本文選題：氮雜環(huán)卡賓　切入點(diǎn)：缺電子聯(lián)烯　出處：《浙江大學(xué)》2017年博士論文

【摘要】：聯(lián)烯能夠發(fā)生諸如親電加成、親核加成和自由基加成等反應(yīng),在過(guò)渡金屬的催化下,聯(lián)烯還能發(fā)生一系列的偶聯(lián)環(huán)化反應(yīng)。不同于烯烴和炔烴,當(dāng)末端的取代基兩兩不同時(shí),聯(lián)烯具有軸手性。在適當(dāng)?shù)姆磻?yīng)條件下,聯(lián)烯的軸手性可以高效地轉(zhuǎn)移到產(chǎn)物的中心手性中,因此需要發(fā)展聯(lián)烯的高對(duì)映選擇性地合成方法。本論文集中于聯(lián)烯的合成和反應(yīng)進(jìn)行研究,分為三個(gè)部分:第一部分:氮雜環(huán)卡賓催化的缺電子聯(lián)烯的反應(yīng)研究氮雜環(huán)卡賓催化的簡(jiǎn)單醛、α,β-不飽和烯醛和α,β-不飽和炔醛的反應(yīng)已經(jīng)得到了充分地研究。然而氮雜環(huán)卡賓催化的缺電子聯(lián)烯的反應(yīng)還未得到細(xì)致地開(kāi)展。1.發(fā)展了一種氮雜環(huán)卡賓催化的聯(lián)烯醛和查耳酮的環(huán)化反應(yīng)生成多取代吡喃醛的方法。我們提出了三條可能的反應(yīng)路徑:氮雜環(huán)卡賓進(jìn)攻聯(lián)烯醛的中間碳原子形成一個(gè)離域化的負(fù)離子中間體,或者直接作為布朗斯特堿拔氫,形成的中間體再與查耳酮發(fā)生1,4-共軛加成,經(jīng)過(guò)后續(xù)的反應(yīng)生成最終產(chǎn)物。2.發(fā)展了一種氮雜環(huán)卡賓催化的芳香醛與1,2-聯(lián)烯酮反應(yīng)高非對(duì)映選擇性地合成環(huán)戊-2-烯酮-4-醇的方法。機(jī)理研究顯示該反應(yīng)中存在四種可能的反應(yīng)路徑。3.發(fā)展了一種氮雜環(huán)卡賓催化的簡(jiǎn)單醛與聯(lián)烯酸酯反應(yīng)高立體選擇性地合成(E)-4-氧代-2-丁烯酸酯的方法。機(jī)理研究表明氯仿作為質(zhì)子載體,而水的量通過(guò)影響中間體的反應(yīng)性影響立體選擇性。第二部分:CuBr_2催化的由醛,末端炔醇和光學(xué)活性的二甲基脯氨醇出發(fā)高對(duì)映選擇性地合成1,3-雙取代聯(lián)烯醇的反應(yīng)研究在我們之前研究的基礎(chǔ)上,發(fā)展了一種更加普適的CuBr_2催化的醛,末端炔醇,(S)-或者(R)-α,α-二甲基脯氨醇三組分偶聯(lián)高對(duì)映選擇性地合成1,3-雙取代的聯(lián)烯醇的方法。反應(yīng)結(jié)果不受聯(lián)烯醇中醇羥基與聯(lián)烯間碳鏈的長(zhǎng)短的影響。脂肪醛和芳香醛底物都能很好的兼容。與此同時(shí),我們還發(fā)現(xiàn)在相同的反應(yīng)條件下,(S)-α,α-二甲基脯氨醇促進(jìn)的反應(yīng)比(S)-α,α-二苯基脯氨醇促進(jìn)的反應(yīng)的對(duì)映選擇性好。合成的光學(xué)活性的1,3-聯(lián)烯醇具有多樣的反應(yīng)應(yīng)用。我們還實(shí)現(xiàn)了 phlomicacid 的全合成。第三部分:一些2,7-雙攜氧的咔唑生物堿的克級(jí)合成反應(yīng)研究由簡(jiǎn)單易得的原料丙二烯甲醚和1-芐基-6-甲氧基吲哚-2-甲醛出發(fā),以高效的金催化的環(huán)化反應(yīng)作為關(guān)鍵步驟,克級(jí)規(guī)模合成了咔唑生物堿7-methoxy-O-methylmukonal,7-methoxymukonal,clausine-O,clausine-K(clauszoline-J),clausine-H(clauszoline-C)和咔唑化合物 methyl 2-hydroxy-7-methoxy-9H-carbazole-3-carboxylate。其中,7-methoxymukonal 和methyl 2-hydroxy-7-methoxy-9H-carbazole-3-carboxylate 是首次被合成。除此之外,methyl 2-hydroxy-7-methoxy-9H-carbazole-3-carboxylate 的結(jié)構(gòu)通過(guò)其乙基化產(chǎn)物的X射線單晶衍射得到了證實(shí),也說(shuō)明Taufiq-Yap等在2007年報(bào)道的clausine-TY的結(jié)構(gòu)是錯(cuò)誤的。
[Abstract]:Biene can take place such as electrophilic addition, nucleophilic addition and radical addition, and a series of coupling cyclization reactions can take place under the catalysis of transition metal.Unlike alkenes and alkynes, bienes have axial chiral properties when the end substituents are different.Under the appropriate reaction conditions, the axial chirality of biene can be transferred to the central chirality of the product efficiently, so it is necessary to develop the highly enantioselective synthesis of diene.The synthesis and reaction of diene were studied in this paper.There are three parts: the first part: the reaction of electron-deficient diene catalyzed by carbene; the reactions of simple aldehydes, 偽, 尾 -unsaturated aldehydes and 偽, 尾 -unsaturated aldehydes catalyzed by aza-heterocyclic carbenes have been fully studied.However, the reaction of electron-deficient diene catalyzed by heterocyclic carbene has not been carried out in detail.A method for the cyclization of diallic aldehyde and chalcone catalyzed by heterocyclic carbene to produce polysubstituted pyranaldehyde was developed.We propose three possible pathways: the heterocyclic carbene attack on the intermediate carbon atom of the diallyl aldehyde to form a delocalized anion intermediate, or direct hydrogen removal as Brownstatin.The intermediate was then added with chalcone, and the final product. 2.A method for the highly enantioselective synthesis of cyclopentyl-2-enone-4-ol from aromatic aldehydes catalyzed by heterocyclic carbene was developed.The mechanism study shows that there are four possible reaction pathways. 3.A high stereoselectivity method for the synthesis of EN-4-oxo-2-butenate catalyzed by heterocyclic carbene-catalyzed simple aldehydes and dienoates has been developed.The mechanism study showed that chloroform was used as proton carrier, and the amount of water affected the stereoselectivity by affecting the reactivity of intermediate.Part two: CuBr2 catalyzes the highly enantioselective synthesis of 1,3-disubstituted enols from aldehydes, terminal alkynols and optically active dimethylpropanol, based on our previous studies.A more general CuBr_2 catalyzed method for the highly enantioselective synthesis of 1 ~ (3) -disubstituted dienol from aldehydes, terminal acetylenol, or rin- 偽, 偽 -dimethylpropanol was developed.The reaction results were not affected by the length of the carbon chain between the alcohol hydroxyl and the diene in the dienol.Aliphatic aldehydes and aromatic aldehydes are well compatible.At the same time, we also found that the enantioselectivity of S- 偽, 偽-dimethylproline was better than that of S- 偽, 偽 -diphenyl proline under the same reaction conditions.The synthesized optical active 1 C 3-dienol has a wide range of reaction applications.We also realized the total synthesis of phlomicacid.Part three: the study on the gram Synthesis of some Carbazole alkaloids with 2o 7-Bis oxygen; starting from the simple and readily available raw materials, allylene ether and 1-benzyl-6-methoxyindole -2-formaldehyde, the cyclization of some carbazole alkaloids catalyzed by high efficiency gold was taken as the key step.Carbazole alkaloids 7-methoxy-O-methylmukonalanine 7-methoxymukonalanine-Oclausine-Oclausine-Knclauszoline-K) and carbazole compound methyl 2-hydroxy-7-methoxy-9H-carbazole-3-carboxylatewere synthesized on a gram scale.Among them, 7-methoxymukonal and methyl 2-hydroxy-7-methoxy-9H-carbazole-3-carboxylate were synthesized for the first time.In addition, the structure of 2-hydroxy-7-methoxy-9H-carbazole-3-carboxylate is confirmed by X-ray single crystal diffraction of its ethylated product, which indicates that the structure of clausine-TY reported by Taufiq-Yap et al in 2007 is wrong.
【學(xué)位授予單位】：浙江大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2017
【分類號(hào)】：O621.3
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本文編號(hào)：1722119