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Controlling 6-endo-selectivity in oxidation/bromocyclization cascades for synthesis of aplysiapyranoids and other 2,2,6,6-substituted tetrahydropyrans

Brücher, Oliver and Bergsträßer, Uwe and Kelm, Harald and Hartung, Jens and Greb, Marco and Svoboda, Ingrid and Fuess, Hartmut (2012):
Controlling 6-endo-selectivity in oxidation/bromocyclization cascades for synthesis of aplysiapyranoids and other 2,2,6,6-substituted tetrahydropyrans.
In: Tetrahedron, 68 (34), Elsevier Science Publishing, pp. 6968-6980, ISSN 00404020,
[Online-Edition: http://dx.doi.org/10.1016/j.tet.2012.05.013],
[Article]

Abstract

A cascade, composed of (i) oxovanadium(V)-catalyzed oxidation of bromide by tert-butyl hydroperoxide and (ii) stereoselective 6-endo-bromocyclization, affords 3-bromo-2-aryl-2,6,6-trimethyltetrahydropyrans from styrene-type tertiary alkenols in synthetically useful yields. (E)-Alkenols add the bromo- and the alkoxy substituent anti-selectively across the double bond, indicating a bromonium ion-mechanism for the ring closure. 6-endo-control of the alkenol cyclization thereby arises from the polar effect of the aryl substituent. Two methyl substituents bound to the alkene terminus are not similarly able to favor 6-endo-cyclization, because strain arising from methyl group repulsion, as the bromonium-activated π-bond and the hydroxyl oxygen approach, directs bromocyclization of tertiary prenyl-type substrates toward tetrahydrofuran formation. A hexasubstituted bromotetrahydropyran prepared from the oxidation/bromocyclization cascade served as starting material for synthesis of racemic aplysiapyranoid A, in a sequence of free radical and polar functional group interconversion.

Item Type: Article
Erschienen: 2012
Creators: Brücher, Oliver and Bergsträßer, Uwe and Kelm, Harald and Hartung, Jens and Greb, Marco and Svoboda, Ingrid and Fuess, Hartmut
Title: Controlling 6-endo-selectivity in oxidation/bromocyclization cascades for synthesis of aplysiapyranoids and other 2,2,6,6-substituted tetrahydropyrans
Language: English
Abstract:

A cascade, composed of (i) oxovanadium(V)-catalyzed oxidation of bromide by tert-butyl hydroperoxide and (ii) stereoselective 6-endo-bromocyclization, affords 3-bromo-2-aryl-2,6,6-trimethyltetrahydropyrans from styrene-type tertiary alkenols in synthetically useful yields. (E)-Alkenols add the bromo- and the alkoxy substituent anti-selectively across the double bond, indicating a bromonium ion-mechanism for the ring closure. 6-endo-control of the alkenol cyclization thereby arises from the polar effect of the aryl substituent. Two methyl substituents bound to the alkene terminus are not similarly able to favor 6-endo-cyclization, because strain arising from methyl group repulsion, as the bromonium-activated π-bond and the hydroxyl oxygen approach, directs bromocyclization of tertiary prenyl-type substrates toward tetrahydrofuran formation. A hexasubstituted bromotetrahydropyran prepared from the oxidation/bromocyclization cascade served as starting material for synthesis of racemic aplysiapyranoid A, in a sequence of free radical and polar functional group interconversion.

Journal or Publication Title: Tetrahedron
Volume: 68
Number: 34
Publisher: Elsevier Science Publishing
Uncontrolled Keywords: Alkyl hydroperoxide, Bromocyclization, Bromoperoxidase model, Marine natural product, Molecular modeling, Oxidation catalysis, Stereoselective synthesis, Strain, Terpenol, Vanadium(V) complex, X-ray crystallography
Divisions: 11 Department of Materials and Earth Sciences > Material Science > Structure Research
11 Department of Materials and Earth Sciences > Material Science
11 Department of Materials and Earth Sciences
Date Deposited: 23 Jan 2015 08:54
Official URL: http://dx.doi.org/10.1016/j.tet.2012.05.013
Identification Number: doi:10.1016/j.tet.2012.05.013
Funders: This work is part of Ph.D. Theses of O.B. and M.G., and was supported by the Deutsche Bundesstiftung Umwelt (DBU; grant 20007/885) and the Deutsche Forschungsgemeinschaft (grant Ha1705/8–1).
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