Organometallic Chemistry in Industry: A Practical Approach

329 Pages·2020·12.269 MB·English

by  Thomas Colacot (editor), Carin Johansson Seechurn (editor)

OrganometallicChemistryinIndustry
Organometallic Chemistry in Industry
APracticalApproach
WithaForewordbyRobertH.Grubbs
Editedby
ThomasJ.Colacot
CarinC.C.JohanssonSeechurn
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v
Contents
Foreword xiii
Preface xvii
1 IndustrialMilestonesinOrganometallicChemistry 1
BenM.Gardner,CarinC.C.JohanssonSeechurn,andThomasJ.Colacot
1.1 DefinitionofOrganometallicandMetal–OrganicCompounds 1
1.1.1 ApplicationsandKeyReactivity 1
1.1.1.1 ElectronicApplications 1
1.1.1.2 Polymers 2
1.1.1.3 OrganicSynthesis 2
1.2 IndustrialProcessConsiderations 7
1.3 BriefNotesontheHistoricalDevelopmentofOrganometallic
ChemistryforOrganicSynthesisApplicationsPertainingtothe
ContentsofthisBook 8
1.3.1 SynthesisofStoichiometricOrganometallicReagents 9
1.3.1.1 ConventionalBatchSynthesis 9
1.3.1.2 OrganometallicsinFlow 10
1.3.2 Cross-couplingReactions 10
1.3.2.1 C—HBondActivation 12
1.3.2.2 Carbonylation 13
1.3.2.3 CatalysisinWater–MicellarCatalysis 13
1.3.3 HydrogenationReactions 14
1.3.4 OlefinFormationReactions 15
1.3.4.1 WittigReaction 15
1.3.4.2 MetathesisReactions 15
1.3.4.3 DehydrativeDecarbonylation 16
1.3.4.4 OlefinsasStartingMaterials 16
1.3.5 Poly-orOligomerizationProcesses 17
1.3.6 PhotoredoxCatalysisforOrganicSynthesis 17
1.4 ConclusionandOutlook 17
Biography 18
References 19
vi Contents
2 Design,Development,andExecutionofa
Continuous-flow-EnabledAPIManufacturingRoute 23
AlisonC.Brewer,PhilipC.Hoffman,TimothyD.White,YuLu,LauraMcKee,
MoussaBoukerche,MichaelE.Kobierski,NessaMullane,MarkPietz,CharlesA.
Alt,JimR.Stout,PaulK.Milenbaugh,andJosephR.Martinelli
2.1 Continuous-flow-EnabledSyntheticStrategy 25
2.2 DesignandScale-upofChan–LamCoupling 28
2.2.1 DevelopmentofHomogeneousConditions 31
2.2.2 ApplicationofaPlatformTechnologytoAerobicOxidation 32
2.2.3 OptimizationofReactionandWorkupParameters 35
2.2.4 SafetyConsiderationsforAerobicOxidationonScale 37
2.2.5 ContinuousScale-upandManufacturing 38
2.3 DesignandScale-upofaBuchwald–HartwigCross-coupling 42
2.3.1 InitialScreening 43
2.3.2 SynthesisandIsolationofPd(dba)DPEPhosPrecatalyst 45
2.3.3 WorkupProcedure,MetalRemoval,andCrystallization 46
2.3.4 Scale-upandManufacturing 48
2.4 ImpurityControl 48
2.4.1 SolubilityandImpuritySpikingStudies 50
2.5 Conclusions 54
Biography 54
References 58
3 ContinuousManufacturingasanEnablingTechnologyfor
Low-TemperatureOrganometallicChemistry 61
AndreasHafnerandJoergSedelmeier
3.1 Introduction 61
3.2 Organo-LiandMgProcessesinFlowMode 62
3.2.1 TechnologicalAdvantagesofFlowTechnologyComparedto
TraditionalBatchOperation 62
3.2.2 TemperatureProfileofContinuousFlowReactions 64
3.2.3 FlashChemistry:FunctionalGroupTolerance 65
3.2.4 FlashChemistry:Selectivity 66
3.2.5 FlashChemistry:StoichiometryandChemoselectivity 67
3.3 ContinuousFlowTechnology 69
3.3.1 CloggingasaMajorHurdleinFlowChemistry 71
3.3.2 Start-upandShutdownOperation 72
3.3.3 MaterialofConstruction 72
3.3.4 SafetyConceptandEmergencyStrategies 73
3.4 DevelopmentofaFlowProcess 73
3.4.1 ScreeningPhase:FeasibilityStudy 74
3.4.2 ProcessDevelopmentPhase:ExtendedEvaluationsIncluding
TechnicalFeasibility 75
3.5 LiteratureExamples:FlowProcessesonMulti100gScale 76
3.5.1 ManufactureofVerubecestat(MK-8931) 77
3.5.2 ManufactureofEdivoxetine 77
3.5.3 Scale-upofHighlyReactiveArylLithiumChemistry 80
Contents vii
3.5.4 SynthesisofBromomethyltrifluoroboratesinContinuousFlow
Mode 81
3.5.5 Two-StepSynthesisTowardBoronicAcids 82
3.5.6 ReactionSequenceTowardaHighlySubstitutedBenzoxazoleBuilding
Block 84
3.6 ConclusionandFutureProspects 86
Biography 86
References 87
4 DevelopmentofaNickel-CatalyzedEnantioselective
Mizoroki–HeckCoupling 91
Jean-NicolasDesrosiersandChrisH.Senanayake
4.1 Introduction 91
4.1.1 NonpreciousMetalCatalysisAdvantagesforIndustry 91
4.1.2 Mizoroki–HeckCouplingsinIndustrywithPalladium 92
4.1.3 EmergenceofNickel-CatalyzedMizoroki–HeckCouplings 93
4.1.4 EnantioselectiveNickel-CatalyzedCouplings 94
4.1.5 SynthesisofOxindolesviaMizoroki–HeckCyclizations 96
4.2 DevelopmentofaNickel-CatalyzedHeckCyclizationtoGenerate
OxindoleswithQuaternaryStereogenicCenters 97
4.2.1 PrecedentsandChallenges 97
4.2.2 OptimizationofReducingAgentandBase 97
4.2.3 LigandScreening 98
4.2.4 ImpactofArylElectrophileandofStereochemistryofAlkene
Moiety 100
4.2.5 ExplorationoftheSubstrateScope 102
4.2.6 LimitationsoftheMethodology 104
4.2.7 MechanisticConsiderations 104
4.3 DevelopmentofFirstEnantioselectiveNickel-CatalyzedHeck
Coupling 107
4.3.1 LigandScreening 107
4.3.2 ImpactofAlkeneStereochemistry 107
4.3.3 NeutralvsCationicPathways 108
4.3.4 NickelPrecatalystComplexSynthesis 109
4.3.5 ExplorationoftheSubstrateScope 110
4.3.6 MechanisticStudies 110
4.4 Conclusions 113
Biography 114
References 115
5 DevelopmentofIron-CatalyzedKumadaCross-couplingforthe
Large-ScaleProductionofAliskirenIntermediate 121
SrinivasAchanta,DebjitBasu,UdayK.Neelam,RajeevR.Budhdev,Apurba
Bhattacharya,andRakeshwarBandichhor
5.1 Introduction 121
5.2 OptimizationofGradeandEquivalentsofMgMetal 123
viii Contents
5.3 OptimizationofEquivalentsof1,2-Dibromoethane 123
5.4 EffectofSolventConcentrationonPreparationofGrignardReagent
andKumada–CorriuCoupling 124
5.5 EffectofAlkylChloride3AdditionTimeontheGrignardReagent
Preparation 125
∘
5.6 StabilityofGrignardReagentat0–5 C 125
5.7 Iron-CatalyzedCross-couplingReaction 127
5.8 OptimizationofEquivalentsofNMPandFe(acac) 129
3
5.9 OptimizationofEquivalentsofSubstrate4andItsRateof
Addition 129
5.10 ExecutionatPilotScaleandScale-upIssues 129
5.11 AgitatedThinFilmEvaporator(ATFE)forPurificationof2 131
5.12 Conclusion 132
Acknowledgments 133
Biography 133
References 135
6 DevelopmentandScale-UpofaPalladium-Catalyzed
IntramolecularDirectArylationintheCommercialSynthesisof
Beclabuvir 137
CollinChan,AlbertJ.DelMonte,ChaoHang,YiHsiao,andEricM.Simmons
6.1 Introduction 137
6.2 KOAc/DMAcProcess 141
6.3 TMAOAc/DMFProcess 141
6.4 TMAOAc/DMAcProcess 149
6.4.1 CyclizationReaction 151
6.4.2 MechanisticUnderstandingoftheCyclizationReactionandImpurity
Formation 159
6.4.3 HydrolysisandWorkup 162
6.4.4 CrystallizationandDrying 164
6.5 Conclusion 167
Biography 168
References 169
7 Ruthenium-CatalyzedC—HActivatedC—C/N/OBond
FormationReactionsforthePracticalSynthesisofHeterocycles
andPharmaceuticalAgents 171
AnitaMehta,NareshKumar,andBiswajitSaha
7.1 Introduction 171
7.2 C–HActivationFollowedbyC—CBondFormation 172
7.2.1 C–HActivationFollowedbyC—CBondFormation:
Biaryl/HeterobiarylSynthesisinOrganicSolvents 172
7.2.2 C–HActivationFollowedbyC—CBondFormation:
Biaryl/HeterobiarylSynthesisinGreenSolvents 181
7.3 Alkyl/Acyl/AlkenylSubstitutiononHeterocycles 185
Contents ix
7.4 C–HActivationFollowedbyC—O/NBondFormation:Heterocycle
Synthesis 187
7.4.1 C–HActivationFollowedbyC—O/NBondFormation:Heterocycle
SynthesisinOrganicSolvents 187
7.4.2 C–HActivationFollowedbyC—OandC—NBondFormation:
HeterocycleSynthesisinGreenSolvents 189
7.5 Conclusion 196
Biography 197
References 198
8 Cross-couplingsinWater–ABetterWaytoAssembleNew
Bonds 203
ThariqueN.Ansari,FabriceGallou,andSachinHanda
8.1 Introduction 203
8.2 TransitionMetalCatalysisinOrganicSolventsvsMicellar
Catalysis 204
8.2.1 Micellization 205
8.2.2 SurfactantSolution–AHighlyOrganizedReactionMediumto
EnhanceReactionRate 206
8.2.3 ReactionTemperature 207
8.2.4 SizeofMicelles 207
8.2.5 NatureofCatalyst 208
8.2.6 IncreasingtheEfficiencyinMicellarCatalysis 209
8.2.7 OrderofAddition 210
8.2.8 ProductPrecipitationorExtraction 211
8.2.9 TraceMetalintheProduct 211
8.3 HighlyValuableReactionsinWater 212
8.3.1 Suzuki–MiyauraCouplings 212
8.3.2 HeckCouplings 217
8.3.3 NegishiCouplings 219
8.3.4 C–HArylations 221
8.3.5 Aminations 225
8.3.6 Borylation 228
8.3.7 ArylationofNitroCompounds 228
8.3.8 AdoptionofMicellarTechnologybyPharmaceuticalIndustry 229
8.4 Conclusions 234
Biography 234
References 235
9 AspectsofHomogeneousHydrogenationfromIndustrial
Research 239
StephenRoseblade
9.1 HomogeneousHydrogenation:ABriefIntroduction 239
9.2 CatalystSelectionbyEffectiveScreeningApproaches 240
9.3 ConsiderationsforReactionScale-up 244
x Contents
9.4 NotesonAdditiveEffects 247
9.5 ANovelApproachtoAliskirenUsingAsymmetricHydrogenationasa
KeyStep 249
9.6 EfficientChemoselectiveAldehydeHydrogenation 252
9.7 ClosingRemarks/Summary 253
Biography 255
References 255
10 LatestIndustrialUsesofOlefinMetathesis 259
JohnH.Phillips
10.1 Introduction 259
10.2 GeneralInformation 260
10.2.1 Non-rutheniumCatalysts 260
10.2.2 RutheniumCatalysts 261
10.3 IndustrialUses 262
10.3.1 Ring-closingMetathesis(RCM) 262
10.3.2 Cross-metathesis(CM) 264
10.3.3 Ring-OpeningMetathesisPolymerization(ROMP) 268
10.4 ReactionConsiderations 270
10.4.1 CatalystChoice 271
10.4.2 CatalystLoading 273
10.4.3 Solvent 273
10.4.4 ReactionConcentration 273
10.4.5 OverallHandling 274
10.4.6 ApplicationGuideandAvailability 274
10.5 Troubleshooting 275
10.5.1 CatalystRemoval 275
10.5.2 FunctionalGroupTolerance 276
10.5.3 SubstratePurity 276
10.5.4 CatalystDecomposition–Isomerization 277
10.6 Conclusion 277
Biography 277
References 278
11 DehydrativeDecarbonylation 283
AlexJohn
11.1 Introduction 283
11.2 UseofSacrificialAnhydrideandCatalyticMechanism 285
11.3 Rh-,Pd-,andIr-Catalysis 286
11.3.1 EarlyStudies 286
11.3.2 RecentStudies 289
11.4 MilderTemperatures 291
11.4.1 PdCl /XantPhos/(tBu) biphenolSystem 291
2 4
11.4.2 Well-DefinedPd-bis(phosphine)Precatalysts 294
11.5 NickelandIronCatalysis 295
11.6 EsterDecarbonylation 297
11.7 SyntheticUtility:α-VinylCarbonylCompounds 299