Metathesis in natural product synthesis : strategies, substrates and catalysts

414 Pages·2010·6.06 MB·English

by  Janine Cossy

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MetathesisinNaturalProductSynthesis
Editedby
JanineCossy,StelliosArseniyadis,
andChristopheMeyer
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Metathesis in Natural Product Synthesis
Strategies, Substrates and Catalysts
Edited by
Janine Cossy, Stellios Arseniyadis, and Christophe Meyer
With a Foreword by Robert H. Grubbs
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V
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
academicandindustriallaboratories,inthefieldofnaturalproducts,haveusedthis
reactionasaverypractical,versatile,andselectivesynthetictool.Olefinmetathesis
hashelpedtoelevatetheartandscienceofchemicalsynthesistoitspresenthigh
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
beobtainedrapidly.Thesynthetictransformationsthatcouplemetathesisstepsin
cascadereactionsareparticularlyelegant.Emphasishasbeenputonthemetathesis
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
alternativepathwaysareconsidered.
Every reaction and catalyst can always be improved. In the area of metathesis,
thedevelopmentofmoreactiveandrobustcatalysts,catalyststhatcancontrolthe
EandZstereoselectivityoftheformedolefins,particularlythestereoselectivityof
trisubstituted olefins, or catalysts that can control the enantioselectivity remains
achallenge.Ashas beendemonstratedinthepast,improvementsofthecatalyts

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
goodsourceofinspirationforthoseplanningfuturedevelopmentsofmetathesis
reactionsinthefieldofnaturalandnon-naturalproducts.
RobertH.Grubbs
MetathesisinNaturalProductSynthesis:Strategies,SubstratesandCatalysts.EditedbyJanineCossy,
StelliosArseniyadis,andChristopheMeyer
Copyright©2010WILEY-VCHVerlagGmbH&Co.KGaA,Weinheim
ISBN:978-3-527-32440-8
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VII
Contents
Foreword V
Preface XV
ListofCatalysts XIX
ListofContributors XXI
Abbreviations XXV
1 SynthesisofNaturalProductsContainingMedium-sizeCarbocyclesby
Ring-closingAlkeneMetathesis 1
NicolasBlanchardandJacquesEustache
1.1 Introduction 1
1.2 FormationofFive-memberedCarbocyclesbyRCM 1
1.3 FormationofSix-memberedCarbocyclesbyRCM 11
1.4 FormationofSeven-memberedCarbocyclesbyRCM 22
1.5 FormationofEight-memberedCarbocyclesbyRCM 30
1.6 FormationofNine-memberedCarbocyclesbyRCM 33
1.7 Formationof10-memberedCarbocyclesbyRCM 34
1.8 Conclusion 39
References 40
2 NaturalProductsContainingMedium-sizedNitrogenHeterocycles
SynthesizedbyRing-closingAlkeneMetathesis 45
Sebastiaan(Bas)A.M.W.vandenBroek,SilvieA.Meeuwissen,
FlorisL.vanDelft,andFlorisP.J.T.Rutjes

2.1 Introduction 45
2.2 Five-memberedNitrogenHeterocycles 47
2.2.1 Dihydropyrroles 47
2.2.2 PyrrolidineAlkaloids 47
2.2.2.1 Pyrrolidines 47
2.2.2.2 Dipyrrolidines 49
2.2.2.3 Polyhydroxypyrrolidines 49
2.2.3 IndolizidineAlkaloids 52
2.2.3.1 PolycyclicIndolizidines 52
MetathesisinNaturalProductSynthesis:Strategies,SubstratesandCatalysts.EditedbyJanineCossy,
StelliosArseniyadis,andChristopheMeyer
Copyright©2010WILEY-VCHVerlagGmbH&Co.KGaA,Weinheim
ISBN:978-3-527-32440-8
VIII Contents
2.2.3.2 Polyhydroxyindolizidines 55
2.2.4 PyrrolizidineAlkaloids 59
2.3 Six-memberedNitrogenHeterocycles 61
2.3.1 PiperidineAlkaloids 61
2.3.1.1 Piperidines 61
2.3.1.2 PiperidineCarboxylicAcids 66
2.3.1.3 Piperidones 68
2.3.1.4 Polyhydroxypiperidines 69
2.3.2 IndolizidineAlkaloids 70
2.3.3 QuinolizidineAlkaloids 73
2.4 Seven-memberedNitrogenHeterocycles 78
2.5 Eight-memberedNitrogenHeterocycles 81
2.6 Conclusion 82
References 83
3 SynthesisofNaturalProductsContainingMedium-sizeOxygen
HeterocyclesbyRing-closingAlkeneMetathesis 87
JonD.Rainier
3.1 Introduction 87
3.2 GeneralRCMApproachestoMediumRings 89
3.3 Laurencin 95
3.4 Eunicellins/Eleutherobin 102
3.5 Helianane 104
3.6 OctalactinA 105
3.7 MicrocarpalideandtheHerbarums 106
3.8 MarineLadderToxins 109
3.8.1 Ciguatoxin 109
3.8.2 Brevetoxin 117
3.8.3 Gambierol,GambiericAcid,Olefinic-ester
Cyclizations 120
3.9 Conclusion 124
Acknowledgments 124
References 124
4 PhosphorusandSulfurHeterocyclesviaRing-closingMetathesis:
ApplicationinNaturalProductSynthesis 129

ChristopherD.ThomasandPaulR.Hanson
4.1 Introduction 129
4.2 SynthesisandReactivityofSultonesDerivedfromRCM 129
4.3 TotalSynthesisoftheOriginallyProposedStructureof
(±)-Mycothiazole 132
4.4 SynthesisandReactivityofPhosphatesfromRCM 134
4.5 ApplicationsofPhosphateTethersintheSynthesisof
DolabelideC 140
4.6 Conclusion 144