Liu Min, Wang Yanwei, Gao Chao, Jia Jingpei, Zhu Zile, Qiu Youai
State Key Laboratory and Institute of Elemento-Organic Chemistry, Frontiers Science Center for New Organic Matter, Haihe Laboratory of Sustainable Chemical Transformations, College of Chemistry, Nankai University, 94 Weijin Road, Tianjin, 300071, China.
Angew Chem Int Ed Engl. 2025 Feb 24;64(9):e202425634. doi: 10.1002/anie.202425634. Epub 2025 Feb 5.
Cyclopropanes are prevalent in natural products, pharmaceuticals, and bioactive compounds, functioning as a significant structural motif. Although a series of methods have been developed for the construction of the cyclopropane skeleton, the development of a direct and efficient strategy for the rapid synthesis of cyclopropanes from bench-stable starting materials with a broad substrate scope and functional group tolerance remains challenging and highly desirable. Herein, we present an electrochemical method for the direct cyclopropanation of unactivated alkenes using active methylene compounds. The strategy shows a broad substrate scope with a high level of functional group compatibility, as well as potential application as demonstrated by late-stage cyclopropanation of complex molecules and drug derivatives. Further mechanistic investigations suggest that CpFe (Fc) plays an essential role as an oxidative mediator in generating radicals from active methylene compounds.
环丙烷广泛存在于天然产物、药物和生物活性化合物中，是一种重要的结构基序。尽管已经开发了一系列构建环丙烷骨架的方法，但从易于储存的起始原料出发，开发一种直接、高效、能快速合成环丙烷且具有广泛底物范围和官能团耐受性的策略仍然具有挑战性且非常必要。在此，我们报道了一种电化学方法，该方法使用活性亚甲基化合物对未活化的烯烃进行直接环丙烷化反应。该策略具有广泛的底物范围和高度的官能团兼容性，并且在复杂分子和药物衍生物的后期环丙烷化反应中展示了其潜在应用。进一步的机理研究表明，CpFe（Fc）作为氧化介质，在从活性亚甲基化合物生成自由基的过程中起着至关重要的作用。
