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

利用元素硫和胺活化偕二氯乙酰胺和环氧化物:合成单硫代草酰胺和α-酮硫代酰胺的途径

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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 (S(8)) 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 I(2)/DMSO, enabling the efficient synthesis of α-ketothioamides through the incorporation of S(8) 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.

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