Mitsunobu approach to the synthesis of optically active alpha,alpha-disubstituted amino acids

Org Lett. 2009 Feb 19;11(4):807-10. doi: 10.1021/ol802325h.

Abstract

Chiral tertiary alpha-hydroxy esters of known stereochemical configuration were transformed to alpha-azido esters by Mitsunobu reaction with HN3. Optimization of this reaction was shown to proceed at room temperature with high chemical yield using 1,1-(azodicarbonyl)dipiperidine (ADDP) and trimethylphosphine (PMe3). Complete inversion of configuration was observed at the alpha-carbon. Several alpha,alpha-disubstituted amino acids were synthesized in high overall chemical yield and optical purity.

MeSH terms

  • Amino Acids / chemical synthesis*
  • Amino Acids / chemistry*
  • Catalysis
  • Chromatography, High Pressure Liquid
  • Combinatorial Chemistry Techniques*
  • Esters
  • Molecular Structure
  • Piperidines / chemistry
  • Stereoisomerism

Substances

  • 1,1-(azodicarbonyl)dipiperidine
  • Amino Acids
  • Esters
  • Piperidines