Regnier Morgan, Vega Clara, Ioannou Dimitris I, Zhang Zhenyu, Noël Timothy
Flow Chemistry Group, Van't Hoff Institute for Molecular Sciences (HIMS), University of Amsterdam, Science Park 904, 1098 XH, Amsterdam, The, Netherlands.
Angew Chem Int Ed Engl. 2025 Apr 7;64(15):e202500203. doi: 10.1002/anie.202500203. Epub 2025 Feb 10.
Cyclopropanes are valuable motifs in organic synthesis, widely featured in pharmaceuticals and functional materials. Herein, we report an efficient electrochemical methodology for the cyclopropanation of alkenes, leveraging a nickel-catalyzed process in continuous-flow. The developed protocol demonstrates broad substrate scope, accommodating both electron-rich and electron-poor alkenes with high functional group tolerance. Beyond dichloromethane as a feedstock methylene source, the methodology enables the synthesis of methylated, deuterated, and chloro-substituted cyclopropanes. Mechanistic investigations suggest the electro-generation of a nickel carbene as key intermediate. Notably, the reaction operates under ambient conditions, tolerates air and moisture, and achieves scalability through continuous-flow technology, offering a straightforward route to multi-gram quantities with enhanced throughput.
环丙烷是有机合成中有价值的结构单元，广泛存在于药物和功能材料中。在此，我们报告了一种高效的电化学方法用于烯烃的环丙烷化反应，该方法利用了连续流动体系中的镍催化过程。所开发的方案展示了广泛的底物范围，对富电子和贫电子烯烃均适用，且具有高官能团耐受性。除了二氯甲烷作为原料亚甲基源外，该方法还能够合成甲基化、氘代和氯代环丙烷。机理研究表明，镍卡宾的电生成是关键中间体。值得注意的是，该反应在环境条件下进行，耐受空气和水分，并通过连续流动技术实现了可扩展性，提供了一条直接制备多克量产物且提高通量的途径。
