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6.1AnswersToChapter6Problems.1.(a)AnewC–CbondisformedbetweenanucleophilicC–ZnandanelectrophilicC–Br.ThisPd-cata-lyzedreactionproceedsthroughthestandardoxidativeaddition,transmetallation,reductiveeliminationprocesscharacteristicofPd-catalyzedcross-couplings.TheoxidativeadditionrequiresPd(0).TheroleoftheDIBAListoreducethePd(II)toPd(0)bytwotransmetallationsandreductiveeliminationofH2.ClPdPh3PPPh3Cli-Bu2AlH2Ph3PPdPh3PHH(a)IIIIPh3PPdPh3P0Ph3PPdPh3P0NBr(c)NPdP2BrII(a)NSO2PhZnCl–BrZnCl+NNSO2PhPdP2(b)Ph3PPdPh3P0II+NSO2PhN(a)transmetallation;(b)reductiveelimination;(c)oxidativeaddition.(b)(b)Anallylicleavinggroupisreplacedbyanucleophile.ThisreactionproceedsthroughthestandardsequenceforallylicsubstitutionscatalyzedbyPd,i.e.twosequentialbacksidedisplacements.Thechiralligandcausesthenucleophiletoattackonlyoneofthetwoprochiralterminiofthemesoπallylinter-mediate.TheNmaybedeprotonatedbeforeorafteritattackstheπallylcomplex.O(Ph)2PPdO(Ph)2P0OArOMeOArP(Ph)2OPdP(Ph)2O––OMeIIP(Ph)2OPdP(Ph)2OArTsHNNHTsAr–O(Ph)2PPdO(Ph)2P0II–+HNTsAr(c)AnewC–CbondisformedbetweenanucleophilicterminalalkynePhC≡CHandanelectrophilicC–I.6.2ThisSonogashirareactionproceedsthroughthestandardoxidativeaddition,transmetallation,reductiveeliminationprocesscharacteristicofPd-catalyzedcross-couplings.TheterminalalkyneisconvertedtoaCu(I)acetylidebeforetransmetallationtoPdoccurs.Themechanismwasdiscussedinthetext(SectionC.2.d).(d)AnewC–CbondisformedbetweenanucleophilicC–BandanelectrophilicC–I.ThisSuzukicouplingproceedsthroughthestandardoxidativeaddition,transmetallation,reductiveeliminationprocesscharacteristicofPd-catalyzedcross-couplings.Themechanismwasdiscussedinthetext(SectionC.2.d).(e)ThereisnonucleophileinthisHeckreaction.ThefirststepmustbeoxidativeadditionofPd(0)totheAr–IbondtogiveaPd(II)complex.(Beforethiscanoccur,thePd(II)complexthatisaddedtothereactionmixturemustbereducedtoPd(0).Inthissystem,itisnotclearhowithappens.EithertheI–ortheSinasmallamountofheterocyclemightactasareducingagent.)ThecrucialC–CbondisthenformedbycoordinationoftheπbondofacrylatetothePd(II)complexandmigratoryinsertion.β-Hydrideelimina-tiongivestheorganicproductandI–Pd(II)–H.DeprotonationanddissociationofI–regeneratesthePd(0).(a)SPhILnPd0SPhPdLnICO2EtSPhLnPdICO2Et(b)(c)IIIISPhCO2EtPdLnIHH(d)SPhCO2EtHHHPdLnIHIIII(e)LnPd0(a)oxidativeaddition;(b)coordination;(c)insertion;(d)β-hydrideelimination;(e)deprotonation.NEt3(f)AnallylicCwithaleavinggroupisbeingepimerizedbythePd(0)complex.OnepossiblemechanismissimpledisplacementofNbyPd(0)toformtheπallylcomplex,thendisplacementofPd(0)byNtoreformthering.TheproblemwiththismechanismisthatallylicsubstitutionreactionscatalyzedbyPdproceedwithretentionofconfiguration(twoSN2-typedisplacements),whereasthisreactionproceedswithinversionofconfiguration.Inthisparticularmolecule,theanionicNcancoordinatetothePdπallyl6.3intermediateinanintramolecularfashion;reductiveeliminationfromthischelatewouldgivetheproductwithoverallinversionofconfiguration.NSO2ArRHHPPh3PdPPh30Ph3PPdPh3PNSO2ArRHHPh3PPdPh3PHArO2SNRHoxidativeadditionPPh3PdPh3PHArO2SNRHreductiveeliminationHSO2ArNRHPh3PPdPh3P0+(g)Make:C4–C5,C1–H.Break:C5–H.CH3HCO2EtPhCN1mol%Pd2(dba)3·CHCl35mol%dppf+CH3CO2EtPhCN1234512345C5isextremelyacidic,andoncedeprotonateditisnucleophilic.C4,though,isnotelectrophilic,soweneedtoconvertittoanelectrophilicC.Lookingattheproduct,oneseesthatthenewC–Cbondisallylic.ThissuggestsattackofC5onaπallylcomplex.ThiscomplexcouldbemadebyinsertionoftheC1≡C2πbondintoaPd–Hbond.ThislastcouldbemadebyprotonationofPd(0)byC5.CH3CO2EtPhCNallylicCH3LnPdCH3LnPdCH3PdLnHProtonationofPd(0)gives[Pd(II)–H]+.CoordinationandinsertionoftheC1≡C2πbondgivesthePdπallylcomplex.Attackofthenucleophileonthelesshinderedterminusgivestheobservedproduct.6.4LnPd0HCO2EtPhCNPdLnHCH3coordination,insertion.CH3LnPdIIIICH3LnPdIICO2EtPhCNCH3CO2EtPhCN+LnPd0(h)ThisreactionissimplyaWackeroxidation.Itsmechanismwasdiscussedinthetext(SectionC.2.f).ThekeystepsareattackofH2OonanelectrophilicPd–alkenecomplex,thenβ-hydrideeliminationtogivetheenol.(i)Make:C1–C5,N4–C5,C3–O6.Break:C1–Br.BrNO2%(Ph3P)2PdCl2,8%PPh3CO,1.3Et3N,EtOHNOEtOO123456123456IncorporationofCOintoanorganicsubstrateusuallyoccursbyinsertionofCOintoaC–metalbond.TherequisiteC1–metalbondisformedbyoxidativeadditionofaPd(0)speciesintotheC1–Brbond,thenormalfirststepuponcombiningaPd(0)compoundandanarylhalide.CoordinationandinsertionofCOfollows.AdditionofNtothecarbonylandlossofPd(0)givesaniminiumion,whichistrappedbyEtOHtogivetheproduct.Ph3PPdPh3P0BrNOPdLnNOoxidativeadditionBrCOcoordinationArPdLnBrCOIIIIinsertion6.5NOLnPdIIBrONO–OPdLnBrIINOOPdLn0+Br–HOEt–H+NOOHOEtNOOOEt(j)ThisisanotherHeckreaction.AftertheinsertiontogivetheσboundPd(II),β-hydrideeliminationoccursinthedirectionoftheOHtogiveanenol.Theenoltautomerizestothealdehyde.(k)Make:C1–Cl,C2–C3.Break:none.1CO2MeCHOxs4LiCl,AcOH2mol%Pd(OAc)2ClCHOCO2Me2341234Infact,amechanismforthisreactioncanbedrawnthatdoesnotinvolvePdatall,butlet’sassumethatPdisrequiredforittoproceed.Cl–mustbenucleophilic.ItcanaddtoC1ofthealkyneifthealkyneisactivatedbycoor