金催化的串联反应于杂环化合物的合成

发布时间：2018-01-02 23:17

  本文关键词：金催化的串联反应于杂环化合物的合成　出处：《山东大学》2017年硕士论文　论文类型：学位论文

  更多相关文章： Au催化 一锅法 串联反应 吗啡啉 含氮桥环化合物

【摘要】：近几年来,金催化剂已经引起了科学家们的广泛关注。金催化的反应通常具有反应活性高、化学选择性强、反应条件温和且对空气和水并不敏感等一系列优点,因此被广泛应用于各种有机合成和天然产物的全合成中。金催化剂参与的反应主要集中于对不饱和键(尤其是炔烃)的活化从而实现的亲核加成反应,另外还有对碳氢键的活化反应和少数氧化还原反应等。本论文利用了金催化剂优异的催化性质,设计了两类金催化剂参与的串联反应,实现了两种杂环化合物的一锅法高效合成。论文主要包含两部分内容:多取代吗啡啉衍生物的合成以及复杂氮桥环化合物的合成。论文的第一部分中,我们以氮杂环丙烷和炔丙醇作为起始底物,高效地得到了多取代的吗啡啉衍生物。首先,氮杂环丙烷在Au(Ⅰ)作用下与炔丙醇发生一步开环亲核加成反应得到炔酰胺中间体,之后金催化剂活化三键,发生分子内环化氢胺化反应生成环外烯胺中间体,该中间体迅速异构成更稳定的环内烯胺结构。在该串联反应进程中,金催化剂同时以lewis酸和π酸两个身份参与了反应,以分别活化氮杂环丙烷和碳碳三键。之后利用Pd/C催化加氢反应便可以极高的产率和dr值高效地得到目标产物。我们还获得了最终产物的单晶结构,从而确定了该产物中取代基团的相对构型。论文的第二部分中,我们以含苯环的炔酰胺类化合物和各种亲双烯体作为原料,成功合成了一类复杂的含氮桥环化合物。在这份工作中,首先由金催化剂催化炔酰胺类化合物发生分子内环化氢胺化得到苯并五元环外烯胺中间体,此时该中间体并未被另一反应物所捕获,而是在生成后迅速发生了[1,5]-氢迁移反应从而构筑了取代的异吲哚中间体,之后该中间体与一分子亲双烯体原料发生Diels-Alder环加成反应从而生成目标产物。我们采用一锅法在单一金催化剂的作用下实现了三步有序的串联反应,且在很短的反应时间内以十分温和的条件引发了[1,5]-氢迁移反应。我们还做了一系列的氘代实验来研究反应机理,从而证明了[1,5]-氢迁移反应历程的存在,进一步证实了我们对反应机理的推测。同时我们也拿到了产物的单晶结构,佐证了我们的反应结果。
[Abstract]:In recent years, gold catalysts have attracted wide attention of scientists. Gold catalytic reactions usually have a series of advantages such as high reaction activity, strong chemical selectivity, mild reaction conditions and insensitivity to air and water. Gold catalysts are mainly involved in the activation of unsaturated bonds (especially alkynes) to achieve nucleophilic addition. In addition, there are the activation of hydrocarbon bonds and a few redox reactions. In this paper, two kinds of gold catalysts are designed to participate in series reactions using the excellent catalytic properties of gold catalysts. One-pot synthesis of two heterocyclic compounds has been realized. The thesis mainly includes two parts: the synthesis of polysubstituted morphine derivatives and the synthesis of complex nitrogen bridged ring compounds. In the first part of the thesis. We used azacyclic propane and propargyl alcohol as starting substrates to efficiently obtain polysubstituted morphine derivatives. The nucleophilic addition reaction of azacyclic propane with propargyl alcohol was carried out in one step under the action of au (I) to obtain the intermediate of acetylidene, and then the gold catalyst activated three bonds. The intramolecular cyclized hydroamination reaction produces an extracyclic enamine intermediate, which rapidly dissolves to form a more stable cyclienamine structure, and in the process of the series reaction. Gold catalyst participated in the reaction as lewis acid and 蟺 acid simultaneously. The target product can be obtained efficiently by Pd/C catalytic hydrogenation with the activation of heterocyclic propane and carbon tribond respectively. The single crystal structure of the final product is also obtained. In the second part of this paper, we use benzene-ring acetylene amides and dienophiles as raw materials. A class of complex nitrogen-containing bridged ring compounds was successfully synthesized. In this work, the intermediates of benzo-pentacyclic enylamine were synthesized by intramolecular cyclization of alkyne amines catalyzed by gold catalysts. At this point, the intermediate is not captured by another reactant, but occurs quickly after its formation. [The substituted isoindole intermediates were constructed by hydrogen migration reaction. Then the intermediate reacts with a molecular dienophile by Diels-Alder cycloaddition reaction to produce the target product. We have realized a three-step ordered series by one-pot method under the action of a single gold catalyst. Combined reaction. And in a very short reaction time, under very mild conditions, [We have also done a series of deuteration experiments to study the mechanism of the reaction. [The existence of 1 / 5] -hydrogen migration mechanism further confirmed our speculation of the reaction mechanism. At the same time, we also obtained the single crystal structure of the product, which confirmed our reaction results.
【学位授予单位】：山东大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：O626
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本文编号：1371357