有机化学讲义（上海有机所）-03ab 第四部分：反合成分析

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1、第四部分：反合成分析第四部分：反合成分析一、基本概念一、基本概念反合成分析•Retrosynthetic(orantithetic)analysisisaproblem-solvingtechniquefortransformingthestructureofasynthetictarget(TGT)moleculetoasequenceofprogressivelysimplerstructuresalongapathwaywhichultimatelyleadstosimpleorcomme

2、rciallyavailablestartingmaterialsforachemicalsynthesis.•Thetransformationofamoleculetoasyntheticprecursorisaccomplishedbyapplicationofatransform,theexactreverseofasyntheticreaction,toatargetstructure.Corey&Cheng,TheLogicofChemicalSynthesis,1989.断裂转化和

3、反合成子(TransformsandRetrons)HHHHCarbo-Diels-AlderTransformHHHHHHHHHHMeMeCOOMeCOOMeMeCOOMeMeOOCCOOMeCOOMeHH练习CO2MeOHMeO2CSHNNPhNSMeO2COHHOHH断裂转化（1）TGTRetronTransformPrecursor(s)MeOPh(E)-EnolatetPhCHO+MeCOButCO2BuHOCCAldol2OHPhPhPhPhOOMichael+CCCOOOOCO2M

4、eMeO2CRobinsonAnnulation+OOOOOOOMannichRxnNMe2+CH2O+Me2NNCCMeNCHOODoubleO++MeCHONCCMannichRxnCHOO断裂转化（2）TGTRetronTransformPrecursor(s)OHOHOOrganometallic+Et-MetHOOMeClaisenMe+RearrangementOXMeOOHHFisherIndole+NH2NNNOHHHOOOxy-lactonizationOOOofOlefinH

5、OHOHO可以考虑或利用的结构因素•分子骨架：连接与重排•官能团：相互转化•立体化学：翻转或转移简化断裂分析的官能团策略•官能团转换（FGI)•官能团移位（FGT)•重排（Rearrangement)•官能团添加（FGA)•官能团消除（FGR)FunctionalGroupInterchange(FGI)H2NOOMeMeConia(Oxo-ene)FGICHOHHCyclizationHHHONO2FGIMeNO2MeMePhPhNefRxnOPhOOFunctionalGroupTransp

6、osition(FGT)OTMSOTMSOHHMeFGTMeMeMeMeMeHHMeOMeOMeORearrangementHOxy-CopeClCNOHO+OHOOPinacolOHRearrangementHOOFunctionalGroupAddition(FGA)Part1OOOOOFGAMeOOMeOMeHOOCHHHHHHPhPhPhPhPhPhPhHHOFGAOCOHClHClClClFunctionalGroupAddition(FGA)Part2NH2NH2IIIIFGAIIO

7、FGASSSRRFunctionalGroupAddition(FGA)Part3OHOFGAR'R'R'RRRSO2PhSO2PhROROMeROMeROFGAOHOHOOOOOHOPhMePhMeMeMeFunctionalGroupRemoval(FGR)1TGTRetronTransformPrecursor(s)OMeOMeAromaticBrominationBrBrMeMeAllylicOxidationofCH2toC=OOOMeMeAllylicOxidation1by∆gO2

8、,withC=CTransportantionHOOHHOOOMeOROMeo-Metallation(RLi)andCarboxylationCO2HCO2HHFunctionalGroupRemoval(FGR)2TGTRetronTransformPrecursor(s)EtMeEtMeAllylicOxidationOHbySeO2HOHHMeHOHHROHOSharplessEpoxidationCOHwith(R,R)-(+)-DETROHHRCO2MeRCO2MeHcis-Addi