Asymmetric Sulfonimidoyl Transfer Reactions by a Chiral 4-(Dimethylamino)pyridine-Type Nucleophilic Organocatalyst for the Construction of Sulfur(VI)-Stereogenic Compounds

Abstract Sulfur(VI)-stereogenic compounds are of growing importance in medicinal chemistry, agrochemical, and materials science, owing to their favorable physicochemical properties and pronounced biological activities. Despite significant advances in organosulfur chemistry, the catalytic asymmetric construction of configurationally stable sulfur-centered chirality at the S(VI) oxidation state remains a formidable challenge. Herein, we disclose a chiral 4-(dimethylamino)pyridine (DMAP)-type nucleophilic organocatalyst for the direct activation of S(VI) moiety, enabling the enantioselective synthesis of sulfur-stereogenic S(VI) compounds from readily accessible sulfonimidoyl chlorides. Distinct from conventional DMAP activation of acyl groups, the generated covalent S(VI)−DMAP intermediates in this study serve as versatile sulfonimidoyl transfer groups, providing access to a broad array of enantioenriched sulfonimidamides, sulfonimidoyl fluorides, and sulfonimidate esters, through highly enantioselective construction of S(VI)−N, S(VI)−F, and S(VI)−O bonds. Mechanistic investigations reveal that the dynamic kinetic resolution process involves a facile inversion of the S(VI) center of the sulfonimidoyl substrate assisted by the generated chloride anion. The resulting chiral S(VI) compounds are readily diversified and exhibit promising antibacterial activity, highlighting the potential of these compounds for agrochemical development.