消去反应分析

TheSyntheticMethodsof1.-Eleminationreactions（-消去反应+CCCCHX-OCOR,卤素,-OSO2Ar,-N+R3TheSyntheticMethodsof1.-Eleminationreactions（-消去反应+CCCCHX-OCOR,卤素,-OSO2Ar,-N+R3,-S+R2etX=-SaytzeffX=-OH,-OCOR,卤素,-HofmannX=-N+R3,-SynSaytzeffAntiHofmannAnti2Pyrolyticeliminations（顺式热消去反应+CCCC300~HOORSynthesisofterminalalkenesfromprimaryCHCHCHPyrolyticeliminations（顺式热消去反应+CCCC300~HOORSynthesisofterminalalkenesfromprimaryCHCHCHCHCHCH32223322Disadvantages:Highreaction3O+CCC Co100~200HOS+CCCC100~HO反应条件比对应的酯热消4胺氧化物热消磺原酸酯热消O+CCC Co100~200HOS+CCCC100~HO反应条件比对应的酯热消4胺氧化物热消磺原酸酯热消3.Wittigand3.Wittigandrelatedreactions（Wittig及有关反应Wittig5G.Wittigreceivedthe1979NobelPrizeinChemistryfor"manysignificantcontributionstoOrganicChemistry"whichincludednotonlytheWittigreaction,butalsoPhLipreparedbymetal-halogenexchange,benzyne,andtheWittigrearrangement.GeneralO CRCC+X+MildreactionThepositionofthedoublebondisGeneralO CRCC+X+MildreactionThepositionofthedoublebondisH-+O6•ExampleExample•ExampleExample7ExampleExampleExampleExample8[2+2][2+2]9•ActivityandstereoselectivityofZ/E(•ActivityandstereoselectivityofZ/E(mixture)R=R=alkenylorR=•Influenceofsolventonthe-++Z/E96/0/DMF++•Schlössermodification:allows•Schlössermodification:allowsthepreparationoftransvs.cisSchlösserAngew.Chem.,Int.Ed.Eng.1966,5,•Stabilized-Stabilized•Stabilized-Stabilizedylidesaresolid;stabletostorage,notparticularlysensitivetomoisture,andcanevenbepurifiedbychromatography.-Becausetheyarestabilized,theyaremuchlessreactivethanalkylylides.Theyreactwellwithaldehydes,butonlyslowlywithketones.-Thefirststep,involvingtheadditiontothealdehyde,isslowandreversiblewithstabilizedylides.•Influenceof•InfluenceofsolventontheHornerChem.Ber.1958,91,61;1959,92,Wadsworth,EmmonsJ.Am.Chem.Soc.1961,83,1733Reviews:Org.React.1977,25,ComprehensiveOrg.Syn.,Vol.1,PreparationofPhosphonatePreparationofPhosphonate-ArbuzovArbuzovJ.Russ.Phys.Chem.Soc.1906,38,-Thesameapproachtothepreparationof-ketophosphonatesisnot-But-ButcanusevariationonClaisen•Modificationsand-•Modificationsand-LiCl/tertiaryamines(DBU,iPr2NEt,Masamune,RoushTetrahedronLett.1984,25,Cansubstituteforconventionalconditionsandisespeciallygoodforbasesensitivesubstrates.-Hinderedphosphonatesandhindered-HinderedphosphonatesandhinderedaldehydesincreaseE-selectivity(-Still–GennarimodificationselectiveforZ-alkenes(-AdditionalZ-selectivestabilized-AdditionalZ-selectivestabilizedSelecteddiarylphosphonatesprovideZ-selectivityasPetersonReviews:Org.React.1990,38,Synlett,1991,Chem.Soc.Rev.,2002,31,PetersonReviews:Org.React.1990,38,Synlett,1991,Chem.Soc.Rev.,2002,31, CH2+COCOC Me3SiOPetersonreactionoffersanalternativetoWittigprocedure.TheyaremorereactiveandsteriocallylessdemandingthanaWittigreagentandthevolatilebyproduct(Me3SiOH/Me3SiOSiMe3)issimplertoremovethanPh3PO.Itdoes,however,requireasecondsteptopromoteeliminationofthe- -The-Theeliminationisacid-promotedbeingantiandbase-promotedbeingHudrlik,PetersonJ.Am.Chem.Soc.1975,97,•StabilizedPeterson•StabilizedPeterson-ThestabilizedPetersonreagentsgivepredominantlythemoststabletransolefins(E)-Additional-Additional4.TheTebbeReactionand4.TheTebbeReactionandRelatedTitanium-stabilized(Tebbe反应及与有关稳定化钛试剂的亚甲基化反应-TheWittig,Wadsworth–Horner–Emmons,andPetersonolefinationdonotconvertestersoramidestothecorrespondingolefin,butratherfailtoreactorresultinthecleavageoftheesteroramide-ToleratesketalandalkeneTebbeTHF,-78oC,OOOOOOrg.Lett.-ToleratesketalandalkeneTebbeTHF,-78oC,OOOOOOrg.Lett.2004,6,5.Sulphoxide-sulphenaterearragement:Synthesisofallyl(亚砜-次磺酸酯重排：烯丙醇类化合物的合/OOOS5.Sulphoxide-sulphenaterearragement:Synthesisofallyl(亚砜-次磺酸酯重排：烯丙醇类化合物的合/OOOSRRCROSHEvansandAndrews,Acc.Chem.Res.,1974,7,Combinedwithalkylationofsulphoxidesthereactionprovidesaversatilesynthesisofdi-andtri-substitutedallylicalcoholsExampleOSOSOS1.LDA/THF2.C6(MeO)3P/ 74Example1.n-2.ExampleOSOSOS1.LDA/THF2.C6(MeO)3P/ 74Example1.n-2.SO1.LDA/THF(MeO)3P/SO2.-alkylationofallylic 6.Alkenesfrom6.Alkenesfromsulphones(-JuliaOlefination（Julia烯烃合成法Review:ComprehensiveOrg.Syn.,Vol.1,-JuliaTetrahedronLett.1973,-BuLi/1.-2.-BuLi/1.-2.Na-93MeOH-JuliaBull.Soc.Chim.,Fr.1993,130,Julia,M.etal.,TetrahedronLett.,1973,4833Kocienski,P.J.etal.,J.Chem.Soc.PerkinI,1978,829.-Ramberg–Backlund-Org.React.1977,25,RR1.HCHO/2.RRCC-Ramberg–Backlund-Org.React.1977,25,RR1.HCHO/2.RRCCR+NicolaouK.C.etal.,J.AmChem.Soc.,1992,114,7360.BoockmanR.K.etal.,J.AmChem.Soc.,1991,113,9682.AlvarzeE.etal.,J.AmChem.Soc.,1995,117, -NaH-OOOOOS-NaH-OOOOOS7.Decarboxylationof-lactones(-内酯的脱羧反应RRSynthesisoftri-orR1 140~+OExampleHHH3CHSOo7.Decarboxylationof-lactones(-内酯的脱羧反应RRSynthesisoftri-orR1 140~+OExampleHHH3CHSOoO140~160 CH (>99%Note:NowasExampleOOCC-PhSO2Cl/CCFCO2 CHCl3,MolbierW.R.ExampleOOCC-PhSO2Cl/CCFCO2 CHCl3,MolbierW.R.etal.J.Org.Chem.,1995,60,Example DMF,FehrC.etal.TetrahedronLett.,1992,33,2COHHNHNCO OHHH-1402COHHNHNCO OHHH-140-Ph3HHHHR'=C6H5-,R"=63%;>99%R'=C6H5-,R"=75%;>97%MulzerJ.,etal.,J.Chem.Soc.Chem.Commun.,1979,8.Stereoselectivesynthesisoftri-andtetra-substituted 三、四取代烯烃的立体选择性合成EarlyOO 2 RCCCCISnCl28.Stereoselectivesynthesisoftri-andtetra-substituted 三、四取代烯烃的立体选择性合成EarlyOO 2 RCCCCISnCl2/NaI/CCCCR1=H,=Me,R3=Me,R4=Et;YieldCornforth,J.W.etal.,J.Chem.Soc.,1959,ThefirststepishighlyTheR4andthelargerofthegroupsR1and areantitoeachMethodHHRRLiMe1. /24CCCC2.I2,-I2RNote:ThesubstituentsorginallypresentinthepropargylalcoholaretranstoeachotherCCIRRLiMe1.LiAlH4/2CCCC2.I2,-MethodHHRRLiMe1. /24CCCC2.I2,-I2RNote:ThesubstituentsorginallypresentinthepropargylalcoholaretranstoeachotherCCIRRLiMe1.LiAlH4/2CCCC2.I2,-HHCH22Corey,E.J.etal.,J.Am.Chem.Soc.,1967,89,1.LiAlH4/MeONa/(54%;97%1.LiAlH4/MeONa/(54%;97%MethodRRR1.I2/THF,-Ciso-CC2.HHAl(iso-3R=Yieldiso-CCCCHAl(iso- CCMeLi/CMethodRRR1.I2/THF,-Ciso-CC2.HHAl(iso-3R=Yieldiso-CCCCHAl(iso- CCMeLi/CCHAl(iso-2HCO-2EZweifel,G.etal.,J.Am.Chem.Soc.,1967,89, HCCZHCCCLi[iso-CHCCZZweifel,G.etHCCZHCCCLi[iso-CHCCZZweifel,G.etal.,J.Am.Chem.Soc.,1967,89,Oxidativedecarboxylationofcarboxylic(羧酸的氧化脱羧反应Oxidativedecarboxylationofcarboxylic(羧酸的氧化脱羧反应Sheldon,R.A.,etal.,OrganicReactions,1972,19,Example与Dieal-Alder反应结Pb(OAc)4/Jahngen,B.G.E.,J.Org.Chem.,1974,39,ExamplePb(OAc)4/.C6H6,ExampleExamplePb(OAc)4/.C6H6,ExamplePb(OAc)4/Cu(OAc)2.+Py,:1TanzawaT.etal.TetrahedronLett.,1992,33,Alkenesfrom(由芳基磺酰腙制备烯烃RRRArSO1.2eq.222.EORRRNNNNRRR-NNEKolonkoK.,etal.J.Org.Chem.,1978,43,1404;AdlingtonR.M.,etAlkenesfrom(由芳基磺酰腙制备烯烃RRRArSO1.2eq.222.EORRRNNNNRRR-NNEKolonkoK.,etal.J.Org.Chem.,1978,43,1404;AdlingtonR.M.,etal.Acc.Chem.Res.,1983,16,55Example1.2eq.-CC 2.DLesssubstitutedExamplei-Pr-Example1.2eq.-CC 2.DLesssubstitutedExamplei-Pr-2eq.BuLiC6H14-TMEDAHReactions(裂解反应aXOHbRORX=leavinggroup,e.g.:Reactions(裂解反应aXOHbRORX=leavinggroup,e.g.:-OSO2C6H4CH3-p,-100%Trans,Cis,Trans,Cis,Cis,Trans,Cis,Trans,12.OlefinInversionReactions(烯烃构型转换反12.OlefinInversionReactions(烯烃构型转换反应RRDeoxygenationofepoxides(withretentionofOtherOtherSrereospecificsynthesisofSrereospecificsynthesisofalkenesfrom1,2-diolsCorey–WinterOlefinCoreyJ.Am.Chem.Soc.1963,85,CoreyJ.Am.Chem.Soc.1965,87,EastwoodAust.J.EastwoodAust.J.Chem.1964,17,EastwoodTetrahedronLett.1970,Burgstahler,BogerTetrahedron1976,32,14.[3,3]-SigmatropicClaisen14.[3,3]-SigmatropicClaisenandCopeEvansJ.Am.EvansJ.Am.Chem.Soc.1975,97,BurgstahlerJ.Am.Chem.Soc.1961,83,CarnduffJ.Chem.Soc.,Chem.Commun.1967,Johnson-Claisen22HROHO3RRR[3,3]-OORRCarnduffJ.Chem.Soc.,Chem.Commun.1967,Johnson-Claisen22HROHO3RRR[3,3]-OORRTheCarrollTheCarrollCarrollJ.Chem.Soc.1940,704,HartungJ.Chem.Soc.1941,CopeJ.Am.Chem.Soc.1943,65,TanabeJ.Am.Chem.Soc.1980,102,Thio-ClaisenCoreyJ.Am.Chem.Thio-ClaisenCoreyJ.Am.Chem.Soc.1970,92,YamamotoJ.Am.Chem.Soc.1973,95,2693andBlockJ.Am.Chem.1985,107,-Anadvantageofthethio-Claisenrearrangementisthattheprecursorcanbedeprotonatedandalkylated.Amino--ThisAmino--ThisreactionoccursbestwhennitrogenisconvertedtotheammoniumGilbertTetrahedronLett.1984,25,StilleJ.Org.Chem.1991,56,15.[2,3]-SigmatropicReview:15.[2,3]-SigmatropicReview:ComprehensiveOrg.Syn.,Vol.6,pp834,Org.React.1994,46,-Analogousto[3,3]-sigmatropicrearrangementexceptitenlistsalocalizedcharge(anion)inplaceofadoublebond.JuliaTetrahedronLett.1974,LythgoeJ.Chem.LythgoeJ.Chem.Soc.,Chem.Commun.1972,SatoJ.Am.Chem.Soc.1990,112,II.OlefinSynthesisExemplifiedII.OlefinSynthesisExemplifiedwithJuvenile(保幼激素的合成JuvenileHormoneTrostSyntexCoreyJohnsonCoreyJohnsonStotter–KondoJ.Am.Chem.Soc.1967,89,J.Am.Chem.Soc.1968,90,J.Am.Chem.Soc.1968,90,J.Am.Chem.Soc.1968,90,J.Am.Chem.Soc.1970,92,6635,6636,J.Am.Chem.Soc.1970,92,J.Am.Chem.Soc.1973,95,J.Chem.Soc.,Chem.Commun.1972,1311.TetrahedronLett.1979,593.J.Am.Chem.Soc.1970,92,StillOtherJ.Am.Chem.Soc.1970,92,(1).Trost(1).Trost React2notmuchdifferencenotmuchdifferencebetweenMeandH(secondatomstericeffect)bothisomersobtainedfromtheWadsworth–Horner–Emmonsreaction(Modernimprovementsnowavailable)RetrosyntheticrepeatingsubunitsrepeatingreactionsJ.Am.Chem.Soc.1967,89,(2).Syntex(2).SyntexJ.Am.Chem.Soc.J.Am.Chem.Soc.1968,90,Selectivesaturatedvs.,-unsaturatedringstrainassociatedwith5-memberedringcarbonylreleasedonreductionattackfromleasthinderedTHPProtectingifRgroupcontainschiralcenters,diastereomersresultremovedbymildRobinsonAnnulationDirectedEpoxidationReactionFragmentationReactionThermodynamic-Thermodynamic-severe1,3-diaxialinteractioninchair-T.S.axial-nostericincumberancetoaxialalkylationonleasthinderedfaceoftwistboatT.S.LiAlH(OtBu)3largereagent,usuallyequatorialH–1,2-interaction(torsionalstrain)relativelyinvarianttoNu–size1,3-stericinteractionhighlydependentonNu–sizeduetoabsenceofaxialC(3)–H,largereagentnowgivesaxialdeliveryinEt2O,inEt2O,coordinationofperacidtosolventgivesdeliveryfromtheleasthindereda-faceinCH2Cl2,H-bondingofOH