Mechanism of Copper/Azodicarboxylate-Catalyzed Aerobic Alcohol Oxidation: Evidence for Uncooperative Catalysis

Cooperative catalysis between Cu^II and redox-active organic cocatalysts is a key feature of important chemical and enzymatic aerobic oxidation reactions, such as alcohol oxidation mediated by Cu/TEMPO and galactose oxidase. Nearly 20 years ago, Markó and co-workers reported that azodicarboxylates, such as di-tert-butyl azodicarboxylate (DBAD), are effective redox-active cocatalysts in Cu-catalyzed aerobic alcohol oxidation reactions [Markó, I. E., et al. Science 1996, 274, 2044], but the nature of the cooperativity between Cu and azodicarboxylates is not well understood. Here, we report a mechanistic study of Cu/DBAD-catalyzed aerobic alcohol oxidation. In situ infrared spectroscopic studies reveal a burst of product formation prior to steady-state catalysis, and gas-uptake measurements show that no O₂ is consumed during the burst. Kinetic studies reveal that the anaerobic burst and steady-state turnover have different rate laws. The steady-state rate does not depend on [O₂] or [DBAD]. These results, together with other EPR and in situ IR spectroscopic and kinetic isotope effect studies, reveal that the steady-state mechanism consists of two interdependent catalytic cycles that operate in sequence: a fast Cu^II/DBAD pathway, in which DBAD serves as the oxidant, and a slow Cu^II-only pathway, in which Cu^II is the oxidant. This study provides significant insight into the redox cooperativity, or lack thereof, between Cu and redox-active organic cocatalysts in aerobic oxidation reactions.