Catalyst Control over S(IV)-stereogenicity via Carbene-derived Sulfinyl Azolium Intermediates

Stereoselective synthesis utilizing small-molecule catalysts, particularly N-heterocyclic carbene (NHC), has facilitated swift access to enantioenriched molecules through diverse activation modes and NHC-bound reactive intermediates. While carbonyl derivatives, imines, and "activated" alkenes have been extensively investigated, the exploration of heteroatom-centered analogues of NHC-bound intermediates has long been neglected, despite the significant potential for novel chemical transformations they offer once recognized. Herein, we disclose a carbene-catalyzed new activation mode by generating unique sulfinyl azolium intermediates from carbene nucleophilic addition to in situ-generated mixed sulfinic anhydride intermediates. Combined experimental and computational mechanistic investigations pinpoint the chiral NHC-catalyzed formation of sulfinyl azolium intermediate as the enantio-determining step. The novel "S"-based carbene reactive intermediate imparts high efficiency for the catalytic construction of sulfur-stereogenic compounds, giving rise to sulfinate esters with high yields and enantioselectivities under mild conditions. Notably, distinct from most of the NHC-catalyzed enantioselective transformations focusing on the "C" central chiral products, our study realizes a unique carbene-catalyst control over chiral "S" stereocenters via direct asymmetric S-O bond formation for the first time. Furthermore, these sulfinyl-containing products could serve as versatile synthetic platforms for enantioenriched