Direct Trifluoromethylation and Chlorodifluoromethylation Enabled by the Reaction of Reformatsky Reagent with YlideFluor.

A general method for the direct trifluoromethylation and chlorodifluoromethylation of Reformatsky reagents derived from various amides or ketones using YlideFluor or YlideFluor-CF2Cl was described. This reaction proceeds under mild conditions and exhibits a broad functional group tolerance. The utility of this protocol was demonstrated through the synthesis of trifluoromethylated derivatives of two pharmaceutical agents, donepezil and ibudilast.