过渡金属催化环氧和二氟环丙烷的开环偶联反应研究

发布时间：2018-05-27 02:21

  本文选题：铜催化交叉偶联反应 + 环氧化合物　； 参考：《中国科学技术大学》2017年博士论文

【摘要】：过渡金属催化C(sp3)-C(sp3)/C(sp3)-B形成的反应,在现代有机化学中占有一个很重要的地位,与此同时,C-F键活化反应在提供新方法合成复杂的有机分子中也起到了一个非常重要的作用。在第一章中,我们首先综述了过渡金属催化环氧乙烷及其简单衍生物交叉偶联反应的历史背景和当前状态,并重点介绍了碳亲核试剂在过渡金属催化条件下与环氧化合物的偶联反应。此外,环氧开环硼化以及该过程中明显的铜催化效应也在这章节中做了说明。值得一提的是,我们进一步展示了氟取代基尤其是含有偕二氟化合物和偕二氟环氧丙烷的交叉偶联反应。一般来说,利用过渡金属催化交叉偶联反应构建C-C,C-B和C-X(X = N,O)合成复杂结构化合物应用广泛、机理明确。通过对比此前的烷基卤素和三元环氧以及偕二氟环丙烷等亲电试剂的交叉偶联反应,我们判断铜和钯可以催化三元环氧和偕二氟环丙烷等亲电试剂实现交叉偶联反应。在第二章中,我们展示了铜催化环氧和偕二硼试剂的开环反应,其中脂肪和芳香取代的环氧乙烷以及氮杂环丙烷可以中到高等产率的转化成相应的γ-羟基硼酸酯或者γ-氨基硼酸酯。这一新反应是对经典环氧乙烷试剂和偕二硼试剂的有效利用。我们的新方法具有良好的官能团兼容性,可以兼容大量具有合成价值的官能团,提供了一个在温和反应条件下合成复杂分子的有效策略。例如,该反应可以使一系列的脂肪族和芳香族化合物转化为相应的二级或三级γ-羟基硼酸酯。此外,也可以使磺酰基氮杂环丙烷转化得到相应的γ-氨基硼酸酯。在第三章中,我们实现了第一例铜催化(促进)环氧丙烷开环硼化。这个过程展示了用易得的二硼试剂(B2pin2,B2neop2)和端基环氧底物开环硼化的反应。含有不同的官能团环氧乙烷衍生物被转换为相应的β-羟基硼酸酯。同时,手性环氧化合物也可以参与到反应中,通过随后的氧化生成手性保持的1,2-二醇化合物。该反应中获得的β-羟基硼酸酯在有机反应中有很多应用,比如和芳基卤化物发生Suzuki-Miyaura偶联可以得到各种芳基取代的二级醇。另外,也可以通过Chan-Lam-Evans交叉偶联反应生成相应的芳香胺或者芳香醇。因此,我们发展的新方法得到的开环产物(β-羟基硼酸酯)也进一步为C-C键和C-N键化合物构建提供了便利。在第四章中,我们发现Pd催化可以选择性的活化偕二氟环丙烷化合物C-C键断裂。钯催化偕二氟化合物C-F键断裂反应是一个官能团兼容性非常好的生成单氟衍生物的途径。这个过程提供了一个生成2-F烯丙基胺、酯、醚的方法。同时生成的烷基化产物是Z式构型,是众多生物活性分子的重要结构。另外这也是偕二氟环丙烷首次在过渡金属催化交叉偶联反应中的应用。我们拓展了"铜、钯催化剂"在交叉偶联反应中的应用。更进一步,我们拓展了环氧化合物开环C-C和C-B键交叉偶联反应。另外,这也是偕二氟环丙烷首次在过渡金属催化交叉偶联中使用。我们实验室在端基环氧和偕二氟环丙烷上的努力是现代有机化学催化领域在底物上的突破。可是,这里面还存在一些挑战,比如铜催化环氧开环反应在1,2-二取代环氧化合物来构建四级碳中心以及更多二硼酯参与该反应的尝试都失败了。因此这需要我们课题组更多的努力来克服这些问题。
[Abstract]:The reaction of transition metal catalyzed by C (SP3) -C (SP3) /C (SP3) -B plays an important role in modern organic chemistry. At the same time, the activation reaction of C-F bond plays a very important role in providing new methods to synthesize complex organic molecules. In Chapter one, we first reviewed the transition metal catalyzed ethylene oxide. The historical background and current state of the cross coupling reaction of the simple derivatives and the coupling reaction of the carbon nucleophilic reagents with the epoxy compounds under the transition metal catalyzed conditions are emphatically introduced. In addition, the epoxation of epoxide ring and the obvious copper catalytic effect in this process are also explained in this chapter. The cross coupling reaction of fluorine substituents, especially containing two fluorine compounds and two fluorine propylene oxide, is shown. Generally, the complex structural compounds of C-C, C-B and C-X (X = N, O) are widely used to synthesize complex structural compounds with the transition metal catalyzed cross coupling reaction. The mechanism is clear. By comparing the previous alkyl halogens and three epoxide and two fluorine together. In the cross coupling reaction of cyclopropane and other electrophilic reagents, we judge that copper and palladium can catalyze the cross coupling reaction of three yuan epoxide and two fluorocyclpropane. In the second chapter, we show the ring opening reaction of copper catalyzed epoxy and the two boron reagent, including adipose and aromatic substituted ethylene oxide and azopropane. The transition from medium to high yield into corresponding gamma hydroxyl borate or gamma aminborate ester. This new reaction is the effective use of the classic ethylene oxide reagents and the two boron reagent. Our new method has good functional group compatibility and can be compatible with a large number of functional groups with synthetic value, providing a mild reaction bar. For example, the reaction can convert a series of aliphatic and aromatic compounds into corresponding two or three grade gamma hydroxyborate esters. In addition, sulfonyl nitrogen heterocyclic propane can be converted to corresponding gamma aminborate ester. In the third chapter, we realized the first copper Catalysis (promotion). Epoxide propane is borated by opening ring. This process shows the reaction of ring boronizing with the easily available two boron reagents (B2pin2, B2neop2) and the end group epoxy substrates. The derivatives of different functional groups of epoxy ethane are converted to corresponding beta hydroxy borate esters. The chiral 1,2- diol compounds have been used in this reaction for many applications in organic reactions. For example, the coupling of aryl halides with aryl halides can lead to a variety of aromatic substituent two alcohols. In addition, the corresponding aromatic amines or aromatic alcohols can be generated by the Chan-Lam-Evans cross coupling reaction. Therefore, the open loop product obtained by our new method (beta hydroxy borate) has also further facilitated the construction of the C-C bond and C-N bond compounds. In the fourth chapter, we found that Pd catalyzes the selective activation of the C-C bond fracture of the activated two fluorocyclopropane compound. The palladium catalyzed C-F bond fracture reaction of the two fluorine compound is a functional group compatibility The process of producing single fluorine derivatives is very good. This process provides a method for generating 2-F allyl amine, ester and ether. The production of alkylated products is Z configuration, which is an important structure of many bioactive molecules. In addition, this is the first application of two fluorocyclopropane in the transition metal catalytic cross coupling reaction. The application of "copper, palladium catalyst" in cross coupling reaction has been developed. Further, we have expanded the cross coupling reaction of epoxides open ring C-C and C-B bonds. In addition, this is the first use of two fluorocyclopropane in transition metal catalytic cross coupling. Our laboratory in the end group of epoxy and two fluorocyclopropane is modern organic There are some challenges in the field of chemical catalysis on the substrate, but there are some challenges, such as the failure of copper catalyzed epoxide ring reactions to replace epoxy compounds in 1,2- two to build four carbon centers and more two borates to participate in the reaction. So it requires more efforts by our group to overcome these problems.
【学位授予单位】：中国科学技术大学
【学位级别】：博士
【学位授予年份】：2017
【分类号】：O621.251
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本文编号：1940009