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Updated: Jul 10, 2026

Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives
Published on: January 19, 2016
Lewis Acid-Catalyzed Alkoxylation/1,3-Nitrogen Migration/Reduction Cascade for the Stereoselective Synthesis of
Santosh J Gharpure1, Sonia Pundir1, Raj Kumar Patel1
1Department of Chemistry, Indian Institute of Technology Bombay, Powai, Mumbai 400076, India.
Abstract:
Herein, we report stereoselective, transition-metal-free, TMSOTf-catalyzed oxyamination of O-alkynyl hydroxylamines for efficient access to 3-aminotetrahydrofuran derivatives under mild conditions. The reaction displays a broad substrate scope, tolerating a range of aryl, heteroaryl, and aliphatic substituents, and affords the desired products with excellent diastereoselectivity. Mechanistic studies, including control, trapping, and crossover experiments, reveal an unprecedented oxyamination/reduction cascade initiated by Lewis acid-promoted 5-endo-dig alkoxylation, followed by a concerted [1,3]-sigmatropic rearrangement ([1,3]-nitrogen shift) and reduction. The protocol can be readily scaled to the gram scale and enables diverse downstream functionalizations of the synthesized product.
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