【作者】 郑冰；

【导师】 王敏；

【作者基本信息】 中国农业大学 ， 农药学， 2014， 博士

【摘要】 手性是生命活动的一个重要特征,而一对对映体通常会具有不同甚至完全相反的生理活性,因此高对映选择性地合成手性化合物具有重要的意义。目前,利用手性配体与金属催化的不对称反应是获得高光学活性化合物最直接和最高效的途径,也是最符合绿色化学理念的方法。因此将手性配体与金属组成的催化剂应用到不对称催化反应及天然产物全合成中是有机化学领域的热点和前沿。本论文在已有研究工作的基础上,进一步将配体L1、L76、L93应用到重要催化反应中,希望能够对其分子结构与催化性能的关系作进一步的探讨,从而获得优异的催化结果。手性硝基仲醇是重要的有机中间体,广泛应用于医药、农药等的合成。因此,我们系统研究配体L73-80与锌组成的催化剂在醛与硝基甲烷的不对称Henry反应中的催化性能。研究结果表明：配体L76与锌用于催化合成手性硝基仲醇化合物的反应时获得了较高的收率和对映选择性,以对甲基苯甲醛为底物时的反应产物ee值最高达到84%。手性炔丙基醇是合成众多精细化工品及天然产物的重要中间体,因此,我们将环丙烷氨基醇配体与锌组成的催化体系应用于1,3-二炔对醛的不对称加成反应中,系统研究配体结构、反应温度、反应溶剂等因素对催化结果的影响。在确定的最优反应条件下,研究了各种取代的1,3-丁二炔与醛的不对称加成反应,获得了优异的结果,大部分炔丙醇产物的ee值均大于90%,其中最高获得了95%的ee值。此外,我们还发展了以手性炔丙醇产物为关键中间体完成了海洋天然产物的合成。我们首先通过偶联、还原、氧化等一系列高收率的反应合成了长链烯醛,然后通过不对称炔基化的方法获得了炔醇片段,最后在碳酸钾的作用下脱去保护基得到了目标产物。该路线步骤简便,总产率较高,虽然加成产物只得到了81-82%的ee值,但经过酯化重结晶的方法ee值高达95%以本论文还系统地研究了配体与钯催化甲基砜与溴苯的芳基化反应。在氮气保护下,以甲苯为溶剂,Pd(OAc)2及配体L93形成的催化体系下,甲基砜与各种芳基溴可以很好地发生芳基化反应,产率在70-90%之间,同时产物的选择性也基本在10-20：1以上。该方法为今后合成砜类化合物提供了一个简便的途径。最后,本论文还研究了配体与钯催化的酰胺与芳基卤化物的芳基化反应,底物均得到了良好至优秀的产率(最高达到95%)。通过对碱和溶剂等反应条件的筛选,有效地控制单双芳基化反应产物的比例,最高的比例可以达到50：1。我们还证明了该催化体系可以应用于酰胺的分子内芳基化反应。更多还原

【Abstract】 Chirality is an important characteristic of life, and enantiomers usually have different or even opposite physiological activity, thus it is extremely significant to synthesize the compounds which have very high enantioselectivity. Recent research indicates that the asymmetric reaction conducted by chiral ligand is the most direct and efficient way to obtain high optical active compounds, so the application of novel ligand in asymmetric catalysis reactionis is still necessary and may stand as hot topics in organic chemistry. In this paper, based on existing ligands of the previous work, the further application of L1、 L76、L93can hope to explore the relationship between the molecular structure and catalytic performance and achieve excellent results in Henry reaction、Alkylation、Total synthesis of marine sponge natural product and Arylation of sulfones and amides.Chiral nitroalcohols are important organic intermediates, which are widely used in medicine, pesticide and others. Therefore, we investigated systematically the catalytic properties of the ligands L73-80in the asymmetric Henry reaction of zinc aldehyde with nitromethane, and ligand L76is applied in catalytic asymmetric Henry reaction finally. The experimental results show that the ligands afforded corresponding nitroalcohol products in good to high yields and enantioselectivities, for the4-methylbenzaldehyde84%ee was obtained.Chiral propargyl alcohols are the important intermediates of many fine chemicals, and natural products, so we applied the Zinc-Amino alcohols system in the highly enantioselective addition of1,3-diynes to aldehydes and investigated the effect of different reaction conditions such as ligand structure, reaction temperature and solvent on the catalytic results. Under the optimal reaction conditions identified, we studied a variety of substituted1,3-diynes to aldehydes which gave excellent results, most products of propargyl alcohol’s ee values were more than90%, in which the best95%ee was obtained. In addition, by using the chiral propargyl alcohol products as the key intermediate, the total asynthesis of marine sponge natural product was developed. The long-chainunsaturated aldehydes were synthesized through coupling reaction, reduction, oxidation and a series of high yield reaction firstly, then the alkynol fragment was prepared by the method of asymmetric alkynylation of above unsaturated aldehydes, finally with the help of potassium carbonate to removethe protectiving group, the target product was achieved. This route is short and the total yield is higher, although the ee of addition product is only81-82%, after recrystallization, the ee value could be increased to95%.Furthermore, this paper also studied systematically the palladium catalyzed arylation of methyl sulfone with bromobenzene. Under the nitrogen atmosphere, using toluene as the solvent and Pd (OAc)2as Pd source, methyl sulfone can smoothly react with bromobenzene, providing the arylated products in70-90%yield and the ratio of mono-to bis-arylation was well controlled (10-20:1) in the reactions. It provides a convient method to synthesize sulfone compounds.Finally, an efficient system for the direct catalytic intermolecular alpha-arylation of acetamide derivatives with aryl halides is presented, which provides the arylated amides in up to95%yield. Excellent chemoselectivities (up to50:1) in the mono-and diarylation with aryl bromides were achieved by careful selection of bases, solvents, and other conditions. We demonstrated the catalyst exhibited excellent reactivity in intramolecular arylation in the synthesis of oxindoles as well.更多还原