Unified Gold-Catalyzed Cyclization Approach Towards Isothiazoles from Propargylic Sulfinamides

Isothiazoles are valuable heterocycles in agrochemical and pharmaceutical research, yet they remain synthetically less accessible than their isoxazole counterparts. We report here a gold-catalyzed cyclization of propargylic N-tert-butanesulfinamides that provides direct and efficient access to isothiazoles under mild conditions. The transformation proceeds through an unusual cascade: cationic gold activation of the alkyne triggers a 5-endo-dig ring closure with sulfur as the nucleophile followed by irreversible loss of the tert-butyl group and dehydrative aromatization. The substrate scope encompasses a range of alkyl and aryl substituents, affording isothiazoles in yields of up to 79%. Reaction monitoring and isolation of key intermediates establish that the cyclic sulfinamide is a direct precursor to the aromatic product and that protic solvents, particularly acetic acid, facilitate the cascade of events, dramatically reducing reaction times. A complementary base-catalyzed pathway from CF3-substituted substrates selectively delivers cyclic sulfoximines, demonstrating that both heterocyclic classes are accessible from a common precursor by simply switching the activation mode. These results originate from a serendipitous observation made during insecticide research at Syngenta and have broader implications for the design of sulfur-containing heterocyclic scaffolds.