Univariate classification of phosphine ligation state and reactivity in cross-coupling catalysis

Chemists often use statistical analysis of reaction data with molecular descriptors to identify structurere-activity relationships, which can enable prediction and mechanistic understanding. In this study, we developed a broadly applicable and quantitative classification workflow that identifies reactivity cliffs in 11 Ni- and Pd-catalyzed cross-coupling datasets using monodentate phosphine ligands. A distinctive ligand steric descriptor, minimum percent buried volume [%V-bur (min)], is found to divide these datasets into active and inactive regions at a similar threshold value. Organometallic studies demonstrate that this threshold corresponds to the binary outcome of bisligated versus monoligated metal and that %V-bur (min) is a physically meaningful and predictive representation of ligand structure in catalysis.

Automated summary

In this study, a classification workflow using monodentate phosphine ligands was developed to identify reactivity cliffs in 11 Ni- and Pd-catalyzed cross-coupling datasets. The minimum percent buried volume descriptor was found to be a physically meaningful and predictive representation of ligand structure in catalysis.