Stereochemistry: A Three-Dimensional Insight

600 Pages·2021·46.33 MB·english

by  Anil V. Karnik and Mohammed Hasan

Stereochemistry
Stereochemistry
A Three-Dimensional Insight
ANIL V. KARNIK
Department of Chemistry,University of Mumbai,
Mumbai, Maharashtra, India
MOHAMMED HASAN
Department of Chemistry,University of Mumbai,
Mumbai, Maharashtra, India
Elsevier
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Contents
Abouttheauthors xvii
Foreword xix
Preface xxiii
Part I Fundamentals of stereochemistry
1. Basic concepts of structureand stereochemistry 3
1.1 Introduction 3
1.2 Abriefhistory 5
1.3 Moleculargeometry 5
1.3.1 VanderWaals’radius 6
1.3.2 Bondlength 7
1.3.3 Bondangle 7
1.3.4 Dihedralangle 8
1.4 Isomers 9
1.4.1 Conformationalisomers 10
1.4.2 Configurationandconfigurationalisomers 11
1.5 Projectionformulae 13
1.5.1 Fischerprojection 13
1.5.2 Newmanprojection 15
1.5.3 Sawhorseprojection 15
1.5.4 Inter-conversionofFischerprojectiontoNewmanprojectionor
Sawhorseprojection 16
1.5.5 Flyingwedge/zig-zagprojectionformula 16
1.5.6 Inter-conversionofFischerprojectionandzig-zagprojection 18
1.6 Summary 20
Questionsandproblems 21
References 23
2. Symmetry andpoint groups 25
2.1 Introduction 25
2.2 Symmetryelementsandsymmetryoperations 27
2.2.1 Simpleorproperaxisofsymmetry(Cn)andproperrotational
operationsðCkÞ 27
n
2.2.2 Planeofsymmetry(σ)(cid:2)Operationofreflection(σ) 29
2.2.3 Centreofsymmetry(i)(cid:2)Operationofinversion(i) 30
2.2.4 Alternatingorrotation-reflectionaxisofsymmetry(Sn) 32
v
vi Contents
2.3 Pointgroupsandtheirclassification 33
2.3.1 Linearmoleculeswithhighsymmetry(Specialgroup) 34
2.3.2 Nonlinearmoleculeswithhighsymmetryandmoleculeswith
platonicgroupstructures 35
2.3.3 NonlinearmoleculeswithhighCnaxis(withoutplatonicgroup
molecules) 37
2.3.4 NonlinearmoleculeswithabsenceofCn,axisn$2 39
2.4 Thechiralcompoundsandthedifferencebetweenasymmetryand
dissymmetry 39
2.5 Symmetrynumber(σ) 41
2.5.1 Practicalmethodtoassignthepointgroupofgivenorganic
compound 43
2.6 Summary 44
Questionsandproblems 45
References 48
3. Elementsof chiralityand chiral stereoisomerism 49
3.1 Introduction 49
3.2 Moleculeswithcentralchirality 49
3.2.1 Configurationaldescriptorsformoleculeswithcentralchirality 52
3.3 Moleculeswithtwoormorechiralcentres 56
3.3.1 Constitutionallyunsymmetricalchiralmolecules 57
3.3.2 Stereoisomerisminconstitutionallysymmetricalchiralmolecules 62
3.3.3 Stereoisomerismincyclicmolecules 64
3.4 Moleculeswiththepresenceofchiralaxis 66
3.4.1 Assignmentofconfigurationaldescriptorstomoleculeswith
presenceofchiralaxis 68
3.4.2 Allenes 68
3.4.3 Alkylidenecycloalkanes/Hemispiranes 69
3.4.4 Spiranes 70
3.4.5 Atropisomerism 71
3.4.6 Atropisomerismofbiaryls,restrictedrotationaroundsp2-sp2,C(cid:2)C
bond 73
3.4.7 Assignmentofconfigurationaldescriptorstochiralbiphenyls 75
3.4.8 Bridgedbiphenyls 76
3.5 Planarchirality 77
3.5.1 Assignmentofconfigurationaldescriptortomoleculeswithchiral
plane 79
3.5.2 Cyclophanesandansacompounds 79
3.5.3 Trans-cyclooctene 80
Contents vii
3.5.4 Chiralferrocenes 81
3.6 Helicity 82
3.7 Cyclostereoisomerism 83
3.8 Summary 85
Questionsandproblems 86
References 90
Part II Enantiomer properties
4. Chiroptical properties: Origin and applications 95
4.1 Introduction 95
4.2 Opticalactivity 97
4.2.1 Originoftheopticalactivity 98
4.2.2 Circularbirefringence 99
4.2.3 Dissymmetriccompoundsandopticalactivity 101
4.2.4 Circulardichroism 102
4.3 Opticalrotatorydispersioncurves(ORD) 104
4.3.1 Cottoneffectcurves 104
4.3.2 TheCottoneffectcirculardichroismandopticalrotatory
dispersioncurves 106
4.3.3 Applicationsoftheplainopticalrotatorydispersioncurves 106
4.3.4 ApplicationsoftheCottoneffectopticalrotatory
dispersion/circulardichroismcurves 107
4.3.5 Empiricalandsemiempiricalrulesforconformationaland
configurationalstudies 110
4.4 Theaxialα-haloketoneruleanditsapplications 111
4.5 Octantrule 114
4.5.1 Applicationsoftheoctantrule 115
4.6 Inherentlysymmetricorinherentlydissymmetricopticallyactive
chromophores 117
4.7 Helicityrulesforinherentlychiralchromophores 118
4.7.1 α,β-Unsaturatedketoneorenone 118
4.7.2 1,3-Conjugateddienes 119
4.7.3 Biaryls 119
4.7.4 Helicenes 119
4.8 Lowe’sruleforallenes 120
4.9 Excitoncouplinganddibenzoatechiralityrule 120
4.10 Summary 123
Questionsandproblems 123
References 125
viii Contents
5. Configurational analysis 129
5.1 Introduction 129
5.2 Methodsforthedeterminationofabsoluteconfiguration 130
5.2.1 BasicterminologyofresonantX-rayscattering 130
5.2.2 DeterminationofabsoluteconfigurationusingresonantX-ray
scattering 132
5.2.3 Determinationofabsoluteconfigurationbyuseofcrystalline
sponge-X-raydiffractionmethod 133
5.2.4 Crystalmorphologicalchangesforassignmentofabsolute
configuration 135
5.2.5 Determinationofabsoluteconfigurationusingchiroptical
methods 139
5.3 Correlativemethodsfordeterminationofconfigurations 140
5.3.1 Chemicalcorrelativemethodsofdeterminationofconfigurations 140
5.3.2 Correlativemethodsbasedoncomparisonofopticalrotations 146
5.3.3 Quasi-racemateformationbetweentwodifferentmolecules 151
5.3.4 NMRmethods 155
5.4 Assignmentofconfigurationbasedonasymmetricsynthesis 159
5.4.1 Cram’srule 160
5.4.2 Prelog’srule 163
5.4.3 Sharplessasymmetricepoxidation 164
5.5 Horeau’smethodofassignmentofconfigurationbasedonkinetic
resolution 165
5.6 ‘Stand-alone’methodsfordeterminationofconfiguration 166
5.6.1 Assignmentofconfigurationtoanalkylidenecycloalkanevia
stereoselectivesynthesis 167
5.6.2 Assignmentofabsoluteconfigurationto(-)-trans-cyclooctene 167
5.6.3 Determinationofabsoluteconfigurationofallenes 169
5.6.4 Assignmentofabsoluteconfigurationtoaspirocompound 170
5.6.5 Assignmentofabsoluteconfigurationtoabiphenylderivative 171
5.7 Methodstodistinguishbetweenconfigurationsofdiastereoisomers 171
5.7.1 Auwer’sSkitarule 172
5.7.2 UV-visspectroscopy 173
5.7.3 IRspectroscopy 173
5.7.4 X-raydiffractionstudies 174
5.7.5 NMRspectroscopy 174
5.8 Chemicalmethod 177
5.9 Summary 178
Questionsandproblems 179
References 183
Contents ix
6. Racemates: Properties and methodsof resolution 187
6.1 Introduction:Propertiesofenantiomersandracemates 187
6.1.1 Meltingpointphasediagrams 188
6.1.2 Crystalshape/morphology 189
6.1.3 Densityofracemicmodificationsinsolidstate 191
6.1.4 Solubilitybehaviourofracemicmodifications 192
6.1.5 IRspectroscopy 192
6.1.6 NMRspectroscopy 192
6.1.7 X-raydiffractionstudies 193
6.1.8 Chromatographicbehaviour 193
6.1.9 Vapourpressure 194
6.2 Resolutionofracemates 195
6.2.1 Resolutionofracemicmodificationexhibitingconglomerate
behaviour:Spontaneouscrystallisation 195
6.2.2 Formationofdiastereomericsaltsorcompoundsfollowedby
preferentialcrystallisation 196
6.2.3 Resolutionthoughformationofdiastereomericcomplexes 202
6.2.4 Chromatographicresolutions 203
6.2.5 Resolutionofracematesviaequilibriumasymmetric
transformation 205
6.2.6 Kineticresolutionsofracemates 208
6.2.7 Dynamickineticresolutions 211
6.3 Racemisationprocesses 213
6.3.1 Formationofaresonancestabilizedcarbanions 214
6.3.2 Involvementoftautomericspecies 214
6.3.3 Racemisationsinvolvingastablecarbocationintermediate 214
6.3.4 Racemisationsinvolvingastablecarbon-freeradicalintermediate 215
6.3.5 Oppositereactionsoccurringsimultaneously 215
6.3.6 RacemisationencounteredinDKR 216
6.3.7 Rotationaroundsinglebond 216
6.4 Summary 216
Questionsandproblems 217
References 219
Part III Conformations and conformational analysis
7. Conformation of acyclic molecules 227
7.1 Introduction 227
7.2 Conformation 228
x Contents
7.2.1 Torsionalstrain 228
7.2.2 Notationsfortorsionangle,theKlyne(cid:2)Prelogmethod 229
7.3 Estimatingstrainenergy 232
7.3.1 Causeofthepotentialenergybarriers 233
7.4 Studyofconformationsduetorotationaboutsp3(cid:2)sp3singlebond 235
7.4.1 RotationsaroundC(cid:2)Cbond 235
7.4.2 Alkaneswithpolarsubstituents 240
7.4.3 RotationaroundC(cid:2)Nsinglebond 241
7.4.4 RotationaroundC(cid:2)Psinglebond 242
7.4.5 RotationaroundC(cid:2)Osinglebond 243
7.4.6 Conformationsduetorotationaroundsp3(cid:2)sp2singlebond 244
7.4.7 Conformationsduetorotationaroundsp2(cid:2)sp2singlebond 246
7.5 Spectral/analytical/theoreticalmeansofinternalrotationstudies 247
7.5.1 Molecularmechanicsandquantummechanicalapproachesto
estimateenergiesofmoleculesindifferentarrangements 247
7.5.2 Dipolemoment 248
7.5.3 UseofNMRandESRtechniques 249
7.5.4 Microwavespectroscopy 250
7.5.5 Electrondiffractionstudies 251
7.5.6 X-raydiffractionstudies 252
7.5.7 InfraredandRamanspectroscopy 252
7.6 Conformationandchemicalreactivity 253
7.6.1 Curtin(cid:2)Hammettprinciple 255
7.6.2 Effectofconformationonkineticand/orstereochemical
outcomeofchemicalreactions 259
7.7 Summary 265
Questionsandproblems 266
References 269
8. Conformations ofcyclic,fusedand bridged ring molecules 273
8.1 Introduction 273
8.2 Cyclohexaneconformations 275
8.2.1 Thechairconformation 275
8.2.2 Ringinversionincyclohexane 279
8.2.3 Nonchairconformationsofcyclohexane 282
8.2.4 Cyclohexanederivativeswithtwoormoresubstituents 286
8.3 Cyclohexanoneconformationalanalysis 295
8.4 Alkylidenecyclohexaneconformation 297
8.5 Cyclohexeneconformation 298
8.6 Cyclopropaneconformation 300