The Art of Problem Solving in Organic Chemistry Second Edition MIGUEL E. ALONSO-AMELOT THE ART OF PROBLEM SOLVING IN ORGANIC CHEMISTRY THE ART OF PROBLEM SOLVING IN ORGANIC CHEMISTRY Second Edition MIGUELE.ALONSO-AMELOT UniversityoftheAndes DepartmentofChemistry Merida,Venezuela Copyright©2014byJohnWiley&Sons,Inc.Allrightsreserved. PublishedbyJohnWiley&Sons,Inc.,Hoboken,NewJersey. PublishedsimultaneouslyinCanada. Nopartofthispublicationmaybereproduced,storedinaretrievalsystem,ortransmittedinanyformor byanymeans,electronic,mechanical,photocopying,recording,scanning,orotherwise,exceptas permittedunderSection107or108ofthe1976UnitedStatesCopyrightAct,withouteithertheprior writtenpermissionofthePublisher,orauthorizationthroughpaymentoftheappropriateper-copyfeeto theCopyrightClearanceCenter,Inc.,222RosewoodDrive,Danvers,MA01923,(978)750-8400, fax(978)750-4470,oronthewebatwww.copyright.com.RequeststothePublisherforpermission shouldbeaddressedtothePermissionsDepartment,JohnWiley&Sons,Inc.,111RiverStreet,Hoboken, NJ07030,(201)748-6011,fax(201)748-6008,oronlineathttp://www.wiley.com/go/permission. LimitofLiability/DisclaimerofWarranty:Whilethepublisherandauthorhaveusedtheirbesteffortsin preparingthisbook,theymakenorepresentationsorwarrantieswithrespecttotheaccuracyor completenessofthecontentsofthisbookandspecificallydisclaimanyimpliedwarrantiesof merchantabilityorfitnessforaparticularpurpose.Nowarrantymaybecreatedorextendedbysales representativesorwrittensalesmaterials.Theadviceandstrategiescontainedhereinmaynotbesuitable foryoursituation.Youshouldconsultwithaprofessionalwhereappropriate.Neitherthepublishernor authorshallbeliableforanylossofprofitoranyothercommercialdamages,includingbutnotlimitedto special,incidental,consequential,orotherdamages. Forgeneralinformationonourotherproductsandservicesorfortechnicalsupport,pleasecontactour CustomerCareDepartmentwithintheUnitedStatesat(800)762-2974,outsidetheUnitedStates at(317)572-3993orfax(317)572-4002. Wileyalsopublishesitsbooksinavarietyofelectronicformats.Somecontentthatappearsinprintmay notbeavailableinelectronicformats.FormoreinformationaboutWileyproducts,visitourwebsiteat www.wiley.com. LibraryofCongressCataloging-in-PublicationData: Alonso-Amelot,MiguelE.,author. Theartofproblemsolvinginorganicchemistry/MiguelE.Alonso-Amelot,Universityofthe Andes,DepartmentofChemistry,Merida,Venezuela.–Secondedition. pagescm Includesbibliographicalreferencesandindex. ISBN978-1-118-53021-4(pbk.) 1.Chemistry,Organic. 2.Problemsolving. I.Title. QD251.3.A462014 547–dc23 2014002867 PrintedintheUnitedStatesofAmerica. 10 9 8 7 6 5 4 3 2 1 ToAdelaandGabrielinthisworld ChristianeandRamo´n,intheother CONTENTS Preface xi PrefacetotheFirstEdition xvii Acknowledgments xix 1 ProblemAnalysisinOrganicReactionMechanism 1 1.1 Overview, 1 1.2 Introduction, 1 1.2.1 “PushingForward”aSolutioninFormaland ExhaustiveTerms, 2 1.2.2 LessonsfromthisExample, 7 1.3 AvoidingtheQuagmire, 7 1.4 TheBasicStepsofProblemAnalysis, 8 1.4.1 RecognizingtheProblem, 8 1.4.2 AnalyzingProblemsbyAskingtheRightQuestions, DiscardingtheIrrelevant, 11 1.4.3 DrawingaFirstOutlineforGuidance, 12 1.4.4 AskingtheRightQuestionsandProposingtheRight Answers... isenough?, 13 1.5 IntuitionandProblemSolving, 14 1.6 SummingUp, 17 ReferencesandNotes, 17 vii viii CONTENTS 2 ElectronFlowinOrganicReactions 19 2.1 Overview, 19 2.2 Introduction, 19 2.3 PracticalRulesGoverningElectronRedeployment, 22 2.3.1 Issue1:ElectronswithinOrbitals, 22 2.3.2 Issue2:ElectronTransferandStereochemistry, 23 2.3.3 Issue3:ElectronEnergyLevelandAccessibility, 24 2.3.4 Issue4:ElectronFlowandMolecularActiveSectors, 26 2.3.4.1 CaseA:π–πInteractions, 26 2.3.4.2 CaseB:π→σInteractions, 27 2.3.4.3 CaseC:WhenReactivityPatternsSeemto BreakDown, 27 2.3.5 Issue5:ElectronTrafficandElectronicDensityDifferences, 31 2.3.5.1 M0MetalsasElectronSource, 31 2.3.5.2 MetalHydridesandOrganicHydridesas ElectronSource, 32 2.3.6 Issue6:CreatingZonesofHighElectronDensity, 34 2.3.6.1 TheNaturalPolarization, 35 2.3.6.2 ReversingtheNaturalPolarization:Umpolung, 35 2.3.7 Issue7:ElectronFlowandLowElectronDensityZones, 36 2.3.7.1 IdentifyingLEDZs, 36 2.3.7.2 CreatingaNewLEDZintheSubstrate, 37 2.3.7.3 FindingUnsuspectedLEDZsamongtheOther ReagentsintheMixture, 41 2.3.7.4 WhenCompoundsShowDoublePersonality, 42 2.4 SummingUp, 42 2.5 AFlowchartofOrganizedProblemAnalysis, 44 ReferencesandNotes, 45 3 AdditionalTechniquestoPostulateOrganicReactionMechanisms 49 3.1 Overview, 49 3.2 TakeYourTime, 50 3.3 ClearandInformativeMolecularRenderings, 50 3.3.1 TheValueofMolecularSketches, 50 3.3.2 Two-VersusThree-DimensionalRenderingsandthe “Flat”OrganicCompounds, 52 3.4 ElementandBondBudgets, 53 3.5 LookingatMoleculesfromVariousPerspectives, 55 3.6 SeparatetheGrainfromtheChaff, 58 3.7 DissectingProductsinTermsofReactants:FragmentationAnalysis, 59 3.7.1 TheFundamentalProposition, 59 3.7.2 AddingPotentiallyNucleophilicorElectrophilic CharactertoFragments, 61