Hypervalent iodine-promoted twofold oxidative coupling of amines with amides and thioamides: chemoselective pathway to oxazoles and thiazoles. Issue 12 (7th March 2023)

• Record Type: Journal Article
• Authors: Nan, Jiang; Ren, Xin; Yan, Qiang; Liu, Shilei; Wang, Jing; Ma, Yangmin; Szostak, Michal
• Is Part Of: Chemical science. Volume 14:Issue 12(2023)
• Page Start: 3338
• Page End: 3345
• Publication Date: 2023-03-07
• Subjects: Chemistry -- Periodicals; 540.5
• DOI: 10.1039/d3sc00301a
• Languages: English
• ISSNs: 2041-6520

Abstract

Abstract : Direct functionalization of the C(O)–N amide bond is one of the most high-profile research directions in the last few decades; however oxidative couplings involving amide bonds and functionalization of thioamide C(S)–N analogues remain an unsolved challenge. Abstract : Direct functionalization of the C(O)–N amide bond is one of the most high-profile research directions in the last few decades; however oxidative couplings involving amide bonds and functionalization of thioamide C(S)–N analogues remain an unsolved challenge. Herein, a novel hypervalent iodine-induced twofold oxidative coupling of amines with amides and thioamides has been established. The protocol accomplishes divergent C(O)–N and C(S)–N disconnection by the previously unknown Ar–O and Ar–S oxidative coupling and highly chemoselectively assembles the versatile yet synthetically challenging oxazoles and thiazoles. Employing amides instead of thioamides affords an alternative bond cleavage pattern, which is a result of the higher conjugation in thioamides. Mechanistic investigations indicate ureas and thioureas generated in the first oxidation as pivotal intermediates to realize the oxidative coupling. These findings open up new avenues for exploring oxidative amide and thioamide bond chemistry in various synthetic contexts.