上海有机所有机合成讲义[中]许杏祥

1()1.RadicalChainMechanismChaintransferAdditionIn+InHRCH2CHR'orRXRCH2CHR'+RRIn++++InitiationRCH2CH2R'RCH2CHR'XRCH2CHR'CH2CHR'InXRX+R(1)FormationofradicalThehomolysis,thefirststepofradicalreaction,couldbeachievedbyphotolysisandthermolysisofthemoleculeswithaweakbond,orbyaredoxsystem.(i)PeroxideY1OOY2+Y1OOY2Y1O(orY2O)+RH+Y1OH(orY2OH)PhCOOCPhOOtBuOOButR(ii)AzocompoundRNNRR2+N2Me2(CN)CNNC(CN)Me2(AIBN)(iii)Organometalliccompound(A)trialkyltinhydride2X=halogen,SePh,SPhBu3SnX+RRX+Bu3SnBu3Sn80oCAIBNBu3SnH(B)alkylmercurysaltRRHgNaBH4Hg+RHgHRHgX(iv)Redoxsystem+e-eX++RRRX[]-RXX-+RX[]+RX(2)TransformationofoneradicalintoanotherItisthisstepwheretherequiredproductsareformed.R+YRYCXYCYXY=C,O,NX=H,Hal+XYA+XYABBα-fragmentationβ-fragmentationXYABαβ32.Radicalcyclization:Radicalcyclizationsconsistofintramolecularadditionstodoubleortriplebonds.Thecyclizationsarefasterfortheformationof5-memberedringsthanforanyotherringsize.(i)Theregioselectivityfor5-exocyclizationsisoftenoutstanding.+exoendo(ii)Thecyclizationgiving5-memberedringcanbehighlystereoselective.(iii)Theconstructionofbicycliccompoundgoesmainlythecis-junction.ciscis()Thechainadditionreaction1.Thetinhydridemethod4Tributyltinhydrideisthereagentmostcommonlyusedtoconductfree-radicalreaction.AIBN/80oCorhvRHYBu3SnHYBu3SnXRXRBu3SnRYBu3SnH1Bu3SnH53%OOOBnO(10eq)O+OOIOBn2β−isomer+OAcOOAcBrOAcAcOCN+Bu3SnH70%OAcOOAcOAcAcOCN88:1253HOHBu3SnHAIBN1.NaBH42.TolOC(S)ClHOTolOC(S)OOOO4Bu3SnHHHIHHH5OHBrCNBu3SnHAIBNPhH,ref.70%OHCN66OOEt1.2eqBu3SnH0.1eqAIBNPhH,ref.OBrOEtNBSOEtOHOORC8H17OHNBSOEtOORC8H17OBrOEtBu3SnHOOC8H17OROEt7HOOHSiOHBu3SnHAIBNPhH,ref.OSiBr8NOPhSOPhBu3SnHNOPhH3CHO79COOHROPhSeH,Im2CODMFOPhSeOBu3SnH,AIBNPhH,refluxOOO10BnOBnOOBnOBnBu3SnHOBnHHBnOOBnBnO+OBnBnOOBnBnO+OBnBnOOBnBnO74%14%12%OOOBnXYHPhOCH3OOBnXYHPhH15XY1,5-cis/transOBnH0/100H77/23OBn99/182.TheMercurichydridemethodRRHgRYRHYHgYRHgHNaBH4RHgX1OHgOAc1.(C6H11)2BH2.Hg(OAc)2ONaBH42NaBH(OCH3)3Hg(OAc)2HOAcOHHOAcOOAcHgOAcO93XYORMe3SiOXR1.Me3SiCl2.CH2I2,Zn/CuXOR1.Hg(OAc)22.Y/NaBH43.ThefragmentationmethodRBu3SnRSnBu3SnBu3Bu3SnXRXR1Bu3Sn+OOCH3OOBnCOOMeOBrOCH3OOBnSnBu3COOMeAIBNPhCH3,80oC102-Bu3Sn72%OTBSOIOEt4eqPhMe,ref.Bu3SnC5H11ONNCNNCOOEtTBSOC5H11SnBu3OOOEtTBSOC5H11OC5H11OTMSBu3SnH(cat.)OOEtTBSOC5H11OTMS1.140oC2.Pd(OAc)23Bu3SnH-Me3SnMe3SnCOOCH3HOIOCOOCH30.3eqBu3SnHSnMe3CH3OOCBr114BrNSO2PhPhSOBnBu3SnHNSO2PhOBn()Thechainatom/grouptransferreaction1.Carbon-halogenatomtransfer179%CClHClClClCOOEtCH3CN140oCCuClCl+Cl3CCOOEt2NIO(Bu3Sn)2EtI,PhH,hvNHIO58%2.Heteroatom-halogenatomtransferHeteroatom-halogenbondsareveryweakandareeasilyhomolyticallycleaved.Theresultingheteroatomcenteredradicalreactviathreepathways.12(A)(B)(C)YXYXHYHYHYYR'YXY+YR'R'ThehydrogenatomabstrationshavebeenusedintheintroductionoffunctionalgroupatunactivatedC-Hbond.1CH3OHAcOCH3OAcPb(OAc)4,I2hv,CCl4AcOCH3OAcOH2CCH3CH3OROHCHOAcOCOO132ROOOROROROHHgO,I2CCl4ROOHOHORORORTheβ-fragmenttionoccurswithoxygen-centeredradicaltogiveacarbonylgroup.Thistransformationisusedinringenlargementprocesses.196%IOHgO,I2PhH,hvHHO260%OOHI2PhI(OAc)2HOOSPhH143.GrouptransferRCOClRCOOHNSOORYRSYNOCORRSYNNSOCORRYRNSO-1NO2SO2PhNSOCORRCOOH1.2.H2,NiROR'RRSO2PhSNTiCl3H2O2,K2CO3ROHRCOOHRNO2SN152COOEtSBut2.NSOH1.HAcOOCOClCOOEt()Thenon-chainredoxreaction1.ReductivemethodRX+X-REHRe-EREe-;H+Reactioninvolvingketylisthemostpopularapplicationofthereductivetechnique.1.e-2.H+OHRCOOR'ROCOOR'OHRCH3RO161OOOHHKNH3/THF(NH4)2SO4OOOHH70%2SmI2OOHOMEMOOOTBSMEMOOO2.OxidationmethodRproductXR+XRX+M(n-1)+M+n-H+XHHXnM+171Mn(III)OROR'R'+ROOH2OC6H5OMn(III)C6H5+OO3COOMeO(EtO)2OPOMn(III)Cu(OAc)277%O(EtO)2OPOCOOMe()π-4n4n+218+-+-+-HCH3HCH3+-HCH3HCH3+-+-H3CC3HHCH3HCH3+-+-+-+-+-+-HCH3HH3C+-+-H3CCH31-100oCSbF5-SO2ClFH3CH3CHHClH3CHH3CH+NROOCROOCHHAr100oCN+ArHHCOORROOC2CH3CH3HH175oCCH3H3CHH19100oCHH200oCHH3HOHCH3CH3RHOHCH3CH3RHOHCH3CH3RHOHCH3CH3RHOHCH3CH3Rhvhv∆∆4∆hvOCH3CH3OCH3HOCH3CH3OHH3COCH3CH3OCH3H20()Diels-AlderTheDiels-Alderreactionisthemostatom-economicalandreliablesix-memberedringformingmethodsknowninorganicchemistry.+R3R4R1R2R4R3R1R2(a)Itaccomplishestheunionofa4π-electronsystemwitha2π-electronsystem,creatingtwonewC-Cbondsanduptofourcontiguousstereocentersinoneefficientstep.(b)ByvaryingtheNatureofthedieneandthedienophilemanydifferenttypeofringstructurescanbebuiltup.(c)Highregio-andstereo-selectivityandtheirpredictability.(d)TheintramolecularD-Areactionhasshownwidespreaduseintheconstructionofpolycyclicringsystems.1.(1)Additionofanunsymmetricaldienetoanunsymmetricaldienophilecouldapparentlytakeplaceintwowaystogivetwostructurallyisomericproducts.Itisfoundinpractice,however,thatformationofoneoftheisomersisstronglyfavored.21(A)1-Proportionsofstructuralisomersformedinadditionofacrylicacidderivativesto1-substitutedbutadienes1,3-1,2-R1HR2CO2RR1R1R2HCO2RCO2RR2+R1R2RT°CRatioofproducts1,2-1,3-N(C2H5)2HC2H5201,2-only--CH3HCH320181CO2HHH701,2-only--CO2NaHNa22011C(CH3)3C(CH3)3CH32000.91CH2OHHCH319011(B)2-Proportionsofstructuralisomersformedinadditionofmethylacrylateto2-substitutedbutadienes1,3-1,4-HCO2CH3R1R1HCO2CH3R1CO2CH3H+R1T°CRatio1,4-to1,3-OC2H51601