Metal-Catalyzed Asymmetric Cyclization Reactions

本工作的目标是设计和测试新的过渡金属催化剂，用于实现不对称碳-碳键形成反应。 两个反应，特别是将详细研究，不对称铑催化的烯反应和银和铜催化的偶氮甲亚胺叶立德的不对称1，3偶极环加成反应。 在每种情况下，将制备新的手性膦配体组，然后将使用对这些反应的机理的理解来“微调”用于这些反应的金属/配体催化剂系统。 铑催化烯炔环化反应将用于天然产物Oppositol和α-红藻氨酸的不对称合成。 银和铜催化的反应将被应用于在六氢三喹并苯、乙内酰脲和含有天然产物的多环稠合内酰胺中发现的核心结构。有了这个奖项，有机和高分子化学计划正在支持宾夕法尼亚州立大学化学系的Xumu Zhang博士的研究。 张博士将探索铑、银和铜试剂催化的立体选择性环化反应。 在手性分子中形成碳-碳键的能力（具有两个不可重叠的镜像），并且仅产生两种可能形式中的一种（单一对映异构体）是当今制药工业面临的最重要的问题之一。 开发后，张博士的铑催化工作可应用于合成天然产物，如Oppositol和α-红藻氨酸。 海洋天然产物海人酸是有效的神经递质，这些化合物的全球短缺阻碍了神经科学界的工作。 银和铜催化的反应将应用于在六氢三喹并苯、乙内酰脲和含有多环稠合内酰胺的天然产物中发现的核心结构，所述天然产物具有广泛的生物活性，如抗病毒、抗真菌、抗菌和杀菌剂。 在这项工作的过程中培训的学生将获得制药行业所需的技能，现在生产一些单一的对映体化合物。

The objectives of this work are to design and test new transition metal catalysts for effecting asymmetric carbon-carbon bond forming reactions. Two reactions in particular will be studied in detail, asymmetric rhodium catalyzed ene reactions and silver and copper catalyzed asymmetric 1,3 dipolar cycloadditions of azomethine ylides. In each case, new sets of chiral phosphine ligands will be prepared and then an understanding of the mechanisms of these reactions will be used to "fine tune" metal/ligand catalysts systems for these reactions. The rhodium catalyzed enyne cycloisomerization will be applied to asymmetric syntheses of the natural products Oppositol and alpha-Kainic acid. The silver and copper catalyzed reactions will be applied to core structures found in hexahydrotriquinacene, hydantoin, and polycyclic fused lactam containing natural products. With this award, the Organic and Macromolecular Chemistry Program is supporting the research of Dr. Xumu Zhang of the Department of Chemistry at Penn State University. Dr. Zhang will explore stereoselective cyclization reactions which are catalyzed by rhodium, silver, and copper reagents. The ability to form carbon-carbon bonds in molecules which are chiral (have two nonsuperimposable mirror images) and make only one of the two possible forms (a single enantiomer) is one of the most important problems facing the pharmaceutical industry today. When developed, Dr. Zhang's rhodium catalyzed work could be applied to the synthesis of natural products such as Oppositol and alpha-Kainic acid. The marine natural product Kainic acids are potent neurotransmitters and a worldwide shortage of these compounds has hindered work in the neuroscience community. The silver and copper catalyzed reactions will be applied to core structures found in hexahydrotriquinacene, hydantoin, and polycyclic fused lactam containing natural products which have a broad range of biological activities as antivirals, antifungals, antibacterials, and herbicidals. Students trained during the course of this work will gain skills needed by the pharmaceutical industry which now produces a number of single enantiomer compounds.