美国威斯康星大学麦迪逊分校Zachary K. Wickens团队报道了通过电致离子将胺和烯烃偶联形成氮杂环丙烷的策略。相关研究成果发表在2021年6月22日出版的《自然》。
含氮的三元环分子，氮杂环丙烷（Aziridins）是一类重要的合成目标化合物。其显著的环应变和导致的开环反应倾向使它们成为多种胺产品的多功能前体，在某些情况下，氮杂环丙烷官能团本身具有重要的生物（如抗肿瘤）活性。将普遍存在的烯烃转化为氮杂环丙烷是一种很有吸引力的合成策略，但通常使用亲电氮源而不是广泛使用的胺亲核试剂来完成。
该文中，研究人员证明了未活化的烯烃可以电化学转化为亚稳的离子中间体，该中间体在碱性条件下与伯胺发生叠氮杂化反应。该新方法相对于最先进的方法扩大了容易获得的N-烷基氮杂环丙烷产品的范围。该新方法的一个关键的战略优势是，烯烃氧化活化与氮杂环丙烷化步骤解耦，允许多种商用易获得的但对氧化敏感的胺作为这种菌株诱导转化的耦合伙伴。更广泛地说，该工作为使用这种离子池方法的各种不同双功能化反应的多样化应用奠定了基础。
附：英文原文
Title: Aziridines by coupling amines and alkenes via an electro-generated dication
Author: Dylan E. Holst, Diana J. Wang, Min Ji Kim, Ilia A. Guzei, Zachary K. Wickens
Issue&Volume: 2021-06-22
Abstract: Aziridines, three-membered nitrogen-containing cyclic molecules, are important synthetic targets. Their significant ring strain and resultant proclivity towards ring opening reactions makes them versatile precursors to diverse amine products1–3 and, in some cases, the aziridine functional group itself imbues important biological (e.g. anti-tumor) activity4–6. Transformation of ubiquitous alkenes into aziridines is an attractive synthetic strategy but is typically accomplished using electrophilic nitrogen sources rather than widely available amine nucleophiles. Here, we demonstrate that unactivated alkenes can be electrochemically transformed into a metastable, dicationic intermediate that undergoes aziridination with primary amines under basic conditions. This new approach expands the scope of readily accessible N-alkyl aziridine products relative to state-of-the-art methods. A key strategic advantage of this new approach is that oxidative alkene activation is decoupled from the aziridination step, allowing a wide range of commercially available but oxidatively sensitive7 amines to act as coupling partners for this strain-inducing transformation. More broadly, this work lays the foundations for a diverse array of difunctionalization reactions using this dication pool approach.
DOI: 10.1038/s41586-021-03717-7
Source: https://www.nature.com/articles/s41586-021-03717-7