Controllable peroxidase-like catalysis of chondroitin sulfate-hemin conjugates for in situ hydrogel formation in biomedical applications.

Catalytic activity of a palladium–Bistheophylline polymer complex with N–Pd–N coordination linkages in copper–free Sonogashira coupling reaction

Developments in Suzuki-Miyaura cross coupling reaction (SMR) towards green synthesis

ConspectusHigh-efficiency catalytic reactions are crucial to the development of a clean and sustainable society. Thermocatalysis specializes in large-scale continuous production, but certain specific thermocatalytic processes are highly endothermic and require high operating temperatures to achieve the desirable equilibrium conversion efficiency. With the rapid development of renewable energy, electrocatalysis has drawn extensive attention because it enables green and precise chemical synthesis. Nevertheless, the electrocatalytic reaction, which undergoes a multiple-electron transfer process and suffers from inherently sluggish kinetics, faces a critical challenge for large-scale application due to its high overpotential and mass transfer limitation.Recently, the synergistic integration of thermocatalysis and electrocatalysis proposed by our group has demonstrated a series of advantages in enabling efficient catalytic reactions, which have attracted widespread research interest. The integration of thermal and electrocatalysis offers a transformative strategy that circumvents thermodynamic limitations of conventional reactions, manipulates reaction energy barriers and pathways, and thereby significantly improves the reaction rates and selectivity. Beyond these benefits, it also simplifies product separation, thereby enhancing the overall process economics. In this Account, we systematically summarize recent progress in synergistic coupling of thermocatalysis and electrocatalysis, focusing on three main strategies: (1) room-temperature thermocatalytic-electrocatalytic coupling, which circumvents traditional high reaction energy barriers via the synergy of spontaneous nonelectrochemical and electrochemical processes; (2) tandem thermocatalytic-electrocatalytic reaction, which accurately addresses the shortcomings of electrocatalytic and thermocatalytic module to break through the conversion-selectivity trade-off; and (3) an integrated thermocatalytic-electrocatalytic pathway, in which the electrochemical procedures can break the thermodynamic equilibrium of the reaction and thereby improve the overall energy efficiency. Together, these approaches provide a versatile way for constructing a high-efficiency catalytic system by revealing the design criterion of the coupling reaction process.Additionally, we discuss the key challenges and prospects in this emerging field in terms of three aspects: (i) further improving the matching degree between thermocatalysis and electrocatalysis; (ii) elucidating the mechanism of reaction activity enhancement; and (iii) trying to scale up the system for industrial-scale level production. We hope this Account will guide the development of more efficient catalytic systems in the years ahead.

Selective defluorinative functionalization of inexpensive and readily available trifluoromethylated arenes represents a promising synthetic strategy for accessing pharmaceutically valuable fluorinated motifs. However, such transformations typically rely on transition-metal catalysts, and the development of sustainable, metal-free catalytic systems, particularly for three-component coupling reactions, remains scarce. Herein, we report a transition-metal-free, photoinduced defluorinative alkylamination of alkenes. This reaction utilizes inexpensive and readily available trifluoromethylarenes and anilines as coupling partners to afford a diverse array of γ,γ-difluoroalkylamines, valuable bioisosteres of β-amino ketones, which are prevalent motifs in pharmaceuticals and biologically active compounds. The transformation proceeds efficiently under blue light irradiation in the presence of an organic photosensitizer. Mechanistic studies indicate that the reaction proceeds via a sequential single-electron transfer (SET) pathway, culminating in C-N bond formation with anilines.

ConspectusHypervalent halogens (I(III) and Br(III) derivatives) represent a versatile and effective class of reagents that are widely used in synthetic organic chemistry. Many of these compounds, however, are unstable and pose risks during handling, which limits their practical application, especially on a larger scale. In this context, the electrochemical in situ generation of hypervalent halogen species represents an interesting alternative to conventional methods. Inspired by these ideas, we launched a collaborative "trans-Baltic" research program 10 years ago that is still ongoing. Our efforts focus on developing electrochemical methods for synthesis of these reactive species, their synthetic application and mechanistic elucidation. After initial studies on the electrochemical generation of dialkoxy-λ3-iodanes, our activities have expanded to include analogous hypervalent bromine compounds as well as diaryliodonium and bromonium salts. Our work has resulted in a large number of new species, most of which exhibit interesting, useful, and versatile reactivity. Their synthesis, electrochemical properties, and reactivity are the focus of this article.Our review starts with the discussion of fluorinated dialkoxy-λ3-iodanes, which are readily formed via anodic oxidation of iodoarenes in fluorinated alcohols such as HFIP or TFE, the latter acting both as solvent and stabilizing ligands. To date, no nonelectrochemical access to such species has been reported, likely due to their sensitivity toward nucleophiles. Although the λ3-iodanes derived from iodoarene conversion in HFIP cannot be isolated, they are effective in various oxidative coupling reactions when generated in situ. Incorporating ionic tags enables dual functionality as mediator and supporting electrolyte and allows facile recovery after electrolysis. In contrast, analogous dialkoxy-λ3-bromanes could not be synthesized electrochemically. However, singly and doubly chelation-stabilized bromanes can be prepared by anodic oxidation in HFIP. The doubly chelated species is significantly more stable and isolable. The less stable singly chelated form can be converted into a stable [Br-O-Br] dimer, which is suitable both as a precursor for other hypervalent bromine compounds and as a reagent for synthetic applications. The intrinsic Br(III) reactivity of the doubly chelated bromane is moderate but can be activated either thermally or with TfOH, enabling both ionic and single-electron transfer (SET) reactions. In contrast, the [Br-O-Br] dimer undergoes homolytic cleavage upon heating or near-UV irradiation, enabling radical coupling.When using noncoordinating solvents such as acetonitrile, anodic oxidation of iodoarenes yields iodonium salts. An acid-free, anion-flexible method was developed, allowing counterion variation via the supporting electrolyte and enabling aryl transfer reactions. Compared to the iodonium species, the bromonium analogues are much more difficult to access and are limited to cyclic species formed from 2,2'-dibromobiphenyls. Together with other newly identified hypervalent species, these compounds offer promising starting points for future research.

A metal-free strategy for the oxidative difunctionalization of indole derivatives has been developed using iodine and DMSO as the key reaction components. This protocol enables an environment friendly and efficient oxidative C(sp2)-H coupling reaction between indoles, amines, and diphenyl dichalcogenides under mild conditions. The transformation provides direct access to a variety of aminochalcogenylated indoles through the formation of C(sp2)-N and C(sp2)-S/Se bonds in moderate to good yields. A broad range of indole substrates and diaryl disulfides/diselenides were found to be compatible with the reaction conditions. Notably, morpholine derivatives were identified as the most effective amine partners, while more nucleophilic amines were less suitable under the optimized conditions. Furthermore, sulfoximines were successfully employed as alternative nitrogen sources, highlighting the versatility and synthetic utility of the present methodology. The operational simplicity, avoidance of transition metals and external oxidants, and broad substrate scope make this protocol an attractive approach for the synthesis of biologically relevant aminochalcogenylated indole derivatives.

Incorporating heteroatoms and non-benzenoid rings-such as pentagons or heptagons-into polycyclic aromatic frameworks represents a key approach for designing advanced optoelectronic materials. In this work, two novel pentacene derivatives, DSH-1 and DSH-2, were synthesized by embedding sulfur-doped heptagons into the conjugation backbone via efficient Ullmann coupling and acid-catalyzed Friedel-Crafts reactions as the key steps. Single-crystal analysis shows that DSH-1 adopts a curved bow-shaped structure, integrating an oxygen-doped pentagon and two sulfur-doped heptagons to form a unique 7-5-7 system. In contrast, DSH-2 features a 7-6-7 system and displays a Z-shaped conformation. Because of their difference in conformation, DSH-1 exhibits a significantly red-shifted absorption, superior thermal stability, and tighter intermolecular interactions, and shows p-type semiconducting property with charge mobility of 0.25cm2 V-1 s-1. Because of the nonplanar configuration of these two molecules, the sulfur atoms can act as anchoring groups in the single-molecule conductance characterization. In addition, DSH-1 can be oxidized to a radical cation DSH-1•+ with red-shifted absorption around 650nm and high stability, resulting from the enhanced aromaticity of the sulfur-doped heptagon rings after oxidation.

Palladium-catalyzed cross-coupling reactions of propargylic electrophiles with carbon nucleophiles have been established as straightforward and reliable methods for the synthesis of allenes and 1,5-enynes. However, such transformations have so far been limited to two-component systems. Herein, we report a palladium-catalyzed three-component coupling reaction involving bromoalkynes, diazoesters, and boronates. The reaction proceeds via allenylpalladium or propargylpalladium intermediates, generated through a sequence of oxidative addition, carbene formation, and migratory insertion upon interaction of haloalkynes with diazo compounds under palladium catalysis. Depending on the structure of the boronate substrate, the three-component coupling selectively delivers either allenes or 1,5-enynes. DFT calculations provide insight into this substrate-dependent chemoselectivity. The method exhibits broad substrate scope and has been successfully applied to the concise synthesis of two pharmaceutical agents-aminoglutethimide and anileridine.

meso-meso', α-α', β-β'-Triply-linked N-confused porphyrin (NCP) dimers were synthesized via stepwise oxidative coupling reactions of 5,10,15-triaryl-NCP, followed by nickel or silver metalation. The novel dimers possess extended π-conjugation throughout the entire fused dimer structures, leading to Hückel 36π-antiaromaticity and 38π-aromaticity for the nickel and silver complexes, respectively. Theoretical investigations using the gauge-including magnetically induced current (GIMIC) method reveal the pivotal role of NCP cross-conjugation and NH tautomerism in forming the global π-conjugation circuit. Redox reactions induce a unique switching of the π-conjugation circuits, transforming delocalized π-conjugation into localized π-conjugation in the NCP macrocycle, giving rise to an antiaromatic domain at the bay area.

Glycine, an indispensable amino acid essential for diverse biological processes, remains challenging to synthesize directly via electrosynthesis from simple carbon and nitrogen precursors. Herein, we report a highly efficient electrochemical route for glycine production through the reductive coupling of oxalic acid (H2C2O4) with hydroxylamine (NH2OH) or nitrate (NO3 -) over a Mott-Schottky Sn/SnO2 heterojunction catalyst enriched with oxygen vacancies. When employing H2C2O4 and NH2OH as feedstocks, a remarkable Faradaic efficiency (FE) of 91.6% for glycine is achieved at -0.7V versus RHE, alongside a high yield of 135mmol gcat. -1h-1. To the best of our knowledge, this represents one of the best performances ever reported in this system. The catalyst also shows strong substrate versatility, enabling efficient glycine formation when NO3 - (in situ reduced to NH2OH) couples with glyoxylic acid or H2C2O4. Mechanistic studies indicate that the Mott-Schottky heterojunction significantly promotes the co-adsorption of H2C2O4 and NH2OH, while oxygen vacancies facilitate the hydrogenation of oxime intermediates to glycine. This study highlights the profound synergistic interplay between Mott-Schottky heterojunctions and oxygen vacancy defects in precisely modulating active sites and accelerating reaction kinetics, thereby offering a sustainable strategy for the green electrosynthesis of amino acids.

Stimuli-responsive heterogeneous catalysis is a powerful concept that unites the possibility for in situ regulation of the reaction parameter space with the enhanced recyclability of solid-state platforms. The presented work reports the first example of a light-responsive heterogeneous catalyst for a three-component coupling reaction that relies on photochromic-molecule-directed modulation of the copper oxidation states in metal-organic frameworks (MOFs) via a stimuli-responsive spiropyran derivative covalently integrated within a host scaffold. Comprehensive spectroscopic analysis, supported by theoretical modeling, establishes the first correlations among isomerization of a photochromic moiety, modulation of metal oxidation states in MOF metal nodes, and the material's overall chemical reactivity in a three-component coupling reaction. Moreover, this work provides the first confirmation that the photophysical performance of integrated spiropyran derivatives is maintained after exposure to selected reaction conditions, leading to material recyclability while preserving its catalytic activity. The developed photochromic MOF-based catalyst promoted the synthesis of 12 different compounds, including commodity chemicals and pharmaceuticals, with near-quantitative yields under mild reaction conditions while maintaining crystallinity and catalytic performance over multiple reaction cycles. Overall, these findings unlock a novel avenue toward noninvasive control of chemical reactivity via on-demand metal oxidation state modulation, establishing a new design principle for adaptive catalytic systems and offering a transformative pathway toward controllable chemical synthesis.

The reductive dicarbofunctionalization of alkenes represents a powerful platform for the rapid construction of complex motifs from abundant materials by forging two chemical bonds in a single operation. Despite significant progress, the use of excessive reductants remains largely limited to environmentally unfriendly metal reductants or pyrophoric/expensive organic reductants, which may lead to serious environmental pollution, high costs, and low functional group tolerance. By leveraging NaI, rarely employed as a reductant in coupling reactions, we developed a novel reductive aminomethylcyanoalkylation of alkenes accelerated by iron electron-shuttle catalysis, allowing for the synthesis of sterically congested amino nitriles, valuable yet synthetically challenging motifs in organic synthesis. Mechanistic studies further confirmed that sodium iodide serves as the decisive terminal reductant.

An unprecedented neutral "masked" non-external-donor-stabilized diborene is generated via intramolecular arene dearomatization of an N-heterocyclic imine (NHI)-supported free diborene. The free diborene intermediate is photochemically accessible from the masked form, as supported experimentally through chalcogenation reactions. Computational studies elucidate an alkyne-like bonding pattern and a triplet ground state with a ΔES-T = +1.2kcal mol-1 for the NHI-supported free diborene. Remarkably, the "masked" diborene activates pyridines, promoting transition-metal-free C-C bond formation with high C2 regioselectivity to afford homocoupling products under mild conditions. Mechanistic investigations reveal that stepwise coordination and B-C bond cleavage produce a bis-pyridine diborene intermediate, which undergoes reductive coupling via intrinsically strong double single-π-electron transfer from the B═B unit to the intramolecular pyridine ligands. Furthermore, oxidation with p-benzoquinone allows the release of free 2,2'-bipyridine derivatives. These findings provide access to insight into a hitherto elusive free diborene species, establish a previously unknown reactivity mode for diborenes, and demonstrate that this "masked" diborene functions as an exceptionally powerful double single-electron donor with the potential to mimic transition-metal behavior in the construction of organic molecules.

The regioselective reductive coupling of o-haloaromatic ketones with alkynes to access indenols still poses a challenge, as existing methods typically rely on stoichiometric metal reductants and elevated temperatures. Herein, we describe a photoredox/cobalt catalytic system that enables selective reductive coupling of o-iodo, o-bromo, and o-chloroaromatic ketones as well as o-bromoaromatic aldehydes, with terminal alkynes to afford 2-substituted indenols. This protocol uses a tertiary amine as the terminal reductant, proceeds at room temperature, and features mild conditions, excellent regioselectivity, and broad substrate scope.

The palladium-catalyzed Heck coupling represents a powerful method for constructing complex molecular structures, including biologically active ingredients. Implementing alternative reaction media in this industrially important transformation is crucial for developing environmentally safer processes and advancing sustainability. Herein, we report the first successful phosphine-free Heck protocol conducted in the biomass-derived solvent 1,4-pentanediol (1,4-PDO). The effects of key reaction parameters, i.e., Pd source, base type, and solvent water content, were systematically evaluated using iodobenzene and styrene as model substrates. Using the Pd(OAc)2/Et3N catalyst system, 4-substituted iodobenzene and styrene derivatives were subsequently employed to investigate the effects of their substituents' electronic parameters on reaction efficiency and functional-group tolerance. Excellent linear correlations (R2 > 0.9) were observed between the substituents' Hammett σ constants and performance. Taking advantage of the products' significant temperature-dependent solubility in 1,4-PDO, facile product separation via simple filtration can be achieved, avoiding high-solvent-consuming column chromatography and facilitating solvent recovery. Using this approach, 24 products were synthesized and isolated with moderate to high yields (53-83%) and high purities (>90%). Solvent and catalyst recycling were demonstrated over three cycles. This protocol reduces the E-factor by more than 90% relative to conventional Heck conditions, highlighting its potential for sustainable synthetic applications.

The binuclear ruthenium-fulvalene complex FvRu2(dmoppb)2Cl2[PF6]2 (1[PF6]2; Fv = fulvalene; dmoppb = 1, 2-bis(di(4-methoxyphenyl)-phosphino)butane) was synthesized by an oxidation-induced C-C coupling reaction, and the mixed-valence complex FvRu2(dmoppb)2Cl2[PF6] (1[PF6]) and reduced-state complex FvRu2(dmoppb)2Cl2 (1) were obtained through the reduction of 1[PF6]2 with ferrocene and bis(pentamethylcyclopentadienyl)iron, respectively. All complexes were characterized by single-crystal X-ray diffraction analysis. The spectral evolution observed during the gradual UV-vis-NIR spectroelectrochemical oxidation of complex 1 reveals a close correspondence to the static UV-vis-NIR spectra of 1[PF6] and 1[PF6]2. NIR spectroscopy analysis reveals that the mixed-valence complex 1[PF6] possesses a high degree of electron delocalization. The two-electron oxidation product 1[PF6]2 adopts a singlet ground state due to strong antiferromagnetic coupling between the two symmetry-equivalent RuIII-based unpaired electrons.This assignment is confirmed by the absence of EPR signals and the diamagnetic behavior and is further supported by theoretical calculations.

The quantification of dopamine (DA) is of great significance because abnormal DA levels are closely linked to several neurological and psychiatric disorders, such as Parkinson's disease, schizophrenia, and depression. In addition, DA analysis plays an important role in clinical diagnosis, pharmaceutical quality assessment, and the investigation of biochemical events in complex biological systems. In this work, a derivatization-based dual-mode sensing strategy was developed for DA determination based on its induced oxidative coupling reaction with 4-hexyl resorcinol (4-HRS) under alkaline conditions. This reaction produces azamonardine, a highly emissive compound that exhibits a strong absorption band at 445 nm and intense fluorescence emission at 490 nm under excitation at 450 nm. The proposed method provided linear responses over the ranges of 0.05–520 µM for colorimetric detection and 10–600 nM for fluorescence detection, with detection limits of 0.018 µM and 3.0 nM, respectively. In addition, the method showed strong sensitivity, acceptable selectivity, mild experimental conditions, and reduced analytical expense. When applied to injection and human serum samples, it produced results consistent with those obtained by LC-MS. Recovery values ranged from 95.0% to 107.2%, and all relative standard deviation (RSD) values were below 3.89%, confirming the method's good accuracy and repeatability.

Dehydrogenation reactions are thermodynamically constrained by their inherent endothermic nature. The concomitant thermodynamic barriers can be overcome via photochemical strategies that harness light to activate intrinsically strong C═O, C─H, and O─H bonds. This review surveys recent progress and challenges in acceptorless light-driven dehydrogenation reactions, focusing on dehydrogenation of linear sp3-hybridized bonds, dehydrogenative coupling reactions, dehydrogenative cyclizations, and dehydrogenation of cyclic hydrocarbons. We identified distinct trends in the catalysts used for light-driven dehydrogenations, including homogeneous unary photocatalysts in which a single molecule absorbs light and catalyzes both oxidation and hydrogen evolution, cooperative homogeneous systems in which two separate catalysts fulfill these roles, as well as heterogeneous systems including nanostructured semiconductors and hybrid materials. In particular, this work uniquely synthesizes mechanistic knowledge across these classes and introduces a unifying classification framework that clarifies how distinct photochemical mechanisms achieve bond activation and hydrogen evolution without external acceptors. First, homogeneous unary photoactive Rh(I) catalysts promote dehydrogenation of both linear and cyclic sp3-hybridized C-C bonds in hydrocarbon substrates via oxidative C-H addition with subsequent β-hydride elimination. Second, binary homogeneous photocatalytic systems, consisting of a photosensitizer and a transition-metal-based proton reduction catalyst, enable all four types of dehydrogenation reactions via SET. Third, heterogeneous catalysts employed in light-driven dehydrogenation reactions often comprise a semiconductive support material integrated with a transition-metal-based active site, functioning via Mott-Schottky type photoinduced charge separation.

Electrochemiluminescence (ECL) originates from excited-state species produced by electrochemical redox processes and has traditionally been attributed exclusively to the working electrode (WE), with the counter electrode (CE) regarded as electrochemically inert. Herein, we fundamentally challenge this paradigm by employing the single/dual-atom iron-doped hollow carbon spheres (Fe-HCS-T) as coreactant accelerants of the luminol-dissolved oxygen (DO) system. The coating of Fe-HCS-T not only catalyzes the formation of reactive oxygen species (ROS) at WE but also modulates the interfacial potential at the CE, thus triggering the luminol electro-oxidation at the CE. And the interelectrode coupling between luminol electro-oxidation and oxygen reduction reaction (ORR) enable high efficiency ECL at 0.025 V. Spatially- and potential-resolved ECL mapping, combined with radical-quenching studies and complementary electrochemical analyses, indicates a synergistic WE-CE coupling reaction mechanism that markedly amplifies light output. Leveraging this coupling effect, the Fe-HCS-T-based platform enables ultrasensitive Trolox detection across a dynamic range of 0.1 nM-10 mM. These results fundamentally challenge the conventional paradigm for ECL systems and highlight interelectrode coupling as a powerful strategy to boost ECL performance and expand capabilities in advanced sensing applications.