Photoredox‐Catalyzed Chem‐ and Stereoselective Thiosulfonylation of Cyclopropylamides

Abstract

ABSTRACT While the thiosulfonylation of C─C π‐bonds is well‐established, the analogous functionalization of kinetically inert C─C σ‐bonds remains a formidable challenge, particularly regarding stereoselective control. Herein, we report a general photocatalytic strategy for the chemo‐ and stereoselective 1,3‐thiosulfonylation of cyclopropylamides. This method successfully addresses the elusive challenge of stereocontrol in σ‐bond thiosulfonylation, enabling the unprecedented asymmetric construction of metastable γ‐thio‐α‐aminosulfones with excellent enantioselectivity. The optimized protocol exhibits a broad scope, accommodating a diverse array of cycloalkylamides as well as mono‐, di‐, and even trithiosulfonates. Furthermore, the utility of this methodology is highlighted by its successful application in the late‐stage functionalization of pharmaceutically relevant compounds, diverse downstream transformations. Most crucially, we have demonstrated that the resulting chiral ɑ‐amidoalkylphenyl sulfones readily undergo stereoselective substitution in SN2‐like pathway, effectively outcompeting the typically predominant E2‐type elimination process.