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Descriptor-led Screening of NHC Ligands

C. Willans (University of Leeds), B. Nguyen (University of Leeds), N. Fey (University of Bristol) & S. Tyler (CatSci Ltd)

As part of the support for the application of statistical methods to chemistry research, the network supported a new collaboration between early career researchers Dr Charlotte Willans and Dr Bao Nguyen (University of Leeds) with Dr Natalie Fey (Bristol) and Dr Simon Tyler (CatSci Ltd, an SME based in Cardiff). The Leeds team had recently reported a novel approach for the electrochemical synthesis of copper complexes with modular bidentate ligands involving at least one N-heterocyclic carbene group in a flow cell. Developing copper complexes for catalysis is of direct relevance to industry, as it offers the potential to move away from costly and toxic precious metals such as palladium and rhodium that are a dwindling resource. Controlling the reactivity at the metal centre, however, is one of the major challenges within this area of research, with ligand design of central importance to achieving this.

The funded project supported the mapping of the synthetically-accessible ligand space by statistical analysis of calculated property descriptors based on prior work at Bristol, allowing ligand modifications to be explored in silico and, thanks to generous data-sharing by CatSci, comparison with other ligand classes similarly characterised. This allowed focussed synthesis and screening of the complexes most likely to show catalytic activity in a copper catalysed transformation, yielding promising initial results for further analysis and screening. The Leeds team estimate that this combination of computational chemistry and statistical analysis has reduced the number of experiments needed by a factor of 4 to date and the project team intends to continue their collaboration, applying more extensive multivariate data analysis to the interpretation and prediction of experimental outcomes for these ligands. This will significantly reduce the number of further experiments required to arrive at the most efficient ligand-metal combination for a particular process.