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Synthesis 2004(14): 2303-2316  
DOI: 10.1055/s-2004-831170
PAPER
© Georg Thieme Verlag Stuttgart · New York

Stereoselective Synthesis of Highly Substituted Bicyclic γ-Lactones Using Homoaldol Addition of 1-(1-Cycloalkenyl)methyl Carbamates

Mustafa Özlügedika, Jesper Kristensenb, Jenny Reubera, Roland Fröhlicha,, Dieter Hoppe*a
a Institut für Organische Chemie, Westfälischen Wilhelms-Universität Münster, Corrensstraße 40, 48149 Münster, Germany
Fax: +49(251)8336531; e-Mail: dhoppe@uni-muenster.de;
b Department of Medicinal Chemistry, The Royal Danish School of Pharmacy, Universitetsparken, 2100, Copenhagen, Denmark
Fax: +4535372209;
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Publikationsverlauf

Received 1 April 2004
Publikationsdatum:
19. August 2004 (online)

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Abstract

Stereoselective addition of aldehydes 4 to metallated 1-(1-cycloalkenyl)methyl N,N-diisopropylcarbamates 1 gave cyclic homoaldol adducts 6. By applying the (-)-sparteine method, enantiomerically enriched products were obtained. These were oxidatively cyclized to diastereomerically pure γ-lactones 8 via the γ-lactol ethers 7. After deprotonation of γ-lactones 8 with lithium hexamethyldisilazide, a further substitution was achieved. By trapping the lactone enolates 11 with β-naphthylmethyl bromide, single dia­stereomers of γ-lactones 12 were produced.

Key words

asymmetric synthesis - 1-alkenyl carbamates - homoaldol addition - (-)-sparteine - bicyclic lactones

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1

Responsible for X-Ray crystal structure data.

7

In related cases, we recently observed an oxidative dimer of 1. We suspect that a one-electron transfer from titanium to the allylic anion is the cause. The use of ClTi(NEt2)3 as exchange reagent is recommended.3d

14

Prasad, K. R.; Özlügedik, M.; Wibbeling, B.; Fröhlich, R.; Hoppe, D., manuscript in preparation.

15

Determined via the lactone derivative.