Dehydrogenative Coupling Reactions with Guanidino-Functionalized Aromatics.

Dehydrogenative coupling (DC) reactions are of importance for the construction of new carbon-element bonds in synthetic organic chemistry. In this work, we report on the synthesis and characterization of several redox-active guanidino-functionalized aromatic molecules (GFAs) for use in DC (C-C and C-O) reactions. In a systematic approach, we first characterize the new DC reagents in all relevant redox and protonation states, and compare their performance in competitive test proton-coupled electron transfer (PCET) reactions. Then, their use in four different DC reactions with different mechanisms is evaluated.

Copper(II)-Amine Complex-Mediated Intramolecular Coupling of Gallates: A Bioinspired Solution to the Atroposelective Synthesis of Ellagitannins.

Total syntheses of the C-glucosidic ellagitannins (-)-punicacortein A, (-)-epipunicacortein A and (+)-castalin were accomplished for the first time, and those of the glucopyranosic ellagitannins (+)-tellimagrandin I and (+)-pedunculagin were revisited. The atroposelective construction of their characteristic hexahydroxydiphenoyl (HHDP) and nonahydroxyterphenoyl (NHTP) units relied on the use of different cupric-amine complexes under different reaction conditions to mediate the intramolecular dehydrogenative coupling of galloyl groups at different positions of glucose cores. In particular, the monodentate n-butylamine and the bidentate (-)-sparteine were found to be complementary in their capacity to promote the regio- and atroposelective coupling of galloyl groups on a 4C1-glucopyranosic core into 2,3-O-(S)- and/or 4,6-O-(S)-HHDP units. Furthermore, replacing (-)-sparteine by its optical antipode not only counteracted the substrate-controlled induction of atroposelectivity to forge a 4,6-O-(R)-HHDP unit, but it also enabled a 4C1 to 1C4 ring flip of the glucopyranosic core and hence the formation of 2,4-O-(R)- and 3,6-O-(R)-HHDP units, such as those featured in the glucopyranosic ellagitannins phyllanemblinin B and geraniin.

Two-Fold Oxidative Coupling of Furan with Indole Provides Modular Access to a New Class of Tetra-(hetero)arylated Furans with up to Four Different Substituents.

Highly arylated propeller-shaped heteroarenes constitute an intriguing class of molecular scaffolds for material science applications. Among these, tetraarylated furans demonstrate differentiated properties as compared to other similar heterocyclic cores. The synthetic complexity to access tetraarylated furans increases significantly with increasing number of different peripheral aryl groups. There are only a very limited number of methodologies available to access furans with four different (hetero)aryl substituents. Notably, none of these involve direct oxidative coupling on the furan core as the method of choice. Herein, we report the first methodology based on a sequential two-fold oxidative C-C coupling of furans with indoles to access bis(indolyl)furans (BIFs) - a new class of 'extremely congested' tetra-(hetero)arylated furans with up to four different substituents. The reaction is mediated by inexpensive, earth-abundant FeCl3.6H2O and displays high efficiency, wide substrate scope, modularity and aqueous compatibility. Moreover, we also present the first validation of the distinct aggregation-caused quenching (ACQ) property of the tetraarylated furans beyond only phenyls as peripheral groups and disclose new mechanistic underpinnings for the same.

Nitrite facilitated transformation of halophenols in ice.

This study investigated the expediated transformation of halophenols in the presence of nitrite (NO2-) under slightly acidic conditions in ice, whereas such transformation was negligible in liquid water at 4 °C. We proposed that this phenomenon was attributed to the freeze-concentration effect, incurring a pH drop and the aggregation of NO2- and halophenols within the liquid-like grain boundary layer amid ice crystals. Within this micro-environment, NO2- underwent protonation to generate reactive nitrous acid (HNO2) and nitrosonium ions (NO+) that facilitate the nitration and oxidation of halophenols. When 10 µÐœ halophenol was treated by freezing in the presence of 5 µÐœ NO2-, the total yields of nitrated products reached 2.4 µÐœ and 1.4 µÐœ within 12 h for 2-chlorophenol (2CP) and 2-bromophenol (2BP), respectively. NO+ drove oxidative coupling reactions, generating hydroxyl polyhalogenated diphenyl ethers (OH-PBDEs) and hydroxyl polyhalogenated diphenyls via C-O or C-C coupling. These two pathways were intricately intertwined. The presence of natural organic matter (NOM) mitigated the formation of nitrated products and completely suppressed the coupling products. This study offers valuable insights into the fate of halophenols in ice and suggests potential pathways for the formation of nitrophenolic compounds and OH-PBDEs in natural cold environments. These findings also open up a new avenue in environmental chemistry research.

Design, Synthesis, Antitumor, and Antiplasmodial Evaluation of New 7-Chloroquinoline-Benzimidazole Hybrids.

Newly synthesized 7-chloro-4-aminoquinoline-benzimidazole hybrids were characterized by NMR and elemental analysis. Compounds were tested for their effects on the growth of the non-tumor cell line MRC-5 (human fetal lung fibroblasts) and carcinoma (HeLa and CaCo-2), leukemia, and lymphoma (Hut78, THP-1, and HL-60) cell lines. The obtained results, expressed as the concentration at which 50% inhibition of cell growth is achieved (IC50 value), show that the tested compounds affect cell growth differently depending on the cell line and the applied dose (IC50 ranged from 0.2 to >100 µM). Also, the antiplasmodial activity of these hybrids was evaluated against two P. falciparum strains (Pf3D7 and PfDd2). The tested compounds showed potent antiplasmodial activity, against both strains, at nanomolar concentrations. Quantitative structure-activity relationship (QSAR) analysis resulted in predictive models for antiplasmodial activity against the 3D7 strain (R2 = 0.886; Rext2 = 0.937; F = 41.589) and Dd2 strain (R2 = 0.859; Rext2 = 0.878; F = 32.525) of P. falciparum. QSAR models identified the structural features of these favorable effects on antiplasmodial activities.

Mild Iron-Catalyzed Oxidative Cross-Coupling of Quinoxalinones with Indoles.

Utilizing iron chloride as a Lewis acid catalyst, we developed a straightforward and mild oxidative cross-coupling reaction between quinoxalinones and indoles, yielding a series of versatile 3-(indol-3-yl)quinoxalin-2-one derivatives. This approach allows for the incorporation of a wide array of functional groups into the final products, demonstrating its synthetic versatility. Notably, the method was successfully scaled up to gram-scale reactions while maintaining high yields. Our mechanistic investigation indicates that iron chloride serves as a catalyst to facilitate the formation of key intermediates which subsequently undergo oxidation to afford the desired products. The merits of this protocol include its cost effectiveness, operational simplicity, and the ease of product isolation via filtration.

Selective Cleavage of Cß-O-4 Bond for Lignin Depolymerization via Paired-Electrolysis in an Undivided Cell.

The cleavage of C-O bonds is one of the most promising strategies for lignin-to-chemicals conversion, which has attracted considerable attention in recent years. However, current catalytic system capable of selectively breaking C-O bonds in lignin often requires a precious metal catalyst and/or harsh conditions such as high-pressure H2 and elevated temperatures. Herein, we report a novel protocol of paired electrolysis to effectively cleave the Cß-O-4 bond of lignin model compounds and real lignin at room temperature and ambient pressure. For the first time, "cathodic hydrogenolysis of Cß-O-4 linkage" and "anodic C-H/N-H cross-coupling reaction" are paired in an undivided cell, thus the cleavage of C-O bonds and the synthesis of valuable triarylamine derivatives could be simultaneously achieved in an energy-effective manner. This protocol features mild reaction conditions, high atom economy, remarkable yield with excellent chemoselectivity, and feasibility for large-scale synthesis. Mechanistic studies indicate that indirect H* (chemical absorbed hydrogen) reduction instead of direct electron transfer might be the pathway for the cathodic hydrogenolysis of Cß-O-4 linkage.

Combining anodic alcohol oxidative coupling for C-C bond formation with cathodic ammonia production.

Electrocatalytic oxidation of alcohols using heterogeneous catalysts is a promising aqueous, energy-efficient and environmentally friendly approach, especially for coupling different alcohols to prolong the carbon chain via co-oxidation. Precisely regulating critical steps to tailor electrode materials and electrolyte composition is key to selectively coupling alcohols for targeted synthesis. However, selectively coupling different alcohols remains challenging due to the lack of effective catalyst and electrolyte design promoting specific pathways. Herein, we demonstrate a paired electrolysis strategy for combining anodic oxidative coupling of ethanol (EtOH) and benzyl alcohol (PhCH2OH) to synthesize cinnamaldehyde (CAL) and cathodic ammonia production. The strategies involve: (i) utilizing the salt-out effect to balance selective oxidation and coupling rates; (ii) developing platinum-loaded nickel hydroxide electrocatalysts to accelerate intermediate coupling kinetics; (iii) introducing thermodynamically favorable nitrate reduction at the cathode to improve coupling selectivity by avoiding hydrogenation of products while generating valuable ammonia instead of hydrogen. We achieved 85% coupling selectivity and 278 µmol/h NH3 productive rate at 100 mA/cm2 with a low energy input (∼1.63 V). The membrane-free, low energy, scalable approach with a wide substrate scope highlights promising applications of this methodology. This work advances heterogeneous electrocatalytic synthesis through rational design principles that integrate anodic oxidative coupling with cathodic nitrate reduction reactions, having synergistic effects on efficiency and selectivity.

Electrochemical Oxidation Enables Radical Dearomative Spiroannulation to 2H-Spiro[benzofuran-3,9'-fluoren]-2-one.

Developing pragmatic strategies for accessing functional benzofuran-2-ones from 3-([1,1'-biphenyl]-2-yl)benzofuran remains an enduring challenge. Herein, we have achieved a highly discriminating electrochemical oxidative dearomative spiroannulation of 3-([1,1'-biphenyl]-2-yl)benzofuran, culminating in the synthesis of 2H-spiro[benzofuran-3,9'-fluoren]-2-one derivatives. By harnessing the electrophilic intermediates of benzofuryl radical cations supported by DFT calculations, we attain exceptional regioselectivity while eliminating the need for stoichiometric oxidants. Mechanistic investigations reveal a sequence of events involving the benzofuran radical cation, encompassing the capture of H2O, nucleophilic arene attack, and subsequent deprotonation, ultimately yielding the final benzofuran-2-ones.

Copper Phenylacetylide and TiO2 Modification for an Efficient Visible-Light-Driven Oxidative Coupling of Amines.

The selective oxidation of amines to imines under mild conditions has attracted much attention. Our study reveals that copper phenylacetylide (PhC2Cu) could serve as an efficient photocatalyst for imine synthesis under visible-light irradiation (>400 nm). Utilizing benzylamine as a model reactant, PhC2Cu achieves an imine yield of 50.4%, which is 5 times higher than that of P25 under the same conditions and comparable to the yield obtained by the 3 wt % Au/P25 photocatalyst (55.4%). Further loading 3.9 nm TiO2 onto PhC2Cu through tetrabutyl titanate hydrolysis increases the imine yield to 84.7%, with a Ti:Cu atomic ratio of 3.65%. Control experiments, photoluminescence (PL) spectra, optical pump terahertz probe (OPTP) spectra, and electron spin resonance (ESR) tests confirm that the optimized TiO2 modification promotes the separation of excited carriers and electron transfer in PhC2Cu and facilitates the activation of surface oxygen, thereby enhancing the formation of superoxide radicals, a key active oxygen species in the reaction system. This work presents a promising strategy for efficient imine synthesis via amine coupling and expands the application field of PhC2Cu-based photocatalysts.

Photocatalytic Transformation of Organics to Valuable Chemicals - Quo Vadis?

Recent development in photocatalysis is increasingly focused on transforming organic compounds toward producing fine chemicals. Simple, non-selective oxidation reactions (degradation of pollutants) and very demanding solar-to-chemical energy conversion processes (production of solar fuels) face severe economic limitations influenced by still low efficiency and insufficient stability of the systems. Synthesis of fine chemicals, including reductive and oxidative selective transformations, as well as C-C and C-N coupling reactions, can utilise the power of photocatalysis. Herein, we present the recent progress in photocatalytic systems designed to synthesise fine chemicals. In particular, we discuss the factors influencing the efficiency and selectivity of the organic transformations, dividing them into intrinsic (related to individual properties of photocatalysts) and extrinsic (originating from the reaction environment). A rational design of the photocatalytic systems, based on a deep understanding of these factors, opens new perspectives for applied photocatalysis.

Exploring the Diverse Landscape of Fungal Cytochrome P450-Catalyzed Regio- and Stereoselective Dimerization of Diketopiperazines.

Dimeric indole-containing diketopiperazines (di-DKPs) are a diverse group of natural products produced through cytochrome P450-catalyzed C-C or C-N coupling reactions. The regio- and stereoselectivity of these reactions plays a significant role in the structural diversity of di-DKPs. Despite their pivotal role, the mechanisms governing the selectivity in fungi are not fully understood. Employing bioinformatics analysis and heterologous expression experiments, five undescribed P450 enzymes (AmiP450, AcrP450, AtP450, AcP450, and AtuP450) responsible for the regio- and stereoselective dimerization of diketopiperazines (DKPs) in fungi are identified. The function of these P450s is consistent with phylogenetic analysis, highlighting their dominant role in controlling the dimerization modes. Combinatorial biosynthesis-based pathway reconstitution of non-native gene clusters expands the chemical space of fungal di-DKPs and reveals that the regioselectivity is influenced by the substrate. Furthermore, multiple sequence alignment and molecular docking of these enzymes demonstrate a C-terminal variable region near the substrate tunnel entrance in AtuP450 that is crucial for its regioselectivity. These findings not only reveal the secret of fungal di-DKPs diversity but also deepen understanding of the mechanisms and catalytic specificity involved in P450-catalyzed dimerization reactions.

Water and Air Stable Copper(I) Complexes of Tetracationic Catenane Ligands for Oxidative C-C Cross-Coupling.

Aqueous soluble and stable Cu(I) molecular catalysts featuring a catenane ligand composed of two dicationic, mutually repelling but mechanically interlocked macrocycles are reported. The ligand interlocking not only fine-tunes the coordination sphere and kinetically stabilizes the Cu(I) against air oxidation and disproportionation, but also buries the hydrophobic portions of the ligands and prevents their dissociation which are necessary for their good water solubility and a sustained activity. These catenane Cu(I) complexes can catalyze the oxidative C-C coupling of indoles and tetrahydroisoquinolines in water, using H2O2 as a green oxidant with a good substrate scope. The successful use of catenane ligands in exploiting aqueous Cu(I) catalysis thus highlights the many unexplored potential of mechanical bond as a design element for exploring transition metal catalysis under challenging conditions.

Solar-Light-Driven Photocatalytic Oxidative Coupling of Phenol Derivatives over Bismuth-Based Porous Metal Halide Perovskites.

The selective oxidative coupling of phenol derivatives, involving carbon-carbon (C-C) and carbon-oxygen (C-O) bond formation, has emerged as a critical approach in the synthesis of natural products. However, achieving precise control over the selectivity in coupling reactions of unsubstituted phenols utilizing solar light as the driving force remains a big challenge. In this study, we report a series of porous Cs3Bi2X9 (X=Cl, Br, I) photocatalysts with tailored band gaps and compositions engineered for efficient solar-light-driven oxidative phenol coupling. Notably, p-Cs3Bi2Br9 exhibited about 73 % selectivity for C-C coupling, displaying a high formation rate of 47.3 µmol gcat -1 h-1 under solar radiation. Furthermore, this approach enables control of the site-selectivity for phenol derivatives on Cs3Bi2X9, enhancing C-C coupling. The distinctive porous structure and appropriate band-edge positions of Cs3Bi2Br9 facilitated efficient charge separation, and surface interaction/activation of phenolic hydroxyl groups, resulting in the kinetically preferred formation of C-C over C-O bond. Mechanistic insights into the reaction pathway, supported by comprehensive control experiments, unveiled the crucial role of interfacial charge transfers and Lewis acid Bi sites in stabilizing phenolic intermediates, thereby directing the regioselectivity of diradical couplings and resulting in the formation of unsymmetrical biphenols.

A Cytochrome P450 Catalyzes Oxidative Coupling Formation of Insecticidal Dimeric Indole Piperazine Alkaloids.

Cytochrome P450 (CYP450)-catalyzed oxidative coupling is an efficient strategy for using simple building blocks to construct complex structural scaffolds of natural products. Among them, heterodimeric coupling between two different monomers is relatively scarce, and the corresponding CYP450s are largely undiscovered. In this study, we discovered a fungal CYP450 (CpsD) and its associated cps cluster from 37208 CYP450s of Pfam PF00067 family member database and subsequently identified a group of new skeleton indole piperazine alkaloids (campesines A-G) by combination of genome mining and heterologous synthesis. Importantly, CYP450 CpsD mainly catalyzes intermolecular oxidative heterocoupling of two different indole piperazine monomers to generate an unexpected 6/5/6/6/6/6/5/6 eight-ring scaffold through the formation of one C-C bond and two C-N bonds, illuminating its first dimerase role in this family of natural products. The proposed catalytic mechanism of CpsD was deeply investigated by diversified substrate derivatization. Moreover, dimeric campesine G shows good insecticidal activity against the global honeybee pest Galleria mellonella. Our study shows a representative example of discovering new skeleton monomeric and dimeric indole piperazine alkaloids from microbial resources, expands our knowledge of bond formation by CYP450s and supports further development of the newly discovered and engineered campesine family compounds as potential biopesticides.

Unexpected side reactions dominate the oxidative transformation of aromatic amines in the Co(II)/peracetic acid system.

Aromatic amines (AAs), ubiquitous in industrial applications, pose significant environmental hazards due to their resistance to conventional wastewater treatments. Peracetic acid (PAA)-based advanced oxidation processes (AOPs) have been proposed as effective strategies for addressing persistent AA contaminants. While the organic radicals generated in these systems are believed to be selective and highly oxidative, acetate residue complicates the evaluation of AA removal efficiency. In this work, we explored transformation pathways of AAs in a representative Co(II)-catalyzed PAA system, revealing five side reactions (i.e. nitrosation, nitration, coupling, dimerization, and acetylation) that yield 17 predominantly stable and toxic by-products. The dominant reactive species was demonstrated as Co-OOC(O)CH3, which hardly facilitated ring-opening reactions. Our findings highlight the potential risks associated with PAA-based AOPs for AA degradation and provide insights into selecting suitable catalytic systems aimed at efficient and by-product-free degradation of pollutants containing aromatic -NH2.

Directional Activation of Oxygen by the Au-Loaded ZnAl-LDH with Defect Structure for Highly Efficient Photocatalytic Oxidative Coupling of Methane.

Photocatalytic oxidative coupling of CH4 (OCM) is a promising CH4 conversion process that can achieve efficient methane conversion with the assistance of O2. It remains to be highly challenging to improve the photocatalytic OCM activity from catalyst design and to deepen the understanding of the reactant activation in the OCM process. In this work, the Au-loaded ZnAl-layered double hydroxides (LDHs) with and without oxygen vacancy are constructed (denoted as Au/ZnAl and Au/ZnAl-v), respectively. When applied for photocatalytic OCM, the Au/ZnAl-v shows a CH4 conversion rate of 8.5 mmol g-1 h-1 with 92% selectivity of C2H6 at 40 °C, outperforming most reported photocatalytic OCM systems at low temperature reported in the literature. Furthermore, the catalytic performance of Au/ZnAl-v can be stable for 100 h. In contrast, the An/ZnAl exhibits a CH4 conversion rate of 0.8 mmol g-1 h-1 with 46% selectivity of C2H6. Detailed characterizations and DFT calculation studies reveal that the introduced Ov sites on Au/ZnAl-v are able to activate O2, and the resulting superoxide radical O2·- greatly promotes the activation of CH4. The coupling of CH3· groups with the assistance of Au cocatalyst leads to the formation of C2H6 with high photocatalytic activity.

Materials Enabling Methane and Toluene Gas Treatment.

This paper summarizes the latest research results on materials for the treatment of methane, an important greenhouse gas, and toluene, a volatile organic compound gas, as well as the utilization of these resources over the past two years. These materials include adsorption materials, catalytic oxidation materials, hydrogen-reforming catalytic materials and non-oxidative coupling catalytic materials for methane, and adsorption materials, catalytic oxidation materials, chemical cycle reforming catalytic materials, and degradation catalytic materials for toluene. This paper provides a comprehensive review of these research results from a general point of view and provides an outlook on the treatment of these two gases and materials for resource utilization.

Structural Conjugation Tuning in Covalent Organic Frameworks Boosts Charge Transfer and Photocatalysis Performances.

Structural conjugation greatly affects the optical and electronic properties of the COF photocatalyst. Herein, we show that 2D hydrazone COFs with either π-extended biphenyl (BPh-COF) or acetylene (AC-COF) frameworks demonstrated distinct charge transfer and photocatalytic performances. The two COFs show good crystallinity and decent porosity as their frameworks are enforced by intra/interlayers hydrogen bonding. However, computational and experimental data reveal that AC-COF managed broader visible-light absorption and narrower optical bandgaps and performed efficient photoinduced charge separation and transfer in comparison with BPh-COF, meaning that the ethynyl skeleton with enhanced planarity better improves the π-conjugation of the whole structure. As a result, AC-COF exhibited an ideal bandgap for rapid oxidative coupling of amines under visible-light irradiation. Furthermore, taking advantage of its better charge transfer properties, AC-COF demonstrated considerable enhanced product conversion and notable functional tolerance for metallaphotocatalytic C-O cross-coupling of a wide range of both aryl bromides and chlorides with alcohols. More importantly, besides being recoverable, AC-COF showcased the previously inaccessible etherification of dihaloarene. This report shows a facile approach for manipulating the structure-activity relationship and paves the way for the development of a COF photocatalyst for solar-to-chemical energy conversion.

Fundamentals of Unanticipated Efficiency of Gd2O3-based Catalysts in Oxidative Coupling of Methane.

Improving the selectivity in the oxidative coupling of methane to ethane/ethylene poses a significant challenge for commercialization. The required improvements are hampered by the uncertainties associated with the reaction mechanism due to its complexity. Herein, we report about 90 % selectivity to the target products at 11 % methane conversion over Gd2O3-based catalysts at 700 °C using N2O as the oxidant. Sophisticated kinetic studies have suggested the nature of adsorbed oxygen species and their binding strength as key parameters for undesired methane oxidation to carbon oxides. These descriptors can be controlled by a metal oxide promoter for Gd2O3.