Synthesis of heterocyclic analogues of epibatidine via 7-azabicyclo[2.2.1]hept-2-yl radical intermediates. 1. Intermolecular reactions

J Org Chem. 2008 Sep 5;73(17):6784-92. doi: 10.1021/jo8011094. Epub 2008 Jul 26.

Abstract

The synthesis and reactivity of the 7-azabicyclo[2.2.1]hept-2-yl radical has been extensively investigated in inter- and intramolecular reaction processes for the first time. In this work we will present the preparation of the radical and its successful intermolecular reaction with radical acceptors such as tert-butylisocyanide and acrylonitrile. Computational analyses have been carried out to show and explain the mechanisms and stereochemical outcome of these transformations. Overall and from the chemical point of view, a new and convenient synthetic approach has been developed for the synthesis of exo-2-(cyano)alkyl substituted 7-azabicyclo[2.2.1]heptane derivatives, a series of compounds of wide interest for the synthesis of heterocyclic analogues of epibatidine. As a result, we describe here the synthesis of the tetrazoloepibatidines (8 and 15) and the oxadiazoloepibatidine (10).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acrylonitrile / chemistry
  • Azabicyclo Compounds / chemistry*
  • Bridged Bicyclo Compounds, Heterocyclic / chemical synthesis*
  • Cyanides / chemistry
  • Free Radicals / chemistry*
  • Heptanes / chemistry*
  • Models, Chemical
  • Nicotinic Agonists / chemical synthesis*
  • Pyridines
  • Receptors, Nicotinic / metabolism*
  • Stereoisomerism

Substances

  • Azabicyclo Compounds
  • Bridged Bicyclo Compounds, Heterocyclic
  • Cyanides
  • Free Radicals
  • Heptanes
  • Nicotinic Agonists
  • Pyridines
  • Receptors, Nicotinic
  • epibatidine
  • Acrylonitrile