Alkylation and aldol reactions of acyl derivatives of N-1-(1 '-naphthyl)ethyl-O-tert-butylhydroxylamine: asymmetric synthesis of alpha-alkoxy-, alpha-substituted-beta-alkoxy- and alpha,beta-dialkoxyaldehydes

Alexander N. Chernega; Stephen G. Davies; Ai M. Fletcher; Christopher J. Goodwin; David Hepworth; R. Shyam Prasad; Paul M. Roberts; Edward D. Savory; Andrew D. Smith; James E. Thomson

doi:10.1016/j.tet.2010.03.105

Alkylation and aldol reactions of acyl derivatives of N-1-(1 '-naphthyl)ethyl-O-tert-butylhydroxylamine: asymmetric synthesis of alpha-alkoxy-, alpha-substituted-beta-alkoxy- and alpha,beta-dialkoxyaldehydes

Alexander N. Chernega, Stephen G. Davies, Ai M. Fletcher, Christopher J. Goodwin, David Hepworth, R. Shyam Prasad, Paul M. Roberts, Edward D. Savory, Andrew D. Smith, James E. Thomson

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

Abstract

Treatment of a range of O-protected glycolate derivatives of the chiral auxiliary N-1-(1'-naphthyl)ethyl-O-tert-butylhydroxylamine with KHMDS in the presence of 18-crown-6 followed by addition of an alkyl halide generates alpha-substituted derivatives with very high levels of diastereoselectivity. Alternatively, reaction of the potassium enolate of a propanoate or O-protected glycolate derivative of N-1-(1'-naphthyl)ethyl-O-tert-butylhydroxylamine with a range of aldehydes gives syn-aldol products with high levels of diastereoselectivity. These adducts may be reductively cleaved with LiAlH4 to give enantiopure alpha-alkoxy-, alpha-substituted-beta-alkoxy- and alpha,beta-dialkoxyaldehydes in good yield. (C) 2010 Elsevier Ltd. All rights reserved.

Original language	English
Pages (from-to)	4167-4194
Number of pages	28
Journal	Tetrahedron
Volume	66
Issue number	23
DOIs	https://doi.org/10.1016/j.tet.2010.03.105
Publication status	Published - 5 Jun 2010

Keywords

Weinreb amide
Glycolate enolate
Diastereoselective alkylation
Aldol reaction
ACYCLIC STEREOSELECTION
SUPERQUAT ENAMIDES
CARBONYL-COMPOUNDS
GRIGNARD-REAGENTS
CARBOXYLIC-ACIDS
STERIC COURSE
ALLYL ETHERS
ALDEHYDES
GLYCOLATE
ALCOHOLS

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Chernega, A. N., Davies, S. G., Fletcher, A. M., Goodwin, C. J., Hepworth, D., Prasad, R. S., Roberts, P. M., Savory, E. D., Smith, A. D., & Thomson, J. E. (2010). Alkylation and aldol reactions of acyl derivatives of N-1-(1 '-naphthyl)ethyl-O-tert-butylhydroxylamine: asymmetric synthesis of alpha-alkoxy-, alpha-substituted-beta-alkoxy- and alpha,beta-dialkoxyaldehydes. Tetrahedron, 66(23), 4167-4194. https://doi.org/10.1016/j.tet.2010.03.105

@article{bea651ba5c0d4b0cb3522edd758d41d1,

title = "Alkylation and aldol reactions of acyl derivatives of N-1-(1 '-naphthyl)ethyl-O-tert-butylhydroxylamine: asymmetric synthesis of alpha-alkoxy-, alpha-substituted-beta-alkoxy- and alpha,beta-dialkoxyaldehydes",

abstract = "Treatment of a range of O-protected glycolate derivatives of the chiral auxiliary N-1-(1'-naphthyl)ethyl-O-tert-butylhydroxylamine with KHMDS in the presence of 18-crown-6 followed by addition of an alkyl halide generates alpha-substituted derivatives with very high levels of diastereoselectivity. Alternatively, reaction of the potassium enolate of a propanoate or O-protected glycolate derivative of N-1-(1'-naphthyl)ethyl-O-tert-butylhydroxylamine with a range of aldehydes gives syn-aldol products with high levels of diastereoselectivity. These adducts may be reductively cleaved with LiAlH4 to give enantiopure alpha-alkoxy-, alpha-substituted-beta-alkoxy- and alpha,beta-dialkoxyaldehydes in good yield. (C) 2010 Elsevier Ltd. All rights reserved.",

keywords = "Weinreb amide, Glycolate enolate, Diastereoselective alkylation, Aldol reaction, ACYCLIC STEREOSELECTION, SUPERQUAT ENAMIDES, CARBONYL-COMPOUNDS, GRIGNARD-REAGENTS, CARBOXYLIC-ACIDS, STERIC COURSE, ALLYL ETHERS, ALDEHYDES, GLYCOLATE, ALCOHOLS",

author = "Chernega, {Alexander N.} and Davies, {Stephen G.} and Fletcher, {Ai M.} and Goodwin, {Christopher J.} and David Hepworth and Prasad, {R. Shyam} and Roberts, {Paul M.} and Savory, {Edward D.} and Smith, {Andrew D.} and Thomson, {James E.}",

year = "2010",

month = jun,

day = "5",

doi = "10.1016/j.tet.2010.03.105",

language = "English",

volume = "66",

pages = "4167--4194",

journal = "Tetrahedron",

issn = "0040-4020",

publisher = "Elsevier",

number = "23",

}

Chernega, AN, Davies, SG, Fletcher, AM, Goodwin, CJ, Hepworth, D, Prasad, RS, Roberts, PM, Savory, ED, Smith, AD & Thomson, JE 2010, 'Alkylation and aldol reactions of acyl derivatives of N-1-(1 '-naphthyl)ethyl-O-tert-butylhydroxylamine: asymmetric synthesis of alpha-alkoxy-, alpha-substituted-beta-alkoxy- and alpha,beta-dialkoxyaldehydes', Tetrahedron, vol. 66, no. 23, pp. 4167-4194. https://doi.org/10.1016/j.tet.2010.03.105

Alkylation and aldol reactions of acyl derivatives of N-1-(1 '-naphthyl)ethyl-O-tert-butylhydroxylamine: asymmetric synthesis of alpha-alkoxy-, alpha-substituted-beta-alkoxy- and alpha,beta-dialkoxyaldehydes. / Chernega, Alexander N.; Davies, Stephen G.; Fletcher, Ai M. et al.
In: Tetrahedron, Vol. 66, No. 23, 05.06.2010, p. 4167-4194.

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

TY - JOUR

T1 - Alkylation and aldol reactions of acyl derivatives of N-1-(1 '-naphthyl)ethyl-O-tert-butylhydroxylamine: asymmetric synthesis of alpha-alkoxy-, alpha-substituted-beta-alkoxy- and alpha,beta-dialkoxyaldehydes

AU - Chernega, Alexander N.

AU - Davies, Stephen G.

AU - Fletcher, Ai M.

AU - Goodwin, Christopher J.

AU - Hepworth, David

AU - Prasad, R. Shyam

AU - Roberts, Paul M.

AU - Savory, Edward D.

AU - Smith, Andrew D.

AU - Thomson, James E.

PY - 2010/6/5

Y1 - 2010/6/5

N2 - Treatment of a range of O-protected glycolate derivatives of the chiral auxiliary N-1-(1'-naphthyl)ethyl-O-tert-butylhydroxylamine with KHMDS in the presence of 18-crown-6 followed by addition of an alkyl halide generates alpha-substituted derivatives with very high levels of diastereoselectivity. Alternatively, reaction of the potassium enolate of a propanoate or O-protected glycolate derivative of N-1-(1'-naphthyl)ethyl-O-tert-butylhydroxylamine with a range of aldehydes gives syn-aldol products with high levels of diastereoselectivity. These adducts may be reductively cleaved with LiAlH4 to give enantiopure alpha-alkoxy-, alpha-substituted-beta-alkoxy- and alpha,beta-dialkoxyaldehydes in good yield. (C) 2010 Elsevier Ltd. All rights reserved.

AB - Treatment of a range of O-protected glycolate derivatives of the chiral auxiliary N-1-(1'-naphthyl)ethyl-O-tert-butylhydroxylamine with KHMDS in the presence of 18-crown-6 followed by addition of an alkyl halide generates alpha-substituted derivatives with very high levels of diastereoselectivity. Alternatively, reaction of the potassium enolate of a propanoate or O-protected glycolate derivative of N-1-(1'-naphthyl)ethyl-O-tert-butylhydroxylamine with a range of aldehydes gives syn-aldol products with high levels of diastereoselectivity. These adducts may be reductively cleaved with LiAlH4 to give enantiopure alpha-alkoxy-, alpha-substituted-beta-alkoxy- and alpha,beta-dialkoxyaldehydes in good yield. (C) 2010 Elsevier Ltd. All rights reserved.

KW - Weinreb amide

KW - Glycolate enolate

KW - Diastereoselective alkylation

KW - Aldol reaction

KW - ACYCLIC STEREOSELECTION

KW - SUPERQUAT ENAMIDES

KW - CARBONYL-COMPOUNDS

KW - GRIGNARD-REAGENTS

KW - CARBOXYLIC-ACIDS

KW - STERIC COURSE

KW - ALLYL ETHERS

KW - ALDEHYDES

KW - GLYCOLATE

KW - ALCOHOLS

U2 - 10.1016/j.tet.2010.03.105

DO - 10.1016/j.tet.2010.03.105

M3 - Article

SN - 0040-4020

VL - 66

SP - 4167

EP - 4194

JO - Tetrahedron

JF - Tetrahedron

IS - 23

ER -