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Updated: Sep 10, 2025

Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives
Published on: January 19, 2016
Gold-Catalyzed Single O-Transfer to Internal CF3-Alkynes. Regioselective Synthesis of 4-Trifluoromethylated Oxazoles
Karina O Mahmedova1, Vadim Yu Kukushkin1,2, Alexey Yu Dubovtsev1
1Saint Petersburg State University, Universitetskaya Nab. 7/9, 199034 Saint Petersburg, Russian Federation.
Abstract:
A highly regioselective gold-catalyzed single oxygen transfer reaction, involving internal trifluoromethylated alkynes, pyridine N-oxides, and nitriles, has been developed. The alkyne-attached CF3-moiety functions through an inductive mechanism to direct O-nucleophilic attack specifically to the β-alkyne position. This three-component transformation yields a diverse array of valuable 4-trifluoromethylated oxazoles in high yields (30 examples; up to 96%) under relatively mild gold-catalyzed conditions, demonstrating significant tolerance for various functional groups. The mechanistic experiments indicate the crucial role of the alkyne-attached CF3-group for the formation of the oxazole products. The potential for the facile modification of the directing CF3-group was also demonstrated.
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