Oxa-quaternary carbon centers are prevalent in bioactive natural products and pharmaceuticals. However, the development of general and practical methods to construct these oxa-quaternary carbon stereocenters remains a formidable challenge. Herein, we report a desymmetrization strategy for the construction of oxa-quaternary carbon stereocenters based on palladium/chiral norbornene cooperative catalysis. With readily available aryl iodides and prochiral 2'-bromo-aryl-substituted tertiary alcohols as the building blocks, a wide variety of 6H-benzo[c]chromenes bearing an oxa-quaternary carbon stereocenter and a versatile C-Br bond are expediently prepared in a highly enantioselective manner (43 examples, up to 99% e.e.). Notably, both enantiomers can be stereodivergently obtained through a simple switch of the same configurated chiral NBE cocatalysts. The synthetic utility of this method is demonstrated by a successful scale-up experiment and diverse late-stage structural modifications through the facile elaboration of the common C-Br bond of the obtained chiral 6H-benzo[c]chromene products. In addition to the experimental studies, DFT calculations are performed to elucidate the reaction mechanism, the origin of enantiodiscrimination, and enantioselectivity inversion in this desymmetrization process.

ConspectusThe study of main-group molecules that mimic transition metal (TM) complexes in bond activation and catalysis has attracted considerable interest in recent decades. However, main-group elements lack the same electronic versatility that endows TM complexes with diverse reactivity patterns. This limitation has driven efforts to develop innovative strategies to harness and expand the reactivity of main-group compounds. Among these, leveraging cooperative effects between main-group centers has emerged as a particularly promising approach to fine-tune their reactivity, as exemplified by frustrated Lewis pairs (FLPs) and bimetallic main-group complexes. Despite these advances, examples of cooperative interactions involving multiple low-valent main-group element centers remain rare. Such cooperativity is of great interest because the presence of multiple low-valent centers facilitates enhanced multielectron transfer capabilities. Consequently, advancing the design and synthesis of multinuclear low-valent main-group compounds holds great promise for unlocking new reactivity in main-group chemistry.This Account details our studies of the synthesis of heavier tetrylene-stabilized low-valent main-group compounds and their applications in cooperative bond activation and catalysis. We describe the design of new types of multidentate silylene ligands and demonstrate their effectiveness in stabilizing boron(I) and aluminum(I) compounds, referred to as borylene and aluminylene, respectively. The cooperation between B(I)/Si(II) and Al(I)/Si(II) centers enables the cleavage of various bonds, including the N-H bond in aniline, the C=O bond in ketones and carbon dioxide, the N=O bond in nitrosoarenes, and the C≡O bond in carbon monoxide. These compounds serve as effective precatalysts for carbon dioxide reduction and the reductive coupling of nitrosoarenes to azoxyarenes, respectively. Using a bis(germylenyl)carborane ligand, we have isolated zerovalent group 14 compounds, such as stannylone and plumbylone. The cooperation between Sn(0)/Ge(II) and Pb(0)/Ge(II) centers enables multiple electron transfers to cleave the N=O bonds of nitrous oxide and nitro compounds. The stannylone acts as an efficient precatalyst for the deoxygenation of nitrous oxide and nitro compounds, leading to the formation of dinitrogen and hydrazines, respectively. These results provide a unique proof-of-concept, underscoring their potential as versatile platforms for challenging bond activation and catalysis.

Tricyclic compounds containing pyrrole or pyrrolidine scaffolds represent a privileged class of structures in pharmaceutical chemistry, owing to their prevalence in natural products and drug molecules. This review systematically summarizes the synthetic methodologies developed over the past five years for the construction of these complex frameworks, with a focus on transition-metal catalysis and organocatalysis. In transition-metal catalysis, significant advances have been made using palladium, rhodium, copper, and other metals, enabling a wide range of transformations such as C-H activation/annulation, [2 + 2 + 1] annulation, and stereodivergent cooperative catalysis. These strategies have facilitated the efficient construction of diverse tricyclic skeletons with high regio-, diastereo-, and enantioselectivity, as well as broad functional group tolerance. Organocatalytic approaches, including the use of chiral phosphoric acids, DMAP, and related catalysts, have emerged as powerful complements, offering metal-free alternatives with excellent stereocontrol and operational simplicity, particularly in cascade and cycloaddition reactions. The review provides an in-depth analysis from perspectives including reaction design, catalytic mechanisms, stereocontrol, and synthetic applications. It aims to serve as an up-to-date reference for researchers in related fields, fostering the further application of these privileged scaffolds in drug discovery and natural product synthesis.

The development of MOF-on-MOF architectures has emerged as a powerful strategy to expand the compositional diversity and hierarchical structures of MOFs, providing new opportunities to tailor their physicochemical properties and catalytic performance. Despite these advantages, their utilization in constructing oxidase-like (OXD-like) nanozymes with cooperative catalytic characteristics remains limited. Herein, a highly active MOF-on-MOF nanozyme was rationally constructed by integrating ZIF-67 with a benzoic acid (BA)-modified Ce-MOF, where ligand-modulated coordination defects were introduced into the heterostructure. Within this heterostructure, the spatially coupled Ce and Co centers enabled defect-coupled cooperative catalysis, which enhanced O2-involved oxidation capability and facilitated electron transfer during substrate oxidation, thereby improving OXD-like activity. Meanwhile, oxidized ABTS exhibited distinctly different reaction behaviors toward dihydroxybenzene isomers on the nanozyme surface. Notably, the reaction between ABTS and resorcinol (RS) generated a characteristic absorption peak at 530 nm, and the absorbance ratio at 530 nm and 417 nm served as a reliable response signal, enabling rapid and sensitive discrimination of RS from catechol (CA) and hydroquinone (HQ). This defect-coupled MOF-on-MOF nanozyme was validated to be an efficient nanozyme with simultaneously high catalytic activity and isomer target discrimination capability, which might provide a reference for the indigenous construction of powerful nanozymes.

Chiral propargylamines are a class of versatile building blocks in organic synthesis. Despite the recent breakthroughs on the catalytic asymmetric reductive alkynylation of amides to access propargylamines, a general protocol amenable to both aromatic and aliphatic tertiary amides remains elusive. Herein, we report that our recently developed methodology for the catalytic asymmetric reductive alkynylation of tertiary aliphatic amides can be extended to tertiary aromatic amides. Employing Vaska's complex/CuI/Carreira's (R,P)-PINAP ligand as the catalytic system and 1,1,3,3-tetramethyl-disiloxane (TMDS) as the hydrosilylation reagent, the method highlights good reagent economy and/ or excellent asymmetric induction as compared to the known ones. Moreover, the reductive alkynylation of tertiary aliphatic amides has been extended to a series of functionalized alkynes. It is expectable that the versatility, excellent functional group tolerance, and chemoselectivity of the method lay the foundation for diverse applications in organic synthesis and medicinal chemistry.

Photocatalytic nonoxidative coupling of methane (CH4, NOCM) to ethane (C2H6) is a promising route for CH4 valorization, yet its efficient implementation requires the seamless coordination of CH4 adsorption, C-H bond activation, and C-C coupling. This intrinsic complexity makes it fundamentally challenging for a single type of active site to drive the entire NOCM process efficiently. Herein, we induce the formation of Ce3+ sites on the surface of CeO2 by loading Ag nanoparticles (NPs) for NOCM, and achieve highly efficient and selective conversion of CH4 to C2H6. Mechanistic studies indicate that the Ce3+ sites enhance CH4 adsorption and facilitate C-H bond activation to generate methyl radicals (˙CH3). Subsequently, Ag NPs promote the coupling of ˙CH3, ultimately producing C2H6. This study presents a synergistic catalysis strategy for designing efficient photocatalysts to achieve the selective coupling of CH4 into higher-value chemicals.

β-Hydroxy allylic sulfides represent privileged motifs in bioactive molecules but remain challenging to synthesize owing to sulfur-mediated catalyst poisoning and stereocontrol issues. We report a nickel/photoredox cooperative catalysis system for the diastereoselective allylation of aldehydes with sulfur-substituted allylic acetates. Using an organic photocatalyst 4CzIPN under 450 nm blue light at room temperature, this protocol affords diverse β-hydroxy allylic tertiary sulfides in good yields with excellent diastereoselectivities (up to >20 : 1 dr). Broad substrate scope, mild conditions, and good functional group tolerance are demonstrated.

Coupling photocatalytic CO2 reduction with organic oxidation promises enhanced solar energy conversion and atom economy but remains challenging due to the difficulty in orchestrating selective redox transformations while suppressing side reactions. Here, we report a metal-free graphdiyne (GDY)/polymeric carbon nitride (PCN) heterojunction that achieves exceptional bifunctional performance in CO2 reduction coupled with tetrahydrofuran oxidation to γ-butyrolactone. The optimized composite delivers a CO production rate of 55 µmol·h-1·g-1 with 95% selectivity, and a γ-butyrolactone yield of 54% with near-unity selectivity (> 99%) under mild photothermal conditions, representing 2.9-fold and 6.8-fold enhancements over thermally treated PCN, respectively. Mechanistic investigations reveal that GDY serves as a hole-transport layer, generating a built-in electric field that drives spatial separation of charge carriers. This configuration confines electrons on PCN for CO2 reduction while directing holes to GDY for tetrahydrofuran activation. Moreover, the metal-free heterojunction suppresses over-oxidation pathways that plague metal-loaded systems, enabling remarkable selectivity control. This work establishes the GDY/PCN heterojunction as a powerful platform for cooperative photoredox catalysis and provides a blueprint for designing metal-free heterojunctions toward sustainable synthesis.

A palladium/norbornene (NBE) cooperative catalysis for the modular, one-pot synthesis of 3-alkenyl-2,3'-bisindoles from 3-iodoindoles and olefins is reported. This protocol enables the concurrent formation of the C2-C3' bisindole linkage and a C3-alkenyl group, affording the desired products in high yields with a broad substrate scope. Density functional theory (DFT) calculations reveal that the addition of p-toluenesulfonic anhydride (Ts2O) accelerates the C-H activation step via an in situ anion exchange. The method's utility is showcased by the synthesis of racemosin B and analogs, featuring two consecutive one-pot reactions.

The rational design of trifunctional electrocatalysts capable of driving the oxygen evolution reaction (OER), oxygen reduction reaction (ORR), and hydrogen evolution reaction (HER) remains a central challenge in renewable energy conversion. In particular, it remains insufficiently understood whether these reactions proceed on a universal active site or arise from reaction-dependent site specialization and multisite cooperation in single-atom catalysts. Herein, we perform a systematic density functional theory (DFT) screening of transition-metal (TM) single atoms anchored at oxygen vacancy sites of Nb2CO2 MXenes to identify stable and experimentally viable trifunctional SACs. Among the candidates, Pt-Nb2CO2 exhibits favorable conductivity, thermodynamic stability, and competitive trifunctional electrocatalytic activity, with overpotentials of 0.42 V for OER, 0.60 V for ORR, and -0.07 V for HER, comparable to benchmark catalysts such as Pt(111) and IrO2(110). Detailed electronic structure analyses reveal that the trifunctional activity originates from multisite cooperative catalysis. The d orbitals of the TM atoms dominate the activity of oxygen-related reactions (OER/ORR), where the d-band center, modulated by bandwidth effects, correlates well with the activity trends. In contrast, the HER activity is governed by TM-induced charge transfer and site-specific hydrogen binding characteristics. This work clarifies the electronic origin of multisite cooperative trifunctional electrocatalysis in TM-MXene SACs and provides a rational theoretical framework for the design of experimentally accessible multifunctional electrocatalysts.

ABSTRACT The development of chiral three‐dimensional, sp 3 ‐rich architectures to facilitate the discovery of potent functional molecules is at the forefront of synthetic chemistry. However, facile synthesis of saturated and bridged Si‐chiral silacycles remains elusive due to a lack of pluripotent Si‐prochiral platforms capable of diversity‐oriented asymmetric synthesis. Herein, we report the invention of functionalized prochiral 4,4‐disubstituted silacyclohexanones (FPDSs) as platforms for the modular synthesis of multifunctional sp 3 ‐rich Si‐chiral sila‐bicyclo[3.3.1]nonanes. The FPDS platforms are readily accessible via a newly established tandem S N 2‑substitution/Krapcho‑decarboxylation sequence as a key step to silacyclohexanone core. The utility of FPDS is demonstrated in catalytic asymmetric synthesis of diverse Si‐chiral sila‐bicyclo[3.3.1]nonanes via desymmetric intramolecular aldol reaction, tandem imine formation/Mannich, or Wittig/Michael sequence by chiral enamine catalysis, as well as α‐arylation by cooperative chiral enamine/palladium catalysis. Notably, this represents the first stereoselective method to produce functionalized sp 3 ‐rich Si‐chiral bridged silacycles and the first asymmetric organo/metal cooperative catalysis for forging Si‐chirality.

An aerobic carboheterocyclization of functionalized alkenes has been developed using secondary nitroalkanes as dual sources of α-nitroalkyl radicals and nitric oxide (NO) under cooperative phase transfer catalysis of KSeCN and TBAI. This method enables efficient synthesis of nitrogen- and oxygen-containing heterocycles via radical redox interplay between nitric oxide and tertiary carbon radicals. The current study highlights the mechanistic role of aerobic nitro-nitrite isomerization and expands the synthetic utility of radical-mediated tandem cyclizations under aerobic conditions.

Isoindolinones are valuable nitrogen-containing heterocycles, yet efficient access to highly functionalized derivatives remains challenging. Herein, we report a bioinspired carbonyl alkylative amination enabled by Ca(II)/HFIP cooperative catalysis for the modular synthesis of 3-alkyl-N-substituted isoindolinones. This three-component cascade combines amines, ketoesters, and alkyl-1,4-dihydropyridines via sequential imine formation, alkyl transfer, and intramolecular cyclization. The protocol proceeds under mild conditions with a broad substrate scope and excellent functional-group tolerance, affording diverse isoindolinones in good to excellent yields. Its synthetic utility is demonstrated in the late-stage functionalization of pharmaceuticals, natural products, and AIEgen labeling. This work extends Ca(II)/HFIP catalysis from hydride to alkyl transfer, providing a practical platform for sustainable C-C and C-N bond formation.

This study develops an efficient tandem catalytic strategy for the direct conversion of styrene into phenylacetaldehyde. The process employs a well-designed metal-organic layer (MOL) catalyst integrated with dual functional active sites: a manganese (Mn) site anchored at the porphyrin center for styrene epoxidation and scandium (Sc) grafted on the secondary building units (SBUs) of the MOL as a Lewis acid for rearrangement. This cooperative catalysis enables a one-pot conversion of styrene to phenylacetaldehyde with a yield reaching 84%, bypassing the need for intermediate isolation. Compared to conventional routes, this system demonstrates high selectivity and offers a green synthetic route to phenylacetaldehyde while highlighting the broad potential of MOLs in complex tandem reactions.

Chiral amino acids are essential building blocks in asymmetric synthesis and drug discovery, yet their efficient preparation from racemic mixtures remains challenging. Here we show that a rationally designed phosphine oxide catalyst derived from L-pyroglutaminol enables the highly efficient kinetic resolution of racemic amino acids under mild conditions. Using L-pyroglutaminol as the esterification reagent, this catalytic system delivers a broad range of chiral esters and recovered amino acids with excellent stereoselectivities (s > 1057). Mechanistic studies suggest that the superior stereocontrol arises from a cooperative double hydrogen-bonding interaction between the catalyst and the pyroglutaminol core. This work provides a practical and scalable approach to enantioenriched amino acids, highlighting the potential of dual chiral cooperative catalysis in asymmetric synthesis.

Polymerization-based wastewater treatment offers reduced oxidant demand and product recovery, yet practical application is hindered by catalyst fouling and unselective reactions due to single-site competition. Here, we report a readily synthesized and scalable ZnO/CuO catalyst featuring dual functional sites that decouple pollutant and oxidant activation. Zn sites preferentially adsorb/activate organics, whereas Cu sites predominantly activate the oxidant. This site differentiation programs two pathway regimes governed by pollutant electronic structure: electron-transfer-mediated polymerization for electron-rich substrates and radical-induced mineralization for electron-deficient substrates. Importantly, radicals generated during mineralization depolymerize the accumulated foulant layer in situ, effecting autonomous catalyst regeneration with a 2.5-fold performance recovery and reduced external regeneration demand. Process performance is validated in a 200 L self-circulating reactor, maintaining 98% removal efficiency for both pollutant classes over ten cycles. Toxicological profiling across multiple biological models, supported by metabolomics, confirmed effective detoxification of multi-pollutant wastewater, including restoration of normal metabolic function in zebrafish (e.g., lipid and glutathione metabolism). This study establishes a dual-site cooperative catalysis framework that leverages intrinsic wastewater chemistry for self-regeneration, showcasing a complete trajectory from atomic-scale design to reactor-scale implementation.

Introduction: The catalytic cycloaddition of CO2 with epoxides to produce cyclic carbonates represents one of the most promising CO2 utilization technologies, offering 100% atomic economy under mild conditions. Nevertheless, the development of cost-effective heterogeneous catalysts with high performance under solvent- and cocatalyst-free conditions remains a grand challenge. Herein, we report the rational design and synthesis of a multifunctional heterogeneous catalyst for efficient CO2/propylene oxide (PO) cycloaddition under solvent- and cocatalyst-free conditions. Methods: The ZnMgAl-Br- heterogeneous catalyst was prepared through an integrated coprecipitation- ion exchange method. Structural and physicochemical properties were systematically characterized using SEM, XRD, EDX mapping, BET, and NH3-TPD, which confirmed the coexistence of abundant Br- nucleophiles and –OH hydrogen-bond donors within the layered matrix. Catalytic tests were conducted in a 50 mL stainless steel autoclave. Results: A Br- intercalated ZnMgAl layered double hydroxide (ZnMgAl-Br-) catalyst was successfully constructed, integrating nucleophilic Br- anions with hydrogen-bond donating –OH groups in a precisely engineered layered framework. Under optimized conditions (140oC, 7 h, 2.5 MPa), the catalyst achieved 99.2% PO conversion, 98.7% PC selectivity, and 97.9% PC yield. The result represents a remarkable improvement compared with benchmark catalysts (MgAl-Br⁻: 50.5% yield; ZnMgAl- NO3⁻: 13.1% yield), highlighting the critical synergy among Br- nucleophiles, Zn species, and – OH groups. Discussion: The results demonstrate that the cooperative interaction between Br- and –OH groups is central to the catalytic efficiency of CO2/PO cycloaddition. Incorporation of Zn species expanded the interlayer spacing and optimized the spatial arrangement of Br⁻/-OH sites, thereby enhancing cooperative catalysis. Conclusion: The findings highlight the critical role of Br- nucleophiles and the Zn-modified layered structures in enabling cooperative catalysis. This work establishes a rational strategy for designing multifunctional heterogeneous catalysts for efficient CO2 utilization through epoxide cycloaddition.

The deliberate engineering of cooperative catalytic microenvironments within metal-organic frameworks (MOFs) offers a powerful strategy for promoting sustainable catalysis. Herein, we report a robust nitro-functionalized trinuclear metal-organic framework, formulated as {[Cu3(NTCB)2(4,4'-bip)(DMF)2]·4DMF·3H2O}n (NUC-180; H3NTCB = 1,3,5-tri(4-carboxy-2-nitrophenyl)-2,4,6-trinitrobenzene, 4,4'-bip = 4,4'-bipyridine), featuring a high void fraction and dual nanoscale channel systems. Upon activation, NUC-180a exposes coordinatively unsaturated metal centers and strongly electron-withdrawing nitro functionalities that collectively regulate the local electronic environment and enhance substrate polarization. As a result, NUC-180a exhibits excellent heterogeneous catalytic performance for the solvent-free cycloaddition of CO2 with epoxides under mild conditions, delivering cyclic carbonates with high efficiency, selectivity, and recyclability. Beyond CO2 fixation, the framework also efficiently catalyzes tandem deacetalization-Knoevenagel condensation reactions. Mechanistic insights reveal that the catalytic activity originates from the synergistic interplay between Lewis-acidic metal sites and polar functional groups within the confined micropores. This work highlights nitro-functionalized MOFs as versatile platforms for cooperative catalysis without invoking classical Lewis basicity from nitro groups.

The selective conversion of syngas to C4+ long-chain alcohols holds significant industrial and scientific interest, but challenges in product selectivity and process efficiency remain. Here, we report a precisely catalytic strategy for C4+ alcohol synthesis with a selectivity of 80% at 17% CO conversion. The reaction channel involves: (i) the development Cs2O-Co2C-Co catalysts, capable of catalyzing CO hydrogenation to long-chain oxygenates/olefins; and (ii) complete conversion to C4+ alcohols is subsequently achieved on the single-Rh-site and Cu-ZrO2 interfaces by integrated cooperative catalysis. A comprehensive catalyst design and compatibility assessment of each catalytic module ensures optimal combinations, meanwhile effectively eliminates costly separation steps, and reduces CO2 selectivity down to 1%. The developed process achieves ultra-high carbon-efficiency (>95%) and improves oxygen-efficiency, effectively overcoming the key limitations of current syngas conversion technologies and thus representing a competitive and sustainable solution for producing high-value long-chain alcohols with a minimal carbon footprint.

The electrosynthesis of cyclohexanone oxime from cyclohexanone and nitrogenous feedstock driven by renewable electricity presents a sustainable alternative to energy-intensive and hazardous industrial processes. However, achieving high activity and selectivity is challenged by the over-reduction of key intermediates and the lack of effective sites for C─N coupling. Herein, we report a Fe1Bi single-atom alloy (Fe1Bi SAA) featuring Fe-Bi atomic interfaces that collaborate for the one-pot electrosynthesis of cyclohexanone oxime. The Fe1Bi SAA achieves a remarkable Faradaic efficiency of 70.9% and a yield rate of 0.94mmol cm-2 h-1 for cyclohexanone oxime. Combined in situ electrochemical spectroscopic measurements and density functional theory calculations reveal an atomic-scale synergistic mechanism: dispersed Fe sites adsorb and activate cyclohexanone, while adjacent Bi sites selectively reduce nitrite to the key hydroxylamine intermediate. The techno-economic analysis based on flow electrolyzer operation confirms the potential economic viability of the electrosynthesis of cyclohexanone oxime. This work provides profound atomic-level insight into cooperative catalysis for C─N coupling reactions toward the electrosynthesis of value-added organonitrogen compounds.