Cu-Catalyzed C–H Phenothiazination toward the Assembly of Cyclopeptides

A modular copper-catalyzed radical macrocyclization for a variety of Tyr-containing compounds bearing phenothiazines has been developed. This approach utilizes cost-efficient Cu­(OAc)2 as a catalyst along with air as the terminal oxidant, thereby enabling the predictable C–N coupling at the ortho C–H bond of phenols in a late-stage fashion. This oxidative and operationally simple coupling technique can proceed intramolecularly to deliver unconventional cyclopeptides featuring a biaryl linkage.本研究开发了一种模块化铜催化自由基大环化反应，可适用于多种带有吩噻嗪结构的含酪氨酸（Tyr）化合物。该策略以经济高效的乙酸铜(II)（Cu(OAc)₂）为催化剂，以空气作为末端氧化剂，能够实现苯酚邻位碳氢键的可控C-N偶联，并可应用于后期修饰流程。此氧化型且操作简便的偶联技术可通过分子内反应路径，得到具有联芳基连接结构的非经典环肽。