Unlocking Catalytic Asymmetric Transformations of Sulfilimidoyl Fluorides: Approach to Chiral Sulfinimidate Esters

The rational design of bioactive molecules increasingly utilizes sulfur-containing groups such as sulfoximines and sulfilimines. While sulfonimidoyl fluorides have enabled efficient asymmetric synthesis of sulfoximines as versatile chiral S(VI) electrophiles, their S(IV) counterparts, sulfilimidoyl fluorides, have not been successfully applied to asymmetric sulfilimine synthesis due to instability and rapid racemization at sulfur. Here, we report the catalytic asymmetric transformation of sulfilimidoyl fluorides, granting direct access to enantioenriched sulfinimidate esters via dynamic kinetic resolution. Central to this process is a bifunctional tertiary amine–hydrogen bond donor catalyst that induces stereocontrol through secondary interactions, stabilizing the transition state during esterification. The method demonstrates broad substrate scope with both sulfenamides and alcohols. Mechanistic studies show that stereoselectivity is established during esterification, distinguishing this strategy from previous methods. This work addresses a key challenge in sulfilimidoyl fluoride chemistry and broadens access to S-stereogenic scaffolds for drug discovery.