中国科学院福建物质结构研究所房新强团队报道了，铜催化不对称亲核打开1,1,2,2-四取代给受体环丙烷，用于合成α-叔胺。相关研究成果于2024年12月26日发表在《美国化学会杂志》。

供体-受体环丙烷（DACs）的催化不对称转化已被证明是，构建不同类型对映体富集分子的一种非常有价值和稳健的策略。然而，使用1,1,2,2-四取代DACs形成带有四元立体中心的产物，仍然是一个长期未解决的挑战。

该文中，研究人员报告了铜催化的四取代炔基DACs的不对称胺化开环，该DACs生成了无数具有高对映选择性的α-叔胺。产品中的炔烃、胺和酯部分能够实现各种进一步的应用，包括生物活性分子的不对称合成。

机理研究表明，带有乙炔铜单元的两性离子中间体在该过程中起着关键作用，这代表了实现DACs催化不对称转化的新模式。

附：英文原文

Title: Copper-Catalyzed Asymmetric Nucleophilic Opening of 1,1,2,2-Tetrasubstituted Donor–Acceptor Cyclopropanes for the Synthesis of α-Tertiary Amines

Author: Shouang Lan, Qinqin Cui, Defu Luo, Siyu Shi, Chengyang He, Shengyu Huang, Chao Xu, Lili Zhao, Jinggong Liu, Cheng-Zhi Gu, Shuang Yang, Xinqiang Fang

Issue&Volume: December 26, 2024

Abstract: Catalytic asymmetric transformation of donor–acceptor cyclopropanes (DACs) has been proven to be a highly valuable and robust strategy to construct diverse types of enantioenriched molecules. However, the use of 1,1,2,2-tetrasubstituted DACs to form products bearing quaternary stereocenters remains a long-term unsolved challenge. Here, we report the copper-catalyzed asymmetric aminative ring opening of tetrasubstituted alkynyl DACs that delivers a myriad of α-tertiary amines with high levels of enantioselectivities. The alkyne, amine, and ester moieties within the products enable diverse further applications, including the asymmetric synthesis of bioactive molecules. Mechanistic studies indicate that the zwitterionic intermediate bearing a copper-acetylide unit plays a key role in the process, which represents a new mode for achieving catalytic asymmetric transformation of DACs.

DOI: 10.1021/jacs.4c14944

Source: https://pubs.acs.org/doi/abs/10.1021/jacs.4c14944