Collective Synthesis of Chiral Tetrasubstituted Cyclobutanes Enabled by Enantioconvergent Negishi Cross-Coupling of Cyclobutenones

Abstract

Cyclobutenones provide a straightforward four-carbon ring platform for further structural elaborations in that every carbon atom of the ring could be potentially functionalized. We report here a nickel catalyzed enantioconvergent Negishi coupling of 4-iodocyclobutenones with an array of aryl or alkenyl zinc reagents to access enantioenriched 4-substituted cyclobutenones, from which a modular approach to the synthesis of 1,2,3,4-tetrasubstituted cyclobutanes was demonstrated.

Keywords: Collective Synthesis; Enantioconvergent; Negishi Coupling; Strained Molecules; Tetrasubstituted Cyclobutane.