有机小分子和酸介入的MBH反应的研究

发布时间：2018-01-10 11:11

  本文关键词：有机小分子和酸介入的MBH反应的研究　出处：《浙江大学》2017年博士论文　论文类型：学位论文

  更多相关文章： MBH α β-不饱和酮 烯丙基化 domino反应 N-烷基化

【摘要】：碳-碳键的形成是有机化学中最基础的反应之一,在多个竞争反应位点选择性地在特定位置上构建碳-碳键是有机合成中非常具挑战性的课题。Morita-Baylis-Hillman(MBH)反应是一个非常重要的碳-碳键形成反应,可以广泛地应用于合成活性中间体以及精细化工产品。本论文主要研究了分子间α,β-不饱和酮与烯丙醇及其衍生物的烯丙基化反应,以及两分子α,β-不饱和酮的domino关环反应。第一章,简单介绍了MBH反应的研究进展,对MBH反应三组分α,β-不饱和化合物、催化剂、亲电试剂分别进行了介绍,并重点介绍了亲电试剂醛、亚胺、α,β-不饱和化合物、环氧化合物、芳基化合物、卤代烃、烯丙基化合物等。第二章,膦与Br(?)nsted酸介入的分子间α,β-不饱和酮与烯丙基醋酸酯的MBH烯丙基化反应。该反应通过Pd(PPh_3)_4与P(n-Bu)_3共催化,AcOH作添加剂,能很好地得到α-烯丙基化产物。酸的加入,可有效抑制MBH插烯二聚副产物的生成。同时,通过中间体的分离鉴别,我们提出了一个经过稳定鳞盐中间体的可能机理。该反应条件温和,且具有很好的区域选择性与E-立体选择性。第三章,膦与Br(?)nsted酸介入的分子间α,β-不饱和酮与烯丙醇的MBH烯丙基化反应。利用Pd(PPh_3)_4与P(n-Bu)_3共催化体系,在toluene/(CF_3)_2CHOH混合溶剂中,开发出一种新颖的α,β-不饱和酮和烯丙醇的MBH反应。并提出了利用(CF_3)_2CHOH生成鳞盐和活化烯丙醇的可能机理。烯丙醇与烯丙基醋酸酯相比较,底物更加容易制备,且没有额外的酯化步骤,烯丙醇作烯丙基化试剂副产物只有水,符合绿色化学与原子经济性的要求。该MBH反应具有底物适用性广、优秀的区域选择性和立体选择性、较好的产率等诸多优点。第四章,膦与Br(?)nsted酸介入的α,β-不饱和酮分子间MBH插烯反应与Wittig串联的domino关环反应。该反应在P(n-Bu)_3介导下,乙酸作添加剂,100℃反应即可以良好的收率得到目标产物。利用这种方法可以很好地得到β,γ-不饱和酮,酸的加入,可有效抑制MBH插烯二聚副产物的生成,同时也可以促使Wittig反应的进行。该反应条件温和,可耐受一系列官能团。在论文的最后,我们也简单介绍了Lewis酸介入的N-烷基化反应。以廉价的Lewis酸AlCl_3为催化剂,均三甲苯为反应溶剂,100-176℃下反应即可生成对应的N-烷基化产物。该方法的优点是底物适用性广,脂肪族胺与芳香族胺、伯醇与仲醇都能有效地发生该反应,对胺的烷基化提供了一个新的参考方法。同时,我们也对Lewis酸介入的N-烷基化反应提出了一个合理的机理解释。
[Abstract]:The formation of carbon-carbon bond is one of the most basic reactions in organic chemistry. The selective construction of carbon-carbon bonds at specific sites at multiple competitive reaction sites is a very challenging topic in organic synthesis. Morita-Baylis-Hillman (MBH). Reaction is a very important carbon-carbon bond formation reaction. It can be widely used in the synthesis of active intermediates and fine chemical products. In this paper, the allylation of 伪, 尾 -unsaturated ketones with allyl alcohols and their derivatives and the two molecules 伪 were studied. The domino ring closing reaction of 尾 -unsaturated ketones. Chapter 1, the research progress of MBH reaction is briefly introduced. The three components 伪, 尾 -unsaturated compounds and catalysts of MBH reaction are studied. The electrophilic reagents were introduced, and the electrophilic reagents, aldehydes, imines, 伪, 尾-unsaturated compounds, epoxy compounds, aryl compounds, halogenated hydrocarbons, allyl compounds, etc. Phosphine and Bran? The MBH allylation of 伪, 尾 -unsaturated ketones with allyl acetate was co-catalyzed by Pd(PPh_3)_4 and Pnsted. The 伪 -allylation product can be obtained by using AcOH as additive. The addition of acid can effectively inhibit the formation of dimeric by-product of MBH intercalation. At the same time, it can be identified by the separation and identification of intermediate. We have proposed a possible mechanism for the intermediate to stabilize the scale salt. The reaction conditions are mild and have good regioselectivity and E-stereoselectivity. The MBH allylation of allyl alcohol with 伪, 尾 -unsaturated ketones and allyl alcohols was studied. The co-catalytic system of Pd(PPh_3)_4 and Pnsted _ Bun _ (3) was used in the reaction of 伪, 尾 -unsaturated ketones with allyl alcohol. In the mixed solvent of toluene/(CF_3)_2CHOH, a novel 伪 was developed. The MBH reaction of 尾 -unsaturated ketones with allyl alcohols. A possible mechanism for the formation of scale salts and activation of allyl alcohols by using CF3CHOH was proposed. The comparison of allyl alcohols with allyl acetate was made. It is easier to prepare the substrate without additional esterification step. The byproduct of allyl alcohol as allylation reagent is only water, which meets the requirements of green chemistry and atomic economy. The MBH reaction has wide applicability of substrate. Excellent regioselectivity and stereoselectivity, good yield and many other advantages. Chapter 4th, phosphine and Brine? The intermolecular MBH intercalation reaction of 伪, 尾 -unsaturated ketones with Wittig was mediated by Pnsted acid mediated domino closure reaction. The target product can be obtained by the reaction of acetic acid as additive at 100 鈩，

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