Rationalizing the Stereoselectivity of Osmium Tetroxide Asymmetric Dihydroxylations with Transition State Modeling Using Quantum Mechanics-Guided Molecular Mechanics

A new transition state force field has been developed for the AD reaction, purely from quantum mechanical reference data. A new methodology was used for converting quantum mechanical normal modes into a form suitable for parametrization. The force field has been thoroughly validated by comparison to structural and energetic data, and by prediction of experimental enantioselectivities. Excellent agreement was observed, frequently within a few percent of the experimental enantioselectivity. The interactions responsible for enantioselectivity have been identified and compared to the Sharpless and Corey models.