药物合成反应_第四章___缩合反应.ppt

4. Azides 5. O3 / Carbonyl Oxides 三、碳烯、氮烯对不饱和键的加成 Carbene-电中性二价碳中间体，两电子自选方向相同为三线态，相反为单线态 单线态与烯烃的反应有立体定向性 三线态与烯烃的反应不具有立体定向性 Simmons-Smith cyclopropanation. (1) a wide range of alkenes can be used: simple alkenes, α,β-unsaturates ketones and aldehydes, electron rich alkenes ; (2) due to the electrophilic nature of the reagent, the rate of cyclopropanation is faster with more electron rich alkenes. However, highly substituted alkenes may react slower due to the increased steric hindrance; (3) the cyclopropanation is stereospecific, so the stereochemical information in the alkene substrates is translated to the products; (4) when the alkene has functional groups containing heteroatoms (e.g., OH, OAc, OMe, OBn, NHR), a strong directing effect is observed and the delivery of the alkylidene occurs from the face of the double bond having the closer proximity of the functional group; Example 习题：P164 第一题 * * ③ the choice of solvent is crucial and the use of dipolar aprotic solvents (e.g., DMF) is advantageous, since protic solvents inhibit the last 1,2-elimination step; 2. Stobbe 反应 （1）反应通式 （2）反应机理 （3）应用 制备烯酸 3. Perkin反应(1) 反应通式 （2）反应机理 （3）影响因素 ①芳香醛结构影响 吸电子活性增强，给电子相反 碘番酸中间体 ②催化剂的影响 相应羧酸的钾盐、钠盐；铯盐效果更好 （4）应用 第五节 a、b -环氧烷基化反应(Darzens反应) 1. 反应通式 EWG = CO2R, CN, SO2R, CONR2, C(=O), C(=NR); Y = O, NR; 2. 反应机理 3. 影响因素 Aliphatic aldehydes usually give lower yields； α-Chloro esters are preferable to bromo or iodo esters, since they give higher yields； α-halo sulfones,nitriles,ketones, ketimines, thiol esters,or amides,can also be used to obtain the corresponding derivatives； 4. 应用特点 醛、酮同系化C+1 布洛芬的合成 第六节 环加成反应 EDG (electron-donating group)= alkyl, O-alkyl, N-alkyl, etc. EWG (electron-withdrawing group) = CN, NO2, CHO, COR, COAr, CO2H, CO2R, COCl etc. 一、D-A反应 Mechanism （3）影响因素及应用特点 ①共轭二烯双键必需是顺型的 ②顺式原理 ③ 内向加成原理 ④加成定位规则 Example 二、1,3偶极环加成 1. Azomethine Ylides 2. Azomethine Imines 3. Nitrones （3）影响因素 ① only β-arylethylamines with electron-donating subs