New Metal-Catalysed Methods for C-H Activation Processes

用于 C-H 活化过程的新金属催化方法

• 批准号: 2740848
• 金额: --
• 依托单位: University of Strathclyde
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2740848
• 关键词: New; Metal; Catalysed; Methods; Activation

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.

这一合作项目将探索使用Strathclyde开发的Ir基催化剂类别直接活化偏碳氢的新方法，这些催化剂类别是通过五元或六元环金属络合物进行邻位碳-氢活化的最先进方法。重要的是，在关于较罕见的meta-C-H活化的文献报道中，在这种情况下所需的较大的金属循环是通过采用扩展的定向基团来获得的，该导向基团共价结合到C-H活化底物上，具有安装和切割以及底物限制的相关缺点。相反，我们认为，与现有的Meta-C-H活化方法相比，与标准的Ir催化剂不可逆地结合并可逆地与共同的定向基团结合的间位导向的“介体”分子将显示出显著的优势。在Strathclyde进行的密度泛函计算表明，含有Lewis碱性基团和Lewis酸性基团的简单多芳香族小分子将强烈结合到Ir催化剂上，进而与所需的底物结合以促进meta-C-H的活化。拟议的工作结合了两个合作伙伴的专业知识，全面探索了适用于这一新方法的meta-C-H活化介体和底物类型，以提供制药业以及更广泛的制备社区特别感兴趣的各种功能化化学支架。作为这项整体工作的一部分，作为方法学研究的一部分，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目标分子系统的合成，以及同位素标记的晚期候选型分子。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计算方法将加深对反应机理的理解，并推动基于结合能的未来偏碳氢活化介体和催化剂的设计。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。