New Metal-Catalysed Methods for C-H Activation Processes

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.