Studies on intramolecular Diels-Alder reactions of furo[3,4-c]pyridines in the synthesis of conformationally restricted analogues of nicotine and anabasine

J Org Chem. 2003 May 30;68(11):4206-14. doi: 10.1021/jo026555p.

Abstract

En route to conformationally restricted analogues of nicotine and anabasine, a novel synthetic route to bridged anabasines is described that hinges on a domino intramolecular [4 + 2]-cycloaddition/ring opening-elimination sequence of 3-amino-substituted furo[3,4-c]pyridines. Extension of this route to bridged nicotines, however, proved abortive, even when the dienophile tether is activated by a p-tolylsulfonyl group or when the diene moiety is activated by an electron-releasing methoxy substituent. A detailed density functional theoretical study (B3LYP/6-31+G) was undertaken to provide insight into the factors that facilitate an intramolecular Diels-Alder reaction in the former case.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anabasine* / analogs & derivatives
  • Anabasine* / chemical synthesis
  • Anabasine* / chemistry
  • Catalysis
  • Combinatorial Chemistry Techniques
  • Cyclization
  • Indicators and Reagents
  • Models, Theoretical*
  • Molecular Conformation
  • Molecular Structure
  • Nicotine* / analogs & derivatives
  • Nicotine* / chemical synthesis
  • Nicotine* / chemistry
  • Nuclear Magnetic Resonance, Biomolecular
  • Pyridines / chemical synthesis*
  • Pyridines / chemistry

Substances

  • Indicators and Reagents
  • Pyridines
  • Nicotine
  • Anabasine