近日，重庆大学李杨团队实现了用扩环[5,5]-异位重排反应合成高应变的准环烷。该项研究成果发表在2025年7月21日出版的《自然-化学》杂志上。

对环芳烃骨架，其特征是具有1,4-二取代苯环结构框架，是一类结构独特且具有重要生物学意义的化合物。尽管这类骨架在天然产物和生物活性分子中广泛存在，但通过传统的关环策略或其他替代方法合成高张力的对环芳烃仍然极具挑战性。

研究组报道了一种简便制备含弯曲1,4-二取代苯亚单元的对环芳烃的方法，该方法基于环状叔胺与芳炔中间体之间的N-芳基化-扩环[5,5]-σ迁移重排反应。这些骨架占据着独特的化学空间，结构分析揭示了其1,4-二取代苯环存在显著的高度角度畸变。值得注意的是，该重排步骤不仅会因取代基位置的不同而表现出多样化的反应模式，还展示了一种引人入胜的点手性到平面手性的传递现象。密度泛函理论（DFT）计算为非对映选择性控制以及点手性到平面手性的传递过程提供了机理见解。

附：英文原文

Title: Synthesis of highly strained para-cyclophanes via ring-expansion [5,5]-sigmatropic rearrangement reaction

Author: Chen, Zhonghong, Yang, Weihao, Jia, Maomao, Shi, Jiarong, Li, Jiyang, Chen, Haohua, Li, Yang

Issue&Volume: 2025-07-21

Abstract: para-Cyclophane scaffolds, characterized by their 1,4-disubstituted benzene frameworks, represent a structurally unique and biologically important class of compounds. Despite their extensive presence in natural products and bioactive molecules, the synthesis of highly strained para-cyclophanes remains challenging through conventional ring-closing strategies and alternative approaches. Here we report a facile preparation of para-cyclophanes containing bent 1,4-disubstituted benzene subunits via a N-arylation–ring-expansion [5,5]-sigmatropic rearrangement between cyclic tertiary amines and aryne intermediates. These scaffolds occupy a distinctive chemical space, with structural analyses revealing a remarkably high degree of angular distortion on the 1,4-disubstituted benzene rings. Notably, the rearrangement step not only exhibits diverse reaction modes in response to the location of the substituents but also demonstrates an intriguing point-to-planar chirality transfer. Density functional theory calculations provide mechanistic insights into both the diastereoselective control and the point-to-planar chirality transfer process.

DOI: 10.1038/s41557-025-01878-w

Source: https://www.nature.com/articles/s41557-025-01878-w