Ligand Selection

Using over 25 computational properties of monodentate phosphine ligands and over 30 computational properties for bidentate phosphine ligands the creation of two databases of over 400 diverse ligands have each been amassed. The 400 ligands and >25 properties have been reduced to 3 principal components (principal properties) which are approximated to sigma and pi donation.

For a given catalytic reaction a suitable subset of ligands can be chosen to investigate the desired design space. The subset can be diverse including ligands across the whole map or restricted to, for instance, consideration of only the electron rich ligands for a given reaction. The selection of ligands typically begins with 9 ligands, but 5 or 17 ligands selections are also available. Ligands can be chosen separately from the monodentate and the bidentate maps or simultaneously from a hybrid map. The ligands are investigated in a Design of Experiments looking at all other appropriate factors simultaneously.

The first set of experiments will focus the selection of ligands into a region, typically ¼ or less of region of space from the original selection while also reducing the number of potential factors to consider in subsequent experimentation. The factors are eliminated as they have been shown to be unimportant for the specific reaction. In general the subsequent selection of 8 to 12 additional ligands will provide a detailed understanding of the requirements the reaction has on the ligand and clearly identify the sweet spot for the reaction. This selection process will identify a suitable ligand, either directly from the screening results or from the identified sweet spot for the specific reaction.

The use of further data modelling can be undertaken to identify the specific ligand properties which are important for the reaction under investigation. Through the development of a model the suitability of all ligands in the database can be predicted, within the confines of the conditions investigated and the main reaction mechanism. The use of ligand properties enables the mapping of ligand space. The selection of a small representative set of ligands enables the rapid focus of effort to suitable ligands in the sweet spot for the reaction enabling informed decision making around ligand choice.

Paul Murray Catalysis Consulting will provide our clients with:

• The selection of ligands from appropriate PCA maps to enable the efficient understanding of the requirements of the catalyst for an efficient reaction.
• The selection of appropriate designs, additional factors and ranges for their experimental investigation.
• The analysis and interpretation of the experimental data.
• Partial Least Squares (PLS) modelling to understand the properties of materials that play a significant role in optimum reaction development and prediction of suitability of additional materials for the chosen reaction.
• The prediction of suitable alternative ligands to meet the needs of the client.