Force Field Development for Ferrocene and the Prediction of Enantioselectivity

Experimentalists commonly explore the use of ferrocene-based chiral ligands in enantioselective catalysis. Being able to computationally predict enantioselectivity for the rhodium-catalyzed hydrogenation of enamides would accelerate experimentalist’s work significantly. To accomplish this feat, force field parameters for ferrocene were optimized using Q2MM. Once the force field was developed, it was combined with a previously developed rhodium force field. Together, the two force fields were tested to predict enantioselectivity in the hydrogenation of enamides.

The force field was tested on several ferrocene derivatives. The energies predicted by the force field and the energies calculated quantum mechanically have shown an R2 of 0.910. This displays the performance of the force field for ferrocene alone. The ferrocene and rhodium force fields were combined and compared to experimental data. The resulting predictions showed initial agreement, however, there could be further improvements toward predicting the enantioselectivity of the rhodium-catalyzed hydrogenation of enamides.