有机反应机理的书写艺术答案ans4

AnswersToChapter4In-ChapterProblems.4.1.Thenumberingoftheatomsisquitedifficultinthisproblem.ThenumberofMegroupsintheproductsuggeststhatatleasttwoequivalentsofthebromideareincorporatedintotheproduct.ButwhichringatomsareC3andwhichoneisC6?AndevenifoneoftheringcarbonsisarbitrarilychosenasC6,thereisstillthequestionofwhetherC3orC2becomesattachedtoC6.Thisproblemissolvedbynotingthatstep1turnsthebromideintoaGrignardreagent,whichisnucleophilicatC3,soitislikelytoattackC6,andelectrophilicatom.Make:C3–C6,C3´–C6,C2–C2´.Break:C6–O7,C6–O8,C3–Br,C3´–Br.MeBrMeMeHMeMeMeMe1234MgCH3COEtOH+567843214´3´2´1´56Inthefirststep,thebromideisconvertedtoaGrignardreagent.Inthesecondstep,twoequivalentsoftheGrignardreagentreactwiththeesterbyaddition–elimination–addition.(Remember,theketonethatisinitiallyobtainedfromreactionofaGrignardreagentwithanesterbyaddition–eliminationismoreelectrophilicthanthestartingester,soadditionofasecondGrignardreagenttotheketonetogiveanalcoholisfasterthantheoriginaladditiontogivetheketone.)Inthelaststep,additionofacidtothetertiary,doublyallylicalcoholgivesapentadienylcationthatundergoeselectrocyclicringclosure.LossofH+givestheobservedproduct.MeBrMeMgMeMgBrMeCH3COEtOMeMeOEtOMeHHHMeMeOMeMeMeMeOMeBrMgMeMeMeH+HHHHMeH2OMeMeMeMeMeMeMeMeMeHHHHMeMeMeMeMeHHproduct4.2.Asusual,thekeytothisproblemisnumberingcorrectly.ThemainquestioniswhethertheesterCintheproductisC3orC4.Becausearingcontractionfrom6-to5-memberedislikelytoproceedbyaFavorskiirearrangement,wherethelaststepiscleavageofacyclopropanone,itmakessensetolabeltheChapter42esterCasC4.Make:C3–C5,C4–C15.Break:C3–O9,C4–C5,C5–O13,O11–Ts12.OOTsOOTsOTsNaOMeOO12345678OMeO910111213141512786515OOOMeO12786515OOOMeO234564113HENCE7815Holdon!IftheO11–Ts12bondisbroken,andtheelectronsgotoO(asseemsreasonable),whathappenstotheTs?Somenucleophilemustformabondtoit.TheonlynucleophileinthemixtureisMeO–,solet’saddTs12–O15toourmakelist.NaOMeisagoodbase,andwithalltheseTsOgroups,anE2eliminationreactiontobreakaC–OTsbondseemsreasonable.EithertheC3–O9ortheC5–O13bondcanbecleaved;wechoosetheC5–O13bondhere,butcleavageoftheotherbondworks,too.Theproductisanenoltosylate.Asecondeliminationreactionisnotpossible,butatthispointwecanformtheTs12–O15bondandcleavetheO11–Ts12bondbyhavingMeO–attackTs12,displacingO11tomakeanenolate.ElectrocyclicringclosingwithconcurrentcleavageoftheC3–O9bondgivesacyclopropanone.AdditionofO15toC4andthenC4–C5bondcleavagewithconcurrentprotonationofC5bysolventgivestheproduct.OOTsOOTsOTsHHH–OMeOOTsOOHHTs–OMeOOTsOOHHOOOHH–OMeOOOHHMeOHOMeOOOHHMeOH4.3.Make:C1–C8.Break:none.OH3CCH3CH3H3CNaOHOH3CCH3CH31234567891012345678910HHHHHHHDeprotonationofC1givesanenolateion,whichinthiscompoundisactuallya1,3,5-hexatriene.Assuchitcanundergoanelectrocyclicringclosing.Protonationgivestheproduct.Chapter43OH3CH2CCH3H3CHOHOH3CCH2CH3H3COH3CCH2CH3CH3productOHHHHHHHHYoumayhavebeentemptedtodrawtheC1–C8bond-formingreactionasaconjugateaddition.However,onceC1isdeprotonated,thecarbonylgroupisnolongerelectrophilic,becauseitisbusystabilizingtheenolate.Itismuchmorepropertothinkofthebond-formingreactionasanelectrocyclicringclosure.Thisproblemillustrateswhyitissoimportanttoconsideralltheresonancestructuresofanyspecies.4.4.Make:C2–C7.Break:C2–C5.OOHDHHHHHHHHHHH12345671234567Youmaybeverytemptedtodrawthefollowingmechanismforthereaction:OHHHHHHOHHHHHH~H+OHHHHHHHowever,thismechanismisnotcorrect.Itisa[1,3]-sigmatropicrearrangement,andforreasonswhicharediscussedinSection4.4.2,[1,3]-sigmatropicrearrangementsareveryrareunderthermalconditions.Amuchbettermechanismcanbewritten.TheC2–C5bondispartofacyclobutene,andcyclobutenesopenveryreadilyunderthermalconditions.Aftertheelectrocyclicringopening,a1,3,5-hexatrieneisobtained,andthesecompoundsreadilyundergoelectrocyclicringclosureunderthermalconditions.Tautomerizationthenaffordstheproduct.OHHHHHHCOHHHHHHOHHHHHH~H+product4.5.Theproducthasacisringfusion.Chapter44HHHHHHHHHHHHHHHH6e–4.6.Thefirstelectrocyclicringclosureinvolveseightelectrons,soitisconrotatoryunderthermalconditions,andthetwohydrogenatomsattheterminusofthetetraene,whicharebothin,becometrans.Thesecondelectrocyclicringclosureinvolvessixelectrons,soitisdisrotatoryunderthermalconditions,andthetwohydrogenatomsattheterminusofthetriene,whicharebothout,becomecis.Thisisthearrangementobservedinthenaturalproduct.CO2RPhCO2RPhHHHHHHHHCO2RPhHHHHHHHPhHHHCO2RDH4.7.TheHOMOofthepentadienylcationisy1,whichisantisymmetric,soaconrotatoryringclosureoccurs,consistentwiththefourelectronsinvolvedinthisreaction.TheHOMOofthepentadienylanionisy2,whichissymmetric,soadisrotatoryringclosureoccurs,consistentwiththesixelectronsinvolvedinthisreaction.+++++·––·–·+–·+–++++–+–++y0y1y2y3y4MOsofthepentadienylpsystempentadienylcationpentadienylanionChapter45pentadienylcationHOMOHHHHconrotatoryHHHHpentadienylanionHOMOHHHHdisrotatoryHHHH4.8.Make:O1–C9,N2–C13,C10–C13.Break:C13–O14.HHNHOHCH3CH2=OONCH3123456789101112131412345678910111213Thenewfive-membered,heterocyclicringcluesyouintothefactthata1,3-dipolarcycloadditionhasoccurredheretoformbondsO1–C9andC10–C13.Disconnectthesebonds,puttinga+chargeonC13anda–chargeonO1,toseetheimmediateprecursortotheproduct.ONCH31291013ONH2CCH3HHNCH3H2COWhenthisdisconnectioniswrittenintheforwarddirectionalongwithsomecurvedarrows,itisthelaststepinthereaction.NowallyouhavetodoismakeN2–C13andbreakC13–O14.Thisiseasytodo:N2attacksC13,protontransferoccurs,N2expelsO14,anddeprotonationgivesthenitrone.HHNHOHCH3CH2=OHHNHCH3H2COHO~H+HHNCH3H2COHHOChapter46HHNCH3H2COHOH~H+ONH2CCH3product4.9.Me2SattacksoneoftheOatomsinvolvedintheO–Obond,displacingO–.Hemiacetalcollapsetothecarbonylcompoundsthenoccurs.OOORR´SMe2OOORR´SMe2OOORR´SMe24.10.Make:C7–C2´,C9–O1´.Break:C2´–O1´.HNNOMeORHNNOORNNMeOHMeORHhnHNNOMeORR=sugarphosphatebackboneofDNA.123456HHH7891´2´3´4´5´6´7´8´9´1234567896´4´5´3´2´1´9´8´7´MakingtheC7–C2´andC9–O1´suggestsa[2+2]photocycloaddition.ThenthelonepaironN3´expelsO1´fromC2´togivetheobservedproduct(afterprotontransfer).HNNOMeORHHNNOMeORHhnHNNOMeORHHNNOMeORHChapter47HNNOMeORHHNNOMeORH~H+product4.11.Thenumberingisnotstraightforwardinthisreaction,butifyoudrawintheHatomsyoucanseethatthetwoCHgroupsinthenewbenzeneringintheproductprobablycomefromtwoCHgroupsinnorbornadiene.AtomsunaccountedforinthewrittenproductincludeC9andO10(canbelostasCO),C17toC21(canbelostascyclopentadiene),andO1andO4(canbelostasH2O).Make:C2–C8,C3–C11,C8–C16,C11–C15.Break:O1–C2,C3–O4,C8–C9,C9–C11,C15–C19,C16–C17.OOH3CCH3OOO,cat.glycine1234567891011121314151617181920212356HHHHHHHHHHHHHHOCH3OCH378141213111516CO910HHHHH1718192021Glycineactsasanacid–basecatalystinthisreaction.C8andC11areveryacidic,andoncedeprotonatedtheyareverynucleophilic,sotheycanattackC2andC3inanaldolreaction.Dehydrationgivesakeycyclopentadienoneintermediate.(Themechanismofthesestepsisnotwrittenoutbelow.)Cyclopentadienonesareantiaromatic,sotheyareverypronetoundergoDiels–Alderreactions.Suchareactionoccursherewithnorbornadiene.Aretro-Diels–Alderreactionfollowedbya[4+1]retrocycloadditionaffordstheproduct.OOH3CCH3OOOHHHHOHOHOH3COH3COHHChapter48OH3COH3COHHHHHHHOH3COH3COHHHHHHHHOH3COH3COHHproduct4.12.Make:C3–C9,C3–C14,C6–C10,C6–C13.Break:C3–N4,N5–C6.HHCNNNCNCN110°CCN+1234HHHHHHHHHH5678910111213141516123786910111213141516TheC3–C9andC6–C10bondscanbemadebyaDiels–Alderreaction.ThenlossofN2andcleavageoftheC3–N4andN5–C6bondscanoccurbyaretro-Diels–Alderreaction.Thisstepregeneratesadiene,whichcanundergoanother,intramolecularDiels–AlderreactionwiththeC13–C14pbondtogivetheproduct.NNCNCNHHHHHHHHNNHHNCNCHHHHHHNCNCproductHH4.13.The[6+4]cycloadditioninvolvesfivepairsofelectrons(anoddnumber),soitisthermallyChapter49allowed.The[4+3]cationiccycloadditioninvolvesthreepairsofelectrons,soitisalsothermallyallowed.4.14.Make:C6–C8.Break:C6–C7.i-Pri-Pri-Pr280°C,24hi-PrHHHHHHHHHHHHHHHHHHHH123456789101112131415151413121110987521436MakingandbreakingbondstoC6suggestsa[1,n]sigmatropicrearrangement,anda[1,5]sigmatropicrearrangement,oneofthemostcommontypes,ispossiblehere.Oncetherearrangementisdrawn,however,themechanismisnotcomplete,eventhoughallbondsonthemake&breaklisthavebeencrossedoff.C8stillhasoneextraHandC9hasonetoofew.Boththeseproblemscanbetakencareofbyanother[1,5]sigmatropicrearrangement.Thisstep,bytheway,reestablishesthearomaticring.i-Pri-PrHHHHHHHHHHi-Pri-PrHHHHHHHHHH6789product84.15.Make:C1–C9.Break:C3–N8.NCO2EtBnDBUNBnCO2Et1234567891012345678910HHHHHHHHHHHDeprotonationofC9byDBUgivesanylide(haspositiveandnegativechargesonadjacentatomsthatcannotquencheachotherwithapbond),acompoundwhichisparticularlypronetoundergo[2,3]sigmatropicrearrangementswhenanallylgroupisattachedtothecationiccenter,asisthecasehere.EstersarenotnormallyacidicenoughtobedeprotonatedbyDBU,butinthisestertheN+stabilizestheenolatebyaninductiveeffect.Chapter410NCO2EtBnDBUHHHHHHNCO2EtBnHHHHHNCO2EtBnHHHHH4.16.Make:C4–C10.Break:Cl1–N2.NRMeSCO2EtNHRSMeCO2EtClHHHHHHHHHHHH1234567891011111092345678ThemostunusualbondinthissystemistheN–Clbond.Thenucleophilicsubstitutionstepmustinvolvecleavageofthisbond.Nobaseispresent,butSisanexcellentnucleophile,eveninitsneutralform,sothefirststepprobablyentailsformationofanS9–N2bond.NowwehavetomaketheC4–C10bondandmaketheS9–N2bond.DeprotonationofC4givesanylide,whichasdiscussedinproblem4.15islikelytoundergoa[2,3]sigmatropicrearrangement.Tautomerizationtorearomatizethengivestheproduct.NRMeSCO2EtClHHHHHHHNRSMeHHHHHHHCO2EtbaseNRSMeHHHHHHCO2EtNRMeSHHHHHHCO2Et~H+product4.17.Thereactioninquestionis:ODOHTonamethereaction,drawadashedlinewherethenewbondismade,drawasquigglylineacrossthebondthatisbroken,andcountthenumberofatomsfromtheterminiofthedashedbondtotheterminiofthesquigglybond.Chapter411O12345123Thisreactionwouldbea[3,5]sigmatropicrearrangement,aneight-electronreaction,andhencewouldrequirethatonecomponentbeantarafacial.Notlikely!Amorereasonablemechanismbeginswiththesame[3,3]sigmatropicrearrangementthatgives2-allylphenol.However,insteadoftautomerizationtogivethearomaticproduct,asecond[3,3]sigmatropicrearrangementoccurs.Thentautomerizationgivestheproduct.OHHHHHHHHHHOHHHHHHHHHHOHHHHHHHHHH~H+product4.18.BoththeStevensrearrangementandthenonallylicWittigrearrangementbeginwithdeprotonationoftheCatomnexttotheheteroatomfollowedbyananionic[1,2]sigmatropicrearrangement.Bothinvolvefourelectrons,anevennumberofelectronpairs,andhenceifeitherisconcertedthenoneofthetwocomponentsofthereactionmustbeantarafacial.Thisconditionisextremelydifficulttofulfill,andhenceitismuchmorelikelythatbothreactionsarenonconcerted.BoththeStevensrearrangementandthenonallylicWittigrearrangementarethoughttoproceedbyhomolysisofaC–SorC–ObondandrecombinationoftheCradicalwiththeneighboringCatom.PhOCH3BuLiHHPhOCH3HPhOCH3HPhO–CH3PhOCH3H4.19.Make:N1–C11,C2–C8.Break:C2–C6,C11–O12.OHNHMePhMeCHOcat.H+NMeOPhHMe1234567891011121234567891011H2O12Chapter412TheN1–C11bondiseasilymadefirst.CleavageoftheC11–O12bondgivesaniminiumionthatisalsoa1,5-(hetero)diene.TheCoperearrangementoccurstogiveanewiminiumionandanenol.Attackoftheenolontheiminiumion(theMannichreaction)affordstheproduct.OHNHMePhMeOHOHNHPhMeOH~H+OHNPhMeOH2MeMeOHNPhMeOHNPhMeOHNPhMe–H+productMeMeMeNowthestereochemistry.Assumethethermodynamicallymorestableiminiumionforms(Megroupscis).TheCoperearrangementoccursfromachairconformation.ThisputsthePh,H2,andH11allpointingupbothbeforeandaftertherearrangement.AssumingtheMannichreactionoccurswithoutachangeinconformation(areasonableassumption,consideringtheproximityofthenucleophilicandelectrophiliccenters),thePh,H2,andH11shouldallbecisintheproduct.NMeOHMePhHHNMeOHMePhHHNMeOMePhHH2112114.20.DeprotonationofoneoftheMegroupsadjacenttoSgivesanylidewhichcanundergoaretro-hetero-enereactiontogivetheobservedproducts.H2CSCH3ORHHNEt3HCH2SCH3ORHHCH3SCH3ORHIf(CD3)2SO(deuteratedDMSO)isusedfortheSwernreaction,theE2mechanismpredictsthatthesulfideproductshouldbe(CD3)2S;theretro-hetero-enemechanismpredictsthatitshouldbe(CD3)S(CHD2).Guesswhichproductisactuallyfound?Chapter413AnswersToChapter4End-of-ChapterProblems.1.(a)Aneight-electron[4+4]cycloaddition.Itproceedsphotochemically.(b)Afour-electronconrotatoryelectrocyclicringopening.Itproceedsthermally.(c)Asix-electronenereaction.(Notethetranspositionofthedoublebond.)Itproceedsthermally.(d)Asix-electron[1,5]sigmatropicrearrangement.Itproceedsthermally.(e)Aten-electron[8+2]cycloaddition.Itproceedsthermally.(f)Asix-electron[2,3]sigmatropicrearrangement.Itproceedsthermally.(g)Asix-electrondisrotatoryelectrocyclicringopening.Itproceedsthermally.(h)Afour-electrondisrotatoryelectrocyclicringclosing.Itproceedsphotochemically.(i)Asix-electrondisrotatoryelectrocyclicringclosing.Itproceedsthermally.(j)Asix-electron[3+2](dipolar)cycloaddition.Itproceedsthermally.(k)Afour-electron[2+2]cycloaddition.Itproceedsphotochemically.(l)Asix-electronconrotatoryelectrocyclicringopening.Itproceedsphotochemically.2.(a)Regio:RNHandCHOare1,2.Stereo:CHOandCH3remaintrans;NHRisout,CHOisendo,sotheyarecisinproduct.BnO2CHNCHOCH3(b)ThetwoCH3groupsarebothoutgroups,sotheyarecisinproduct.OOH3CCH3(c)Regio:C4ofdieneisnucleophilic,soitmakesabondtoelectrophilicCofdienophile.Stereo:EtOisout,CO2Etgroupisendo,sotheyarecisinproduct.OEtOCO2Et(d)Regio:CHOandOSiMe3are1,4.Stereo:theCH2CH2bridgeisinatbothendsofthediene,CHOisendo,sotheyaretransinproduct.Me3SiOH3CCHOCH3Chapter414(e)Dienophileaddstolesshinderedfaceofdiene.C(sp3)offive-memberedringisin,NO2isendo,sotheyaretransinproduct.NO2HEtOEtO(f)Regio:NucleophilicOaddstoelectrophilicbCofunsaturatedester.Stereo:alkylandCO2Megroupsremaintrans;Hisin,CO2Meisendo,sotheyaretransinproduct.NOCO2MeHOMs(g)Stereo:CO2Megroupsremaintrans.Argroupisprobablyoutforstericreasons,CO2Meisendo,sothetwoarecisintheproduct.NCO2MeMeO2CArPh(h)The[14+2]cycloadditionmustbeantarafacialwithrespecttoonecomponent.Thetwoingroupsofthe14-atomcomponentbecometransintheproduct.CNCNNCNCHH3.1,3,5,7-Cyclononatetraenecantheoreticallyundergothreedifferentelectrocyclicringclosures.HH8e–electrocyclicringclosingconrotatoryHH”HHH6e–electrocyclicringclosingdisrotatoryHHH”HHChapter415H4e–electrocyclicringclosingconrotatoryHHH”HHWhensmallringsarefusedtootherrings,thecisringfusionisalmostalwaysmuchmorestablethanthetransringfusion.Theoppositeistrueonlyforsaturated6-6orlargerringsystems.(Makemodelstoconfirmthis.)Theorderofstabilityofthethreepossibleproductsshownaboveis:cis-6-5>trans-7-4>trans-8-3.4.(a)ChairTS,withtheMeontheC(sp3)equatorial.OPhOPhCH3H3CH3CCH3”OPhH3CCH3(b)ChairTS,withthePhequatorial.OPhOPh”OSiR3OBnOSiR3OPhOSiR3BnOBnO(R)H(S)(c)ChairTS,withbothsubstituentsequatorial.PhCH3PhH3CHH”PhH3CHH(d)Twodifferentchairsarepossible,butone(Phequatorial)islowerinenergythantheother.PhCH3PhHCH3H”PhHCH3HPhHHCH3(e)AchairTSisnotpossible,soitgoesthroughaboatTS.Chapter416HH3CO2CCH3OHH3CHCH3H3CO2CCH3OHchairTSnowayJoséHH3CO2CCH3OHH3CH”H3COHH3CO2CCH3HboatTSmuchbetter(f)Again,aboatTSisnecessary.HHH60°CHHHH”(g)AchairTSwouldproduceatransdoublebondintheseven-memberedring,sotheboatTSisoperative,andtheHandOSiR3groupsonthetwostereogenicatomsarecistooneanother.OSiR3HOSiR3HHHOSiR3HOSiR3HHHtransdoublebondOSiR3HHHOSiR3HHHOSiR3OSiR3H”OSiR3HOSiR3H(h)ThechairTSisenforcedinthismacrocycliccompound.Chapter417CH3OH3CCH3H3CHOHCH3OOHHH3C”CH3CH3OOHHH3C5.(a)Firststep:hetero-Diels–Alderreaction(six-electron,[4+2]cycloaddition).Secondstep:Claisenrearrangement(six-electron,[3,3]sigmatropicrearrangement).(b)Thedieneiselectron-rich,soitrequiresanelectron-poordienophileforanormalelectrondemandDiels–Alderreaction.TheC=Cbondofketenesisprettyelectron-rich,duetooverlapwiththelonepairsonO:H2C=C=O¨«H2C––C”O+.OnlytheC=Obondoftheketeneisofsufficientlylowenergytoreactwiththedieneatareasonablerate.(c)First,itisimportanttorememberthatinketenes,theporbitalsoftheC=ObondarecoplanarwiththesubstituentsontheterminalC.RSRLOBecauseoftheketene’sgeometry,intheTSofthehetero-Diels–Alderreaction,eitherRSorRLmustpointdirectlyatthediene.ThelowerenergyapproachtowardsRSischosen,andtheproductinwhichRSpointsbacktowardtheformerdieneportionofthecompoundisobtained.CORSRLORSRL+CORSRLSecondstep:Thenewsbondformsbetweenthebottomfaceofthedoublebondontheleftandthebottomfaceofthedoublebondontheright,givingtheobserved,lessthermodynamicallystableproduct.Chapter418ORSRLHHHORSRLHHHHORSRLHHHH”ORSRLHHHH6.(a)NumbertheC’s.C1,C2,C5andC6areclearinbothstartingmaterialandproduct.Therestfollows.H3COOSiMe3DH3CMe3SiOOH123456789563214789WebreaktheC4–C6bond,andweformC3–C8andC4–C9.Theformationofthelattertwobondsandthefactthatwe’reformingacyclobutanonesuggestsa[2+2]cycloadditionbetweenaketeneatC3=C4=OandtheC8=C9pbond.WecangeneratetherequisiteC3=C4pbondbyelectrocyclicringopeningofthecyclobuteneringintheS.M.H3COOSiMe3DMe3SiOCOH3CMe3SiOH3CCO(b)Electrocyclicringclosingfollowedbybase-catalyzedtautomerization(bothstartingmaterialandproductarebases)givestheproduct.NHNMeNSMeNONHNMeNSMeNHOBNHNMeNSMeNOHNHNMeNSMeNO–HBChapter419(c)Diels–AlderreactionfollowedbyspontaneouseliminationofMe3SiO–andaromatizationgivestheproduct.LossofMe3SiO–occurssoreadilybecausetheMe3Sigroupisapelectronwithdrawerlikeacarbonylgroup.OSiMe3ArOMe3SiOCO2MeCO2MeOSiMe3ArOMe3SiOCO2MeArOMe3SiOHH–OSiMe3CO2MeArOMe3SiOwork-upCO2MeArOHO(d)ThekeyatomsfornumberingtheC’sareC1(withthe2-bromoallylgroupattached),C7(estergroupattached),andC8(Oattached).WeformbondC1–C9andbreakbondC3–C7.SinceC3–C7isthecentralbondofa1,5-dienesystemterminatinginC1andC9,i.e.C1=C2–C3–C7–C8=C9,thismustbeaCoperearrangement.789563214789BrCO2MeOSiMe3DBrCO2MeOH123456BrCO2MeOSiMe3BrCO2MeOSiMe3”BrCO2MeOSiMe3Haq.workupBrCO2MeOHHBrCO2MeOH(e)NumberingthecarbonsismadeeasierbyC9,C8,andC4.TheseatomsmakeiteasytolabelC4throughC9.SinceC11isacarbanion,wecanexpectthatitwilladdtoC4,theonlyelectrophilicCinthestartingmaterial,andsinceC11hasaCH3groupattached,wecanidentifyitandC10intheproductastheChapter420easternmostC’s,withC11attachedtoC4.ForC1toC3,wepreservethemostbondsifweretaintheC9–C3–C2–C1sequence.Sooverall,weformC4–C11,C4–C2,andC10–C1,andwebreakC4–C3.789564789123456H3CMe3SiOOHLi;warmtoRT;NaHCO3CH3CH3OHOHHCH310111132110ThefirststepisadditionofC11toC4.WestillneedtoformC10–C1andbreakC4–C3.Sincewehavea1,5-diene(C11=C10–C4–C3–C2=C1),wecandoanoxy-Coperearrangement.Thisgivesa5-8systeminwhichweonlyhavetoformtheC4–C2bond.C4isneithernucleophilicnorelectrophilic,whileC11isnucleophilic(conjugationfromOSiMe3).Uponquenchingwithwater,however,C4becomesanelectrophiliccarbonylC,whereuponC11attackswithconcomitantdesilylationofOtogivetheproduct.H3CMe3SiOOHCH3H3CMe3SiOHCH3O–11041143LiH3CMe3SiOHCH3O–”CH3Me3SiOHO–HCH3HOH42CH3OHOHCH3Me3SiHO–CH3OHO–HCH3CH3OHOHHCH3(f)It’sclearthatweformC4–C5andC1–C6bonds,andwebreakC1–C4.ThestrainedC1–C4bondcanbeopenedbyanelectrocyclicringopeningtogiveano-xylylene,whichundergoesan[8+2]cycloadditiontogivetheobservedproduct.Chapter421Me3SiMe3SiCH3OHMe3SiMe3SiCH3OHHH123456234561Me3SiMe3SiCH3OHMe3SiMe3SiCH3OHMe3SiMe3SiCH3OHHH(g)WeformC2–C11andC5–C9bonds,andweeliminatetheelementsofMe3SiO2CCF3.TheZnCl2isaLewisacid,soitcoordinatestotheca