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 -