【作者】 张海峰；

【导师】 张锁秦；

【作者基本信息】 吉林大学 ， 有机化学， 2010， 硕士

【摘要】 有机小分子催化剂来源广泛,不含有金属离子,无毒并且在反应过程中不需要对反应底物进行修饰,因而有机小分子催化剂的设计、合成及其不对称催化得到了人们的极大关注,并且成为了当前研究的热点和前沿。自从List等人发现脯氨酸在催化不对称Aldol反应、不对称Michael加成反应以来,脯氨酸及其衍生物也就成了化学工作者研究的重点。Michael加成反应,Aldol反应是有机合成中形成C-C键,C-S键等的重要反应。近年来科研工作者设计的脯氨酸衍生物在催化不对称直接Michael加成反应和Aldol反应都体现出了较好的不对映选择性。本文的工作就是利用已知的有机催化剂来催化合成手性3-乙硫基丁醛及其衍生物。我们通过参考文献了解到苯基以及取代的苯基脯胺醇硅醚类催化剂,在催化手性不对称Michael加成反应中表现出了良好的活性。因此我们合成了催化剂1,2,3以及我们组林健博士设计合成的催化剂4-6,利用这些催化剂催化手性3-乙硫基丁醛的合成。通过筛选确定催化剂2为最佳催化剂,并且讨论了溶剂,温度的影响。最佳条件下得到91%的ee值和82%的产率。同时在3-乙硫基丁醛的衍生物6-乙硫基-3-庚烯-2-酮的合成方面,我们设计了两条路线,路线一是通过Knoevenagel反应得到目标产物;路线二是通过Aldol反应得到目标产物。通过实验最终确定了路线二,产率和ee值方面还需进一步研究提高,这些工作为手性烯草酮的合成奠定了良好的基础。更多还原

【Abstract】 Small molecule organic catalysts with its own merits, have been recognized by researchers and become a research focus at the present stage. More prominent in this regard is the catalyst for the class of proline and its derivatives, their asymmetric C-C bond, C-N bond, C-S bond formation reactions, such as the Aldol reaction, Michael reaction played a significant role.Clethodim herbicide is a new good, has been widely used. John Whittington, who found that l-configuration of clethodim is surprisingly more effective in regulating the growth of grass plants than the corresponding racemic mixture or the optically pure (L)-enantiomer. And they prepared a single hand of clethodim by a preparative HPLC column.In this paper, we discuss the study synthesis of chiral(S)- 3-(ethylthio)butanal and its Derivatives. We discss the main two steps : The first is the Synthesis of chiral (S)-3-(ethylthio)butanal. In this step, we first synthesized catalysts 1-3, and also used catalysts 4-6 which were prepared by Dr.lin jian. We investigated the application of catalysts for asymmetric Michael addition reaction between crotonaldehyde and ethanethiol. We selected the best catalyst 2, by which we investigated the reaction temperature,reaction solvent effect,and ultimately determine the best conditions. Under these conditions, we can get the product with 91% ee and 82% yield. The second we synthesize Chiral 6-ethylthio-3-heptene -2-one, we used two synthetic routes. First, the 3-(ethylthio)butanal and ethyl acetoacetate in the pyrrolidine and other organic base catalyst, occur Knoevenagel reaction. After we obtain product by hydrolysis of keto-type. Unfortunately, this line did not achieve the desired effect . Line 2, 3-(ethylthio)butanal and acetone asymmetric occurr Aldol reaction. First we try the proline, List and others reported as acetone as solvent and at 0℃, the self-condensation of aliphatic aldehydes has been inhibited, aldehydes and ketones occurs only asymmetric Aldol reaction, and received only two addition Product:α-hydroxy ketones andα,β-unsaturated ketone. The latter is exactly what we want results, while the former has been the latter through dehydration. We have also added to the reaction system, a small amount of methanol to increase the solubility of proline, thus shortening the reaction time increased the yield of reaction. Second, we use solid sodium hydroxide to catalytic reaction. See the strong sodium oxide highly, along with a lot of byproducts. Second, we use solid sodium hydroxide to catalytic reaction. See the strong sodium oxide highly, along with a lot of byproducts,we only get the product of low yield rate. Through the TLC detection, we obtained the mostlyα-hydroxy ketone compounds. Again we get the target product by concentrated phosphoric acid.Finalized through the line of the second experiment, to proline as the catalyst we began to test the continuous synthesis of (S) -6 - ethylthio -3-heptene -2-one, but the result is not ideal. Aspects of yield and ee value of further research is required to improve, but they work for the chiral synthesis of clethodim laid a good foundation.更多还原