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Updated: Jul 5, 2025

Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives
Published on: January 19, 2016
Silver-Enabled Dearomative Trifluoromethoxylation of Indoles
Zhijie Deng1, Lingduan Meng1, Xiao Bing1
1State Key Laboratory and Institute of Elemento-Organic Chemistry, College of Chemistry, Nankai University, Tianjin 300071, China.
Abstract:
The only known method for the dearomative trifluoromethoxylation of indoles is preliminary, with only one substrate successfully undergoing the reaction. In this study, we not only developed a broadly applicable method for indole dearomative trifluoromethoxylation but also achieved divergent trifluoromethoxylation by fine-tuning the reaction conditions. Under optimized conditions, with a silver salt and an easily handled OCF3 reagent, various indoles smoothly underwent dearomatization to afford a diverse array of ditrifluoromethoxylated indolines in 50-84% isolated yields with up to 37:1 diastereoselectivity, and fluorinated trifluoromethoxylated indolines were obtained with exclusive trans selectivity. In addition, the reaction conditions were compatible with other heteroaromatic rings as well as styrene moieties.
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