本文關(guān)鍵詞： 不對(duì)稱催化 金雞納堿 β-二羰基化合物 α-羥基化 光致氧化 分子氧　出處：《大連理工大學(xué)》2016年博士論文　論文類型：學(xué)位論文

【摘要】：手性是自然界的基本屬性之一,與化學(xué)、生物、醫(yī)藥、工程等學(xué)科密切相關(guān),產(chǎn)業(yè)界對(duì)手性化合物的巨大需求推動(dòng)了手性科學(xué)的迅速發(fā)展。具有光學(xué)活性的α-羥基-β-二羰基化合物是一類非常重要的結(jié)構(gòu)單元,催化β-二羰基化合物的不對(duì)稱α-羥基化是獲得該類結(jié)構(gòu)簡(jiǎn)單、直接和高效的方法。首先,本文以金雞納堿奎寧及奎尼丁為先導(dǎo)有機(jī)催化劑,重點(diǎn)對(duì)金雞納堿C-2'和C-6'位進(jìn)行結(jié)構(gòu)修飾,制備并篩選了21種金雞納堿催化劑。以有機(jī)催化5-氯茚酮甲酸甲酯不對(duì)稱α-羥基化為模型反應(yīng),考察催化劑結(jié)構(gòu)與模型反應(yīng)的構(gòu)效關(guān)系。奎尼丁衍生C-2'位溴代、C-9和C-6'為羥基的QD-3催化該反應(yīng)具有92%ee和98%收率;反應(yīng)放大至克級(jí)仍有91%ee和96%收率。在該反應(yīng)體系中,使用過(guò)氧化氫異丙苯為氧化劑,得到S構(gòu)型的產(chǎn)物,對(duì)映選擇性80%-98%ee,收率87%-99%；使用30%雙氧水為氧化劑,得到R構(gòu)型的產(chǎn)物,對(duì)映選擇性36%-87%ee,收率35%-96%。該催化體系同時(shí)可實(shí)現(xiàn)β-酮酰胺類底物的不對(duì)稱α-羥基化,產(chǎn)物具有38%-92%ee和51%-94%收率。本文還對(duì)反應(yīng)機(jī)制進(jìn)行了探討,認(rèn)為催化劑、底物、氧化劑之間的氫鍵作用是反應(yīng)高效進(jìn)行的主要原因。其次,以二氫奎寧為催化劑,實(shí)現(xiàn)了肼活化分子氧制備手性α-羥基-β-酮酸酯的方法,獲得了55%-85%ee和67%-95%收率的a-羥基化產(chǎn)物。分子氧活化過(guò)程是肼在堿的作用下形成自由基正離子,與氧分子反應(yīng)生成過(guò)氧化氫,最后氧化底物實(shí)現(xiàn)α-羥基化。最后,通過(guò)光致氧化策略,實(shí)現(xiàn)分子氧參與的有機(jī)-光催化β-二羰基化合物不對(duì)稱a-羥基化,具有100%的原子經(jīng)濟(jì)性。通過(guò)對(duì)金雞納堿相轉(zhuǎn)移催化劑的設(shè)計(jì)、合成與篩選,發(fā)現(xiàn)辛可寧衍生C-2'帶有取代苯基的催化劑PTC 3I能夠催化30種β-酮酸酯以及β-酮酰胺底物不對(duì)稱α-羥基化,最高90%ee和99%收率。此外,發(fā)現(xiàn)N-氧化辛可寧衍生物相轉(zhuǎn)移催化劑PTC-Cn-7具有易回收重復(fù)使用的性質(zhì),催化β-二羰基化合物不對(duì)稱α-羥基化具有最高83%ee和99%收率。催化劑循環(huán)使用6次,產(chǎn)物仍有78%ee以及91%收率。本文還對(duì)光致氧化可能的機(jī)理進(jìn)行了闡述,推測(cè)氧化反應(yīng)經(jīng)歷了單線態(tài)氧過(guò)程,以及過(guò)氧化物中間體氧化過(guò)程。
[Abstract]:Chirality is one of the basic attributes of nature, which is closely related to chemistry, biology, medicine, engineering and so on. The rapid development of chiral science is driven by the huge demand of chiral compounds in industry. The optically active 偽-hydroxyl-尾-dicarbonyl compounds are very important structural units. Catalytic asymmetric 偽 -hydroxylation of 尾 -dicarbonyl compounds is a simple, direct and efficient method for obtaining this kind of compounds. Firstly, quinine and quinidine are used as lead organic catalysts. The structural modification of the C-2 'and C-6' sites of cinchonabine was emphasized, and 21 kinds of cinchona base catalysts were prepared and screened. The asymmetric 偽 -hydroxylation of methyl 5-chlorindenone formate was modeled by organic catalysis. The structure-activity relationship between the catalyst structure and the model reaction was investigated. The yields of quinidine derived C-2'brominated C-9 and C-6 '-hydroxyl QD-3 were 92 and 98% respectively. In this system, isopropylbenzene hydrogen peroxide was used as oxidant to obtain the product of S configuration. The enantioselectivity of the product was 80-98. The yield is 87-99; The product of R configuration was obtained by using 30% hydrogen peroxide as oxidant, and the enantioselectivity was 36-87. The catalytic system can realize asymmetric 偽 -hydroxylation of 尾 -ketoamides at the same time. The yield of the product was 38-92 and 51- 94% respectively. The reaction mechanism was also discussed and the catalyst and substrate were considered. The hydrogen bond between oxidants is the main reason for the high efficiency of the reaction. Secondly, using dihydroquinine as catalyst, the method of preparing chiral 偽 -hydroxy- 尾 -ketoate by activating molecular oxygen with hydrazine was realized. The a-hydroxylation products in 55- 85 and 67-95% yields were obtained. The process of molecular oxygen activation was that hydrazine formed free radical positive ions under the action of alkali and reacted with oxygen molecules to form hydrogen peroxide. Finally, 偽 -hydroxylation of the oxidized substrate was achieved. Finally, the asymmetric a-hydroxylation of 尾 -dicarbonyl compounds with the participation of molecular oxygen was realized by photooxidation strategy. It has atomic economy of 100%. Through the design, synthesis and screening of Jinchona alkaloid phase transfer catalyst. It was found that C-2'substituted phenyl catalyst PTC 3i could catalyze 30 尾 -ketoacid esters and asymmetric 偽 -hydroxylation of 尾 -ketoamide substrates. The highest yields of 90 and 99% were obtained. In addition, it was found that the phase transfer catalyst PTC-Cn-7 was easy to be recycled and reused. The asymmetric 偽 -hydroxylation of 尾 -dicarbonyl compounds has the highest yields of 83 and 99%, and the catalyst is recycled for 6 times. The yield of the product is still 78 and 91%. The possible mechanism of photo-induced oxidation is also discussed. The oxidation reaction has undergone a singlet oxygen process and an intermediate peroxide oxidation process.
【學(xué)位授予單位】：大連理工大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2016
【分類號(hào)】：R914
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本文編號(hào)：1480798