Lebin Qian, Yue Wang, Lei Zhu, Xiaotian Qi, Xinjun Luan, Zhijun Zuo
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.