The rate-determining step in the rhodium-Xantphos-catalyzed hydroformylation of 1-octene

The rate-determining step in the hydroformylation of 1-octene, catalysed by the rhodium-Xantphos catalyst system, was determined by using a combination of experimentally determined H-1/H-2 and C-12/C-13 kinetic isotope effects and a theoretical approach. From the rates of hydroformylation and deuterioformylation, a small H-1/H-2 isotope effect of 1.2 was determined for the hydride moiety of the rhodium catalyst. C-12/C-13 isotope effects of 1.012(1) and 1.012(3) for the a-carbon and beta-carbon atoms of 1-octene were determined, respectively. Both quantum mechanics/molecular mechanics (QM/MM) and full quantum mechanics calculations were carried out on the key catalytic steps, for "real-world" ligand systems, to clarify whether alkene coordination or hydride migration is the rate-determining step. Our calculations (21.4 kcal mol(-1)) quantitatively reproduce the experimental energy barrier for CO dissociation (20.1 kcal mol(-1)) starting at the (bisphosphane)RhH(CO)(2) resting state. The barrier for hydride migration lies 3.8 kcal mol(-1) higher than the barrier for CO dissociation (experimentally determined trend similar to 3 kcal mol(-1)). The computed H-1/H-2 and C-12/C-13 kinetic isotope effects corroborate the results of the energy analysis.