一些联烯的合成和反应研究

发布时间：2018-04-08 15:01

  本文选题：氮杂环卡宾　切入点：缺电子联烯　出处：《浙江大学》2017年博士论文

【摘要】：联烯能够发生诸如亲电加成、亲核加成和自由基加成等反应,在过渡金属的催化下,联烯还能发生一系列的偶联环化反应。不同于烯烃和炔烃,当末端的取代基两两不同时,联烯具有轴手性。在适当的反应条件下,联烯的轴手性可以高效地转移到产物的中心手性中,因此需要发展联烯的高对映选择性地合成方法。本论文集中于联烯的合成和反应进行研究,分为三个部分:第一部分:氮杂环卡宾催化的缺电子联烯的反应研究氮杂环卡宾催化的简单醛、α,β-不饱和烯醛和α,β-不饱和炔醛的反应已经得到了充分地研究。然而氮杂环卡宾催化的缺电子联烯的反应还未得到细致地开展。1.发展了一种氮杂环卡宾催化的联烯醛和查耳酮的环化反应生成多取代吡喃醛的方法。我们提出了三条可能的反应路径:氮杂环卡宾进攻联烯醛的中间碳原子形成一个离域化的负离子中间体,或者直接作为布朗斯特碱拔氢,形成的中间体再与查耳酮发生1,4-共轭加成,经过后续的反应生成最终产物。2.发展了一种氮杂环卡宾催化的芳香醛与1,2-联烯酮反应高非对映选择性地合成环戊-2-烯酮-4-醇的方法。机理研究显示该反应中存在四种可能的反应路径。3.发展了一种氮杂环卡宾催化的简单醛与联烯酸酯反应高立体选择性地合成(E)-4-氧代-2-丁烯酸酯的方法。机理研究表明氯仿作为质子载体,而水的量通过影响中间体的反应性影响立体选择性。第二部分:CuBr_2催化的由醛,末端炔醇和光学活性的二甲基脯氨醇出发高对映选择性地合成1,3-双取代联烯醇的反应研究在我们之前研究的基础上,发展了一种更加普适的CuBr_2催化的醛,末端炔醇,(S)-或者(R)-α,α-二甲基脯氨醇三组分偶联高对映选择性地合成1,3-双取代的联烯醇的方法。反应结果不受联烯醇中醇羟基与联烯间碳链的长短的影响。脂肪醛和芳香醛底物都能很好的兼容。与此同时,我们还发现在相同的反应条件下,(S)-α,α-二甲基脯氨醇促进的反应比(S)-α,α-二苯基脯氨醇促进的反应的对映选择性好。合成的光学活性的1,3-联烯醇具有多样的反应应用。我们还实现了 phlomicacid 的全合成。第三部分:一些2,7-双携氧的咔唑生物碱的克级合成反应研究由简单易得的原料丙二烯甲醚和1-苄基-6-甲氧基吲哚-2-甲醛出发,以高效的金催化的环化反应作为关键步骤,克级规模合成了咔唑生物碱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 的结构通过其乙基化产物的X射线单晶衍射得到了证实,也说明Taufiq-Yap等在2007年报道的clausine-TY的结构是错误的。
[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, 伪, 尾 -unsaturated aldehydes and 伪, 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- 伪, 伪 -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- 伪, 伪-dimethylproline was better than that of S- 伪, 伪 -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.
【学位授予单位】：浙江大学
【学位级别】：博士
【学位授予年份】：2017
【分类号】：O621.3
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本文编号：1722119