Three-component Coupling Reaction Research Articles

Catalyst-Free, Three-Component Synthesis of Amidinomaleimides.

Maleimide and amidine functionalities often appear in medicinal and natural product targets. We describe a catalyst-free, three-component coupling reaction for the synthesis of amidinomaleimides. This one-pot reaction fuses a broad range of secondary amines and aldehydes with azidomaleimides. The conditions are mild, simple, modular, high yielding, and amenable to aqueous solvents. Most reaction products can be sufficiently purified without column chromatography. The synthesis creates complex, multifunctional molecules with four different molecules, including a tripeptide, arrayed around an amidinomaleimide core.

1,2,4-Triazolo-quinazolinones as Effective Antifoulants: Molecular Design, Synthesis, and Biological Evaluation.

A series of 1,2,4-triazolo-quinazolinones and 1,2-benzisothiazolone derivatives (S1-S12) were successfully synthesized as environmentally friendly alternatives to copper-based antifouling paints using N-alkylation, cyclocondensation, and one-pot three-component and amide coupling reactions. The monoclinic structure of single-crystal 1,2,4-triazolo-quinazolin-acetic acid (S8) was confirmed by single-crystal X-ray diffraction analysis. All the synthesized molecules were studied for their in silico molecular docking interactions with three target proteins, namely, RbmA, ToxR, and Bap. Following that, the antialgal activity was assessed against two types of marine algae: Chlorella sp. and Chaetoceros curvisetus. The minimal inhibitory concentration and zone of inhibition have been used to evaluate the antibacterial activities of S1-S12 against both marine Gram-positive (Staphylococcus aureus) and Gram-negative (Vibrio parahemolyticus and Vibrio vulnificus) bacteria. Additionally, antifouling studies have been done on all the compounds, and among them, 1,2,4-triazolo-quinazolinyl-acetate (S7), 1,2,4-triazolo-quinazolinyl-acetic acid (S8), 1,2,4-triazolo-quinazolinyl-oxobutanoate (S9), benzo[d]isothiazolyl butanoate (S10), benzo[d]isothiazolyl-acetic acid (S11), and 1,2,4-triazolo-quinazolinyl-acetyl-benzo[d]isothiazolone (S12) exhibited good antialgal, antibacterial, and antifouling activities.

Iron-Catalyzed Sulfonylmethylation of Imidazo[1,2-α]pyridines with N,N-Dimethylacetamide and Sodium Sulfinates.

Functionalized imidazo[1,2-α]pyridines are important scaffolds in pharmaceuticals. Herein, we present an efficient 3-sulfonylmethylation protocol for imidazo[1,2-α]pyridines by sodium sulfinates in DMA and H2O (2:1) via an FeCl3-catalyzed three-component coupling reaction. Various sulfonylmethyl imidazo[1,2-α]pyridines were thus afforded in high yields with excellent functional group tolerance. A plausible oxidation-addition mechanism was proposed.

Charge-induced aggregation of emulsified oil droplets in water with the presence of functionalized stainless steel felt

Oil-water mixtures, especially the surfactant-stabilized oil-in-water emulsions with high stability, are causing great difficulties in effective separation. In this work, a modification strategy was established to prepare functionalized stainless steel felt for emulsion separation by coating the felt with 3-triethoxysilylpropylamine, followed by the introduction of silica nanoparticles using a sulfur-based three-component coupling reaction. To satisfy the pore size requirement for effective emulsion separation, the developed felt was processed using a compression molding. With special wettability, optimized pore size, and electrostatic demulsification mechanism, the positive charged felt delivered outstanding separation capabilities for oil-in-water emulsions stabilized by various surfactants. Specifically, the flux and COD removal efficiency for the anionic-stabilized emulsion were up to 3911 L m-2h−1 and 95.3 %, while for cationic-stabilized emulsions, which were 1305 L m-2h−1 and 93.1 %. Our comparative results indicated that surface charges played an essential role in governing the separation performance of the felt, and the demulsification arising from the electrostatic attraction demonstrated better separation capability than that caused by the electrostatic repulsion. In addition, the developed felt showed controlled surface charge and anti-fouling performance under cyclic operations. The findings of this study are beneficial for constructing separation material with high separation efficiency and long-term durability for practical applications.

Copper-Catalyzed Three-Component Synthesis of β-Hydroxysulfides from Styrene Oxide, Aryl Iodide, and Carbon Disulfide.

A copper-catalyzed three-component coupling reaction of styrene oxide, aryl iodide, and carbon disulfide for the construction of β-hydroxysulfides has been developed. In this process, readily available CS2 was used as the sulfur source to construct C-S bonds for the synthesis of phenyl-β-hydroxysulfides and (benzo[d]thiazol)-β-hydroxysulfides. This process features mild reaction conditions, simple operation, and wide substrate scope (>50 examples).

Yolk-Shell Au NPs@Carbon Porous Nanoreactors Derived from ZIF-8: A High-Efficiency Catalyst for Three-Component Coupling Reaction.

A yolk-shell Au NPs@carbon porous nanoreactor with an active gold (Au) core and a porous carbon shell has been fabricated and demonstrates excellent high activity and cyclic stability as a heterogeneous catalyst for the three-component coupling reaction of aldehyde, amine, and alkyne. Remarkably, the unique yolk-shell nanostructure can protect gold nanoparticles (Au NPs) from aggregation, allow for efficient mass transport, and benefit substrate enrichment, giving rise to enhanced activity, stability, and recyclability.

Synthetic Strategies toward Ortho-3-propanoate Substituted Aryl Phosphonates by Three-Component Coupling Reactions of Arynes, Phosphites, and Acrylates.

Mild, metal-free, and operationally simple three-component coupling reactions involving arynes, phosphites, and acrylates have been achieved. The reaction proceeded well with α- or β-substituted acrylates. Additionally, various functional groups were tolerated under these reaction conditions, resulting in diverse ortho-3-propanoate-substituted aryl phosphonates. Moreover, the reaction can be used to synthesize a range of organophosphorus compounds present in natural products, materials, and biologically active compounds.

Silver-Catalyzed Coupling of Ethynylbenziodoxolones with CO2 and Amines to Afford O-β-Oxoalkyl Carbamates.

A novel three-component coupling reaction of ethynylbenziodoxolones (EBXs) with CO2 and amines has been achieved via silver catalysis, thereby providing an efficient method for the construction of a range of structurally diverse and valuable O-β-oxoalkyl carbamates. The transformation proceeds under mild reaction conditions and exhibits a wide substrate scope and good functional group compatibility. In addition, this strategy could be extended to the synthesis of α-acyloxyketones using carboxylic acids as the nucleophiles to react with EBXs.

One-Pot and Three-Component Coupling Synthesis of Novel p-[(Benzothiazolylamino)(aryl/heteroaryl)methyl]phenols and Its Corresponding O-Tosylates under Catalyst- and Solvent-Free Conditions

AbstractA catalyst- and solvent-free procedure has been developed for the synthesis of p-[( benzothiazolylamino)(aryl/heteroaryl)methyl]-functionalized phenols and its O-tosylates via one-pot three-component coupling reaction of thymol or carvacrol, aryl/heteroaryl aldehydes, and 2-aminobenzothiazoles with high selectivity. The present amino methylation process is convenient to perform even on large scale with a broad scope. The products were likely formed through the initial para attack of thymol on aldehydes to generate p-quinone methide intermediate and subsequent 1,6-aza-Michael addition of 2-aminobenzothiazoles on in-situ generated p-quinone methide intermediate.

Catalytic 1,1-Cyanoalkylation of Electron-Deficient Olefins.

A catalytic 1,1-dicarbofunctionalization of electron-deficient olefins was effected on the basis of the three-component coupling reactions involving olefins bearing vicinal electron-withdrawing groups, potassium cyanide, and an alkyl halide, which afforded geminally cyanoalkylated products in high yields via conjugate cyanation, 1,2-proton transfer, and enolate alkylation. The use of suitable chiral phase-transfer catalysts enabled asymmetric induction in this transformation.

Access to N-Aryl (Iso)quinolones via Aryne-Induced Three-Component Coupling Reaction.

N-Aryl (iso)quinolones are of increasing interest in material and medicinal chemistry, although general routes for their provision remain underexplored, especially when compared with its N-alkyl counterparts. Herein, we report a modular and transition-metal-free, aryne-induced three-component coupling protocol that allows the facile synthesis of structurally diverse N-aryl (iso)quinolones from readily accessible halo-(iso)quinolines in the presence of water. Preliminary results highlight the applicability of our method through scale-up synthesis, downstream derivatization, and flexible synthesis involving other types of aryne precursors.

Silver Metal-Organic Framework Derived N-Doped Carbon Nanofibers for CO2 Conversion into β-Oxopropylcarbamates.

Developing efficient heterogeneous catalysts for chemical fixation of CO2 to produce high-value-added chemicals under mild conditions is highly desired but still challenging. Herein, we first reported an approach to prepare a novel catalyst (Ag@NCNFs), featuring Ag nanoparticles (NPs) embedded within porous nitrogen-doped carbon nanofibers (NCNFs), via growing a Ag metal-organic framework on one-dimensional electrospun nanofibers followed by pyrolysis. Benefiting from the abundant nitrogen species and porous structure, Ag NPs is well dispersed in the obtained Ag@NCNFs. Catalytic studies indicated that Ag@NCNFs exhibited excellent catalytic activity for the three-component coupling reaction of CO2, secondary amines, and propargylic alcohols to generate β-oxopropylcarbamates under mild conditions with a turnover number (TON) of 16.2, and it can be recycled and reused at least 5 times without an obvious decline in catalytic activity. The reaction mechanism was clearly clarified by FTIR, NMR, 13C isotope labeling, control experiments, and density functional theory calculations. The results suggest that Ag@NCNFs and 1,8-diazabicyclo[5.4.0]undec-7-ene can synergistically activate propargylic alcohol to react with CO2, and then the generated α-alkylidene cyclic carbonate was invaded by secondary amine to produce β-oxopropylcarbamate. Importantly, to the best of our knowledge, this is the first experimental and theoretical investigation on this reaction.

A novel three-component coupling reaction of aryne, CN derivatives, and acrylonitrile

A three-component aryne coupling reaction with CN derivatives as a nucleophile, and acrylonitrile as a third component, acting as both a proton donor and a nucleophile, has been developed.

Advances in Three-Component Coupling Reactions Involving CO2

Advances in Three-Component Coupling Reactions Involving CO₂

Three-component dicarbofunctionalization of allylamines via nucleopalladation pathway: unlocking vicinal and geminal selectivity.

A palladium(ii)-catalyzed vicinal as well as geminal selective dicarbofunctionalization of allylamine embedded in a removable picolinamide auxiliary is developed by exploiting a nucleopalladation-triggered intermolecular three-component coupling reaction. The vicinal selectivity was accomplished by engaging allylamine, indoles, and aryl or styrenyl halides through a Pd(ii)/Pd(iv) reaction manifold, while the two-fold coupling of allylamine and indoles via a Pd(ii)/Pd(0) reaction modality resulted in geminal selectivity. The protocol is operationally simple, scalable, and offers two distinct types of products bearing functionalized tryptamine and bisindolyl frameworks in very high to excellent yields. The reaction features a wide substrate generality and also remains effective in the presence of various medicinally relevant scaffolds. Notably, this work represents the first example of nucleopalladation-guided intermolecular dicarbofunctionalization of allylamines.

Three-component coupling reaction of white phosphorus, alcohols and diaryl disulfides: a chlorine-free avenue for accessing phosphorothioates

Synthesis of valuable compounds directly from small and simple molecules is an area of great interest in chemical research.

Organocatalyst-mediated asymmetric one-pot/two domino/three-component coupling reactions for the synthesis of trans-hydrindanes.

Highly substituted trans-hydrindanes were synthesized by the three-component coupling reactions of 1,3-diethyl 2-(2-oxopropylidene)propanedioate and two different α,β-unsaturated aldehydes catalyzed by diphenylprolinol silyl ether. The reaction proceeds via two successive independent catalytic domino reactions in a one-pot reaction by a single chiral catalyst. Domino reactions involve Michael/Michael and Michael/aldol reactions to afford trans-hydrindanes with excellent diastereoselectivity and nearly optically pure form.

An Attractive Route to Benzothiazole or Benzoxazole-Sulfide Aryls: CuFe2O4 NPs as a Highly Efficient Recoverable Nanocatalyst for Three-Component Coupling Reaction of Benzoazoles with Aryl Iodides and Sulfur Source in ChCl-Urea

Magnetic nanoparticles are efficient catalytic systems for various reactions because of their high efficiency and easy separation. Amongst magnetic nanoparticles, copper ferrite (CuFe2O4 NPs) is one of the different types of ferrites, which is widely used in catalytic reactions because of its magnetic properties. On the other hand, deep eutectic solvents (DESs) consisting of a hydrogen bond acceptor component and a hydrogen bond donor component have recently attracted the attention of many researchers as green solvents. ChCl-urea is considered a green DES that has been reported several times to carry out chemical reactions. In recent years, research on the synthesis of 2-thioaryl-benzothiazoles and 2-thioaryl-benzoxazoles (compounds containing C-S aryls and benzothiazoles and benzoxazoles scaffolds) has become an attractive challenge in organic chemistry. In this research, we report the synthesis of 2-thio-benzothiazoles and 2-thioaryl-benzoxazoles by CuFe2O4 NPs in ChCl-urea as an efficient nanocatalyst. These compounds were synthesized via a one-pot, three-component coupling reaction of benzoxazoles or benzothiazoles with aryl iodides and S8 as a sulfur source in the presence of KOAc as a base.

Atomically precise ultrasmall copper cluster for room-temperature highly regioselective dehydrogenative coupling

Three-component dehydrogenative coupling reactions represent important and practical methodologies for forging new C–N bonds and C–C bonds. Achieving highly all-in-one dehydrogenative coupling functionalization by a single catalytic system remains a great challenge. Herein, we develop a rigid-flexible-coupled copper cluster [Cu3(NHC)3(PF6)3] (Cu3NC(NHC)) using a tridentate N-heterocyclic carbene ligand. The shell ligand endows Cu3NC(NHC) with dual attributes, including rigidity and flexibility, to improve activity and stability. The Cu3NC(NHC) is applied to catalyze both highly all-in-one dehydrogenative coupling transformations. Mechanistic studies and density functional theory illustrate that the improved regioselectivity is derived from the low energy of ion pair with copper acetylide and endo-iminium ions and the low transition state, which originates from the unique physicochemical properties of the Cu3NC(NHC) catalyst. This work highlights the importance of N-heterocyclic carbene in the modification of copper clusters, providing a new design rule to protect cluster catalytic centers and enhance catalysis.

Post-synthetic modification of UIO-66-NH2 as a highly efficient and recyclable nanocatalyst in the three-component coupling (A3) reaction for the synthesis of propargylamine derivatives

In this work, modified metal-organic frameworks (MOFs) of UIO-66-NH2-Glyoxal@Pd nanoparticles (UIO-66-NH2-Gl@Pd NPs) and UIO-66-NH2-Furfural@Ni (UIO-66-NH2-Fu@Ni) NPs were prepared to investigate their performance as nanocatalysts in synthesis of propargylamine derivatives using three-component coupling reaction. A number of analyzes were used to confirm the synthesis of the modified frameworks. ICP-OES analysis showed the presence of 2.98 wt.% of Pd in the UIO-66-NH2-Gl@Pd NPs framework structure and 2.98 wt.% of Ni in the UIO-66-NH2-Fu@Ni. The catalytic activities of the modified frameworks were considered in the A3-coupling reaction by benzaldehyde derivatives, amine, and phenylacetylene for the preparation of propargylamine derivatives. High surface area and porosity of UIO-66-NH2 cause to high catalytic activity of nanocatalysts in the A3-coupling reaction. The nanocatalysts can be recycle and reuse several times. The proposed method for the synthesis of propargylamine derivatives is feasible to wide range of substrates and cause to some benefits such as short time of reaction and fruitful results.