Informatics-driven Catalyst Design towards Enhanced Iridum(I) Catalysts for Radiolabelling Applications

The isotopic labelling of molecules is crucial to ADMET studies within the pharmaceutical industry, and for the elucidation of reaction mechanisms. Foremost amongst the methods for isotope labelling is hydrogen isotope exchange (HIE). In terms of Csp2-H HIE directed by Lewis basic groups, we have developed an extensive range of iridium(I) NHC/phosphine complexes, which accommodate a broad range of directing groups and demonstrate excellent levels of deuterium and tritium incorporation.
In an extension of this work, we have applied our emerging catalysts to directed C-H activation and intramolecular C-C bond formation. More specifically, using the carboxylate directing group in a range of benzoic acid derivatives, C-H activation and alkene arylation, using our specifically designed NHC-phosphine chelated complex, has facilitated the synthesis of bi- and tricycles featuring tertiary and quaternary benzylic stereocentres.
The objectives of this project will be to:
- Further optimise this C-C bond forming process, and expand the substrate scope;
- Employ computational techniques and ligand parameterisation to enhance our understanding of the system and guide catalyst design; and
- Extend and combine these data driven approaches to related C-C, C-X and C-D bond formation processes.
Overall, this approach combines preparative studies with kinetics, mechanistic studies, parameterisation, and a broad range of computational techniques, to allow a data-driven approach to novel catalyst design and reaction optimisation.