Toward an understanding of the high enantioselectivity in the osmium-catalyzed asymmetric dihydroxylation (AD). 1. Kinetics

Article abstract of DOI:10.1021/ja00083a014

A systematic study of the relationship between ligand structure and saturation rate constants (k_c) in the amine-catalyzed osmylation of terminal olefins was carried out with the aim of learning more about the interactions between the reactants (i.e. OsO₄, the ligand, and the olefin) and of establishing the origin of the large rate accelerations 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_eq) for OsO₄ and the test ligands were measured, and the observed trends show that K_eq can be regarded as an approximate measure of the steric hindrance in the vicinity of the ligand-binding site. Interestingly, the binding constants and the saturation rate constants k_c are not correlated, indicating that the observed rate variations are apparently not caused by variations in ground-state energy due to steric interactions. Rather, the rate data can be interpreted in terms of a relative stabilization 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, and this theory is consistent with the fact that flat aromatic substrates give much higher rate constants than aliphatic ones. Further support for this theory was obtained from solvent effect and Hammett studies as well as from X-ray data on osmium glycolate complexes. Phthalazine ligand 1 gives exceptionally high rate constants with aromatic substrates, an effect which can be attributed to the presence of a 'binding pocket', set up by the phthalazine and methoxyquinoline moieties of the ligand, which enables especially good transition-state stabilization for aromatic olefins within the pocket. The enantioselectivity trends were found to parallel the rate trends; therefore, our results allow us to draw conclusions with regard to the mode of chirality transfer in the reaction, leading to a revised mnemonic device.