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

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.