Organocatalytic kinetic resolution of sulfinamides by N/O exchange.

Abstract

Kinetic resolution is a promising strategy for accessing enantioenriched molecules from racemic mixtures. However, this method has not previously been realized in the synthesis of chiral sulfinyl scaffolds via S(IV)-X bond exchange. We disclose a kinetic resolution reaction of sulfinamides with alcohols in this report. It affords sulfinate esters and enantioenriched sulfinamides with high enantioselectivity across a broad substrate scope. These two products serve as versatile chiral sulfinyl reagents, enabling further transformation into diverse functional molecules. Mechanistic studies suggest a dual activation transition state, wherein both the sulfinamide and alcohol substrates are engaged by a squaramide catalyst through hydrogen-bonding interactions. This method offers a mechanistic and synthetic complement to established dynamic asymmetric processes for constructing chiral sulfinyl frameworks.