有机化合物的合成与分析-药明康德培训资料

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1、WuXiAppTecAlkene/AlkyneMetathesisTrainingCommitteeJianguangLeiBackground-MilestonesOverviewoftopicstobediscussed:CarboncarbondoublebondformationviaAlkeneoralkynemetathesisreactionsCatalystsiPriPrCpNPhRW(CO)5CpTi(F3C)2HCOCMoGeneralmechanismClAlPh(F3C)2HCOC(Katz,1974)19781990R

2、=Ph;OMeTebbereagentSchrockR3RR12RR2RR3R1NNCyCyR[M][M]PhClR'[M]RPcy3Pcy3RuPh1AC2ClClClBRuPhRuPhClClCyNNCyR'RPcy3Pcy31[M]F1992199519985Grubbs'1stgenerationcatalystHermannR'PcyNMesR'RNN3R11MesMesClRuN[M]RR3ClRuPhClOMesClRu[M]R2ClClOR2R23Pcy34EDGrubbs'2ndHoveyda-GrubbsCatalystHo

3、veyda-GrubbsCatalystgenerationcatalyst1stGeneration2ndGenerationWuXiAppTecAlkene/AlkyneMetathesisTrainingCommitteeJianguangLeiSchrock’sCatalystPcy3ClRuPh©LigandEffectonCatalystActivity:Cl1.CommerciallyavailablePcy3Halides:I

4、eteroatoms(RCO2H,RSH,ROH,NN©Phosphines:CatalystactivityMesMesetc.)andsomefunctionalities(eg.RCHO)ClincreasesasconeangleandRuPhClEletrondonatingabilityincreasePcy3©ElectrondeficientMo(VI),4-especiesRingClosingMetathesis(RCM)iPriPr©NArligand,ORligands,andONPhSiSiReADMET(F3C)2H

5、COCMoinitialalkylidene,needtobeSiSi2O7/Al2O3-SnBu4Odilute(F3C)2HCOCbulkytoallowforisolation86%14%©ElectronwithdrawingSchrock'scatalystalkoxidesincreasereactivityconcentrated95%5%1.IntramolecularmetathesisofadienetoformacyclicGrubbs'MetathesisCatalystolefin1.Commerciallyavail

6、able2.Reactionpathwayofdienedependsoncatalyst,dilution,2.ReasonablystabletowardH2O,O2,andminorimpuritiesringsize,andsubstrateeaseofhandling3.Dilution:IntermolecularADMETcangenerallybe3.Lowerreactivityvs.MolybdenumimidoalkylidenepreventedbyapplyingdilutionprinciplecatalystFin

7、kel'shsteinetal.J.Mol.Cat.1992,76,133.4.HighfunctionalgrouptoleranceForbesetal.J.Am.Chem.Soc.1992,114,10978.RCMofSmallRings:OlefinSubstitution1.Synthesisof5-7memberedringsisfairlyfacile2.TypicallyrutheniumcatalystsarepreferredovermolybdenumcatalystsWuXiAppTecAlkene/AlkyneMet

8、athesisTrainingCommitteeJianguangLeisubstrateproducttimeyield(%)usingERCMof