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Updated: Sep 25, 2025

Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives
Published on: January 19, 2016
2,2,2-Trifluoroethanol-mediated hydroarylation of fluorinated alkynes with indoles: Application to diindolylmethanes
Philipp Flury1, Olga Eppler1, Dieter Schollmeyer2
1Institute of Pharmacy, Pharmaceutical/Medicinal Chemistry and Tübingen Center for Academic Drug Discovery, Eberhard Karls University Tübingen, Tübingen, Germany.
Abstract:
A new mild and practically simple alkyne hydroarylation protocol for the synthesis of 3-(indol-3-yl)-3-(trifluoromethyl)acrylic acid esters by the reaction of indole derivatives with ethyl/methyl 4,4,4-trifluoro-3-(indol-3-yl)but-2-enoates in trifluoroethanol was developed. This method has the following advantages: no catalyst, atom economy, high yields, broad substrate scope, and large-scale synthesis. The potential application of this protocol was further demonstrated by the synthesis of a variety of CF3 -substituted synthons and a new class of (un)symmetrical 3,3'-diindolylmethanes with a quaternary carbon core that might be biologically active.
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