How Accurate is DFT for Iridium-Mediated Chemistry?

Abstract

Iridium chemistry is versatile and widespread, with\nsuperior performance for reaction types such as enantioselective\nhydrogenation and C−H activation. In order to gain insight into the\nmechanistic details of such systems, density functional theory (DFT)\nstudies are often employed. But how accurate is DFT for modeling\niridium-mediated transformations in solution? We have evaluated how\nwell DFT reproduces the energies and reactivities of 11 iridium-mediated\ntransformations, which were carefully chosen to correspond to\nelementary steps typically encountered in iridium-catalyzed chemistry\n(bond formation, isomerization, ligand substitution, and ligand association). Five DFT functionals, B3LYP, PBE, PBE0, M06L,\nand M11L, were evaluated as-is or in combination with an empirical dispersion correction (D2, D3, or D3BJ), leading to 13\ncombinations. Different solvent models (IEFPCM and SMD) were evaluated, alongside various correction terms such as big basis\nset effects, counterpoise corrections, frequency scaling, and different entropy modifications. PBE-D type functionals are clearly\nsuperior, with PBE-D2,IEFPCM providing average absolute errors for uncorrected Gibbs free energies of 0.9 kcal/mol for the\nnine reactions with a constant number of moles (1.2 kcal/mol for all 11 reactions). This provides a straightforward and accurate\ncomputational protocol for computing free energies of iridium-mediated transformations in solution. However, because the good\nresults may originate from favorable error cancellations of larger and oppositely signed enthalpy and entropy errors, this protocol\nis recommended for free energies only.