有机合成中的氧化还原反应.ppt

1,Oxidation reaction in organic synthesis,Wang Jinliang 01/13/2011,2,Outline,Introduction 氧化反应-定义 氧化反应的分类 氧化剂种类 经典反应举例 Questions,3,The utility of oxidation in organic synthesis: 胡跃飞，林国强现在有机反应(第一卷：氧化反应) Chem. Rev. 2006, 106, 2943-2989 Large-Scale Oxidations in the Pharmaceutical Industry,一. Introduction：,4,2. 氟轻松,5,2. 氧化反应定义,狭义的氧化：物质与氧化合，加氧去氢；氧化时氧化值升高；氧化也称氧化作用或氧化反应。有机物反应时把有机物引入氧或脱去氢的作用叫氧化； 广义的氧化：物质发生了电子转移，使C上电子云密度降低。 氧化反应:物质失电子的作用叫氧化反应；得电子的作用叫还原。,6,2. 氧化反应定义,按照这样的定义，下列强亲电性试剂是适宜的氧化剂：其中有：硝酸、氧、过氧化物（过氧化氢、金属过氧化物、无机和有机过氧酸)硫，二氧化硒、氯、溴、次卤酸。过碘酸、高价金属化物（铁和钛/四氧化锇、四氧化钌、二氧化锰、高锰酸钾、铬酸及铬酐、二氧化铅和四醋酸铅）。 化合物被氧化的容易程度随亲核性的增强而增加，大致顺序：,另外，一个有机化合物的可氧化性一般与其可被利用的氢原子有关，氧化伴随着氢的给出或者氧的获得。例如甲苯可被氧化为苯甲醛，进一步氧化为苯甲酸。,7,3.氧化反应的分类,8,1. Transition metal drivatives Cr, Mn等。PCC (Coreys Reagent CrO3+Pyridine+HCl),PDC (Pyridinium dichromate CrO3+ H2O + Pyridine),2. Oxygen, Ozone and peroxides non-metalic oxidants O2, O3, RCOOOH, H2O2, t-BuOOH 3. other reagents Some Strongly electrophilic reagents,etc.,etc.,4. Oxidants,9,5. 经典反应举例,1. Swern Oxidation：,General features of Swern Oxidation 1. DMSO can also be activated by other reagents such as TFAA, SO3/Py, (AcO)2O and P2O5; 2. When (COCl)2 is used, the initial intermediate is unstable above -60 0C for benzyl or allylic alcohols, or above -20 0C for other alcohols 3. Yield of Swern Oxidation is high. However, the condition can cause epimerization of alfa -chiral center and C=C migration and was not good in too small (mg) or too large scale (Kg). 4. 位阻大的2o羟基反应活性降低较多,10,Mechanism:,11,Swern Oxidation examples：,12,2. KMnO4：,KMnO4氧化的特点： 强氧化性 氧化产物与体系的PH密切相关，酸性条件下氧化性更强，KMnO4的副产物也与PH关系很大。,13,14,3. MnO2：,General features of Swern Oxidation Used in oxidizing benzyl or allylic alcohols; 2. MnO2 can be re-activated at 110-130 0C for 3-4 h before used (Infra-red oven); 3. The reaction was carried out at room temperature, excess (10 eq) MnO2 needed to get to completion.,MnO2 example：,15,4. Dess-Martin 氧化,Mechanism of Dess-Martin oxidation：,16,Preparation of IBX and DMP,17,General features of Dess-Martin Oxidation： 1. Mild reaction conditions (room temperature, neutral pH); selectively oxidizing alcohol. 2. IBX can oxidizing 1and 2alcohol to carboxyl product in DMSO under mild conditions. 3. Configuration of conjugating C=C remained 4. DMP is especially good for Fluo-containing compounds,Dess Martin examples：,Synlett. 2001, 1974-1976,J. Org. Chem. 1989, 54, 661-668,18,5. Good ee retention of near chiral center,Swern :81% ee; Tempo:90% ee; DMP:96% ee Tetrahedron lett. 2000, 41, 1359-1362,19,5. TEMPO Oxidation:,Mechanism of tempo oxidation：,20,General features of Tempo Oxidation： 1. The oxidation is cheap, mild and can be carried out in small and large scales 2. Selectively oxidizing primary alcohols . 3. Alcohols can be converted to aldehydes or acids at different conditions (pH, oxidants).,Tempo oxidation example：,J. Org. Chem. 1999, 64, 2564-2566,21,6. Sharpless epoxidation：,General features of tempo Oxidation： 1. 简易；2. 可靠，对于大多数烯丙醇反应都能成功， 3. 高光学选择性，一般9