Rhodium dihydride complexes as models for the theoretical analysis of enantioselective hydrogenation reactions

Abstract

A combination of molecular mechanics methods and extended Hückel calculations has been applied in order to have access to the more stable complexes expected to be involved as catalytic intermediates in the enantioselective hydrogenation of ketopantolactone (KPL) using chiral aminophosphine-phosphinite (AMPP) chlororhodium complexes. The product selectivity has been deduced from correlations between the prevailing configuration of the hydrogenated derivatives and the energetics of competing diastereomeric dihydride complexes of formula [RhCl(H) 2(AMPP)(KPL)] with the assumption that the enantioselectivity is controlled by the relative energies of such intermediates. The calculations have been obtained from the application of sequential and exhaustive search methodologies. The procedure has been applied to complexes bearing the aminophosphine-phosphinites ( S)-Cp,Cp-ProNOP ( IV) and ( S)-Ph,Cp-ProNOP ( V) and bis(aminophosphanes) derived from 2-(anilinomethyl)pyrrolidine ( VI– IX). The latter induce a reversal of configuration of the major enantiomer of the hydrogenation product when varying specific substituents at the phosphorus atoms. Computations were carried out also for complexes bearing the two enantiomers ( S)- and ( R)-Ph,Cp-isoAlaNOP. The lowest energy complexes present enantiomeric structures. A novel insight into the local reactivity of the intermediates has been gained from determining the first migrating hydride according to the superdelocalizability parameter calculated for all isomers. Thus, the configurations of pantolactone arising from the alkoxyrhodium species obtained when assuming a nucleophilic attack of one of the hydrides to the carbonyl group of the ketone has been defined and are in total agreement with the experimental data.