aromatization-driven C-C bond cleavage.