The Sharpless enantioselective dihydroxylation of terminal olefins by OsO4 using the catalytic chiral ligand (DHQD)(2)PYDZ (1) has been shown to follow Michaelis-Menten kinetics, demonstrating fast reversible formation of a complex of olefin, OsO4, and 1 prior to the rate-limiting conversion to the Os(VI) ester intermediate. There is a good correlation between the observed binding constants, K-m, and the degree of enantioselectivity of the dihydroxylation indicating that van der Waals binding of the substrate by 1 . OsO4 is important to enantioselective rate enhancement. Inhibition of the oxidation by various compounds has been demonstrated kinetically using Dixon analysis of the data, and K-i values have been determined and correlated with inhibitor structure. The strongest inhibitors are compounds with the ability to coordinate to Os(VIII) of the 1 . OsO4 complex while simultaneously binding in the pocket formed by the aromatic subunits of the ligand. Parallelism between K-m and K-i values and their relationship with structure indicate similar binding in the substrate and inhibitor complexes with 1 . OsO4. The kinetic, structural, and stereochemical data, as summarized in Tables 1 and 3, support a mechanism for the enantioselective dihydroxylation which involves (1) rapid, reversible formation of an olefin-Os(VIII) pi-d complex and (2) slow rearrangement to the [3 + 2] cycloaddition transition state which is exemplified in Figure 12. In terms of this mechanism, enantioselective acceleration is the result of two factors : (1) enzyme-substrate-like complexation which brings the reactants together in the appropriate geometry for further conversion to the predominating enantiomer, thereby providing a high effective reactant concentration (entropic effect) and (2) a driving force in the next step due to relief of eclipsing strain about the OsO4-N bond which lowers the activation enthalpy. Taken together with existing data on the Sharpless enantioselective dihydroxylation, the present results strongly support the [3 + 2] cycloaddition pathway and the U-shaped binding pocket which was advanced earlier.