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

Research output: Contribution to journal › Article › peer-review

29 Citations (SciVal)

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

Access to Document

10.1021/jo200528s

Cite this

@article{7cc33e77f70e43a7aa1d113b4acf9582,

title = "Asymmetric Strecker Synthesis of alpha-Arylglycines",

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}",

year = "2011",

month = aug,

day = "5",

doi = "10.1021/jo200528s",

language = "English",

volume = "76",

pages = "6038--6047",

journal = "Journal of Organic Chemistry",

issn = "0022-3263",

publisher = "American Chemical Society",

number = "15",

}

TY - JOUR

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.

UR - http://www.scopus.com/inward/record.url?scp=79961064173&partnerID=8YFLogxK

UR - http://dx.doi.org/10.1021/jo200528s

U2 - 10.1021/jo200528s

DO - 10.1021/jo200528s

M3 - Article

SN - 0022-3263

VL - 76

SP - 6038

EP - 6047

JO - Journal of Organic Chemistry

JF - Journal of Organic Chemistry

IS - 15

ER -

Asymmetric Strecker Synthesis of alpha-Arylglycines

Abstract

Access to Document

Other files and links

Fingerprint

Cite this