Electroreductive intramolecular coupling of aromatic beta- and gamma-imino esters: a new synthetic method for N-alkoxycarbonyl-2-aryl-3-ones and cis-2-aryl-3-ols of pyrrolidines and piperidines

J Org Chem. 2004 Oct 29;69(22):7710-9. doi: 10.1021/jo0488917.

Abstract

The electroreduction of aromatic beta- and gamma-imino esters prepared from beta-alanine and GABA in the presence of chlorotrimethylsilane and subsequent N-alkoxycarbonylation of the resulting five- and six-membered cyclized amines gave mixed ketals of N-alkoxycarbonyl-2-arylpyrrolidin-3-ones and 2-arylpiperidin-3-ones, respectively. The best result of the electroreductive intramolecular coupling was achieved using Bu(4)NClO(4) as a supporting electrolyte and a Pb cathode in THF. Acid hydrolysis of the mixed ketals afforded N-alkoxycarbonyl-2-arylpyrrolidin-3-ones and 2-arylpiperidin-3-ones in good yields. The reduction of these ketones with NaBH(4) in methanol afforded the corresponding N-alkoxycarbonyl-cis-2-arylpyrrolidin-3-ols and cis-2-arylpiperidin-3-ols diastereospecifically.

MeSH terms

  • Amines / chemistry
  • Catalysis
  • Esters / chemistry
  • Imino Acids / chemistry*
  • Molecular Structure
  • Oxidation-Reduction
  • Piperidines / chemical synthesis*
  • Pyrrolidines / chemical synthesis*
  • Stereoisomerism
  • beta-Alanine / chemistry
  • gamma-Aminobutyric Acid / chemistry

Substances

  • Amines
  • Esters
  • Imino Acids
  • Piperidines
  • Pyrrolidines
  • beta-Alanine
  • gamma-Aminobutyric Acid