Catalytic asymmetric hydrogenation of ketopantolactone by rhodium(I) aminophosphine-phosphinite complexes. A theoretical analysis by molecular mechanics and extended Hückel calculations

A combination of molecular mechanics methods and extended Hückel calculations has been used as a tool in an attempt to rationalize experimental results obtained during catalytic asymmetric hydrogenation of dihydro-4,4-dimethyl-2,3-furandione (ketopantolactone, KPL) using chiral aminophosphine-phosphinite (AMPP) chlororhodium complexes. This study is based upon the hypothesis that the enantioselectivity of prochiral ketone hydrogenation is controlled by the relative energies of the different diastereomeric intermediates obtained from oxidative addition of hydrogen and ketone coordination to the chiral chlororhodium complexes. Thus, a series of possible six-coordinate structures of general formula [RhCl(H)₂(AMPP)(KPL)] has been generated for three AMPP ligands, (S)-Ph,Cp-isoAlaNOP (I), (R)-Ph,Cp-isoAlaNOP (II) and (S)-Cp,Cp-isoAlaNOP (III), and each octahedral dihydrido complex has been optimized first by molecular mechanics (steric energy) and then by extended Hückel calculations (total energy). For the most stable complex (lowest total energy) in each series, the configuration of pantolactone arising from reductive elimination was determined assuming nucleophilic attack of the preferred H atom to the carbonyl C atom of KPL. This procedure has been shown to reproduce the enantioselectivities observed with ligands I-III. Namely, this methodology suggests the inversion in the configuration of the prevailing enantiomer of pantolactone upon using system I instead of system III, in perfect agreement with the experiments. The most stable six-coordinate intermediates arising from the latter systems are both cis-dihydrido structures differing from each other from the respective localization of hydride and chloride ligands at the apical sites, and from the conformation adopted by the seven-membered metallacycle. Computations conducted on systems I and II also indicate the inversion of configuration of the produced pantolactone, as expected from ligands of opposite absolute configuration. For systems I and II, the most stable cis-dihydrido octahedral complexes are shown to be almost antipodal structures, only differing from each other from the conformation of the chiral backbone. © CNRS-Gauthier-Villars.