Metathesis in Natural Product Synthesis E-Book

• Herausgeber: Wiley-VCH
• Kategorie: Wissenschaft und neue Technologien
• Sprache: Englisch

Seitenzahl: 507

Veröffentlichungsjahr: 2011

Beschreibung

Emphasizing the impact of metathesis in natural product synthesis through the different types of key reactions, this is a comprehensive view of a hot topic. Written by top international authors, this ready reference is clearly structured and packed with important information, including representative experimental procedures for practical applications. A real must-have for anyone working in natural product synthesis.

Leseprobe

Contents

Cover

Half Title page

Title page

Copyright page

Foreword

Preface

List of Catalysts

List of Contributors

Abbreviations

Chapter 1: Synthesis of Natural Products Containing Medium-size Carbocycles by Ring-closing Alkene Metathesis

1.1 Introduction

1.2 Formation of Five-membered Carbocycles by RCM

1.3 Formation of Six-membered Carbocycles by RCM

1.4 Formation of Seven-membered Carbocycles by RCM

1.5 Formation of Eight-membered Carbocycles by RCM

1.6 Formation of Nine-membered Carbocycles by RCM

1.7 Formation of 10-membered Carbocycles by RCM

1.8 Conclusion

References

Chapter 2: Natural Products Containing Medium-sized Nitrogen Heterocycles Synthesized by Ring-closing Alkene Metathesis

2.1 Introduction

2.2 Five-membered Nitrogen Heterocycles

2.3 Six-membered Nitrogen Heterocycles

2.4 Seven-membered Nitrogen Heterocycles

2.5 Eight-membered Nitrogen Heterocycles

2.6 Conclusion

References

Chapter 3: Synthesis of Natural Products Containing Medium-size Oxygen Heterocycles by Ring-closing Alkene Metathesis

3.1 Introduction

3.2 General RCM Approaches to Medium Rings

3.3 Laurencin

3.4 Eunicellins/Eleutherobin

3.5 Helianane

3.6 Octalactin A

3.7 Microcarpalide and the Herbarums

3.8 Marine Ladder Toxins

3.9 Conclusion

Acknowledgments

References

Chapter 4: Phosphorus and Sulfur Heterocycles via Ring-closing Metathesis: Application in Natural Product Synthesis

4.1 Introduction

4.2 Synthesis and Reactivity of Sultones Derived from RCM

4.3 Total Synthesis of the Originally Proposed Structure of (±)-Mycothiazole

4.4 Synthesis and Reactivity of Phosphates from RCM

4.5 Applications of Phosphate Tethers in the Synthesis of Dolabelide C

4.6 Conclusion

Acknowledgment

References

Chapter 5: Synthesis of Natural Products Containing Macrocycles by Alkene Ring-closing Metathesis

5.1 Introduction

5.2 Organization of the Chapter

5.3 Macrocyclic Polyketides

5.4 Terpenoids

5.5 Macrocycles of Amino Acid Origin

5.6 Macrocyclic Glycolipids

5.7 Conclusions and Outlook

References

Chapter 6: Synthesis of Natural Products and Related Compounds Using Ene–Yne Metathesis

6.1 Introduction

6.2 Synthesis of Natural Products and Related Compounds Using Ene–yne Metathesis

6.3 Synthesis of Natural Products and Related Compounds Using Ene–yne Cross-metathesis (CM)

6.4 Synthesis of Natural Products Using Skeletal Reorganization

References

Chapter 7: Ring-closing Alkyne Metathesis in Natural Product Synthesis

7.1 Introduction

7.2 Alkyne Metathesis

7.3 Ring-closing Alkyne Metathesis

7.4 Applications of RCAM in Natural Product Synthesis

7.5 Conclusions

References

Chapter 8: Temporary Silicon–Tethered Ring–Closing Metathesis Reactions in Natural Product Synthesis

8.1 Introduction

8.2 Temporary Silicon–Tethered Ring–Closing Metathesis Reactions

8.3 Conclusions and Outlook

Acknowledgments

References

Chapter 9: Metathesis Involving a Relay and Applications in Natural Product Synthesis

9.1 Introduction

9.2 Early Relay Metathesis Discoveries

9.3 Examples of Relay Metathesis Directed at Targets Other than Natural Products

9.4 Examples of Relay Metathesis Motivated by Natural Product Synthesis

9.5 Examples of Relay Metatheses Thwarted in Achieving the Desired Outcome

9.6 Conclusion

Acknowledgments

References

Chapter 10: Cross-metathesis in Natural Products Synthesis

10.1 Introduction

10.2 Functionalization of Olefins

10.3 Appending a Side Chain

10.4 Couplings

10.5 Cascade Processes Involving CM

10.6 Ene–yne CM

10.7 Alkyne CM

10.8 Conclusion and Perspectives

Acknowledgments

References

Chapter 11: Cascade Metathesis in Natural Product Synthesis

11.1 Introduction

11.2 RCM–CM Sequences

11.3 Ene–yne–ene RCM–RCM

11.4 ROM–CM Sequences

11.5 RCM–ROM Sequences – Ring-rearrangement Metathesis (RRM)

11.6 RCM–ROM Sequences Combined with Other Metathesis Reactions

11.7 Conclusions and Outlook

References

Chapter 12: Catalytic Enantioselective Olefin Metathesis and Natural Product Synthesis

12.1 Introduction

12.2 Total Synthesis of Natural Products with Enantiomerically Pure Chiral Olefin Metathesis Catalysts Bearing a C2-symmetric Diolate Ligand

12.3 Enantioselective Synthesis of Quebrachamine through an Exceptionally Challenging RCM Reaction

12.4 Synthesis of Baconipyrone C by Ru-catalyzed Enantioselective ROCM

12.5 Conclusions and Future Outlook

Acknowledgments

References

Chapter 13: Metathesis Reactions in Solid-phase Organic Synthesis

13.1 Introduction

13.2 Metathesis-based Cyclorelease Reaction

13.3 Ring-closing Metathesis (RCM)

13.4 Intraresin Dimerization

13.5 Restricting Peptide Conformation through Cyclization

13.6 Cross-metathesis on Solid Phase

13.7 Ene–yne Metathesis on Solid Phase

13.8 Conclusion

Acknowledgments

References

Index

Metathesis in Natural Product Synthesis

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The Editors

Prof. Janine CossyLaboratorie de ChimieOrganique, ESPCI10 Rue Vauquelin75231 Paris Cedex 05France

Dr. Stellios ArseniyadisLaboratoire de ChimieOrganique, ESPCI10 Rue Vauquelin75231 Paris Cedex 05France

Dr. Christophe MeyerLaboratoire de ChimieOrganique, ESPCI10 Rue Vauquelin75231 Paris Cedex 05France

CoverThe gryffon painting being part of the front cover picture has been kindly provided by Dominique Escortell

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Foreword

In the last few decades, metathesis has been among the key reactions that have revolutionized the synthesis of complex molecules. Many organic chemists in academic and industrial laboratories, in the field of natural products, have used this reaction as a very practical, versatile, and selective synthetic tool. Olefin metathesis has helped to elevate the art and science of chemical synthesis to its present high level.

The examples in this book will demonstrate that organic chemists, with the metathesis reaction in hand, have a new way to consider the connections that are required for efficient access to natural products. This book assembles the most important and interesting examples in the synthesis of natural products using metathesis. Owing to the possibilities opened by olefin and acetylenic metathesis, a great variety of carbocyclic – nitrogen-, oxygen-, sulfur-containing heterocycles – natural products with small-, medium-, and macrocyclic size can be obtained rapidly. The synthetic transformations that couple metathesis steps in cascade reactions are particularly elegant. Emphasis has been put on the metathesis step showing the importance of the catalysts that are tolerant of a large variety of functional groups, very regio-, stereoselective, and even enantioselective. The power of the catalysts and of the metathesis reaction can be appreciated when alternative pathways are considered.

Every reaction and catalyst can always be improved. In the area of metathesis, the development of more active and robust catalysts, catalysts that can control the E and Z stereoselectivity of the formed olefins, particularly the stereoselectivity of trisubstituted olefins, or catalysts that can control the enantioselectivity remains a challenge. As has been demonstrated in the past, improvements of the catalyts give rise to increasingly exciting applications in the field of complex molecules and particularly in the field of natural products synthesis. This book will be a good source of inspiration for those planning future developments of metathesis reactions in the field of natural and non-natural products.

Robert H. Grubbs

Preface

In the 1960s, the ring-opening polymerization of cycloalkenes and the disproportionation of linear alkenes, both used by the polymer and the petroleum industry, were the first reported examples of “olefin metathesis reactions.” Whereas those transformations were generally carried out with ill-defined catalysts, the mechanism of olefin metathesis proposed by Chauvin and Hérisson in 1971 identified metal carbenes as catalytically active species with reactions proceeding through metallacyclobutane intermediates. The mid-1970s saw the emergence of the first well-defined alkylidene–metal complexes for olefin metathesis initially based on tantalum and tungsten. However, in the late 1980s, the quest for higher functional group tolerance resulted in the development of the molybdenum complex, also known as Schrock’s catalyst, which was later used by Grubbs and Fu in ring-closing metathesis (RCM) to access oxygen and nitrogen heterocycles. Up to now, several applications of RCM to natural products synthesis have been reported using Schrock’s catalyst as the initiator; however, its air- and moisture sensitivity, which implies the use of a glove box or Schlenk techniques, has certainly hampered its more widespread use by organic chemists. In 1992, Grubbs and coworkers reported the first stable vinylidene ruthenium catalyst to be active in both ring-opening metathesis (ROM) and RCM. In 1995, further refinements led to the development of an air- and moisture-stable as well as highly functional group-tolerant benzylidene ruthenium complex also known as Grubbs first-generation catalyst. The latter became the first user-friendly metathesis catalyst and has allowed numerous synthetic applications. The replacement of one phosphine by a strongly σ-donating N-heterocyclic carbene ligand to further improve the stability of the active species and accelerate the initiation phase stimulated the discovery of the second-generation catalysts. To date, many catalysts have been devised with the goal of improving the rate of initiation and the stability of the catalytic propagating species to enable the metathesis of sterically hindered substrates. This was attained by fine-tuning the steric and/or electronic properties of the benzylidene part or the N-heterocyclic carbene of the ruthenium complexes, and/or other subtle ligand exchange. For the tremendous impact of metathesis in the science of organic synthesis, Chauvin, Grubbs, and Schrock received the Nobel Prize in Chemistry in 2005.

The aim of the book is to emphasize the impact of metathesis on the synthesis of natural products and/or biologically active compounds, and highlight how they have provided new and elegant solutions to many synthetic puzzles. As RCM has been the first class of metathesis reactions routinely used in natural products chemistry, the first three chapters of the book will highlight its applications to the synthesis of small- to medium-size carbocycles (Chapter 1, N. Blanchard and J. Eustache), nitrogen heterocycles (Chapter 2, L. van Delft and Floris P. J. T. Rutjes), and oxygen heterocyles (Chapter 3, J. D. Rainier). Phosphorus and sulfur heterocycles synthesized via RCM also deserved a section since they have found useful applications in the stereoselective synthesis of acyclic subunits found in various natural products (Chapter 4, C.D. Thomas and P.R. Hanson). The use of RCM for the synthesis of macrocyclic compounds has also been covered (Chapter 5, A. Gradillas and J. Pérez-Castells) since it constitutes an attractive alternative to traditional routes such as macrolactonization or macrolactamization. Alkynes can also be used as reacting partners in metathesis reactions as illustrated in the two following chapters of the book. Indeed, while ene–yne metathesis catalyzed by alkylidene ruthenium complexes allows a convenient access to conjugated dienes (Chapter 6, M. Mori), ring-closing alkyne metathesis using a well-defined tungsten–alkylidyne complex or molybdenum precatalysts activated in situ offers a convenient route toward cycloalkynes (Chapter 7, P. Davies). As for many reactions, there are situations where a planned metathesis event was found to be either unsuccessful or did not operate with high efficiency, stereoselectivity, and/or chemoselectivity. Silicon-tethered metathesis (Chapter 8, P. A. Evans) and the use of an unsaturated relay allowing initiation of metathesis at an appropriate reactive site (Chapter 9, T. R. Hoye and J. Jeon) are two strategies that have been used to circumvent some of these problems. More recently, cross-metathesis (CM) has emerged as a useful catalytic and chemoselective alternative to traditional olefination methods. Applications in the context of natural product synthesis have therefore been covered (Chapter 10, J. Prunet and L. Grimaud). After disclosing the synthetic potential of each of the different metathesis reactions, it appeared important to illustrate how their combination in cleverly designed cascades has led to some impressive and elegant synthesis of structurally complex natural products (Chapter 11, M. Porta and S. Blechert). The development of chiral molybdenum or ruthenium catalyst has also enabled the achievement of enantioselective metathesis reactions whose applications yet reported to the synthesis of natural products have been listed in one chapter (Chapter 12, A. H. Hoveyda, S. J. Malcolmson, S. J. Meek, and A. R. Zhugralin). Finally, the last section of the book is devoted to solid-phase metathesis, which constitutes a useful tool in diversity-oriented synthesis for chemical biology while also simplifying the purification stages (Chapter 13, S. Barluenga, P.-Y. Dakas, R. Jogireddy, G. Valot, and N. Winssinger).

We would like to warmly thank all the authors for contributing to this book and acknowledge their expertise on the different topics that have been covered. We also thank the team at Wiley-VCH and especially Stefanie Volk for her helpful assistance during the preparation of this book.

We sincerely hope that this book will be a valuable source of information for researchers working in both academic and industrial laboratories and that it will stimulate new applications and developments of metathesis in the field of natural product synthesis.

Janine Cossy, Stellios Arseniyadis, and Christophe Meyer.

List of Catalysts

List of Contributors

Sofia BarluengaUniversité Louis Pasteur deStrasbourgOrganic and BioorganicChemistry LaboratoryInstitut de Science et IngénierieSupramoléculaire8 Allée Gaspard Monge67000 StrasbourgFrance

Nicolas BlanchardUniversité de Haute-AlsaceEcole Nationale Supérieure deChimie de MulhouseLaboratoire de Chimie Organiqueet Bioorganique associé au CNRS3 Rue Alfred Werner68093 Mulhouse CedexFrance

Siegfried BlechertTechnische Universität BerlinInstitute of ChemistryStraße des 17. Juni 13510623 BerlinGermany

Pierre-Yves DakasUniversité Louis Pasteur deStrasbourgOrganic and BioorganicChemistry LaboratoryInstitut de Science et IngénierieSupramoléculaire8 Allée Gaspard Monge67000 StrasbourgFrance

Paul W. DaviesUniversity of BirminghamSchool of ChemistryBirminghamB15 2TTUnited Kingdom

Jacques EustacheUniversité de Haute-AlsaceEcole Nationale Supérieure deChimie de MulhouseLaboratoire de Chimie Organiqueet Bioorganique associé au CNRS3 Rue Alfred Werner68093 Mulhouse CedexFrance

P. Andrew EvansThe University of LiverpoolDepartment of ChemistryCrown StreetLiverpool L69 7ZDUK

Ana GradillasUniversidad CEU-San PabloDepartamento de QuímicaFacultad de FarmaciaUrb. Montepríncipe28668 Boadilla del MonteMadridSpain

Laurence GrimaudEcole Nationale Supérieure desTechniques AvancéesUnité Chimie et Procédés32 boulevard Victor75739 Paris Cedex 15France

Paul R. HansonUniversity of KansasDepartment of Chemistry1251 Wescoe Hall DriveMalott HallLawrence, KS 66045USA

Amir H. HoveydaBoston CollegeDepartment of ChemistryEugene F. MerkertChemistry CenterChestnut HillMA 02467USA

Thomas R. HoyeUniversity of MinnesotaDepartment of Chemistry207 Pleasant StreetSEMinneapolisMinnesota 55455USA

Junha JeonUniversity of MinnesotaDepartment of Chemistry207 Pleasant StreetSEMinneapolisMinnesota 55455USA

Rajamalleswaramma JogireddyUniversité Louis Pasteur deStrasbourgOrganic and BioorganicChemistry LaboratoryInstitut de Science et IngénierieSupramoléculaire8 Allée Gaspard Monge67000 StrasbourgFrance

Steven J. MalcolmsonBoston CollegeDepartment of ChemistryEugene F. MerkertChemistry CenterChestnut HillMA 02467USA

Simon J. MeekBoston CollegeDepartment of ChemistryEugene F. MerkertChemistry CenterChestnut HillMA 02467USA

Silvie A. MeeuwissenRadboud University NijmegenInstitute for Molecules andMaterialsHeyendaalseweg 1356525 ED NijmegenThe Netherlands

Miwako MoriHealth Sciences University ofHokkaidoIshikari-TobetsuHokkaido061-0293Japan

Marta PortaTechnische Universität BerlinInstitute of ChemistryStraße des 17. Juni 13510623 BerlinGermany

Joëlle PrunetEcole PolytechniqueLaboratoire de SynthèseOrganiqueUMR CNRS 7652DCSO91128 PalaiseauFrance

Javier Pérez-CastellsUniversidad CEU-San PabloDepartamento de QuímicaFacultad de FarmaciaUrb. Montepríncipe28668 Boadilla del MonteMadridSpain

Jon D. RainierUniversity of UtahDepartment of Chemistry315 East 1400 SouthSalt Lake CityUT 84112USA

Floris P. J. T. RutjesRadboud University NijmegenInstitute for Molecules andMaterialsHeyendaalseweg 1356525 ED NijmegenThe Netherlands

Christopher D. ThomasUniversity of KansasDepartment of Chemistry1251 Wescoe Hall DriveMalott HallLawrence, KS 66045USA

Sebastiaan (Bas) A. M. W.van den BroekRadboud University NijmegenInstitute for Molecules andMaterialsHeyendaalseweg 1356525 ED NijmegenThe Netherlands

Floris L. van DelftRadboud University NijmegenInstitute for Molecules andMaterialsHeyendaalseweg 1356525 ED NijmegenThe Netherlands

Gaële ValotUniversité Louis Pasteur deStrasbourgOrganic and BioorganicChemistry LaboratoryInstitut de Science et IngénierieSupramoléculaire8 Allée Gaspard Monge67000 StrasbourgFrance

Nicolas WinssingerUniversité Louis Pasteur deStrasbourgOrganic and BioorganicChemistry LaboratoryInstitut de Science et IngénierieSupramoléculaire8 Allée Gaspard Monge67000 StrasbourgFrance

Adil R. ZhugralinBoston CollegeDepartment of ChemistryEugene F. MerkertChemistry CenterChestnut HillMA 02467USA

Abbreviations

AcacetylacacacetylacetonatoAIBNazobisiisobutyronitrileArarylAROMasymmetric ring-closing metathesisBBN9-borabicyclononane9-BBN9-borabicyclo[3.3.0]nonan-9-ylBnbenzylBoctert-butyloxycarbonylBOMbenzyloxymethylBQ1,4-benzoquinoneBzbenzoylCANceric ammonium nitrateCatcatalyticCbzbenzyloxycarbonylCMcross-metathesisCODcycloocta-1,5-dieneCpcyclopentadienylCp*1,2,3,4,5-pentamethylcyclopentadienylCSA10-camphorsulfonic acidCycyclohexyldbadibenzylideneacetoneDBU1,8-diazabicyclo[5.4.0]undec-7-eneDCCN,N′-dicyclohexylcarbodiimideDCE1,2-dichloroethaneDDQ2,3-dichloro-5,6-dicyanobenzoquinoneDIADdiisopropyl azodicarboxylateDIPEAdiisopropylethylamineDMAPN,N-dimethylaminopyridineDMB3′,5′-dimethoxybenzoindmdbabis(3,5-dimethoxybenzylidene)acetoneDMDOdimethyldioxiraneDMFN,N-dimethylformamideDMPDess-Martin periodinaneDMPdimethoxypropaneDMPU1,3-dimethyl-3,4,5,6-tetrahydro-2-(1H)-pyrimidinoneDMSOdimethylsulfoxydeDPPAdiphenylophosphoryl azidedppp1,3-bis(diphenylphosphino)propaneEDC1-ethyl-3-(3-dimethylaminopropyl)carbodiimideEtethylFmoc9-fluorenylmethoxycarbonylGrubbs IIbenzylidene[1,3-bis(2,4,6-trimethylphenyl)-2-imidazolidinylidene] dichloro(tricyclohexylphosphine) rutheniumHMDShexamethyldisilazaneHMPAhexamethylphosphoroamideHOBthydroxybenzotriazolei-prisopropylIBX2-iodoxybenzoic aciddIcr(+)-?2-caranylImimidazoleIpcdiisopinocampheylKHMDSpotassium hexamethyldisilazideLDAlithium N,N-diisopropylamideLiHMDSlithium bistrimethylsilylamidem-CPBAm-chloroperbenzoic acidMemethylMEM2-methoxyethoxymethoxyMesmesitylMOMmethoxymethylMsmethanesulfonylMSmolecular sievesNaHMDSsodium hexamethyldisilazideNBSN-bromosuccinimideNCSN-chlorosuccinimideNISN-iodosuccinimideNMON-methylmorpholine N-oxidePCCpyridinium chlorochromatePhphenylPhthphthalylPivpivaloylPMBp-methoxybenzylPMP4-methoxyphenylPPTSpyridinium p-toluenesulfonatepTspara-toluensulfonylPypyridineQuantquantitativeRCAMring-closing alkyne metathesisRCEYMring-closing ene-yne metathesisRCMring-closing metathesisROMring-opening metathesisROMPring-opening metathesis polymerizationRRCMrelay ring-closing metathesisRRMring-rearrangement metathesisrtroom temperaturet-Butertiary butylTBAFtetrabutylammonium fluorideTBDPStert-butyldiphenylsilylTBStert-butyldimethylsilylTCEtrichloroethoxymethoxyTeoc2-(trimethylsilyl)ethoxycarbonylTEStriethylsilylTftrifluoromethanesulfonylTFAtrifluoroacetic acid2-Th2-thienylTHFtetrahydrofuranTHPtetrahydropyranTIPStriisopropylsilylTMEDAN,N,N′,N′-tetramethylethylenediamineTMStrimethylsilylTol-BINAP2,2′-bis(ditolylphosphino)-1,1′-binaphthaleneTPAPtetra(n-propyl)ammonium perruthenateTrtriphenylmethyl (trityl)TrttritylTsp-toluenesulfonylTStransition state

Chapter 1

Synthesis of Natural Products Containing Medium-size Carbocycles by Ring-closing Alkene Metathesis

Nicolas Blanchard and Jacques Eustache

1.1 Introduction

This chapter deals with the synthesis of naturally occurring molecules (or related models) and focuses on the construction of medium-size carbocycles by ring-closing metathesis (RCM). We have arbitrarily chosen to organize this chapter by increasing ring size. Strategic aspects and potential problems are discussed.

1.2 Formation of Five-membered Carbocycles by RCM

Strategic positioning of the double bonds of a 1,6-diene prior to RCM can be efficiently accomplished via [3,3]-sigmatropic rearrangements. Only selected examples are discussed below, based on originality and efficiency criteria. Catalytic asymmetric Claisen rearrangement was reported by Hiersemann et al. in the enantioselective synthesis of the C10–C18 segment of ecklonialactone B (1), a C18-oxylipin isolated from the brown algae Ecklonia stolonifera and Egregia menziessi [1]. The [3,3]-sigmatropic rearrangement of 2 using catalyst 3 led to the acyclic α-keto ester 4 that can be reduced and cyclized to the corresponding disubstituted cyclopentene 5 using [Ru]-II. Further functional group transformations led to the desired C10–C18 fragment 6 of the natural product (Scheme 1.1).

Scheme 1.1

A [3,3]-sigmatropic rearrangement/RCM sequence [2] was also used as a key step in the total synthesis of a bioactive spirobenzofuran 7 isolated from the mycelium cultures of Acremonium sp. HKI 0230 [3]. The two consecutive quaternary centers embedded in the 1,6-diene 9 are worthy of note in the context of cyclopentene formation by RCM, and the five-membered ring compound 10 was obtained in high yield (97%) using catalyst [Ru]-I. The same type of strategy was applied for the efficient construction of the two vicinal quaternary carbon atoms present in the herbertanes sesquiterpenes (Scheme 1.2) [4].

Scheme 1.2

Besides the Ireland–Claisen [3,3]-sigmatropic rearrangement/RCM sequence, some examples of Johnson–Claisen/RCM were reported by Ghosh and Maity [5]. In the first total synthesis of sequosempervirin A (11), a norlignan isolated from Sequoia sempervirens, the γ, δ-unsaturated carbonyl derivative was prepared from by Johnson–Claisen rearrangement. Further steps led to , the precursor of the key RCM reaction catalyzed by [Ru]-, which established the desired spiro structure of compound ().