武汉大学周强辉团队报道了对映选择性远程C–H活化合成平面手性二茂铁。相关研究成果于2023年4月17日发表在国际顶尖学术期刊《自然—化学》。

平面手性二茂铁是不对称催化、材料科学和药物化学中广泛研究的结构。尽管1,2-二取代平面手性二茂铁的合成方法是众所周知的，但直接构建1,3-二取代平板手性二茂铁的方法仍然难以捉摸。

该文中，研究人员报道了一个模块化平台，用于通过对映选择性中继远程C–H激活策略在1，3-二取代二茂铁/钌并苯中构建平面手性。该方法证明了一种远程对映控制的机制，即通过手性单-N-保护的天然氨基酸配体在C2位置进行对映异构初始C-H活化，然后通过桥头堡取代的降冰片烯介体传递到远程C3位置。研究人员制备了多种1，3-二取代平面手性茂金属，具有较高的对映选择性（96-99%e.e.）。

该反应表现出良好的官能团耐受性和高阶跃经济性，芳基碘化物/溴化物作为偶联配偶体是相容的。所得的茂金属可以很容易地衍生，以产生用于不对称催化的平面手性配体和催化剂以及用于其他应用的构建块。

附：英文原文

Title: Synthesis of planar chiral ferrocenes via enantioselective remote C–H activation

Author: Zhou, Lan, Cheng, Hong-Gang, Li, Lisha, Wu, Kevin, Hou, Jing, Jiao, Chengkang, Deng, Shuang, Liu, Zirui, Yu, Jin-Quan, Zhou, Qianghui

Issue&Volume: 2023-04-17

Abstract: Planar chiral ferrocenes are widely studied structures in asymmetric catalysis, materials science and medicinal chemistry. Although synthetic methods for 1,2-disubstituted planar chiral ferrocenes are well known, methods for the direct construction of 1,3-disubstituted planar chiral ferrocenes remain elusive. Here we report a modular platform for the construction of planar chirality in 1,3-disubstituted ferrocenes/ruthenocenes via an enantioselective relay remote C–H activation strategy. This method demonstrates a mechanism for remote enantiocontrol via enantiodetermining initial C?H activation at the C2 position, enabled by a chiral mono-N-protected natural amino-acid ligand, and subsequent relay to the remote C3 position by a bridgehead-substituted norbornene mediator. A wide variety of 1,3-disubstituted planar chiral metallocenes are prepared with high enantioselectivity (96?99% e.e.). The reaction shows good functional-group tolerance and high step-economy, and aryl iodides/bromides are compatible as coupling partners. The resulting metallocenes can be readily derivatized to yield planar chiral ligands and catalysts for asymmetric catalysis as well as building blocks for other applications. 

DOI: 10.1038/s41557-023-01176-3

Source: https://www.nature.com/articles/s41557-023-01176-3