5(6)-anti-Substituted-2-azabicyclo[2.1.1]hexanes: a nucleophilic displacement route

J Org Chem. 2009 Nov 6;74(21):8232-42. doi: 10.1021/jo901725k.


Nucleophilic displacements of 5(6)-anti-bromo substituents in 2-azabicyclo[2.1.1]hexanes (methanopyrrolidines) have been accomplished. These displacements have produced 5-anti-X-6-anti-Y-difunctionalized-2-azabicyclo[2.1.1]hexanes containing bromo, fluoro, acetoxy, hydroxy, azido, imidazole, thiophenyl, and iodo substituents. Such displacements of anti-bromide ions require an amine nitrogen and are a function of the solvent and the choice of metal salt. Reaction rates were faster and product yields were higher in DMSO when compared to DMF and with CsOAc compared to NaOAc. Sodium or lithium salts gave products, except with NaF, where silver fluoride in nitromethane was best for substitution by fluoride. The presence of electron-withdrawing F, OAc, N(3), Br, or SPh substituents in the 6-anti-position slows bromide displacements at the 5-anti-position.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Azabicyclo Compounds / chemistry*
  • Crystallography, X-Ray
  • Hexanes / chemistry*
  • Magnetic Resonance Spectroscopy
  • Mass Spectrometry


  • Azabicyclo Compounds
  • Hexanes