近日，英国牛津大学Darren J. Dixon团队研究了烷基烷环丙烷的催化对映选择性合成。相关论文于2025年8月11日发表在《自然》杂志上。

小环碳环的对映选择性结构为有机化学家带来了持久的挑战。尽管它们具有商业重要性，但制备亚烷基环丙烷（ACP）的对映选择性合成路线仍然不发达，ACP是一类小环碳环。重要的是，ACP可以转化为环丙烷，这是药物分子中的一个常见特征（如Nirmatrelvir，1），以及天然和合成的农用化学品（如氯菊酯2）。 

研究组现在描述了通过使用双官能亚氨基磷烷（BIMP）催化、立体控制、缓解菌株的解偶联，轻松合成高度对映体富集的亚烷基环丙烷。对基本催化剂体系进行了小幅修改，以将反应范围扩大到含有酯、酰胺、氧化膦和酮官能团的底物。通过设计合适的底物和重新调整催化剂的亚氨基磷烷部分，该转化有效地应用于合成常见杀虫剂氯菊酯的单一立体异构体以及一系列基于环丙烷的杀虫剂核心。研究组进行了最先进的计算研究，以详细了解非对映体和对映体选择性的机制途径和起源。

附：英文原文

Title: Catalytic enantioselective synthesis of alkylidenecyclopropanes

Author: Golec, Jonathan C., Tan, Dong-Hang, Yamazaki, Ken, Tiekink, Eveline H., Christensen, Kirsten E., Hamlin, Trevor A., Dixon, Darren J.

Issue&Volume: 2025-08-11

Abstract: The enantioselective construction of small ring carbocycles provides organic chemists with an enduring challenge.1 Despite their commercial importance, enantioselective synthetic routes towards alkylidenecyclopropanes (ACPs), a class of small ring carbocycles, remain underdeveloped.2,3 Importantly, ACPs can be converted into cyclopropanes, a common feature in drug molecules (e.g. Nirmatrelvir, 1),4 as well as both naturally occurring and synthetic agrochemicals (e.q. permethrin 2).5,6 We now describe the facile synthesis of highly enantioenriched alkylidenecyclopropanes through the use of a bifunctional iminophosphorane (BIMP) catalysed, stereo-controlled, strain-relieving deconjugation. Small modifications to the basic catalyst system were used to broaden the scope of the reaction to substrates containing ester, amide, phosphine oxide, and ketone functionalities. Through the design of a suitable substrate and re-tuning of the catalyst’s iminophosphorane moiety, the transformation was effectively applied to the synthesis of a single stereoisomer of the commonplace insecticide permethrin as well as a range of cyclopropane-based insecticide cores. State-of-the-art computational studies were performed to provide detailed insight into the mechanistic pathway and origin of both diastereo- and enantioselectivities.

DOI: 10.1038/s41586-025-09485-y

Source: https://www.nature.com/articles/s41586-025-09485-y