Asymmetric Strecker Synthesis of alpha-Arylglycines

Y Perez-Fuertes; James E Taylor; David A Tickell; Mary F Mahon; Steven D Bull; Tony D James

doi:10.1021/jo200528s

Asymmetric Strecker Synthesis of alpha-Arylglycines

Y Perez-Fuertes, James E Taylor, David A Tickell, Mary F Mahon, Steven D Bull, Tony D James

Department of Chemistry

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24 Citations (Scopus)

Abstract

A practically simple three-component Strecker reaction for the asymmetric synthesis of enantiopure alpha-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)-alpha-aminonitriles that are easily obtained in diastereomerically pure form. Heating the resultant (S,S)-alpha-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)-alpha-arylglycines. The enantiopurities of these (S)-a-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.

Original language	English
Pages (from-to)	6038-6047
Number of pages	10
Journal	Journal of Organic Chemistry
Volume	76
Issue number	15
DOIs	https://doi.org/10.1021/jo200528s
Publication status	Published - 5 Aug 2011

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Perez-Fuertes, Y., Taylor, J. E., Tickell, D. A., Mahon, M. F., Bull, S. D., & James, T. D. (2011). Asymmetric Strecker Synthesis of alpha-Arylglycines. Journal of Organic Chemistry, 76(15), 6038-6047. https://doi.org/10.1021/jo200528s

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abstract = "A practically simple three-component Strecker reaction for the asymmetric synthesis of enantiopure alpha-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)-alpha-aminonitriles that are easily obtained in diastereomerically pure form. Heating the resultant (S,S)-alpha-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)-alpha-arylglycines. The enantiopurities of these (S)-a-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.",

author = "Y Perez-Fuertes and Taylor, {James E} and Tickell, {David A} and Mahon, {Mary F} and Bull, {Steven D} and James, {Tony D}",

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T1 - Asymmetric Strecker Synthesis of alpha-Arylglycines

AU - Perez-Fuertes, Y

AU - Taylor, James E

AU - Tickell, David A

AU - Mahon, Mary F

AU - Bull, Steven D

AU - James, Tony D

PY - 2011/8/5

Y1 - 2011/8/5

N2 - A practically simple three-component Strecker reaction for the asymmetric synthesis of enantiopure alpha-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)-alpha-aminonitriles that are easily obtained in diastereomerically pure form. Heating the resultant (S,S)-alpha-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)-alpha-arylglycines. The enantiopurities of these (S)-a-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.

AB - A practically simple three-component Strecker reaction for the asymmetric synthesis of enantiopure alpha-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)-alpha-aminonitriles that are easily obtained in diastereomerically pure form. Heating the resultant (S,S)-alpha-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)-alpha-arylglycines. The enantiopurities of these (S)-a-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.

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10.1021/jo200528s