Thioamide synthesis via copper-catalyzed C–H activation of 1, 2, 3-thiadiazoles enabled by slow release and capture of thioketenes. Issue 9 (23rd March 2022)

• Record Type: Journal Article
• Authors: Lu, Changhui; Li, Xiaohong; Chang, Shunqin; Zhang, Yuqi; Xing, Donghui; Wang, Shuo; Lin, Yueping; Jiang, Huanfeng; Huang, Liangbin
• Is Part Of: Organic chemistry frontiers. Volume 9:Issue 9(2022)
• Page Start: 2382
• Page End: 2389
• Publication Date: 2022-03-23
• Subjects: Chemistry, Organic -- Periodicals; 547.005
• DOI: 10.1039/d2qo00152g
• Languages: English
• ISSNs: 2052-4110

Abstract

Abstract : A copper-catalyzed coupling of 1, 2, 3-thiadiazoles with various amines under base-free conditions was developed as a robust protocol for the synthesis of thioamide derivatives via C–H activation/Cu coordination strategy. Abstract : Thioketenes, as highly reactive intermediates, are extremely prone to dimerization, which severely limits their further synthetic applications. Herein we developed a Cu-catalyzed thioacylation of amines via a C–H activation/coordinated stabilization protocol to ensure the slow-release of thioketenes, which are captured by various amines to afford thioamides. This method is characterized by its simplicity, efficiency and broad substrate scope in both 1, 2, 3-thiadiazoles and amines. Its versatility is further illustrated by the late-stage thioamidation of N -containing drugs, peptides, catalysts, and ligands. Mechanism studies demonstrate that the active Cu(i ) species is formed via the reduction of Cu(ii ) during the induction period, and the rate-determining step is the C–H activation of 1, 2, 3-thiadiazole.