Zn(II)‐Catalyzed Enantioselective Nucleophilic Substitution Reactions: Access to Sulfur(VI)‐Stereogenic Sulfonimidate Esters

The construction of stereogenic S(VI) centers remains a formidable challenge in asymmetric catalysis, despite incremental advances. The enantioselective transformation of racemic sulfonimidoyl chlorides is rarely described for forming chiral S(VI)─O bonds and limited to covalent organocatalytic manners. Herein, we report the first chiral Lewis acid catalyzed asymmetric nucleophilic substitution of sulfonimidoyl chlorides, using 2-hydroxypyridines as nucleophiles, affording sulfur(VI)-stereogenic chiral sulfonimidate esters with good yields (up to 94% yield), excellent chemoselectivities (O-functionalization) and high enantioselectivities (up to 99% ee). Enantioenriched sulfonimidate esters are stereospecifically transformed into chiral S(VI) derivatives, with the 2-hydroxypyridine unit acting as the leaving group. The practicality of this method is enhanced via a directed one-pot procedure of in situ-generated sulfonimidoyl chloride from S(IV) sulfonamide. Furthermore, the addition of quinuclidine as an additive can trigger rapid racemization of sulfonimidoyl chloride, establishing a dynamic kinetic process instead of a kinetic resolution. Mechanistic studies indicate that the reaction proceeds via an S_N2 pathway with kinetic resolution characteristics. A bifunctional activation mode is elucidated by mechanistic experiments and density functional theory calculations, in which Zn(II)-ligand complex activates the sulfonimidoyl chloride, while imidazolidine N-H forms a H-bond with the nitrogen atom in 2-hydroxypyridines.