二基团切断(教案)2

Claissen缩合，b路线的对称性强baPhOPh+OEtCO2EtaOPh+PhCO2EtbOEtPhCO2EtPhOPhCO2EtEtOEtOH_PhCO2EtOPhPhCO2EtCO2EtbaPhBr+CO2EtCO2EtaPhCO2Et_+OEtCO2Etb还有其它设计路线吗？OCH3OCH3BrOCH3CHOBrOCH3CHOOHOH2-,bMeCHOOMeOHOEtO+MeOHOEtO+aCO2EtCHOaHOEtO是引进醛基的试剂MeOHCOMeCHOOMeHOO_MeHOO_OCH3CHOOH,H2OOCH3HOOHOCH3HOOH___OCH3_OCH3HCOOH脱CO2EtOHCHOHCHCOOEt2+2-CHHEtOOCCOOEtOHCHO1,3___氧OHC+CH2OOOCHOCH2OK3CO3CHOOHCH2(CO2Et)2NH3OOOOPhHONMe2FGlPhHOCOOEt+NMe2HO+CO2EtPh__1,3二氧OHOBrCO2EtPhOH+ONMe2-HNMe2OOPhHONMe2PhCO2H1.P,Br2Et2O2.BrPhCO2Et1.2.Zn,Et2OOCO2EtPhHOEOHNMe2HONMe2E交换脂OONMe2PhHOReformatsky反应1,5-二羰基化合物•1,5-二羰基化合物生成反应Michael反应:活泼亚甲基化合物和,-不饱和羰基化合物碱催化加成–活泼亚甲基化合物:丙二酸酯、氰乙酸酯、乙酰乙酸酯、乙酰丙酮、硝基烷类–,-不饱和羰基化合物：,-烯醛、,-烯(炔)酮、,-烯(炔)酯、,-烯腈、,-烯酰胺、,-不饱和硝基化合物、对醌类、杂环,-不饱和烃类1,5-二羰基化合物aR'ROOOR+OR'a_OR+OR'b_ba、b切断的选择原则：生成稳定的碳负离子CO2EtOOOCO2Et_+OABPhPhCHOOOPhPhCHO_bDPhPhOOH_aCabCNPhEtO2C+ObCNEtO2C+CHOPhCNEtO2C+PhOaPhCHO+OabOOPhCO2EtPhCOOEtOPhPhO+OPhO+PhHPhOCO2EtPhEtO2CCNOPhOOOOO1,5二羰基OO+O_OOMeCOOEtO+CO2EtOOMeCHO+OOOMeOMeCHOCO2EtOMeOCO2EtO碱(只生成一种产物)OCO2Et碱OCO2EtOCO2EtHH2OMeO+OOOMe不选择b切断的原因:1.中间体B的合成较A的合成难2.中间体A引入一个控制基COOEt,即利于烷基化的合成又利于Michael加成反应OOa加以控制O+OCOOEtACO2EtHO+IbaO+OBbOOHCHO+？CO2EtO_EtOCO2EtOEtO_OOCO2EtO1.碱2.水解和脱羧O+CH2OOAIO+CH2O+Me2NHHNMe2O'+'NR2'OMeI'NMe2'OMe+碱迈克尔反应条件OABB可以代替A直接参加Michael反应Mannich反应•具活泼氢原子化合物(酮、醛、酸、酯、氰、硝基烷、炔、酚类及某些杂环)与甲醛（其它活性大的醛）及氨、仲氨、伯胺缩合反应——又称-氨甲基化反应OR+CH2O+R2NHHNR2RO'+PhOPhOO1,5-二羰基O+PhOPhOCOOEtONMe3+FGIOCH2O,Me2NH,HMeI+OCH2O+OCO2Et碱PHCH2BrCO2EtOPhCO2EtOPh碱OCH2O,Me2NH,H2.MeIONMe3+1.PhOH+H2O+HNMe2+MeI课堂练习CO2EtO练习一练习二练习三OEtOOCONCH3PhCOOCH3练习四练习五OO