Ligand and solvent selection in challenging catalytic reactions

Abstract

Transition metal-catalysed reactions are often strongly dependent on ligand and selection, among other factors, which makes discovering the ideal metal/ligand/solvent combination demanding. Furthermore, the effect of ligand and solvent choice is often subtle and unpredictable. This perspective describes how two statistical techniques, design of experiments (DoE) and principal component analysis (PCA), can be combined to guide the decision-making process. The general approach to using these techniques is described, and illustrated with a brief worked example on challenging 'borrowing hydrogen' chemistry. The unique combination of DoE and PCA is a useful decision-making tool to support the selection of ligands and solvents for challenging catalytic reactions.

Computational Ligand Descriptors for Catalyst Design

“…124 Ligand maps can be used in their own right to select alternative ligands and set novel designs into context, as demonstrated for fluorophosphines 106 and a range of unusual ligand designs. 97,127 Going beyond a comparison of ligand properties, such maps can also be used to explore the sampling of ligand space by a set of ligands, either, as is the case in this review, driven by commercial and data availability, or for the Design of Experiments (DoE) 56,200 and the identification of areas of ligand space that correspond to favourable catalyst performance, as described by both us 96 and others 200 for LKB-P. 96 Such applications crucially depend on the availability of suitable experimental data. Here, catalyst screening with designed ligand sets, followed by several iterations of data analysis and further screening, are perhaps most promising.…”

The Application of Advanced Design of Experiments for the Efficient Development of Chemical Processes

“…morpholine using 5 mol% IrCp*Cl dimer, 5 mol% potassium carbonate in toluene at 100°C for 4 h showed only trace levels of product (generic reaction in Scheme 3) [20]. The same reaction using Ru(p-cymene)Cl dimer with DPEphos showed 13% conversion after 1 hr and full conversion after 24 hrs.…”

“…Replicate plot showing range in conversion of benzyl alcohol with monodentate ligands after 9 hrs. Figure 7 Coefficient plot from the model for conversion in the DoE investigating monodentate phosphines [20].…”

“…Monodentate ligand map using PC1 and PC2 highlighting the maximum catalyst activity [20]. Figure 10 Monodentate ligand map using PC1 and PC2 highlighting activity for experiments with Ru as catalyst.…”

Experimental and Theoretical Investigation of Distribution Equilibria and Kinetics of Copper(II) Extraction with LIX 84 I and TFA

“…Here the extraction system means the choice of a chelating component, a solvent, its concentration, temperature and pH of solution. Separation of metals by solvent extraction is mainly based on the affinity of metal ions with the extractant and insolubility of the extractant in an aqueous phase (7)(8)(9)(10). Numerous studies have been reported in literature on the experimental and theoretical analyses of copper and other heavy metals with acid extractants (11)(12)(13)(14)(15).…”