Catalytic Methodology Research Articles

Strategy for C−H Functionalization of Cubanes: From Stoichiometric Reaction to Catalytic Methodology

AbstractWe summarized a strategy for C−H functionalization of cubanes, highlighting recent progress in the field. Cubane, known as a bioisostere of benzene ring, and its functionalization hold significant potential for future drug development. However, owing to its highly strained and thermodynamically unstable nature, the methodologies are limited and their precise and diverse functionalization is challenging in current organic chemistry. In this Concept, we categorized and explained these methodologies, which represents a majority of current cubane C−H functionalization. In addition, we discussed recent advancements in catalytic C−H functionalization methods, demonstrating their potential to address these challenges effectively.

Pd/C-Catalyzed Selective N-Monomethylation by Transfer Hydrogenation of Urea Derivatives using Methanol as H2 and C1 Sources.

N-monomethyl amines are useful intermediates in drugs, natural products, paints. Yet their synthesis is a tremendous challenge due to their high reactivity, typically leading to overmethylation. In this contribution, a highly selective catalytic N-methylation methodology is reported, converting urea derivatives to monomethylated amines, using a commercially available heterogeneous Pd/C catalyst and methanol as unique reagent. Methanol provides a sustainable alternative protocol for the selective preparation of mono-methylated derivatives as it acts as both H2 and C1 sources. In addition, several control experiments were performed to provide a proposal for the mechanism, namely dehydrogenation of methanol and subsequent hydrogenation of urea derivatives, followed by reduction of the in situ formed methyl imine. Importantly, the approach is simple, highly productive and enables novel synthetic procedures for the preparation of monomethylamines from urea derivatives.

Catalytic N-Alkylation of (Hetero)Aromatic Amines and Tandem Annulation Reactions.

A general and practical approach for N-alkylation of heteroaromatic amines with heteroaromatic alcohols is always challenging and rarely reported. Here, we designed and synthesized phosphine-free, robust, and efficient N,N-bidentate-Co(II) complexes for a universal N-alkylation of amines strategy. This present catalytic methodology can be applied to a wide range of substrates by varying alcohols, including aryl, aliphatic, acyclic, and cyclic groups, with heteroaromatic amines such as aminopyridine, 2-aminopyrimidine, and aminoquinoline to provide diverse monoalkylated organonitrogen compounds in good to excellent yields (108 examples). In addition, the utility of the developed catalytic protocol was also extended successfully for the dehydrogenative synthesis of biologically important quinoline derivatives (11 examples). Particularly, 8-aminoquinoline reacted differently with tandem N-alkylated-transfer hydrogenative byproduct (N-benzyl-1,2,3,4-tetrahydroquinolin-8-amine) was obtained, revealing the catalytic activity of the complex I. The reaction proceeded under environmentally benign conditions, which liberates water as the sole byproduct. Notably, a concise synthesis of acetylcholinesterase inhibitors (AChEIs) scaffolds as potential cognition enhancers illustrated the utility of the present protocol. Interestingly, various control and deuterium-labeled experiments were performed, suggesting that the reaction proceeds via the borrowing hydrogen pathway.

Cross-Coupling of Gaseous Alkanes with (Hetero)Aryl Bromides via Dual Nickel/Photoredox Catalysis.

Gaseous alkanes represent the most abundant carbon-based chemical feedstocks in our planet. However, the intrinsic inertness of their C-H bonds has rendered the use of these alkanes very difficult for purposes beyond aerobic combustion and energy intensive processes. Thus, clean and energy-efficient transformations for their use in synthetic organic chemistry are still rare. Here we report a catalytic methodology for the direct cross-coupling of gaseous alkanes with (hetero)aryl bromides through the combination of metallaphotoredox-mediated hydrogen atom transfer and nickel catalysis. This protocol provides an efficient platform for the addition of short alkyl groups into diverse (hetero) aromatic rings, providing a wide range of high-value alkyl(hetero)arenes, and bypassing the longstanding need of using preactivated alkylating agents in C(sp2)-C(sp3) cross-couplings. The method features high chemoselectivity, regioselectivity and a remarkable functional group tolerance, operates under mild conditions, and exhibits operational simplicity.

Cross‐Coupling of Gaseous Alkanes with (Hetero)Aryl Bromides via Dual Nickel/Photoredox Catalysis

Gaseous alkanes represent the most abundant carbon‐based chemical feedstocks in our planet. However, the intrinsic inertness of their C‐H bonds has rendered the use of these alkanes very difficult for purposes beyond aerobic combustion and energy intensive processes. Thus, clean and energy‐efficient transformations for their use in synthetic organic chemistry are still rare. Here we report a catalytic methodology for the direct cross‐coupling of gaseous alkanes with (hetero)aryl bromides through the combination of metallaphotoredox‐mediated hydrogen atom transfer and nickel catalysis. This protocol provides an efficient platform for the addition of short alkyl groups into diverse (hetero) aromatic rings, providing a wide range of high‐value alkyl(hetero)arenes, and bypassing the longstanding need of using preactivated alkylating agents in C(sp2)‐C(sp3) cross‐couplings. The method features high chemoselectivity, regioselectivity and a remarkable functional group tolerance, operates under mild conditions, and exhibits operational simplicity

Catalytic Enantioselective Synthesis of Planar Chiral Pillar[5]arenes via Asymmetric Sonogashira Coupling.

As a novel type of macrocycles with attractive planar chirality, pillar[5]arenes have gained increasing research interest over the past decades, enabling their widespread applications in diverse fields such as porous materials, molecular machines, and chiral luminescence materials. However, the catalytic methodology towards the enantioselective synthesis of planar chiral pillar[5]arenes remains elusive. Here we report a novel method for the enantioselective synthesis of planar chiral pillar[5]arenes via asymmetric Sonogashira coupling, giving access to a wide range of highly functionalized planar chiral pillar[5]arenes, including both homo- and hetero-rimmed ones, with excellent enantioselectivities. Attractively, the resultant planar chiral pillar[5]arenes show great potential for widespread use in many areas such as chiral luminescent materials. This work not only enables the successful synthesis of planar chiral pillar[5]arenes with abundant structural and functional diversity as key building blocks for practical applications but also enriches the asymmetric cross-coupling methodologies in organic synthetic chemistry.

Rapid and Metal-Free Green Synthesis of Coumarins Catalyzed by Humic Acid

Abstract: In recent years, numerous methods have been developed for the synthesis of coumarins via Pechmann reaction catalyzed by various catalysts. Although each of the synthetic strategies previously reported has its own merit, most of these methods are associated with certain disadvantages, including the use of commercially unavailable metal catalysts and organic solvents, low yields, and long reaction times. Therefore, the development of a highly efficient, green, and sustainable catalytic methodology for the synthesis of coumarins is still desirable. Humic acid has been found to be an efficient catalyst for the synthesis of coumarins via the Pechmann reaction at 80oC under solvent-free conditions. The methodology enables the synthesis of structurally diverse coumarins from phenols and β-keto esters within 5-8 min in high yields (91-99%). The green, commercially available, inexpensive organocatalyst can be effectively recycled and reused five times with no significant dropdown in the yield of the product. The method reported has the advantages of high yield, no need for metal catalysts, short reaction time, simple operation, and green and reusable catalyst.

Pickering Emulsions in Catalytic Processes

AbstractPickering emulsions, which are emulsions stabilized by solid particles adsorbed at the interface between two immiscible liquids, provide a highly versatile platform for catalytic processes and offer distinct advantages over conventional systems. These emulsions combine the benefits of traditional biphasic catalysis with enhanced contact between reactive species due to their large interfacial area, which contribute to their high catalytic efficiency. Furthermore, Pickering emulsions offer significant advantages in catalytic processes, including improved extraction efficiency, a wider range of operational variables, the possibility of continuous operation, and the ease of recovery of the emulsifier and/or catalyst. Moreover, through strategic selection and design of solid particles, researchers can tailor interfacial properties to optimize catalytic performance, selectivity and stability. This comprehensive review discusses recent breakthroughs in Pickering emulsion research and their applications in catalysis, examining how Pickering emulsions have transformed catalytic methodologies. By discussing the latest developments, this review demonstrates the potential of Pickering emulsions as a catalyst platform and highlights their role in advancing sustainable and efficient catalytic processes.

Organocatalytic Synthesis of (Hetero)arylidene Malononitriles Using a More Sustainable, Greener, and Scalable Strategy.

The establishment of a green and sustainable Knoevenagel condensation reaction in organic chemistry is still crucial. This work aimed to provide a newly developed metal-free and halogen-free catalytic methodology for the synthesis of CS and (hetero-) arylidene malononitriles in the laboratory and industrial scale. The Knoevenagel condensation reaction of various carbonyl groups with malononitrile was investigated in ethanol, an ecofriendly medium, in the presence of seven nitrogen-based organocatalysts. A comparative study was conducted using two as-obtained and four commercially available nitrogen-based organocatalysts in Knoevenagel condensation reactions. The synthesis of CS gas (2-chlorobenzylidene malononitrile) using a closed catalytic system was optimized based on their efficiency and greener approach. The conversion of 100% and excellent yields were obtained in a short time. The products could be crystallized directly from the reaction mixture. After separating pure products, the residue solution was employed directly in the next run without any concentration, activation, purification, or separation. Furthermore, the synthesis of 2-chlorobenzylidenemahmonitrile (CS) was carried out on a large scale using imidazole as a selected nitrogen-based catalyst, afforded crystalline products with 95 ± 2% yield in five consecutive runs. Energy efficiency, cost saving, greener conditions, using only 5 mol% of organocatalyst, high recyclability of catalyst, prevention of waste, recycling extractant by a rotary evaporator for non-crystallized products, demonstrated the potential commercial production of CS using imidazole in ethanol as an efficient and highly recyclable catalytic system.

NNO Pincer-Supported Pd(II)-Catalyzed Reductive N-Alkylation of Challenging Nitroarenes with Alcohols via Borrowing Hydrogen Strategy.

A sustainable catalytic synthesis of selective monoalkylated amines from nitroarenes and alcohols by new palladium(II)-NNO pincer-type complexes has been described. Herein, a series of Pd(II) complexes [Pd(NNO)PPh3] (1-3) are synthesized and characterized by analytical and spectroscopic (IR, NMR, and HR-MS) methods. The solid-state molecular structures of two complexes are established by X-ray single-crystal diffraction. Furthermore, the catalytic N-alkylation of challenging nitroarenes with primary and secondary alcohols has been performed by the well-defined palladium(II) complexes via borrowing hydrogen strategy. The current protocol offers a wide range of monoalkylated amines (26 examples) with a maximum yield of 87% utilizing 1 mol % of catalyst loading. Gratifyingly, the catalytic system works well under mild reaction conditions and atom economy with water is the only byproduct. Furthermore, control experiments confirm the formation of probable intermediates (aniline, aldehyde, and imine), and deuterium labeling authenticates the borrowing hydrogen mechanism. A gram-scale synthesis of an alkylated product clearly demonstrates the synthetic efficacy of the present catalytic methodology.

Kanamycin−Cu(II) Complex Catalyzed Ullmann Amine Synthesis at Room Temperature: A Tool for Mechanistic Insights into Methylene Blue Degradation

AbstractThis study highlights the significance of the Ullmann coupling reaction in modern organic synthesis and advances catalytic methodologies through the introduction of a kanamycin−copper complex as a highly efficient catalyst for the synthesis of diverse N−aryl compounds. We demonstrate the catalyst's versatility by synthesizing 20 diaryl−amine instances, 21 Ar(het)−N compounds, and 10 miscellaneous examples. NMR, IR, and UV spectroscopy offer insights into the catalyst's behaviour. Additionally, DFT studies support the catalyst's proficiency in generating SO4−⋅ radicals by stabilizing with amino sugar moieties. Ex‐situ NMR experiments confirm a ternary complex‐based mechanism at concentrations below 0.1 μM. Furthermore, we showcase the degradation of methylene blue to its precursor amine under optimized conditions. Overall, this research underscores the potential of Ullmann condensation reactions in contemporary organic synthesis and contributes significantly to the advancement of catalytic methodologies.

Asymmetric 2,3-Addition of Sulfinylamines with Arylboronic Acids Enabled by Nickel Catalysis.

Sulfinamides have been widely used in organic synthesis, with research on their preparation spanning more than a century. Despite advancements in catalytic methodologies, creating sulfur stereocenters within these molecules remains a significant challenge. In this study, we present an effective and versatile method for synthesizing a diverse range of S-chirogenic sulfinamides through catalytic asymmetric aryl addition to sulfinylamines. By utilizing a nickel complex as a catalyst, this process exhibits impressive enantioselectivity and can incorporate various arylboronic acids at the sulfur position. The resulting synthetic sulfinamides are stable and highly adaptable, allowing for their conversion to a variety of sulfur-containing compounds. Our study also incorporates detailed experimental and computational studies to elucidate the reaction mechanism and factors influencing enantioselectivity.

A Modular and Catalytic Methodology To Access 2,5-Furan-Based Phenylene/Thiophene Oligomers through a One-Pot Decarboxylative Cross-Coupling from 5-Bromofurfural.

A library of 2,5-furan-based phenylene/thiophene oligomers were synthesized starting from 5-bromofurfural, a derivative of biomass-derived furfural. Varied electronic groups are coupled onto the furan motif, followed by the installation of a phenylene or thiophene central linker through a one-pot Pd-catalyzed decarboxylative cross-coupling reaction. Resulting oligomers containing the furan-phenylene-furan core possess high photoluminescent quantum yields in solution (83-98%), which are crucial for optoelectronic devices. Absorbance and photoluminescence maxima are tuned by changing peripheral functional groups and the center linker coupled onto the furan backbone.

Catalytic Strategies for the Cycloaddition of CO2 to Epoxides in Aqueous Media to Enhance the Activity and Recyclability of Molecular Organocatalysts.

The cycloaddition of CO2 to epoxides to afford versatile and useful cyclic carbonate compounds is a highly investigated method for the nonreductive upcycling of CO2. One of the main focuses of the current research in this area is the discovery of readily available, sustainable, and inexpensive catalysts, and of catalytic methodologies that allow their seamless solvent-free recycling. Water, often regarded as an undesirable pollutant in the cycloaddition process, is progressively emerging as a helpful reaction component. On the one hand, it serves as an inexpensive hydrogen bond donor (HBD) to enhance the performance of ionic compounds; on the other hand, aqueous media allow the development of diverse catalytic protocols that can boost catalytic performance or ease the recycling of molecular catalysts. An overview of the advances in the use of aqueous and biphasic aqueous systems for the cycloaddition of CO2 to epoxides is provided in this work along with recommendations for possible future developments.

Lactone Enolates of Isochroman-3-ones and 2-Coumaranones: Quantification of Their Nucleophilicity in DMSO and Conjugate Additions to Chalcones.

Owing to stereoelectronic effects, lactones often deviate in reactivity from their open-chain ester analogues as demonstrated by the CH acidity (in DMSO) of 3-isochromanone (pKa = 18.8) and 2-coumaranone (pKa = 13.5), which is higher than that of ethyl phenylacetate (pKa = 22.6). We have now characterized the reactivity of the lactone enolates derived from 3-isochromanone and 2-coumaranone by following the kinetics of their Michael reactions with p-quinone methides and arylidenemalonates (reference electrophiles) in DMSO at 20 °C. Evaluation of the experimentally determined second-order rate constants k2 by the Mayr-Patz equation, lg k2 = sN(N + E), furnished the nucleophilicity parameters N (and sN) of the lactone enolates. By localizing their position on the Mayr nucleophilicity scale, the scope of their electrophilic reaction partners becomes predictable, and we demonstrate a novel catalytic methodology for a series of carbon-carbon bond-forming reactions of lactone enolates with chalcones under phase transfer conditions in toluene.

Enantioselective Synthesis of α-Chiral Bicyclo[1.1.1]pentanes via Multicomponent Asymmetric Allylic Alkylation.

Bicyclo[1.1.1]pentanes (BCPs) have emerged as important structural motifs in drug design. However, asymmetric transformations that provide chiral BCPs bearing an adjacent stereocenter are still scarce. Here, we report a catalytic methodology for the enantioselective synthesis of α-chiral 1,3-difunctionalized BCPs from a three-component coupling of [1.1.1]propellane, a Grignard reagent, and an allylic phosphate. The reaction proceeds via the addition of the Grignard reagent to [1.1.1]propellane followed by an asymmetric N-heterocyclic carbene (NHC)-catalyzed allylic substitution of the resulting BCP-Grignard, providing a broad range of α-chiral BCPs with excellent levels of regioselectivity and enantioselectivity.

Multimodal Acridine Photocatalysis Enables Direct Access to Thiols from Carboxylic Acids and Elemental Sulfur.

Development of photocatalytic systems that facilitate mechanistically divergent steps in complex catalytic manifolds by distinct activation modes can enable previously inaccessible synthetic transformations. However, multimodal photocatalytic systems remain understudied, impeding their implementation in catalytic methodology. We report herein a photocatalytic access to thiols that directly merges the structural diversity of carboxylic acids with the ready availability of elemental sulfur without substrate preactivation. The photocatalytic transformation provides a direct radical-mediated segue to one of the most biologically important and synthetically versatile organosulfur functionalities, whose synthetic accessibility remains largely dominated by two-electron-mediated processes based on toxic and uneconomical reagents and precursors. The two-phase radical process is facilitated by a multimodal catalytic reactivity of acridine photocatalysis that enables both the singlet excited state PCET-mediated decarboxylative carbon-sulfur bond formation and the previously unknown radical reductive disulfur bond cleavage by a photoinduced HAT process in the silane-triplet acridine system. The study points to a significant potential of multimodal photocatalytic systems in providing unexplored directions to previously inaccessible transformations.

Chemoselective Transfer Hydrogenation of Nitroarenes with Ammonia Borane Catalyzed by Copper N‐heterocyclic Carbene Complexes

Comprehensive SummaryHerein, we present a method for the homogeneous hydrogenation of nitroarenes to produce anilines using low catalyst loading (1 mo%) of copper N‐heterocyclic carbene complexes as the catalyst and ammonia borane as the source of hydrogen. A wide range of nitroarenes, featuring diverse functional groups, were selectively transformed into their corresponding primary aromatic amines with high yields. This process can be readily scaled up and exhibits compatibility with various sensitive functional groups, including halogen, trifluoromethyl, aminomethyl, alkenyl, cyano, ester, amide, and hydroxyl. Notably, this catalytic methodology finds application in the synthesis of essential drug compounds. Mechanistic investigations suggest that the in‐situ‐generated Cu‐H species may serve as active intermediates, with reduction pathways involving species such as azobenzene, 1,2‐diphenylhydrazine, nitrosobenzene, and N‐phenylhydroxylamine.

Asymmetric Deoxygenative Functionalization of Secondary Amides with Vinylpyridines Enabled by a Triple Iridium-Photoredox-Chiral Phosphoric Acid System.

An enantioselective deoxygenative functionalization of secondary amides with vinylpridines is developed by merging relay iridium catalysis and cooperative photoredox-chiral Brønsted acid catalysis, affording a series of valuable chiral amines in moderate to good yields with good enantioselectivities. The intriguing multiple catalytic system invoking triple-catalysis was found to be the key to the success of the current reactions, which may stimulate further development of catalytic methodologies for asymmetric deoxygenative transformations of amides.

Hydrocracking Rubber Seeds Oil for Biofuel Production Using Bifunctional Sarulla‐Derived Natural Zeolite–Ni and Ni–Mo/SNZ Catalyst

Rubber seeds, due to their rich vegetable oil content, emerge as a promising substrate for biofuel production. Harnessing the progressive catalytic hydrocracking methodology, this research delves into the activation of Sarulla‐derived natural zeolite followed by Ni and Ni–Mo metal impregnation, subsequently subjecting rubber seed oil to hydrocracking at 400, 450, and 500 °C under atmospheric pressure at 0.1 MPa. Zeolite characteristics undergo notable transformations postmetal impregnation. Importantly, at 500 °C, gasoline fraction selectivity exhibits superior efficacy, with the Ni/SNZ‐A catalyst demonstrating consistently high selectivity (>85%) across varied temperatures. Posthydrocracking reveals an amplification in n‐paraffin, aromatic, olefin, and methyl ester profiles to 19.6%, 7.3%, 25.7%, and 17.7%, respectively, contrasting the diminution of cycloparaffin, carboxylic acid, and ketones to 3.6%, 0.2%, and 2.5%, respectively. The aforementioned discoveries hold significant importance in the realm of further investigation into the generation of gasoline fractions through the utilization of natural zeolite catalysts and the incorporation of metals with lower mass, all conducted under atmospheric pressure conditions with the ultimate objective of mitigating production expenses.