(666a) Oxidation By Reduction: Electrocatalytic Reduction of Peroxydisulfate for Efficient and Selective Oxidation of Alcohols

The selective activation of C-H bonds is critical in synthesizing pharmaceuticals, natural products, and fine chemicals. Alcohol oxidation, however, is often carried out under harsh conditions with organometallic complexes as catalysts. Electrochemical routes typically require larger overpotentials to overcome the sluggish kinetics for C-H activation. Mediators such as TEMPO have been successfully employed to reduce these large overpotentials. Unfortunately, these mediators are relatively expensive, unsuitable for large-scale reactions, and show limited modularity. Baran and coworkers further developed N-Ammonium ylide mediators to resolve the modularity issue. However, oxidation with these mediators still requires large positive overpotentials.

Herein, we discuss a new electrochemical synthetic method developed by the White group called reductive oxidation, where peroxydisulfate (S₂O₈^2–) is reduced and subsequently used to drive alcohol oxidation. Thus, alcohol oxidation occurs due to an electrochemical reduction reaction. First-principles density functional theory calculations and ab-initio molecular dynamics simulations are presented that examine the mechanism and provide insights into the mediated oxidation of alcohols. Explicit solvent dynamics of solution-phase mediator species and Marcus Theory capture the kinetics of electron transfers. Electrocatalytic reduction of S₂O₈^2– is first mediated by a Ru(NH₃)₆^3+/2+ mediator. Ru(NH₃)₆²⁺ transfers an electron to S₂O₈^2– in a rate-limiting electron transfer step. S₂O₈^{3–●}, with a lifetime of the order of picoseconds, concertedly disproportionate to generate SO₄^2- and the highly oxidizing SO₄^-●. This dual-mediated strategy reduces the overpotential for the reduction of S₂O₈^2– and homogeneously forms SO₄^-● away from the electrode, mitigating the direct reduction of this species. SO₄^{–●} then carries out subsequent hydrogen atom abstractions and proton-coupled-electron transfer steps. This approach thus provides a selective synthetic route for the oxidation of alcohols carried out under mild conditions to aldehydes, ketones, and carboxylic acids with up to 99% conversion yields.