Electrochemical Cyclopropanation of Unactivated Alkenes with Methylene Compounds

Abstract

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 Cp₂Fe (Fc) plays an essential role as an oxidative mediator in generating radicals from active methylene compounds.