Gold-catalyzed intramolecular allylic amination of 2-tosylaminophenylprop-1-en-3-ols. A concise synthesis of (+/-)-angustureine

J Org Chem. 2009 Aug 21;74(16):5947-52. doi: 10.1021/jo900917q.

Abstract

An efficient synthetic route to 1,2-dihydroquinolines that relies on AuCl(3)/AgSbF(6)-catalyzed intramolecular allylic amination of 2-tosylaminophenylprop-1-en-3-ols is described herein. Uniquely, the reactions were found to only proceed rapidly at room temperature in the presence of the gold and silver catalyst combination and produce the 1,2-dihydroquinoline products in yields of 40-91%. The method was shown to be applicable to a broad range of 2-tosylaminophenylprop-1-en-3-ols containing electron-withdrawing, electron-donating, and sterically demanding substrate combinations. The mechanism is suggested to involve activation of the alcohol substrate by the AuCl(3)/AgSbF(6) catalyst. This is followed by ionization of the starting material, which causes intramolecular nucleophilic addition of the sulfonamide unit to the allylic cation moiety and construction of the 1,2-dihydroquinoline. The utility of this N-heterocyclic ring forming strategy as a synthetic tool that makes use of alcohols as pro-electrophiles was exemplified by its application to the synthesis of the bioactive tetrahydroquinoline alkaloid (+/-)-angustureine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Propanol / chemistry*
  • Alkaloids / chemical synthesis*
  • Alkaloids / chemistry*
  • Alkenes / chemistry*
  • Amination
  • Catalysis
  • Gold / chemistry*
  • Quinolines / chemical synthesis*
  • Quinolines / chemistry*
  • Quinones / chemistry
  • Silver / chemistry
  • Stereoisomerism
  • Temperature

Substances

  • 1,4-dihydroquinone
  • Alkaloids
  • Alkenes
  • Quinolines
  • Quinones
  • angustureine
  • Silver
  • Gold
  • 1-Propanol