PeerKirsch ModernFluoroorganicChemistry RelatedTitles Wirth,T.(ed.) Ojima,I.(ed.) OrganoseleniumChemistry FluorineinMedicinalChemistry SynthesisandReactions andChemicalBiology 2012 2009 ISBN:978-3-527-32944-1 ISBN:978-1-4051-6720-8 Petrov,V.A. Mohr,F.(ed.) Fluorinated Heterocyclic Gold Chemistry Compounds ApplicationsandFutureDirectionsinthe LifeSciences Synthesis,Chemistry,andApplications 2009 2009 ISBN:978-3-527-32086-8 ISBN:978-0-470-45211-0 Peer Kirsch Modern Fluoroorganic Chemistry Synthesis, Reactivity, Applications Second, Completely Revised and Enlarged Edition TheAuthor AllbookspublishedbyWiley-VCHare carefullyproduced.Nevertheless,authors, Prof.Dr.PeerKirsch editors,andpublisherdonotwarrantthe MerckKGaA informationcontainedinthesebooks, LiquidCrystalsR&DChemistry includingthisbook,tobefreeoferrors. FrankfurterStr.250 Readersareadvisedtokeepinmindthat 64293Darmstadt statements,data,illustrations,procedural Germany detailsorotheritemsmayinadvertentlybe inaccurate. LibraryofCongressCardNo.:appliedfor BritishLibraryCataloguing-in-Publication Data Acataloguerecordforthisbookisavailable fromtheBritishLibrary. Bibliographicinformationpublishedbythe DeutscheNationalbibliothek TheDeutscheNationalbibliothek liststhispublicationintheDeutsche Nationalbibliografie;detailedbibliographic dataareavailableontheInternetat <http://dnb.d-nb.de>. ©2013Wiley-VCHVerlagGmbH &Co.KGaA,Boschstr.12,69469 Weinheim,Germany Allrightsreserved(includingthoseof translationintootherlanguages).Nopart ofthisbookmaybereproducedinany form–byphotoprinting,microfilm,orany othermeans–nortransmittedortranslated intoamachinelanguagewithoutwritten permissionfromthepublishers.Registered names,trademarks,etc.usedinthisbook, evenwhennotspecificallymarkedassuch, arenottobeconsideredunprotectedbylaw. PrintISBN:978-3-527-33166-6 ePDFISBN:978-3-527-65138-2 ePubISBN:978-3-527-65137-5 mobiISBN:978-3-527-65136-8 oBookISBN:978-3-527-65135-1 CoverDesign Grafik-DesignSchulz, Fußgo¨nheim Typesetting LaserwordsPrivateLimited, Chennai,India PrintingandBinding MarkonoPrint MediaPteLtd,Singapore PrintedinSingapore Printedonacid-freepaper v ToAnnetteandAlexander ‘‘Thefuryofthechemicalworldistheelementfluorine.Itexistspeacefullyinthecompany with calcium in fluorspar and alsoin a few other compounds;but when isolated,as it recentlyhasbeen,itisarabidgasthatnothingcanresist.’’ ScientificAmerican,April1888. ‘‘Fluorineleavesnobodyindifferent;itinflamesemotionsbethataffectionsoraversions. As a substituent, it is rarely boring, always good for a surprise, but often completely unpredictable.’’ M.Schlosser,Angew.Chem.Int.Ed.1998,37,1496–1513. VII Contents PrefacetotheSecondEdition XIII PrefacetotheFirstEdition XV Abbreviations XVII 1 Introduction 1 1.1 WhyOrganofluorineChemistry? 1 1.2 History 1 1.3 TheBasicMaterials 3 1.3.1 HydrofluoricAcid 3 1.3.2 Fluorine 5 1.4 TheUniquePropertiesofOrganofluorineCompounds 7 1.4.1 PhysicalProperties 7 1.4.2 ChemicalProperties 13 1.4.3 EcologicalImpact 15 1.4.3.1 OzoneDepletionbyChlorofluorocarbons 15 1.4.3.2 GreenhouseEffect 17 1.4.4 PhysiologicalProperties 18 1.4.5 AnalysisofFluorochemicals:19FNMRSpectroscopy 20 References 21 PartI SynthesisofComplexOrganofluorineCompounds 25 2 IntroductionofFluorine 27 2.1 PerfluorinationandSelectiveDirectFluorination 27 2.2 ElectrochemicalFluorination(ECF) 34 2.3 NucleophilicFluorination 36 2.3.1 FinkelsteinExchange 36 2.3.2 ‘‘Naked’’Fluoride 36 2.3.3 LewisAcid-AssistedFluorination 39 2.3.4 The‘‘GeneralFluorineEffect’’ 41 2.3.5 Amine–HydrogenFluorideandEther–HydrogenFluoride Reagents 42 VIII Contents 2.3.6 Hydrofluorination,Halofluorination,andEpoxideRingOpening 43 2.4 SynthesisandReactivityofFluoroaromaticCompounds 46 2.4.1 SynthesisofFluoroaromaticCompounds 46 2.4.2 ReductiveAromatization 47 2.4.3 TheBalz–SchiemannReaction 47 2.4.4 TheFluoroformateProcess 49 2.4.5 TransitionMetal-CatalyzedAromaticFluorination 49 2.4.6 TheHalexProcess 55 2.4.7 ThinkNegative! – ‘‘Orthogonal’’ReactivityofPerfluoroaromaticand PerfluoroolefinicSystems 55 2.4.8 The‘‘SpecialFluorineEffect’’ 58 2.4.9 AromaticNucleophilicSubstitution 59 2.4.10 ActivationoftheCarbon–FluorineBondbyTransitionMetals 63 2.4.10.1 ElectrophilicallyActivatedArylationbyFluoroarenes 63 2.4.11 ActivationofFluoroaromaticCompoundsbyOrtho-Metalation 64 2.5 TransformationsofFunctionalGroups 67 2.5.1 HydroxyintoFluoro 67 2.5.1.1 Two-StepActivation–Fluorination 68 2.5.1.2 α,α-Difluoroalkylamineandα-FluoroenamineReagents 68 2.5.1.3 SulfurTetrafluoride,DAST,andRelatedReagents 71 2.5.1.4 Amine–HydrogenFluorideReagents 73 2.5.2 ConversionofCarbonylintogem-Difluoromethylene 74 2.5.2.1 SulfurTetrafluoride,DAST,andRelatedReagents 74 2.5.3 CarboxylintoTrifluoromethyl 77 2.5.4 OxidativeFluorodesulfuration 78 2.6 ‘‘Electrophilic’’Fluorination 85 2.6.1 XenonDifluoride 85 2.6.2 PerchlorylFluorideandHypofluorides 86 2.6.3 ‘‘NF’’-Reagents 88 References 98 3 Perfluoroalkylation 107 3.1 RadicalPerfluoroalkylation 107 3.1.1 Structure,Properties,andReactivityofPerfluoroalkylRadicals 107 3.1.2 PreparativelyUsefulReactionsofPerfluoroalkylRadicals 110 3.1.3 ‘‘Inverse’’RadicalAdditionofAlkylRadicalstoPerfluoroolefins 115 3.2 NucleophilicPerfluoroalkylation 118 3.2.1 Properties,Stability,andReactivityofFluorinatedCarbanions 118 3.2.2 PerfluoroalkylMetalCompounds 120 3.2.3 Perfluoroalkylsilanes 130 3.3 ‘‘Electrophilic’’Perfluoroalkylation 139 3.3.1 PropertiesandStabilityofFluorinatedCarbocations 139 3.3.2 ArylperfluoroalkyliodoniumSalts 142 3.3.3 PerfluoroalkylSulfonium,Selenonium,Telluronium,andOxonium Salts 149