TOWARD AN UNDERSTANDING OF THE HIGH ENANTIOSELECTIVITY IN THE OSMIUM-CATALYZED ASYMMETRIC DIHYDROZYLATION (AD) .1. KINETICS

A systematic study of the relationship between ligand structure and sa turation rate constants (k(c)) in the amine-catalyzed osmylation of te rminal olefins was carried out with the aim of learning ning more abou t the interactions between the reactants (i.e. OsO4, the ligand, and t hee olefin) and of establishing the origin of the large rate accelerat ions observed with cinchona alkaloid ligands. The results reveal that the saturation rate constants are influenced principally by the nature of the O9 substituent of the cinchona analogs studied, especially if aromatic substrates are used. Additionally, the binding constants (K-e q4 and the test ligands were measured, and the observed trends show th at K-eq can be regarded as an approximate measure of the steric hindra nce in the vicinity of the ligand-binding site. Interestingly, the bin ding constants and the saturation rate constants k(c) are not correlat ed, indicating that the observed rate variations are apparently not ca used by variations in ground-state energy due to steric inters,ctions. Rather, the rate data can be interpreted in terms of a relative stabi lization of the transition state of the reaction in the case of 'fast' ligands. A transition-state stabilization may result from stacking of the olefin and ligand substituents:uents, and this theory is consiste nt with the fact that flat aromatic substrates give much higher rate c onstants than aliphatic ones. Further support for this theory was obta ined from solvent effect and Hammett studies as well as from X-ray dat a on osmium glycolate complexes. Phthalazine ligand 1 gives exceptiona lly high rate constants with aromatic substrates, an effect which can be attributed to the presence of a 'binding pocket', set up by the pht halazine and methoxyquinoline moieties of the ligand, which enables es pecially good transition-state stabilization for aromatic olefins with in the packet. The enantioselectivity trends were found to parallel th e rate trends, therefore, our results allow us to draw conclusions wit h regard to the mode of chirality transfer in the reaction, leading to a revised mnemonic device.