Organic mechanisms : reactions, methodology, and biological applications

434 Pages·2013·21.2 MB·English

by  Sun

ORGANIC MECHANISMS

ORGANIC MECHANISMS
Reactions, Methodology, and
Biological Applications
XIAOPINGSUN
UniversityofCharleston
Charleston,WestVirginia,USA
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LibraryofCongressCataloging-in-PublicationData:
Sun,Xiaoping,1960–
Organicmechanisms:reactions,methodology,andbiologicalapplications/XiaopingSun,
UniversityofCharleston,Charleston,WestVirginia,USA.
pagescm
Includesbibliographicalreferencesandindex.
ISBN978-1-118-06564-8(hardback)
1.Organicreactionmechanisms. I.Title.
QD502.5.S862013
547(cid:3).139–dc23
2013002855
PrintedintheUnitedStatesofAmerica
ISBN:9781118065648
10 9 8 7 6 5 4 3 2 1
CONTENTS
Preface xiii
1 FundamentalPrinciples 1
1.1 ReactionMechanismsandtheirImportance 1
1.2 Elementary(Concerted)andStepwiseReactions 2
1.3 Molecularity 4
1.3.1 UnimolecularReactions 4
1.3.2 BimolecularReactions 4
1.4 Kinetics 5
1.4.1 RateLawsforElementary(Concerted)Reactions 5
1.4.2 ReactiveIntermediatesandtheSteady-StateAssumption 9
1.4.3 RateLawsforStepwiseReactions 12
1.5 Thermodynamics 13
1.5.1 Enthalpy,Entropy,andFreeEnergy 13
1.5.2 ReversibleandIrreversibleReactions 14
1.5.3 ChemicalEquilibrium 15
1.6 TheTransitionState 17
1.7 TheMolecularOrbitalTheory 19
1.7.1 FormationofMolecularOrbitalsfromAtomicOrbitals 19
1.7.2 MolecularOrbitalDiagrams 25
1.7.3 ResonanceStabilization 25
1.7.4 FrontierMolecularOrbitals 28
1.8 Electrophiles/NucleophilesversusAcids/Bases 29
1.8.1 CommonElectrophiles 29
1.8.2 CommonNucleophiles 33
v
vi CONTENTS
1.9 IsotopeLabeling 35
Problems 38
References 40
2 TheAliphaticC HBondFunctionalization 41
2.1 AlkylRadicals:BondingandtheirRelativeStability 42
2.2 RadicalHalogenationsoftheC HBondsonsp3-Hybridized
Carbons:MechanismandNatureoftheTransitionStates 47
2.3 EnergeticsoftheRadicalHalogenationsofAlkanesandtheir
Regioselectivity 51
2.3.1 EnergyProfilesforRadicalHalogenationReactions
ofAlkanes 51
2.3.2 RegioselectivityforRadicalHalogenationReactions 52
2.4 KineticsofRadicalHalogenationsofAlkanes 56
2.5 RadicalInitiators 61
2.6 Transition-Metal-Compounds-CatalyzedAlkaneC HBond
ActivationandFunctionalization 64
2.6.1 TheC HBondActivationviaAgosticBond 64
2.6.2 MechanismsfortheC HBondOxidative
Functionalization 65
2.7 Superacids-CatalyzedAlkaneC HBondActivationand
Functionalization 68
2.8 NitrationofAliphaticC HBondsviatheNitroniumNO +Ion 69
2
2.9 Enzyme-CatalyzedAlkaneC HBondActivationand
Functionalization:BiochemicalMethods 71
Problems 75
References 77
3 FunctionalizationoftheAlkeneC CBondby
ElectrophilicAdditions 78
3.1 MarkovnikovAdditionsviaIntermediateCarbocations 79
3.1.1 AdditionsofAlkenestoHydrogenHalides
(HCl,HBr,andHI):Mechanism,Regiochemistry,
andStereochemistry 79
3.1.2 Acid-andTransition-Metal-CatalyzedHydrationof
AlkenesandItsApplications 84
3.1.3 Acid-CatalyzedAdditionsofAlcoholstoAlkenes 89
3.1.4 SpecialElectrophilicAdditionsoftheAlkeneC CBond:
MechanisticandSyntheticAspects 89
3.1.5 ElectrophilicAdditiontotheC CTripleBondviaa
VinylCationIntermediate 94
3.2 ElectrophilicAdditionofHydrogenHalidestoConjugatedDienes 95
3.3 Non-MarkovnikovRadicalAddition 96
CONTENTS vii
3.4 Hydroboration:Concerted,Non-Markovnikovsyn-Addition 97
3.4.1 Diborane(B H ):StructureandProperties 97
2 6
3.4.2 Concerted,Non-Markovnikovsyn-AdditionofBorane
(BH )totheAlkeneC CBond:Mechanism,
3
Regiochemistry,andStereochemistry 98
3.4.3 SynthesisofSpecialHydroboratingReagents 102
3.4.4 ReactionsofAlkeneswithSpecialHydroborating
Reagents:Regiochemistry,Stereochemistry,andtheir
ApplicationsinChemicalSynthesis 103
3.5 Transition-Metal-CatalyzedHydrogenationoftheAlkeneC C
Bond(syn-Addition) 107
3.5.1 MechanismandStereochemistry 107
3.5.2 SyntheticApplications 110
3.5.3 Biochemically-RelatedApplications:Hydrogenated
Fats(Oils) 111
3.6 HalogenationoftheAlkeneC CBond(Anti-Addition):
MechanismandItsStereochemistry 113
Problems 117
References 120
4 FunctionalizationoftheAlkeneC CBondby
CycloadditionReactions 121
4.1 CycloadditionsoftheAlkeneC CBondtoForm
Three-MemberedRings 122
4.1.1 Epoxidation 122
4.1.2 CycloadditionsviaCarbenesandRelatedSpecies 124
4.2 CycloadditionstoFormFour-MemberedRings 128
4.3 Diels–AlderCycloadditionsoftheAlkeneC CBondtoForm
Six-MemberedRings 131
4.3.1 FrontierMolecularOrbitalInteractions 132
4.3.2 SubstituentEffects 135
4.3.3 OtherDiels–AlderReactions 138
4.4 1,3-DipolarCycloadditionsoftheC CandotherMultipleBonds
toFormFive-MemberedRings 142
4.4.1 OxidationofAlkenesbyOzone(O )andOsmium
3
Tetraoxide(OsO )viaCycloadditions 142
4
4.4.2 CycloadditionsofNitrogen-Containing1,3-Dipoles
toAlkenes 145
4.4.3 CycloadditionsofAlkenes,Alkynes,andNitrilestothe
Dithionitronium(NS +)Ion:MakingCNS-Containing
2
AromaticHeterocycles 147
4.5 PericyclicReactions 154
Problems 158
References 161
viii CONTENTS
5 TheAromaticC HBondFunctionalizationandRelatedReactions 162
5.1 AromaticNitration:AllReactionIntermediatesandFull
MechanismfortheAromaticC HBondSubstitutionby
Nitronium(NO +)andRelatedElectrophiles 163
2
5.1.1 Charge-TransferComplex[ArH,NO +]betweenArene
2
andNitronium 164
5.1.2 Ion-RadicalPair[ArH+(cid:2),NO (cid:2)] 164
2
5.1.3 Arenium[Ar(H)NO ]+Ion 165
2
5.1.4 FullMechanismforAromaticNitration 166
5.2 MechanismsandSyntheticUtilityforAromaticC HBond
SubstitutionsbyOtherRelatedElectrophiles 167
5.3 TheElectrophilicAromaticC HBondSubstitutionReactions
viaS 1andS 2Mechanisms 174
N N
5.3.1 ReactionsInvolvingS 1Steps 175
N
5.3.2 ReactionsInvolvingS 2Steps 179
N
5.4 SubstituentEffectsontheElectrophilicAromatic
SubstitutionReactions 181
5.4.1 Ortho-andPara-Directors 183
5.4.2 Meta-Directors 185
5.5 IsomerizationsEffectedbytheElectrophilicAromatic
SubstitutionReactions 187
5.6 ElectrophilicSubstitutionReactionsontheAromatic
Carbon–MetalBonds:MechanismsandSyntheticApplications 191
5.7 NucleophilicAromaticSubstitutionviaaBenzyne(aryne)
Intermediate:FunctionalGroupTransformationson
AromaticRings 193
5.8 NucleophilicAromaticSubstitutionviaanAnionic
MeisenheimerComplex 197
5.9 BiologicalApplicationsofFunctionalizedAromaticCompounds 200
Problems 204
References 207
6 NucleophilicSubstitutionsonsp3-HybridizedCarbons:Functional
GroupTransformations 209
6.1 NucleophilicSubstitutiononMono-Functionalized
sp3-HybridizedCarbon 209
6.2 FunctionalGroupswhichareGoodandPoorLeavingGroups 211
6.3 GoodandPoorNucleophiles 213
6.4 S 2Reactions:Kinetics,Mechanism,andStereochemistry 215
N
6.4.1 MechanismandStereochemistryforS 2Reactions 215
N
6.4.2 StericEffectonS 2Reactions 218
N
6.4.3 EffectofNucleophiles 220
6.4.4 SolventEffect 222