华中师范大学肖文精团队报道了钯催化的(3+2)环加成反应中通过远距离H键立体感应控制手性第四元立体中心。相关研究成果发表在2022年11月15日出版的《德国应用化学》。

环丙烷供体-受体（D–A）的开环转化使复杂分子能够快速组装。然而，使用带有两个不同受体的底物对映选择性形成手性四元立体中心仍然是一个挑战。

该文中，研究人员描述了第一次钯催化的具有两个不同吸电子基团的乙烯基环丙烷的、高度非对映选择性和对映选择性（3+2）环加成反应，这是D–A环丙烷的一个子集。该反应成功的关键是通过手性配体的氢键进行远程立体诱导，从而解决了上述挑战。各种手性五元杂环以良好的产率和高的立体选择性（高达99%产率，99:1er和>19:1dr）产生。深入的机制研究，包括控制实验和理论计算，揭示了立体选择性的起源以及氢键在立体控制中的重要性。

附：英文原文

Title: Taming Chiral Quaternary Stereocenters via Remote H-Bonding Stereoinduction in Palladium-Catalyzed (3+2) Cycloadditions

Author: Yu-Qing Xiao, Miao-Miao Li, Zheng-Xin Zhou, Yu-Jie Li, Meng-Yue Cao, Xiao-Peng Liu, Hai-Hua Lu, Rao Li, Liang-Qiu Lu, Andr, Wen-Jing Xiao

Issue&Volume: 2022-11-15

Abstract: Ring-opening transformations of donor–acceptor (D–A) cyclopropanes enable the rapid assembly of complex molecules. However, the enantioselective formation of chiral quaternary stereocenters using substrates bearing two different acceptors remains a challenge. Herein, we describe the first palladium-catalyzed highly diastereo- and enantioselective (3+2) cycloaddition of vinyl cyclopropanes bearing two different electron-withdrawing groups, a subset of D–A cyclopropanes. The key to the success of this reaction is the remote stereoinduction through hydrogen bond from chiral ligands, which thereby addressed the aforementioned challenge. A variety of chiral five-membered heterocycles were produced in good yields and with high stereoselectivity (up to 99% yields, 99:1 er and >19:1 dr). In-depth mechanistic investigations, including control experiments and theoretical calculations, revealed the origin of the stereoselectivity and the importance of H-bonding in stereocontrol.

DOI: 10.1002/anie.202212444

Source: https://onlinelibrary.wiley.com/doi/10.1002/anie.202212444