Thermodynamic-Kinetic Comparison of Palladium(II)-Mediated Alcohol and Hydroquinone Oxidation

Palladium(II) catalysts promote oxidative dehydrogenation and dehydrogenative coupling of many organic molecules. Oxidations of alcohols to aldehydes or ketones are prominent examples. Hydroquinone (H₂Q) oxidation to benzoquinone (BQ) is conceptually related to alcohol oxidation, but it is significantly more challenging thermodynamically. The BQ/H₂Q redox potential is sufficiently high that BQ is often used as an oxidant in Pd-catalyzed oxidation reactions. A recent report (J. Am Chem. Soc. 2020, 142, 19678-19688) showed that certain ancillary ligands can raise the Pd^II/0 redox potential sufficiently to reverse this reactivity, enabling (L)Pd^II(OAc)₂ to oxidize hydroquinone to benzoquinone. Here, we investigate the oxidation of tert-butylhydroquinone ( BuH₂Q) and 4-fluorobenzyl alcohol (^4FBnOH), mediated by (bc)Pd(OAc)₂ (bc = bathocuproine). Although alcohol oxidation is thermodynamically favored over H₂Q oxidation by more than 400 mV, the oxidation of BuH₂Q proceeds several orders of magnitude faster than ^4FBnOH oxidation. Kinetic and mechanistic studies reveal that these reactions feature different rate-limiting steps. Alcohol oxidation proceeds via rate-limiting β-hydride elimination from a Pd^II-alkoxide intermediate, while H₂Q oxidation features rate-limiting isomerization from an O-to-C-bound Pd^II-hydroquinonate species. The enhanced rate of H₂Q oxidation reflects the kinetic facility of O─H relative to C─H bond cleavage.