Stereochemistry and Stereoselective Synthesis: an Introduction

283 Pages·2016·11.35 MB·English

by  Nógrádi

LászlóPoppeand
MihályNógrádi
Editors
LászlóPoppe,JózsefNagy,Gábor
HornyánszkyandZoltánBoros
ContributingAuthors
StereochemistryandStereoselective
Synthesis

Editedby
LászlóPoppeandMihályNógrádi
ContributingAuthors
LászlóPoppe,JózsefNagy,GáborHornyánszkyand
ZoltánBoros
Stereochemistry and Stereoselective
Synthesis
AnIntroduction
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V
Contents
AbouttheCompanionWebsite XI
Introduction XIII
PartI BasicConceptsattheMolecularLevel 1
1 StructureandProperties 3
1.1 TheCovalentBondandtheOctetRule 3
1.2 RepresentationofChemicalStructures 6
1.3 DescriptionofChemicalStructure 8
1.4 ProblemsofCorrelatingChemicalStructurewithProperties 10
References 16
2 ConceptsofStereochemistry 17
2.1 ElementsandGroupsofSymmetry 17
2.2 ClassificationoftheBasicConceptsofStereochemistry 21
2.2.1 ConceptsRelatedtoaSingleObject(Molecule)orPartsof
Thereof 23
2.2.2 ConceptsReferringtotheRelationshipofTwoObjects(Molecules)
(Isomerism,IsomericRelationship) 25
2.2.3 ConceptsReferringtotheRelationshipofPartsofanObject
(Molecule)orModesofApproachtoanObject(Topicity) 31
2.3 Stereodescriptors 37
2.3.1 TheD/LSystem,Fischer’sProjection 39
2.3.2 TheR/SSystem 41
2.3.3 HinderedRotationaroundaDoubleBond,E/ZIsomerism 43
2.3.4 AxialChirality,Helicity,M/PDescriptors 44
2.3.5 PlanarChirality,R /S -Descriptors 46
p p
2.4 ProstereogenicElements,Prochirality 48
2.4.1 ProstereoisomerismandProchirality 48
2.4.2 DistinctionofStereoheterotopicGroups,thepro-R/pro-S
Notation 50
2.4.3 ProchiralandmesoCompounds,CenterofPseudoasymmetry 52
2.4.4 DistinguishingofStereoheterotopicFaces,theRe/SiNotation 54
References 56
VI Contents
ProblemstoChapters1and2 57
PartII PropertiesattheLevelofMaterialAssemblies 65
3 Timescale,ConformationalChanges 67
3.1 ConformationalMotionofEthaneandItsOpticalInactivity 67
3.2 ConformationsandOpticalInactivityofn-Butaneand
1,2-Dichloroethane 70
3.3 BiphenylandSubstitutedBiphenyls,Atropisomerism 71
References 74
4 AbsoluteConfiguration 75
4.1 MethodstoDetermineAbsoluteConfiguration 78
4.2 StrategiestoDetermineAbsoluteConfigurationbyChemical
Correlation 79
4.2.1 TransformationsoftheLigandsAttachedtoanAsymmetricUnit
withoutInfluencingtheBondsbetweentheAsymmetricUnitand
theLigands 81
4.2.2 DegradationofMultipleAsymmetricUnitsofaMoreComplex
MoleculeuntilOnlyOneRemainsIntact 81
4.2.3 StereoconstructiveStrategyThatAddsFurtherAsymmetricElements
toOneoftheKnownAbsoluteConfigurationwithoutInfluencing
theBondsbetweenItsAsymmetricUnitandLigands 82
4.2.4 SymmetrizationofOneorMoreAsymmetricUnitsLeadingtoa
CommonCompoundwithLess(butMoreThanOne)Asymmetric
Elements 82
4.2.5 TransformationsInvolvingStereospecificReactionsofKnown
StereochemistryInfluencingtheBondsbetweentheAsymmetric
UnitandtheLigands 83
References 84
5 MethodsfortheDeterminationofEnantiomericComposition 87
5.1 ChiropticalMethods 89
5.2 NMRMethodsBasedonDiastereotopicity 89
5.2.1 MethodsBasedonFormingDiastereomericDerivatives 89
5.2.2 NMRMethodsBasedontheUseofChiralSolvents(Solvating
Agents) 92
5.2.3 NMRMethodsBasedonChiralShiftReagents 93
5.3 ChromatographicandRelatedMethodsBasedonDiastereomeric
Interactions 94
5.3.1 SeparationonaDiastereoselective(Achiral)StationaryPhase 94
5.3.2 UseofanEnantioselective(Chiral)StationaryPhase 96
5.3.2.1 GasChromatography 97
5.3.2.2 High-PerformanceLiquidChromatography 98
5.4 KineticMethodsBasedonEnantiomerSelectivity 99
Contents VII
5.4.1 EnzymaticMethods 100
5.4.2 Nonenzymatic(Chemical)Methods 101
5.5 FusionMethods 102
5.6 MethodsBasedonIsotopeDilution 102
5.7 PotentiometricMethods 102
References 103
6 Tautomerism 105
6.1 TypesofTautomerism 106
6.1.1 ValenceTautomerism 106
6.1.2 ClassicTautomerism 107
6.2 Prototropy 108
6.2.1 Oxo–EnolTautomerism 108
6.2.2 Imine–EnamineTautomerism 110
6.2.3 Amide–ImidoAcidandRelatedTautomerisms 112
6.2.4 TautomerismofAliphaticNitroCompounds 113
6.2.5 TautomerismofCarbonicAcidDerivativesContainingCumulated
DoubleBonds 113
6.2.6 Ring–ChainTautomerism 114
6.3 MethodsforStudyingTautomerism 115
6.4 NitrogenInversion 115
References 116
ProblemstoPartII 117
PartIII GeneralCharacteristicsofStereoselectiveReactions 125
7 TypesandClassificationofSelectivities 127
7.1 MainTypesofSelectivity 127
7.1.1 SubstrateSelectivity 127
7.1.2 ProductSelectivity 127
7.2 ClassificationofSelectivities 128
7.2.1 Chemoselectivity 130
7.2.1.1 InterpretationofChemoselectivity 130
7.2.1.2 ChemoselectivityinBiocatalysis 131
7.2.2 Regioselectivity 131
7.2.2.1 SubstrateRegioselectivity 132
7.2.2.2 ProductRegioselectivity 132
References 135
8 StereoselectiveandStereospecificReactions 137
8.1 Stereospecificity 137
8.2 Stereoselectivity 138
8.3 SelectiveSynthesesofEnantiomers 139
8.4 DiastereomerSelectivity 141
VIII Contents
8.5 DiastereotopeSelectivity 142
8.5.1 DiastereotopeSelectivitywiththeFormationofaNewChiral
Element 143
8.5.2 ChiralAuxiliaryGroups 145
8.5.3 EnantiodivergentSyntheticStrategyEmployingChiralAuxiliary
Groups 146
8.5.4 SignificanceofSeparatingtheDiastereomersFormed 147
8.5.4.1 PurificationofEnantiomersbytheSeparationofDiastereomers
FormedwiththeAidofanAchiralBidentateReagent 149
8.5.5 DiastereotopicVersionofAsymmetricTransformationbyInduced
Crystallization(CIAT)InvolvingDiastereotopicInteractions 149
8.5.6 DiastereotopeSelectivityinBiotransformations 153
8.5.6.1 SelectiveBiotransformationsofDiastereotopicGroups 153
8.5.6.2 SelectiveBiotransformationofDiastereotopicFaces 153
8.6 EnantiomerSelectivity 154
8.6.1 DegreeofEnantiomerSelectivityinIrreversibleProcesses 155
8.6.2 KineticResolutionUsingChemicalSystems 158
8.6.2.1 ParallelKineticResolutionwithChemicalSystems 160
8.6.3 KineticResolutionwithBiocatalysts 160
8.6.3.1 ParallelKineticResolutionwithBiocatalysis 166
8.6.4 DynamicKineticResolution(DKR) 166
8.6.4.1 DynamicKineticResolutionUsingChemicalSystems 167
8.6.4.2 DynamicKineticResolutionswithBiocatalysis 168
8.6.4.3 DynamicKineticResolution(DKR)InvolvingBase-Catalyzed
Racemization 168
8.6.4.4 DKRInvolvingAcid-CatalyzedRacemization 169
8.6.4.5 DKRCombinedwithRacemizationbyRingOpening 169
8.6.4.6 DKRInvolvingMetal-CatalyzedRacemization 170
8.6.4.7 DynamicKineticResolutionsUtilizingOtherChemical
RacemizationProcesses 171
8.6.4.8 DynamicKineticResolutionComprisingBiocatalytic
Racemization 171
8.6.5 Crystallization-InducedDynamicResolution(CIDR) 172
8.6.6 KineticResolutionFollowedbyConfigurationalInversion 174
8.7 EnantiotopeSelectivity 175
8.7.1 EnantiotopeSelectivityinChemicalSystems 177
8.7.2 EnantiotopeSelectivityinBiocatalyticSystems 179
8.7.2.1 TransformationsofEnantiotopicGroupsbyBiocatalysis 179
8.7.3 ConsequencesofOpposingEnantiotope-Selective
Transformations 182
8.7.4 KineticAmplification 183
8.7.5 EnantiodivergentReactionsFollowingtheTransformationof
EnantiotopicGroups 185
8.8 CombinationofMoreThanOneTypeofSelectivity 186
References 187