Computer-assisted catalyst development via automated modelling of conformationally complex molecules: application to...

Simulation of conformationally complicated molecules requires multiple levels of theory to obtain accurate thermodynamics, requiring significant researcher time to implement. We automate this workflow using all open-source code (XTBDFT) and apply it toward a practical challenge: diphosphinoamine (PNP) ligands used for ethylene tetramerization catalysis may isomerize (with deleterious effects) to iminobisphosphines (PPNs), and a computational method to evaluate PNP ligand candidates would save significant experimental effort. We use XTBDFT to calculate the thermodynamic stability of a wide range of conformationally complex PNP ligands against isomeriation to PPN (ΔG_PPN), and establish a strong correlation between ΔG_PPN and catalyst performance. Finally, we apply our method to screen novel PNP candidates, saving significant time by ruling out candidates with non-trivial synthetic routes and poor expected catalytic performance.