Publication type: Article in scientific journal
Type of review: Peer review (publication)
Title: Chirality transfer in an Ireland-Claisen rearrangement : a new approach toward the Iboga alkaloids
Authors: Höck, Stefan
Koch, Florian
Borschberg, Hans-Jürg
DOI: 10.1016/j.tetasy.2004.04.028
Published in: Tetrahedron: Asymmetry
Volume(Issue): 15
Issue: 11
Pages: 1801
Pages to: 1808
Issue Date: 2004
Publisher / Ed. Institution: Elsevier
ISSN: 0957-4166
1362-511X
Language: English
Subjects: Indole alkaloids; Chirality transfer; Ireland-Claisen rearrangemenent
Subject (DDC): 572: Biochemistry
Abstract: The synthesis of the isoquinuclidine core of the Iboga alkaloid family is described. This building block contains the entire stereochemical information of the targeted natural products. Starting with (S)-4-(hydroxymethyl)-4-butanolide, a derivative available in two steps from l-glutamate, (S)-4-benzyloxy-5,5-dimethoxypentanoic acid was obtained in four steps. Mitsunobu esterification with (S)-but-3-en-2-ol furnished the inverted ester, which was then subjected to an Ireland–Claisen rearrangement. This crucial step took place with a very satisfactory chirality transfer from the alcohol component to the new carbon backbone of the product. After transformation of the resulting silyl ester function into a hydroxylamino group, the dimethyl acetal moiety was hydrolyzed with 3 M sulfuric acid at 47°C. Under these conditions, the resulting cyclic nitrone could not be isolated, because it underwent a rapid intramolecular nitrone–olefin [3+2]-cycloaddition reaction to furnish the expected tricyclic isoxazolidine derivative in 67% yield. After chromatographic purification, this product was obtained enantiomerically pure and with a chemical purity of 96%. The targeted isoquinuclidine building block was thus obtained from (S)-4-(hydroxymethyl)-4-butanolide in 13 steps with an overall yield of 9.2%, which amounts to an average yield of 83.3% per step.
URI: https://digitalcollection.zhaw.ch/handle/11475/11998
Fulltext version: Published version
License (according to publishing contract): Licence according to publishing contract
Departement: Life Sciences and Facility Management
Organisational Unit: Institute of Chemistry and Biotechnology (ICBT)
Appears in collections:Publikationen Life Sciences und Facility Management

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