Tomas Horsten

An electroreductive cross-electrophile coupling (eXEC) reaction to produce ketones has been developed with simple N,N-dimethylamides and organic halides as coupling partners through highly inert C(O)−N bond cleavage. The C–C bond formation from C(O)–N cleavage of N,N-dimethylamides by single-electron activation is achieved for the first time and offers an unprecedented synthetic method that transcends the existing routes to activate amide C(O)–N bond cleavage transformations.

ABSTRACT

The conversion of amides to ketones via C(O)−N bond cleavage has attracted significant attention, with cross-electrophile coupling (XEC) between amides and organic halides emerging as a particularly valuable strategy. However, such transformations have so far been limited to activated amides and transition metal catalysis. The cross-electrophile coupling acylation of simple N,N-dimethylamides via C(O)−N bond cleavage remains challenging due to their higher chemical inertness and lower electrophilicity compared to activated amides. Herein, we report the successful development of an electroreductive cross-electrophile coupling (eXEC) reaction between N,N-dimethylamides and organic halides, which affords ketones through the highly inert C(O)−N bond cleavage. This work establishes an unprecedented electrochemical reduction method for C(O)−N bond cleavage of N,N-dimethylamides by single-electron activation. Extensive experimental and computational studies elucidate the detailed reaction mechanism. The process begins with the single-electron reduction of the N,N-dimethylamide in a lithium-ion electroreduction system, generating a ketyl radical anion. This key intermediate disrupts the amide resonance, weakening the C(O)−N bond. Consequently, this facilitates the typically challenging radical-radical cross-coupling, followed by scission of the C(O)−N bond. The observed selectivity of the cross-coupling is governed by the combined effects of a thermodynamic preference for coupling and the high concentration disparity between the two distinct radical species.

An electrochemical, metal-free three-component strategy for direct C(sp ²)─H sulfonation of electron-rich heteroarenes using SO₂ and alcohols is described. Utilizing inexpensive graphite electrodes and practical SO₂ stock solutions under mild conditions, this method provides straightforward access to heteroaryl sulfonates from simple building blocks. Application to different electron-rich five-membered heterocycles, scalability, and electrode/electrolyte reusability highlight its potential as a sustainable approach to valuable sulfonate scaffolds.

An electrochemical three-component reaction for the synthesis of heteroaryl sulfonates from heteroarenes, SO₂, and alcohols is described. The metal-free protocol uses inexpensive graphite electrodes and practical SO₂ stock solutions to achieve a direct C(sp ²)─H sulfonation of different electron-rich heterocycles under mild conditions. Thereby, this strategy provides direct access to the heteroaryl sulfonate scaffold from simple building blocks. Application to different electron-rich five-membered heterocycles, scalability, and electrode/electrolyte reusability highlight the potential of this process for a sustainable synthesis of heteroaryl sulfonates with relevance to medicinal and synthetic chemistry.

Publication date: Available online 1 June 2026

Source: Trends in Chemistry

Author(s): Vishal Jyoti Roy, Nishan Khanal, Dennis Chung-Yang Huang

The Front Cover illustrates the concept of “Back to the Electro-Future,” where classical named reactions are reimagined through electro-organic synthesis. Electrical sparks linking traditional laboratory glassware with an electrochemical cell symbolize electron-driven activation. This imagery represents how electricity revitalizes well-known transformations, offering sustainable and modern approaches to established reactions in organic chemistry. More information can be found in the Review by M. Kim, I. Choi and co-workers (DOI: 10.1002/cssc.70613).

A new class of 1-azabicyclo[1.1.0]butanes (ABBs) is synthesized, and the first electrochemical method for synthesizing chemo-selective trifluoromethanesulfonylated and trifluoromethylated azetidine derivatives from ABBs. This strategy involves the anodic oxidation of ABB to generate a nitrogen-centered radical cation, a rare [2, 3]-sigmatropic shift of the sulfone, and selective oxidation of Langlois' reagent. The generated azetidines were integrated into drug motifs, demonstrating their utility. Mechanistic investigations through control experiments, cyclic voltammetry, and electrochemical impedance spectroscopy (EIS) provided deep insights into the reaction pathways.

ABSTRACT

Due to the favorable pharmaceutical properties of the azetidine ring, it can serve as a bioisostere to replace saturated heterocycles such as piperazines, piperidines, and pyrrolidines in drug discovery. The diverse methods for azetidine synthesis are still limited and challenging. Herein, we design a new class of 1-azabicyclo[1.1.0]butanes (ABBs) and report the first electrochemical protocol for the synthesis of chemo-selective trifluoromethanesulfonylated and trifluoromethylated azetidine derivatives via direct anodic oxidation. The key features of this strategy involve: (i) electrochemical anodic oxidation of ABB to form a N-centered radical cation, (ii) a rare [2,3]-sigmatropic shift of sulfone, (iii) selective oxidation of Langlois’ reagent (NaSO₂CF₃), and (iv) the kinetic study of the developed methodology. The strategy exhibits broad substrate scope and scalability, making it practical. Installation of generated azetidines into marketed drug motifs, including ibuprofen, naproxen, and olaparib derivative, demonstrates the method's utility. Mechanistic investigations, supported by control experiments, cyclic voltammetry, and electrochemical impedance spectroscopy (EIS), provided key insights into the reaction pathway. This electrochemical approach advances the strain-release chemistry of ABBs and offers a promising platform for future developments.

This review systematically summarizes the research progress on the electrocatalytic reduction of furfural, elucidates the formation mechanisms of furfuryl alcohol, 2-methylfuran, and hydrofuroin, describes the methods for reaction pathway control through reaction environment and catalyst engineering, proposes core principles for catalyst design, and outlines future research challenges in this field.

Furfural serves as a critical bridge connecting lignocellulosic feedstocks with the biorefinery industry. Its catalytic upgrading, particularly hydrogenation and reduction, constitutes a core pathway for synthesizing diverse chemicals and biofuels. In recent years, the electrochemical reduction of furfural has gained significant interest, driven by the large-scale development of renewable electricity and its mild reaction conditions. This review comprehensively summarizes recent advances in the electrocatalytic reduction of furfural into value-added chemical products (such as furfuryl alcohol, 2-methylfuran, and hydrofuroin). It places a strong emphasis on the comprehensive elucidation of reaction mechanisms and advanced strategies for modulating reaction pathways through catalyst design, thereby establishing the groundwork for future electrocatalyst development. Furthermore, it provides a detailed discussion of key experimental characterization techniques and theoretical computational methods employed in mechanistic and active site studies, while outlining the challenges and future directions in this field.

An efficient electrochemical intermolecular annulation of diarylphosphine oxides with alkynes is established. Using DABCO as an organic mediator, benzo[b]phosphole oxides are synthesized under transition-metal- and oxidant-free conditions. High-surface-area carbon electrodes are essential for the reaction. The electrochemical reaction proceeded via phosphine radical intermediates through multiple reaction pathways.

The electrochemical intermolecular annulation of diarylphosphine oxides with alkynes for the synthesis of benzo[b]phosphole oxides has been reported. The reaction proceeded under transition-metal- and oxidant-free conditions via indirect electrolysis, using 1,4-diazabicyclo[2.2.2]octane as a mediator. High-surface-area carbon electrodes, such as carbon felt and reticulated vitreous carbon, are essential for this reaction. Several diarylphosphine oxides and alkynes were applied to electrochemical annulation, and the corresponding benzo[b]phosphole oxides were obtained. Mechanistic studies suggested that the reaction proceeds via radical intermediates generated through multiple pathways.

Silver-catalyzed [3 + 2] cycloaddition of aryldiazonium salts and (diazomethyl)dimethylphosphine oxide is developed as an approach to 2,5-disubstituted tetrazoles bearing a P(O)(Alkyl)₂ group. The method has wide scope and low susceptibility toward electronic and steric effects in the diazonium salt component.

A convenient approach to 2,5-disubstituted tetrazoles bearing a dialkylphosphine oxide substituent at the C-5 position is developed. The method involves silver-catalyzed [3 + 2] cycloaddition of (diazomethyl)dialkylphosphine oxide and aryl diazonium salts. The proposed reaction is compatible with various substituents at the aryl ring and has low susceptibility to their electronic and steric effects. Several heterocyclic diazonium salts were also involved into the transformation successfully. The proposed reaction pathway may include synchronous [3 + 2] cycloaddition or two-step formation of the tetrazole ring starting with electrophilic attack of aryl diazonium salt at the diazoalkane carbon atom.

Selective electrochemical benzylic C─H pyridination is achieved in an undivided flow cell using a tailored pyridine. Electronic tuning suppresses competing aromatic substitution and enables the formation of versatile benzylic pyridinium intermediates, which undergo diverse downstream transformations to afford primary benzylamines and a wide range of carbon- and heteroatom-functionalized products under practical and scalable conditions.

ABSTRACT

C─H diversification strategies that enable access to various C─X (X = heteroatom) and C─C bonds are of central importance in synthetic chemistry. Here we present a benzylic C─H diversification protocol that merges electrochemical C─H pyridination with subsequent aminolysis or substitution to access unprotected benzylamines and a wide range of benzylic products. The electrochemical transformation proceeds in an undivided flow cell under oxidant- and transition-metal-free conditions and shows broad generality across electron-rich, electron-deficient, and halogenated alkylarenes. A key element is the use of a tailored pyridine with appropriate electronic properties, which suppresses undesired aromatic substitution while facilitating aminolysis and nucleophilic substitution of the pyridinium intermediate. The practicality of this method is underscored by a continuous operation in parallel microreactors, which furnished more than 100 g of benzylamine product.

Co/CoO heterostructured composites supported on reduced graphene oxide (rGO) are prepared via rapid synthesis based on magnetic induction heating for 10 s, and the sample prepared at 400 A exhibits the best bifunctional activity toward HER and OER in alkaline media. In electrochemical water splitting, the performance is over 260 mV better than that based on commercial benchmarks.

ABSTRACT

Metal/carbon-based nanocomposites have attracted significant interest for electrochemical water splitting due to their unique interfacial electronic structures, abundant active sites, and catalytic bifunctionality toward both hydrogen evolution reaction (HER) and oxygen evolution reaction (OER). Herein, Co/CoO-rGO composites consisting of Co/CoO heterostructured nanoparticles encapsulated within a graphitized carbon scaffold are produced via magnetic induction heating at controlled currents for 10 s with cobalt(II) nitrate and reduced graphene oxide (rGO) loaded on nickel foam and effectively catalyze both HER and OER in alkaline media. Among the series, the sample prepared at 400 A for 10 s exhibits the best performance, featuring an overpotential of −144 mV for HER and +390 mV for OER at 10 mA cm^{− 2} and 50 mA cm^{− 2}, respectively. The bifunctional activity can then be exploited for full water splitting, where a low cell voltage of 1.61 V is needed to generate a current density of 10 mA cm⁻², 260 mV better than that with commercial Pt/C and RuO₂. The remarkable performance is attributed to the synergistic interaction between the Co and CoO domains, enhanced charge transfer at the heterojunction interface, and conductive carbon support. These results highlight the potential of Co/CoO-based nanocomposites as efficient and low-cost catalysts for overall water splitting and the scalability of the MIH technology.