Nucleophilic trifluoromethoxylation of alkyl halides without silver

The biological properties of molecules containing the trifluoromethoxy group have made these compounds important targets in pharmaceuticals and agrochemicals, yet their preparation is still a substantial challenge. Herein, we present a practical nucleophilic trifluoromethoxylation of alkyl halides with (E)-O-trifluoromethyl-benzaldoximes (TFBO) as a trifluoromethoxylation reagent in the absence of silver under mild reaction conditions. The trifluoromethoxylation reagent TFBO is easily prepared and thermally stable, and can release CF(3)O(−) species in the presence of a base. Furthermore, broad scope and good functional group compatibility are demonstrated by application of the method to the late-stage trifluoromethoxylation of alkyl halides in complex small molecules.