How Accurate is DFT for Iridium-Mediated Chemistry?

Iridium chemistry is versatile and widespread, with superior performance for reaction types such as enantioselective hydrogenation and C–H activation. In order to gain insight into the mechanistic details of such systems, density functional theory (DFT) studies are often employed. But how accurate is DFT for modeling iridium-mediated transformations in solution? We have evaluated how well DFT reproduces the energies and reactivities of 11 iridium-mediated transformations, which were carefully chosen to correspond to elementary steps typically encountered in iridium-catalyzed chemistry (bond formation, isomerization, ligand substitution, and ligand association). Five DFT functionals, B3LYP, PBE, PBE0, M06L, and M11L, were evaluated as-is or in combination with an empirical dispersion correction (D2, D3, or D3BJ), leading to 13 combinations. Different solvent models (IEFPCM and SMD) were evaluated, alongside various correction terms such as big basis set effects, counterpoise corrections, frequency scaling, and different entropy modifications. PBE-D type functionals are clearly superior, with PBE-D2,IEFPCM providing average absolute errors for uncorrected Gibbs free energies of 0.9 kcal/mol for the nine reactions with a constant number of moles (1.2 kcal/mol for all 11 reactions). This provides a straightforward and accurate computational protocol for computing free energies of iridium-mediated transformations in solution. However, because the good results may originate from favorable error cancellations of larger and oppositely signed enthalpy and entropy errors, this protocol is recommended for free energies only.铱化学应用广泛且通用性强，在对映选择性氢化、C-H活化等反应类型中表现优异。为深入探究此类体系的反应机理细节，密度泛函理论（DFT）研究常被采用。然而，DFT用于模拟溶液中铱介导的转化反应时，其准确性究竟如何？本研究评估了DFT对11种铱介导转化反应的能量与反应活性的重现效果；这些反应均经过精心挑选，涵盖了铱催化化学中常见的基元步骤，包括键形成、异构化、配体取代以及配体缔合。本研究对5种DFT泛函（B3LYP、PBE、PBE0、M06L及M11L）分别进行了单独测试，或结合经验色散校正（D2、D3或D3BJ）进行测试，最终得到13种泛函-校正组合。此外，本研究还测试了不同的溶剂化模型（IEFPCM与SMD），并考察了多种校正手段，包括大基组效应修正、均衡校正、频率缩放以及不同的熵修正方案。PBE-D类泛函的表现明显更优，其中PBE-D2结合IEFPCM溶剂化模型的组合，对9个摩尔数恒定的反应的未校正吉布斯自由能的平均绝对误差为0.9 kcal/mol（所有11个反应的平均绝对误差为1.2 kcal/mol）。该结果为模拟溶液中铱介导转化反应的自由能提供了一套简便且精准的计算方案。不过，由于该良好效果可能源于焓与熵的较大反向误差之间的有利抵消，因此该方案仅推荐用于自由能的计算。