Organomagnesium Based Flash Chemistry: Continuous Flow Generation and Utilization of Halomethylmagnesium Intermediates.

Timo Von Keutz,David Cantillo,C Oliver Kappe

doi:10.1021/acs.orglett.0c02725

Abstract

The generation of highly unstable chloromethylmagnesium chloride in a continuous flow reactor and its reaction with aldehydes and ketones is reported. With this strategy, chlorohydrins and epoxides were synthesized within a total residence time of only 2.6 s. The outcome of the reaction can be tuned by simply using either a basic or an acidic quench. Very good to excellent isolated yields, up to 97%, have been obtained for most cases (30 examples).

Highlights

The generation of highly unstable chloromethylmagnesium chloride in a continuous flow reactor and its reaction with aldehydes and ketones is reported
Organolithium and organomagnesium compounds were developed at the onset of the past century and are arguably the two most commonly employed organometallic species.[3,4]
The generation of several unstable halomethyl lithium species has been reported during the past years

Summary

Corresponding Authors

David Cantillo − Institute of Chemistry, University of Graz, 8010 Graz, Austria; Center for Continuous Flow Synthesis and Processing (CC FLOW), Research Center Pharmaceutical Engineering GmbH (RCPE), 8010 Graz, Austria; orcid.org/0000-0001-7604-8711; Email: david.cantillo@ uni-graz.at. C. Oliver Kappe − Institute of Chemistry, University of Graz, 8010 Graz, Austria; Center for Continuous Flow Synthesis and Processing (CC FLOW), Research Center Pharmaceutical Engineering GmbH (RCPE), 8010 Graz, Austria; orcid.org/0000-0003-2983-6007; Email: oliver.kappe@ uni-graz.at. Continuous addition of a solution containing an aldehyde or a ketone resulted in a highly selective protocol for the preparation of 1aryl chlorohydrins 2 or 2-aryl epoxides 3, depending on the acid or basic character of the reaction quench employed. Timo von Keutz − Institute of Chemistry, University of Graz, 8010 Graz, Austria; Center for Continuous Flow Synthesis and Processing (CC FLOW), Research Center Pharmaceutical Engineering GmbH (RCPE), 8010 Graz, Austria.

■ ACKNOWLEDGMENTS

Findings

■ REFERENCES