Asymmetric Strecker synthesis of α-arylglycines

J Org Chem. 2011 Aug 5;76(15):6038-47. doi: 10.1021/jo200528s. Epub 2011 Jun 27.

Abstract

A practically simple three-component Strecker reaction for the asymmetric synthesis of enantiopure α-arylglycines has been developed. Addition of a range of aryl-aldehydes to a solution of sodium cyanide and (S)-1-(4-methoxyphenyl)ethylamine affords highly crystalline (S,S)-α-aminonitriles that are easily obtained in diastereomerically pure form. Heating the resultant (S,S)-α-aminonitriles in 6 M aqueous HCl at reflux resulted in cleavage of their chiral auxiliary fragments and concomitant hydrolysis of their nitrile groups to afford enantiopure (S)-α-arylglycines. The enantiopurities of these (S)-α-arylglycines were determined via derivatization of their corresponding methyl esters with 2-formylphenylboronic acid and (S)-BINOL, followed by (1)H NMR spectroscopic analysis of the resultant mixtures of diastereomeric iminoboronate esters.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Benzaldehydes / chemistry*
  • Boronic Acids / chemistry*
  • Esters
  • Glycine / analogs & derivatives
  • Glycine / chemical synthesis*
  • Glycine / chemistry*
  • Hydrolysis
  • Magnetic Resonance Spectroscopy
  • Molecular Structure
  • Stereoisomerism

Substances

  • 2-formylphenylboronic acid
  • Benzaldehydes
  • Boronic Acids
  • Esters
  • Glycine