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

Newman-Stonebraker, Samuel H; Smith, Sleight R; Borowski, Julia E; Peters, Ellyn; Gensch, Tobias; Johnson, Heather C; Sigman, Matthew S; Doyle, Abigail G · Science · 2021

basic_science · Level V

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Abstract

Chemists often use statistical analysis of reaction data with molecular descriptors to identify structure-reactivity 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 [%<i>V</i><sub>bur</sub> (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 %<i>V</i><sub>bur</sub> (min) is a physically meaningful and predictive representation of ligand structure in catalysis.