Advanced computation of enthalpies for a range of hydroformylation reactions with a predictive power to match experiments

While hydroformylation is a central homogeneous catalytic industrial processes, we find a relatively large (17 kcal/mol) scatter of DFT reaction enthalpies with a range of widely-employed DFT methods, unexpected in organic chemistry. Thus, we obtained gold standard hydroformylation enthalpies for a large variety of substrates exploiting the local natural orbital method. The corresponding hydroformylation enthalpies of ethylene and propylene agree with the experiments within a few tenth of a kcal/mol. This predictive power enabled the study of nuanced trends in the hydroformylation for a wide range of aliphatic and aromatic substrates as a function of chain elongation, branching, and substituent effects. • Large DFT scatter for a key catalytic industrial process: hydroformylation. • Gold standard CCSD(T) reaction enthalpies excellently match the experiments. • Local natural orbital CCSD(T) enabled predictive enthalpies for the entire study. • Explored nuanced elongation, branching, and substituent effects for many substrates.