Modern Methods in Stereoselective Aldol Reactions

The selective formation of bondings between molecules is one of the major challenges in organic chemistry, and the so-called aldol reaction is one of the most important for this purpose. These reactions are a highly useful tool for developing such novel substances as natural products and pharmaceuticals.

Likes its highly successful and much appreciated predecessor, "Modern Aldol Reactions", this ready reference provides a systematic overview of methodologies for installing a required configuration during an aldol addition step, but shifts the focus so as to cover the latest developments.

As such, it presents a set of brand new tools, including vinylogous Mukaiyama-aldol reactions and substrate-controlled aldol reactions, as well as asymmetric induction in aldol additions. Furthermore, new developments in existing stereoselective aldol additions are described, such as the deployment of supersilyl groups or organocatalyzed aldol additions. All of these methodologies are presented in the context of their deployment in the total synthesis of natural products.

Born in 1950,Rainer Mahrwald studied chemistry at MLU Halle and subsequently joined the "Manfred von Ardenne" Research Institute in Dresden, where he led the synthetics group. He gained his doctorate under G. Wagner in Leipzig in 1979, and went on to the Institute of Organic Chemistry at the Academy of Science in Berlin, where he remained until 1990. Following a stay at the Philipps-University in Marburg, Dr. Mahrwald qualified as a lecturer at the Humboldt University Berlin, where he is now full professor.

Preface

STEREOSELECTIVE ACETATE ALDOL REACTIONS
Introduction
Mukaiyama Aldol Reaction
Metal Enolates
Conclusions

THE VINYLOGOUS MUKAIYAMA ALDOL REACTION IN NATURAL PRODUCT SYNTHESIS
Introduction
Aldehyde-Derived Silyl Dienol Ethers
Ester-Derived Silyl Dienol Ethers
Amide-Derived Silyl Dienol Ethers -
Vinylketene Silyl N,O-Acetals
Acyclic Acetoacetate-Derived Silyl Dienolates -
Chan's Diene
Cyclic Acetoacetate-Derived Dienolates
Furan-Derived Silyloxy Dienes
Pyrrole-Based 2-Silyloxy Dienes
Comparison with Other Methods

ORGANOCATALYZED ALDOL REACTIONS
Introduction
Proline as Organocatalyst
Proline Derivatives as Organocatalysts
Conclusions and Outlook

SUPERSILYL PROTECTIVE GROUPS IN ALDOL REACTIONS
Introduction
Aldol Addition with Acetaldehyde-Derived Super Silyl Enol Ether
Alpha-Substituted Silyl Enol Ethers Derived from Aldehydes
Aldol Addition to Chiral Aldehydes
One-Pot Sequential Aldol Reactions
Sequential Aldol-Aldol Reactions of Acetaldehyde
Double Aldol Reactions with Alpha-Substituted Silyl Enol Ethers
Stereochemical Considerations
Aldol Reactions of Beta-Supersiloxy Methyl Ketones
Total Synthesis of Natural Products Using Supersilyl Aldol Reactions
Conclusion and Outlook

ASYMMETRIC INDUCTION IN ALDOL ADDITIONS
Introduction
Asymmetric Induction Using Chiral Ketones
Asymmetric Induction Using Chiral Aldehydes
Asymmetric Induction in the Aldol Addition of Chiral Enolates to Chiral Aldehydes

POLYPROPIONATE SYNTHESIS VIA SUBSTRATE-CONTROLLED STEREOSELECTIVE ALDOL COUPLINGS OF CHIRAL FRAGMENTS
Introduction
Principles of Stereoselective Aldol Reactions
Stereoselective Aldol Coupling of Chiral Reactants
2-Alkoxyalkyl Ethyl Ketones: 2-Desmethyl Polypropionate Equivalents
Conclusions

APPLICATION OF OXAZOLIDINETHIONES AND THIAZOLIDINETHIONES IN ALDOL ADDITIONS
Introduction
Preparation of Oxazolidinethione and Thiazolidinethione Chiral Auxiliaries
Acylation of Oxazolidinethione and Thiazolidinethione Chiral Auxiliaries
Propionate Aldol Additions
Acetate Aldol Additions
Glycolate Aldol Additions

ENZYME-CATALYZED ALDOL ADDITIONS
Introduction
Pyruvate Aldolases
N-Acetylneuraminic Acid Aldolase (NeuA)
Dihydroxyacetone Phosphate (DHAP) Aldolases
D-Fructose-6-Phosphate Aldolase and Transaldolase B Phe178Tyr: FSA-Like Aldolases
2-Deoxy-D-Ribose-5-Phosphate Aldolase (RibA or DERA)
Glycine/Alanine Aldolases
Aldol Reactions Catalyzed by Non Aldolases
Conclusions and Perspectives

Index