Stereocontrolled synthesis of trisubstituted cyclopropanes: expedient, atom-economical, asymmetric syntheses of (+)-Bicifadine and DOV21947

Org Lett. 2006 Aug 17;8(17):3885-8. doi: 10.1021/ol061650w.

Abstract

[reaction: see text] An expedient, atom-economical, asymmetric synthesis of 1-aryl-3-azabicyclo[3.1.0]hexanes, including (+)-Bicifadine and DOV21947, in a single-stage through process without isolation of any intermediates has been developed. The key of this synthesis is the in-depth mechanistic understanding of the complicated epoxy nitrile coupling at each reaction stage. Therefore, the desired trisubstituted cyclopropane can be prepared in high ee and yield by controlling the reaction pathway through manipulating the nitrile anion aggregation state.

MeSH terms

  • Aza Compounds / chemical synthesis*
  • Aza Compounds / chemistry
  • Bridged Bicyclo Compounds, Heterocyclic / chemical synthesis*
  • Bridged Bicyclo Compounds, Heterocyclic / chemistry
  • Cyclopropanes / chemical synthesis*
  • Cyclopropanes / chemistry
  • Molecular Structure
  • Nitriles / chemistry
  • Stereoisomerism

Substances

  • 1-(3,4-dichlorophenyl)-3-azabicyclo-(3.1.0)hexane hydrochloride
  • Aza Compounds
  • Bridged Bicyclo Compounds, Heterocyclic
  • Cyclopropanes
  • Nitriles
  • bicifadine