A Combined QM/MM Method for the Determination of Regioselectivities in Rhodium-Catalyzed Hydroformylation

Hydroformylation regioselectivities of rhodium−phosphine ligand systems are calculated according to a perspicuous formula that connects the regioselectivity of one phosphine coordination mode to the relative energies of the corresponding transition states of olefin insertion. If only one coordination mode is preferred which may be fulfilled by bidentate chelating ligands the formula quantifies the experimentally observed regioselectivities. To determine the relative transition-state energies, a combined QM/MM method with frozen reaction centers was applied and is discussed in detail. Tendencies in regioselectivites of four systems with the bidentate chelating ligands DIPHOS 4, BISBI 5, NAPHOS 6, and the monodentate reference ligand triphenylphosphine (TPP) could be reproduced for the first time. As has been demonstrated previously, our method is also useful for the explanation of hydroformylation stereoselectivities.