1、2023-2-151Introduction to Organic Synthesis有机合成简介2023-2-152合成化学家在旧的自然界旁又建起了一个新的自然界。R.B.Woodward2023-2-153E.J.CoreyRetrosynthetic analysis The Noble Prize in 1990 2023-2-1541.Retrosynthetic analysis(逆合成分析)In this procedure the target molecule is transformed progressively into simpler structures by di
2、sconnecting selected carbon-carbon bonds.These disconnections rest on transforms,which are the reverse of plausible synthetic constructions.Each simpler structure,so generated,becomes the starting point for further disconnections,leading to a branched set of interrelated intermediates.A retrosynthet
3、ic transform is depicted by the=symbol,as shown in next slide.Once a complete analysis has been conducted,the desired synthesis may be carried out by application of the reactions underlying the transforms.2023-2-155SynthonEquivalentDisconnection rest on transforms2023-2-1562023-2-157C+ROCRClOCROROR+
4、RXOHC+RRHOOC-RSSRLiR-RMgXC-RC-Na+RCMgXRSynthon（合成子)Equivalent（等价物）PolarInversion极性反转2023-2-158OOC-+BrSSLiSSH+CHOOSSNBSaq.acetonePolar Inversion极性反转2023-2-159CHOCHO1.O32.Zn/AcOHSymbol2023-2-1510NH2CNH2Pd/CBrNaCNOHOH策略1 Functional Group transforms（官能团转换）2023-2-1511OOHPCC1.B2H62.H2O2 NaOH2023-2-1512策略2
5、.Disconnection on TMs without FG（无官能团时的切断策略）adding FG（添加官能团）+-BrNaCHBrHH+2023-2-1513OClO+AlCl32023-2-1514BrBrBrBrBrBrNH21.NaNO2,HCl2.EtOHNH2NH2NH2CN+CN2023-2-1515策略3.Disconnection on TMs with mono FG3.1Application of Malonic ester（丙二酸二酯，活泼亚甲基）OOHRCO2EtCO2EtRCO2EtCO2Et-R+RBrCO2EtC-CO2Et1.NaOH,H2O2.H3
6、O+,-CO2EtONa2023-2-1516CH2(CO2Et)21.EtONa2.RXRCH(CO2Et)21.OH-2.H3O+,RCH2CO2H1.EtONa2.RXRRC(CO2Et)21.OH-2.H3O+,RRCHCO2H2023-2-15172023-2-15181.OH-2.H3O+,CH3(CH2)4C(CO2Et)2CH3CH3(CH2)4CHCO2HCH380%99%CH2(CO2Et)21.EtONa,EtOH2.n-C5H11BrCH3(CH2)4CH(CO2Et)21.EtONa,EtOH2.CH3I80%2023-2-1519OC2H5OOOC2H5OOH酮式酮
7、式 烯醇式烯醇式3.2 Application of Ethyl Acetoacetate（乙酰乙酸乙酯）pKa 112023-2-1520OCH3CH2OOEtEtONaOOEtOCH3CHOOEtCH3CHONa+RXOOEtOCH3CHRNaX+OOEtOCH3CHROOHOCH3CHR1.NaOH,H2O2.H3O+-CO2CH3CCH2RO2023-2-1521OCH3CH2OOEt1.EtONa2.RXOOEtOCH3CHR1.EtONa2.R2XOOEtOCH3CRR1.NaOH,H2O2.H3O+-CO2CH3CCHORROOHOCH3CRR2023-2-1522OPhOPhC
8、O2EtOPhCO2EtCl+OEtOOBr+2023-2-15233.3 Application of Epoxy compounds（环氧化物）R1R2OHR1-R2OH+OR1R2MgBr2023-2-1524HOO+CH2MgX2023-2-1525HOO+CMgXC4H9-nn-C4H9HO1.Et2O2.H3O+H2Pd/C2023-2-15263.4 Disconnection on Cyclohexene（环己烯）a)D-A 反应+Diels-Alder Reacton2023-2-1527CO2EtCO2EtCO2Et+2023-2-1528Birch还原还原ORLi,liq
9、.NH3 EtOHORCO2RCO2RNa,liq.NH3EtOHLi,liq.NH3 EtOHb)Birch还原2023-2-15294.Disconnection on Bifunctional groups（双官能团化合物）（1）,-unsaturated compoundsORR1R2RO+OR1R2AldolcondesationOOO2023-2-1530ORLi,liq.NH3 EtOHOROHClMeOHOMeOMeOLi,liq.NH3 EtOHHClMeOH2023-2-1531ArCO2HArCHO+(CH3CO)2OPerkinReactionOCHOAc2O,AcON
10、a 150oCOCHCHCO2H（2）,-unsaturated carboxylic acid2023-2-1532（3）-Hydroxyester2023-2-1533OHCO2EtOBrCH2CO2Et+O+-CH2MgBrCOCl2023-2-1534（4）1,3-bicarbonyl（1,3-二羰基化合物）ROEtOOC+ROOEtO-ROOEtOEtORROOC+RORO-ROOEtROClaisen缩合2023-2-1535OCO2EtCO2EtCO2Et1.NaOEt2.H3O+1.KMnO42.EtOH,H+2023-2-1536（5）1,4-bicarbonyl（1,4-二
11、羰基化合物）ROROROHROCO2EtOREtO2COR+2023-2-1537（6）1,5-bicarbonyl CH2(CO2Et)2 +CH3COCHCH2CH3COCH2CH2CH(CO2Et)2KOHEtOH迈克尔（Michael）加成反应 RROORROOCO2EtRROOCO2Et+2023-2-1538OOCO2EtOCO2EtOOOOEtO+OOOEtBr+2023-2-1539OOOOO+2023-2-1540OMe+CH2CHCCH3OEtONaMichael加成MeOONaOH羟醛缩合54%MeOHO草酸MeO86%2023-2-1541CHOCHO1.O32.Zn/
12、AcOH（7）1,6-bicarbonyl2023-2-1542OMeMeCHOCO2MeOMeMe2023-2-1543OMeMe1.O3,MeOH2.Me2SCHOCO2MeOMeMeLi,liq.NH3EtOHBirch还原还原2023-2-15444.RearrangmentO-O+HO+HOOH2023-2-1545嚬哪醇重排：嚬哪醇重排：H3C CCH3OHCOHCH3CH3H3C CCH3OHCOH2CH3CH2H3C CCH3OHCCH3CH3CCH3CCH3CH3CH3OHCCH3CCH3CH3CH3OHHH2OHCCH3CCH3CH3CH3O（i）（ii）（iii）2023-2-1546OHOHOClaisen重排O-Na+Br+2023-2-1547OOMeOOOHOOHOHOHCO2HO2N习题尝试逆合成分析并合成以下目标化合物）
