Metal-catalyzed Reactions in Organic Synthesis

新化学反应的发现和发展是有机化学研究活动的主要焦点。在有机化学中发现最广泛适用的反应和反应类别是那些解决区域、立体和对映体控制问题并与各种官能团相容的反应和类别。形成多个键、环和/或立体中心的反应是有效组装复杂分子结构的特别重要的工具。 我们研究计划的长期目标是开发新的合成方法来构建不同的环系，包括：含氮杂环化合物、螺环化合物、连接环化合物和多环化合物。这些环系统存在于许多具有生物重要性的天然产品中，这些产品已被用于抗艾滋病毒、抗癌、抗病毒和抗逆转录病毒的研究。能够快速构建具有高区域、立体和对映体选择性的这些环系统的合成方法将是非常有用的。 金属催化的反应由于能够通过微调金属及其周围的配体来控制区域、立体和对映体的选择性而引起人们的特别兴趣。在过去的二十年里，过渡金属在有机合成中的使用急剧增加。过渡金属催化剂为高选择性反应提供了新的机会，而传统的合成方法无法实现这些反应。 我们将调查： (I)Ru催化的烯烃和炔烃之间的[2+2]环加成反应； (Ii)Ru催化的氮杂环化反应[3+2]和[3+3]； (Iii)金属介导的环丙烷化双环烯反应；和 (Iv)合成新型手性螺旋有机结构/聚合物。 在这里描述的针对长期目标的研究期间，将实现几个短期目标。这些短期目标包括：开发新颖的金属催化反应，研究这些金属催化反应的各个方面，包括解决反应性、区域选择性、立体选择性和对映体选择性的问题，调查这些反应的分子内和不对称形式，以及开发新型金属催化剂和配体。该研究计划不仅对科学发展具有重要意义，而且还为对制药和化学工业职业感兴趣的学生提供培训。

The discovery and development of new chemical reactions are major foci of research activity in organic chemistry. The reactions and classes of reactions which have found the broadest applicability in organic chemistry are those that address the issues of regio-, stereo- and enantiocontrol and are compatible with a variety of functional groups. Reactions which form multiple bonds, rings and/or stereocenters are particularly important tools for the efficient assembly of complex molecular structures. The long-term objective of our research program is to develop novel synthetic methodologies for the construction of different ring systems, including: nitrogen-containing heterocyclic compounds, spirocyclic compounds, attached-ring compounds and polycyclic compounds. These ring systems are present in many biologically important natural products, which have found use in anti-HIV, anticancer, antiviral and antiretroviral researches. Synthetic methods which allow for the rapid construction of these ring systems with high regio-, stereo- and enantioselectivities would be very useful. Metal-catalyzed reactions are of particular interest due to their ability to control the regio-, stereo- and enantioselectitivities by fine-tuning of the metal and surrounding ligands. The use of transition metals in organic synthesis has increased dramatically in the last two decades. Transition metal catalysts provide new opportunities for highly selective reactions that are not achievable by traditional synthetic methods. We will investigate: (i) Ru-catalyzed [2+2] cycloadditions between an alkene and an alkyne; (ii) Ru-catalyzed [3+2] and [3+3] cycloadditions of aziridines; (iii) Metal-mediated reactions of cyclopropanated bicyclic alkenes; and (iv) Synthesis of novel chiral helical organic structures/polymers. During the studies described herein towards the long-term goal, several short-term goals will be accomplished. These short-term objectives include: the development of novel metal-catalyzed reactions, studies on various aspects of these metal-catalyzed reactions, including addressing the questions of reactivity, regio-, stereo- and enantioselectivities, investigation of intramolecular and asymmetric versions of these reactions, and the development of novel metal catalysts and ligands.  This research program is important not only in science development but also provides the training for students interested in careers in pharmaceutical and chemical industries.