Palladium-catalyzed C-H activation/C-O bond-forming reactions have emerged as attractive tools for organic synthesis. Typically, these reactions require strong chemical oxidants, which convert organopalladium(II) intermediates into the Pd or Pd oxidation state to promote otherwise challenging C-O reductive elimination. However, previously reported oxidants possess significant disadvantages, including poor atom economy, high cost, and the formation of undesired byproducts. To overcome these issues, we report an electrochemical strategy that takes advantage of anodic oxidation of Pd to induce selective C-O reductive elimination with a variety of oxyanion coupling partners.

Conspectus Electrochemical synthesis of organic compounds has emerged as an attractive and environmentally benign alternative to conventional approaches for oxidation and reduction of organic compounds that utilizes electric current instead of chemical oxidants and reductants. As such, many useful transformations have been developed, including the Kolbe reaction, the Simons fluorination process, the Monsanto adiponitrile process, and the Shono oxidation, to name a few. Electrochemical C–H functionalization represents one of the most promising reaction types among many electrochemical transformations, since this process avoids prefunctionalization of substrates and provides novel retrosynthetic disconnections. However, site-selective anodic oxidation of C–H bonds is still a fundamental challenge due to the high oxidation potentials of C–H bonds compared to organic solvents and common functional groups. To overcome this issue, indirect electrolysis via the action of a mediator (a redox catalyst) is regularly employed, by which the selectivity can be controlled following reaction of said mediator with the substrate. Since the redox potentials of transition metal complexes can be easily tuned by modification of the ligand, the synergistic use of electrochemistry and transition metal catalysis to achieve site-selective C–H functionalization is an attractive strategy. In this Account, we summarize and contextualize our recent efforts toward transition metal-catalyzed electrochemical C–H functionalization proximal to a suitable directing group. We have developed C–H oxygenation, acylation, alkylation, and halogenation reactions in which a Pd­(II) species is oxidized to a Pd­(III) or Pd­(IV) intermediate by anodic oxidation, followed by reductive elimination to form the corresponding C–O, C–C, and C–X bonds. Importantly, improved monofunctionalization selectivity is achieved in the Pd-catalyzed C­(sp3)–H oxygenation compared to conventional approaches using PhI­(OAc)2 as the chemical oxidant. Physical separators are sometimes used to prevent the electrochemical deposition of Pd black on the cathode resulting from reduction of high valent Pd species. We skirted this issue through the development a Cu-catalyzed electrochemical C­(sp2)–H amination using n-Bu4NI as a redox cocatalyst in an undivided cell. In addition, we developed Ir-catalyzed electrochemical vinylic C–H functionalization of acrylic acids with alkynes in an undivided cell, affording various substituted α-pyrones in good to excellent yield. More importantly, chemical oxidants, including Ag2CO3, Cu­(OAc)2, and PhI­(OAc)2, resulted in much lower yields in the absence of electrical current under otherwise identical conditions. As elaborated below, progress in the area of electrochemical transition metal-catalyzed synthesis provides an effective platform for environmentally friendly and sustainable selective chemical transformations.

Electrochemical oxidation represents an environmentally friendly solution to conventional methods that require caustic stoichiometric chemical oxidants. However, C-H functionalizations merging transition-metal catalysis and electrochemical techniques are, to date, largely confined to the use of precious metals and divided cells. Herein, we report the first examples of copper-catalyzed electrochemical C-H aminations of arenes at room temperature using undivided electrochemical cells, thereby providing a practical solution for the construction of arylamines. The use of n-BuNI as a redox mediator is crucial for this transformation. On the basis of mechanistic studies including kinetic profiles, isotope effects, cyclic voltammetric analyses, and radical inhibition experiments, the reaction appears to proceed via a single-electron-transfer (SET) process, and a high valent Cu(III) species is likely involved. These findings provide a new avenue for transition-metal-catalyzed electrochemical C-H functionalization reactions using redox mediators.

Synergistic use of electrochemistry and organometallic catalysis has emerged as a powerful tool for site-selective C–H functionalization, yet this type of transformation has thus far mainly been limited to arene C–H functionalization. Herein, we report the development of electrochemical vinylic C–H functionalization of acrylic acids with alkynes. In this reaction an iridium catalyst enables C–H/O–H functionalization for alkyne annulation, affording α-pyrones with good to excellent yields in an undivided cell. Preliminary mechanistic studies show that anodic oxidation is crucial for releasing the product and regeneration of an Ir­(III) intermediate from a diene-Ir­(I) complex, which is a coordinatively saturated, 18-electron complex. Importantly, common chemical oxidants such as Ag­(I) or Cu­(II) did not give significant amounts of the desired product in the absence of electrical current under otherwise identical conditions.

Organic electrochemistry has a rich history in organic synthesis and has been considered as a promising alternative to traditional chemical oxidants and reductants because it obviates the use of stoichiometric amount of dangerous and toxic reagents. In particular, the electrochemical C—H bonds functionalization is one of the most desirable approaches for the construction of carbon–carbon (C—C) and carbon–heteroatom (C—X) bonds. This review summarizes the substantial progress made in the last few years in C—H functionalization via organic electrochemistry. It is divided into sections on C—C, C—N, C—O, C—S, C–Halogen and C—P bond formation.

Palladium-catalyzed arene C(sp)-H acetoxylation has emerged as a powerful tool to construct a carbon-oxygen (C-O) bond. However, the requirement of stoichiometric chemical oxidants for this transformation possesses a significant disadvantage. To solve this fundamental problem, we now report an anodic oxidation strategy to achieve arene C(sp)-H acetoxylation.

We have developed a Ni-catalyzed enantioselective hydroarylation of styrenes with arylboronic acids using MeOH as the hydrogen source, providing an efficient method to access 1,1-diarylalkanes, which are essential structural units in many biologically active compounds. In addition, Ni-catalyzed enantioselective hydrovinylation of styrenes with vinylboronic acids is also realized with good yields and enantioselectivities. The synthetic utility was demonstrated by the efficient synthesis of (R)-(−)-ibuprofen.

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