Facile reductive amination of aldehydes with electron-deficient anilines by acyloxyborohydrides in TFA: application to a diazaindoline scale-up

J Org Chem. 2009 May 1;74(9):3587-90. doi: 10.1021/jo900157z.

Abstract

A scale-up of diazaindoline 1 was achieved in four stages and 32% overall yield. The key step involved rapid reductive amination of aldehyde 8 with aniline 5 by sodium triacetoxyborohydride (STAB-H) and TFA followed by ring closure of intermediate amine 9 to compound 1 in the same pot. These reaction conditions were also applied to facile reductive aminations with anilines known to have little reactivity under STAB-H/AcOH conditions. Spectral data supported the tris(trifluoroacetoxy)borohydride anion (16) as the active reducing agent.

MeSH terms

  • Aldehydes / chemistry*
  • Amination
  • Aniline Compounds / chemistry*
  • Aza Compounds / chemistry*
  • Boranes / chemistry*
  • Electrons*
  • Fluorenes / chemistry*
  • Indoles / chemistry*
  • Oxidation-Reduction

Substances

  • Aldehydes
  • Aniline Compounds
  • Aza Compounds
  • Boranes
  • Fluorenes
  • Indoles
  • trifluorenylamine
  • aniline