Flow Electroreductive Nickel‐Catalyzed Cyclopropanation of Alkenes Using <i>gem</i>‐Dichloroalkanes
Morgan Regnier, Clara Vega, Dimitris I. Ioannou, Zhenyu Zhang, Timothy Noël
Abstract
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.