Optimizing the Synthetic Potential of O₂: Implications of Overpotential in Homogeneous Aerobic Oxidation Catalysis

Abstract

Molecular oxygen is the quintessential oxidant for organic chemical synthesis, but many challenges continue to limit its utility and breadth of applications. Extensive historical research has focused on overcoming kinetic challenges presented by the ground-state triplet electronic structure of O2 and the various reactivity and selectivity challenges associated with reactive oxygen species derived from O2 reduction. This Perspective will analyze thermodynamic principles underlying catalytic aerobic oxidation reactions, borrowing concepts from the study of the oxygen reduction reaction (ORR) in fuel cells. This analysis is especially important for “oxidase”-type liquid-phase catalytic aerobic oxidation reactions, which proceed by a mechanism that couples two sequential redox half-reactions: (1) substrate oxidation and (2) oxygen reduction, typically affording H2O2 or H2O. The catalysts for these reactions feature redox potentials that lie between the potentials associated with the substrate oxidation and oxygen reduction reactions, and changes in the catalyst potential lead to variations in effective overpotentials for the two half reactions. Catalysts that operate at low ORR overpotential retain a more thermodynamic driving force for the substrate oxidation step, enabling O2 to be used in more challenging oxidations. While catalysts that operate at high ORR overpotential have less driving force available for substrate oxidation, they often exhibit different or improved chemoselectivity relative to the high-potential catalysts. The concepts are elaborated in a series of case studies to highlight their implications for chemical synthesis. Examples include comparisons of (a) NO x /oxoammonium and Cu/nitroxyl catalysts, (b) high-potential quinones and amine oxidase biomimetic quinones, and (c) Pd aerobic oxidation catalysts with or without NO x cocatalysts. In addition, we show how the reductive activation of O2 provides a means to access potentials not accessible with conventional oxidase-type mechanisms. Overall, this analysis highlights the central role of catalyst overpotential in guiding the development of aerobic oxidation reactions.

Highly Selective Electrochemical Baeyer–Villiger Oxidation through Oxygen Atom Transfer from Water

“…7 Traditionally, this class of reactions relies on strong oxidants such as peroxyacids, peroxides, or molecular oxygen (O 2 ), which are often difficult to handle. 8,9 As a result, it presents a challenge for large-scale implementations, such as the preparation of monomers for polymeric materials. 10,11 Recent advances have inspired researchers to address these challenges by exploiting in situ generated oxidants.…”

“…In the pursuit of developing sustainable alternatives for catalysis, − oxygen atom transfer (OAT) reactions are of great importance for chemical synthesis . Traditionally, this class of reactions relies on strong oxidants such as peroxyacids, peroxides, or molecular oxygen (O 2 ), which are often difficult to handle. , As a result, it presents a challenge for large-scale implementations, such as the preparation of monomers for polymeric materials. , Recent advances have inspired researchers to address these challenges by exploiting in situ generated oxidants. − Promising results have been obtained by electrochemically (or photoelectrochemically) oxidizing H 2 O to produce intermediates, including oxo species, , peroxo species, hydroperoxo species, , hydroxyl radicals, and reactive atomic surface oxygen species, which can be directly utilized for OAT. For instance, it was recently reported that manganese oxo species generated through an electrochemical approach can efficiently oxidize thioethers to sulfoxides .…”

A diacetylene covalent organic framework through a one-step two-electron O2 reduction pathway for efficient photosynthesis of H2O2

“…Hydrogen peroxide (H 2 O 2 ) is a valuable chemical used in medical sterilization, 1 fuel cells, 2 and water pollution treatment. 3 The anthraquinone method, as the traditional method of H 2 O 2 preparation, involves the use of hazardous chemicals such as hydrogen and requires significant energy consumption.…”

Synthetic dioxygenase reactivity by pairing electrochemical oxygen reduction and water oxidation

“…Energetic considerations indicate that O 2 should be able to add oxygen to two organic molecules with perfect atom economy. Such reactions are favorable ( 1 ), but thermodynamically challenging oxidations, such as C–H hydroxylation, thioether oxygenation, and alkene epoxidation (Fig. 1A), have relatively small potential difference between O 2 reduction and substrate oxidation.…”