Revealing the Mechanistic Features of an Electrosynthetic Catalytic Reaction and the Role of Redox Mediators through DFT Calculations and Microkinetic Modeling.

Organic electrosynthesis is an emerging field that provides original selectivity while adding features of atom economy, sustainability, and selectivity. Electrosynthesis is often enhanced by redox mediators or electroauxiliaries. The mechanistic understanding of organic electrosynthesis is however often limited by the low lifetime of intermediates and its difficult detection. In this work, we report a computational analysis of the mechanism of an appealing reaction previously reported by Mei and co-workers which is catalyzed by copper and employs iodide as redox mediator. Our scheme combines DFT calculations with microkinetic modeling and covers both the reaction in solution and the electrodic steps. A detailed mechanistic scheme is obtained which reproduces well experimental data and opens perspectives for the general treatment of these processes.

Single-Atom Iron Catalyst as an Advanced Redox Mediator for Anodic Oxidation of Organic Electrosynthesis.

Homogeneous electrocatalysts can indirect oxidate the high overpotential substrates through single-electron transfer on the electrode surface, enabling efficient operation of organic electrosynthesis catalytic cycles. However, the problems of this chemistry still exist such as high dosage, difficult recovery, and low catalytic efficiency. Single-atom catalysts (SACs) exhibit high atom utilization and excellent catalytic activity, hold great promise in addressing the limitations of homogeneous catalysts. In view of this, we have employed Fe-SA@NC as an advanced redox mediator to try to change this situation. Fe-SA@NC was synthesized using an encapsulation-pyrolysis method, and it demonstrated remarkable performance as a redox mediator in a range of reported organic electrosynthesis reactions, and enabling the construction of various C-C/C-X bonds. Moreover, Fe-SA@NC demonstrated a great potential in exploring new synthetic method for organic electrosynthesis. We employed it to develop a new electro-oxidative ring-opening transformation of cyclopropyl amides. In this new reaction system, Fe-SA@NC showed good tolerance to drug molecules with complex structures, as well as enabling flow electrochemical syntheses and gram-scale transformations. This work highlights the great potential of SACs in organic electrosynthesis, thereby opening a new avenue in synthetic chemistry.

Alanine Formation in a Zero-Gap Flow Cell and the Role of TiO2/Ti Electrocatalysts.

The electrochemical synthesis of α ${\alpha }$ -amino acids at room temperature and pressure is a sustainable alternative to conventional methods like microbial fermentation and Strecker synthesis. A custom-built zero-gap flow electrolyzer was used to study the electrosynthesis of alanine via the electrocatalytic reductive amination (ERA) of the corresponding biomass-derivable α ${\alpha }$ -keto acid precursor - pyruvic acid (PA), and hydroxylamine (NH2OH) at very low pH. Non-toxic, abundant, and easy to prepare TiO2/Ti electrocatalysts were utilized as the cathode. Three TiO2/Ti felt electrodes with different oxide thicknesses were prepared and their characterization results were correlated with their respective electrochemical performance in terms of Faradaic efficiency η ${\eta }$ , and partial current density j ‾ ${\left|\overline{j}\right|}$ . Cyclic voltammetry indicated a different electrocatalytic reduction process on hydrothermally treated electrodes, compared to thermally oxidized ones. Hydrothermally treated electrodes were also found to have the thickest porous anatase layer and achieved 50-75 % alanine conversion efficiencies. Optimization showed that the cell potential, reactant flow rate and the PA: NH2OH ratio were crucial parameters in determining the conversion efficiency. η ${\eta }$ and j ‾ ${\left|\overline{j}\right|}$ were found to significantly decrease when an excess of is used and, an optimal alanine η ${\eta }$ of 75 % was achieved at 2.0 V applied cell potential and 10 mL/h reactant flow rate.

Access to carbonyl compounds via the electroreduction of N-benzyloxyphthalimides: Mechanism confirmation and preparative applications.

A method to access carbonyl compounds using reductive conditions was evaluated via electrochemical reduction of their corresponding N-benzyloxyphthalimide derivatives (NBOPIs). The mechanism of this originally reported electrochemical reaction was proposed based on DFT calculation and is experimentally confirmed herein, contrasting simulated and experimental cyclic voltammetry data. The reaction scope studied in a preparative scale and using redox sensitive functional groups showed good selectivity and tolerance toward oxidation under the reaction conditions with a moderate to good yield (50-71%). Nevertheless, some restrictions with reducible functional groups, like benzyl-brominated and nitro-aromatic derivatives, were observed. The present approach can be considered a self-sustainable electrochemical catalysis for the synthesis of aromatic carbonylic compounds passing through anion radical intermediates produced by a cathodic reaction.

Electrohydrogenation of Nitriles with Amines by Cobalt Catalysis.

Catalytic hydrogenation of nitriles represents an efficient and sustainable one-step synthesis of valuable bulk and fine chemicals. We report herein a molecular cobalt electrocatalyst for selective hydrogenative coupling of nitriles with amines using protons as the hydrogen source. The key to success for this reductive reaction is the use of an electrocatalytic approach for efficient cobalt-hydride generation through a sequence of cathodic reduction and protonation. As only electrons (e- ) and protons (H+ ) as the redox equivalent and hydrogen source, this general electrohydrogenation protocol is showcased by highly selective and straightforward synthesis of various functionalized and structurally diverse amines, as well as deuterium isotope labeling applications. Mechanistic studies reveal that the electrogenerated cobalt-hydride transfer to nitrile process is the rate-determining step.

Unraveling the electrophilic oxygen-mediated mechanism for alcohol electrooxidation on NiO.

Aqueous organic electrosynthesis such as nucleophile oxidation reaction (NOR) is an economical and green approach. However, its development has been hindered by the inadequate understanding of the synergy between the electrochemical and non-electrochemical steps. In this study, we unravel the NOR mechanism for the primary alcohol/vicinal diol electrooxidation on NiO. Thereinto, the electrochemical step is the generation of Ni3+-(OH)ads, and the spontaneous reaction between Ni3+-(OH)ads and nucleophiles is an electrocatalyst-induced non-electrochemical step. We identify that two electrophilic oxygen-mediated mechanisms (EOMs), EOM involving hydrogen atom transfer (HAT) and EOM involving C-C bond cleavage, play pivotal roles in the electrooxidation of primary alcohol to carboxylic acid and the electrooxidation of vicinal diol to carboxylic acid and formic acid, respectively. Based on these findings, we establish a unified NOR mechanism for alcohol electrooxidation and deepen the understanding of the synergy between the electrochemical and non-electrochemical steps during NOR, which can guide the sustainable electrochemical synthesis of organic chemicals.

Electrochemical Preparation of Sm(II) Reagent Facilitated by Weakly Coordinating Anions.

Samarium diiodide (SmI2 ) is widely used as a strong one-electron reducing agent and is often employed to form C-C bonds in complex systems. Despite their utility, SmI2 and related salts suffer from several drawbacks that render the use of Sm reducing agents in large-scale synthesis impractical. Here, we report factors influencing the electrochemical reduction of Sm(III) to Sm(II), towards the goal of electrocatalytic Sm(III) reduction. We probe the effect of supporting electrolyte, electrode material, and Sm precursor on Sm(II)/(III) redox and on the reducing power of the Sm species. We find that the coordination strength of the counteranion of the Sm salt affects the reversibility and redox potential of the Sm(II)/(III) couple and establish that the counteranion primarily determines the reducibility of Sm(III). Electrochemically generated SmI2 performs similarly to commercial SmI2 solutions in a proof-of-concept reaction. The results will provide fundamental insight to facilitate the development of Sm-electrocatalytic reactions.

Eletrocarboxylation Reactions Using CO2 Both as Promoter and Carboxylative Reagent.

Electrocarboxylation reaction, which employs organic electrosynthesis to achieve the utilization of CO2 as a carboxylative reagent, provides a powerful and efficient tool for the preparation of organic carboxylic acid. In some electrocarboxylation reactions, CO2 also acts as a promoter to facilitate the desired reaction. This concept mainly highlights recent CO2 -promoted electrocarboxylation reactions via CO2 ⋅- intermediate or transiently protective carboxylation of active intermediate with CO2 .

Electrochemical Manufacturing Routes for Organic Chemical Commodities.

Electrochemical synthesis of organic chemical commodities provides an alternative to conventional thermochemical manufacturing and enables the direct use of renewable electricity to reduce greenhouse gas emissions from the chemical industry. We discuss electrochemical synthesis approaches that use abundant carbon feedstocks for the production of the largest petrochemical precursors and basic organic chemical products: light olefins, olefin oxidation derivatives, aromatics, and methanol. First, we identify feasible routes for the electrochemical production of each commodity while considering the reaction thermodynamics, available feedstocks, and competing thermochemical processes. Next, we summarize successful catalysis and reaction engineering approaches to overcome technological challenges that prevent electrochemical routes from operating at high production rates, selectivity, stability, and energy conversion efficiency. Finally, we provide an outlook on the strategies that must be implemented to achieve large-scale electrochemical manufacturing of major organic chemical commodities.

Metal-Free Synthesis of N-Heterocycles via Intramolecular Electrochemical C-H Aminations.

N-heterocycles are key structural units in many drugs, biologically interesting molecules and functional materials. To avoid the residues of metal catalysts, the construction of N-heterocycles under metal-free conditions has attracted much research attention in academia and industry. Among them, the intramolecular electrochemical C-H aminations arguably constitute environmentally friendly methodologies for the metal-free construction of N-heterocycles, mainly due to the direct use of clean electricity as the redox agents. With the recent renaissance of organic electrosynthesis, the intramolecular electrochemical C-H aminations have undergone much progress in recent years. In this article, we would like to summarize the advances in this research field since 2019. The emphasis is placed on the reaction design and mechanistic insight. The challenges and future developments in the intramolecular electrochemical C-H aminations are also discussed.

Direct and Selective Electrocarboxylation of Styrene Oxides with CO2 for Accessing ß-Hydroxy Acids.

Highly selective and direct electroreductive ring-opening carboxylation of epoxides with CO2 in an undivided cell is reported. This reaction shows broad substrate scopes within styrene oxides under mild conditions, providing practical and scalable access to important synthetic intermediate ß-hydroxy acids. Mechanistic studies show that CO2 functions not only as a carboxylative reagent in this reaction but also as a promoter to enable efficient and chemoselective transformation of epoxides under additive-free electrochemical conditions. Cathodically generated α-radical and α-carbanion intermediates lead to the regioselective formation of α-carboxylation products.

Recent Updates on Electrogenerated Hypervalent Iodine Derivatives and Their Applications as Mediators in Organic Electrosynthesis.

With the renaissance of chemical electrosynthesis in the last decade, the electrochemistry of hypervalent iodine compounds has picked up the pace and achieved significant improvements. By employing traceless electrons instead of stoichiometric oxidants as the alternative clean "reagents", many hypervalent iodine compounds were efficiently electro-synthesized via anodic oxidation methods and utilized as powerful redox mediators triggering valuable oxidative coupling reactions in a more sustainable way. This minireview gives an up-to-date overview of the recent advances during the past 3 years, encompassing enhanced electrosynthesis technologies, novel synthetic applications, and ideas for improving reaction sustainability.

Activated Ni-OH Bonds in a Catalyst Facilitates the Nucleophile Oxidation Reaction.

The nucleophile oxidation reaction (NOR) is of enormous significance for organic electrosynthesis and coupling for hydrogen generation. However, the nonuniform NOR mechanism limits its development. For the NOR, involving electrocatalysis and organic chemistry, both the electrochemical step and non-electrochemical process should be taken into account. The NOR of nickel-based hydroxides includes the electrogenerated dehydrogenation of the Ni2+ -OH bond and a spontaneous non-electrochemical process; the former determines the electrochemical activity, and the nucleophile oxidation pathway depends on the latter. Herein, the space-confinement-induced synthesis of Ni3 Fe layered double hydroxide intercalated with single-atom-layer Pt nanosheets (Ni3 Fe LDH-Pt NS) is reported. The synergy of interlayer Pt nanosheets and multiple defects activates Ni-OH bonds, thus exhibiting an excellent NOR performance. The spontaneous non-electrochemical steps of the NOR are revealed, such as proton-coupled electron transfer (PCET; Ni3+ -O + X-H = Ni2+ -OH + X• ), hydration, and rearrangement. Hence, the reaction pathway of the NOR is deciphered, which not only helps to perfect the NOR mechanism, but also provides inspiration for organic electrosynthesis.

Electrochemical Heteroatom-Heteroatom Bond Construction.

Heteroatom-heteroatom linkage, with S-S bond as a presentative motif, served a crucial role in biochemicals, pharmaceuticals, pesticides, and material sciences. Thus, preparation of the privileged scaffold has always been attracting tremendous attention from the synthetic community. However, classic protocols suffered from several drawbacks, such as toxic and unstable agents, poor functional group tolerance, multiple steps, and explosive oxidizing regents as well as the transitional metal catalysts. Electrochemical organic synthesis exhibited a promising alternative to the traditional chemical reaction due to the sustainable electricity can be employed as the traceless redox agents. Hence, toxic and explosive oxidants and/or transitional metals could be discarded under mild reaction with high efficiency. In this context, a series of electrochemical approaches for the construction of heteroatom-heteroatom bond were reviewed. Notably, most of the cases illustrated the dehydrogenative feature with the clean energy molecules hydrogen as the sole by-product.

Indirect Electrosynthesis with Halogen Ions as Mediators.

Organic electrosynthesis has gained increasing research interest as it harvests electric current as redox regents, thereby providing a sustainable alternative to conventional approaches. Compared with direct electrosynthesis, indirect electrosynthesis employs mediator(s) to lower the overpotentials for substrate activation, and enhance the reaction efficiency and functional group compatibility by shifting the heterogenous electron transfer process to be homogenous. As one of the most versatile and cost-efficient mediators, halogen mediators are always combined with an irreversible halogenation reaction. Thus, the electrochemical reaction between halogen mediators and substrates doesn't directly controlled by the two standard potentials difference. In this account, our recent developments in the area of halogen-mediated indirect electrosynthesis are summarized. The anodically generated halogen species from halogenide salts have the abilities to undergo electron-transfer (ET) or hydrogen-atom- transfer (HAT) processes. The reaction features, scopes, limitations, and mechanistic rationalisations are discussed in this account. We hope our studies will contribute to the future developments to broaden the scope of halogen-mediated electrosynthesis.

Recent advances in organic electrosynthesis employing transition metal complexes as electrocatalysts.

Organic electrosynthesis has been widely used as an environmentally conscious alternative to conventional methods for redox reactions because it utilizes electric current as a traceless redox agent instead of chemical redox agents. Indirect electrolysis employing a redox catalyst has received tremendous attention, since it provides various advantages compared to direct electrolysis. With indirect electrolysis, overpotential of electron transfer can be avoided, which is inherently milder, thus wide functional group tolerance can be achieved. Additionally, chemoselectivity, regioselectivity, and stereoselectivity can be tuned by the redox catalysts used in indirect electrolysis. Furthermore, electrode passivation can be avoided by preventing the formation of polymer films on the electrode surface. Common redox catalysts include N-oxyl radicals, hypervalent iodine species, halides, amines, benzoquinones (such as DDQ and tetrachlorobenzoquinone), and transition metals. In recent years, great progress has been made in the field of indirect organic electrosynthesis using transition metals as redox catalysts for reaction classes including C-H functionalization, radical cyclization, and cross-coupling of aryl halides-each owing to the diverse reactivity and accessible oxidation states of transition metals. Although various reviews of organic electrosynthesis are available, there is a lack of articles that focus on recent research progress in the area of indirect electrolysis using transition metals, which is the impetus for this review.

CuPd Nanoparticles as a Robust Catalyst for Electrochemical Allylic Alkylation.

An efficient CuPd nanoparticle (NP) catalyst (3 nm CuPd NPs deposited on carbon support) is designed for catalyzing electrochemical allylic alkylation in water/isopropanol (1:1 v/v) and 0.2 m KHCO3 solution at room temperature. The Pd catalysis was Pd/Cu composition-dependent, and CuPd NPs with a Pd/Cu ratio close to one are the most efficient catalyst for the selective cross-coupling of alkyl halides and allylic halides to form C-C hydrocarbons with product yields reaching up to 99 %. This NP-catalyzed electrochemical allylic alkylation expands the synthetic scope of cross-coupling reactions and can be further extended to other organic reaction systems for developing green chemistry electrosynthesis methods.

Optimizing organic electrosynthesis through controlled voltage dosing and artificial intelligence.

Organic electrosynthesis can transform the chemical industry by introducing electricity-driven processes that are more energy efficient and that can be easily integrated with renewable energy sources. However, their deployment is severely hindered by the difficulties of controlling selectivity and achieving a large energy conversion efficiency at high current density due to the low solubility of organic reactants in practical electrolytes. This control can be improved by carefully balancing the mass transport processes and electrocatalytic reaction rates at the electrode diffusion layer through pulsed electrochemical methods. In this study, we explore these methods in the context of the electrosynthesis of adiponitrile (ADN), the largest organic electrochemical process in industry. Systematically exploring voltage pulses in the timescale between 5 and 150 ms led to a 20% increase in production of ADN and a 250% increase in relative selectivity with respect to the state-of-the-art constant voltage process. Moreover, combining this systematic experimental investigation with artificial intelligence (AI) tools allowed us to rapidly discover drastically improved electrosynthetic conditions, reaching improvements of 30 and 325% in ADN production rates and selectivity, respectively. This powerful AI-enhanced experimental approach represents a paradigm shift in the design of electrified chemical transformations, which can accelerate the deployment of more sustainable electrochemical manufacturing processes.