Enhanced Homogeneous Iridium Complexes for Extensive Application in Isotope Labelling Processes and as New Catalysts in Wider Organic Synthetic Proced

过渡金属介导的氢同位素交换（HIE）是一种越来越重要的技术，其应用范围涵盖有机合成的各个方面。对于药物化学家来说，重要的是，这种直接和灵活的标记过程现在代表了将示踪剂快速有效地掺入候选药物中的核心工具，使各种代谢，稳定性和毒性研究能够在药物设计过程中更早地进行。在这方面，克尔实验室最近建立的铱物种已经成为同位素标记化学中最活跃的物种之一。在应用我们开发的催化剂对广泛的芳香族和非芳香族不饱和体系进行高效标记后，我们还开始了对更具挑战性的底物类别标记的初步研究，并探索了我们的催化剂在更广泛意义上的C-H活化的用途。该工作计划的总体目标涉及继续探索直接，灵活，以及在极其温和的反应条件下使用专门开发的有机过渡金属催化剂的C-H活化的选择性手段。作为该项目的一部分，将设计和制备一系列新的铱催化剂，调整其空间和电子参数，以应用于C-H活化和交换过程。这些配合物的设计将基于对标记过程的新的、具有挑战性的底物的需求，以及该催化剂家族的新兴更广泛的应用。一般底物结构类和指导官能团将根据其在药物设计和合成环境中的相关性进行选择和指导。相对于EPSRC组合，该计划的主要目标与催化，化学反应动力学和机理以及合成有机化学的研究领域保持一致，并将在医疗保健技术，物理科学，制造未来。

Transition metal-mediated hydrogen isotope exchange (HIE) is a technique of increasing importance, with a range of applications spanning all aspects of organic synthesis. Importantly for medicinal chemists, such direct and flexible labelling processes now represent a central tool for the fast and efficient incorporation of a tracer into drug candidates, enabling various metabolic, stability, and toxicity studies to be performed earlier in the drug design process. In this regard, recently established iridium species from the Kerr laboratories have emerged to become some of the most active species in isotopic labelling chemistry. Having applied our developed catalysts to enable the highly efficient labelling of a broad range of both aromatic and non-aromatic unsaturated systems, we have also initiated preliminary investigations into the labelling of more challenging substrate classes as well as probed the use of our catalysts for C-H activation in a wider sense.The overarching aims of this programme of work relate to the continued exploration of direct, flexible, and selective means of C-H activation under extremely mild reaction conditions, using specifically developed organotransition metal catalysts. As part of this project, a series of new iridium catalyst will be designed and prepared with their steric and electronic parameters tuned for application within C-H activation and exchange processes. The design of these complexes will be based on the demands of new, challenging substrates for labelling processes as well as emerging wider applications for this family of catalysts. The general substrate structural classes and directing functional groups will be chosen and guided based on their relevance within the drug design and synthesis setting.In relation to the EPSRC Portfolio, the main objectives of this programme align with and will address the Research Areas of Catalysis, Chemical Reaction Dynamics and Mechanism, and Synthetic Organic Chemistry and as of importance within the Themes of Healthcare Technologies, Physical Sciences, and Manufacturing the Future.