转自：康龙化成
Flow Electroreductive Nickel-Catalyzed Cyclopropanation of Alkenes Using gem-Dichloroalkanes
MorganRegnier, Clara Vega, Dimitris I. Ioannou, Zhenyu Zhang, TimothyNoël*
Flow Chemistry Group, Van ’t HoffInstitute for Molecular Sciences (HIMS), University of Amsterdam, Science Park904, 1098 XH Amsterdam, The Netherlands
—Angew. Chem. Int. Ed. 2025, 10.1002/anie.202500203
Recommended by Rui Jin _ MC5
KEYWORDS: electro chemistry,flow chemistry,cyclopropanation, Ni catalysis (反应类型), C(sp3)- C(sp3)- C(sp3)(成键类型), alkenes (原料), gem-dichloroalkanes (原料), cyclopropanes (产物)
ABSTRACT: Cyclopropanesare valuable motifs in organic synthesis, widely featured in pharmaceuticalsand functional materials. Herein, Prof. Timothy Noël et al. report an efficientelectrochemical methodology for the cyclopropanation ofalkenes, leveraging a nickel-catalyzed process in continuous-flow. Thedeveloped protocol demonstrates broad substrate scope, accommodating bothelectron-rich and electron-poor alkenes with high functional group tolerance.Beyond dichloromethane as a feedstock methylene source, the methodology enablesthe synthesis of methylated, deuterated, and chlorosubstituted cyclopropanes. Mechanistic investigations suggest the electro-generation of anickel carbene as key intermediate. Notably, the reaction operates underambient conditions, tolerates air and moisture, and achieves scalabilitythrough continuous-flow technology, offering a straightforward route tomulti-gram quantities with enhanced throughput.
Background and this work
Scope of the flow electroreductive nickel-catalyzed cyclopropanation ofalkenes (selected examples)
Substrate scope of Scope of the flow electroreductive nickel-catalyzed methylation of cyclic enones
Proposed mechanism
Prof. Timothy Noël et al. havedeveloped an efficient and practical electrochemical cyclopropanation method in continuous-flow.The substrate scope encompasses a wide range of electron-poor and electron-richalkenes, demonstrating high functional group tolerance. Moreover, themethodology extends beyond simple dichloromethane to enable the synthesis ofmethylated, deuterated, and chloro-substituted cyclopropanes. Our findingsstrongly support that this novel cyclopropanation process operates via the reductive in-situ generation ofnickel carbenes.We believe this method represents an advancement for the rapid synthesis ofhigh-value cyclopropanes, as it can be performed under ambient conditions,including in the presence of air and moisture. Furthermore, its compatibilitywith continuous-flowtechnology enables scalability to multi-gram scales,offering enhanced throughput compared to existing protocols usingdichloromethane as a methylene source.
阿姆斯特丹大学TimothyNoël教授课题组开发了一种高效实用的流体电化学环丙烷化反应。该方法的底物范围广，官能团耐受性高，不受空气和水分的影响，可适用于多种缺电子和富电子的烯烃。除了二氯甲烷外，还可以使用其他C1卡宾前体用于合成甲基化、氘代及氯取代的环丙烷。机理研究表明该反应通过原位还原生成镍卡宾中间体进行。此外，该反应与连续流动技术结合能够实现多克级规模的放大生产，与现有的环丙烷化反应提高了产量与效率。
（转自：康龙化成）
