Modern Aldol Reactions

344 Pages·2004·3.31 MB·English

by  Evans D. A.

R.Mahrwald(Ed.)
ModernAldolReactions
Vol.1:Enolates,
Organocatalysis,
BiocatalysisandNatural
ProductSynthesis
ModernAldolReactions.Vol.1:Enolates,Organocatalysis,BiocatalysisandNaturalProductSynthesis.
EditedbyRainerMahrwald
Copyright82004WILEY-VCHVerlagGmbH&Co.KGaA,Weinheim
ISBN:3-527-30714-1
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Rainer Mahrwald (Ed.)
Modern Aldol Reactions
Vol. 1: Enolates, Organocatalysis, Biocatalysis
and Natural Product Synthesis
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v
Foreword
Historically, the stimulus for the development of a particular reaction has
beeninterconnectedwithaclassofnaturalproductswhosesynthesiswould
begreatlyfacilitatedbytheuseofthatparticularbondconstruction.Forex-
ample,thesteroidsynthesischallengesprovedinstrumentalinthedevelop-
mentoftheDiels–Alderreaction.Sotoothesynthesischallengesassociated
with the macrolide antibiotics have provided the motivation for the devel-
opmentofthefullpotentialofthealdoladditionreaction.R.B.Woodward’s
1956 quote on the ‘‘hopelessly complex’’ architecture of the erythromycins
wasprobablystimulated,inpart,bythefactthatthealdolreactionexistedin
acompletelyunderdevelopedstatefivedecadesago.
O
Me Me
Me
OH OH
Me Me
OH O
Theerythromycin-Astructure,asviewed
Me byWoodwardinthe’50s
Et O O NMe
2
H ‘‘Erythromycin,withallofour
OH
O O advantages,looksatpresentquite
hopelesslycomplex,particularlyinview
Me
ofitsplethoraofasymmetriccenters.’’
O
Me H
R.B.WoodwardinPerspectivesin
Me OrganicChemistry;Todd,A.Ed.;Wiley-
MeO
Interscience,NewYork,1956,page160.
OH
The challenges associated with the development of this reaction are also
embodied in the more general goals of acyclic stereocontrol that have been
under active investigation for nearly twenty-five years. In these studies, the
goal of understanding pi-face selectivity at trigonal carbon centers for a
multitudeoforganictransformationshasbeentheultimateobjective.From
theseresearchactivities,ahostofstereochemicalmodelshaveevolved,such
as the Felkin–Anh model for carbonyl addition and the Zimmermann–
Traxleraldolstereochemicalmodelforaldoldiastereoselection.
vi Foreword
The development of modern aldol reaction methods has evolved through
a succession of pivotal discoveries that have advanced the whole field of
stereoselectivesynthesis:
A. Development of enolization strategies for the formation of (E) and (Z)
enolates.
B. Development of kinetic diastereoselective aldol addition variants
through the discovery of optimal metal architectures [B(III), Ti(IV),
Sn(II)].
C. Discovery of aldol reaction variants such as the Lewis acid catalyzed
additionofenolsilanestoaldehydes(Mukaiyamaaldolvariant).
D. Developmentofchiralenolatesexhibitingexceptionalpi-faceselectivities.
E. DevelopmentofchiralmetalcomplexesasLewisacidaldolcatalysts.
Thistwo-volumeseriesonaldoladditionreactionmethodologybringsto-
gether an up-to-date discussion of all aspects of this versatile process. The
readerwillgainanappreciationfortheroleofmetalenolatearchitecturein
aldoldiastereoselectivities(Vol.I;Chapters1–3)andfortheutilityofchiral
metal complexes in the catalysis of the Mukaiyama aldol reaction (Vol. II;
Chapters 1–3, 5). In Vol. II; Chapter 6, enantioselective catalytic processes
incorporating both enolization and addition are surveyed, as is the exciting
progress being made in the use of chiral amines as aldol catalysts (Vol. I;
Chapter4).Thishighlyactiveareaofresearchwillcontinuetodevelopever
moreversatilechiralcatalystsandstereochemicalcontrolconcepts.
Studentsandresearchersinthefieldofasymmetricsynthesiswillgreatly
profit from the contributions of this distinguished group of authors who
havesoinsightfullyreviewedthistopic.
May2004 DavidA.Evans
HarvardUniversity
vii
Contents
Volume 1
Preface xvii
ListofContributors xix
1 FundamentalsandTransition-stateModels.AldolAdditionsofGroup
1and2Enolates 1
ManfredBraun
1.1 Introduction 1
1.2 TheAcidorBase-mediated‘‘Traditional’’AldolReaction 2
1.3 TheAldolAdditionofPreformedEnolates–Stereoselectivityand
Transition-stateModels 9
1.4 StereoselectiveAldolAdditionofLithium,Magnesiumand
SodiumEnolates 25
1.4.1 AdditionofChiralEnolatestoAchiralCarbonylCompounds 26
1.4.1.1 a-SubstitutedEnolates 26
1.4.1.2 a-UnsubstitutedEnolates 32
1.4.2 AdditionofAchiralEnolatestoChiralCarbonylCompounds 41
1.4.3 AdditionofChiralEnolatestoChiralCarbonylCompounds 49
1.4.4 AdditionofAchiralEnolatestoAchiralCarbonylCompoundsin
thePresenceofChiralAdditivesandCatalysts 51
1.5 Conclusion 52
References 53
2 TheDevelopmentofTitaniumEnolate-basedAldolReactions 63
ArunK.Ghosh,M.Shevlin
2.1 Introduction 63
2.2 AdditionsofEnolatestoKetones 65
2.3 AdditionofEnolatesWithouta-SubstituentstoAldehydes 66
2.3.1 StereoselectiveAcetateAldolReactionsUsingChiral
Auxiliaries 67
2.3.2 StereoselectiveAcetateAldolReactionsInvolvingChiralTitanium
Ligands 69
viii Contents
2.3.3 AlternativeApproachestoAcetateAldolAdducts 70
2.4 AdditionofEnolateswitha-SubstituentstoAldehydes 72
2.4.1 SynDiastereoselectivity 74
2.4.1.1 SynthesisofsynAldolsinRacemicForm 75
2.4.1.1.1 ReactionsofKetones 75
2.4.1.1.2 ReactionsofEstersandThiolEsters 77
2.4.1.1.3 AldolReactionsofAldehydeHydrazones 78
2.4.1.2 SynthesisofOpticallyActivesynAldolsUsingChiral
Auxiliaries 80
2.4.1.2.1 AminoAcid-derivedOxazolidinoneandRelatedAuxiliaries 80
2.4.1.2.2 Camphor-derivedChiralAuxiliaries 84
2.4.1.2.3 AminoindanolandAminoAcid-derivedChiralAuxiliaries 87
2.4.1.2.4 OtherChiralAuxiliaries 90
2.4.1.3 SynthesisofOpticallyActivesynAldolsUsingChiralTitanium
Ligands 92
2.4.1.4 SynthesisofOpticallyActivesynAldolswithChiralEnolates 95
2.4.2 AntiDiastereoselectivity 98
2.4.2.1 SynthesisofantiAldolsinRacemicForm 98
2.4.2.2 SynthesisofOpticallyActiveantiAldolsbyUseofChiral
Auxiliaries 99
2.4.2.2.1 AminoindanolandRelatedChiralAuxiliaries 99
2.4.2.2.2 OxazolidinethioneandOxazolidineseloneChiralAuxiliaries 103
2.4.2.3 SynthesisofOpticallyActiveantiAldolsbyUseofChiral
TitaniumLigands 104
2.5 NaturalProductSynthesisviaTitaniumEnolateAldol
Reactions 105
2.5.1 LactoneNaturalProducts 105
2.5.1.1 Tetrahydrolipstatin 106
2.5.1.2 MyxopyroninsAandB 106
2.5.1.3 CallystatinA 107
2.5.1.4 AI-77-B 108
2.5.2 MacrolideNaturalProducts 110
2.5.2.1 Epothilone490 110
2.5.2.2 CryptophycinB 110
2.5.2.3 AmphidinolideT1 111
2.5.2.4 Rapamycin 112
2.5.2.5 Spongistatins1and2 113
2.5.3 MiscellaneousNaturalProducts 114
2.5.3.1 Tautomycin 114
2.5.3.2 CrocacinC 115
2.5.3.3 StigmatellinA 116
2.5.3.4 DenticulatinB 117
2.5.3.5 MembrenoneC 119
2.6 TypicalExperimentalProceduresforGenerationofTitanium
Enolates 120
2.6.1 ExperimentalProcedures 120
Contents ix
2.6.2 AlternativeApproachestoTitaniumEnolateGeneration 121
2.7 Conclusion 121
References 122
3 BoronandSiliconEnolatesinCrossedAldolReaction 127
TeruakiMukaiyamaandJun-ichiMatsuo
3.1 Introduction 127
3.2 CrossedAldolReactionsUsingBoronEnolates 127
3.2.1 DiscoveryofAldolReactionMediatedbyBoronEnolates 127
3.2.2 NewMethodforDirectGenerationofBoronEnolates 129
3.2.3 RegioselectivityonGenerationofBoronEnolates 130
3.2.4 StereoselectiveFormationof(E)or(Z)BoronEnolates 131
3.2.5 syn-SelectiveAsymmetricBoronAldolReactions 134
3.2.6 anti-SelectiveAsymmetricAldolReaction 135
3.3 CrossedAldolReactionsUsingSiliconEnolates 137
3.3.1 DiscoveryofSiliconEnolate-mediatedCrossedAldol
Reactions 137
3.3.2 LewisAcid-catalyzedAldolReactionsofSiliconEnolates 143
3.3.3 Non-catalyzedAldolReactionsofSiliconEnolates 147
3.3.4 LewisBase-catalyzedAldolReactionsofTrimethylsilyl
Enolates 148
3.3.5 DiastereoselectiveSynthesisofPolyoxygenated
Compounds 149
3.3.6 AsymmetricAldolReactionsUsingChiralTin(II)LewisAcid
Catalysts 150
3.3.6.1 StoichiometricEnantioselectiveAldolReaction 151
3.3.6.2 CatalyticEnantioselectiveAldolReaction 154
References 155
4 Amine-catalyzedAldolReactions 161
BenjaminList
4.1 Introduction 161
4.2 AminocatalysisoftheAldolReaction 162
4.2.1 IntermolecularAldolizations 163
4.2.1.1 AldehydeDonors 164
4.2.1.2 KetoneDonors 166
4.2.2 IntramolecularAldolizations 167
4.2.2.1 EnolexoAldolizations 167
4.2.2.2 EnolendoAldolizations 171
4.3 AsymmetricAminocatalysisoftheAldolReaction 173
4.3.1 IntramolecularAldolizations 173
4.3.1.1 EnolendoAldolizations 173
4.3.1.2 EnolexoAldolizations 177
4.3.2 IntermolecularAldolizations 179
4.3.2.1 KetoneDonors 179
x Contents
4.3.2.2 AldehydeDonors 193
References 196
5 Enzyme-catalyzedAldolAdditions 201
Wolf-DieterFessner
5.1 Introduction 201
5.2 GeneralAspects 202
5.2.1 ClassificationofLyases 202
5.2.2 EnzymeStructureandMechanism 204
5.2.3 PracticalConsiderations 207
5.3 PyruvateAldolases 208
5.3.1 N-AcetylneuraminicAcidAldolase 208
5.3.2 KDOAldolase 216
5.3.3 DAHPSynthase 217
5.3.4 KDPGAldolaseandRelatedEnzymes 218
5.4 DihydroxyacetonePhosphateAldolases 221
5.4.1 FruA 222
5.4.2 TagA 224
5.4.3 RhuAandFucA 224
5.4.4 DHAPSynthesis 227
5.4.5 Applications 230
5.4.6 AldolTransferEnzymes 246
5.5 TransketolaseandRelatedEnzymes 247
5.6 2-Deoxy-D-ribose5-PhosphateAldolase 250
5.7 GlycineAldolases 254
5.8 RecentDevelopments 257
5.9 SummaryandConclusion 258
References 260
6 Antibody-catalyzedAldolReactions 273
FujieTanakaandCarlosF.Barbas,III
6.1 Introduction 273
6.2 GenerationofAldolaseAntibodies 273
6.2.1 AntibodyasCatalystScaffold 273
6.2.2 GenerationofAldolaseAntibodiesthatOperateviaanEnamine
Mechanism 274
6.2.2.1 ReactiveImmunizationwiththeSimpleDiketoneDerivative 275
6.2.2.2 CombiningReactiveImmunizationwithTransition-state
Analogs 277
6.2.2.3 ReactiveImmunizationwithotherDiketones 279
6.3 AldolaseAntibody-catalyzedAldolandRetro-aldol
Reactions 279
6.3.1 Antibody38C2-catalyzedAldolReactions 280
6.3.2 Antibody38C2-CatalyzedRetro-aldolReactionsandtheir
ApplicationtoKineticResolution 283