Mild and practical: Trifluoromethylation of (hetero)aromatic aldehyde N,N‐dialkylhydrazones was achieved at room temperature by using Togni's trifluoromethylation reagent under CuCl catalysis (see scheme). This simple reaction is believed to occur by a CF3‐radical‐transfer mechanism and yields useful trifluoromethylated building blocks.

This study describes the development and understanding of a palladium-catalyzed cross-coupling of fluoroacetamides with boronic acids, under base-free conditions, to selectively give valuable α,α-difluoroketone derivatives. Detailed mechanistic studies were conducted to assess the feasibility of each elementary step, that is, C­(acyl)–N bond oxidative addition, followed by base-free transmetallation and reductive elimination. These investigations allowed the structural characterization of palladium­(II)­fluoroacyl intermediates derived from C–N bond oxidative addition of an amide electrophile. They also revealed the high reactivity of these intermediates for transmetallation with boronic acids without exogenous base. The mechanistic studies also provided a platform to design a practical catalytic protocol for the synthesis of a diversity of α,α-difluoroketones, including CF2H–ketones. Finally, the synthetic potential of this fluoroacylation methodology is highlighted in sequential, orthogonal C–Br and C–N bond functionalization of an α-bromo-α,α-difluoroacetamide with a focus on compounds of potential biological relevance.