Catalytic Asymmetric Cyclopropanations with Nonstabilized Carbenes

J Am Chem Soc. 2023 May 3;145(17):9441-9447. doi: 10.1021/jacs.3c01949. Epub 2023 Apr 22.

Abstract

Cyclopropanes are common building blocks in pharmaceuticals, agrochemicals, and organic materials. The most general methods for the synthesis of chiral cyclopropanes are catalytic additions of diazoalkanes to alkenes. However, a limitation of this approach is that diazoalkanes can only be safely handled on preparative scales if they possess stabilizing substituents. Here we show that gem-dichloroalkanes can serve as precursors to nonstabilized carbenes for asymmetric cyclopropanation reactions of alkenes. The process uses a cobalt catalyst and is proposed to involve the formation of a cationic carbenoid species bearing structural resemblance to the Simmons-Smith reagent. High levels of enantioselectivity are observed for monosubstituted, 1,1-disubstituted, and internal alkenes. The reaction is compatible with alkyl-substituted carbenes, which are susceptible to undergoing competing 1,2-hydride shifts.