中国科学技术大学龚流柱团队报道了亚乙炔基铜的远程对映选择性ε-烷基化——中心和轴向手性的精确控制。相关研究成果于2024年10月17日发表于国际顶尖学术期刊《德国应用化学》。

手性四取代烯已成为工程生物活性化合物的重要结构。构建独特的四取代丙二烯支架，精确控制连续的中心和轴向手性，仍有待开发。

该文中，研究人员报告了一种由NHC和铜协同催化的，炔炔丙基乙酸酯与烯醛的远程对映选择性ε-烷基化反应，产生了一系列具有优异对映选择性（高达>99%ee）和非对映选择性的四取代二烯烃（高达>95:5 dr）。

该方法具有高区域选择性和同时控制轴向和中心手性的特点。机理研究表明，乙炔亚铜具有协同激活模式和协同控制远端手性的作用。

附：英文原文

Title: Remote Enantioselective ε-Alkylation of Copper Ethynylallenylidenes: Precise Control of Central and Axial Chirality

Author: Yu-Hua Wen, Minghao Liu, Yu-Hao Wang, Qian-Wei Gong, Shuai Li, Jin Song, Liu-Zhu Gong

Issue&Volume: 2024-10-17

Abstract: Chiral tetrasubstituted allenes have emerged as important architectures for engineering biologically active compounds. The construction of unique tetrasubstituted allene scaffolds with precise control of continuous central and axial chirality remains yet to be developed. Here, we report a remote enantioselective ε-alkylation of yne-propargylic acetates with enals enabled by NHC and copper cooperative catalysis, leading to a series of tetrasubstituted allenes with excellent enantioselectivities (up to >99% ee) and diastereoselectivities (up to >95:5 dr). This method features high regioselectivity and simultaneous control of axial and central chirality. Mechanistic studies suggest a cooperative activation mode and synergistical control of distal chirality created from the copper ethynylallenylidenes.

DOI: 10.1002/anie.202416089

Source: https://onlinelibrary.wiley.com/doi/10.1002/anie.202416089