New Metal-Catalysed Methods for C-H Activation Processes

该合作项目将探索使用Strathclyde开发的铱基催化剂类定向活化元碳氢化合物的新方法，这些催化剂类是通过5-或6元环金属化配合物进行邻位碳氢化合物活化的最新技术。重要的是，在罕见的meta-C-H活化的文献报告中，这种情况下所需的更大的金属环是通过使用一个扩展的导向基团来获得的，它与C-H活化底物共价结合，具有安装和切割的相关缺点，以及底物限制。相比之下，我们提出了一种与标准铱催化剂不可逆结合，并与普通定向基团可逆结合的元定向“中介”分子，将比现有的元碳氢活化方法具有显着优势。Strathclyde进行的DFT计算表明，带有Lewis碱性和Lewis酸性基团的简单小多芳分子将与铱催化剂强烈结合，进而与所需的底物结合，促进meta-C-H活化。拟议的工作结合了双方的专业知识，以充分探索适用于这种新方法的meta-C-H活化介质和底物类型，以提供广泛的功能化化学支架，这将对制药行业以及更广泛的制备界特别感兴趣。作为这个整体项目工作的一部分，并且作为对方法学研究的背离，新的和优化的方法将应用于具有医学重要性和当前合成兴趣的目标分子系统的合成，以及同位素标记的后期候选型分子。计算研究将进一步补充本研究计划中的预备训练，并为参与研究的学生提供全面的研究能力组合。在这方面，定量DFT计算方法将提供对反应机理的更深入理解，并推动未来基于结合能的meta-C-H活化介质和催化剂的设计。EPSRC的主要研究领域是催化、化学反应动力学和机理以及合成有机化学。

This collaborative project will explore new methods for directed meta-C-H activation using iridium-based catalyst classes developed at Strathclyde, which are state-of-the-art in ortho-C-H activation via 5- or 6-membered cyclometallated complexes. Importantly, in literature reports of the rarer meta-C-H activation, the larger metallacycle required in this case is accessed by employing an extended directing group, covalently bound to the C-H activation substrate, with associated drawbacks of installation and cleavage, and substrate limitation. In contrast, we propose that a meta-directing "mediator" molecule, which binds irreversibly to a standard iridium catalyst, and reversibly to common directing groups, would present significant advantages over existing meta-C-H activation methodology. DFT calculations performed at Strathclyde indicate that simple small polyaromatic molecules bearing Lewis basic and Lewis acidic groups will bind strongly to the iridium catalyst and, in turn, engage the required substrate to facilitate meta-C-H activation.The proposed work combines the expertise of both partners to fully explore the meta-C-H activation mediators and substrate types amenable to this new methodology, to deliver a wide range of functionalised chemical scaffolds that will be of particular interest to the pharmaceutical industry, as well as to the wider preparative community. As part of this overall project of work, and as a departure from methodological studies, the new and optimised methods will be applied to the synthesis of target molecular systems of medicinal importance and current synthetic interest, as well as to isotopically-labelled, late-stage candidate-type molecules.Computational studies will further complement the preparative training within this research programme and provide the engaged student with a well-rounded portfolio of research abilities. In this latter regard, quantitative DFT computational methods will provide a deeper understanding of reaction mechanism and drive the design of future meta-C-H activation mediators and catalysts based on binding energies.The main EPSRC research areas addressed are Catalysis, Chemical Reaction Dynamics and Mechanism, and Synthetic Organic Chemistry.