Abstract

Sulfilimines have garnered increasing attention as valuable scaffolds in drug discovery and asymmetric synthesis. Nevertheless, catalytic enantioselective construction of sulfilimines in both axial and point chirality chemical space remains a substantial challenge. Herein, we report copper-catalyzed atroposelective sulfilimination of terminal alkynes with sulfenamides via a radical relay mechanism, enabling the direct assembly of axially chiral vinyl sulfilimines with high levels of chemo-, regio-, diastereo-, and enantioselectivity. The success of this strategy hinges on the atroposelective trapping of transient high active vinyl radicals by a chiral Cu–sulfinimidoyl intermediate. Experimental and computational mechanistic studies reveal a novel asymmetric radical sulfilimination mechanism through an enantioselective reductive elimination of a Cu(III) intermediate, thereby establishing a mechanism distinct from outer-sphere HAT-initiated radical–radical coupling or SH2 pathway.

DOI: https://doi.org/10.1002/anie.202523530