Catalytic Cycle Research Articles

Synthesis, Characterization, and Application of MOF/COF Hybrid Composite as a Highly Active and Recyclable Catalyst for Multicomponent Synthesis of Chromeno[4,3‐b]quinoline‐6‐ones

ABSTRACTThe conjugation of metal–organic frameworks (MOFs) with covalent organic frameworks (COF), as a catalytically active nanocomposite with integrated properties, is a smart strategy for developing efficient catalytic systems. Herein, we report the design and synthesis of NH2‐Glu‐MOF/MT‐COF nanocomposite using the integration of glutamate MOF (NH2‐Glu‐MOF) and melamine‐terephthaldehyde COF (MT‐COF) via imine bond connection. The synthesized NH2‐Glu‐MOF/MT‐COF nanocomposite has been fully characterized using FT‐IR, XRD, BET, TEM, FE‐SEM, EDX, EDX mapping, TGA, and ICP‐OES techniques. Analyses demonstrate that NH2‐Glu‐MOF/MT‐COF nanocomposite has ideal structural and compositional properties such as good specific surface area (241.631 m2 g−1), high pore volume, and high thermal stability (530°C). Because of such unbeatable structural and compositional features, NH2‐Glu‐MOF/MT‐COF nanocomposite shows much better catalytic activity for the synthesis of a wide library chromeno[4,3‐b]quinoline‐6‐one derivatives than parent materials (NH2‐Glu‐MOF or MT‐COF). Additionally, NH2‐Glu‐MOF/MT‐COF nanocomposite demonstrated supreme recyclability during five catalytic cycles.

XFEL crystallography reveals catalytic cycle dynamics during non-native substrate oxidation by cytochrome P450BM3

Cytochrome P450s are haem-containing enzymes, catalysing the regio- and stereospecific oxidation of non-activated hydrocarbons. Among these, the bacterial P450BM3 is a promising biocatalyst due to its high enzymatic activity. Given the significant conformational flexibility of this enzyme, understanding protein-substrate interactions and associated structural dynamics are crucial for designing P450BM3-based biocatalysts. Herein, employing an X-ray free electron laser in combination with freeze-trap crystallography and spectroscopy techniques, we captured the intact structures of engineered P450BM3s in the initial stages of catalysis during styrene epoxidation, in the presence of a decoy molecule. We found that the iron reduction significantly altered the active-site orientation of styrene, driven by structural changes in surrounding helices and hydrogen-bonding networks. Oxygen binding to iron further stabilised its productive orientation, providing a molecular basis for the experimentally observed enzyme kinetics and enantioselectivities. This study reveals the substrate dynamics of a P450 enzyme, showcasing how changes in haem chemistry affect enzyme structure and substrate orientation.

Ladderenes as Covalently Condensed Acetylene: A DFT Investigation of Gold(I)-Catalyzed Mechanism, Substituent Effects and Energy Storage Potential.

Ladderenes, unique polymers composed of fused cyclobutane rings, exhibit promising properties for energy storage applications, including reversible redox behavior and structural tunability. This density functional theory (DFT) study investigates the formation of ladderenes via gold(I)-catalyzed alkyne-alkene coupling reactions. Our calculations reveal a step-wise chain propagation mechanism where the alkene product of each step reacts with a ligand-gold-alkyne complex, leading to the sequential addition of cyclobutene units. We demonstrate that electron-withdrawing substituents on the alkynes, such as chlorine, facilitate the dissociation of the gold catalyst (PMe3Au+) from the cyclobutene adduct, enhancing catalytic efficiency. Solvent effects are also shown to significantly influence the reaction energetics. This finding highlights the significant impact of alkyne substitution on the catalytic cycle. The inherent exothermicity of ladderene formation, coupled with their unique structural features, suggests their potential for storing energy in the form of "covalently condensed acetylene".

Access to Enantiopure Spiropyridines Enabled by Enantio-Relay Double [2 + 2 + 2] Cycloaddition and Kinetic Resolution [2 + 2 + 2] Cycloaddition of Alkynes and Nitriles.

The synthesis of enantiopure and structurally unique spiro-type molecules is of utmost significance in catalysis, synthetic chemistry, and related fields. We present here a general solution, a nickel-catalyzed [2 + 2 + 2] cycloaddition, for accessing enantioenriched spiropyridines from readily available nitriles and alkynes in a single synthetic step, including (1) enantio-relay double [2 + 2 + 2] cycloaddition of malononitriles with alkynes and (2) kinetic resolution [2 + 2 + 2] cycloaddition of racemic pyridine-containing nitriles with alkynes. Both strategies feature a broad substrate scope and exclusive regioselectivities, and are scalable to multigram. Remarkably, the double [2 + 2 + 2] cycloaddition integrates enantio-induction by desymmetrizing dinitriles during the initial catalytic cycle with additional enantio-enhancement during the second cycloaddition (enantio-relay), yielding excellent enantioselectivities (>99% ee for all examined examples). Furthermore, the highly efficient kinetic resolution strategy enables the achievement of exceptionally high enantioselectivities without compromising yields (s > 200 for most examples), overcoming the general challenges of kinetic resolution toward yield and enantioselectivity. The ability to construct previously inaccessible spiro structures lays the groundwork for advancing spiropyridine derivatives, especially the multinitrogen-containing compounds as potential ligands. Due to the perpendicular molecular orientation and inherent rigidity of the architectures obtained, we anticipate significant promise of the presented synthetic approaches for enhancing efforts in synthesis and catalysis.

P(═O)R2-Directed Asymmetric Catalytic C-H Olefination Leading to C-N Axially Chiral Targets.

A novel P(═O)R2-directed asymmetric catalytic olefination has been developed, enabling efficient access to carbon-nitrogen axially chiral products with excellent yields (up to 92%) and enantioselectivity (up to 99% enantiomeric excess). The synergistic coordination of phosphine oxide functionality and l-pGlu-OH with the Pd metal center, serving as an efficient directing group and chiral ligand, was key to the success of this C-H functionalization system. The reaction demonstrated a broad substrate scope, yielding 33 distinct C-N axial products. The absolute configuration of the products was unambiguously confirmed via X-ray diffraction analysis. Additionally, three representative applications were showcased, involving reduction and oxidation to produce chiral phosphines and related derivatives. A plausible catalytic cycle mechanism has been proposed, supported by detailed experimental studies. Aggregates in the system were identified by aggregation-induced polarization experiments.

Aryl halide cross-coupling via formate-mediated transfer hydrogenation.

Transfer hydrogenation is widely practised across all segments of chemical industry, yet its application to aryl halide reductive cross-coupling is undeveloped because of competing hydrogenolysis. Here, exploiting the distinct reactivity of PdI species, an efficient catalytic system for the reductive cross-coupling of activated aryl bromides with aryl iodides via formate-mediated hydrogen transfer is described. These processes display orthogonality with respect to Suzuki and Buchwald-Hartwig couplings, as pinacol boronates and anilines are tolerated and, owing to the intervention of chelated intermediates, are effective for challenging 2-pyridyl systems. Experimental and computational studies corroborate a unique catalytic cycle for reductive cross-coupling where the PdI precatalyst, [Pd(I)(PtBu3)]2, is converted to the dianionic species, [Pd2I4][NBu4]2, from which aryl halide oxidative addition is more facile. Rapid, reversible Pd-to-Pd transmetallation delivers mixtures of iodide-bridged homo- and hetero-diarylpalladium dimers. The hetero-diarylpalladium dimers are more stable and have lower barriers to reductive elimination, promoting high levels of cross-selectivity.

Zinc Fumarate MOF: An Efficient and Facile Catalyst for Biginelli Reaction

ABSTRACTDihydropyrimidinones (DHPMs) and its thione derivatives are the well‐known heterocyclic compounds recognized for their vast biological potential. In this work, we report the synthesis and characterization of zinc fumarate (Zn‐fum) MOF and its use as a novel catalyst in the Biginelli reaction. The metal–organic framework (MOF) was synthesized using a solvothermal method and characterized by analytical methods including XRD, FTIR, FESEM, HRTEM, and EDX. As per XRD, SEM, and TEM analysis, the synthesized Zn‐fum MOF has elongated hexagonal crystalline structure with significant porosity. The MOF possesses a high specific surface area and total pore volume of 1298 m2g−1 and 0.10221 cm3g−1 with 11.82 nm pore diameter as per BET analysis. The catalytic presence of the Zn‐fum MOF in the Biginelli reaction delivered a range of dihydropyrimidinones in high to excellent yield (89%–98%) in a short span of 20 min at 80°C under solvent‐less conditions. Being heterogeneous, the Zn‐fum MOF was easily recoverable and reusable for multiple catalytic cycles without significant loss of activity. The synthesized DHPM derivatives were also evaluated for their antibacterial and antioxidant abilities. Among the 10 compounds tested, several demonstrated significant inhibition of both Gram‐positive and Gram‐negative bacteria, as indicated by the disc diffusion method. The antioxidant activity, as assessed by DPPH and reducing power assays, showed %RSA (radical scavenging activity) values ranging from 60.7% to 65.7%, compared to 80.9% for the standard ascorbic acid. These findings highlight the promising catalytic, antibacterial, and antioxidant properties of the synthesized compounds.

Iron-Catalyzed Reductive Ring-Rearrangement Reaction of Bridged Benzo[b]oxocin-4-ones with Grignard Reagents to Afford Bridged Benzo[b]oxocin-2-ols.

An iron-catalyzed reductive ring-rearrangement reaction of bridged benzo[b]oxocin-4-ones with Grignard reagents to produce bridged benzo[b]oxocin-2-ols is reported. Mechanistic studies indicate that an iron redox catalysis cycle involving oxidative addition to the C-O bond by low-valence iron and β-methoxyl elimination as key steps operates in this reaction.

Solvent‐Driven Mechanistic Insights into Cu‐Catalyzed Asymmetric C‒H Amidation via Nitrene Transfer

Copper‐catalyzed asymmetric C‒H amidation via nitrene transfer (NT) is a powerful strategy for synthesizing nitrogen heterocycles and amines that are found as key structural components in many pharmaceuticals and agrochemicals. While asymmetric Cu‐catalyzed aziridinations are well‐known, enantioselective methods for the intramolecular insertion of a nitrene into a C(sp3)‒H bond are surprisingly underdeveloped for reasons that are poorly understood. Herein, we investigate the role of solvent, particularly acetonitrile (MeCN) and dichloromethane (DCM), and the ligand in tuning the reactivity and enantioselectivity of a series of copper‐bisoxazoline (Cu‐BOX) catalysts for asymmetric benzylic C‒H bond amidation. Mechanistic studies reveal that while MeCN promotes high yields, it compromises enantioselectivity through the proposed formation of a monoligated Cu species. In contrast, DCM enhances enantioselectivity through the desired bis‐ligated Cu species, but the potential for product inhibition to induce a second, less enantioselective catalytic cycle should be considered. Cyclic voltammetry and kinetic analyses support the likelihood of distinct catalytic mechanisms in MeCN and DCM, highlighting the role solvent plays in determining the equilibrium between active Cu species. These results provide valuable insights into the future design of improved catalysts for achieving high levels of enantioselectivity in Cu‐catalyzed C‒H functionalizations.

Pallada‐Electrocatalysis Enables Distal Regioselective and Atroposelective Olefination Reactions

AbstractRegioselective and enantioselective C‐H functionalization is a valuable method for synthesizing chiral and complex molecules. However, it often requires large amounts of toxic oxidants and high temperature, making it environmentally and economically adverse. Additionally, these traditional approaches generally suffer from regioselectivity and enantioselectivity issues. To overcome these limitations, a new mechanism is needed to control both of these simultaneously. Herein, we report the first Pd catalyzed regioselective distal and atroposelective olefination of simple arenes/biaryls via an electrooxidative reaction pathway. This unique electro‐oxidative strategy with Pd(II) catalysis demonstrates unprecedented access to ‘regio‐resolved’ reactions, furnishing chiral molecule synthesis under dynamic kinetic resolution without the conventional requirement of metal‐based oxidants and thermal energy. Both electroanalytical studies and DFT calculations suggest the involvement of a Pd(II)/Pd(IV) catalytic cycle via a crucial Pd(III) intermediate that initiates both the distal and atroposelective olefination reactions.

Influence of Hemilabile Arm and Amide Functionality in the Ligand Backbone on Chemical and Electrochemical Dioxygen Reduction Catalyzed by Mononuclear Copper(II) Complexes.

Four mononuclear copper(II) complexes, [(DPA-OH)Cu(CH3OH)(ClO4)](ClO4) (1), [(DPA-OMe)Cu(CH3OH)(ClO4)](ClO4) (2), [(6-Amide-DPA-OMe)Cu](ClO4)2 (3) and [(6-Amide2-DPA-OMe)Cu](ClO4)2 (4), of flexidentate ligands bearing hemilabile (hydroxy)methoxyethyl and/or amide group on DPA (di(2-picolyl)amine) backbone were isolated to explore their potency in catalyzing chemical and electrochemical oxygen reduction reaction (ORR). The role of a hemilabile arm, as well as amide functionality on the ligand backbone in affecting the rate-determining step (RDS) of the overall catalytic cycle has been explored and compared with that of the analogous [(tmpa)Cu](ClO4)2 (tmpa = tris(2-pyridylmethyl)amine) and [(PV-tmpa)Cu](ClO4)2 (PV-tmpa = bis(pyrid-2-ylmethyl){[6-(pivalamido)pyrid-2-yl]methyl}-amine) complexes. The hemilabile arm in these complexes results in an overall third-order rate, with kcat values ranging from 103 to 104 M-2s-1 during dioxygen reduction catalysis. All the complexes except complex 4 selectively reduce dioxygen via the 4e-/4H+ reduction pathway to water (H2O) using decamethylferrocene (Fc*) as a sacrificial reductant in acidic acetone at 298 K. In contrast, altering the reaction conditions from a chemical to an electrochemical ambiance in phosphate buffer displays a reverse order of ORR activity of the complexes while maintaining the same product selectivity as observed in chemical ORR catalysis in acetone.

Green Light‐Driven Organophosphine‐Catalyzed Iododifluoroalkylation of Alkynes

A green light‐driven, organophosphine‐catalyzed iododifluoroalkylation of alkynes using iododifluoroketones has been developed, eliminating the need for additional metal catalysts and bases. This protocol enables the efficient and sustainable synthesis of CF2‐derived alkenyl iodides under mild conditions, demonstrating excellent tolerance to iododifluoroketones, iododifluoroesters, and perfluoroalkyl iodides. Preliminary mechanistic studies suggest that the catalytic phosphine functions not only as a Lewis base, forming a charge‐transfer complex with difluoroalkyl iodides through halogen‐bonding interactions to generate Rf radicals, but also as a halogen transfer shuttle catalyst to facilitate the catalytic cycle.

Deciphering Reaction Mechanisms of Molecular Proton Reduction Catalysts with Cyclic Voltammetry: Kinetic vs Thermodynamic Control.

ConspectusThe kinetics and thermodynamics of elementary reaction steps involved in the catalytic reduction of protons to hydrogen define the reaction landscape for catalysis. The mechanisms can differ in the order of the elementary proton transfer, electron transfer, and bond-forming steps and can be further differentiated by the sites at which protons and electrons localize. Access to fully elucidated mechanistic, kinetic, and thermochemical details of molecular catalysts is crucial to facilitate the development of new catalysts that operate with optimal efficiency, selectivity, and durability. The mechanism by which a catalyst operates, as well as the kinetics and thermodynamics associated with the individual steps, can often be accessed through electroanalytical studies.This Account details the application of cyclic voltammetry to interrogate reaction mechanisms and quantify the kinetics and thermodynamics of elementary reaction steps for a series of molecular catalysts that mediate electrochemical proton reduction. I distinguish the limiting scenarios wherein a catalyst operates under kinetic control vs thermodynamic control, with a focus on detecting how cyclic voltammetry features shift with proton source strength and concentration, as well as scan rate. For systems that operate under kinetic control, catalytic currents are observed at, or slightly positive toward, the formal potential for the redox process that triggers catalysis. Under thermodynamic control, catalytic responses shift as a function of the proton source pKa and effective pH of the solution. After drawing this distinction, we introduce the appropriate voltammetry experiments and accompanying analytical expressions for extracting key metrics from the data.To illustrate analytical strategies to quantify elementary reaction steps of catalysts operating under kinetic control, I describe our studies of proton reduction catalysts Co(dmgBF2)2(CH3CN)2 (dmgBF2 = difluoroboryl-dimethylglyoxime) and [Ni(P2PhN2Ph)2]2+ (P2PhN2Ph = 1,5-phenyl-3,7-phenyl-1,5-diaza-3,7-diphosphacyclooctane). Here, peak shift analysis, foot-of-the-wave analysis, and plateau current analysis are applied to data sets wherein voltammetric response are recorded as a function of catalyst concentration, proton source concentration, proton source strength, and scan rate to quantify rate constants for elementary proton transfer and bond-forming steps in a catalytic cycle. Further, the case study of [Ni(P2PhN2Ph)2]2+ illustrates how complementary spectroscopic methods can bolster the mechanistic assignment. Collectively, these two studies showcase how detailed mechanistic studies inform on rate-limiting elementary steps in catalysis and other key processes underpinning catalysis.Second, I present analytical strategies to interrogate catalysts operating under thermodynamic control, centered on the case study of [NiII(P2PhN2Bn)2]2+ (P2PhN2Bn = 1,5-dibenzyl-3,7-diphenyl-1,5-diaza-3,7-diphosphacyclooctane). Here, the application of nonaqueous Pourbaix theory to extract thermodynamic information is introduced, and the construction of a coupled Pourbaix diagram is detailed. This study identifies ligand-based protonation as the key process that places catalysis under thermodynamic control and influences the reaction mechanism.Together, the work detailed in this Account showcases the utility of electroanalytical methods to disentangle complex reaction mechanisms and extract key thermochemical and kinetic parameters for elementary steps of catalysis. Through detailed presentation of the key analytical expressions that underpin these analyses, this Account seeks to facilitate the adoption of cyclic voltammetry by the community to fully extract kinetic, thermochemical, and mechanistic information on electrochemical small-molecule activation.

Biosynthesis of l-theanine via one-step purification and immobilization enzyme system.

l-theanine, a non-protein amino acid derived from green tea, was synthesized by a relatively substantial amount of γ-glutamylmethylamide synthetase (GMAS) and polyphosphate kinase (PPK) without efficient recycling. This study establishes a cost-efficient, industrially scalable, and continuous biocatalytic platform for sustainable l-theanine production. A functional catalyst system was engineered by fusing GMAS and PPK with the cell wall-binding domain derived from the Listeria monocytogenes p60 protein (Lm-p60). The enzyme complex was immobilized onto Gram-positive enhancer matrix particles, enabling facile separation and reuse over catalytic cycles. The enzymes were reusable and could be applied for six cycles with an l-theanine yield achieving 86%-93%. The reusable catalyst demonstrates operational sustainability over multiple cycles, offering cost savings and continuous utility.

Pd-Catalyzed Strain-Releasing Dyotropic Rearrangement: Ring-Expanding Amidofluorination of Methylenecyclobutanes.

Under the Pd(II)/Pd(IV) catalytic cycle, the cyclization of pent-4-en-1-amine derivatives typically yields either pyrrolidines or piperidines depending on the N-protecting group. We report herein an unprecedented Pd(II)-catalyzed oxidative domino process that converts readily accessible N-protected 2-(2-amidoethyl)-1-methylenecyclobutane derivatives to 1-fluoro-2-azabicyclo[3.2.1]octanes. This transformation constructs three chemical bonds under mild conditions [Pd(hfacac)2 (5.0 mol %), Selectfluor (2.0 equiv), MeCN, 60 °C, 10 min] through a domino sequence involving 5-exo-trig amidopalladation/Pd(II)-oxidation/chemoselective dyotropic rearrangement/C-F bond-forming reductive elimination. Notably, the cyclization mode remains independent of the N-protecting group under these conditions. Furthermore, diverse functional groups can be introduced at the bridgehead position of a bicyclic compound via an apparent anti-Bredt bridgehead iminium intermediate.

Mechanism and Selectivity of Iron-Catalyzed [4+2] Cycloadditions of Unactivated Dienes: A Computational Study.

The mechanisms of iron-catalyzed [4 + 2] cycloadditions of unactivated dienes were investigated using density functional theory calculations. The calculation results show that the reaction involves sequential key steps of an initial ligand exchange followed by oxidative coupling, isomerization to form a seven-membered ferracycle intermediate, and C-C reductive elimination to form the cyclohexene product. The C-C reductive elimination step is shown to be the rate-determining step of the catalytic cycle. Moreover, energy profiles with three possible spin states (SFe = 0, 1, 2) have been considered. The results show that spin crossing occurs mainly through quintet intermediates and triplet transition states, which indicates that the reaction has a two-state reactivity. In addition, the origins of the chemical selectivities and enantioselectivities are analyzed in detail. It was found that the spatial effect between the catalyst ligand and the substrate leads to high [4 + 2] chemoselectivity, while the stabilizing attractive interaction between the ligand and the substrate leads to high enantioselectivity.

Development of a Nano-toughened multifunctional composite hydrogel based on chitosan and its applications in catalytic and flexible sensors.

Development of a Nano-toughened multifunctional composite hydrogel based on chitosan and its applications in catalytic and flexible sensors.

Noncanonical inhibition of topoisomerase II alpha by oxidative stress metabolites.

Noncanonical inhibition of topoisomerase II alpha by oxidative stress metabolites.

Palladium-Catalyzed meta-C-H Alkoxylation and Amidation via the Polarity Reversal of Nucleophilic Reagents.

Norbornene-mediated remote meta-selective C-H functionalizations of arenes have been limited to relatively weakly electronegative and "soft" species, such as aryl, alkyl, and alkylamino moieties. Herein, we describe the first example of the use of a nucleophilic reagent, such as an alcohol or amide, to replace the electrophilic reagent during the palladium-catalyzed meta-C-H alkoxylation or amidation reaction of an arene. The reaction conditions are mild and highly site-selective, thereby facilitating the direct introduction of natural products or drug molecules containing hydroxyl or amido groups at the meta-positions of arenes. In addition, the directing group is rapidly convertible into the corresponding aldehyde, which further enhances the applicability of the reaction. Control experiments and density functional theory (DFT) calculations revealed that alcohol and amide polarity reversal induced by hypervalent iodine reagents and the subsequent formation of a Pd(IV) intermediate via the oxidative addition of the aryl-norbornyl-palladacycle intermediate are crucial for promoting the entire catalytic reaction cycle.

Nano-structured polyaniline in biocatalysis: Manifesting simultaneous competence of polyaniline nanofibers and nanotubes as immobilization matrices for laccase mediated synthesis of drug intermediates.

Nano-structured polyaniline in biocatalysis: Manifesting simultaneous competence of polyaniline nanofibers and nanotubes as immobilization matrices for laccase mediated synthesis of drug intermediates.