Intermolecular haloesterification of alkenes is a practical platform for modular ester synthesis. However, current methods are restricted to aryl-activated and directing-group-containing alkenes, leaving low-reactivity, electron-deficient alkenes with alkyl substituents largely underexplored. Notably, electrophilic reactions involving chloroesterification of electron-deficient alkenes are also challenging due to the difficulty in controlling selectivity. In this work, we present an electrochemically cooperative halogen-cation delivery strategy that achieves modular electrophilic haloesterification of both activated and unactivated alkenes with good chemo-, regio-, and diastereoselectivity levels. It exhibits enhanced reactivity (with yields of up to 90%) and selectivity (regioselectivities and diastereoselectivities exceeding 20 : 1), as the amide mediates the transfer of Cl+ to the alkene, enabling the formation of stable halogen-containing cationic intermediates (β-halo carbocation or halonium) in the electrochemically oxidative 'electrophile-nucleophile' ('E-Nu') approach. Di-, tri-, and tetrasubstituted alkenes displaying various electronic properties, as well as terminal alkenes, have been successfully haloesterified, showcasing the good tolerance of the strategy to the presence of functional groups. Moreover, the strategy is applicable to gram-scale synthesis and late-stage elaboration of bioactive compounds. It also enables the construction of quaternary carbons, even multiple contiguous ones, in reactions.

Organic electrosynthesis has emerged as a powerful platform for sustainable molecular synthesis, while continuous-flow electrochemistry is often viewed primarily as a technology for process intensification and scaleup. In our studies, however, we have found that the significance of continuous-flow electrochemistry extends far beyond improved productivity. The unique reaction environments created by single-pass flow electrolysis─including short residence times, spatially evolving electrochemical conditions, efficient mass transfer, and distinctive electrode interfacial microenvironments─can fundamentally alter reaction outcomes and facilitate transformations that are difficult to achieve in conventional batch reactors. In this Account, we summarize our efforts in developing continuous-flow electrosynthesis as a synthetic platform for challenging oxidative molecular transformations. We first show how single-pass flow electrolysis suppresses undesired secondary electrode reactions, enabling selective oxidative cyclizations, C-H oxygenation, and C-H amination reactions. We then discuss how continuous-flow electrolysis expands the accessible reactivity space of electro-oxidation by promoting productive utilization of highly reactive intermediates, exemplified by sulfur-centered radical chemistry and phosphorus radical cation chemistry. Particular emphasis is placed on electrochemical microenvironment engineering, where local ion distributions and acid-base properties within the electric double layer can be exploited to control reactivity. We further demonstrate how these concepts culminate in electro-oxidative asymmetric catalysis, where continuous-flow electrolysis provides an expanded operational window for simultaneously optimizing electrochemical and stereochemical parameters. Finally, we describe the translation of these transformations from laboratory-scale reactions to continuous production through reactor number-up and process integration. We anticipate that the next phase of development in flow electrosynthesis will be driven as much by advances in reactor engineering as by advances in synthetic methodology, ultimately enabling increasingly sophisticated continuous and electrified manufacturing platforms.

N-Fluoroalkyl amides have emerged as highly attractive targets because N-fluoromethylation can modulate conformation, stability, lipophilicity, and molecular recognition. However, despite the rapidly advancing chemistry of N-CF3 and N-CF2H amides, access to the corresponding N-monofluoromethyl (N-CH2F) amides remains significantly underdeveloped. Existing approaches are often constrained by the use of silver-based fluorinating reagents, unstable intermediates, and limited compatibility with peptide substrates. In this study, we report an electrochemical strategy for the synthesis of N-monofluoromethyl amides using fluoride as the fluorine source. Employing N-CH2TMS amides as readily accessible precursors, the target framework is efficiently constructed through electrochemical oxidative activation. The transformation proceeds under mild conditions and exhibits broad compatibility with amino acid-derived amides and peptide substrates of varying chain lengths.

The allylic phosphonates are unique reagents for the preparation of dienes and polyenes. Hitherto, there is still no method for the stereodivergent synthesis of allylic phosphonates. In this article, a transition-metal-free method has been developed under mild conditions for the stereodivergent synthesis of allylic phosphonates from readily available dialkyl phosphites, vinyltriphenylphosphonium chloride, and aldehydes. An array of cis- and trans-allylic phosphonates is produced on demand with good to excellent stereoselectivities and yields.

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.

Restricted by functional-group compatibility and monomer synthesis, functional polymers are difficult to obtain directly, whereas post-polymerization modification (PPM) provides an alternative efficient synthetic approach. Accordingly, efficient and selective orthogonal PPM under mild conditions could provide a higher degree of complexity and diversity. Herein, we propose a novel and efficient strategy for selective orthogonal PPM, which utilizes the high reactivity of aryl silyl ethers toward -SO2F groups (SuFEx click reaction) and of alkylamines toward pentafluorophenyl esters (active ester-amine chemistry) for sequential PPM of the copolymer of 4-vinylbenzenesulfonyl fluoride (VBSF) and pentafluorophenyl methacrylate (PFPMA) under mild conditions. NMR and GPC characterization studies demonstrate that silyl ethers react selectively with VBSF alone, and that PFPMA units are converted exclusively by alkylamines, while other functional groups remain inert throughout the process, enabling efficient selective orthogonal PPM and the preparation of structurally complex, well-defined polymers. Overall, the introduction of orthogonal functional groups into polymer precursors provides multiple independent reaction sites for PPM, thus offering a new synthetic pathway for functional materials.

Direct decarboxylative borylation of aliphatic carboxylic acids offers an attractive route to alkyl organoboron compounds from abundant and readily available feedstocks, yet a general and practical method for this transformation remains underdeveloped. Herein, we report a molecular photoelectrocatalytic strategy for the direct decarboxylative borylation of unactivated aliphatic carboxylic acids. The method relies on iron-catalyzed, photoinduced ligand-to-metal charge transfer (LMCT) activation of aliphatic carboxylic acids to generate alkyl radicals under mild conditions, thereby avoiding the preactivation of carboxylic acids as redox-active derivatives. By merging photochemical and electrochemical activation of the iron catalyst, this protocol enables oxidative decarboxylative C–B bond formation without the use of stoichiometric chemical oxidants. The method exhibits good functional-group tolerance, and its practicality is demonstrated by gram-scale synthesis. This work provides a concise platform for the direct conversion of unactivated aliphatic carboxylic acids into valuable alkyl boronates.

Quinolinones have been prepared by an intramolecular radical annulation of alpha-EWG (electron-withdrawing group) substituted amides and alkynes involving an electrochemical oxidation enabled hydrogen atom transfer (HAT) pathway, with commercially available Cp 2 Fe as a molecular electrochemical catalyst, thereby eliminating the need for stoichiometric chemical oxidants or reductants. An electrochemically generated carbon radical centered on an alpha-electron-deficient amide adds to a tethered alkyne followed by HAT and tautomerism, giving a wide variety of quinolinones in high yield, with good functional group compatibility in up to a gram scale under mild conditions.

The sustainable and efficient synthesis of hydrogen peroxide (H2O2) through photocatalysis remains highly desirable but challenging due to sluggish reaction kinetics and charge recombination. Herein, we report a sulfur vacancy-engineered 2D/2D S-scheme heterojunction constructed via the in situ growth of sulfur-vacancy-rich ZnIn2S4 (Vs-ZIS) nanosheets on Zn-TCPP (ZT) nanosheets for efficient H2O2 production. The intimate heterojunction interface facilitates rapid and directional separation of photogenerated electron-hole pairs while simultaneously retaining strong redox capability. Moreover, experimental results and density functional theory (DFT) calculations reveal that the introduced sulfur vacancies act as critical active sites, which significantly enhance the adsorption and activation of both O2 and H2O molecules. As a result, the optimized Vs-ZIS/ZT-20 heterojunction photocatalyst achieves a superior photocatalytic H2O2 production rate of 658.0 µmol·g-1·h-1 under visible-light irradiation (300 W) in pure water without sacrificial electron donors, which is 4.3 and 5.1 times higher than that of pristine Vs-ZIS and ZT nanosheets, respectively. Crucially, the as-prepared catalyst exhibits robust photocatalytic activity across diverse water sources, confirming its practical applicability. This work provides new insights into designing defect-rich S-scheme photocatalysts for green energy applications.

The strategic incorporation of fluorine into heterocyclic scaffolds is pivotal for drug discovery. Herein, we report a TBAF-initiated annulation of α-trifluoromethyl alkenes with alkynoates to assemble functionalized 2-fluoro-4H-pyran frameworks. This is an exceptional case of the annulation with alkynoates, in that just extra 10 mol % fluoride is needed.

A transition-metal-free method for the selective hydroxylation of o-fluorobenzamides has been developed, providing efficient access to salicylamides under basic conditions. The reaction proceeds with KOt-Bu and H2O in DMSO, affording the desired products in good to excellent yields with broad functional group tolerance and high ortho selectivity. Mechanistic studies indicate that the reaction critically depends on the hydrogen-bond donor ability and conformational flexibility of the amide. This work provides a practical approach to salicylamides and related derivatives and highlights hydrogen-bond-controlled reactivity in nucleophilic aromatic substitution.

The catalytic upgrading of bulk feedstock chemicals into value-added products represents a powerful approach in modern chemical synthesis. Herein, we describe an iron-catalyzed photoelectrochemical strategy that enables the efficient conversion of nitromethane (MeNO2), an abundant industrial feedstock, into synthetically valuable nitric oxide (·NO). This proof-of-concept platform allows the direct synthesis of structurally diverse oximes from MeNO2 and alcohols and exhibits broad functional group tolerance, including compatibility with carbonyl groups and acid-sensitive motifs such as esters and silyl ethers. Mechanistic investigations reveal that the iron catalyst plays a dual role: promoting radical deformylation of alcohols or ring-opening of cycloalkanols and mediating the conversion of MeNO2 into ·NO.

Selective functionalization of inert C(sp3)–H bonds remains a central challenge in modern organic synthesis. Molecular electrocatalysis provides a sustainable platform for C(sp3)–H activation by enabling catalyst-controlled electron transfer or atom transfer under mild conditions. This review highlights recent advances in molecular electrocatalytic systems, including both transition metal-based and metal-free catalysts, for efficient C(sp3)–H functionalization. Mechanistic insights into outer- and inner-sphere electron transfer pathways are discussed, along with their applications in enhancing regio- and enantioselectivity in asymmetric radical transformations. Special emphasis is placed on emerging photoelectrocatalytic approaches that integrate electrochemical redox control with photochemical excitation. Through critical evaluation of representative systems, this review illustrates the growing potential of molecular electrocatalysis for achieving selective and sustainable C(sp3)–H functionalization.

Despite the increasing interest in radical-based fluoroalkylation techniques, the organofluorine compounds bearing the partially fluorinated hexafluoroisopropyl group remain extremely scarce due to the lack of appropriate reagents. Herein we report an unprecedented photoelectrocatalytic method for the C-H hexafluoroisopropylation of indoles and tryptophan peptides, utilizing the readily available hexafluoro-2-propanol (HFIP) as the fluoroalkylation reagent. In this process, HFIP is converted into hexafluoroisopropyl radicals, enabling fluoroalkylation reactions. This study broadens the potential applications of molecular photoelectrocatalysis, highlighting its capacity to enable transformations that are difficult to accomplish through traditional electrochemical or photochemical approaches.

Reported herein is a transition metal catalyst- and oxidant-free platform for diversity-oriented benzylic C–H functionalization. The process involves electrochemical C(sp3)–H oxygenation followed by elimination/substitution with diverse nucleophiles.

Enantioselective hydroarylation of alkenes with aryl halides offers direct access to chiral C(sp2)-C(sp3) bonds, but available protocols typically require stoichiometric silane reductants and remain inefficient for aryl bromides under nickel catalysis. Here we describe an electrochemical nickel-catalyzed method that achieves intermolecular enantioselective hydroarylation of aryl alkenes with aryl bromides under mild, external-reductant-free conditions. The transformation operates through electrochemically generated Ni-H species together with cathodic modulation of nickel valence states, thereby sustaining the catalytic cycle without additional reductants. A broad range of aryl bromides, including electron-deficient, electron-rich, polysubstituted, and heteroaryl substrates, participate smoothly, affording chiral 1,1-diarylalkanes in good yields and up to 96% ee. Notably, the protocol also enables remote migratory hydroarylation via nickel-mediated chain walking, delivering products with excellent regio- and enantioselectivity (>20:1 rr and up to 95% ee). This work establishes electrochemical nickel catalysis as a general and sustainable platform for asymmetric hydrofunctionalization of alkenes.

Aromatic aldehydes are pivotal synthetic intermediates with applications in fine chemicals, pharmaceuticals, agrochemicals, and advanced materials. Although the oxidation of methylarenes represents an ideal route to aromatic aldehydes due to the availability of starting materials, existing methods face significant challenges, including reliance on hazardous oxidants, costly catalysts, poor scalability, and limited compatibility with electron-deficient substrates. To address these limitations, we report a practical and scalable electrochemical method for the oxidation of electron-deficient methylarenes to access aromatic aldehydes, eliminating the need for chemical oxidants or homogeneous transition-metal catalysts. This approach operates under industrially viable conditions-high current densities (75 mA cm⁻2), minimal electrolyte loading (0.05 equiv), and operation in an undivided cell without additives-to produce aromatic acetals, which are readily hydrolyzed to the corresponding aldehydes. The use of minimal electrolyte not only reduces costs and simplifies product isolation but also significantly enhances anodic oxidation selectivity, ensuring high efficiency and practicality. This protocol exhibits a broad substrate scope, compatibility with both batch and continuous flow systems, and exceptional scalability, as demonstrated by successful kilogram-scale synthesis.

Alcohols and ketones are abundant and structurally diverse feedstocks, yet their direct transformation into organosilicon compounds remains challenging due to the difficulty in selective cleaving C─OH and C═O bonds. Here, we report an electrochemically driven deoxygenative C─Si bond formation strategy that converts alcohols and ketones directly to organosilicon compounds. The reactions operate under mild conditions without external redox reagents and sacrificial electrodes. A wide range of alcohols, including primary, secondary, and tertiary alcohols, as well as ketones, are efficiently converted to the corresponding organosilane products. Overall, this study provides a step-economical, highly efficient, and synthetically versatile platform for the direct conversion of feedstock chemicals into valuable organosilicon compounds.

ConspectusMolecular photoelectrocatalysis, which combines the merits of photocatalysis and organic electrosynthesis, including their green attributes and capacity to offer novel reactivity and selectivity, represents an emerging field in organic chemistry that addresses the growing demands for environmental sustainability and synthetic efficiency. This synergistic approach permits access to a wider range of redox potentials, facilitates redox transformations under gentler electrode potentials, and decreases the use of external harsh redox reagents. Despite these potential advantages, this area did not receive significant attention until 2019, when we and others reported the first examples of modern molecular photoelectrocatalysis. These studies showcased the immense synthetic potential of this hybrid strategy, which not only inherits the strengths of its parent fields but also unlocks unprecedented reactivity and selectivity, enabling challenging transformations under mild conditions while minimizing the reliance on external stoichiometric harsh oxidants or reductants.In this Account, we present our efforts to develop photoelectrocatalytic strategies that leverage homogeneous catalysts to facilitate diverse radical reactions. By integrating electrocatalysis with key photoinduced processes such as single electron transfer (SET), ligand-to-metal charge transfer (LMCT), and hydrogen atom transfer (HAT), we have established photoelectrocatalytic methods to transform substrates such as organotrifluoroborates, arenes, carboxylic acids, and alkanes into reactive radical intermediates. These intermediates subsequently engage in heteroarene C-H functionalization reactions. Importantly, under these photoelectrochemical conditions with homogeneous catalysts, reactive radical intermediates generated in the bulk solution readily participate in efficient radical reactions without undergoing further overoxidation into carbocations, a common challenge in conventional electrochemical systems.By further integration of photoelectrocatalysis with asymmetric catalysis, we have developed photoelectrochemical asymmetric catalysis (PEAC), which proves to be efficient in the enantioselective synthesis of chiral nitriles. This approach involves two relay catalytic cycles: the initial photoelectrocatalytic process engenders benzylic radicals from precursors such as alkyl arenes, benzylic carboxylic acids, and aryl alkenes, and these C-radicals are then subjected to enantioselective cyanation in a subsequent copper-electrocatalytic cycle.Within the realm of oxidative photoelectrochemical transformations, the anode serves as a crucial component for recycling or generating the photocatalyst, while the cathode promotes proton reduction. This dual functionality enables oxidative transformations via H2 evolution, eliminating the reliance on external chemical oxidants. Furthermore, the adaptability of electrochemical systems, achieved through precise manipulation of electric current or potential, ensures meticulous control over the generation and turnover of multiple catalytic species of diverse electrochemical properties. This unique tunability allows for exceptional control over the catalytic process. As a result, despite being a relatively nascent field, molecular photoelectrocatalysis has become instrumental in enabling numerous challenging transformations that were once difficult or required harsh conditions.

The direct C─H amination of arenes is a powerful strategy for synthesizing arylamines, yet existing methods often suffer from limited substrate scope, poor selectivity, or scalability issues, particularly for electron-deficient arenes. Here, we introduce a continuous flow electrochemical C─H amination via a pyridination-aminolysis sequence, enabling the efficient functionalization of arenes with diverse electronic properties. The method operates under continuous flow electrochemical conditions, avoiding the need for divided cells, strong chemical oxidants, or homogeneous transition-metal catalysts. The broad substrate scope includes a wide range of electron-rich, electron-deficient, and halogenated arenes, as well as heterocycles, demonstrating excellent functional group tolerance. Furthermore, the process is readily scalable, as shown by a 4-day continuous operation in parallel microreactors, producing over 100 grams of aniline product with high efficiency. This study highlights the potential of continuous-flow electrochemistry as a versatile and practical platform for sustainable C─H functionalization in organic synthesis.