Hale Emma A, Zhu Qilei
Department of Chemistry, University of Utah 315 S 1400 E Salt Lake City UT 84112 USA
Chem Sci. 2025 Jul 17. doi: 10.1039/d5sc03101j.
Although amines and nitrogen-containing heterocycles are prominent scaffolds in bioactive compounds, functional materials, and commodity chemicals, their synthesis and functionalization often suffer from lengthy pre-installation of the appropriate functional groups, employing exotic amination/aziridination reagents and the use of expensive or toxic catalysts. Herein, we developed a mild and economical electrochemical amination method to access aziridine, pyrrolidine and oxazoline motifs from the corresponding amino alcohol substrates. Compared to the classic Mitsunobu reaction, this method exhibits an expanded scope of nucleophiles, including weakly acidic amides and primary amines. Mechanistic studies provided direct evidence for the proposed two-electron oxidation of alcohol and PPh to yield the alkoxyphosphonium cation intermediate. This reaction demonstrates the potential of using electrochemistry to not only replace azo-oxidants in classic Mitsunobu reactions, but also improve the synthetic applicability by overcoming the p limit due to the azo-derived betaine intermediate.
尽管胺类和含氮杂环是生物活性化合物、功能材料和日用化学品中的重要骨架，但其合成和官能团化常常因需要预先长时间安装合适的官能团、使用奇特的胺化/氮丙啶化试剂以及使用昂贵或有毒的催化剂而受到困扰。在此，我们开发了一种温和且经济的电化学胺化方法，可从相应的氨基醇底物制备氮丙啶、吡咯烷和恶唑啉结构单元。与经典的 Mitsunobu 反应相比，该方法显示出亲核试剂范围的扩展，包括弱酸性酰胺和伯胺。机理研究为所提出的醇和三苯基膦的双电子氧化生成烷氧基鏻阳离子中间体提供了直接证据。该反应证明了利用电化学不仅可以替代经典 Mitsunobu 反应中的偶氮氧化剂，还可以通过克服偶氮衍生的甜菜碱中间体导致的 p 限制来提高合成适用性。
