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 krel 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.
American Chemical Society
Mueller, J. A., Cowell, A., Chandler, B. D., & Sigman, M. S. (2005). Origin of enantioselection in chiral alcohol oxidation catalyzed by pd[(–)-sparteine]Cl2. Journal of the American Chemical Society, 127(42), 14817-14824. https://doi.org/10.1021/ja053195p
Journal of the American Chemical Society