The-Art-of-writing-reasonable-organic-mechanism-an

1ANSWERSTOPROBLEMSINBODYOFCHAPTER4.4.1.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+HHHH2MeH2OMeMeMeMeMeMeMeMeMeHHHHMeMeMeMeMeHHproduct4.2.Theproductwhenα-chloro-α-phenylacetoneistreatedwithNaOMeismethylhydrocinnamate.CH3OClHOMeONaOMeHHHHThesemibenzilicacidrearrangementmechanism:CH3OClHOMeCH3OClHOMeOCH3HOMewrongproduct!TheFavorskiirearrangementmechanism:CH2OClHOMeHCH2OClHCH2OHOMeCH2OHOMeCH2OHOMeHOMeCH2OHOMeHrightproduct!4.3.Make:C1–C8.Break:none.OH3CCH3CH3H3CNaOHOH3CCH3CH31234567891012345678910HHHHHHH3DeprotonationofC1givesanenolateion,whichinthiscompoundisactuallya1,3,5-hexatriene.Assuchitcanundergoanelectrocyclicringclosing.Protonationgivestheproduct.OH3CH2CCH3H3CHOHOH3CCH2CH3H3COH3CCH2CH3CH3productOHHHHHHHHYoumayhavebeentemptedtodrawtheC1–C8bond-formingreactionasaconjugateaddition.However,onceC1isdeprotonated,thecarbonylgroupisnolongerelectrophilic,becauseitisbusystabilizingtheenolate.Itismuchmorepropertothinkofthebond-formingreactionasanelectrocyclicringclosure.Thisproblemillustrateswhyitissoimportanttoconsideralltheresonancestructuresofanyspecies.4.4.Make:C2–C7.Break:C2–C5.OOHΔHHHHHHHHHHH12345671234567Youmaybeverytemptedtodrawthefollowingmechanismforthereaction: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.4OHHHHHHCOHHHHHHOHHHHHH~H+product4.5.Theproducthasacisringfusion.HHHHHHHHHHHHHHHH6e–4.6.Thefirstelectrocyclicringclosureinvolveseightelectrons,soitisconrotatoryunderthermalconditions,andthetwohydrogenatomsattheterminusofthetetraene,whicharebothin,becometrans.Thesecondelectrocyclicringclosureinvolvessixelectrons,soitisdisrotatoryunderthermalconditions,andthetwohydrogenatomsattheterminusofthetriene,whicharebothout,becomecis.Thisisthearrangementobservedinthenaturalproduct.CO2RPhCO2RPhHHHHHHHHCO2RPhHHHHHHHPhHHHCO2RΔH54.7.TheHOMOofthepentadienylcationisψ1,whichisantisymmetric,soaconrotatoryringclosureoccurs,consistentwiththefourelectronsinvolvedinthisreaction.TheHOMOofthepentadienylanionisψ2,whichissymmetric,soadisrotatoryringclosureoccurs,consistentwiththesixelectronsinvolvedinthisreaction.+++++·––·–·+–·+–++++–+–++ψ0ψ1ψ2ψ3ψ4MOsofthepentadienylπsystempentadienylcationpentadienylanionpentadienylcationHOMOHHHHconrotatoryHHHHpentadienylanionHOMOHHHHdisrotatoryHHHH4.8.Make:O1–C9,N2–C13,C10–C13.Break:C13–O14.HHNHOHCH3CH2=OONCH3123456789101112131412345678910111213Thenewfive-membered,heterocyclicringcluesyouintothefactthata1,3-dipolarcycloadditionhasoccurredheretoformbondsO1–C9andC10–C13.Disconnectthesebonds,puttinga+chargeonC13anda–chargeonO1,toseetheimmediateprecursortotheproduct.6ONCH31291013ONH2CCH3HHNCH3H2COWhenthisdisconnectioniswrittenintheforwarddirectionalongwithsomecurvedarrows,itisthelaststepinthereaction.NowallyouhavetodoismakeN2–C13andbreakC13–O14.Thisiseasytodo:N2attacksC13,protontransferoccurs,N2expelsO14,anddeprotonationgivesthenitrone.HHNHOHCH3CH2=OHHNHCH3H2COHO~H+HHNCH3H2COHHOHHNCH3H2COHOH~H+ONH2CCH3product4.9.Me2SattacksoneoftheOatomsinvolvedintheO–Obond,displacingO–.Hemiacetalcollapsetothecarbonylcompoundsthenoccurs.OOORR´SMe2OOORR´SMe2OOORR´SMe24.10.Make:C7–C2´,C9–O1´.Break:C2´–O1´.7HNNOMeORHNNOORNNMeOHMeORHhνHNNOMeORR=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).HNNOMeORHHNNOMeORHhνHNNOMeORHHNNOMeORHHNNOMeORHHNNOMeORH~H+product4.11.Thenumberingisnotstraightf