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Updated: Feb 19, 2026

Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives
Published on: January 19, 2016
Direct Dehydroxytrifluoromethoxylation of Alcohols
Xiaohuan Jiang1, Zhijie Deng1, Pingping Tang1
1State Key Laboratory and Institute of Elemento-Organic Chemistry, College of Chemistry, Nankai University, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin, 300071, China.
Abstract:
The first example of a direct dehydroxytrifluoromethoxylation of alcohols has been developed. This method generated an alkyl fluoroformate in situ from alcohols, followed by nucleophilic trifluoromethoxylation with trifluoromethyl arylsulfonate (TFMS) as the trifluoromethoxylation reagent. The reaction is operationally simple and scalable, and it proceeds under mild reaction conditions to provide access to a wide range of trifluoromethyl ethers from alcohols. In addition, this method is suitable for the late-stage trifluoromethoxylation of complex small molecules.
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