Coupling Reaction Research Articles

Palladium catalysed cross coupling reactions on 2,3-isoxazol-17α-ethynyltestosterone, their anti-cancer activity, molecular docking studies and ADMET analysis

In the current study, the Sonogashira coupling reaction of danazol with aryl halides was carried out, yielding new aryl substituted danazol derivatives. The synthetic compounds were examined for anti-cancer potential on the HeLa human cervical cancer cell line, and they showed promising cytotoxic action. Synthesized compounds 2, 4 and 5 inhibited the growth of HeLa cervical cancer cells, potentially making them effective anti-cancer drugs in the future. Furthermore, molecular docking studies were performed to evaluate the inhibitory impact of danazol derivatives on the Human Papillomavirus (HPV) target protein (1F9F). The docking results showed a significant inhibitory action against the cervical cancer protein (1F9F). The binding energy (ΔG) values of 1, 2, 3, 4 and 5 against the protein 1F9F were −8.01, −8.70, −9.43, −9.58 and −9.75 kcal/mol, indicating a high affinity of the synthesized compounds to bind with the HPV target proteins compared to their parent compound danazol (1). ADMET analyses of all derivatives have also been carried out

Ligand-Free, Copper-Catalyzed Coupling Reaction of Aryl Aluminum Reagents with N-Aryl Thiosuccinimides

: A highly efficient and simple cross-coupling reaction of N-aryl aluminum reagents with Naryl thiosuccinimides for the synthesis of diarylsulide derivatives using CuCl (20 mol%) as a catalyst is reported. Under the optimum reaction conditions, the coupling reaction between aryl aluminum reagents with different substituents and N-aryl thiosuccinimides with different substituents can be carried out smoothly with 18-94% isolated yields of diarylsulides. The method avoids the use of expensive transition metals, such as Pd, Ir, or Rh, phosphine ligands, and has the advantages of simple operation and high reaction efficiency. The structures of all the target compounds are confirmed by 1HNMR and 13CNMR.

Electricity-driven reductive coupling reaction of imines with N-(acyloxy)phthalimides

Electricity-driven reductive coupling reaction of imines with N-(acyloxy)phthalimides

Oxidative Coupling: An Important Tool for Pyrrole Synthesis

: In oxidative coupling, two molecules combine with the help of different oxidants and transition metals. It is used to form various natural and synthetic compounds. Oxidative coupling reactions catalyzed by transition metals (Pd or Cu), Iodine, Cobalt, Ti, etc, are used widely for the synthesis of pyrroles. Pyrrole is a 5-membered heterocyclic ring structure that consists of a single nitrogen. Several methods have been adopted and reported for the synthesis of pyrroles and their analogs in the recent past. Synthesis of pyrrole via oxidative coupling takes place in the presence of various catalysts, bases, and solvents and at different temperatures and times. In another method, Oxidative reactions between diols and primary amines utilizing copper/nitroxyl as the catalyst also yield pyrroles. Rhodium has also been used as a catalyst in oxidative coupling reactions between alkynes and carboxylic acid (substituted by heteroarene or arene) to obtain pyrroles. Paal-Knorr reaction is also one of the most common reactions in the synthesis of pyrrole. In the present study, we summarized different oxidative reactions that have been reported for the synthesis of pyrrole. Hopefully, the study will be helpful for the researchers.

A Carbazole‐Centered Expanded Helicene Stabilized with Hexabenzocoronene (HBC) Units

The synthesis and stabilization of heteroatom‐doped nanocarbon molecules, such as carbazole‐containing (super)helicenes, present significant challenges due to the complexities involved in maintaining structural integrity and electronic functionality. In this study, we successfully synthesized a carbazole‐centered expanded tris‐hexabenzo[7]helicene (1) via a facile FeCl3‐mediated Scholl coupling reaction. 1 exhibits both chemical and chiral stability and demonstrates fluorescence at 628 nm with a quantum yield of 0.40. Additionally, the enantiomers of 1 display pronounced chiroptical properties, including a distinct circular dichroism (CD) signal spanning from 300 to 600 nm. The absorption dissymmetry factor (|gabs|) is determined to be 2.98 × 10−3, while the circularly polarized luminescence brightness (BCPL) is measured as 32.50 M−1 cm−1.

N-Heterocyclic Silylene-Cu(I) Complexes as Efficient Catalysts for Three-Component Coupling Reactions.

We have explored NHSi-supported copper(I) complexes as active and highly efficient catalysts for A3 (aldehyde-alkyne-amine) and KA2 (ketone-alkyne-amine) three-component coupling reactions to synthesize propargyl amines in excellent yields with high TOF under solvent-and additive-free conditions.

Non-Innocent Role of Sacrificial Anodes in Electrochemical Nickel-Catalyzed C(sp2)-C(sp3) Cross-Electrophile Coupling.

Sacrificial anodes composed of inexpensive metals such as Zn, Fe, and Mg are widely used to support electrochemical nickel-catalyzed cross-electrophile coupling (XEC) reactions, in addition to other reductive electrochemical transformations. Such anodes are appealing because they provide a stable counter-electrode potential and typically avoid interference with the reductive chemistry. The present study outlines the development of an electrochemical Ni-catalyzed XEC reaction that streamlines access to a key pharmaceutical intermediate. Metal ions derived from sacrificial anode oxidation, however, directly contribute to homocoupling and proto-dehalogenation side products that are commonly formed in chemical and electrochemical Ni-catalyzed XEC reactions. Use of a divided cell limits interference by the anode-derived metal ions and supports a high product yield with negligible side product formation, introducing a strategy to overcome one of the main limitations of Ni-catalyzed XEC.

Synthesis and Mechanistic Study of Naphthalimide Derivative Formation via Cu-Mediated Ullmann-Type Reactions.

Cu-mediated Ullmann-type coupling reactions are fundamental to organic synthesis, garnering significant academic and industrial interest since their inception. Optimizing reaction parameters, particularly temperature control, is crucial for maximizing efficiency while maintaining high yields. Bidentate ligands, such as amino acids, have demonstrated potential in facilitating these reactions at lower temperatures (<100 °C). This study explores the Cu-catalyzed Ullmann-type coupling of naphthalimide derivatives with amino acid substitutions. Naphthalimide dyes, known for their diverse applications in bioimaging, solar cells, medicine, and sensors, were selected for their potent anticancer properties. The synthesized compounds were characterized by using 1H NMR, ESI-MS, and melting point analyses. Compounds with significant steric hindrance exhibited lower yields, leading to the development of a novel catalytic system employing l-carnosine as a bidentate ligand, which significantly improved yields. Mechanistic insights, derived from density functional theory calculations, identified "L-complex 3" as the most stable and reactive intermediate during oxidative addition to aryl halides. The oxidative addition transition state "OX1-TS" was found to be the most favorable, with a relatively low energy barrier of 6.13 kcal/mol, suggesting that this step, despite being the rate-limiting stage, is energetically accessible. In contrast, reductive elimination was facilitated by a Cu(III) penta-coordinated intermediate, with a barrier of just 8.34 kcal/mol, making it a more straightforward process. Theoretical findings aligned closely with experimental data, reinforcing the oxidative addition/reductive elimination pathway as the operative mechanism for this reaction.

Visible-Light-Mediated Three-Component Decarboxylative Coupling Reactions for the Synthesis of 4-Alkylpyridines.

4-Alkylation of pyridines has been achieved by a photocatalyzed three-component reaction of an olefin, an aryloxyacetic acid, and cyanopyridine using Ir[dF(CF3)ppy]2(dtbbpy)PF6 as a photocatalyst. In this way, a new type of 4-alkylpyridines bearing aryl and aryloxy substituents on the phenyl was accessed with potential pharmaceutical value. In addition to mild reaction conditions, the method has several other advantages, including a multicomponent one-pot protocol, good functional group tolerance, and easy amplification of the reaction scale. The reaction mechanism has been clarified by control experiments and computation of the reaction energy profile.

Solvent Free Ambient Pressure CO2 Cycloaddition Catalyzed by Cobalt-Impregnated 2D-Nanofibrous COFs.

Covalent organic frameworks (COFs) constitute an evolving class of permanently porous and ordered materials, and they have recently attracted increased interest due to their intriguing morphological features and numerous applications in gas storage, adsorption, and catalysis. However, their low aqueous stabilities and tedious syntheses generally hamper their use in heterogeneous catalysis. Nonetheless, a capable and water-stable heterogeneous catalytic system for coupling CO2/epoxides to generate industrially important cyclic carbonates is still of great interest. Herein, exceedingly water- and thermally stable 2D-cobalt-impregnated hydrazone-linked fibrous COFs are reported as a catalyst for CO2/epoxide coupling reactions at ambient pressure. The functionalized cobalt (Co)-doped COFs demonstrated excellent catalytic activities with the high TONs (80925) and TOFs (6466 h-1), outperforming reported heterogeneous catalysts for CO2/epoxide coupling at ambient pressure. We found that the Co2+ ions within the COF matrix catalyze CO2 cycloaddition through density functional theory calculations. We also confirmed the excellent structural stability and consistent activity of Co-doped COFs up to ten repeating cycles.

Effect of Calcination Temperature in Large-Aperture Medium-Entropy Oxide (FeCoCuZnNa)O on CO2 Hydrogenation for Light Olefins

The catalytic hydrogenation of carbon dioxide is not only a way to mitigate the greenhouse effect but also provides high-value chemicals. In this work, a medium-entropy oxide catalyst (FeCoCuZnNa)O was prepared by the sol–gel method for highly active and selective hydrogenation of CO2 to value-added hydrocarbons. When reacted at 290 °C, 2.5 MPa, and 2500 mL·gcat−1·h−1, the CO2 conversion and selectivity of olefin were affected by the calcination temperature of the catalyst, and the best performances were 39% and 41.3%. The large pore size and oxygen vacancies (Ov) formed by (FeCoCuZnNa)O promote the activation of CO2 and promote the C-C coupling reaction of Fe5C2 in a hydrogenation reaction. The promoted C-C coupling reaction was related to the surface enrichment of iron species. The presence of Ov also inhibited the excessive hydrogenation reaction, further improving the selectivity of light olefins. In addition, (FeCoCuZnNa)O did not show significant deactivation within 75 h, indicating that the catalyst has strong industrial potential.

Catalytic Benefits of an Ethynylphenyl-Based PdII Bis(NHC) over a Phenyl-Based PdII Bis(NHC): Insights into the Structural Aspects and Donor Strength Probing.

The amount of cooperation between the metal centers by tailored ligand design is vital to achieve the multimetallic catalytic benefits. Herein, a bimetallic PdII NHC/pyridine complex is synthesized utilizing a novel extended C2-symmetric bis-NHC ligand featuring 1,4-disubstituted ethynylbenzene as a central ligand platform. The complex was further employed for the preparation of a dinuclear complex possessing a combination of NHC and PPh3 ligands. Dinuclear complexes have also been synthesized using a 1,4-di(NHC)-substituted parent benzene ring platform with no acetylene linker units. The donor strengths of both bis-NHC ligands were compared with the help of 13C and 31P chemical shift values as probes. All of the bimetallic complexes were tested as precatalysts in the intermolecular α-arylation of 1-methyl-2-oxindole and Sonogashira coupling reactions. The dinuclear PdII complexes with the ethynylbenzene-bridged bis-NHC ligand showed impressive catalytic outcomes that outweigh the catalytic outcomes obtained with dinuclear bis-NHC complexes possessing no such acetylene linkers. The corresponding mononuclear PdII complexes were synthesized for comparison purposes utilizing both types of central ligand platforms. The dinuclear complexes appeared more active than the corresponding mononuclear complexes in catalysis. Furthermore, higher cooperative index values were obtained in catalysis using the dinuclear PdII complexes with an acetylene-bridged bis-NHC ligand compared to those with no such acetylene linkers.

Silver Nanoparticle‐Embedded Zirconium‐Based Metal‐Organic Framework for Photoreduction of Carbon Dioxide to Acetic Acid in Aqueous Medium

AbstractCatalytic conversion of CO2 into value‐added chemicals is necessary to mitigate the increasing global warming and energy‐related issues. The selective production of C2 or C2+ products by photoreduction of CO2 is a challenging task due to the sluggish kinetics of C─C coupling. Herein, the potential of a silver nanoparticle (Ag NP) incorporated metal‐organic framework (MOF), NU‐1000 is introduced, to harvest light and ease the uphill electron transfer. The growth of silver nanoparticles on thiol‐functionalized NU‐1000 is studied using the atomic pair distribution function (PDF) analysis. The C2 product formed using Ag@NU‐1000‐SH without any sacrificial agents is acetic acid, which is confirmed by 1H‐NMR and HRMS data. The catalyst displays a high acetate output of 293.58 µmolg−1h−1 with a selectivity of 79.4%. The XPS and DFT calculations evidence that the presence of the charge‐polarised states in the as‐synthesized catalyst act as asymmetric centers that favor the C─C coupling reaction. The combined experimental (in situ DRIFT spectroscopic studies) and theoretical calculations reveal that the C─C coupling takes place via the coupling of COOH*intermediates.

Distinct Pathways Determined by Photocatalytic C─H or O─H Bond Activation for Hydroxyl Compounds Conversion Paired With Hydrogen Production

AbstractSelective control of C─H or O─H bond activation in photocatalytic conversion coupled with hydrogen production is a promising yet challenging goal. Here, an efficient photocatalytic system is reported that can produce high‐valued tartaric acid or formaldehyde and simultaneous producing hydrogen. At optimized conditions, the directional conversion of glycolic acid into tartaric acid is achieved with a selectivity of 76.24%, and the selectivity of methanol oxidation into formaldehyde reaches 88.21%. A high hydrogen production rate of 21.43 mmol·g−1·h−1 is obtained using glycolic acid as substrate. Mechanism studies reveal that α‐C─H bond is preferentially activated in glycolic acid adsorbed on the photocatalyst, while O─H bond is preferentially activated in methanol, forming carbon‐centered radical (•CH(OH)COOH) or oxygen‐centered radical (CH3O•) for subsequent coupling or oxidation reactions. This work demonstrates the selective control of the photocatalytic conversion process of different hydroxyl compounds, providing a new perspective for achieving organic compounds selective activation coupled with hydrogen production.

Ynone Promoted Deaminative Coupling of Gramines with C- and N-Nucleophiles.

The deaminative coupling of gramines with nucleophiles represents a versatile approach for structure diversification, but often involves non innocent conditions and/or reagents. Here a new acetylenic reagent 2 is developed for the C-N bond activation of gramines and their in situ coupling with C- and N-centered nucleophiles. Using the new acid/base- and redox-neutral ynone reagent 2 the coupling reactions proceed exceedingly as exemplified by the synthesis of several indol-3-ylmethyl derivatives, including new indole-benzodiazepine and indole-hydrazone conjugates.

Uncommon Phosphonylation of Pyrazine‐2,3‐dicarbonitrile Derivatives via C(sp2)‐CN Bond Cleavage

A direct phosphonylation of the sp2C−CN bond under mild catalytic and non‐catalytic reaction conditions is disclosed. Pyrazine‐2,3‐dicarbonitriles are readily coupled with HPO(OEt)2 to produce the corresponding dialkoxyphosphoryl‐substituted pyrazines. The phosphonylation reaction occurs in the presence of a base (Et3N, Cs2CO3) as nucleophilic substitution of the CN groups. The yield of target diphosphonates depends on the nature of substituents in the 5,6‐positions of the pyrazine ring: it exceeds 90% for di‐5,6‐aryl‐substituted pyrazines and is significantly lower when electron‐donating alkyl (n‐propyl) groups are attached to the 5,6‐positions. It should be noted that for pyrazine‐2,3‐dicarbonitriles bearing vicinal 4‐bromophenyl groups, the nucleophilic phosphonylation leading to C‐‐CN/P‐‐H coupling in the pyrazine ring is predominant over Pd‐catalyzed Hirao’s C‐‐Br/P‐‐H coupling reaction in phenyl rings. Detailed structural characterization, both in solution by means of 1H, 13C and 31P NMR spectroscopy and in the solid state by single crystal X‐ray diffraction, of a series of newly synthesized pyrazine phosphonates is reported.

Bidentate NHC‐Containing Ligands for Copper Catalysed Synthesis of Functionalised Diaryl Ethers

Diaryl and heteroaryl ethers are important and common motifs in drug discovery and agrochemicals. Here we present a catalytic system for the copper catalysed arylation of phenols with aryl halides. Bidentate N‐heterocyclic carbene ligands provide a well‐defined catalytic system that enable low loading of copper in effective coupling reactions (0.5 mol% Cu or lower). The reaction scope of aryl iodides and aryl bromides is developed, that is tolerant of functional groups and a library of biaryl ethers with lead‐like properties is prepared. The presence of excess ligand (in a 1:3 ratio) is shown to be optimal to prevent catalyst degradation, presumably by avoiding decomplexation of the ligand. This is also supported by the catalytic results obtained with pre‐formed copper complexes. The kinetics of the reaction are examined and shown to be first order in copper, supportive of a well‐defined catalyst species, first order in phenol and aryl iodide, and zero order in base under the developed conditions. Computational studies performed using Minnesota MN15‐L parametrisation method support an oxidative addition–reductive elimination pathway. Reductive elimination would be turnover limiting and occurr through an intimate ion pair intermediate.

From In Situ Monitoring to Better Understanding of the Suzuki‐Miyaura Cross Coupling in the Solid State

AbstractEffects of various Additives, Base, Catalyst, as well as substrates on the mechanochemically‐induced Suzuki‐Miyaura reaction have been studied. In situ Raman monitoring of the solid‐state reactions gave a detailed view of the reaction course and allowed a direct comparison of the time‐resolved product formation. The acquired knowledge allows in‐depth understanding of the reaction, especially the action of the catalyst in presence of diverse chemicals, leading to the more efficient cross coupling reactions in the solid state.

Iron-Catalyzed Cross-Electrophile Coupling

AbstractMetal-catalyzed cross-coupling reactions have transformed molecular synthesis. Although metal-catalyzed reactions have been used for cross-electrophile coupling reactions, they remain challenging due to homodimer formation. Recently, our group developed an iron-catalyzed cross-electrophile coupling of benzyl halides and disulfides to produce thioethers without the use of an exogenous reductant or photoredox conditions, and with undetectable levels of elimination. This Synpacts article highlights both our design strategy to obviate detrimental homodimer formation and the generality of the method.1 Introduction2 Conceptualization and Development3 Mechanistic Studies and Hypothesis4 Conclusion and Future Directions

Aldehyde Directed In Situ Loading of Ag Nanodots Around the Open Metal Sites of MOFs for the Tandem Catalysis of Nitrate to Ammonia.

Both spatial arrangement and intrinsic activity of electrocatalysts with dual-active sites are widely designed to match the coupling reaction between nitrate and water, in which most of the reactive intermediates can be optimized to achieve a high yield rate of ammonia. Herein, by introducing the aldehyde group inside metal-organic frameworks (MOFs) in advance, an aldehyde-induced method is achieved to direct the in situ nucleation of Ag nanodots depending on the mesopores of MOFs via a simple silver mirror reaction. The key point here is that the spatial arrangement between the aldehyde group and open metal sites is fixed end to end, which makes the aldehyde group a built-in redox-active site to drive the in situ nucleation of Ag nanodots next to the open metal sites of MOFs. Accordingly, by varying the metal sites of MOFs, a group of M-MOFs@Ag (M = Fe, Co, Ni, Cu, etc.) hybrids with dual active sites are acquired. Taking Ni-MOFs@Ag as an example, the interaction between Ni2+ and Ag sites makes it available for the tandem catalysis of nitrate-to-ammonia, in which the H· and NO2 - generated on the open Ni2+ sites and Ag nanodots, respectively, can migrate to each other to evolve into ammonia.