Asymmetric Synthesis of Nitrogen Heterocycles

426 Pages·2009·3.6 MB·English

by  Jacques Royer

AsymmetricSynthesisofNitrogen
Heterocycles
Editedby
JacquesRoyer
FurtherReading
Cornils,B.,Herrmann,W.A.,Muhler,M., Hiersemann,M.,Nubbemeyer,U.(eds.)
Wong,C.-H.(eds.) TheClaisenRearrangement
Catalysisfrom AtoZ
MethodsandApplications
AConciseEncyclopedia
2007
2007 Hardcover
Hardcover ISBN:978-3-527-30825-5
ISBN:978-3-527-31438-6
Dalko,P.I.(ed.)
Knipe,C.,Watts,W.E.(eds.) EnantioselectiveOrganocatalysis
OrganicReaction Mechanisms,
ReactionsandExperimentalProcedures
2005
2007
Hardcover Hardcover
ISBN:978-0-470-03403-3 ISBN:978-3-527-31522-2
OnlineBuchWileyInterscience
ISBN:978-0-470-06661-4
Roberts,S.M.
CatalystsforFineChemical
Mikami,K.,Lautens,M.(eds.)
Synthesis
New Frontiersin Asymmetric
Volume5:Regio-andStereo-Controlled
Catalysis
OxidationsandReductions
2007 2007
Hardcover Hardcover
ISBN:978-0-471-68026-0 ISBN:978-0-470-09022-0
Sheldon,R.A.,Arends,I.,Hanefeld,U. Wyatt,P.,Warren,S.
Green ChemistryandCatalysis OrganicSynthesis
StrategyandControl
2007
Hardcover 2007
ISBN:978-3-527-30715-9 E-Book
ISBN:978-0-470-06120-6
Asymmetric Synthesis of Nitrogen
Heterocycles
Edited by
Jacques Royer
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ISBN:978-3-527-32036-3
V
Foreword
It is a great pleasure to see a new volume of Asymmetric Synthesis of Nitrogen
Heterocyclesgoingtopress.
Since the nineteenth century, the study of nitrogen-containing products, es-
pecially alkaloids, has often provided the impetus for great advances in organic
chemistry.Ononehand,theunceasingproliferationofalkaloidliteratureaccounts
for the interest in this class of natural products.On the other hand, heterocyclic
chemistry,ingeneral,representsaspecialtopicinmedicinalchemistry.Moreover,
opticallyactiveaminesconstituteanimportantclassofcompoundsthatfindawide
range of interest as chiral building blocks and as part of many pharmaceutical
products.Indeed,asymmetricsynthesisismorethananacademicspecialty.
It is the goal of this book to bring all these aspects up to date and to extend
the scope of asymmetric synthesis of nitrogen heterocycles to a large variety of
structures, that is, with respect to ring size and number of heteroatoms. The
objective of the Editor,who is also contributorof a chapter, has beenreached in
receivingthecollaborationofleadersinthisfieldfromEurope,ChinaandJapan.
This volume is divided into two parts. Part One describes in four chapters
asymmetric synthesis of nitrogen heterocycles containing only one heteroatom
in 3-,4-,5-,6-,7- (and more) membered rings. Part Two consists of four chapters
covering the asymmetric synthesis of nitrogen heterocycles with more than one
heteroatom.
Iamsurethatthistreatise,whichhighlightsanimportantfieldofenantioselective
chemistry, should be of value to both academic and pharmaceutical chemists as
wellasPhDstudents.
Paris,October2008 ProfessorH.-P.Husson
AsymmetricSynthesisofNitrogenHeterocycles.EditedbyJacquesRoyer
Copyright2009WILEY-VCHVerlagGmbH&Co.KGaA,Weinheim
ISBN:978-3-527-32036-3

VII
Contents
Preface XIII
ListofContributors XV
PartOne AsymmetricSynthesisofNitrogenHeterocyclesContainingOnlyOne
Heteroatom 1
1 AsymmetricSynthesisofThree-andFour-MemberedRing
Heterocycles 3
GiulianaCardillo,LucaGentilucciandAlessandraTolomelli
1.1 SubstitutedAziridines 3
1.1.1 Generalities 3
1.1.2 AsymmetricAziridinationviaCyclizationMethods 6
1.1.2.1 CyclizationofaNucleophilicNonanElectrophilicC(PathwayA) 7
1.1.2.2 CyclizationofaStabilizedAniononanElectrophilicN(PathwayB) 9
1.1.3 AsymmetricAziridinationviaCycloadditionMethods 12
1.1.3.1 AdditionofNitrenestoAlkenes 12
1.1.3.2 ReactionbetweenCarbenesandImines 16
1.1.4 RingTransformationMethods 27
1.1.4.1 AziridinesfromEpoxides 27
1.1.4.2 AziridinesfromOtherHeterocycles 30
1.1.5 RacemateResolution 31
1.1.6 AsymmetricSynthesisofAzirines 33
1.1.6.1 TheNeberReaction 33
1.1.6.2 ThermalorPhotochemicalTreatmentofVinylAzides 34
1.1.6.3 EliminationfromAziridines 34
1.1.6.4 ResolutionofRacemicAzirines 35
1.1.6.5 OxidationofAziridines 36
1.2 SubstitutedMonocyclicAzetidinesandCarbocyclic-Fusedsystems 36
1.2.1 Generalities 36
1.2.2 CyclizationMethods:Introduction 38
AsymmetricSynthesisofNitrogenHeterocycles.EditedbyJacquesRoyer
Copyright2009WILEY-VCHVerlagGmbH&Co.KGaA,Weinheim
ISBN:978-3-527-32036-3
VIII Contents
1.2.2.1 Cyclizationmethods:EnantiopureAzetidinesviaFormationofC–N
Bond 39
1.2.2.2 CyclizationMethods:EnantiopureAzetidinesviaFormationofC–C
Bond 40
1.2.3 AzetidinesbyResolutionofRacemates 42
1.2.4 AzetidinesbyRingTransformation 44
References 45
2 AsymmetricSynthesisofFive-MemberedRingHeterocycles 51
Pei-QiangHuang
2.1 MonocyclicPyrrolidinesandPyrrolidinones 51
2.1.1 Generalities 51
2.1.2 CyclizationMethods 52
2.1.2.1 CyclizationviaC /C –NBondFormation 52
1 5
2.1.2.2 CyclizationviaC –C BondFormation 61
2 3
2.1.2.3 CyclizationInvolvingC –C BondFormation 62
3 4
2.1.3 CycloadditionMethods 64
2.1.3.1 CycloadditionApproach 64
2.1.3.2 AnnulationApproach 66
2.1.4 RingTransformationMethods 67
2.1.4.1 RingExpansionMethods 67
2.1.4.2 RingContractionMethods 68
2.1.5 SubstitutionofAlreadyFormedHeterocycle 68
2.1.5.1 ByNucleophilicReactionofPyrrolidiniumIons 71
2.1.5.2 ByNucleophilicReactionofCyclicImides 72
2.1.5.3 ByNucleophilicAddition/CycloadditionofPyrrolidineNitrones 74
2.1.5.4 ByFunctionalizationof2-Pyrrolines 76
2.1.5.5 ByEnantioselectiveReactions 77
2.1.5.6 ByFunctionalizationatC /C PositionsofPyrrolidines 77
3 4
2.2 Pyrrolines 79
2.2.1 SynthesisofPyrrolinesbyCyclizationandAnnulationReactions 79
2.2.2 SynthesisofPyrrolinesbySubstitutionofAlreadyFormed
Heterocycles 80
2.3 FusedBicyclicSystemswithBridgeheadNitrogen 82
2.3.1 Pyrrolizidines 82
2.3.1.1 ThroughExtensionofMethodsfortheSynthesisofPyrrolidines 82
2.3.1.2 OtherMethodsfortheSynthesisofPyrrolizidines 83
2.3.1.3 AsymmetricSynthesisofPolyhydroxylatedPyrrolizidines 85
2.4 Acknowledgments 87
References 87
3 AsymmetricSynthesisofSix-MemberedRingHeterocycles 95
NaokiToyooka
3.1 Introduction 95
3.2 Dihydropyridines 95
Contents IX
3.3 Tetrahydropyridines 98
3.3.1 Ring-ClosingMetathesis(RCM) 98
3.3.2 ReductionofPyridineDerivatives 101
3.3.3 DeracemizationProcesses 101
3.3.4 MichaelAdditionFollowedbyElimination 102
3.3.5 EnamineReaction 102
3.3.6 Electrocyclization 105
3.4 MonocyclicPiperidinesandCarbocyclicFusedSystems 107
3.4.1 Generalities 107
3.4.2 CyclizationMethods 107
3.4.2.1 NitrogenasaNucleophile 108
3.4.2.2 C–CBondFormation 113
3.4.3 CycloadditionMethods 117
3.4.3.1 [4+2]AzadieneCycloaddition 117
3.4.3.2 [4+2]AcylnitrosoCycloaddition 117
3.4.3.3 [3+2]Cycloaddition 119
3.4.4 RingTransformationMethods 119
3.4.4.1 RingEnlargementofPyrrolidinestoSubstitutedPiperidines 120
3.4.4.2 RingTransformationofLactonesto2-Piperidones 121
3.4.4.3 RingEnlargementofγ-Lactamto2-Piperidones 122
3.4.5 SubstitutionofAlreadyFormedHeterocycle 123
3.4.5.1 Phenylglycinol-DerivedOxazolidine 123
3.4.5.2 AsymmetricMichaelAddition 125
3.4.5.3 NitroneCycloaddition 127
3.4.5.4 IminiumStrategies 128
3.4.5.5 OxidativeMethods 131
3.5 FusedTri-orBicyclicSystemwithBridgeheadNitrogen 132
References 135
4 AsymmetricSynthesisofSeven-andMore-MemberedRing
Heterocycles 139
YvesTroinandMarie-EveSinibaldi
4.1 SubstitutedAzepines 139
4.1.1 Generalities 139
4.1.2 CyclizationMethods 142
4.1.2.1 Lactamization:C–NBondFormation 142
4.1.2.2 RadicalCyclization 146
4.1.2.3 IntramolecularCyclization 149
4.1.2.4 OxidativePhenolCouplingReaction 155
4.1.2.5 TheRingClosureMetathesis 155
4.1.3 CycloadditionMethods 161
4.1.3.1 [5+2]Cycloaddition 162
4.1.3.2 [4+3]Cycloaddition 162
4.1.3.3 NitroneCycloaddition 162