烯烃氢羧化反应研究

发布时间：2018-01-08 07:39

本文关键词：烯烃氢羧化反应研究　出处：《南京大学》2017年博士论文　论文类型：学位论文

【摘要】：羰基化反应作为一类重要的基元反应,已经成为实验室基础研究和工业生产中的焦点。其中,烯烃羰基化反应以其原子经济性的特点而被广泛研究,随着对该领域的不断深入研究,其作为一种功能广泛且简便的有机合成方法,在复杂有机分子合成中的应用更加广泛。通常,羰基化反应使用CO作为羰基源,然而,该方法的主要缺点是CO有毒且易燃,使其在储存、运输以及操作上都存在困难,该缺点大大限制了羰基化反应的实际应用和发展。因此,发展一种安全、高效、易操作且不使用CO气体的烯烃羰基化反应已成为当下的研究热点。本论文主要是围绕非CO的区域选择性羰基化反应展开的,主要工作包括以下三部分:1.研究了钯催化的1,1-二取代烯胺的区域选择性的氢羧化反应。该反应中以简单易得的HCOOPh来代替传统羰基化反应中CO的使用,使得反应操作简单安全。研究发现,该反应的反应条件温和,当使用0.5 mol%APD为催化剂,2 mol%DPEphos为膦配体,在0.2 equiv HCOOPh和2 equiv HCOOH存在下,1,1-二取代烯胺可顺利进行氢羧化反应。该反应适用的底物类型广泛,对各种链状烷基取代、环状烷基取代、芳基取代和萘基取代的烯胺都表现出很好的反应活性,以60-98%收率得到相应高区域选择性的羧酸产物,且所得β-氨基酸通过肼解即可以98%的收率得到相应的游离β-氨基酸。当使用2.5 mol%APD为催化剂,10 mol%DPEphos为膦配体,1.2 equiv HCOOPh为羰基源时,1,1-二取代烯胺可顺利进行氢酯化反应,高区域选择性的得到相应的β-氨基酯,产率高达86%。2.研究了钯催化的1,2-二取代烯胺的区域选择性的氢羧化反应。β-氨基酸广泛存在于自然界中,是具有生物活性及药物活性分子的重要组成部分,因此,快速高效的合成β-氨基酸对于生物医学和药物化学都具有重要意义。本论文通过1,2-二取代烯胺的氢羧化反应可以快速高效的合成各种β2-氨基酸。该反应中不需使用到不易存储、运输和操作的有毒易燃气体CO。研究发现,配体对反应活性具有决定性的作用。1,2-二取代烯胺在APD(2.5mol%)和 PPh3(20mol%)的催化下,与 HCOOPh(1.2equiv)和 HCOOH(2.0 equiv)发生氢羧反应,能够以68-99%的收率高区域选择性的得到β2-氨基酸。此外,本论文还研究了烯烃的几何构型对氢竣化反应的影响,发现不论是顺式烯胺还是反式烯胺,进行氢羧化反应都具有较高的区域选择性,且所得产物相同,同时顺式-1,2-二取代烯胺表现出更高的反应活性。同样,所得氨基酸在水合肼作用下肼解能够以98%的收率得到相应的游离β2-氨基酸。3.研究了钯催化的1,2-二芳基乙烯类化合物的氢羧化反应。1,2-二芳基取代烯烃可以分为对称和非对称的,在对称的1,2-二芳基取代烯烃的氢羧化反应中,只需解决其反应活性问题,而在非对称的1,2-二芳基取代烯烃的氢羧化反应中,除了需要解决反应活性问题,还需解决区域选择性的问题。本论文通过对过渡金属、配体、温度等方面的调控,已经顺利解决对称的1,2-二芳基取代烯烃氢羧化反应的活性问题,非对称的1,2-二芳基取代烯烃氢羧化反应还需进一步研究。
[Abstract]:Carbonylation reaction as a kind of important elementary chemical reactions, has become the focus of the laboratory study and industrial production. Among them, olefin carbonylation reaction to its atom economy and has been studied, with the deepening of research in this field, as a function of the organic synthesis method widely and simple and the application in the synthesis of complex organic molecules in the more widely. Usually, the carbonylation reaction using CO as a carbonyl source, however, the main drawback of this method is CO toxic and flammable, so that in the storage, transportation and operation difficulties exist, practical application and development of the disadvantages greatly limits the carbonylation reaction. Therefore and the development of a safe, efficient, easy to operate and carbonylation of olefins without the use of CO gas has become a hot research topic at present. This thesis mainly focuses on the regioselective carbonylation reactions show non CO open, mainly The work includes the following three parts: 1. research on the hydrogen carboxylation reaction of palladium catalyzed regioselective 1,1- two substituted enamines. The reaction is easy to use the HCOOPh to replace the traditional carbonylation of CO, the reaction is simple and safe operation. The study found that mild reaction condition of the reaction, when using mol%APD 0.5 as catalyst, 2 mol%DPEphos phosphine ligands, in the presence of 0.2 equiv HCOOPh and 2 equiv HCOOH, two 1,1- substituted enamines can be carried out smoothly. The hydrogen carboxylation reaction reaction of suitable substrate types widely, instead of different kinds of chain alkyl, cyclic alkyl substituted enamines, aryl substituted naphthyl substituted and the exhibit good reaction activity, obtained the corresponding carboxylic acid product with high regioselectivity in 60-98% yield, and the yield obtained by hydrazinolysis of beta amino acids that can get 98% free beta corresponding amino acids. When using 2.5 mol% APD as catalyst Agent, 10 mol%DPEphos for 1.2 equiv HCOOPh phosphine ligands, carbonyl source, 1,1- two substituted enamines can be smoothly carried out hydrogen esterification reaction, high regioselectivity of corresponding beta amino ester, high yield of 86%.2. carboxylation reaction of hydrogen by palladium catalyzed regioselective 1,2- two substituted enamines beta. Amino acids are widespread in nature, is an important part of the activity, with molecular biological activity and drug so fast and efficient synthesis of beta amino acids for biomedical and pharmaceutical chemistry are of great significance. This paper through 1,2- two carboxylation reaction instead of hydrogen enamines can quickly and efficiently synthesize a variety of amino acids. The 2- beta in response to the need to use is not easy to store, transport and CO. of toxic flammable gas operation that has decisive role in.1,2- two ligand substituted enamines on reaction activity in APD (2.5mol%) and PPh3 (20mol%). Under the HCOOPh, and (1.2equiv) and HCOOH (2 equiv) hydrogen decarboxylation, with selective high yield regions of 68-99% are 2- beta amino acids. In addition, the effect of geometry on hydrogen olefin reaction method is studied in this paper, either cis or trans enamine enamine, regioselectivity has higher hydrogen carboxylation reaction, and the products of the same, and two cis -1,2- substituted enamines showed higher reactivity. Similarly, the amino acid can hydrazinolysis in hydrazine hydrate under the action of the 98% of the yield of the corresponding free beta amino acid.3. 2- on palladium hydrogen carboxylation the catalytic reaction of.1,2- two 1,2- two aryl aryl vinyl compounds substituted olefins can be divided into symmetric and asymmetric and symmetric 1,2- in two aryl substituted hydrogen carboxylation reaction of olefins, only need to solve the problem in the non reactive, and to call 1,2- two Aryl substituted hydrogen carboxylation reaction of olefins, in addition to the need to solve the problem of reactive, but also need to solve the problem. The regioselectivity of the ligands on the transition metal, the temperature control, and other aspects of the problem has been solved successfully, the activity of 1,2- two symmetry aryl substituted olefin hydrogen carboxylation reaction, carboxylation of olefins the reaction also need further study to replace the non symmetric 1,2- two aryl.

【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】：O621.25

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