CuI Catalyst Research Articles

Copper-Catalyzed Cascade Cyclization of 2-Nitrochalcones with NH-Heterocycles.

We developed a method for allowing cascade cyclization of 2-nitrochalcones with pyrazoles, imidazole, and indazole in the presence of CuI catalyst, DBU base, and THF solvent. The conditions were tolerant of an array of useful functionalities including ester, nitro, cyano, halogen groups. A mechanistic consideration was also provided, as H2O2 was presumably a byproduct. Our method appears to be a rare example to directly prepare C3-heterocyclic unprotected indoles.

Synthesis of novel isostere analogues of naphthyridines using CuI catalyst: DFT computations (FMO, MEP), molecular docking and ADME analysis

An approach towards the synthesis of novel isosteres of benzonaphthyridines and benzonaphthonaphthyridines from the condensation reaction between 4-chloro-2-methylquinolines/4-chloro-2-methylbenzo[h]quinoline and appropriate o-amino aromatic and heteroaromatic carboxylic acids by using solvent (ethanol)/solvent free (neat) condition to yield the intermediate followed by the cyclization with PPA. The intermediate yield has been slightly increased in neat (solvent-free) conditions compared to solvent conditions. Further, the target isosteres of benzonaphthyridines and benzonaphthonaphthyridines were achieved in the one-pot synthesis using a CuI catalyst with a higher yield than the stepwise method. Quantum chemical calculations of synthesized compounds are performed by using M06-2X with 6-311+G(d,p) basis set in water, DFT calculations of the molecular electrostatic potential (MEP), frontier molecular orbitals (FMOs), and the optimized geometry of the XRD values are compared with experimental values. All the synthesized novel isosteres molecules are investigated under molecular docking studies using MMP1 and MMP2 proteins, which showed all the molecules have the potential to heal pancreatic cancer. The most potent molecules among them are 3i and 3h due to their better docking scores. Furthermore, the molecules' pharmacokinetic (ADME) parameters have been observed to be effective in future biological evaluations of these compounds to be active.

Constructing Pd and Cu Crowding Single Atoms by Protein Confinement to Promote Sonogashira Reaction.

For multicenter-catalyzed reactions, it is important to accurately construct heterogeneous catalysts containing multiple active centers with high activity and low cost, whichis more challenging compared to homogeneous catalysts because of the low activity and spatial confinement of active centers in the loaded state. Herein, a convenient protein confinement strategy is reported to locate Pd and Cu single atoms in crowding state on carbon coated alumina for promoting Sonogashira reaction, the most powerful method for constructing the acetylenic moiety in molecules. The single-atomic Pd and Cu centers take advantage in not only the maximized atomic utilization for low cost, but also the much-enhanced performance by facilitating the activation of aryl halides and alkynes. Their locally crowded dispersion brings them closer to each other, which facilitates the transmetallation process of acetylide intermediates between them. Thus, the Sonogashira reaction is drove smoothly by the obtained catalyst with a turnover frequency value of 313 h-1, much more efficiently than that by commercial Pd/C and CuI catalyst, conventional Pd and Cu nanocatalysts, and mixed Pd and Cu single-atom catalyst. The obtained catalyst also exhibits the outstanding durability in the recycling test.

C1 − H morpholinomethylation and formylation of pyrrolo[1,2-a]quinoxalines

We report two methods for selective morpholinomethylation and formylation of C1 − H bonds in pyrrolo[1,2-a]quinoxalines. Reaction of pyrrolo[1,2-a]quinoxalines and morpholine using CuI catalyst, (bis(trifluoroacetoxy)iodo)benzene oxidant, and DMSO solvent yielded the morpholinomethylation products. Meanwhile, formylation of C1 − H bonds in pyrrolo[1,2-a]quinoxalines progressed in the presence of CuI catalyst, trifluoroacetic acid, and DMSO solvent. Compounds bearing halogen, methylsulfonyl, pyridine, and thiophene groups were isolated in moderate yields.

Copper Catalyzed Three-Component Ullmann C-S Coupling in PEG for the Synthesis of 6-Aryl/alkylthio-purines.

To tackle the environmental unfriendly issue in existing synthesis strategies for 6-substitued thiopurine derivatives, such as poor step economy, frequent use of malodorous organic sulfur starting materials, toxic organic solvents, and equivalent dosage of base, we have developed a CuI-catalyzed base-free three-component Ullmann C-S coupling synthetic strategy, featured using inorganic salt Na2S as the sulfur source and nontoxic PEG-600 as the solvent. The newly developed strategy is particularly effective for the synthesis of 6-arylthiopurines. The high catalytic efficiency in PEG-600 can be rationalized by the high soluble ability of CuI catalyst, likely due to the presence of multiple oxygen coordination sites in PEG.

Copper-Catalyzed Cyclization of 2-Alkynylanilines to Give 2-Haloalkoxy-3-alkyl(aryl)quinolines.

Herein we describe a method to produce 2-haloalkoxy-3-substituted quinolines via the cyclization of 2-alkynylanilines with TMSCF3 and THF. This synthetic method uses inexpensive and easy-to-handle TMSCF3 and employs a commercially available CuI catalyst to transform a broad range of 2-alkynylanilines into versatile 2-difluoromethoxy-3-substituted quinolines and 2-iodoalkoxy-3-substituted quinolines with excellent chemoselectivity.

Immobilization of copper(I) iodide on polyaza-ligand-functionalized polyacrylonitrile fibers as highly active catalysts for the 1,3-dipolar cycloaddition reaction

Copper(I) iodide (CuI) was grafted on oxa- and aza-ligand-functionalized polyacrylonitrile fibers (PANFs) to obtain highly active catalysts for the 1,3-dipolar cycloaddition reaction. The fibers were characterized using techniques such as inductively coupled plasma optical atomic emission spectrometry, Fourier-transform infrared spectroscopy, X-ray diffraction, elemental analysis, and X-ray photoelectron spectroscopy, which collectively confirmed that the functionalized fibers were successfully prepared. The catalytic performances of the prepared fibers in the 1,3-dipolar cycloaddition reaction were evaluated. Among the catalysts prepared, the polyaza-ligand-functionalized PANF-immobilized CuI catalyst (PANPAL-1F–CuI) exhibited the best catalytic activity, achieving a high yield of 99%. Furthermore, PANPAL-1F–CuI was chosen for the synthesis of 1,2,3-triazoles with an extensive scope (32 examples) under mild reaction conditions. PANPAL-1F–CuI could be recycled 8 times with a slight decrease in catalytic activity. Finally, a possible mechanism for the PANPAL-1F–CuI-catalyzed 1,3-dipolar cycloaddition was proposed herein.

Copper-Catalyzed Regioselective Iodoformylation of Terminal Alkynes to Access Versatile Electrophiles (E)-β-Iodo-α,β-Unsaturated Aldehydes.

Herein, we describe a method for synthesizing (E)-β-iodo-α,β-unsaturated aldehydes via the iodoformylation of terminal alkynes with TMSCF3 and NaI. This synthetic method uses inexpensive and easy-to-handle chemical feedstocks and employs a commercially available CuI catalyst. It can transform a broad range of terminal alkynes into bis-electrophile (E)-β-iodo-α,β-unsaturated aldehydes with excellent chemoselectivity, regioselectivity, and stereoselectivity. Moreover, it was demonstrated that this protocol has abundant organic reactivity.

Click inspired novel pyrazole-triazole-persulfonimide & pyrazole-triazole-aryl derivatives; Design, synthesis, DPP-4 inhibitor with potential anti-diabetic agents

This work presented the first report on designing, synthesizing of novel pyrazole-triazole-persulfonimide (7a-i) and pyrazole-triazole-aryl derivatives (8a-j) via click reaction using CuI catalyst and evaluated for their anti-diabetic activity and DPP-4 inhibitory effect. Click reactions went smoothly with CuI catalyst in the presence of tridentate chelating ligands and produced copper-free target pyrazole-triazole-persulfonimide analogues in excellent yield at RT. The designed compounds were docked against DPP-4 enzyme and showed excellent interaction with active amino acids residue. Further, all novel pyrazole-triazole-persulfonimide and pyrazole-triazole derivatives were subjected to enzyme-based in vitro DPP-4 inhibitory activity. Based on the SAR study DPP-4 inhibitory capacity compounds 7f (9.52 nM) and 8h (4.54 nM) possessed the significant inhibition of DPP-4. Finally compounds 7f and 8h were evaluated for their in vivo anti-diabetic activity using STZ induced diabetic mice model, and 8h showed a significant diabetic control effect compared to the sitagliptin drug. These studies demonstrated that the novel pyrazole-triazole-persulfonimide and pyrazole-triazole-aryl derivatives might be used as the leading compounds to develop novel DPP-4 inhibitors as potential anti-diabetic agents.

A relay catalysis strategy for enantioselective nickel-catalyzed migratory hydroarylation forming chiral α-aryl alkylboronates

A relay catalysis strategy for enantioselective nickel-catalyzed migratory hydroarylation forming chiral α-aryl alkylboronates

Exfoliated black phosphorous-mediated CuAAC chemistry for organic and macromolecular synthesis under white LED and near-IR irradiation.

The development of long-wavelength photoinduced copper-catalyzed azide–alkyne click (CuAAC) reaction routes is attractive for organic and polymer chemistry. In this study, we present a novel synthetic methodology for the photoinduced CuAAC reaction utilizing exfoliated two-dimensional (2D) few-layer black phosphorus nanosheets (BPNs) as photocatalysts under white LED and near-IR (NIR) light irradiation. Upon irradiation, BPNs generated excited electrons and holes on its conduction (CB) and valence band (VB), respectively. The excited electrons thus formed were then transferred to the CuII ions to produce active CuI catalysts. The ability of BPNs to initiate the CuAAC reaction was investigated by studying the reaction between various low molar mass alkyne and azide derivatives under both white LED and NIR light irradiation. Due to its deeper penetration of NIR light, the possibility of synthesizing different macromolecular structures such as functional polymers, cross-linked networks and block copolymer has also been demonstrated. The structural and molecular properties of the intermediates and final products were evaluated by spectral and chromatographic analyses.

CuI‐catalyzed, one‐pot synthesis of 3‐aminobenzofurans in deep eutectic solvents

An environmentally friendly method is presented here for the synthesis of various benzofuran derivatives using CuI catalyst. In this line, a one‐pot, 3‐component reaction of alkynes, different aldehydes, and amines is employed in choline chloride‐ethylene glycol deep eutectic solvent as an available, cheap, and green media. The employed method includes easy workup and good yields. In this work, 12 different benzofuran derivatives have been prepared in 7 h at 80°C.

Heterometallic PdII–Cl–CuI Catalyst for Efficient Hydrolysis of β-1,4-Glycosidic Bonds in 1-Butyl-3-methylimidazolium Chloride

Heterometallic Pd^II–Cl–Cu^I Catalyst for Efficient Hydrolysis of β-1,4-Glycosidic Bonds in 1-Butyl-3-methylimidazolium Chloride

Magnetic nanostructure-anchored mixed-donor ligand system based on carboxamide and N-heterocyclic thiones: An efficient support of CuI catalyst for synthesis of imidazo[1,2-a]pyridines in eutectic medium

A Cu-incorporated nanocatalyst has been developed by immobilizing copper iodide on a magnetically retrievable mixed-donor ligand system, containing carboxamide, imidazolidine-2-thione and imidazole-2-thione donor groups and characterized by various analysis techniques such as FT-IR, XRD, FE-SEM, EDX elemental mapping, TEM, ICP-OES, TGA, and VSM. The versatility of the synthesized nanocatalyst has been demonstrated for the one-pot synthesis of imidazo[1,2-a]pyridine derivatives via three-component reaction of 2-aminopyridines, aldehydes and alkynes using tetrabutyl ammonium bromide/glycerol (TBAB/glycerol) deep eutectic mixture as a sustainable medium. The nanocatalyst has exhibited high activity and stability under the reaction conditions with a negligible copper leaching, which can be due to the effective coordination interaction between the oxygen atom of carbonyl group as well as the sulfur atoms of thiocarbonyl groups in the supported ligand with copper iodide. The catalyst system can be readily recovered and successfully reused at least five times. Eco-friendly conditions, solvent recoverability, higher TON, wide functional group tolerance and lower E factor (0.2) are some other merits of the present work.

Cancer‐Cell‐Activated in situ Synthesis of Mitochondria‐Targeting AIE Photosensitizer for Precise Photodynamic Therapy

AbstractMaximization of phototoxic damage on tumor with minimized side effect on normal tissue is essential for effective anticancer photodynamic therapy (PDT). This requires highly cancer‐cell‐specific or even cancer‐cell‐organelle‐specific synthesis or delivery of efficient photosensitizers (PSs) in vitro and in vivo, which is difficult to achieve. Herein, we report a strategy of cancer‐cell‐activated PS synthesis, by which an efficient mitochondria‐targeting photosensitizer with aggregation‐induced‐emission (AIE) feature can be selectively synthesized as an efficient image‐guided PDT agent inside cancer cells. MOF‐199, a CuII‐based metal‐organic framework, was selected as an inert carrier to load the PS precursors for efficient delivery and served as a CuI catalyst source for in situ click reaction to form PSs exclusively in cancer cells. The in situ synthesized PS showed mitochondria‐targeting capability, allowing potent cancer‐cell‐specific ablation under light irradiation. The high specificity of PSs produced in cancer cells also makes it safer post‐treatment.

Simultaneous ultrasound- and microwave-assisted one-pot 'click' synthesis of 3-formyl-indole clubbed 1,2,3-triazole derivatives and their biological evaluation.

An environment friendly, high yielding, promising one-pot protocol for the click reaction of N-propargyl-3-formylindole 2(a-b), chloroacetic acid/ester 3(a-b) and sodium azide, leading to the formation of 3-formyl-indole clubbed 1,4-disubstituted-1,2,3-triazole derivatives 4(a-b), 5(a-b) and 6(a-f) aided by CuI catalyst accomplished under acceleration of simultaneous ultrasound and microwave irradiation in a very short reaction time has been described. Further, acid derivative 4(a-b) is subjected to acid-amine coupling reaction with secondary amine (p-t) in the presence of HATU to afford 6(p-t) and 7(p-t). The perspective of this protocol is to get rid of the hectic preparation and handling of organic azide which are generated in situ. Consequently, this protocol blossoms the click process by making it environment benign, user-friendly, safe and clean technique. All the synthesized compounds have been preliminarily screen for their in vitro antimicrobial activity against a panel of pathogenic strains. The majority of compounds possess noticeably inhibitory action against E. Coli, S. Typhi, P. Aeruginosa, C. tetani, S. aureus and B. subtillis. Among all compounds, 6p and 7q exhibit excellent inhibitory action against E.Coli and P. Aeruginosa strain, respectively, as compared to standard drug. One compound 5b shows remarkable potency against fungal strain. Molecular docking study was carried out to understand binding of compound with protein. In silico ADME prediction was carried out to check physicochemical properties of synthesized compound.

Silver Benzoate Facilitates the Copper-Catalyzed C-N Coupling of Iodoazoles with Aromatic Nitrogen Heterocycles.

In the literature, C–N coupling methods for the reaction of iodo-oxazole with 2-pyridinone were found to be low yielding. C–N coupling using silver benzoate additives with CuI catalysts and 4,7-dimethoxy-1,10-phenanthroline ligands has been developed to afford synthetically useful yields of the desired heterobicycle product. The reaction conditions are applied to the coupling of a range of iodo-heterocycles with 2-pyridinone. The coupling of a variety of NH-containing heterocycles with 4-iodo-oxazole is also demonstrated. The use of 2-, 4-, or 5-iodo-oxazole allows for the coupling of pyridinone to each oxazole position.

One-pot synthesis of 3-aminofurans using a simple and efficient recyclable CuI/[bmim]PF6 system

A one-pot three-component reaction of several 2-ketoaldehydes, secondary amines and terminal alkynes to access 3-aminofurans proceeded well in [bmim][PF6] using a simple and cheap CuI catalyst. The resultant 3-aminofuran products were easily isolated using diethyl ether and the CuI/[bmim][PF6] system was reused six times with a slight decrease in the activity.

Poly(3,9-carbazole)s: A Chemically Stable Extended Form of Polyaniline for Nitro-Aromatic Sensor Applications

Abstract Self-polycondensation of 3-iodocarbazole derivatives in the presence of CuI catalysts produces the corresponding 3,9-carbazole-based polymers. Unsubstituted poly(3,9-carbazole) P2 has a limited solubility, whereas poly(3,9-carbazole) P1 with a tert-butyl group at the 6-position of the carbazole is soluble in common organic solvents. These polymers are regarded as an extended form of polyaniline. However, contrary to polyaniline, they are thermally and chemically stable owing to the highly twisted structure between adjacent repeat units. In addition, P1 is highly stable when applying potentials of up to 1.50 V. Due to the high stability toward oxidation, the cast films of these polymers display well-defined visible fluorescence in their neutral states. When the films are exposed to nitro-aromatic vapors (modeled by nitro-explosives), energy transfer induced fluorescent quenching occurs. Upon exposure of the quenched films to air, the fluorescence is restored. Overall, the substituted P1 film exhibits better sensing abilities than the unsubstituted P2 film due to the bulky tert-butyl groups.

Electro-Mechanochemical Atom Transfer Radical Cyclizations using Piezoelectric BaTiO3.

The formation and regeneration of active CuI species is a fundamental mechanistic step in copper‐catalyzed atom transfer radical cyclizations (ATRC). Typically, the presence of the catalytically active CuI species in the reaction mixture is secured by using high CuI catalyst loadings or the addition of complementary reducing agents. In this study it is demonstrated how the piezoelectric properties of barium titanate (BaTiO3) can be harnessed by mechanical ball milling to induce electrical polarization in the strained piezomaterial. This strategy enables the conversion of mechanical energy into electrical energy, leading to the reduction of a CuII precatalyst into the active CuI species in copper‐catalyzed mechanochemical solvent‐free ATRC reactions.