手性诱导下的不对称Baylis-Hillman反应

发布时间：2018-05-20 22:45

本文选题：Baylis-Hillman反应 + 手性诱导　；参考：《湘潭大学》2017年硕士论文

【摘要】：Baylis-Hillman反应是一类能高效构建碳-碳键的三组分反应,其产物具有多个可以进一步转换的官能团,因此该类型反应在有机合成中得以广泛关注。近年来,发展了众多诱导不对称Baylis-Hillman反应的体系,针对这些体系中存在的底物选择范围窄、反应时间长、对映选择性低等问题。本论文展开了对手性诱导不对称Baylis-Hillman反应的方法研究,优化了两类手性诱导下的反应条件,获得新型、高效的手性诱导体系。1、手性底物的设计合成及在Baylis-Hillman反应中的应用分别以L-薄荷醇、托品醇、右旋冰片、巴豆酸与肉桂酸为原料,设计合成了五类手性活泼烯烃并应用于不对称Baylis-Hillman反应中,考察了催化剂种类、用量、时间、温度与溶剂体系对反应的诱导效果的影响。结果表明:以2-硝基苯甲醛与丙烯酸薄荷醇酯为底物时的Baylis-Hillman反应为模型,反应溶剂为DMF:H2O=9:1,DABCO与底物摩尔比为1:2:2时,20℃下反应36 h时诱导效果最佳,收率达84%,de值达91%;在最优反应条件下进行底物拓展,发现含拉电子基的芳香醛为底物时反应效果较好(收率高达91%,de值高达95%),而供电子基的芳香醛反应效果欠佳;同时考察丙烯酸托品醇酯、丙烯酸冰片酯、肉桂酸薄荷醇酯和巴豆酸薄荷醇酯这四种手性活泼烯烃与硝基苯甲醛的Baylis-Hillman反应,得到较好的结果;在此基础上,进一步探究了不对称反应产物酯水解反应,产物具有较高的立体选择性。2、手性溶剂的合成及在Baylis-Hillman反应中的应用分别以L-丙氨酸、L-苯丙氨酸、L-脯氨酸与L-组氨酸为原料,合成了十二种氨基酸类离子液体。并将其作为手性溶剂,在普通条件下(即催化剂、底物为非手性)利用溶剂控制诱导不对称Baylis-Hillman反应。对反应的催化剂种类、用量、手性溶剂及共溶剂、温度与时间进行优化,结果表明:以2-硝基苯甲醛和丙烯酸甲酯的Baylis-Hillman反应为模型,DABCO与2-硝基苯甲醛和丙烯酸甲酯摩尔比为1:1:6,L-脯氨酸乙酯[BF4-]为手性溶剂,在-10℃下反应36 h,诱导效果最佳,收率达41%,ee值达46%;在最优反应条件下,对底物的普适性进行考察,发现4-硝基苯甲醛为底物时反应效果较好(收率为51%,ee值56%);考察了不同的活泼烯烃在氨基酸类离子液体作为手性溶剂下的Baylis-Hillman反应,得到了较好的结果。
[Abstract]:Baylis-Hillman reaction is a class of three component reactions that can efficiently construct carbon carbon bonds. The products have many functional groups that can be further converted. Therefore, this type of reaction has been widely concerned in organic synthesis. In recent years, many systems to induce asymmetric Baylis-Hillman reactions have been developed to select the substrates that exist in these systems. The narrow range, long reaction time, low enantioselectivity and low enantioselectivity have been carried out in this paper. The method of asymmetric Baylis-Hillman reaction was studied in this paper. The reaction conditions of two classes of chiral inducers were optimized. A new and efficient chiral induction system.1 was obtained. The design and synthesis of chiral substrates and the application of L- in Baylis-Hillman reaction were respectively Five kinds of chiral active olefins were designed and synthesized from menthol, atropol, dextra, and cinnamic acid as raw materials. In the asymmetric Baylis-Hillman reaction, the effects of the type, dosage, time, temperature and solvent system on the reaction induced by the catalyst were investigated. The results showed that 2- nitrobenzaldehyde and menthol acrylate were used. When the Baylis-Hillman reaction is a model for substrate, the reaction solvent is DMF:H2O=9:1 and the molar ratio of DABCO to substrate is 1:2:2, the reaction is best when the reaction is 36 h at 20 C, the yield is 84%, the de value reaches 91%. Under the optimal reaction conditions, the substrate is expanded and the reaction effect is better when the aromatic aldehyde containing the tensile electron is the substrate (the yield is up to 91%, de The value is up to 95%) and the reaction effect of the aromatic aldehyde for the electronic base is not good. At the same time, the Baylis-Hillman reaction of four kinds of chiral active olefin and nitrobenzaldehyde, such as acrylic acid ester, borneol, cinnamic acid menthol ester, and menthol ester of Croton acid, has been investigated. On the basis of this, the asymmetric reaction is further explored. The product has high stereoselective.2, the synthesis of chiral solvent and the application of Baylis-Hillman in the synthesis of twelve kinds of amino acid ionic liquids, respectively, are L- alanine, L- phenylalanine, L- proline and L- histidine, and are used as chiral solvents under ordinary conditions (catalyst, bottom). Asymmetric Baylis-Hillman reaction was induced by solvent control. The type, dosage, chiral solvent and co solvent of the reaction were used to optimize the temperature and time. The results showed that the Baylis-Hillman reaction of 2- nitrobenzaldehyde and methyl acrylate was the model, and the molar ratio of DABCO to 2- nitrobenzaldehyde and methyl acrylate was 1: 1:6, L- proline ethyl [BF4-] is a chiral solvent, and the reaction is 36 h at -10 C. The yield is best, the yield is 41%, the EE value reaches 46%. Under the optimal reaction conditions, the universality of the substrate is investigated and the reaction effect is better when 4- nitrobenzaldehyde is the substrate (the yield is 51%, EE value 56%), and the different active olefin in the amino acid ions is investigated. As a Baylis-Hillman reaction under chiral solvents, the liquid obtained good results.
【学位授予单位】：湘潭大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：O621.25

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