Control Over S(VI) Stereogenicity for the Asymmetric Synthesis of Sulfonimidoyl Derivatives by Isothiourea‐Catalyzed Covalent Activation of Sulfur(VI) Atoms

Abstract In contrast to the notable advancements focusing on the preparation of optically enriched S(IV) frameworks in recent years, achieving catalyst stereocontrol over S(VI) stereogenicity to generate chiral S(VI) scaffolds remains a largely underexplored challenge. Herein, we document a new activation mode of isothiourea organocatalysis for the highly enantioselective synthesis of S(VI)‐chiral sulfonimidates. This method involves the covalent activation of racemic S(VI) sulfonimidoyl chlorides through the formation of a pivotal isothiourea‐bound sulfonimidoyl intermediate. The newly formed S(VI)‐based isothiourea reactive species further governs the subsequent asymmetric S─O bond formation to afford the chiral sulfonimidate products with high yields and selectivity. Mechanistic studies reveal that the facile inversion of the tetrasubstituted S(VI) stereogenic center assisted by the chiral catalyst is crucial in the dynamic kinetic asymmetric transformation (DYKAT) process. Notably, distinct from the extensively studied isothiourea catalysis focused on the activation of “C”‐centered substrates, our method introduces a novel S‐atom activation approach, enabling the efficient construction of S(VI) stereogenic centers. Furthermore, the obtained enantioenriched sulfonimidates serve as linchpin intermediates in efficient sulfur‐phenolate exchange for rapid access to diverse S(VI)‐stereogenic frameworks, including sulfoximines, sulfonimidamides, and their derivatives, with notable antimicrobial activity against various plant pathogens.