【摘要】：“無(wú)過(guò)渡金屬催化的偶聯(lián)反應(yīng)”,由于該類反應(yīng)能夠高效地構(gòu)建C-C鍵或CX(雜)鍵,引起了有機(jī)化學(xué)家的大量關(guān)注并得到了長(zhǎng)足的發(fā)展。結(jié)合本組的實(shí)際研究工作和一貫堅(jiān)持的高原子經(jīng)濟(jì)性和綠色化學(xué)的理念,我們圍繞著無(wú)金屬、高效性和綠色可持續(xù)三個(gè)基本點(diǎn)開展了以下的探索工作并取得了一些成果。其主要內(nèi)容如下:(1)TEA/DMF體系促進(jìn)的分子間環(huán)化反應(yīng)在TEA(三乙胺)/DMF(N,N-二甲基甲酰胺)體系的促進(jìn)下,一步構(gòu)建CC鍵和C-N鍵。這一堿催化的串聯(lián)環(huán)化過(guò)程適用于多種3-(雜)芳基-3-鹵代丙烯醛類化合物與1,2,3,4-四氫異喹啉(及其衍生物)之間進(jìn)行反應(yīng),并以高收率獲得相應(yīng)的吡咯[2,1-a]異喹啉類化合物(產(chǎn)率高達(dá)97%)。機(jī)理控制實(shí)驗(yàn)揭示出該過(guò)程并不經(jīng)歷自由基中間體,依據(jù)所有的實(shí)驗(yàn)結(jié)果,我們謹(jǐn)慎提出了可能的機(jī)理,該過(guò)程很可能經(jīng)歷了亞胺中間體,進(jìn)而完成最后的偶聯(lián)反應(yīng);或者,該過(guò)程還有可能經(jīng)過(guò)先親核加成再消除的途徑來(lái)進(jìn)行。(2)TBAC/TBHP體系促進(jìn)的分子間環(huán)化反應(yīng)在TBAC(四丁基氯化銨)/TBHP(叔丁基過(guò)氧化氫)體系的促進(jìn)下,一步構(gòu)建兩根C-C鍵。在簡(jiǎn)單的K2HPO4存在的條件下,TBAC和TBHP催化了2-異氰基聯(lián)苯(及其衍生物)與DMF間的反應(yīng),對(duì)應(yīng)產(chǎn)物可以以中等到優(yōu)秀的產(chǎn)率得到(產(chǎn)率高達(dá)86%)。這是我們初次通過(guò)一個(gè)可能的自由基環(huán)化過(guò)程來(lái)構(gòu)建啡啶-6-羧酸酰胺類化合物。雖然,這一部分的工作仍有欠佳之處,但是,這它卻為之后的自由基偶聯(lián)工作積累了寶貴的經(jīng)驗(yàn)。(3)TBAB/TBHP體系促進(jìn)的分子間環(huán)化反應(yīng)在TBAB(四丁基溴化銨)/TBHP體系的促進(jìn)下,一步構(gòu)建C-C鍵和C-S鍵。這一簡(jiǎn)單的反應(yīng)適用于多種2-異氰基聯(lián)苯與硫醇類(亦或苯硫酚類)化合物進(jìn)行反應(yīng),對(duì)應(yīng)的6-芳基(烷基)噻啡啶可以以中等到優(yōu)秀的產(chǎn)率獲得(產(chǎn)率高達(dá)86%)。此外,根據(jù)一系列機(jī)理控制實(shí)驗(yàn)的結(jié)果和HRMS檢測(cè)到的被TEMPO捕獲的巰基自由基,我們知道了這是一個(gè)自由基類型的反應(yīng),并且該反應(yīng)是一個(gè)直接活化S-H鍵的過(guò)程,進(jìn)而我們給出了一個(gè)可能的機(jī)理。(4)NH4I/TBHP體系促進(jìn)的分子間環(huán)化反應(yīng)在NH4I/TBHP體系的促進(jìn)下,一步構(gòu)建C-C鍵和C-N鍵。與第一部分工作不同,我們希望這一反應(yīng)可以通過(guò)自由基途徑來(lái)完成�？紤]到無(wú)金屬體系下N-自由基中心構(gòu)建及其他的一些困難,基于我們現(xiàn)有的經(jīng)驗(yàn),我們正在著手探索通過(guò)自由基偶聯(lián)的手段合成6-氨基取代的啡啶類化合物。經(jīng)過(guò)篩選,我們以糖精作為最優(yōu)氮源,以之與2-異氰基聯(lián)苯進(jìn)行反應(yīng),NH4I/TBHP是目前的最優(yōu)的催化體系,該體系下產(chǎn)率可達(dá)46%,后續(xù)優(yōu)化和探索工作仍在進(jìn)行中。
[Abstract]:"Coupling reaction without transition metal catalysis", which can efficiently construct C-C bond or CX bond, has attracted a lot of attention of organic chemists and has been greatly developed. Combined with the practical research work and the concept of high atom economy and green chemistry, we have carried out the following exploration work around the three basic points of metal-free, high efficiency and green sustainability, and obtained some achievements. The main contents are as follows: (1) the intermolecular cyclization promoted by TEA/DMF system was promoted by TEA (triethylamine) / DMF (NN- dimethylformamide) system, and the CC bond and C-N bond were constructed in one step. This alkali-catalyzed series cyclization process is suitable for the reaction between a variety of 3- (hetero-aryl-3-haloacrolein) compounds and 1t2O3H _ 3N _ 4-tetrahydroisoquinoline (and its derivatives). The corresponding isoquinoline compounds (yield as high as 97%) of pyrrole [2o 1-a] were obtained in high yield. The mechanism control experiment revealed that the process did not undergo free radical intermediates. According to all the experimental results, we carefully proposed a possible mechanism, this process probably experienced the imine intermediate, and then completed the final coupling reaction. Alternatively, the process may be carried out by nucleophilic addition and then elimination. (2) the intermolecular cyclization promoted by the TBAC/TBHP system is promoted by the TBAC (tetraDing Ji ammonium chloride) / TBHP (tertiary Ding Ji hydrogen peroxide) system. Two C-C bonds are constructed in one step. In the presence of simple K2HPO4, TBAC and TBHP catalyze the reaction between 2-isocyanobyls (and their derivatives) and DMF, and the corresponding products can be obtained in medium to excellent yields (up to 86%). This is the first time we have synthesized enkephalin-6-carboxylic acid amides through a possible radical cyclization process. Although there are still some shortcomings in this part of the work, however, It has accumulated valuable experience for the later free radical coupling work. (3) the intermolecular cyclization promoted by TBAB/TBHP system was promoted by TBAB (tetraDing Ji ammonium bromide) / TBHP system, and C-C bond and C-S bond were constructed in one step. This simple reaction is suitable for a variety of 2-isocyanated biphenyls to react with mercaptan (or phenylthiophenols) compounds, corresponding to which 6-aryl (alkyl) pyruvorphine can be obtained in medium to excellent yields (up to 86%). In addition, based on the results of a series of mechanism control experiments and the sulfhydryl radical trapped by TEMPO detected by HRMS, we know that this is a free radical type reaction, and that the reaction is a process of direct activation of S-H bond. Furthermore, a possible mechanism is given. (4) the intermolecular cyclization promoted by NH4I/TBHP system is promoted by NH4I/TBHP system, and C-C bond and C-N bond are constructed in one step. As opposed to the first part of the work, we hope that this reaction can be done through the free radical pathway. Considering some difficulties in the construction of N- radical centers in metal-free systems and based on our existing experience, we are exploring the synthesis of 6-amino-substituted enkephaline compounds by means of free radical coupling. After screening, we used saccharin as the optimal nitrogen source and reacted with 2-isocyanobenzene. NH4I/TBHP is the best catalytic system at present. The yield of the system can reach 46%. The further optimization and exploration are still under way.
【學(xué)位授予單位】：吉林大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2017
【分類號(hào)】：O621.251

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