Asymmetric synthesis of beta-substituted Baylis-Hillman products via lithium amide conjugate addition

Alexander Chernega; Stephen G. Davies; Dirk. L. Elend; Christian A. P. Smethurst; Paul M. Roberts; Andrew D. Smith; G. Darren Smyth

doi:10.1016/j.tet.2007.05.015

Asymmetric synthesis of beta-substituted Baylis-Hillman products via lithium amide conjugate addition

Alexander Chernega, Stephen G. Davies, Dirk. L. Elend, Christian A. P. Smethurst, Paul M. Roberts, Andrew D. Smith, G. Darren Smyth

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

Abstract

A three-step protocol for the asymmetric synthesis of a range of beta-substituted Baylis-Hillman products has been developed. This procedure involves the diastereoselective conjugate addition of lithium (R)-N-methyl-N-(alpha-methylbenzyl) amide to an alpha, beta-unsaturated ester to generate an N-protected beta-amino ester in high de. Subsequent asymmetric aldol reaction via deprotonation with LDA, transmetallation with B(OMe)(3) and addition of an aldehyde gives a range of syn-aldol products in moderate to high de. Purification of the syn-aldol products to homogeneity followed by tandem N-oxidation and Cope elimination gives the desired b-substituted Baylis-Hillman products in good yield and high de and ee. (C) 2007 Elsevier Ltd. All rights reserved.

Original language	English
Pages (from-to)	7036-7046
Number of pages	11
Journal	Tetrahedron
Volume	63
Issue number	30
DOIs	https://doi.org/10.1016/j.tet.2007.05.015
Publication status	Published - 23 Jul 2007

Keywords

CARBON BOND-FORMATION
COPE ELIMINATION
AMINO ALDEHYDES
ALDOL REACTION
PRESSURE
ADDUCTS
ESTERS
4-OXOAZETIDINE-2-CARBALDEHYDES
EQUIVALENTS
CYCLIZATION

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@article{cacc3510a4bb44eba31abcf0aee1d830,

title = "Asymmetric synthesis of beta-substituted Baylis-Hillman products via lithium amide conjugate addition",

abstract = "A three-step protocol for the asymmetric synthesis of a range of beta-substituted Baylis-Hillman products has been developed. This procedure involves the diastereoselective conjugate addition of lithium (R)-N-methyl-N-(alpha-methylbenzyl) amide to an alpha, beta-unsaturated ester to generate an N-protected beta-amino ester in high de. Subsequent asymmetric aldol reaction via deprotonation with LDA, transmetallation with B(OMe)(3) and addition of an aldehyde gives a range of syn-aldol products in moderate to high de. Purification of the syn-aldol products to homogeneity followed by tandem N-oxidation and Cope elimination gives the desired b-substituted Baylis-Hillman products in good yield and high de and ee. (C) 2007 Elsevier Ltd. All rights reserved.",

keywords = "CARBON BOND-FORMATION, COPE ELIMINATION, AMINO ALDEHYDES, ALDOL REACTION, PRESSURE, ADDUCTS, ESTERS, 4-OXOAZETIDINE-2-CARBALDEHYDES, EQUIVALENTS, CYCLIZATION",

author = "Alexander Chernega and Davies, \{Stephen G.\} and Elend, \{Dirk. L.\} and Smethurst, \{Christian A. P.\} and Roberts, \{Paul M.\} and Smith, \{Andrew D.\} and Smyth, \{G. Darren\}",

year = "2007",

month = jul,

day = "23",

doi = "10.1016/j.tet.2007.05.015",

language = "English",

volume = "63",

pages = "7036--7046",

journal = "Tetrahedron",

issn = "0040-4020",

publisher = "Elsevier",

number = "30",

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TY - JOUR

T1 - Asymmetric synthesis of beta-substituted Baylis-Hillman products via lithium amide conjugate addition

AU - Chernega, Alexander

AU - Davies, Stephen G.

AU - Elend, Dirk. L.

AU - Smethurst, Christian A. P.

AU - Roberts, Paul M.

AU - Smith, Andrew D.

AU - Smyth, G. Darren

PY - 2007/7/23

Y1 - 2007/7/23

N2 - A three-step protocol for the asymmetric synthesis of a range of beta-substituted Baylis-Hillman products has been developed. This procedure involves the diastereoselective conjugate addition of lithium (R)-N-methyl-N-(alpha-methylbenzyl) amide to an alpha, beta-unsaturated ester to generate an N-protected beta-amino ester in high de. Subsequent asymmetric aldol reaction via deprotonation with LDA, transmetallation with B(OMe)(3) and addition of an aldehyde gives a range of syn-aldol products in moderate to high de. Purification of the syn-aldol products to homogeneity followed by tandem N-oxidation and Cope elimination gives the desired b-substituted Baylis-Hillman products in good yield and high de and ee. (C) 2007 Elsevier Ltd. All rights reserved.

AB - A three-step protocol for the asymmetric synthesis of a range of beta-substituted Baylis-Hillman products has been developed. This procedure involves the diastereoselective conjugate addition of lithium (R)-N-methyl-N-(alpha-methylbenzyl) amide to an alpha, beta-unsaturated ester to generate an N-protected beta-amino ester in high de. Subsequent asymmetric aldol reaction via deprotonation with LDA, transmetallation with B(OMe)(3) and addition of an aldehyde gives a range of syn-aldol products in moderate to high de. Purification of the syn-aldol products to homogeneity followed by tandem N-oxidation and Cope elimination gives the desired b-substituted Baylis-Hillman products in good yield and high de and ee. (C) 2007 Elsevier Ltd. All rights reserved.

KW - CARBON BOND-FORMATION

KW - COPE ELIMINATION

KW - AMINO ALDEHYDES

KW - ALDOL REACTION

KW - PRESSURE

KW - ADDUCTS

KW - ESTERS

KW - 4-OXOAZETIDINE-2-CARBALDEHYDES

KW - EQUIVALENTS

KW - CYCLIZATION

UR - https://www.scopus.com/pages/publications/34249988237

U2 - 10.1016/j.tet.2007.05.015

DO - 10.1016/j.tet.2007.05.015

M3 - Article

SN - 0040-4020

VL - 63

SP - 7036

EP - 7046

JO - Tetrahedron

JF - Tetrahedron

IS - 30

ER -

Asymmetric synthesis of beta-substituted Baylis-Hillman products via lithium amide conjugate addition

Abstract

Keywords

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