A synthesis of 6-azabicyclo[3.2.1]octanes. The role of N-substitution

J Org Chem. 2008 Feb 15;73(4):1462-7. doi: 10.1021/jo702444c. Epub 2008 Jan 23.

Abstract

The intramolecular cyclization reactions of aziridines with pi-nucleophiles can be a useful route to a number of heterocyclic and carbocyclic ring systems. We were particularly interested in the use of this cyclization reaction for the synthesis of 6-azabicyclo[3.2.1]octanes. We report here the development of a new synthesis of the aziridine necessary for the aziridine--pi-nucleophile cyclization. We also report on the cyclization of aziridines with three different substitutions on the aziridine nitrogen. We have found that N-diphenylphospinyl and N-H aziridines, while participating in the initial ring-opening reaction, do not lead to the desired bicyclic ring systems. In contrast, a nosyl group on the aziridine nitrogen leads efficiently to the bicyclic ring system and can be readily deprotected.

Publication types

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

MeSH terms

  • Bridged Bicyclo Compounds / chemical synthesis*
  • Bridged Bicyclo Compounds / chemistry
  • Magnetic Resonance Spectroscopy
  • Mass Spectrometry
  • Octanes / chemical synthesis*
  • Octanes / chemistry
  • Spectrophotometry, Infrared

Substances

  • Bridged Bicyclo Compounds
  • Octanes