近日，天津师范大学王超团队报道了通过烯烃迁移官能化的非相邻立体中心的立体发散构造。相关论文于2025年11月12日发表在《自然-化学》杂志上。

立体发散性构建多重立体中心是不对称合成中最核心的课题之一。然而，针对含有非相邻立体中心光学活性化合物的全构型异构体组装策略仍十分有限，且在反应类型与化学空间维度上存在明显局限。

研究组成功利用链行走策略，通过镍催化的三取代烯烃迁移氢烷基化反应，实现了非相邻1,n-位（n=3或4）无环立体中心的对映选择性与非对映发散性同步构建。多种烷基单元可实现氮相邻α-C(sp³)–H位点的区域选择性引入，从而生成含有α-手性中心及远端（γ或δ位）全烷基取代立体中心的手性胺类化合物。通过精准选择烯烃构型与配体构型，仅使用单一催化剂即可获得全部四种立体异构体，并实现卓越的立体化学控制。这一简洁温和的合成平台为复杂生物活性分子及药物相关骨架的高效合成开辟了新途径。

附：英文原文

Title: Stereodivergent construction of non-adjacent stereocentres via migratory functionalization of alkenes

Author: Ju, Guodong, Yan, Xueyuan, Bai, Haohao, Liu, Mengyuan, Xi, Xinping, Liu, Yi, Huang, Genping, Wang, Chao

Issue&Volume: 2025-11-12

Abstract: Stereodivergent construction of multiple stereocentres is one of the most essential tasks in asymmetric synthesis. However, strategies for assembling all possible stereoisomers of optically active compounds bearing non-adjacent stereocentres remain scarce and suffer from certain limitations in terms of reaction types and chemical space. Here we succeed in utilizing the chain walking strategy to realize the simultaneous construction of acyclic 1,n-non-adjacent (n=3 or 4) stereocentres via Ni-catalysed migratory hydroalkylation of trisubstituted alkenes in an enantioselective and diastereodivergent manner. A series of alkyl units can be site-selectively installed at α-C(sp3)–H sites adjacent to nitrogen, affording chiral amines bearing an α-stereogenic centre and a remote (γ- or δ-) all-alkyl-substituted stereocentre. All four stereoisomers can be accessed using a single catalyst via an appropriate selection of the olefin geometry and ligand configuration, with exceptional control of stereochemistry. This simple and mild platform offers opportunities for the streamlined synthesis of complex bioactive molecules and medicinally relevant scaffolds.

DOI: 10.1038/s41557-025-01994-7

Source: https://www.nature.com/articles/s41557-025-01994-7