Highly enantioselective Henry (nitroaldol) reaction of aldehydes and alpha-ketoesters catalyzed by N,N'-dioxide-copper(I) complexes

J Org Chem. 2007 Nov 23;72(24):9323-8. doi: 10.1021/jo701898r. Epub 2007 Nov 1.

Abstract

A new chiral N,N'-dioxide-Cu(I) catalyst has been developed for the asymmetric Henry (nitroaldol) reaction. The approach benefited from the easy modification of the chiral space. As the highly effective N-oxide ligand, 1d has been adopted for the Henry reaction with both aromatic and heteroaromatic aldehydes. The corresponding nitro-alcohol products were obtained in good yields with high enantiomeric excesses up to 98%. Moreover, alpha-ketoesters were also catalyzed by this catalyst to give attractive optically active alpha-hydroxy beta-nitro esters containing chiral quaternary carbon centers (up to 99% ee). On the basis of a combination of several techniques including the 1H NMR, ESI-HRMS, and MM2 calculations, the proposed mechanism was presented to explain the origin of reactivity and asymmetric inductivity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aldehydes / chemistry*
  • Algorithms
  • Catalysis
  • Copper / chemistry*
  • Esters / chemistry*
  • Ketones / chemistry*
  • Ligands
  • Magnetic Resonance Spectroscopy
  • Nitro Compounds / chemistry*
  • Organometallic Compounds / chemistry*
  • Oxides / chemistry*
  • Spectrometry, Mass, Electrospray Ionization

Substances

  • Aldehydes
  • Esters
  • Ketones
  • Ligands
  • Nitro Compounds
  • Organometallic Compounds
  • Oxides
  • Copper