钯催化烯烃不对称氢酯化反应研究
发布时间：2019-03-17 14:14
【摘要】：羧酸和酯是具有多种生物活性的重要化合物。金属催化的烯烃氢羧/酯化反应为该类化合物的合成提供了一种有效的方法。不对称氢羧/酯化反应能够构建一个手性中心,合成具有光学活性的羧酸和酯,因而具有十分重要的意义。此外,开发新型CO替代源,并用它来进行烯烃氢羧/酯化反应以避免使用有毒的CO气体,也是一个重要的研究方向。本文围绕钯催化的烯烃不对称氢酯化反应,进行了以下三个方面的研究。(1)本课题组报道了以甲酸苯酯为CO替代源,在钯催化下烯烃高效地进行内酯化的反应。在此工作的基础上,课题组研究发现使用手性配体(R)-(-)-DTBM-SEGPHOS能够不对称合成3,4-二氢香豆素类产物,取得最高92%的收率和91%的ee值。反应以甲酸苯酯为CO替代源,反应温度低,操作简单。通过同位素实验,证明产物中的羰基来自于甲酸苯酯而不是甲酸。最后基于机理实验提出了一个可能的反应循环。这部分研究为后面的分子间不对称反应研究奠定了基础。(2)在分子内烯烃不对称氢酯化反应研究的基础上,研究发现手性配体(R)-(-)-DTBM-SEGPHOS同样适用于分子间烯烃不对称氢酯化反应,且能够以最高94%的收率,95%的ee值以及大于20/1的支链选择性得到2-芳基丙酸苯酯类化合物。反应底物类型广泛,各类间位,对位以及多取代底物都能很好地发生催化反应。该反应可以放大到克级规模。产物酯可以高收率地转化为相应的羟酸和酰胺产物,且ee值不会下降,这进一步扩大了反应的适用范围。同时研究还发现,使用CO气体进行反应时,能够以相似的ee值和更高的选择性得到酯产物。这一发现也为后期的研究提供了方向。(3)基于分子间不对称氢酯化反应的研究,课题组还研究了 2-苯基丙烯的不对称氢酯化反应。反应的立体选择性一般,ee值仅达到10%。添加强酸能促使反应有效进行,但ee值没有提高。此外,课题组还开发了使用CO的不对称烯烃氢酯化反应。通过对反应条件进行了初步的筛选,发现CO的压力和苯酚的量会影响到反应的产率、支链选择性和ee值。过高或过低的CO压力都会降低反应速率;过量的苯酚会使产物的支链选择性及ee值降低。之后的研究将着力于底物范围的扩展,以此来扩展反应的适用范围。
[Abstract]:Carboxylic acids and esters are important compounds with a variety of biological activities. Metal-catalyzed hydrocarboxylation / esterification of olefins provides an effective method for the synthesis of these compounds. Asymmetric hydrocarboxylation / esterification can construct a chiral center to synthesize optical active carboxylic acids and esters, so it is of great significance. In addition, it is an important research direction to develop a new alternative source of CO and use it for hydrocarboxylation / esterification of olefins in order to avoid the use of toxic CO gases. In this paper, the palladium-catalyzed asymmetric hydroesterification of olefins has been studied in three aspects. (1) the internal esterification of alkenes catalyzed by palladium was studied by using phenyl formate as an alternative source of CO. On the basis of this work, the research team found that the chiral ligand (R)-(-)-DTBM-SEGPHOS can be asymmetric synthesis of 3,4-dihydrocoumarin products, with the highest yield of 92% and the maximum of 91% ee value. 3, 4-dihydrocoumarin can be synthesized unsymmetrically by using the chiral ligand (R)-(-)-DTBM-SEGPHOS. Phenyl formate was used as the substitute source of CO. The reaction temperature was low and the operation was simple. It is proved by isotope experiments that the carbonyl group in the product comes from phenyl formate rather than formic acid. Finally, a possible reaction cycle is proposed based on the mechanism experiment. This part of the study laid a foundation for the later study of intermolecular asymmetric reaction. (2) on the basis of the study of intramolecular asymmetric hydroesterification of olefins, It was found that the chiral ligand (R)-(-)-DTBM-SEGPHOS was also suitable for asymmetric hydroesterification of olefin between molecules, and the yield was up to 94%. 2-arylpropionic acid phenyl esters were obtained with 95% ee value and more than 20 渭 1 branched chain selectivity. A wide range of substrate types, such as interposition, para-position and polysubstituted substrate, can be used to catalyze the reaction. The reaction can be scaled up to the gram scale. The ester can be converted into the corresponding hydroxylic acid and amide products in high yield, and the ee value will not decrease, which further expands the scope of application of the reaction. At the same time, it is found that the ester products can be obtained with similar ee value and higher selectivity when CO gas is used in the reaction. This discovery also provides a direction for later studies. (3) based on the study of intermolecular asymmetric hydroesterification, the asymmetric hydroesterification of 2-phenylpropene was also studied. The stereoselectivity of the reaction was normal, and the ee value was only 10%. The addition of acid can promote the reaction to proceed effectively, but the ee value does not increase. In addition, the hydroesterification of asymmetric olefins using CO has been developed. Through the preliminary screening of the reaction conditions, it was found that the pressure of CO and the amount of phenol affected the yield, branched chain selectivity and ee value of the reaction. Too high or too low CO pressure will decrease the reaction rate, and excessive phenol will decrease the branched chain selectivity and ee value of the product. Subsequent studies will focus on the expansion of the substrate range to extend the scope of the reaction.
【学位授予单位】：南京大学
【学位级别】：博士
【学位授予年份】：2017
【分类号】：O621.251
本文编号：2442382
[Abstract]:Carboxylic acids and esters are important compounds with a variety of biological activities. Metal-catalyzed hydrocarboxylation / esterification of olefins provides an effective method for the synthesis of these compounds. Asymmetric hydrocarboxylation / esterification can construct a chiral center to synthesize optical active carboxylic acids and esters, so it is of great significance. In addition, it is an important research direction to develop a new alternative source of CO and use it for hydrocarboxylation / esterification of olefins in order to avoid the use of toxic CO gases. In this paper, the palladium-catalyzed asymmetric hydroesterification of olefins has been studied in three aspects. (1) the internal esterification of alkenes catalyzed by palladium was studied by using phenyl formate as an alternative source of CO. On the basis of this work, the research team found that the chiral ligand (R)-(-)-DTBM-SEGPHOS can be asymmetric synthesis of 3,4-dihydrocoumarin products, with the highest yield of 92% and the maximum of 91% ee value. 3, 4-dihydrocoumarin can be synthesized unsymmetrically by using the chiral ligand (R)-(-)-DTBM-SEGPHOS. Phenyl formate was used as the substitute source of CO. The reaction temperature was low and the operation was simple. It is proved by isotope experiments that the carbonyl group in the product comes from phenyl formate rather than formic acid. Finally, a possible reaction cycle is proposed based on the mechanism experiment. This part of the study laid a foundation for the later study of intermolecular asymmetric reaction. (2) on the basis of the study of intramolecular asymmetric hydroesterification of olefins, It was found that the chiral ligand (R)-(-)-DTBM-SEGPHOS was also suitable for asymmetric hydroesterification of olefin between molecules, and the yield was up to 94%. 2-arylpropionic acid phenyl esters were obtained with 95% ee value and more than 20 渭 1 branched chain selectivity. A wide range of substrate types, such as interposition, para-position and polysubstituted substrate, can be used to catalyze the reaction. The reaction can be scaled up to the gram scale. The ester can be converted into the corresponding hydroxylic acid and amide products in high yield, and the ee value will not decrease, which further expands the scope of application of the reaction. At the same time, it is found that the ester products can be obtained with similar ee value and higher selectivity when CO gas is used in the reaction. This discovery also provides a direction for later studies. (3) based on the study of intermolecular asymmetric hydroesterification, the asymmetric hydroesterification of 2-phenylpropene was also studied. The stereoselectivity of the reaction was normal, and the ee value was only 10%. The addition of acid can promote the reaction to proceed effectively, but the ee value does not increase. In addition, the hydroesterification of asymmetric olefins using CO has been developed. Through the preliminary screening of the reaction conditions, it was found that the pressure of CO and the amount of phenol affected the yield, branched chain selectivity and ee value of the reaction. Too high or too low CO pressure will decrease the reaction rate, and excessive phenol will decrease the branched chain selectivity and ee value of the product. Subsequent studies will focus on the expansion of the substrate range to extend the scope of the reaction.
【学位授予单位】：南京大学
【学位级别】：博士
【学位授予年份】：2017
【分类号】：O621.251
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