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Synthesis 2004(12): 1903-1928  
DOI: 10.1055/s-2004-831161
REVIEW
© Georg Thieme Verlag Stuttgart · New York

Radical Cyclization of Haloacetals: The Ueno-Stork Reaction

Xavier J. Salom-Roig, Fabrice Dénès, Philippe Renaud*
University of Berne, Department of Chemistry and Biochemistry, Freiestrasse 3, 3000 Berne 9, Switzerland
Fax: +41(31)6313426; e-Mail: philippe.renaud@ioc.unibe.ch ;
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Publication History

Received 19 April 2004
Publication Date:
10 August 2004 (online)

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Abstract

The formation of the C-C bond using radical cyclization of haloacetals (Ueno-Stork reaction) has proven to be an extremely efficient method to access γ-lactones and related compounds. This reaction is also highly attractive for the regio- and stereoselective introduction of side chains to cyclic and acyclic allylic alcohols. It has been used as a key step in many natural product syntheses and has proven to be particularly efficient for the stereoselective generation of quaternary carbon centers. This review focuses on the different methods available to carry out this radical cyclization, as well as on the stereochemical aspect of the reaction and its applications in total synthesis.

  • 1 Introduction

  • 2 Preparation of Haloacetals and Related Compounds

  • 3 Methods for Radical Cyclization

  • 3.1 Radical Chain Reactions

  • 3.1.1 Tin Hydride

  • 3.1.2 Substitute for Tin Hydride

  • 3.1.3 Atom and Group Transfer Reactions

  • 3.1.4 The Fragmentation Method

  • 3.1.5 Cyclization Followed by Formation of a C-X Bond

  • 3.2 Non-Chain Reactions

  • 3.2.1 Reductive Processes

  • 3.2.1.1 Samarium(II) Diiodide

  • 3.2.1.2 Indium

  • 3.2.1.3 Titanium and Zirconium

  • 3.2.1.4 Organomagnesium Reagents

  • 3.2.1.5 Organomanganese Reagents

  • 3.2.1.6 Chromium(II) Species

  • 3.2.1.7 Nickel-Catalyzed Carbozincation

  • 3.2.1.8 Cobalt-Mediated Cyclizations

  • 3.2.1.9 Photoelectron Transfer

  • 3.2.2 Oxidative Processes

  • 4 Stereochemical Considerations

  • 4.1 The Role of the Acetal Center

  • 4.1.1 4-Substituted 2-Alkoxytetrahydrofurans

  • 4.1.2 3,4-Disubstituted 2-Alkoxytetrahydrofurans

  • 4.1.3 4,5-Disubstituted 2-Alkoxytetrahydrofurans

  • 4.1.4 3,4,5-Trisubstituted 2-Alkoxytetrahydrofurans

  • 4.1.5 3-Substituted 2-Alkoxy-4-methylene-tetrahydrofurans

  • 4.1.6 Tetrahydrofurans Derivatives

  • 4.1.7 Control of the Absolute Configuration of the Acetal Center

  • 4.1.8 Regioselectivity Control by the Acetal Center

  • 4.2 The Role of the Allylic Center

  • 4.3 Stereochemistry of the Ring Junction

  • 4.4 Cyclizations Leading to Fused Bicyclic Systems

  • 4.5 Reactions Leading to Spiro Compounds

  • 4.6 Control of the Stereochemistry of Follow-Up Reactions

  • 5 Application in Natural Product Synthesis

  • 5.1 Monocyclic Tetrahydrofurans and γ-Lactones

  • 5.2 Fused Bicyclic Compounds

  • 5.2.1 Use of Cyclic Alkenes

  • 5.2.2 Use of Cyclic Radicals

  • 5.3 Spirocyclic Compounds

  • 5.4 Six-Membered Rings

  • 5.5 Bridged Systems

  • 5.6 Bicyclic Compounds via Transannular Reactions

  • 5.7 Polycyclic Systems via Cascade Cyclizations

  • 5.8 Introduction of Side Chain via an Acetal Tether

  • 5.8.1 Acyclic Compounds

  • 5.8.2 Cyclic Systems

  • 5.8.3 Addition of Two Side Chains at Once: Prostaglandin and Related Syntheses

  • 6 Conclusion

Key words

radicals - cyclizations - acetals - lactones - tethers - total synthesis - stereoselectivity