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Updated: Sep 19, 2025

Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives
Published on: January 19, 2016
Access to 2-(Trifluoromethyl)indoles via Pd(0)-Catalyzed Intramolecular Cyclization of Trifluoroacetimidoyl Chlorides
Chunjie Ni1, Zhanhang Liang1,2, Yantao Zhu1
1School of Pharmacy, Yancheng Teachers University, Yancheng 224007, China.
Abstract:
A novel Pd(0)-catalyzed intramolecular 5-exo-dig cyclization between trifluoroacetimidoyl halides and alkynes has been established, involving a key alkyne oxypalladation process with H2O serving as the nucleophile. This protocol exhibits broad functional group tolerance under mild conditions, providing 2-(trifluoromethyl)indole derivatives in moderate to excellent yields. Notably, the streamlined synthesis of a trifluoromethylated pravadoline analogue and the anticancer bioactivities of three products highlight the potential of this methodology for practical applications.
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