發(fā)布時(shí)間：2018-05-27 02:21

  本文選題：銅催化交叉偶聯(lián)反應(yīng) + 環(huán)氧化合物��； 參考：《中國科學(xué)技術(shù)大學(xué)》2017年博士論文

【摘要】：過渡金屬催化C(sp3)-C(sp3)/C(sp3)-B形成的反應(yīng),在現(xiàn)代有機(jī)化學(xué)中占有一個(gè)很重要的地位,與此同時(shí),C-F鍵活化反應(yīng)在提供新方法合成復(fù)雜的有機(jī)分子中也起到了一個(gè)非常重要的作用。在第一章中,我們首先綜述了過渡金屬催化環(huán)氧乙烷及其簡單衍生物交叉偶聯(lián)反應(yīng)的歷史背景和當(dāng)前狀態(tài),并重點(diǎn)介紹了碳親核試劑在過渡金屬催化條件下與環(huán)氧化合物的偶聯(lián)反應(yīng)。此外,環(huán)氧開環(huán)硼化以及該過程中明顯的銅催化效應(yīng)也在這章節(jié)中做了說明。值得一提的是,我們進(jìn)一步展示了氟取代基尤其是含有偕二氟化合物和偕二氟環(huán)氧丙烷的交叉偶聯(lián)反應(yīng)。一般來說,利用過渡金屬催化交叉偶聯(lián)反應(yīng)構(gòu)建C-C,C-B和C-X(X = N,O)合成復(fù)雜結(jié)構(gòu)化合物應(yīng)用廣泛、機(jī)理明確。通過對比此前的烷基鹵素和三元環(huán)氧以及偕二氟環(huán)丙烷等親電試劑的交叉偶聯(lián)反應(yīng),我們判斷銅和鈀可以催化三元環(huán)氧和偕二氟環(huán)丙烷等親電試劑實(shí)現(xiàn)交叉偶聯(lián)反應(yīng)。在第二章中,我們展示了銅催化環(huán)氧和偕二硼試劑的開環(huán)反應(yīng),其中脂肪和芳香取代的環(huán)氧乙烷以及氮雜環(huán)丙烷可以中到高等產(chǎn)率的轉(zhuǎn)化成相應(yīng)的γ-羥基硼酸酯或者γ-氨基硼酸酯。這一新反應(yīng)是對經(jīng)典環(huán)氧乙烷試劑和偕二硼試劑的有效利用。我們的新方法具有良好的官能團(tuán)兼容性,可以兼容大量具有合成價(jià)值的官能團(tuán),提供了一個(gè)在溫和反應(yīng)條件下合成復(fù)雜分子的有效策略。例如,該反應(yīng)可以使一系列的脂肪族和芳香族化合物轉(zhuǎn)化為相應(yīng)的二級或三級γ-羥基硼酸酯。此外,也可以使磺�；s環(huán)丙烷轉(zhuǎn)化得到相應(yīng)的γ-氨基硼酸酯。在第三章中,我們實(shí)現(xiàn)了第一例銅催化(促進(jìn))環(huán)氧丙烷開環(huán)硼化。這個(gè)過程展示了用易得的二硼試劑(B2pin2,B2neop2)和端基環(huán)氧底物開環(huán)硼化的反應(yīng)。含有不同的官能團(tuán)環(huán)氧乙烷衍生物被轉(zhuǎn)換為相應(yīng)的β-羥基硼酸酯。同時(shí),手性環(huán)氧化合物也可以參與到反應(yīng)中,通過隨后的氧化生成手性保持的1,2-二醇化合物。該反應(yīng)中獲得的β-羥基硼酸酯在有機(jī)反應(yīng)中有很多應(yīng)用,比如和芳基鹵化物發(fā)生Suzuki-Miyaura偶聯(lián)可以得到各種芳基取代的二級醇。另外,也可以通過Chan-Lam-Evans交叉偶聯(lián)反應(yīng)生成相應(yīng)的芳香胺或者芳香醇。因此,我們發(fā)展的新方法得到的開環(huán)產(chǎn)物(β-羥基硼酸酯)也進(jìn)一步為C-C鍵和C-N鍵化合物構(gòu)建提供了便利。在第四章中,我們發(fā)現(xiàn)Pd催化可以選擇性的活化偕二氟環(huán)丙烷化合物C-C鍵斷裂。鈀催化偕二氟化合物C-F鍵斷裂反應(yīng)是一個(gè)官能團(tuán)兼容性非常好的生成單氟衍生物的途徑。這個(gè)過程提供了一個(gè)生成2-F烯丙基胺、酯、醚的方法。同時(shí)生成的烷基化產(chǎn)物是Z式構(gòu)型,是眾多生物活性分子的重要結(jié)構(gòu)。另外這也是偕二氟環(huán)丙烷首次在過渡金屬催化交叉偶聯(lián)反應(yīng)中的應(yīng)用。我們拓展了"銅、鈀催化劑"在交叉偶聯(lián)反應(yīng)中的應(yīng)用。更進(jìn)一步,我們拓展了環(huán)氧化合物開環(huán)C-C和C-B鍵交叉偶聯(lián)反應(yīng)。另外,這也是偕二氟環(huán)丙烷首次在過渡金屬催化交叉偶聯(lián)中使用。我們實(shí)驗(yàn)室在端基環(huán)氧和偕二氟環(huán)丙烷上的努力是現(xiàn)代有機(jī)化學(xué)催化領(lǐng)域在底物上的突破�？墒�,這里面還存在一些挑戰(zhàn),比如銅催化環(huán)氧開環(huán)反應(yīng)在1,2-二取代環(huán)氧化合物來構(gòu)建四級碳中心以及更多二硼酯參與該反應(yīng)的嘗試都失敗了。因此這需要我們課題組更多的努力來克服這些問題。
[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.
【學(xué)位授予單位】：中國科學(xué)技術(shù)大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2017
【分類號】：O621.251
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本文編號：1940009