Cascade condensation, cyclization, intermolecular dipolar cycloaddition by multi-component coupling and application to a synthesis of (+/-)-crispine A

Org Biomol Chem. 2009 Apr 21;7(8):1674-9. doi: 10.1039/b822743h. Epub 2009 Mar 6.

Abstract

A general approach for the synthesis of various nitrogen-containing heterocyclic compounds is described using an intermolecular dipolar cycloaddition reaction of azomethine ylides and nitrones. Stabilized and non-stabilized azomethine ylide dipoles or the related nitrones were generated by condensation of 4-, 5- or 6-halo-aldehydes with a readily available amino-acid, amino-ester or hydroxylamine to give an imine followed by cyclization and either decarboxylation or loss of a proton. After intermolecular cycloaddition with an activated dipolarophile, bicyclic or polycyclic (if the ylide dipole and/or dipolarophile contain a ring) amines were produced. A short synthesis of the alkaloid (+/-)-crispine A was achieved based on this tandem/domino 3-component coupling chemistry.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aldehydes / chemical synthesis*
  • Aldehydes / chemistry
  • Amines / chemical synthesis
  • Amines / chemistry
  • Azo Compounds / chemical synthesis*
  • Azo Compounds / chemistry
  • Cyclization
  • Heterocyclic Compounds / chemical synthesis*
  • Heterocyclic Compounds / chemistry
  • Isomerism
  • Isoquinolines / chemical synthesis*
  • Isoquinolines / chemistry
  • Nitrogen Oxides / chemical synthesis*
  • Nitrogen Oxides / chemistry
  • Thiosemicarbazones / chemical synthesis*
  • Thiosemicarbazones / chemistry

Substances

  • Aldehydes
  • Amines
  • Azo Compounds
  • Heterocyclic Compounds
  • Isoquinolines
  • Nitrogen Oxides
  • Thiosemicarbazones
  • azomethine
  • crispine A
  • nitrones