Asymmetric Synthesis of S(IV)‐Stereogenic Sulfinimidate Esters by Sulfinamide Activation

Abstract

AbstractCatalyst‐controlled approaches for the synthesis of S‐stereogenic compounds have propelled significant advancements in asymmetric synthetic chemistry. In contrast, control over S‐heteroatom (e.g., O) bond formation to access sulfinimidate esters remains an underexplored area. Drawing inspiration from recent progress in electrophilic amide activation, herein, we present a sulfinamide activation strategy for the enantioselective synthesis of S‐chiral sulfinimidate esters. This method involves the activation of racemic sulfinamides by sulfonyl chloride, yielding a reactive aza‐sulfinyl mixed anhydride intermediate. Employing a naturally occurring cinchonidine catalyst, the process achieves excellent enantiocontrol in the subsequent formation of S─O bonds with alcohols involving a dynamic kinetic resolution (DKR) process, resulting in sulfinimidate esters with excellent enantioselectivity. The catalytically obtained enantioenriched sulfinimidate esters offer a versatile platform for the construction of S‐stereogenic frameworks, including sulfilimines and sulfoximines, with promising applications in asymmetric synthesis and drug discovery.