Indazole serves as an important organic synthetic intermediate with significant pharmaceutical activity. Herein, we report the first example of efficiently constructing the indazole framework through an acceptorless dehydrogenative annulation reaction using alcohols and hydrazines as starting materials. This strategy, which employs an N-heterocyclic carbene (NHC)-imine-phosphine (CNP) pincer ruthenium catalyst, operates under mild conditions with high efficiency, offering a new pathway to simplify indazole synthesis.

Pyridine is a privileged scaffold in pharmaceuticals, and selective C2-alkylation, particularly methylation, represents a valuable strategy to fine-tune drug-like properties such as metabolic stability and solubility. However, achieving highly site-selective methylation at the C2 position remains challenging. Herein, we report a ruthenium-catalyzed, copper-mediated protocol that enables direct C2-methylation of pyridines. The transformation proceeds through a formal N-to-C methyl migration in N-methylpyridinium salts, which serve dually as activated substrates and internal methyl donors, thereby ensuring excellent atom economy. This operationally simple and scalable approach is compatible with the late-stage modification of complex bioactive molecules. Furthermore, the migratable groups can be extended to longer alkyl and benzyl substituents, highlighting the broad synthetic utility of this strategy.

Constructing quaternary carbon centers represents a significant yet challenging task in synthetic and medicinal chemistry. Herein, we report an efficient electrochemical nickel-catalyzed reductive cross-electrophile coupling for the modular synthesis of diverse quaternary carbon centers from readily available tertiary alkyl bromides and benzyl chlorides. This electrochemical protocol eliminates the dependence on stoichiometric metallic reductants, making this method more sustainable and attractive.

Selective producing CH4 by CO2 electroreduction remains challenging, primarily hindered by the complexity of reduction products, sluggish protonation kinetics, and competitive hydrogen evolution reaction. Herein, we developed a silica-copper composite catalyst (CuO/SiO2), where CuO nanoparticles are dispersed on the hydroxyl-functionalized SiO2 nanosheet. The hydroxyl-functionalized SiO2 support promotes the formation and transfer of interfacial reactive hydrogen species, lowers the energy barrier for the reduction of CO2 to CH4 by stabilizing *COOH, *CO, and *H intermediates. Meanwhile, it favors the hydrogenation of *CHO over C-C coupling between C1 intermediates, thereby shifting product selectivity from multi-carbon products towards CH4. As a result, CuO/SiO2 catalyst delivers high CH4 selectivity over a broad current density range of 0.2-0.9 A/cm(2), with a peak Faradaic efficiency of 66.2% at 0.6 A/cm(2). This work demonstrates an effective interfacial engineering strategy for enhancing the selectivity of CO2-to-CH4 conversion.

Developing a stereodivergent approach to access chiral metal-organic cages is an appealing yet challenging goal in the field of supramolecular chemistry. In this work, we report a stereodivergent method for constructing chiral cages via subcomponent self-assembly of a chiral diamine, 3-substituted 2-formylpyridines, and iron(II) ions, yielding structurally well-defined architectures. Remarkably, simply altering the steric properties of the subcomponents allows for selective control of the handedness at the metal vertices, thereby enabling the stereodivergent synthesis of chiral cages. Systematic modulation of the 2-formylpyridine substituents revealed a linear correlation between the molecular volume and diastereomeric excess, providing a predictable means of achieving stereoselective assembly. Furthermore, gas sorption studies revealed distinct N2 uptake behaviors between the two diastereomers, with the Δ-isomer exhibiting significantly enhanced CO2 selectivity. This work establishes a sterically governed strategy for tuning both the chirality and functional properties of metal-organic cages.

A Brønsted acid-promoted exo-cyclization of bicyclo[1.1.0]butyl ketones with hydrazines has been established. This approach enables efficient ring expansion, leading to a diverse range of 2,3-diazabicyclo[3.1.1]heptenes. Mechanistic studies reveal that the carbonyl group is pivotal, fulfilling a dual role as both the reactive center and a latent activating group. Moreover, the unique dual nucleophilic character of hydrazines, featuring two nitrogen-based nucleophilic sites, is crucial to the success of this transformation.

To develop highly stable and active Ru complex catalysts for CO(2 )hydrogenation, we synthesized Ru complexes bearing rigid pincer & hybull;type tridentate NNN (pyrazole & hybull;pyridine & hybull;pyrazole) ligands and weakly coordinated triphenylphosphine (PPh3) ligands. The NNN ligands can strongly chelate with the Ru metal center, contributing to the overall robustness of the catalytic system. Meanwhile, PPh3 can easily dissociate to form vacant coordination sites, thereby enhancing catalytic activity. As a result, the Ru(||)& hybull;NNN complex [Ru(L & hybull;NNN)Cl(PPh3)(2)]Cl (1, L & hybull;NNN=2,6 & hybull; bis(5 & hybull;methyl & hybull;1H & hybull;pyrazol & hybull;3 & hybull;yl)pyridine) was not only quite stable, but also showed high activity for CO(2 )hydrogenation to formate, achieving a TON of up to 150 000. In the mechanism study, based on the results of in & hybull;situ NMR, in & hybull;situ HPLC & hybull;HRMS spectra, and density functional theory calculations, it is speculated that the active intermediates with empty coordination sites are highly active species in CO(2 )hydrogenation. CCDC: 2367151, [Ru2(L & hybull;NNN)2Cl(2) (PPh3)(2)]Cl-2 (2).

Skeletal editing, especially for nitrogen-containing aromatic heterocycles, has become an increasingly important strategy for drug modification and development, enabling rapid compound diversification without the need for de novo synthesis. Notably, despite their pervasiveness, established methods fall short in selective atomic swap due to the high stability of aromatic compounds. In this study, we report a CN-to-S atom swap approach for direct skeletal editing of pyridines into thiophenes via the addition of nucleophiles, ring-opening, and ring-closing (ANRORC) processes. Elemental sulfur, acting as an amphiphilic reagent, mediated this process through successive electrophilic and nucleophilic addition of the central sulfur atom at predictable sites. The power of this skeletal editing strategy was highlighted through the modification of the frameworks of natural products and drug molecules in a precise and controllable manner.

Chiral-induced spin selectivity (CISS) has emerged as a powerful concept for directing spin-dependent transport in chiral materials design. Although helicenes are attractive chiral scaffolds for spin-selective functions, achieving high spin polarization remains challenging due to the difficulty in constructing highly ordered solid-state architectures. Here we report an electrochemical C‒H/N‒H coupling that enables rapid construction of a library of luminescent aza[5–9]helicenes. Single-crystal X-ray diffraction (SC-XRD) reveals rare β-type columnar packing and narcissistic chiral self-sorting into homochiral columns in both racemic and enantiopure crystals of bromo- and trifluoromethyl-substituted azahelicenes, driven by intermolecular π–π interactions together with intercolumnar C‒Br···N halogen bonding and C‒H···F contacts. As a result, thin films of these aza[7]helicenes exhibit pronounced chirality-dependent spin-selective charge transport with spin polarization ratios of up to 94% measured by magnetic conductive-probe atomic force microscopy (mc-AFM), along with circularly polarized luminescence (CPL) with dissymmetry factors of up to 1.4×10 − 2 . This work establishes a structure-driven strategy for enhancing chirality-induced spin selectivity, providing new insights into the design of chiral materials for spin-selective transport.

Coordination-driven self-assembly provides a powerful tool for constructing chiral metal-organic cages with well-defined stereochemistry and function; however, enantiopure cages with high structural complexity remain rare, and their governing design principles are not yet well established. Here we report the synthesis of O -symmetric, face-capped Pd 6 L 8 octahedral cages assembled from bowl-shaped, helically chiral ligands with Pd II . Assembly of the racemic ligand afforded rac -Pd 6 L 8 as a pair of enantiomers, Pd 6 L P 8 and Pd 6 L M 8 , via narcissistic chiral self-sorting. Single-crystal X-ray diffraction (SC-XRD) and reduced density gradient (RDG) analysis demonstrated that the twelve interligand π–π stacking interactions provide main driving force for such chiral self-sorting. Enantiopure ligands also self-assembled with Pd II to give enantiopure Pd 6 L P 8 and Pd 6 L M 8 , that could be used for enantioselective recognition of BINOL-derived chiral phosphoric acids, with enantioselectivity proven by distinct binding constants, emission responses and 1 H NMR discrimination. This study demonstrates how interligand noncovalent interactions can be used to govern stereochemical outcomes in complex polyhedral cages formation and highlights their potential application in chiral sensing.

An efficient multicomponent cascade reaction for the synthesis of structurally diverse 2-pyrazolines has been developed through a MnI-CNP complex-catalyzed acceptorless dehydrogenative coupling (ADC) strategy. The transformation integrates alcohol dehydrogenation, aldol reaction, and subsequent cyclization with hydrazines in a single operation, enabling direct access to 2-pyrazolines from readily available alcohols, ketones, and hydrazines without the need for stoichiometric oxidants. A broad substrate scope was achieved, tolerating both alkyl and aryl substituents at the 3- and 5-positions. Control experiments show that the MnI catalyst operates exclusively in the initial alcohol-to-aldehyde dehydrogenation step, with the in situ-generated alpha,beta-unsaturated ketone serving as a key intermediate. This work provides a practical and sustainable entry to 2-pyrazolines and expands the synthetic utility of MnI-catalyzed ADC chemistry.

The development of novel chiral phosphine ligands is a key area of research in organic synthesis. An efficient synthetic method for the preparation of helically chiral monophosphorus ligands was reported. Using this approach, four structurally distinct, helically chiral, bowl-shaped monophosphorus ligands were successfully synthesized. Their catalytic activities were systematically evaluated in palladium-catalyzed C-C and C-N bond-forming reactions. Enantiopure ligands were obtained via HPLC resolution. Although these reactions did not achieve high enantiocontrol, the ligands demonstrated a unique helical chiral cavity and excellent catalytic activity. These findings suggest that this class of compounds warrants further exploration in other asymmetric catalytic reactions.

A mild and efficient skeletal editing strategy for the synthesis of fully substituted pyrroles from pyridinium salts is described. The transformation proceeds through a sequence of pyridinium salt ring opening, imidation, ring closing, and bromination steps, demonstrating broad substrate scope, good functional group tolerance, and scalability to the gram scale. Mechanistic studies support a pathway involving the regioselective addition of a succinimidyl radical to a Zincke aldehyde intermediate, followed by cyclization and bromination. The resulting pyrrole products are equipped with multiple orthogonal functional handles that enable diverse downstream derivatization.

The development of novel chiral phosphine ligands is a key area of research in organic synthesis.An efficient syn-thetic method for the preparation of helically chiral monophosphorus ligands was reported.Using this approach,four structur-ally distinct,helically chiral,bowl-shaped monophosphorus ligands were successfully synthesized.Their catalytic activities were systematically evaluated in palladium-catalyzed C-C and C-N bond-forming reactions.Enantiopure ligands were ob-tained via HPLC resolution.Although these reactions did not achieve high enantiocontrol,the ligands demonstrated a unique helical chiral cavity and excellent catalytic activity.These findings suggest that this class of compounds warrants further ex-ploration in other asymmetric catalytic reactions.

ConspectusSkeletal editing has emerged as a transformative strategy in synthetic chemistry, providing a direct route to modify molecular frameworks that are challenging to access by conventional methods. This approach is particularly valuable for privileged, electron-deficient heteroarenes such as pyridines and pyrimidines─scaffolds ubiquitous in pharmaceuticals and functional materials. The inherent aromatic stability and electron-deficient nature of these compounds pose significant challenges to skeletal modification. Current methodologies address these challenges through dearomatization to access activated intermediates for subsequent skeletal restructuring. These strategies can be broadly divided into three categories. The first involves the photochemical activation of pyridine N-oxides or N-ylides to generate high-energy intermediates, such as 1,3-oxazepines and 1,2-diazepines. The second approach employs a dearomative addition to convert electron-deficient pyridines into electron-rich cyclic dieneamine intermediates. The third approach is the quaternization-facilitated ANRORC (Addition of the Nucleophile, Ring Opening, and Ring Closure) pathway, wherein N-activated pyridinium salts undergo nucleophilic ring-opening to form Zincke-type intermediates that exhibit versatile reactivity. Through these reactive intermediates, various skeletal editing systems for pyridines and pyrimidines have been developed. Among them, the Zincke intermediate involved in the ANRORC strategy provides exceptional tunability via systematic variation of three key elements: activators, nucleophiles, and functional modifiers, enabling precise control over the editing outcomes while maintaining excellent functional group compatibility. Our research program has systematically advanced the ANRORC process into a powerful strategy for skeletal editing of the electron-deficient N-heteroarenes. Through the rational design of activators (including alkyl, vinyl, benzyl, dinitrophenyl and Tf groups) and the incorporation of diverse nucleophiles (O-, C-, and N-based), we have established a modular system capable of generating a range of key open-chain intermediates such as Zincke aldehydes, azatrienes (including Zincke imines), streptocyanines, and vinamidinium salts. Strategic modification of these versatile intermediates using a wide range of electrophilic, amphiphilic, or dipolar reagents enables multiple editing paradigms, including efficient pyridine ring contractions to functionalized pyrroles, degenerate ring transformations of pyridines with concurrent core functionalization, and denitrogenative annulation of pyridine to arene dialdehydes or thiophene motifs. Moreover, it facilitates the transformation of pyrimidines into diverse nitrogen-containing heterocycles via vinamidinium salt intermediates. In this Account, we systematically summarize our work on skeletal editing using tunable Zincke intermediates generated via the ANRORC pathway, with particular emphasis on mechanistic understanding, substrate scope, and synthetic applications. By outlining prospective research directions, we anticipate this Account will set the stage for future exploration of the ANRORC strategy in skeletal editing of heterocycles, promote the discovery of novel reactivity patterns, and thereby contribute to further progress in this dynamic field.

Abstract We report a pyridine-to-pyridazine skeletal editing strategy that enables a formal CN-to-NN atom-pair exchange from readily available pyridines. Key to this transformation is hydrazine-mediated ring opening of N-(2,4-dinitrophenyl)pyridinium salts, followed by mCPBA-promoted oxidation to a 5-diazenylpenta-2,4-dienal intermediate that undergoes 6π-electrocyclization and oxidative deformylation to deliver pyridazines. This method features mild reaction conditions, broad substrate scope, late-stage applicability, and gram-scale scalability.

The electrochemical CO2 reduction reaction (eCO2RR) typically yields low-carbon products (Cn, n ≤ 3), thereby limiting its application scope. Herein, we design a cascaded eCO2RR-hydroformylation system for synthesizing high-carbon (C9) aldehydes from CO2. NixCo1-x@NCNT catalysts enable the production of syngas with a tunable H2/CO ratio ranging from 0 to 5.3 using CO2 and H2O as feedstocks. Subsequently, Rh-based complexes are constructed to catalyze the downstream phenylacetylene hydroformylation. As a result, this tandem electrocatalysis-hydroformylation approach achieves a high phenylacetylene conversion efficiency of 87%, with aldehyde selectivity up to 53% under room pressure and temperature.

High-fidelity kidney function imaging is important for assessing the nephrotoxicity of drugs and diagnosing renal diseases. However, the current challenges in achieving accurate kidney imaging include unspecific signal enhancement due to albumin binding and relatively low distribution of imaging agents in kidneys. Here, for the first time, a side-chain engineering strategy that incorporates hydrophilic six-membered heterocycles into aza-hemicyanine for generating high-performance kidney imaging agents with protein-interference-free and kidney-targeting features is proposed. Based on these unique aza-hemicyanine dyes, the first kidney-targeting and albumin-insensitive H2S2 near-infrared (NIR) fluorescent probe NA-H2S2 is designed, which demonstrates effective kidney distribution following intravenous injection and is specifically activated by H2S2. The designed probe presents a highly rapid, selective and sensitive response to H2S2 with a detection limit as low as 24.21 nm. Additionally, it successfully achieves real-time in vivo NIR fluorescence imaging of H2S2 during erastin/cisplatin induced renal ferroptosis. Moreover, it also enables rapid detection of H2S2 through in vitro optical urinalysis, offering significant diagnostic value for renal ferroptosis. Overall, this study not only presents a practical kidney-targeting H2S2 fluorescent probe NA-H2S2 with increased imaging accuracy but also provides promising kidney-targeting and albumin-insensitive aza-hemicyanine dyes for further development of kidney disease-related probes.

The overall energy efficiency (EE) is critical for commercializing promising electrochemical technologies, such as the carbon dioxide reduction reaction (CO2RR). Despite the rapid development of advanced catalysts and reactors for CO2RR, its commercial potential is still hindered by the sluggish oxygen evolution reaction (OER), which causes high cell voltages and low EEs. Herein, we developed a NiOOH@Ni3S2 catalyst on the surface of nickel foam (NF) via an electrochemical surface reconstruction strategy. We observed that the oxidation of glycerol (GLY) to formate (FA) is more thermodynamically favorable than the OER on the developed NiOOH@Ni3S2/NF catalysts. The Ni2+/Ni3+ redox couples within the NiOOH@Ni3S2 heterojunction enhance the charge transfer kinetics between the active sites and adsorbed reaction intermediates, facilitating the highly selective and active generation of FA from GLY oxidation reaction (GOR), with a remarkable Faradaic efficiency (FE) of 94% achieved at 100 mA·cm−2. Comprehensive mechanistic studies identified that the reaction pathway towards FA generation starts from glyceraldehyde intermediates, and glycolate was considered as the key species. Moreover, benefiting from the efficient conversion of CO2 to FA on bismuth nanosheets, the GOR//CO2RR paired electrolysis system realizes a remarkable overall FE of ca. 190% for FA co-production at 160 mA·cm−2 (cathodic FE: 91.25% and anodic FE: 98.70%). This proceeds at a cell voltage of ca. 2.32 V, which is ca. 0.85 V lower than that of OER-assisted CO2RR system at the same current density. This work provides new insights for co-upgrading CO2 and biomass to value-added chemicals.