The selective activation of C-H bonds is a critical step in synthesizing pharmaceuticals, natural products, and fine chemicals. Alcohol oxidation, however, is often carried out under harsh conditions with organometallic complexes as catalysts. The selective alcohol oxidation via electrochemical routes typically requires larger overpotentials to overcome the sluggish kinetics for C-H activation. Mediators such as 2,2,6,6-Tetramethylpiperidinyloxyl (TEMPO) have been successfully employed to reduce large overpotentials for electrochemical C–H activation in alcohol oxidation. 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 referred to as reductive oxidation, where peroxydisulfate (S2O82–) is reduced and subsequently used to drive alcohol oxidation. Thus, counter-intuitively, 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. First-principles simulations, cyclic voltammetry, and finite-difference simulations establish the resulting reaction pathways and provide insights into the mechanism. Electrocatalytic reduction of S2O82– is first mediated by a Ru(NH3)63+/2+ mediator. Ru(NH3)62+ transfers an electron to S2O82– in a rate-limiting electron transfer step. S2O83–●, with a lifetime of the order of picoseconds, concertedly disproportionate to generate SO42- and the highly oxidizing SO4-●. This dual-mediated strategy reduces the overpotential for the reduction of S2O82– and homogeneously forms SO4-● away from the electrode, mitigating the direct reduction of this species. SO4–● then carries out subsequent hydrogen atom abstractions and/or 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.

Electrocatalytic reduction of peroxydisulfate for efficient and selective oxidation of alcohols

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