Origin of enantioselection in chiral alcohol oxidation catalyzed by Pd[(-)-sparteine]Cl₂

A kinetic investigation into the origin of enantioselectivity for the Pd[(-)-sparteine]Cl₂-catalyzed aerobic oxidative kinetic resolution (OKR) is reported. A mechanism to account for a newly discovered chloride dissociation from Pd[(-)-sparteine]Cl₂ prior to alcohol binding is proposed. The mechanism includes (1) chloride dissociation from Pd[(-)-sparteine]Cl₂ to form cationic Pd(-)-sparteine]Cl, (2) alcohol binding, (3) deprotonation of Pd-bound alcohol to form a Pd-alkoxide, and (4) β-hydride elimination of Pd-alkoxide to form ketone product and a Pd-hydride. Utilizing the addition of (-)-sparteine HCl to control the [Cl ^-] and [H⁺] and the resulting derived rate law, the key microscopic kinetic and thermodynamic constants were extracted for each enantiomer of sec-phenethyl alcohol. These constants allow for the successful simulation of the oxidation rate in the presence of exogenous (-)-sparteine HCl. A rate law for oxidation of the racemic alcohol was derived that allows for the successful prediction of the experimentally measured k_rel values when using the extracted constants. Besides a factor of 10 difference between the relative rates of β-hydride elimination for the enantiomers, the main enhancement in enantiodetermination results from a concentration effect of (-)-sparteine HCl and the relative rates of reprotonation of the diastereomeric Pd-alkoxides.