Origin of enantioselective hydrogenation of ketones by RuH2(diphosphine)(diamine) catalysts:: A theoretical study

The origin of the enantioselective hydrogenation of acetophenone by the (S-BINAP)RuH2(S,S-cydn) (cydn = 1,2-cyclohexanediamine) catalyst has been investigated by a theoretical DFT study. Computations for hydrogenation of acetone and acetophenone by the model system RuH2(PH3)(2)(en) (en = 1,2 ethylenediamine) confirm the previously proposed mechanism. These calculations show that reaction involving two of the four NH protons, which adopt a pseudoaxial orientation in the catalyst, is favored by ca. 2 kcal/mol over reaction involving the other two pseudoequatorial protons. The results for the model system reacting with acetophenone show that approach of the ketone with the phenyl group oriented away from the phosphine ligands ("out" approach) is favored by weak hydrogen bonding between the ketone phenyl group and one of the ruthenium-coordinated NH2 groups. In the full (S-BINAP)RuH2(S,S-cydn) catalyst, steric interactions also contribute to establishing the R selectivity in hydrogenation, and the magnitude of this selectivity is reproduced semiquantitatively. Study of the mismatched (S-BINAP)RuH2(R,R-cydn) also semiquantitatively reproduces the much reduced R selectivity of this catalyst and contributes to rationalizing it. Transfer of the less favored pseudoequatorial NH2 proton plays a key role in this case. It is shown that the results can also be used to discuss selectivity in other related systems.