Asymmetric Strecker Synthesis of α-Arylglycines

• Published in: Journal of organic chemistry Vol. 76; no. 15; pp. 6038 - 6047
• Main Authors: Pérez-Fuertes, Yolanda, Taylor, James E, Tickell, David A, Mahon, Mary F, Bull, Steven D, James, Tony D
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 05.08.2011; Amer Chemical Soc
• Subjects: Benzaldehydes - chemistry; Boronic Acids - chemistry; Chemistry; Chemistry, Organic; Condensed benzenic and aromatic compounds; Esters; Exact sciences and technology; Glycine - analogs & derivatives; Glycine - chemical synthesis; Glycine - chemistry; Hydrolysis; Magnetic Resonance Spectroscopy; Molecular Structure; Noncondensed benzenic compounds; Organic chemistry; Physical Sciences; Preparations and properties; Science & Technology; Stereoisomerism; CHIRAL DERIVATIZATION PROTOCOLS; OPTICALLY-ACTIVE ARYLGLYCINES; ENANTIOSELECTIVE SYNTHESIS; AMINO-ACIDS; ONE-POT; ENANTIOMERIC PURITY; BIS-LACTIM ETHER; NMR ANALYSIS; HIGHLY DIASTEREOSELECTIVE SYNTHESIS; SOLVENT-FREE SYNTHESIS; Hydrogen Chlorides; Nitrile; Multicomponent reaction; NMR spectrometry; Imine; Thermal reaction; Sodium Cyanides; Aldehyde; Derivatization; Glycine; Hydrogen 1; Hydrolysis; Ester; α-Aminoacid; Chiral auxiliary; Asymmetric synthesis; Aminoacid; Phenols; Cleavage; Optical purity; Strecker synthesis; Aromatic compound; Aqueous solution; Aminonitrile
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo200528s

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 1H NMR spectroscopic analysis of the resultant mixtures of diastereomeric iminoboronate esters.