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

1ANSWERSTOPROBLEMSINBODYOFCHAPTER1.1.1.Theresonancestructureontherightisbetterbecauseeveryatomhasitsoctet.1.2.CH2+COO–OCH2CH2CH2CONMe2NNMe2NMe2NMe2NMe2NMe2NNNNNCH2H3CH3CONCH2H3CH3COthesecondstructureishopelesslystrained1.3.OONNPhO–PhCH3H3CCH3CH3H3CCH3spsp2sp3spsp2sp2sp2sp2allsp2allsp2sp3sp3sp2sp3sp3sp3sp32H2COCH3HHHHBFFFsp2sp2sp2sp3sp2sp2sp1.4.(a)Noby-products.C(1–3)andC(6–9)arethekeystonumbering.OHPhOH+,H2OOPhHO1234567891011121312131098213457611(b)Afternumberingthemajorproduct,C6andBr25areleftover,somakeabondbetweenthemandcallittheby-product.123456789101112131415161718HNBrOMeOOMeHNBrOOOMeBr1920212223BrBr2425MeBr12345678109191817161524141320211112251.5.(a)MakeC4–O12,C6–C11,C9–O12.BreakC4–C6,C9–C11,C11–O12.(b)MakeC8–N10,C9–C13,C12–Br24.BreakO5–C6,C8–C9.1.6.PhC≡CHismuchmoreacidicthanBuC≡CH.BecausethepKbofHO–is15,PhC≡CHhasapKa≤23andBuC≡CHhaspKa23.1.7.TheOHismoreacidic(pKa≈17)thantheCαtotheketone(pKa≈20).Becausetheby-productofthereactionisH2O,thereisnoneedtobreaktheO–Hbondtogettoproduct,buttheC–Hbondαtotheketonemustbebroken.3ANSWERSTOPROBLEMSINBODYOFCHAPTER2.2.1.LDAisastrongbase.TwoE2eliminationsgiveanalkyne,whichisdeprotonatedbytheexcessLDAtogiveanalkynylanion.ThisspeciesthenreactswithMeIbyanSN2process.ClOMeOMeHHH–N(i-Pr2)HOMeOMeH(i-Pr2)N–HOMe–N(i-Pr2)MeOMeIMeOMe2.2(a).LDAdeprotonatestheCαtotheester,whichaddstothealdehydetogivethealdolproductafterworkup.OOH3CH3COCH3HOOH3CH3COCH3EtO–H–N(i-Pr2)OOH3CH3COCH3OEtworkupproduct2.2(b).BuLideprotonatestheCαtothenitrile,whichaddstotheketonetogivethealdolproductafterworkup.workupproductNCHHHLiBuNCHHOEtEtNCHHEtO–Et2.3.Make:C2–C3.Break:none.NotethatbecausetheNaCNiscatalytic,itsatomsarenotincorporatedintotheproduct,andhencethereisnoneedtonumberthem.cat.NaCNPhPhOOHEtOH,H2OPhHOPhHO12341234+4C2iselectrophilic,andC4is...electrophilic!Tomakeabondbetweenthem,C2mustbeturnedintoanucleophile(umpolung).Thismustbethepurposeofthe–CN.AldehydesarenotacidicatthecarbonylC,sothe–CNcannotsimplydeprotonateC2.Instead,itmustaddtoC2.NowC2isαtoanitrile,itismuchmoreacidic,anditcanbedeprotonatedbyexcess–CNtogiveanenolate,whichcanaddtoC4.Finally,deprotonationofO1andeliminationof–CNgivestheobservedproduct.PhHO–CNPhHO–CNHOEtPhHHOCN–OEtPhHOCNPhHOPhHOCNO–PhPh–OCNOHPhPhOOHPh2.4.(a)Make:C2–C5,C2–C6.Break:C2–Br4.EtO2CCO2EtBrNaOEtEtO2CEtO2CCHOCHO123456781235678HBr4C2isbothelectrophilicandparticularlyacidic.C5iselectrophilic,andC6hasnoreactivity,sothefirstbondtobemademustbeC2–C5.Therefore,deprotonationofC2givesanucleophile,whichcanattackelectrophilicC5togiveanenolateatC6.NowC6isnucleophilic,andintramolecularSN2substitutionatC2givestheproduct.AlthoughC2isatertiaryalkylhalideandisnotnormallyexpectedtoundergoSN2substitution,thisreactionworksbecauseitisintramolecular.EtO2CCO2EtBrCHOH–OEtEtO2CCO2EtBrEtO2CCO2EtBrCHOEtO2CCO2EtCHO(b)Make:C7–C8,C4–C9.Break:none.5OH3CCH3CH3LiN(i-Pr)(c-Hex);CO2MeH3CCH3CH3OCO2MeH1234567891010981234567ThethingabovethearrowisafancyversionofLDA.C4andC8areelectrophilic,C9isunreactive,andC7isacidic,sofirststepmustbetodeprotonateC7tomakeitnucleophilic.ConjugateadditiontoC8generatesanucleophileatC9,whichaddstoC4togiveanewenolate.Workupthenprovidestheproduct.OH3CCH3CH3CO2MeHH–NR2OH3CCH3CH3HOH3CCH3CH3HCO2MeOH3CCH3CH3HMeO2CworkupOH3CCH3CH3HMeO2C(c)Make:C2–C21,C5–C11,C6–C22.Break:none.CO2t-BuOOOOCO2MeCs2CO3CH3CH3HCO2t-BuOOHHHOOOOMeCO2t-BuOOOOCO2MeCH3CH3HCO2t-BuOOHHHOOOOMe12356789101112131415416171819202122232322211617181920123456789101112131415Amongthesixatomsinvolvedinbond-making,three(C6,C10,C21)areelectrophilic,two(C5,C22)areunreactive,andonlyC2isacidic,sofirststepisdeprotonationofC2.ThenucleophileaddstoC21,makingC22nucleophilic.ItaddstoC6,makingC5nucleophilic.ItaddstoC10,givingtheproduct.6CO2t-BuOOOOCO2MeCH3HHCsCO3–CO2t-BuOOOCH3HCH3HCO2t-BuOOOOOOMeCH3HCO2t-BuOOOOOOMeCH3HCO2t-BuOOOOOOMeproductHOCO2Cs2.5.Becauseunderbasicconditionscarboxylicacidsaredeprotonatedtothecarboxylateions,whicharenolongerelectrophilicenoughthataweaknucleophilelikeMeO–canattackthem.Uponworkupthecarboxylateisneutralizedtogivebackthecarboxylicacid.2.6.(a)BalancingtheequationshowsthatEtOHisaby-product.Make:C2–C11.Break:O1–C2.1235678910114H3CEtO2CCH3ONaOEtEtO2COOH3COOEt119108746532EtOH1+C2iselectrophilic,sofirststepmustbetodeprotonateC11tomakeitnucleophilic.AdditiontoC2followedbyeliminationofO1affordstheproduct.Becausetheproductisaveryacidic1,3-diketone,though,itisdeprotonatedunderthereactionconditionstogiveananion.Workupthenaffordstheneutralproduct.H3CEtO2CCH2OOOEtH–OEtH3CEtO2CCH2OOOEtEtO2COH3COOEt7EtO2COH3COEtOHHEtO2COH3COHworkupEtO2COH3COHH(b)Make:C3–C9.Break:O8–C9.1235678910114ONaOEt,EtOHOOEtOOEtOOEt119101235674+EtOH8Themechanismisexactlythesameasdrawninpart(a).2.7.(a)Make:O1–C9.Break:S8–C9.121314151191012356748OHO2SNO2NaOHOSO2–NO2121314151191012345678ThebasedeprotonatesO1,whichaddstoC9,givingananionthatisdelocalizedoverC10,C12,C14,andintotheNO2group.TheanionthenexpelsSO2–togivetheproduct.OHO2SNO2–OHOO2SNO2OO2SNO2product(b)Make:O1–P5,C2–Br4.Break:O1–C2,Br4–P5.NHONBrBrPBr2HOPBr2+1234523415O1isclearlyanucleophile,andC2iscl