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DOI: 10.1055/s-2007-967958
The Nicholas Reaction: A Powerful Tool for the Stereoselective Synthesis of Bioactive Compounds
Publikationsverlauf
Publikationsdatum:
07. Februar 2007 (online)
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Abstract
Polyether units are a frequent heterocyclic fragment present in numerous natural products of great biological importance and constitute significant synthons for the synthesis of pharmacologically relevant compounds. Likewise, compounds having stereochemically defined alkyl-branched hydrocarbon chains are widespread in nature and the development of new synthetic methodologies to achieve their preparation in high yields and levels of stereocontrol is currently a challenging endeavour in organic synthesis. In this account, we describe our own approach to the stereoselective synthesis of bioactive compounds using the Nicholas reaction, the discovery of unexpected reaction pathways as well as some unreported results. The scope of the title reaction, within our research interests, and its synthetic applications are outlined. Reference to important related work from others in the field is also included.
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1 Introduction
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2 Synthesis of Symmetrical and Unsymmetrical Linear Propargylic Ethers
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3 Synthesis of Cyclic Propargylic Ethers
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3.1 Primary and Secondary Alcohols as Nucleophiles
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3.2 Epoxides as Nucleophiles
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4 Asymmetric Intermolecular Nicholas Reaction
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5 Synthesis of Homopropargylic Ketones
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6 Intramolecular Propargylic Reduction
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7 Summary
Key words
alkynes - cobalt complexes - Nicholas reaction - stereoselective synthesis - natural products - ethers
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References and Notes
Present address: Departamento de Química Orgánica, Universidad Autónoma de Madrid, 28049 Madrid, Spain.
2Present address: Phenomix Corporation, 5871 Oberlin Dr., San Diego, CA 92126, U.S.A.
47(a) Unpublished results. (b) X-ray data can be obtained directly from the authors upon request.
51We had difficulties separating both diastereoisomers. At the present time we cannot ensure which isomer is predominant.
52Montmorillonite K-10 has been recently reported as a convenient acid component in the Nicholas reaction, see ref. 41.
62These complexes possess an outstanding resolution under silica gel chromatography and both diastereoisomers can be readily separated in this way.