近日，斯克里普斯研究所Phil S. Baran团队研究了1,1-二芳基环丁烷、氮杂环丁烷和氧杂环丁烷的三重会聚镍电催化组装。该项研究成果发表在2025年11月11日出版的《自然-化学》杂志上。

对日益复杂三维分子的探索正在突破现代有机合成的边界，尤其在药物发现领域，环丁烷、氮杂环丁烷和环氧乙烷等刚性饱和骨架备受青睐。

研究组提出了一种模块化、可扩展且具化学选择性的解决方案，以简单易得的α-溴酸和芳基卤化物作为直观起始原料。如文中所示，通过一系列镍电催化交叉偶联反应的级联操作，可快速构建此类结构——许多传统方法因需依赖耗时的极性键断裂而几乎无法触及。该研究验证了该反应序列的可扩展性，并直接应用于已知专利分子的合成。同时提供了简明用户指南，以加速该策略在药物化学及相关领域的应用。

附：英文原文

Title: Triply convergent Ni-electrocatalytic assembly of 1,1-diaryl cyclobutanes, azetidines and oxetanes

Author: Massaro, Luca, Neigenfind, Philipp, Feng, Andrew, Kuehn, Gannon, Attard, Flynn C., DeSanti, Ava, Collins, Michael R., Bravo, Martin, Twumasi, Raymond K., Chen, Doris, Bolduc, Philippe N., Nicastri, Michael, Emmanuel, Megan A., Oderinde, Martins S., Palkowitz, Maximilian D., Zheng, Xiaofan, Hunter, Arianne C., Harper, Kaid C., Tyrol, Chet C., Mykhailiuk, Pavel K., Kawamata, Yu, Baran, Phil S.

Issue&Volume: 2025-11-11

Abstract: The pursuit of increasingly complex, three-dimensional molecules is pushing the boundaries of modern organic synthesis, particularly in drug discovery where rigid, saturated scaffolds such as cyclobutanes, azetidines and oxetanes are in high demand. Here we outline a modular, scalable, chemoselective approach to solve this problem using simple α-bromoacids and aryl halides as intuitive starting materials. As demonstrated herein, a sequential series of nickel-electrocatalytic cross-couplings can be enlisted to enable rapid access to such structures, many of which have been nearly impossible to access before without recourse to time-consuming polar bond disconnections that are inherently limiting in terms of accessible chemical space. The scalability of this new reaction sequence is demonstrated, alongside direct applications to known patented structures. A simple user guide is also presented to accelerate adoption of this strategy in medicinal chemistry and related fields.

DOI: 10.1038/s41557-025-01990-x

Source: https://www.nature.com/articles/s41557-025-01990-x