Rapid and Safe Continuous-Flow Simmons-Smith Cyclopropanation using a Zn/Cu Couple Column

Flow chemistry has recently opened new chemistry windows thanks to the safer use of hazardous and sensitive reagents. Furthermore, flow procedures usually outperform their batch counterparts due to improved mass and heat transfer, offering a good opportunity for industrial application. Herein, a rapid Simmons-Smith cyclopropanation flow process is presented. Taking advantage of the in situ production of the zinc carbenoid species, several olefins bearing aromatic rings of different electronic nature, aliphatic chains or heterocycles were smoothly cyclopropanated with a residence time of just 15 minutes. In addition, industrial applicability of the protocol is assured thanks to a successful 12-mmol scale experiment, which represents a 3.59 grams per hour production of a selected example, and to the satisfactory synthesis of pharmaceutical drugs. image

Automated summary

Flow chemistry has opened new chemistry windows by enabling the safer use of hazardous and sensitive reagents. It outperforms batch counterparts due to improved mass and heat transfer, offering great potential for industrial application.