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
posted on 2024-01-03, 13:05authored byTerrence-Thang
H. Nguyen, Antonio Navarro, J. Craig Ruble, Huw M. L. Davies
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.