Activation of gem-Dichloroacetamides and Epoxides Using Elemental Sulfur and Amines: A Route to Monothiooxalamides and α-Ketothioamides

Abstract

The selective activation of C–X bonds to generate value-added products via transition metal-free methodologies remains a formidable challenge in modern synthetic chemistry. Herein, we report a metal-free didechlorinative strategy for the construction of unsymmetrical monothiooxalamides through C–S and C–N bond formation. This transformation proceeds via a one-pot functionalization of gem-dichloroacetamides with various amines and elemental sulfur (S₈) under ambient conditions in an open-air atmosphere, offering a sustainable and operationally simple approach. Additionally, a regioselective epoxide ring-opening approach was implemented using I₂/DMSO, enabling the efficient synthesis of α-ketothioamides through the incorporation of S₈ and diverse amine nucleophiles. Furthermore, ligand studies revealed that monothiooxalamides exhibit high efficacy as ligands in Cu-catalyzed C–N cross-coupling reactions. The method’s synthetic utility was further demonstrated through gram-scale synthesis and the preparation of natural product derivatives and drug analogues, highlighting its potential for industrial applications.