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进行定向间位C-H活化的新方法，这些催化剂类是通过5元或6元环化络合物进行邻位C-H活化的最新技术。重要的是，在罕见的间位-C-H活化的文献报道中，在这种情况下所需的较大的金属乳糖通过采用共价结合至C-H活化底物的延伸的导向基团来获得，具有安装和切割以及底物限制的相关缺点。相比之下，我们提出，一个元指导的“介质”分子，它不可逆地结合到一个标准的铱催化剂，并可逆地共同的指导基团，将呈现显着的优势，现有的元-C-H活化方法。在Strathclyde进行的DFT计算表明，带有刘易斯碱性和刘易斯酸性基团的简单小聚芳族分子将与铱催化剂强烈结合，进而与所需的底物结合以促进间-C-H活化。拟议的工作结合了双方的专业知识，以充分探索适合这种新方法的间-C-H活化介质和底物类型，以提供广泛的功能化化学支架，这将是特别感兴趣的制药工业，以及更广泛的制备社区。作为该总体工作项目的一部分，并且作为方法学研究的出发点，新的和优化的方法将被应用于具有医学重要性和当前合成兴趣的靶分子系统的合成，以及同位素标记的，计算研究将进一步补充本研究计划中的准备培训，并为参与的学生提供一个良好的，全面的研究能力组合。在后者方面，定量DFT计算方法将提供更深入的理解反应机理和驱动未来的间-C-H活化介体和催化剂的设计基于bindingenergy.The主要EPSRC的研究领域是催化，化学反应动力学和机制，和合成有机化学。

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.