近日，浙江大学化学系史炳锋及其课题组报道了通过钴催化的对映选择性C-H活化合成两个遥远的不同C-N轴的吡哆酮。该研究于2025年3月13日发表于国际一流学术期刊《美国化学会杂志》上。

在这里，该团队报道了一种新的通过钴催化的不对称碳氢环合成具有6-5和6-6 C-N轴的双轴手性吡啶吲哚酮。该方法显示出卓越的效率，产生了多种手性吡啶多酮，具有优异的产率和抗选择性（60个实例，产率高达>99%，ee值>99%，dr值>20:1）。机理研究表明，在C-H环金属化过程中，两个C-N轴的立体化学同时产生和固定，并伴有意想不到的不对称放大效应。成功的克级合成和各种转化，包括手性膦配体的形成，进一步强调了该方案的实用性。值得注意的是，观察到异常的光致发光量子产率（ΦF高达0.99）和正溶剂化变色，加上显著的热学性质，强调了这些化合物在有机荧光材料中的潜在应用。

据了解，C-N轴向手性化合物是一类重要的旋回异构体，普遍存在于生物活性分子和物质分子中。尽管近年来合成方法取得了进步，但具有多个C-N轴的不对称结构的atropisomer很少被探索，这极大地限制了它们的进一步应用。

附：英文原文

Title: Atroposelective Synthesis of Pyridoindolones Bearing Two Remote Distinct C–N Axes through Cobalt-Catalyzed Enantioselective C–H Activation

Author: Pu-Fan Qian, Yan-Xuan Wu, Jia-Heng Hu, Jia-Hao Chen, Tao Zhou, Qi-Jun Yao, Zi-Hang Zhang, Bing-Jie Wang, Bing-Feng Shi

Issue&Volume: March 13, 2025

Abstract: C–N axially chiral compounds represent an important class of atropisomers that are prevalent in bioactive and material molecules. Despite recent advances in synthetic methodologies, the asymmetric construction of atropisomers featuring multiple C–N axes has been rarely explored, significantly limiting their further applications. Herein, we report a novel atroposelective synthesis of diaxially chiral pyridoindolones featuring both six–five and six–six C–N axes through cobalt-catalyzed asymmetric C–H annulation. This approach demonstrates exceptional efficiency, yielding a diverse array of chiral pyridoindolones with excellent yields and atroposelectivities (60 examples, up to >99% yield, >99% ee, and >20:1 dr). Mechanistic studies revealed that the stereochemistry of both C–N axes were generated and fixed simultaneously during the C–H cyclometalation step, along with an unexpected asymmetric amplification effect. The practicality of this protocol is further underscored by successful gram-scale syntheses and various transformations, including the formation of a chiral phosphine ligand. Notably, exceptional photoluminescence quantum yields (ΦF up to 0.99) and positive solvatochromism were observed, coupled with significant chiroptical properties, underscoring the potential applications of these compounds in organic fluorescent materials.

DOI: 10.1021/jacs.5c02428

Source: https://pubs.acs.org/doi/abs/10.1021/jacs.5c02428