Cross-coupling catalysts for inactive substrates from a three-dimensional virtual screening

We report a three-dimensional virtual screening method to search a chemical space formed of ligands from the tmQMg-L library for Pd Suzuki–Miyaura cross-coupling catalysts that has future potential to be applied to a broader range of catalytic reactions. It utilises three criteria related to important steps in the catalytic cycle of the reaction to distinguish between candidate Pd(0) species, namely the oxidative addition and reductive elimination barriers and the binding energy of acetonitrile. This method ultimately leads to identifying a region of chemical space that provides a good compromise between the three search criteria, highlighting a smaller set of ligands that merits further exploration. After the screening, several candidates are confirmed as catalysts based on literature searches. We also found Pd(0) complexes with high potential in catalytic cross-couplings involving less reactive substrates that require the oxidative addition of strong C–O bonds.