Asymmetric catalytic hydrogenation is a reaction of great interest in total organic synthesis and with valuable applications in the pharmaceutical industry. This project will apply and extend recent developments in the state-of-the art for reactive force fields and reactive molecular dynamics (MD) to the simulation of iridium-catalyzed asymmetric hydrogenation reactions recently developed by Pfaltz and co-workers at Basel.
The initial step will be the parameterization of the ReaxFF force field for iridium, based on a library of DFT structures and energies for a variety of conformations and transition structures, based on Pfaltz's asymmetric hydrogenation phosphinooxazoline (PHOX) catalysts. Once the force field is ready, it will be used for running extensive conformational searches using Monte Carlo and molecular dynamics methods, for a variety of ligands and substrates; the most promising structures will be refined using more accurate DFT methods. This will be followed by reactive MD simulations of the react ion process itself, with inclusion of solvent effects. The result will be a detailed understanding of the reaction mechanism, and will ultimately facilitate the screening of new ligands and substrates for the hydrogenation reaction.
The project will involve a close collaboration with Prof. Pfaltz, who will provide additional experimental data for calibrating and testing the methods, and who can test our predictions.
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