Aryl Coupling Reactions Research Articles

Remote Selective Cross‐Dehydrogenative Coupling Reactions of Aryl C−H Bonds with Carboxylic Acids at Room Temperature

AbstractAn efficient Pd(II)‐catalyzed remote selective cross‐dehydrogenative coupling of broadly useful synthetic building blocks biphenyl Weinreb amides with carboxylic acids is developed. This acetoxylation protocol is performed under room temperature using N‐fluorobenzene‐sulfonimide (NFSI) as the oxidant, exhibiting a wide range of functional group tolerance and affording δ‐position‐ selective products up to 85 % yield. Notably, a diverse set of carboxylic acid‐containing drugs is also found to be compatible under the current reaction conditions. Preliminary mechanistic studies indicate that this reaction presumably proceeds through a seven‐membered palladacycle intermediate.

Chemical modification of marigold (Tagetes erecta) dye via diazo-coupling reaction for enhanced dyeing on polyester: A sustainable approach

Plant-derived natural extracts contain large amounts of polyphenolic compounds, presenting opportunities for chemical modification. The present study deals with the extraction of dye from Marigold (Tagetes erecta), a widely cultivated and commercially utilised flower, using water as an extraction medium followed by its chemical modification for sustainable synthesis of yellow dye and dyeing of polyester fabric. Phytochemical analysis and FTIR spectroscopy of the natural dye extract from Marigold flowers indicated the presence of polyphenolic flavonoids. The water-extracted natural dye was subsequently chemically modified with aniline, a primary aryl amine, via diazotisation and coupling reactions to yield a semi-synthetic natural dye with a 1.2 ± 0.3 g yield. The major constituents in the marigold natural extract and the Modified Marigold Extract (MME) dye were characterised using High-Resolution Liquid Chromatography-Mass Spectrometry (LC-HRMS). The marigold water extract contained a high concentration of Gossypetin 8-Glucoside, a yellow-coloured flavonoid compound with a mass-to-charge ratio (m/z) of 480.0904. LC-HRMS analysis further confirmed the presence of a constituent (m/z 424.0485) in the MME dye, corresponding to the predicted mass of chemically modified Gossypetin 8-Glucoside. The MME dye was subsequently employed for dyeing polyester fabric, exhibiting maximum colour strength at 10 % shade under acidic condition. The dyeing performances of the MME-dyed fabrics were evaluated in terms of fastness and post-dyeing strength. This study demonstrates a unique and novel approach to develop a yellow semi-synthetic natural dye, emphasising its potential utility for polyester dyeing.

Immobilized zirconium‐thiouracil complex on MCM‐41 magnetic mesoporous as a recyclable nanocatalyst for carbon‐sulfide bond formation

The synthesis and characterization of MCM‐41 magnetic mesoporous material, which has been modified with zirconium‐thiouracil complex (M‐MCM‐41@TU‐ZrO), has been conducted and thoroughly analyzed using an array of techniques such as X‐ray diffraction (XRD), energy‐dispersive X‐ray spectroscopy (EDX), elemental mapping, scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT‐IR), Brunauer‐Emmett‐Teller (BET), inductively coupled plasma‐optical emission spectrometry (ICP‐OES), thermogravimetric analysis (TGA) and vibrating sample magnetometer (VSM). The catalytic performance of M‐MCM‐41@TU‐ZrO was tested in the synthesis of phenyl aryl sulfides through a three‐component coupling reaction of aryl halides/phenolic esters with phenylboronic acid and sulfur powder in the presence of a base in PEG200 at 80–90°C. Also, the synthesis of symmetrical diaryl sulfides using aryl halides and sulfur powder and M‐MCM‐41@TU‐ZrO as a nanocatalyst in dimethyl sulfoxide at 120°C was investigated. A major novelty is that this is the first time that a highly efficient magnetically recyclable zirconium nanocatalyst is used for the synthesis of unsymmetrical diaryl sulfides in the presence of arylboronic acid/S8 system as thiolating agent and phenolic esters as cross‐coupling partners. The other advantages of this method are as follows: (a) the structurally diverse phenyl aryl sulfides have been synthesized in good to high yields in PEG as a green solvent; (b) starting materials, sulfur source, and catalyst are commercially available, cheap, non‐toxic, and chemically stable; and (c) M‐MCM‐41@TU‐ZrO nanocatalyst was easily removed from the reaction mixture using an external magnet and reused numerous times without any significant change in activity.

Computational and theoretical chemistry of newly synthesized and characterized 2,2’-(5,5’-(1,4-phenylene)bis(1H-tetrazole-5,1-diyl))bis-N-acetamides

Energetic heterocycles, including pyridines, triazoles, and tetrazoles, exhibit greater density, heats of formation, and oxygen balance compared to their carbocyclic counterparts, making them a promising approach for synthesizing novel bis-tetrazole acetamides. Synthesized compounds A-F, some of which feature a chlorine atom attached to the phenyl ring, serve as valuable synthons for aryl coupling reactions. Analysis via 1H-NMR and 13C-NMR spectroscopy, as well as density functional considerations through B3LYP functional correlation with 6-311 + + G(d) and 6-31G(d) basis set, revealed the observed LUMO/HOMO energies and charge transfer within the molecule. Additionally, the dipole moment, chemical hardness, softness, ionization potential, local reactivity potential via Fukui indices and thermodynamic properties (entropy, enthalpy, and Gibbs free energy) of the molecule were calculated through density functional theory studies. In addition, Molecular Docking studies were conducted to investigate the anti-cancer potential of synthesized heterocyclic compounds against caspase 3, NF-KAPPA-B and P53 protein. Molecular docking analysis demonstrated a potent interaction between 2,2’-(5,5’-(1,4-phenylene)bis(1H-tetrazole-5,1-diyl))bis-N-(2,4-dinitrophenyl) acetamides (6d) and TP53 and NF-KAPPA-B with binding energies of − 11.8 kJ/mol and − 10.9 kJ/mol for TP53 and NF-KAPPA-B, respectively. Similarly, 2,2’-(5,5’–(1,4-phenylene)bis(1H-tetrazole-5,1-diyl))bis-N-(2-chlorophenyl) acetamides (6f) exhibited a strong interaction with caspase-3 with binding energy of -10.0 kJ/mol, indicating their potential as therapeutic agents against these proteins. Furthermore, the findings of current study was further strengthen by 100 ns molecular dynamics (MD) simulations. Finally, theoretical studies of oxygen balance and nitrogen percentage suggest that these molecules can be utilized as energetic materials.Graphical

Controlling Ni redox states by dynamic ligand exchange for electroreductive Csp3-Csp2 coupling.

Cross-electrophile coupling (XEC) reactions of aryl and alkyl electrophiles are appealing but limited to specific substrate classes. Here, we report electroreductive XEC of previously incompatible electrophiles including tertiary alkyl bromides, aryl chlorides, and aryl/vinyl triflates. Reactions rely on the merger of an electrochemically active complex that selectively reacts with alkyl bromides through 1e- processes and an electrochemically inactive Ni0(phosphine) complex that selectively reacts with aryl electrophiles through 2e- processes. Accessing Ni0(phosphine) intermediates is critical to the strategy but is often challenging. We uncover a previously unknown pathway for electrochemically generating these key complexes at mild potentials through a choreographed series of ligand-exchange reactions. The mild methodology is applied to the alkylation of a range of substrates including natural products and pharmaceuticals.

Towards the Highly Efficient Synthesis and Selective Methylation of C(sp 3 )‐Bridged [6]Cycloparaphenylenes from Fluoren[3]arenes

AbstractAn approach to the highly efficient synthesis of C(sp3)‐bridged [6]cycloparaphenylenes (C[6]CPPs) from fluoren[3]arenes (F[3]As) was developed. Consequently, F[3]As as a new kind of macrocyclic arenes were synthesized. Followed by the demethylation, triflation and intramolecular aryl–aryl coupling reactions, C[6]CPPs were then conveniently obtained. Interestingly, C[6]CPPs could be selectively methylated to produce their fully outer‐methyl‐substituted derivatives. The crystal structures showed the hydroxyl‐substituted F[3]As had bowl‐shaped conformations, and the C[6]CPPs exhibited rigid belt‐shaped structures with deep cavities. Moreover, C[6]CPPs exhibited high HOMO energies and narrow energy gaps. An unclosed belt was further obtained, and it not only showed a similar narrow energy gap to those of the aromatic belts, but also displayed strong fluorescence property, which can play a vital role in the design and synthesis of new aromatic belts.

Iron‐Catalyzed Fluoroalkylation of Arylborates with Sulfone Reagents: Beyond the Limitation of Reduction Potential

AbstractThe iron‐catalyzed alkyl–aryl coupling reaction between sulfones and arylboron compounds has remained a challenge. We report the first iron‐catalyzed radical difluoroalkylation of arylborates with N‐heteroaryl sulfones. The coordination between the iron catalyst and the nitrogen atom of N‐heteroaryl sulfones was identified to be important in overcoming the reduction potential limitation of sulfones in the intermolecular single‐electron‐transfer process, which enables both fluoroalkyl N‐heteroaryl sulfones (with relatively high reduction potentials) and nonfluorinated alkyl N‐heteroaryl sulfones (with low reduction potentials) to serve as powerful alkylation reagents.

Metal-Free Three-Component Coupling Reaction of Ketones with Electron-rich Arenes and Selenium Dioxide for the Synthesis of α-Arylselanyl Ketones.

A metal-free three-component coupling reaction of aryl alkyl/alkyl ketones, SeO2, and phenols/anisoles is described. This multicomponent reaction provides a straightforward and facile pathway for the synthesis of α-((4-hydroxy/methoxyphenyl)selanyl)-aryl alkyl/alkyl ketones in the presence of p-toluenesulfonic acid for the C-Se bond formation process. The method offers an attractive and simple procedure using commonly available shelf reagents to deliver organoselenides that, to our knowledge, are being reported here for the first time.

C4-Alkylamination of C4-Halo-1H-1-tritylpyrazoles Using Pd(dba)2 or CuI.

Alkylamino coupling reactions at the C4 positions of 4-halo-1H-1-tritylpyrazoles were investigated using palladium or copper catalysts. The Pd(dba)2 catalyzed C-N coupling reaction of aryl- or alkylamines, lacking a β-hydrogen atom, proceeded smoothly using tBuDavePhos as a ligand. As a substrate, 4-Bromo-1-tritylpyrazole was more effective than 4-iodo or chloro-1-tritylpyrazoles. Meanwhile, the CuI mediated C-N coupling reactions of 4-iodo-1H-1-tritylpyrazole were effective for alkylamines possessing a β-hydrogen atom.

Geodesic Phenine Frameworks

Abstract The planar trigonal structure of 1,3,5-trisubstituted benzene, named phenine, has been adopted as basic units of polygonal networks to shape nanometer-sized curved organic π-molecules. The phenine design allows for concise syntheses of large carbonaceous molecules reaching 4 kDa by stitching geodesic lines with aryl coupling reactions. In this Account, the development of the defective nanocarbon molecules, i.e., geodesic phenine frameworks, is summarized to overview unique structural/electronic features.

Homogeneous Gold-Catalyzed Aryl–Aryl Coupling Reactions

Synthesis of biaryl motifs are crucial for the development and synthesis of pharmaceuticals, natural products, and functional materials. During the last decade, gold-catalyzed aryl–aryl coupling reactions have evolved from a curiosity to a well-established research field. This review summarizes the field from early examples up to the latest developments. Facile C–H functionalization and orthogonal reactivity compared to many other types of transition metal catalysis, for example, palladium catalysis, makes gold-catalyzed aryl–aryl coupling reactions highly appealing and valuable.1 Introduction2 Early Examples3 Cross-Coupling with External Oxidants4 Cross-Coupling without External Oxidants5 Conclusions

Synthesis of Enaminone‐Pd(II) Complexes and Their Application in Catalysing Aqueous Suzuki‐Miyaura Cross Coupling Reaction

Summary of main observation and conclusionA series of Pd(II)‐enaminone complexes, termed Pd(eao)2, have been synthesized and characterized. The investigation on the catalytic activities of these new Pd(II)‐reagents has proved that the Pd(eao)2‐1 possesses excellent catalytic activity for the Suzuki‐ Miyaura cross coupling reactions of aryl bromides/chlorides with aryl/vinyl boronic acids in the environmentally benign media of aqueous PEG400 at low loading (5 mol‰). The superiority of this Pd(II)‐reagent to those commercial Pd(II) and Pd(0) catalysts in catalyzing the reactions has been confirmed by parallel experiments. What's more, Pd(eao)2‐2 has been found as a practical catalyst for the homo‐coupling reactions of aryl boronic acids.

Microwave-assisted synthesis of phosphonic and phosphinic esters and phosphine oxides by the Hirao reaction

Phosphinic- and phosphonic esters, as well as phosphine oxides can be easily obtained by P–C coupling reactions of aryl- and vinyl halides with dialkyl phosphites, H-phosphinates and secondary phosphine oxides in the presence of mostly Pd catalysts. The use of the microwave (MW) technique allows the realization of the Hirao reaction more efficiently, economically and environmentally-friendly.

Hydroxyl-functionalized triazolylidene-based PEPPSI complexes: metallacycle formation effect on the Suzuki coupling reaction.

We report the preparation and full characterization of a series of hydroxyl functionalized 1,2,3-triazolylidene-based PEPPSI complexes 2a-c and their catalytic application in the Suzuki cross coupling reaction of aryl chlorides/amides with boronic acids. Under basic reaction conditions, complexes 2a-c show a notable increase in their catalytic efficiency compared with two ether-wingtip functionalized PEPPSI analogues (3 and 4) and a commercially available NHC-Pd complex (5). The catalytic results suggest that deprotonation of the hydroxyl group in complexes 2a-c plays an important role in the overall process. Deprotonation of the alcohol moiety of complexes 2a-b with sodium tert-butoxide allows for the isolation of metallacycles 6a-b, which are proposed as the active species of cross coupling reactions.

Novel Magnetically-Recyclable, Nitrogen-Doped Fe3O4@Pd NPs for Suzuki–Miyaura Coupling and Their Application in the Synthesis of Crizotinib

Novel magnetically recyclable Fe3O4@Pd nanoparticles (NPs) were favorably synthesized by fixing palladium on the surface of nitrogen-doped magnetic nanocomposites. These catalysts were fully characterized by Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), transmission electron microscopy (TEM), thermogravimetric analysis (TG), and X-ray photoelectron spectroscopy (XPS). The prepared catalyst exhibited good catalytic activity for Suzuki–Miyaura coupling reactions of aryl or heteroaryl halides (I, Br, Cl) with arylboronic acids. These as-prepared catalysts could be readily isolated from the reaction liquid by an external magnet and reused at least ten times with excellent yields achieved. In addition, using this protocol, the marketed drug crizotinib (anti-tumor) could be easily synthesized.

Suzuki–Miyaura Coupling Reactions Using Low Loading of Ligand-activated Palladium Catalyst by Cooperative Copper Catalysis

A highly active Pd/Cu cooperative catalytic system based on biphenylene-substituted di-tert-butylruthenocenylphosphine (R-Phos) was developed for performing Suzuki–Miyaura coupling reactions of (hetero)aryl, alkenyl, and benzyl bromides with (hetero)arylboronic acid pinacol esters. A variety of sterically and/or electronically diverse bromides and boronate esters were successfully coupled in good to excellent yields at room temperature using 0.1 mol % Pd and 5 mol % Cu.

Pd-Catalyzed Thiophene-Aryl Coupling Reaction via C-H Bond Activation in Deep Eutectic Solvents.

Direct arylation of 5-octylthieno[3,4-c]pyrrole-4,6-dione with a series of functionalized aryl iodides via C-H bond activation is demonstrated in a deep eutectic solvent made of choline chloride and urea in non-anhydrous conditions and without exclusion of air. This is the first demonstration of a thiophene-aryl coupling via direct arylation in deep eutectic solvents.

Total Synthesis of Tetrahydroisoquinoline-Based Bioactive Natural Products Laudanosine, Romneine, Glaucine, Dicentrine, and Their Unnatural Analogues Isolaudanosine and Isoromneine

Starting from suitably substituted homophthalic acids, total synthesis of titled alkaloids have been demonstrated in very good yields. The obtained natural products laudanosine and romneine were utilized to accomplish synthesis of two isoquinoline-based alkaloids glaucine and dicentrine. Base-induced selective generation of two different types of benzylic carbanions, their coupling reactions with 3,4-dimethoxybenzyl mesylate, and the regioselective iodination followed by intramolecular aryl–aryl coupling reactions to form the fused biaryl systems were the strategic steps.

Cerium Photosensitizers: Structure-Function Relationships and Applications in Photocatalytic Aryl Coupling Reactions.

Two complete mixed-ligand series of luminescent Ce(III) complexes with the general formulas [(Me3Si)2NC(N(i)Pr)2]xCe(III)[N(SiMe3)2]3-x (x = 0, 1-N; x = 1, 2-N, x = 2, 3-N; x = 3, 4) and [(Me3Si)2NC(N(i)Pr)2]xCe(III)(OAr)3-x (x = 0, 1-OAr; x = 1, 2-OAr, x = 2, 3-OAr; x = 3, 4) were developed, featuring photoluminescence quantum yields up to 0.81(2) and lifetimes to 117(1) ns. Although the 4f → 5d absorptive transitions for these complexes were all found at ca. 420 nm, their emission bands exhibited large Stokes shifts with maxima occurring at 553 nm for 1-N, 518 nm for 2-N, 508 nm for 3-N, and 459 nm for 4, featuring yellow, lime-green, green, and blue light, respectively. Combined time-dependent density functional theory (TD-DFT) calculations and spectroscopic studies suggested that the long-lived (2)D excited states of these complexes corresponded to singly occupied 5dz(2) orbitals. The observed difference in the Stokes shifts was attributed to the relaxation of excited states through vibrational processes facilitated by the ligands. The photochemistry of the sterically congested complex 4 was demonstrated by C-C bond forming reaction between 4-fluoroiodobenzene and benzene through an outer sphere electron transfer pathway, which expands the capabilities of cerium photosensitizers beyond our previous results that demonstrated inner sphere halogen atom abstraction reactivity by 1-N.

ChemInform Abstract: Rapid Threefold Cross‐Couplings with Sterically Bulky Triarylbismuths under Pd—Cu Dual Catalysis.

The threefold cross-coupling reactivity of sterically highly demanding bulky triarylbismuths was addressed with task specific Pd–Cu dual catalytic conditions. In this study, an unprecedented hitherto unknown cross-coupling reactivity of sterically bulky triarylbismuths was demonstrated with a diverse range of aryl iodides and bromides. The intermediacy and in situ formation of arylcopper was probed with mesitylcopper in support of the proposed dual catalysis. This study opened up an easy way forward for application of sterically bulky bismuth reagents in threefold aryl–aryl coupling reactions.