Nucleophilic trifluoromethoxylation of alkyl halides without silver

无需银催化的烷基卤化物亲核三氟甲氧基化反应

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Abstract

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.

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