鈀催化烯烴不對稱氫酯化反應研究
發(fā)布時間：2019-03-17 14:14
【摘要】：羧酸和酯是具有多種生物活性的重要化合物。金屬催化的烯烴氫羧/酯化反應為該類化合物的合成提供了一種有效的方法。不對稱氫羧/酯化反應能夠構建一個手性中心,合成具有光學活性的羧酸和酯,因而具有十分重要的意義。此外,開發(fā)新型CO替代源,并用它來進行烯烴氫羧/酯化反應以避免使用有毒的CO氣體,也是一個重要的研究方向。本文圍繞鈀催化的烯烴不對稱氫酯化反應,進行了以下三個方面的研究。(1)本課題組報道了以甲酸苯酯為CO替代源,在鈀催化下烯烴高效地進行內(nèi)酯化的反應。在此工作的基礎上,課題組研究發(fā)現(xiàn)使用手性配體(R)-(-)-DTBM-SEGPHOS能夠不對稱合成3,4-二氫香豆素類產(chǎn)物,取得最高92%的收率和91%的ee值。反應以甲酸苯酯為CO替代源,反應溫度低,操作簡單。通過同位素實驗,證明產(chǎn)物中的羰基來自于甲酸苯酯而不是甲酸。最后基于機理實驗提出了一個可能的反應循環(huán)。這部分研究為后面的分子間不對稱反應研究奠定了基礎。(2)在分子內(nèi)烯烴不對稱氫酯化反應研究的基礎上,研究發(fā)現(xiàn)手性配體(R)-(-)-DTBM-SEGPHOS同樣適用于分子間烯烴不對稱氫酯化反應,且能夠以最高94%的收率,95%的ee值以及大于20/1的支鏈選擇性得到2-芳基丙酸苯酯類化合物。反應底物類型廣泛,各類間位,對位以及多取代底物都能很好地發(fā)生催化反應。該反應可以放大到克級規(guī)模。產(chǎn)物酯可以高收率地轉化為相應的羥酸和酰胺產(chǎn)物,且ee值不會下降,這進一步擴大了反應的適用范圍。同時研究還發(fā)現(xiàn),使用CO氣體進行反應時,能夠以相似的ee值和更高的選擇性得到酯產(chǎn)物。這一發(fā)現(xiàn)也為后期的研究提供了方向。(3)基于分子間不對稱氫酯化反應的研究,課題組還研究了 2-苯基丙烯的不對稱氫酯化反應。反應的立體選擇性一般,ee值僅達到10%。添加強酸能促使反應有效進行,但ee值沒有提高。此外,課題組還開發(fā)了使用CO的不對稱烯烴氫酯化反應。通過對反應條件進行了初步的篩選,發(fā)現(xiàn)CO的壓力和苯酚的量會影響到反應的產(chǎn)率、支鏈選擇性和ee值。過高或過低的CO壓力都會降低反應速率;過量的苯酚會使產(chǎn)物的支鏈選擇性及ee值降低。之后的研究將著力于底物范圍的擴展,以此來擴展反應的適用范圍。
[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.
【學位授予單位】：南京大學
【學位級別】：博士
【學位授予年份】：2017
【分類號】：O621.251
本文編號：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.
【學位授予單位】：南京大學
【學位級別】：博士
【學位授予年份】：2017
【分類號】：O621.251
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