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Synthesis 2006(4): 557-588  
DOI: 10.1055/s-2006-926315
REVIEW
© Georg Thieme Verlag Stuttgart · New York

Stereoselective Synthesis of 1,3-Diols

Silke E. Bodea, Michael Wolbergb, Michael Müller*a
a University of Freiburg, Institute of Pharmaceutical Sciences, Department of Pharmaceutical and Medicinal Chemistry, Albertstr. 25, 79104 Freiburg, Germany
e-Mail: michael.mueller@pharmazie.uni-freiburg.de;
b DSM Pharma Chemicals GmbH, Donaustaufer Str. 378, 93055 Regensburg, Germany
Further Information

Publication History

Received 20 July 2005
Publication Date:
25 January 2006 (online)

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Abstract

Many polyketide-derived natural products contain a syn- or anti-1,3-diol unit. No general and simple approach exists for the flexible synthesis of polyols and other polyketide-derived structural units, therefore a multitude of methods for the stereoselective synthesis of 1,3-diols has been developed. Asymmetric homogeneous and heterogeneous hydrogenation and diastereoselective reduction, chain elongation, enzymatic and nonenzymatic desymmetrization, or dynamic kinetic resolution are some of these methods. The development of different methods to synthesize these 1,3-diols stereoselectively is important, as often small structural changes in a molecule result in low yields or low stereoselectivity with a known method. This review article highlights some of the recent developments in this field.

1 Introduction

2 C-C Bond-Forming Reactions

2.1 Alkylation

2.2 Allylation

2.3 Crotylation

2.4 Prins Reaction

2.5 anti-1,3-Diols and Polyols via SAMP/RAMP Hydrazones

3 Aldol Reaction

3.1 Aldol Reaction with 1,3-Induction

3.2 Tandem Aldol-Tishchenko Reaction

3.3 Vinylogous Aldol Reaction

4 Stereoselective Reduction

4.1 Substrate-Induced Diastereoselective Reduction of β-Hydroxyketones

4.2 Stereoselective Reduction of 1,3-Diketones

5 Hydrogenation

5.1 Hydrogenation of 1,3-Hydroxyketones to syn- and anti-1,3-Diols

5.2 Hydrogenation of 1,3-Diketones

5.3 Stereoselective Reduction of 4-Hydroxypyranones

6 Allylic and Homoallylic Alcohols as Substrates

6.1 1,3-Diols via Addition of Alkoxide Nucleophiles

6.2 Iodocarbonation

6.3 1,3-Diols via Olefin Carbonylation

6.4 Miscellaneous

7 Biocatalytic Methods

7.1 Enzymatic Reduction of 1,3-Diketones

7.2 Enzymatic Reduction of β-Hydroxyketones

7.3 Enzymatic Aldol Addition

7.4 Enzymatic Resolution of Racemic 1,3-Diols by Hydrolytic Enzymes

7.5 Enzymatic Desymmetrization of meso-1,3-Diols

8 Desymmetrization

8.1 Desymmetrization via Chain Elongation

8.2 Desymmetrization via Racemic Resolution

8.3 Diastereo-Differentiating Hydrolysis of 1,3-Diol Acetonides

8.4 Desymmetrization of 8-Oxabicyclo[3.2.1]oct-6-en-3-one and Derivatives

9 Miscellaneous

9.1 [2+2] Cycloaddition

9.2 1,3-Diols via 1-Oxa-2-silacyclopentanes

9.3 Radical-Based Asymmetric Synthesis

9.4 Butyrolactone Strategy

9.5 Various

10 Determination of Relative and Absolute Configuration

10.1 Assignment of Relative Configuration

10.2 Assignment of Absolute Configuration

11 Conclusion

Key words

asymmetric synthesis - reductions - aldol reactions - biocatalysis - desymmetrizations - alcohols