Lithium enolates from a (-)-quinic acid-derived cyclohexanone with a beta-alkoxy leaving group: regioselective preparation and evaluation of enolate stability towards beta-elimination

L M  Murray; Peter Andrew O'Brien; R J K  Taylor; S  Wunnemann

doi:10.1016/j.tetlet.2004.01.148

Lithium enolates from a (-)-quinic acid-derived cyclohexanone with a beta-alkoxy leaving group: regioselective preparation and evaluation of enolate stability towards beta-elimination

L M Murray, Peter Andrew O'Brien, R J K Taylor, S Wunnemann

Chemistry

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

Abstract

Deprotonation of a (-)-quinic acid-derived ketone {2S,3S,4aR,8R,8aS)-8-[(tert-butyl(dimethyl)silyl)oxy]-2,3-dimethoxy-2,3-dimethylhexahydro-1,4-benzodioxin-6(5H)-one} using lithium hexamethyldisilazide (LHMDS) at -78 degreesC gave one regioisomeric enolate. The regiocontrol is governed by the axial beta-silyloxy substituent and the resulting lithium enolate is stable towards beta-elimination at temperatures up to -40 degreesC. It was found that the axial beta-silyloxy group could be conveniently eliminated using 2.1 equiv of LHMDS at 0 degreesC for 1h and that an equatorial beta-alkoxy group was much more resistant to beta-elimination. A chiral lithium amide base was used to overturn the inherent regioselectivity of ketone deprotonation with LHMDS. (C) 2004 Elsevier Ltd. All rights reserved.

Original language	English
Pages (from-to)	2597-2601
Number of pages	5
Journal	Tetrahedron Letters
Volume	45
Issue number	12
DOIs	https://doi.org/10.1016/j.tetlet.2004.01.148
Publication status	Published - 15 Mar 2004

Keywords

cyclohexanones
deprotonation
elimination reactions
regiocontrol
(-)-quinic acid
ENANTIOSELECTIVE DEPROTONATION STRATEGY
ASYMMETRIC-SYNTHESIS
AMIDE BASES
STEREOSELECTIVE REACTIONS
KETONE ENOLIZATION
STEMONA ALKALOIDS
CYCLIC-KETONES
SYSTEM
4-TERT-BUTYLCYCLOHEXANONE
CONSTRUCTION

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@article{f2c6a5e15d6247faa09d051aa0773e0f,

title = "Lithium enolates from a (-)-quinic acid-derived cyclohexanone with a beta-alkoxy leaving group: regioselective preparation and evaluation of enolate stability towards beta-elimination",

abstract = "Deprotonation of a (-)-quinic acid-derived ketone {2S,3S,4aR,8R,8aS)-8-[(tert-butyl(dimethyl)silyl)oxy]-2,3-dimethoxy-2,3-dimethylhexahydro-1,4-benzodioxin-6(5H)-one} using lithium hexamethyldisilazide (LHMDS) at -78 degreesC gave one regioisomeric enolate. The regiocontrol is governed by the axial beta-silyloxy substituent and the resulting lithium enolate is stable towards beta-elimination at temperatures up to -40 degreesC. It was found that the axial beta-silyloxy group could be conveniently eliminated using 2.1 equiv of LHMDS at 0 degreesC for 1h and that an equatorial beta-alkoxy group was much more resistant to beta-elimination. A chiral lithium amide base was used to overturn the inherent regioselectivity of ketone deprotonation with LHMDS. (C) 2004 Elsevier Ltd. All rights reserved.",

keywords = "cyclohexanones, deprotonation, elimination reactions, regiocontrol, (-)-quinic acid, ENANTIOSELECTIVE DEPROTONATION STRATEGY, ASYMMETRIC-SYNTHESIS, AMIDE BASES, STEREOSELECTIVE REACTIONS, KETONE ENOLIZATION, STEMONA ALKALOIDS, CYCLIC-KETONES, SYSTEM, 4-TERT-BUTYLCYCLOHEXANONE, CONSTRUCTION",

author = "Murray, {L M} and O'Brien, {Peter Andrew} and Taylor, {R J K} and S Wunnemann",

year = "2004",

month = mar,

day = "15",

doi = "10.1016/j.tetlet.2004.01.148",

language = "English",

volume = "45",

pages = "2597--2601",

journal = "Tetrahedron Letters",

issn = "0040-4039",

publisher = "Elsevier",

number = "12",

}

Lithium enolates from a (-)-quinic acid-derived cyclohexanone with a beta-alkoxy leaving group: regioselective preparation and evaluation of enolate stability towards beta-elimination. / Murray, L M ; O'Brien, Peter Andrew ; Taylor, R J K et al.
In: Tetrahedron Letters, Vol. 45, No. 12, 15.03.2004, p. 2597-2601.

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

TY - JOUR

T1 - Lithium enolates from a (-)-quinic acid-derived cyclohexanone with a beta-alkoxy leaving group: regioselective preparation and evaluation of enolate stability towards beta-elimination

AU - Murray, L M

AU - O'Brien, Peter Andrew

AU - Taylor, R J K

AU - Wunnemann, S

PY - 2004/3/15

Y1 - 2004/3/15

N2 - Deprotonation of a (-)-quinic acid-derived ketone {2S,3S,4aR,8R,8aS)-8-[(tert-butyl(dimethyl)silyl)oxy]-2,3-dimethoxy-2,3-dimethylhexahydro-1,4-benzodioxin-6(5H)-one} using lithium hexamethyldisilazide (LHMDS) at -78 degreesC gave one regioisomeric enolate. The regiocontrol is governed by the axial beta-silyloxy substituent and the resulting lithium enolate is stable towards beta-elimination at temperatures up to -40 degreesC. It was found that the axial beta-silyloxy group could be conveniently eliminated using 2.1 equiv of LHMDS at 0 degreesC for 1h and that an equatorial beta-alkoxy group was much more resistant to beta-elimination. A chiral lithium amide base was used to overturn the inherent regioselectivity of ketone deprotonation with LHMDS. (C) 2004 Elsevier Ltd. All rights reserved.

AB - Deprotonation of a (-)-quinic acid-derived ketone {2S,3S,4aR,8R,8aS)-8-[(tert-butyl(dimethyl)silyl)oxy]-2,3-dimethoxy-2,3-dimethylhexahydro-1,4-benzodioxin-6(5H)-one} using lithium hexamethyldisilazide (LHMDS) at -78 degreesC gave one regioisomeric enolate. The regiocontrol is governed by the axial beta-silyloxy substituent and the resulting lithium enolate is stable towards beta-elimination at temperatures up to -40 degreesC. It was found that the axial beta-silyloxy group could be conveniently eliminated using 2.1 equiv of LHMDS at 0 degreesC for 1h and that an equatorial beta-alkoxy group was much more resistant to beta-elimination. A chiral lithium amide base was used to overturn the inherent regioselectivity of ketone deprotonation with LHMDS. (C) 2004 Elsevier Ltd. All rights reserved.

KW - cyclohexanones

KW - deprotonation

KW - elimination reactions

KW - regiocontrol

KW - (-)-quinic acid

KW - ENANTIOSELECTIVE DEPROTONATION STRATEGY

KW - ASYMMETRIC-SYNTHESIS

KW - AMIDE BASES

KW - STEREOSELECTIVE REACTIONS

KW - KETONE ENOLIZATION

KW - STEMONA ALKALOIDS

KW - CYCLIC-KETONES

KW - SYSTEM

KW - 4-TERT-BUTYLCYCLOHEXANONE

KW - CONSTRUCTION

U2 - 10.1016/j.tetlet.2004.01.148

DO - 10.1016/j.tetlet.2004.01.148

M3 - Article

SN - 0040-4039

VL - 45

SP - 2597

EP - 2601

JO - Tetrahedron Letters

JF - Tetrahedron Letters

IS - 12

ER -