A3 Coupling Research Articles

Copper-catalyzed tandem A3-coupling–isomerization–hydrolysis reactions of aldehydes and terminal alkynes leading to chalcones

A3 coupling is not the end: catalyzed by a simple copper salt, the reaction of aldehyde, alkyne, and amine can afford chalcone.

Copper(ii) carboxymethylcellulose (CMC-CuII) as an efficient catalyst for aldehyde–alkyne–amine coupling under solvent-free conditions

A novel heterogeneous Cu(ii) carboxymethylcellulose catalyst was prepared and successfully employed in the A3 coupling without using any co-catalyst, other additives, bases under solvent-free conditions.

Highly efficient three-component coupling reaction catalysed by atomically precise ligand-protected Au38(SC2H4Ph)24 nanoclusters.

The catalytic potential of atomically precise quantum-sized gold nanoclusters (Au38(SC2H4Ph)24) is explored for the three-component coupling of an aldehyde, an alkyne and an amine to synthesize propargylamines. A high catalytic efficiency with a very low loading (0.01 mol%) is achieved. Furthermore, the synergistic effect of the electron-deficient surface (i.e. Auδ+, 0 < δ+ < 1) and the electron-rich Au23 core of the ligand-protected nanoclusters is critical for this catalytic reaction.

Copper nanoparticles supported on starch micro particles as a degradable heterogeneous catalyst for three-component coupling synthesis of propargylamines

Starch supported Cu NPs as a degradable heterogeneous catalyst for A3 coupling reaction.

Gold Nanoparticles Supported on Polyacrylamide Containing a Phosphorus Ligand as an Efficient Heterogeneous Catalyst for Three-Component Synthesis of Propargylamines in Water

Gold nanoparticles supported on a polyacrylamide containing a phosphinite ligand have been synthesized and characterized using different techniques such as TEM, SEM, EDX, XPS, and solid UV analyses. The new material was successfully applied as a heterogeneous catalyst for the three-component A3 coupling of amines, aldehydes, and alkynes to give propargylamines. Reactions are performed in neat water at 80 °C with only 0.05 mol% catalyst loading. The heterogeneous catalyst is recyclable during seven consecutive runs with small decrease in activity.

Silver(I) complexes as efficient source for silver oxide nanoparticles with catalytic activity in A3 coupling reactions

New silver(I) complexes [Ag7(μ4-Cl)(μ3-Cl)2(μ2-Cl)3(MPI)6] (1), and [Ag(μ3-I)(BI)]n (2) [MPI=1-(4-methoxyphenyl)-1H-imidazole; BI=1-Benzylimidazole] have been prepared starting with AgX (X=Cl, I) and 1-(4-methoxyphenyl)-1H-imidazole/1-Benzylimidazole. The complexes have been characterized by elemental analysis, IR, 1H NMR, and electronic absorption spectroscopy. Molecular structure of the complexes 1 and 2 were determined crystallographically. Complex 1 has a twofold axis with Ag3 in special position and bisecting the Ag4–Ag4′ vector. It contains six 1-(4-methoxyphenyl)-1H-imidazole molecules and seven chlorine atoms bridging the seven silver atoms. Complex 2 exists as a one-dimensional (1D) polymeric chain of [(μ3-I)Ag(μ3-I)Ag] fragments bridged via the 1-Benzylimidazole ligand. The weak argentophilic Ag⋯Ag interaction distances in complexes 1 and 2 are 3.1014(4)Å–3.2998(15)Å, respectively. The complexes 1 and 2, yielded silver oxide nanoparticles on pyrolysis and were characterized by PXRD and TEM. The catalytic properties of the resulting silver oxide nanoparticles and the silver(I) complexes have also been studied for A3-coupling of amines, alkynes and aldehydes in microwave which gave moderate to good yields of propargylamines. Silver(I) complexes exhibit higher catalytic activity compared to silver oxide nanoparticles. The silver oxide nanoparticles as well as silver(I) complexes could be separated easily from the reaction mixture and reused at least four to five times without significant loss of the catalytic activity.

One-Pot Synthesis of Aminoindolizines and Chalcones Using CuI/CSP Nanocomposites with Anomalous Selectivity under Green Conditions

CuI/CSP nanocomposites were found to be efficient and recyclable nanocatalysts for one-pot synthesis of aminoindolizines via A3 coupling reaction in the presence of ethylene glycol (EG) as a recyclable solvent. In contrast, chalcones were isolated when the reaction was performed in the presence of secondary amines such as piperidine, 3-methylpiperidine, pyrrolidine, and piperazine under solvent free conditions. The CuI/CSP was recycled for five times without significant loss in its catalytic activity. The anomalous selectivity in the formation of aminoindolizines and chalcones was dependent on solvents and secondary amines used for the reaction. The present methodology is facile and follows green principles with higher atom economy (94%) and smaller E-factor (0.06).

Green synthesis of CuO nanoparticles by aqueous extract of Anthemis nobilis flowers and their catalytic activity for the A3 coupling reaction

CuO nanoparticles (NPs) were prepared by Anthemis nobilis flowers extract as a reducing and stabilizing agent and employed in catalyzing an aldehyde–amine–alkyne coupling reaction. The synthesized CuO NPs was characterized by SEM, EDS, XRD, FT-IR and UV–visible techniques. A diverse range of propargylamines were obtained in a good to high yield. Furthermore, the separation and reuse of CuO NPs was very simple, effective and economical.

Development of gold nanoparticle-fungal hybrid based heterogeneous interface for catalytic applications

Unsupported and free gold nanoparticles (Au NPs) represent great potential in the field of catalysis. However, shortcomings like agglomeration and loss of the precious catalyst has encouraged the development of supported Au NPs as catalyst with increased activity, selectivity, ease of separation from the reaction mixture and recyclability. The present work demonstrates an eco-friendly, rapid and facile synthesis of catalytically active bio-supported Au NPs using a soil fungus, Aspergillus japonicus AJP01. The dual role of the fungal isolate in synthesis as well as immobilization of Au NPs is the remarkable feature of the study. The fungus successfully reduced Au(III) into Au NPs containing principally Au(0) with a small percentage of Au(I) as revealed by X-ray photoelectron spectroscopy. The particles were spherical in shape and well distributed on fungal mycelia with size ranging predominantly between 15 and 20nm. The as-synthesized nanoparticle-fungal hybrid was found to be highly efficient in catalyzing sodium borohydride mediated reduction reactions of 4-nitrophenol and hexacyanoferrate(III). The versatility of the bionanocatalyst was further demonstrated by catalyzing the A3 coupling reactions for the synthesis of propargylamines.

Synthesis, Crystal Structure of Mg(II) Complex Material and its Application as Catalysts for A3 Coupling Reaction

The ligand of 1, 2-phenylenedioxydiacetic acid (HL) has been employed to react with MgCl2·6H2O in water/ethanol solution (v:v = 1:1), to yield a novel Mg(II) complex [MgL(H2O]3·3.5H2O. The complex was characterized by infrared spectroscopy and single crystal X-ray diffraction structural analysis. The results show that the Mg(II) complex belongs to monoclinic, space group C2/c with a = 2.9160(6) nm, b = 0.67617(14) nm, c = 1.7319(4) nm, β = 109.06(3)°, V= 3.2275(11) nm, Z = 8, Dc= 1.562 µg·m-3, µ = 0.184 mm, F (000) = 1560, and final R1 = 0.0703, ωR2= 0.2256. The complex molecules form a 3D network structure through hydrogen bonds and π-π stack. The A3 coupling reaction of phenylacetylene, aldehyde and amine (piperidine) in the presence of Au@Mg(II) complex as an efficient heterogeneous catalyst has been studied.

Acridine based (S,N,S) pincer ligand: designing silver(I) complexes for the efficient activation of A³ (aldehyde, alkyne and amine) coupling.

Complexes [AgL(NO3)CH3CN](1) and [AgLNO3] (2) were formed on reacting AgNO3 with L in acetonitrile for 12 h (at room temperature) and 24 h (at 90 °C), respectively, where L is a (S,N,S) pincer ligand, 4,5-bis(phenylthiomethyl)acridine, synthesized by the reaction of in situ generated PhS(-) with 4,5-bis(bromomethyl)acridine under N2 atmosphere. (1)H and (13)C{(1)H} NMR and the mass spectra of L and its two Ag-complexes were characterized. The structures of complexes 1 and 2 were established with single crystal X-ray crystallography. The Ag-S bond distances of complexes 1 and 2 are 2.5682 (11)/2.5017 (11) Å and 2.4894 (15)/2.4834 (15) Å, respectively. The ligand L in complex 2 is coordinated with the metal in a pincer mode and the complex has a pseudo-pyramidal geometry of donor atoms around the Ag. In 1, the metal is encapsulated by a ten-membered chelate ring. The two Ag(I) complexes were explored for the coupling of aldehyde, alkyne and amine (A(3) reaction) and were found to be efficient as a 2.0 mol% loading of 1 and 0.5 mol% of 2 for good conversion. Complex 2 is a rare example of a catalyst that can efficiently activate A(3) coupling at a 0.5 mol% loading of Ag.

Lanthanum loaded CuO nanoparticles: synthesis and characterization of a recyclable catalyst for the synthesis of 1,4-disubstituted 1,2,3-triazoles and propargylamines

A click and three component A3coupling reactions were achieved by lanthanum loaded CuO NPs under ultrasonication. 1,4-Disubstituted 1,2,3-triazoles and propargylamines were synthesized in a short reaction time with high regioselectivity and yields.

Aldehyde–alkyne–amine (A3) coupling catalyzed by a highly efficient dicopper complex

A dicopper(i) complex was developed as highly efficient catalyst for A3 coupling reactions, which led to the formation of propargylamines.

Gold immobilized onto poly(ionic liquid) functionalized magnetic nanoparticles: a robust magnetically recoverable catalyst for the synthesis of propargylamine in water

Supported gold(iii) on poly(ionic liquid) coated on magnetic nanoparticles produced a highly active, stable, recoverable and high loading for the synthesis of propargylamines (A3 coupling reaction) under green conditions.

Combined A3 Coupling and Click Chemistry Approach for the Synthesis of Dendrimer-Based Biological Tools.

We report a versatile approach in which two highly efficient chemical reactions, multicomponent A3 coupling and alkyne-azide click chemistry, are combined to construct dendrimer-based tools for applications in biology. Using a convergent approach, dendrons with desired architecture and an alkyne at the focal point are first assembled and then stitched together via multicomponent A3 coupling reaction. The desired functional groups, including a stealth agent, imaging dye, and drug molecules, could be easily covalently linked to the surfaces of these hyperbranched macromolecules using alkyne-azide click chemistry. These A3-click dendrimers are noncytotoxic at concentrations as high as 1 μM and in fact reduce the toxicity of the drug. The dye-coated dendrimers specifically target and localize in lipid droplets. This unison methodology represents an attractive chemical strategy in exploiting the untapped potential of A3 coupling and facilitating the development of nanodevices for imaging and drug delivery.

Cationic copper(I) complexes as highly efficient catalysts for single and double A(3) -coupling Mannich reactions of terminal alkynes: mechanistic insights and comparative studies with analogous gold(I) complexes.

Cationic CuL complexes (L=Buchwald-type phosphane) with N co-ligands have been characterised by structural and spectroscopic properties. These copper(I) complexes are extremely active catalysts, far more active than analogous gold(I) complexes, to promote the single and double A(3) coupling of terminal alkynes, pyrrolidine and formaldehyde. The activity data show the possible ways in which the solvent can influence the catalytic performance by limiting complex solubility, by solvent decomposition or instability of the copper(I) redox state. Isolation of copper(I) complexes that are likely to be the key catalytic species has allowed light to be shed on the reaction mechanism.

Synthesis, Crystal Structure of Tetra-Nuclear Macrocyclic Cu(II) Complex Material and Its Application as Catalysts for A3 Coupling Reaction

A novel tetra-nuclear macrocyclic Cu(II) complex has been synthesized by the reaction of cupric acetate monohydrate with N-acetyl-l-phenylalanine and 4,4-bipyridine in water/ethanol (v:v = 1:1) solution, and characterized by elemental analysis, IR and X-ray single crystal diffraction analysis. The results show that the Cu(II) complex belongs to monoclinic, space group P21 with a = 14.993(3) A, b = 14.831(3) A, c = 22.262(4) A, β = 99.37(3)°, V = 4884.2(16) A3, Z = 2, Dc = 1.420 μg m−3, μ = 0.942 mm−1, F(000) = 2,160, and final R1 = 0.0701, ωR2 = 0.1905. The molecules form three dimensional tubular structures by the interaction of hydrogen bonds and π–π interaction. The A3 coupling reaction of phenylacetylene, aldehyde and amine (piperidine) in the presence of Cu(II) complex as an efficient heterogeneous catalyst has been studied. The catalyst displayed high activity and afforded the corresponding propargylamines with excellent yields. The Cu(II) complex catalyst was reused three times without significant loss of its catalytic activity.

One-Pot Synthesis of Propargylamines Using Ag(I)-Exchanged K10 Montmorillonite Clay as Reusable Catalyst in Water

Ag(I)-exchanged K10 montmorillonite clay is found to be an efficient heterogeneous catalyst for the one-pot three-component coupling of terminal alkynes, amines, and aqueous formaldehyde (A3 coupling) to yield corresponding propargylamines in water. In all the cases, quantitative yields of the desired products are obtained. The catalyst is recovered by filtration and reused several times with only a slight decrease in its catalytic activity. This atom economical methodology does not require an additional co-catalyst or activator, and water is the only byproduct. Interestingly, the reaction can also be performed under solvent-free conditions in the case of aromatic and aliphatic aldehydes, along with formaldehyde, affording propargylamine derivatives in higher yields. A tentative mechanism is also proposed for this transformation.

Copper modified spherical MCM-41 nano particles: an efficient catalyst for the three-component coupling of aldehydes, amines and alkynes in solvent-free conditions

Cu-MCM-41 nano particles have been shown to effectively catalyze the multi-component synthesis of propargylamines by the reaction of aldehydes, amines, and alkynes (A3 coupling) effectively at 100 °C under solvent-free conditions.

Catalysis by metal–organic frameworks: proline and gold functionalized MOFs for the aldol and three-component coupling reactions

Homochiral MOFs were engineered using postsynthetic modification and a one-pot synthetic strategy. l-Proline functionalized IRMOF-3 show high ee for aldol reaction. Gold functionalized CUP-1 catalysts are highly efficient for the A3 coupling reaction.