氮杂环卡宾催化羰基化合物β-位不对称环加成反应的研究

发布时间：2018-06-04 22:38

  本文选题：氰基 + 氮杂环卡宾　； 参考：《贵州大学》2017年硕士论文

【摘要】：氰基类化合物作为有机合成中的基本合成砌块广泛存在于天然产物、医药及农药分子中,如何通过绿色、简洁、高效的反应过程一步构建手性氰基类化合物特别是含氰基的手性季碳分子一直是本领域的研究热点及难点。有机小分子催化剂自从被概念化以后受到了科研人员的广泛关注并对其进行了深入研究,目前已得到了长足发展。由于其具有操作简单、无毒、反应条件温和及后处理简单等优点,已经广泛应用于有机合成领域。氮杂环卡宾(N-heterocyclic carbine,NHC)作为有机小分子催化剂中的后起之秀,由于其独特的催化活化模式不仅能够对已有的反应进行高收率及高立体选择性控制,而且能够合成出传统方法无法合成的结构新颖的新化合物。经过近二十年的研究与发展,目前氮杂环卡宾催化剂已经广泛应用于高效构建C-C键及C-X(X=O,N,S)键并取得了显著成果。本论文主要研究了利用氮杂环卡宾为催化剂一步合成含氰基的手性季碳类化合物及初步探讨此类化合物的生物活性两个方面的内容。1.利用手性氮杂环卡宾为催化剂和联苯二醌为氧化剂的作用下,催化氧化β-氰基烯醛生成a(11)b-unsaturated acylazolium类中间体,选用1,3-二羰基化合物为亲核试剂,在0℃条件下,以四氢呋喃(THF)为溶剂一步合成出具有高收率及高立体选择性控制的含氰基的手性季碳分子。通过底物拓展我们可以看出此方法对不同取代基取代的β-氰基烯醛类化合物具有很好的普适性,其中部分底物收率可高达95%,ee值最高可达98%。我们所用的底物β-氰基烯醛类化合物合成简单、易得,此方法避免了有毒氰源,如HCN,KCN的使用,为手性氰基类化合物的高效构建提供了新策略。2.通过使用浊度法对已合成出的部分目标化合物,进行生物活性测试。结果表明,上述化合物对水稻白叶枯病菌基有一定的活性,对烟草青枯病菌基本没有活性,其中手性化合物化合(R)-ethyl-4-(4-chlorophenyl)-4-cyano-6-methyl-2-oxo-3,4-dihydro-2H-pyran-5-carboxylate在浓度为200μg/m L时对水稻白叶枯病菌的抑制率为90±7.6%,在浓度为100μg/mL时对水稻白叶枯病菌的抑制率为52±6.0%。
[Abstract]:Cyanide compounds are widely used in natural products, medicine and pesticide molecules as basic synthetic blocks in organic synthesis. The synthesis of chiral cyanide compounds, especially the chiral quaternary carbon molecules containing cyanide, has been a hot and difficult point in this field. Since its conceptualization, organic small molecular catalysts have been paid more and more attention by researchers. Because of its advantages of simple operation, non-toxic, mild reaction conditions and simple post-treatment, it has been widely used in the field of organic synthesis. N-heterocyclic carbonic acid (N-heterocyclic carbineHCl) is a rising star in small organic catalyst. Because of its unique catalytic activation mode, it can not only control the reaction with high yield and stereoselectivity, but also can control the reaction in high yield and stereoselectivity. Moreover, new compounds with novel structure can be synthesized which cannot be synthesized by traditional methods. After nearly two decades of research and development, nitrogen heterocyclic carbene catalysts have been widely used in the efficient construction of C-C bonds and C-XOXOON-N (S) bonds, and remarkable results have been obtained. In this paper, the synthesis of chiral quaternary carbohydrates containing cyanide by using heterocyclic carbene as catalyst was studied and the biological activities of these compounds were preliminarily discussed. Using chiral aza-heterocyclic carbene as catalyst and biphenyl diquinone as oxidant, 尾 -cyanenaldehyde was oxidized to form a(11)b-unsaturated acylazolium intermediates, and 1o _ 3-dicarbonyl compound was used as nucleophilic reagent at 0 鈩，

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