Access to chiral sulfones with an all-carbon quaternary stereocenter from sulfur dioxide

Abstract

Sulfur dioxide (SO₂), as an atmospheric pollutant, has been increasingly attracting the interest of scientists regarding its chemical utilization. Vicinal sulfonyl-functionalization of alkenes through SO₂ insertion offers an innovative method to introduce both sulfonyl and other functional groups into a single molecule. This approach boosts compound diversity while eliminating the need for multi-step operation. On the other hand, the asymmetric construction of quaternary all-carbon stereocenters remains a persistent synthetic challenge. In particular, methods for the synthesis of chiral sulfones bearing an all-carbon quaternary stereocenter are rare. Herein, we present a copper-catalyzed vicinal cyano-arylsulfonylation of acrylamides via the insertion of sulfur dioxide (SO₂), providing an easy way to achieve this goal with minimally functionalized starting materials. The reaction proceeds under mild conditions through a verified single-electron-transfer (SET) mechanism with excellent enantioselectivity (mostly >99% ee), good functional group tolerance, and a broad substrate scope (>50 examples). Notably, this four-component reaction is applicable to the direct chiral functionalization of amino acid and peptide derivatives.