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Updated: Sep 16, 2025

Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives
Published on: January 19, 2016
Nickel-Catalyzed Reductive Cross-Coupling of Aryl Iodides and Trifluoromethyl Oxirane
Yiqiang Tian1, Qitao Guan1, Yanru Li1
1Institute of Molecular Plus, Department of Chemistry, State Key Laboratory of Synthetic Biology, School of Pharmaceutical Science and Technology, Faculty of Medicine, Tianjin University, 92 Weijin Road, Tianjin 300072, China.
Abstract:
This study developed a novel nickel-catalyzed reductive cross-coupling reaction between aryl iodides and trifluoromethyl oxirane. This reaction enables the highly selective ring-opening of trifluoromethyl oxirane and the efficient synthesis of 1-trifluoromethyl-2-phenyl-ethanol derivatives. The reaction exhibits excellent functional group compatibility and can be used to modify a wide range of bioactive drug molecules. Notably, with this new method, novel synthetic routes for a drug molecule and an organic functional material have been established. At the same time, this study shows that the reaction mechanism should involve a direct oxidative addition process of the three-membered oxygen ring to the nickel complex. By exploring and capturing the reaction intermediates, we propose a reasonable reaction mechanism.
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