Organocatalytic asymmetric Michael addition of aliphatic aldehydes to indolylnitroalkenes: access to contiguous stereogenic tryptamine precursors

J Org Chem. 2013 Mar 15;78(6):2362-72. doi: 10.1021/jo3024945. Epub 2013 Feb 21.

Abstract

Because of the importance of the indole framework and the versatile transformation of nitro and formyl groups, the efficient synthesis of optically pure 2-alkyl-3-(1H-indol-3-yl)-4-nitrobutanals, one type of tryptamine precursors are of great interest for pharmaceutical and biological research. Herein, the Michael addition of aliphatic aldehydes to indolylnitroalkenes has been developed using (S)-diphenylprolinol trimethylsilyl ether as an organocatalyst, which provides the desired optically pure syn 2-alkyl-3-(1H-indol-3-yl)-4-nitrobutanal derivatives in up to 98% yield with up to >99:1 dr and >99% ee. To show the synthetic usefulness of this methodology, optically active 2-alkyl-4-nitro-3-(1-tosyl-1H-indol-3-yl)butan-1-ol and tryptamine derivatives are readily obtained by stepwise systematic transformations.

MeSH terms

  • Aldehydes / chemistry*
  • Catalysis
  • Fatty Acids / chemistry*
  • Indoles / chemistry*
  • Molecular Structure
  • Nitro Compounds / chemistry*
  • Stereoisomerism
  • Tryptamines / chemistry*

Substances

  • Aldehydes
  • Fatty Acids
  • Indoles
  • Nitro Compounds
  • Tryptamines
  • tryptamine