Site-Selective Electrophilic Trifluoromethylthiolation for the Synthesis of C5- or C7-SCF3-Substituted Indolines
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Updated: Jun 4, 2025

Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives
Published on: January 19, 2016
Xiaolong Wang1, Yan Fu2, Zhenshan Guo1
1School of Pharmacy, Hebei Medical University, Shijiazhuang 050017, China.
Abstract:
We report herein an efficient and site-selective electrophilic trifluoromethylthiolation of indolines. In the absence of any catalyst or additive, C5-selective trifluoromethylthiolation could proceed at room temperature. With palladium used as the catalyst, the selectivity was reversed completely, giving C7-selecive trifluoromethylthiolated products. This reaction features good functional group tolerance, simple operation, mild conditions, and scale-up application. The potential utilities of the products were shown by further transformations.
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Alcohols can be synthesized from alkyl halides via nucleophilic substitution reactions. The highly polar carbon-halogen bond in the substrate makes halide a good leaving group. The hydroxide ion or water can act as a nucleophile to take the place of halide and form an alcohol. The substitution reactions occur via two different reaction pathways, SN1 or SN2, depending on the nature of carbon attached to the halide.
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