1.1.1.3 Intramolecular aldol condensation between different groups in a same molecule 稀 l20 碳钠 Robinson annulations ∩ 对甲苯磺酸 苯,回流
1.1.1.3 Intramolecular aldol condensation between different groups in a same molecule Robinson Annulations
Robinson annulations Definition: The robinson annulation is an organic reaction used to create a six-member ringa, B- unsaturated cyclic ketone, using a ketone(or aldehyde) and methyl vinyl ketone. In addition to methyl vinyl ketone, 1-chloro-3-butanone and isoxazoles will give the same product. Base Methyl vinyl ketone(or variants thereof) Oxford, UK
Robinson Annulations Definition: The Robinson annulation is an organic reaction used to create a six-member ringα,β- unsaturated cyclic ketone, using a ketone (or aldehyde) and methyl vinyl ketone. In addition to methyl vinyl ketone, 1-chloro-3-butanone and isoxazoles will give the same product. Methyl vinyl ketone (or variants thereof) Oxford，UK
Mechanism Analysis Methyl vinyl ketone are essential for the annulation as they are simultaneously a Michael acceptor and able to take part in an aldol condensation 1. The first step: Michael addition; 2. Second step: Aldol reaction: as the annelation step 3. Third step Elimination: via aldol condensation to make the cyclohexenone ring. Aldol Addition Elimination
Mechanism Analysis • Methyl vinyl ketone are essential for the annulation as they are simultaneously a Michael acceptor and able to take part in an aldol condensation. • 1. The first step: Michael addition; • 2. Second step: Aldol reaction: as the annelation step; • 3. Third step: Elimination: via aldol condensation to make the cyclohexenone ring
1.1.1.4 Directed aldol condensation ·含不同α-H醛酮之间的缩合反应,情况复杂,需要定向醇 醛缩合反应。 a)烯醇盐法:与强碱LDA作用定向生成动力学盐; b)烯醇硅醚化:单一组分成硅醚化; c)烯胺法:定向活化αH生成参与反应 含不同a-H醛酮 之间的定向反应 烯醇盐法 烯醇硅醚化 烯胺法
1.1.1.4 Directed aldol condensation • 含不同α-H 醛酮之间的缩合反应，情况复杂，需要定向醇 醛缩合反应。 • a） 烯醇盐法：与强碱LDA作用定向生成动力学盐； • b） 烯醇硅醚化：单一组分成硅醚化； • c） 烯胺法：定向活化α-H生成参与反应。 含不同α-H 醛酮 之间的定向反应 烯醇盐法 烯醇硅醚化 烯胺法
a)烯醇盐法(低温强碱条件) 与LDA作用定向生成动力学盐 LDA OLi HO R-C-R C3H7-C-CH3 H3 CH2 CH2C-C=CH2 R-C-CH2; C-CH2CH2CH3 -78°C LDA二异丙胺锂 Special example and explanation: OLI LDATHF C3H7 COCH3-78%C- C3H7-C=CH2 1)CH3 (CH2)2-C-H 2)H3O C3H7C-CH2-CH(CH2)2 CH3 O OH
a）烯醇盐法(低温强碱条件) 与LDA作用定向生成动力学盐 C3 H7 C O CH3 R C R O R C CH2 HO R C CH2 CH2 CH3 O C CH2 OLi H3CH2CH2C -78℃ LDA二异丙胺锂 LDA C3H7COCH3 LDA/THF -78℃ C3H7 C CH2 OLi C3H7C CH2 CH(CH2) 2CH3 O OH 1) 2) CH3(CH2) 2 C H O H3O CH3CH2CH2CHO + C6H5CH2CH CH O Si(CH3) 3 1) 2) H2O TiCl 4/CH2Cl 2,-78℃ CH3CH2CH2CH OH CHCH2C6H5 CHO TsOH/PhH CH3CH2CH2CH CCH2C6H5 CHO Special example and explanation：