Access to S-Stereogenic Free Sulfoximines via Bifunctional Phosphonium Salt-Catalyzed Desymmetrization of Bisphenols

Sulfur-stereogenic sulfoximines particularly with a free N-H unit exhibit intriguing chemical and biological activities, and thus have received continuous attention from chemists. However, there are currently no examples of guiding catalytic asymmetric strategies available to directly access these molecules. Herein, we disclose an efficient and practical protocol for the direct enantioenrichment of free N-H sulfoximines, via a bifunctional phosphonium salt-catalyzed desymmetrization triggered by the Atherton–Todd reaction together with a further extended nucleophilic acyl substitution-type reaction. A series of free N-H sulfoximines bearing an assortment of aromatic groups (70 examples) are tolerated in this desymmetrization with incidentally involving minority kinetic resolution (KR). The desymmetrized products can be easily transformed into chiral sulfoxides and other classes of active sulfur-stereogenic compounds. Mechanistic studies provided insights into the reaction pathway particularly suggesting a desymmetrization/KR synergic process, and also offered support on hydrogen-bonding interactions as the key elements to successful stereocontrol.