The Nicholas Reaction: A Powerful Tool for the Stereoselective Synthesis of Bioactive Compounds

David D. Díaz; Juan M. Betancort; Víctor S. Martín

doi:10.1055/s-2007-967958

ACCOUNT

The Nicholas Reaction: A Powerful Tool for the Stereoselective Synthesis of Bioactive Compounds

David D. Díaz, Juan M. Betancort, Víctor S. Martín*
Instituto Universitario de Bio-Orgánica ‘Antonio González’, Universidad de La Laguna, Avenida Astrofísico Francisco Sánchez 2, 38206 La Laguna, Tenerife, Spain
Fax: +34(922)318571; e-Mail: vmartin@ull.es;

Abstract

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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.

1 Introduction
2 Synthesis of Symmetrical and Unsymmetrical Linear Propargylic Ethers
3 Synthesis of Cyclic Propargylic Ethers
3.1 Primary and Secondary Alcohols as Nucleophiles
3.2 Epoxides as Nucleophiles
4 Asymmetric Intermolecular Nicholas Reaction
5 Synthesis of Homopropargylic Ketones
6 Intramolecular Propargylic Reduction
7 Summary

Key words

alkynes - cobalt complexes - Nicholas reaction - stereoselective synthesis - natural products - ethers

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References

References and Notes

Present address: Departamento de Química Orgánica, Universidad Autónoma de Madrid, 28049 Madrid, Spain.

Present address: Phenomix Corporation, 5871 Oberlin Dr., San Diego, CA 92126, U.S.A.

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