Control over S(VI)-Stereogenic Center: NHC-Catalyzed Enantioselective Synthesis of N-Acyl Cyclic Sulfonimidamides

Abstract

The catalytic enantioselective synthesis of aza-sulfur(VI) compounds holds significant potential in pharmaceuticals owing to their broad spectrum of biological properties. Herein, we report the first N-heterocyclic carbene (NHC)-catalyzed enantioselective synthesis of cyclic sulfonimidamides (SIAs). The free N–H containing SIAs often exhibit configurational lability through tautomerization. We investigated this by demonstrating their nonsymmetric nature in both solid state and solution. The in situ generated chiral acylazolium intermediates from easily accessible aldehydes in the presence of NHC and oxidant were trapped with the prochiral cyclic SIA anions, allowing the enantioselective synthesis of configurationally stable N-acyl cyclic SIAs. Mechanistic studies reveal that the present strategy proceeds via the desymmetrization of the prochiral SIA anions. Moreover, the derivatization of the synthesized N-acyl SIAs highlights the practical utility of the present methodology.