Continuous chirality measure in reaction pathways of ruthenium-catalyzed transfer hydrogenation of ketones

Here we report theoretical studies on the ruthenium-catalyzed reduction of acetophenone (and 2-hexanone) with the intent of understanding the relative roles of catalyst and substrate along the reaction path. Overall ten reaction pathways are examined. The first eight are for acetophenone: they arise from the presence of two catalysts, with the more enantioselective one labeled 1, and the poorer one labeled 2, multiplied by the two configurations that the metal center of the catalysts can assume, multiplied by the two approaches, Re- and Si-side, of the substrate to the catalyst. Two pathways are examined for 2-hexanone and entail the two approaches to the ketone of the more effective catalyst. Density functional theory calculations provide structures of the minima and transition states, which subsequently have been assessed with the "continuous chirality measure" model developed by Avnir and collaborators. The picture that emerges is that the asymmetric induction is due to the interplay between the organometallic system and the organic substrate; This is effective only for catalyst 1, which can interact effectively with acetophenone along only one in four of the reaction pathways, but not for 2 for which two out of four pathways are opened. For the hydrogenation of 2-hexanone, the same catalyst 1 cannot produce enantiomeric excesses because the conformation of the substrate in the transition state induced by the catalyst has a relative low chirality.