Reagent-Regulated Organocatalytic Enantiodivergent Synthesis of Chiral Sulfinimidate Esters

Achiral parameter-regulated enantiodivergent synthesis of chiral sulfur compounds has rarely been reported. Driven by the increasing importance of aza-sulfur stereogenic centers in drug discovery, we present herein organocatalytic tandem enantioselective chlorination and nucleophilic substitution for the synthesis of chiral sulfinimidate esters. The enantiopreference is modulated by <i>N</i>-chlorophthalimide (NCP) and trichloroisocyanuric acid (TCCA) with the same enantiomer of chiral pentanidium catalyst, and both enantiomers of sulfinimidate esters are obtained with high enantiocontrol. Notably, the reactions with TCCA are very fast and completed in 5 min, and the efficiency is well maintained for gram-scale synthesis. The resulting sulfinimidate esters are versatile precursors for diverse aza-S(IV) and S(VI) stereogenic centers. Studies on the enantiodivergent mechanism reveal that the sulfur stereogenic center is inverted twice in reactions with NCP, and only a single inversion is verified with TCCA, representing a novel strategy for enantiodivergent catalysis.