The direct catalytic asymmetric alpha-aminooxylation reaction: development of stereoselective routes to 1,2-diols and 1,2-amino alcohols and density functional calculations

Chemistry. 2004 Aug 6;10(15):3673-84. doi: 10.1002/chem.200400137.

Abstract

Proline-catalyzed direct asymmetric alpha-aminooxylation of ketones and aldehydes is described. The proline-catalyzed reactions between unmodified ketones or aldehydes and nitrosobenzene proceeded with excellent diastereo- and enantioselectivities. In all cases tested, the corresponding products were isolated with >95 % ees. Methyl alkyl ketones were regiospecifically oxidized at the methylene carbon atom to afford enantiomerically pure alpha-aminooxylated ketones. In addition, cyclic ketones could be alpha,alpha'-dioxidized with remarkably high selectivity, furnishing the corresponding diaminooxylated ketones with >99 % ees. The reaction mechanism of the proline-catalyzed direct asymmetric alpha-aminooxylation was investigated, and we performed density functional theory (DFT) calculations in order to investigate the nature of the plausible transition states further. We also screened other organocatalysts for the asymmetric alpha-oxidation reaction and found that several proline derivatives were also able to catalyze the transformation with excellent enantioselectivities. Moreover, stereoselective routes for the synthesis of monoprotected vicinal diols and hydroxyketones were found. In addition, short routes for the direct preparation of enantiomerically pure epoxides and 1,2-amino alcohols are presented. The direct catalytic alpha-oxidation is also a novel route for the stereoselective preparation of beta-adrenoreceptor antagonists.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alcohols / chemical synthesis*
  • Aldehydes / chemistry*
  • Amino Acids / chemistry*
  • Amino Alcohols / chemical synthesis*
  • Catalysis
  • Ketones / chemistry*
  • Models, Molecular
  • Molecular Conformation
  • Molecular Structure
  • Oxidation-Reduction
  • Proline / chemistry
  • Stereoisomerism

Substances

  • Alcohols
  • Aldehydes
  • Amino Acids
  • Amino Alcohols
  • Ketones
  • Proline