Nan Jiang, Ren Xin, Yan Qiang, Liu Shilei, Wang Jing, Ma Yangmin, Szostak Michal
The Youth Innovation Team of Shaanxi Universities, Shaanxi Key Laboratory of Chemical Additives for Industry, College of Chemistry and Chemical Engineering, Shaanxi University of Science and Technology Xi'an 710021 China
Department of Chemistry, Rutgers University 73 Warren Street Newark New Jersey 07102 USA.
Chem Sci. 2023 Feb 27;14(12):3338-3345. doi: 10.1039/d3sc00301a. eCollection 2023 Mar 22.
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.
C（O）-N酰胺键的直接官能团化是过去几十年中最受关注的研究方向之一；然而，涉及酰胺键的氧化偶联以及硫代酰胺C（S）-N类似物的官能团化仍然是一个尚未解决的挑战。在此，已经建立了一种新型的高价碘诱导的胺与酰胺和硫代酰胺的双重氧化偶联反应。该方案通过前所未有的Ar-O和Ar-S氧化偶联实现了不同的C（O）-N和C（S）-N断键，并以高度化学选择性的方式组装了通用但合成具有挑战性的恶唑和噻唑。使用酰胺而不是硫代酰胺会产生另一种键断裂模式，这是硫代酰胺中较高共轭作用的结果。机理研究表明，第一次氧化生成的脲和硫脲是实现氧化偶联的关键中间体。这些发现为在各种合成环境中探索氧化酰胺和硫代酰胺键化学开辟了新途径。
