Direct and Chemoselective Synthesis of Tertiary Difluoroketones via Weinreb Amide Homologation with a CHF₂-Carbene Equivalent

The homologation of Weinreb amides into difluoromethylketones with a formal nucleophilic CHF₂ transfer agent is reported. Activating TMSCHF₂ with potassium tert-amylate enables a convenient access to the difluorinated homologation reagent, which adds to the acylating partners. The high chemoselectivity showcased in the presence of variously multifunctionalized Weinreb amides, jointly with uniformly high yields, enables the strategy of general applicability without requiring any stabilization element for the putative carbanion.