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.

Preface XI List of Contributors XIII 1 Stereoselective Acetate Aldol Reactions 1 Pedro Romea and Félix Urpí 1.1 Introduction 1 1.2 Mukaiyama Aldol Reaction 2 1.3 Metal Enolates 41 1.4 Conclusions 68 References 69 2 The Vinylogous Mukaiyama Aldol Reaction in Natural Product Synthesis 83 Martin Cordes and Markus Kalesse 2.1 Introduction 83 2.2 Aldehyde–Derived Silyl Dienol Ethers 84 2.3 Ester–Derived Silyl Dienol Ethers 90 2.4 Amide–Derived Silyl Dienol Ethers – Vinylketene Silyl N,O –Acetals 108 2.5 Acyclic Acetoacetate–Derived Silyl Dienolates – Chan’s Diene 117 2.6 Cyclic Acetoacetate–Derived Dienolates 124 2.7 Furan–Derived Silyloxy Dienes 133 2.8 Pyrrole–Based 2–Silyloxy Dienes 142 2.9 Comparison with Other Methods 148 References 151 3 Organocatalyzed Aldol Reactions 155 Gabriela Guillena 3.1 Introduction 155 3.2 Proline as Organocatalyst 156 3.3 Proline Derivatives as Organocatalysts 179 3.4 Conclusions and Outlook 253 References 253 4 Supersilyl Protective Groups in Aldol Reactions 269 Patrick B. Brady and Hisashi Yamamoto 4.1 Introduction 269 4.2 Aldol Addition with Acetaldehyde–Derived Super Silyl Enol Ether (1) 270 4.3 α–Substituted Silyl Enol Ethers Derived from Aldehydes 270 4.4 Aldol Addition to Chiral Aldehydes 272 4.5 One–Pot Sequential Aldol Reactions 274 4.6 Sequential Aldol–Aldol Reactions of Acetaldehyde 275 4.7 Double Aldol Reactions with α–Substituted Silyl Enol Ethers 277 4.8 Stereochemical Considerations 281 4.9 Aldol Reactions of β–Supersiloxy Methyl Ketones 282 4.10 Total Synthesis of Natural Products Using Supersilyl Aldol Reactions 285 4.11 Conclusion and Outlook 288 References 288 5 Asymmetric Induction in Aldol Additions 293 Luiz C. Dias, Ellen C. Polo, Emílio C. de Lucca Jr, and Marco A.B. Ferreira 5.1 Introduction 293 5.2 Asymmetric Induction Using Chiral Ketones 295 5.3 Asymmetric Induction Using Chiral Aldehydes 317 5.4 Asymmetric Induction in the Aldol Addition of Chiral Enolates to Chiral Aldehydes 360 References 371 6 Polypropionate Synthesis via Substrate–Controlled Stereoselective Aldol Couplings of Chiral Fragments 377 Dale E. Ward 6.1 Introduction 377 6.2 Principles of Stereoselective Aldol Reactions 378 6.3 Stereoselective Aldol Coupling of Chiral Reactants 398 6.4 2–Alkoxyalkyl Ethyl Ketones: 2–Desmethyl Polypropionate Equivalents 406 6.5 Conclusions 420 References 424 7 Application of Oxazolidinethiones and Thiazolidinethiones in Aldol Additions 431 Michael T. Crimmins 7.1 Introduction 431 7.2 Preparation of Oxazolidinethione and Thiazolidinethione Chiral Auxiliaries 431 7.3 Acylation of Oxazolidinethione and Thiazolidinethione Chiral Auxiliaries 433 7.4 Propionate Aldol Additions 434 7.5 Acetate Aldol Additions 437 7.6 Glycolate Aldol Additions 443 References 471 8 Enzyme–Catalyzed Aldol Additions 475 Pere Clapés and Jesús Joglar 8.1 Introduction 475 8.2 Pyruvate Aldolases 477 8.3 N –Acetylneuraminic Acid Aldolase (NeuA) 478 8.4 Dihydroxyacetone Phosphate (DHAP) Aldolases 494 8.5 D–Fructose–6–Phosphate Aldolase and Transaldolase B Phe178Tyr: FSA–Like Aldolases 503 8.6 2–Deoxy–D–Ribose–5–Phosphate Aldolase (RibA or DERA; EC 4.1.2.4) 510 8.7 Glycine/Alanine Aldolases 514 8.8 Aldol Reactions Catalyzed by Non aldolases 520 8.9 Conclusions and Perspectives 520 References 522 Index 529

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.