Origins of opposite syn-anti diastereoselectivities in primary and secondary amino acid-catalyzed intermolecular aldol reactions involving unmodified alpha-hydroxyketones

J Org Chem. 2008 Jul 18;73(14):5264-71. doi: 10.1021/jo800089q. Epub 2008 Jun 13.

Abstract

The effects of different amino acid catalysts on the stereoselectivity of the direct intermolecular aldol reactions between alpha-hydroxyketones and isobutyraldehyde or 4-nitrobenzaldehyde have been studied with the aid of density functional theory methods. The transition states of the crucial C-C bond-forming step with the enamine intermediate addition to the aldehyde for the proline and threonine-catalyzed asymmetric aldol reactions are reported. B3LYP/6-31+G** calculations provide a good explanation for the opposite syn vs anti diastereoselectivity of these two kinds of amino acid catalysts (anti-selectivity for the secondary cyclic amino acids proline, syn-selectivity for the acyclic primary amino acids like threonine). Calculated and observed diastereomeric ratio and enantiomeric excess values are in good agreement.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aldehydes / chemistry*
  • Amino Acids / chemistry*
  • Catalysis
  • Hydroxylation
  • Ketones / chemistry*
  • Models, Molecular
  • Molecular Structure
  • Stereoisomerism

Substances

  • Aldehydes
  • Amino Acids
  • Ketones
  • 3-hydroxybutanal