One of the holy grails of computational chemistry is to achieve the status of a truly predictive science, not just a convenient tool for understanding the underlying causes of observed reactivity. We are not yet at a stage where we can take a given reaction mix and, by modeling, predict the products, if any. However, given a known reaction, we are now at the stage where we can begin to predict the selectivity that will be observed. In the area of asymmetric catalysis, we have earlier shown that the enantioselectivity can be calculated with high accuracy using transition state force fields derived by the Q2MM method. The force fields are derived solely from QM data for transition states of the relevant step for small model systems, and used to locate the full ensemble of competing diastereomeric transition states. Final Boltzmann-weighted selectivities generally match experimental values to within 2-3 kJ/mol.<br/><br/>We have now taken the next step, and incorporated Q2MM force fields into an automated screening tool, usable by non-experts. The tool will merge a given substrate with a metal center for the desired reaction, combine it with a library of ligands, perform extended conformational searches, and finally collate the data into a list of ligands with expected enantioselectivities for each. Testing using a published force field for Rh-catalyzed enamide hydrogenation demonstrates significant enrichment, despite the substrates being well outside the original parameterization scope.

Virtual screening of asymmetric selectivity in catalysis

252nd National Meeting (2016)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.