Ligand Effects on the Regioselectivity of Rhodium-Catalyzed Hydroformylation: Density Functional Calculations Illuminate the Role of Long-Range Noncovalent Interactions

Density functional theory calculations have been performed to gain insight into the origin of ligand effects in rhodium (Rh)-catalyzed hydroformylation of olefins. In particular, the olefin insertion step of the Wilkinson catalytic cycle, which is commonly invoked as the regioselectivity-determining step, has been examined by considering a large variety of density functionals (e.g., B3LYP, M06-L); a range of substrates, including simple terminal (e.g., hexene, octene), heteroatom-containing (e.g., vinyl acetate), and aromatic-substituted (e.g., styrene) alkenes, and different ligand structures (e.g., monodentate PPh3 ligands and bidentate ligands such as DIOP, DIPHOS). The calculations indicate that the M06-L functional reproduces the experimental regioselectivities with a reasonable degree of accuracy, while the commonly employed B3LYP functional fails to do so when the equatorial–equatorial arrangement of phosphine ligands around the Rh center is considered. The different behavior of the two functionals is attributed to the fact that the transition states leading to the Rh–alkyl intermediates along the pathways to isomeric aldehydes are stabilized by the medium-range correlation containing π–π (ligand–ligand) and π–CH (ligand–substrate) interactions that cannot be handled properly by the B3LYP functional due to its inability to describe nonlocal interactions. This conclusion is further validated using the B3LYP functional with Grimme’s empirical dispersion correction term: i.e., B3LYP-D3. The calculations also suggest that transition states leading to the linear Rh–alkyl intermediates are selectively stabilized by these noncovalent interactions, which gives rise to the high regioselectivities. In the cases of heteroatom- or aromatic-substituted olefins, substrate electronic effects determine the regioselectivity; however, these calculations suggest that the π–π and π–CH interactions also make an appreciable contribution. Overall, these computations show that the steric crowding-induced ligand–ligand and ligand–substrate interactions, but not intraligand interactions, influence the regioselectivity in Rh-catalyzed hydroformylation when the phosphine ligands are present in an equatorial–equatorial configuration in the Rh catalyst.