Cu-Catalyzed Synthesis of Isoxazolidine/1,2-Oxazinane-3-ylidene Sulfonamide from O-Alkynyl Hydroxylamines: A Route to Sulfamethoxazole Analogues.

Cu-catalyzed cascade [3+2] azide-alkyne cycloaddition (CuAAC)/ketenimine/hydroamination reaction of alkynyl hydroxylamines that enables the rapid synthesis of isoxazolidine/1,2-oxazinane-3-ylidene sulfonamides. Notably, this study presents the first examples of 1,2-oxazinane-3-ylidene sulfonamide. The synthetic utility of this transformation is highlighted by the direct conversion of isoxazolidine-3-ylidine sulfonamides into 3-amino isoxazolines and isoxazole derivatives. This strategy was used as a key step in the total synthesis of antibiotic sulfamethoxazole and its analogues.