Chirality transfer in an Ireland-Claisen rearrangement : a new approach toward the Iboga alkaloids

Höck, Stefan; Koch, Florian; Borschberg, Hans-Jürg

doi:10.1016/j.tetasy.2004.04.028

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
Page(s):	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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Höck, S., Koch, F., & Borschberg, H.-J. (2004). Chirality transfer in an Ireland-Claisen rearrangement : a new approach toward the Iboga alkaloids. Tetrahedron: Asymmetry, 15(11), 1801–1808. https://doi.org/10.1016/j.tetasy.2004.04.028

Höck, S., Koch, F. and Borschberg, H.-J. (2004) ‘Chirality transfer in an Ireland-Claisen rearrangement : a new approach toward the Iboga alkaloids’, Tetrahedron: Asymmetry, 15(11), pp. 1801–1808. Available at: https://doi.org/10.1016/j.tetasy.2004.04.028.

S. Höck, F. Koch, and H.-J. Borschberg, “Chirality transfer in an Ireland-Claisen rearrangement : a new approach toward the Iboga alkaloids,” Tetrahedron: Asymmetry, vol. 15, no. 11, pp. 1801–1808, 2004, doi: 10.1016/j.tetasy.2004.04.028.

HÖCK, Stefan, Florian KOCH und Hans-Jürg BORSCHBERG, 2004. Chirality transfer in an Ireland-Claisen rearrangement : a new approach toward the Iboga alkaloids. Tetrahedron: Asymmetry. 2004. Bd. 15, Nr. 11, S. 1801–1808. DOI 10.1016/j.tetasy.2004.04.028

Höck, Stefan, Florian Koch, and Hans-Jürg Borschberg. 2004. “Chirality Transfer in an Ireland-Claisen Rearrangement : A New Approach toward the Iboga Alkaloids.” Tetrahedron: Asymmetry 15 (11): 1801–8. https://doi.org/10.1016/j.tetasy.2004.04.028.

Höck, Stefan, et al. “Chirality Transfer in an Ireland-Claisen Rearrangement : A New Approach toward the Iboga Alkaloids.” Tetrahedron: Asymmetry, vol. 15, no. 11, 2004, pp. 1801–8, https://doi.org/10.1016/j.tetasy.2004.04.028.