Lewis Acid-Catalyzed Alkoxylation/1,3-Nitrogen Migration/Reduction Cascade for the Stereoselective Synthesis of 3-Aminotetrahydrofuran.

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.