Stereoselective Synthesis of Either Exo- or Endo-3-Azabicyclo[3.1.0]hexane-6-carboxylates by Dirhodium(II)-Catalyzed Cyclopropanation with Ethyl Diazoacetate under Low Catalyst Loadings.

Abstract

Although cyclopropanation with donor/acceptor carbenes can be conducted under low catalyst loadings (<0.001 mol %), such low loading has not been generally effective for other classes of carbenes such as acceptor carbenes. In this current study, we demonstrate that ethyl diazoacetate can be effectively used in the cyclopropanation of N-Boc-2,5-dihydropyrrole with dirhodium(II) catalyst loadings of 0.005 mol %. By appropriate choice of catalyst and hydrolysis conditions, either the exo- or endo-3-azabicyclo[3.1.0]hexanes can be formed cleanly with high levels of diastereoselectivity with no chromatographic purification.