Coupling Reaction Of Aldehydes Research Articles

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.

Design of a Copper(II) Complex with Tetradentate Bis‐Benzotriazole‐Appended Bipyridine Ligand and its Catalytic Application in A3 Coupling Reaction

AbstractIn this report, a Cu(II) complex Cu‐L4 containing a new tetradentate benzotriazole‐appended bipyridine ligand was synthesized and characterized fully via spectroscopic and crystallographic techniques. The crystal structure of the complex revealed that the ligand is bound to copper in a tetradentate fashion in a plane and the axial positions are occupied by an anion and a solvent molecule, resulting in a distorted octahedral geometry of the complex in solid‐state. This air‐stable complex was utilized as homogeneous precatalyst for the synthesis of several propargylamine derivatives by 3‐component A3 coupling reactions of aldehydes, amines, and alkynes under aerial atmosphere.

N‐Heterocyclic Carbenes (NHCs)‐Catalyzed Coupling Reactions of Aldehydes and Organic Halides

AbstractThis concept aims to summarize the direct coupling of aldehydes and organic halides (including activated and unactivated organic halides) catalyzed by N‐heterocyclic carbenes (NHCs). The key factor of this transformation is the formation of Breslow intermediates, which are either nucleophilic or reductive. Additionally, the activation of inert C−H bond also was reviewed in this performance via the processes of single electron transfer (SET) and subsequent intramolecular 1,n‐ hydrogen atom transfer (HAT) or intermolecular HAT. Finally, the key differences and reactivity of various Breslow intermediates, generated from different NHCs, have been discussed to give a deeper understanding of the ongoing popularity of NHC‐organocatalysis.

Synthesis of propargylamines catalyzed by in situ generated copper nanoparticles in water

An efficient and green protocol for the A3 coupling reaction of aldehyde, amine and alkyne involves the use of copper nanoparticles and β-cyclodextrin in water. The copper nanoparticles are generated in situ by reduction with green and cheap sodium hydroxymethanesulfinate (rongalite) while β-cyclodextrin serves as a stabilizing agent and a phase-transfer catalyst.

A sustainable avenue for the synthesis of propargylamines and benzofurans using a Cu-functionalized MIL-101(Cr) as a reusable heterogeneous catalyst

A heterogeneous copper-catalyzed A3 coupling reaction of aldehydes, amines, and alkynes for the synthesis of propargylamines and benzofurans has been developed. Here, the modified metal–organic framework MIL-101(Cr)-SB-Cu complex was chosen as the heterogeneous copper catalyst and prepared via post-synthetic modification of amino-functionalized MIL-101(Cr). The structure, morphology, thermal stability, and copper content of the catalyst were determined by FT-IR, PXRD, SEM, TEM, EDX, TGA, XPS, and ICP-OES. The catalyst shows high catalytic activity for the aforementioned reactions under solvent-free reaction conditions. High yields, low catalyst loading, easy catalyst recovery and reusability with not much shrink in catalytic activity, and a good yield of 82% in gram-scale synthesis are some of the benefits of this protocol that drove it towards sustainability.

Electron-modulating effects of intercalating molecules in functionalized graphene oxide: Optimizing the coordination microenvironment of Ag nanoparticles for efficient catalytic A3 coupling reactions

In this paper, functionalized graphene oxide (GO) nanosheets were modified by forming benzamide (BzA) bonds using aniline with different substituents (4-tertbutylaniline, 4-nitroaniline, aniline) as intercalating molecules. Then the Ag@R-BzA/GO composite catalysts were prepared by loading Ag nanoparticles to reveal the electronic modulation of functionalized graphene oxide interfaces by aniline molecules effects with different substituents. The experimental results showed that the layer spacing of the composites obtained after intercalation with aniline whose substituent is an electron-giving group increased by about 40%. Moreover, the electron donating role of tert‑butyl regulates the charge distribution on the graphene oxide material and provides a good coordination environment for the loading of Ag nanoparticles. AgNPs are stably present in the interlayer of graphene oxide nanosheets by ligating with amide bonds and oxygen-containing functional groups to produce strong metal-carrier interactions. Ag@4‑tert-BzA/GO composites showed high catalytic activity in the A3 coupling reaction of aldehydes, alkynes and amines for the synthesis of alkynylamines(TON=19225.82). The electronic effect of the substituent groups on the intercalated molecules reported in this paper is a modulation on the molecular and atomic scale, which provides a new idea for the modulation of the microenvironment in metal-loaded catalysts.

Mesoionic Carbene‐Catalyzed Formyl Alkylation of Aldehydes

AbstractKetones are among the most useful functional groups in organic synthesis, and they are commonly encountered in a broad range of compounds with various applications. Herein, we describe the mesoionic carbene‐catalyzed coupling reaction of aldehydes with non‐activated secondary and even primary alkyl halides. This metal‐free method utilizes deprotonated Breslow intermediates derived from mesoionic carbenes (MICs), which act as super electron donors and induce the single‐electron reduction of alkyl halides. This mild coupling reaction has a broad substrate scope and tolerates many functional groups, which allows to prepare a diversity of simple ketones as well as bio‐active molecules by late‐stage functionalization.

Mesoionic Carbene-Catalyzed Formyl Alkylation of Aldehydes.

Ketones are among the most useful functional groups in organic synthesis, and they are commonly encountered in a broad range of compounds with various applications. Herein, we describe the mesoionic carbene-catalyzed coupling reaction of aldehydes with non-activated secondary and even primary alkyl halides. This metal-free method utilizes deprotonated Breslow intermediates derived from mesoionic carbenes (MICs), which act as super electron donors and induce the single-electron reduction of alkyl halides. This mild coupling reaction has a broad substrate scope and tolerates many functional groups, which allows to prepare a diversity of simple ketones as well as bio-active molecules by late-stage functionalization.

Insights into the Three-Component Coupling Reactions of Aldehydes, Alkynes, and Amines Catalyzed by N-heterocyclic Carbene Silver: A DFT Study

Density functional theory (DFT) was used to investigate the three-component coupling reactions of aldehydes, alkynes, and amines (A3 coupling) using N-heterocyclic carbene silver as the catalyst. This study reveals that the addition reaction between the catalyst N-heterocyclic carbene silver and phenylacetylene (PAE) forms Ag_PAE. Subsequently, one hydrogen atom of the Ag_PAE migrates to the nitrogen atom of the Amine. Thereafter, the amine aldehyde condensation reaction generates a molecule of water and an imine ion with (Path one) or without (Path two) another amine catalyst. Path one has a lower reaction barrier than Path two. Subsequently, the imine ion reacts with silver phenylacetylide to generate the A3 coupling reaction product propargylamine (PPA). Furthermore, the triple bond and −N3 group in PPA undergo a cycloaddition reaction and generate the final product (PR). The entire reaction is strongly exothermic, and, therefore, the reaction is easy to conduct. Moreover, conceptual density functional theory calculations confirm the reaction mechanism. Investigating the mechanism of these reactions will be helpful for understanding and developing new synthesis strategies for similar functional compounds.

Magnetic nanoparticles modified with a copper(i) complex as a novel and efficient reusable catalyst for A3 coupling leading to C-N bond formation.

Propargylamines are an important and valuable family of nitrogen-containing compounds with many applications in the fields of medical, industrial, and chemical processes. One-pot multicomponent A3 coupling reactions of aldehydes, amines, and alkynes in the presence of transition metals as catalysts is an efficient strategy for preparing propargylamines. In this study, we fabricated a novel magnetically reusable copper nanocatalyst [Fe3O4-BIm-Pyrim-CuI] through the immobilization of the copper(i) complex on the surface of the magnetic nanoparticles modified with benzimidazole-pyrimidine ligand and evaluated its catalytic activity in the preparation of propargylamines through one-pot multicomponent A3 coupling reactions of aldehydes, amines, and alkynes. Under this catalytic system, aryl substrates with both electron-donating and electron-withdrawing substituents also gave the desired products in excellent yields under standardized conditions. The Fe3O4-BIm-Pyrim-CuI catalyst was easily separated using an external magnet, and the recovered catalyst was reused in 8 cycles without significant loss of activity.

Development of magnetic Fe3O4-chitosan immobilized Cu(II) Schiff base catalyst: An efficient and reusable catalyst for microwave assisted one-pot synthesis of propargylamines via A3 coupling

A novel heterogeneous catalyst (Fe3O4@CS@Schiffbase@Cu) is developed by generating the Cu(II) Schiff base complex on the Fe3O4-chitosan surface. The structural and morphological characteristics of the catalyst is confirmed by all physicochemical techniques. A low catalyst loading (1.1 mol% Cu) of the immobilized Cu(II) Schiff base complex shows its catalytic activity for A3 coupling reaction of Aldehyde, Alkyne, and Amines under microwave irradiation. The catalyst was proven very active for a wide variety of propargylamines syntheses using different substituted aromatic aldehydes, secondary amines, and phenylacetylene under optimized conditions. The recyclability of the catalyst was efficient even after six cycles with a 95% efficiency.

Ag nanoparticles grafted porous organic polymer as an efficient heterogeneous catalyst for solvent-free A3 coupling reactions

Designing of low cost catalytic system for new CC/CN/CO bond formation reactions is very challenging in synthetic organic chemistry. Herein, we report a new Ag NPs immobilized porous organic polymer (POP) material Ag-NPs@PDVTA-1 by grafting of Ag nanoparticles at the surface of a POP material PDVTA-1. PDVTA-1 has been synthesized via radical co-polymerization of divinylbenzene and triallylamine under solvothermal reaction conditions. PDVTA-1 as well as the Ag-loaded catalyst Ag-NPs@PDVTA-1 are fully characterized to understand their physico-chemical properties. Ag-NPs@PDVTA-1 is used as heterogeneous nanocatalyst for the one pot three component A3 coupling reaction of aldehyde, secondary amine and terminal alkyne for the synthesis of a wide range of propargylamine derivatives under mild and eco-friendly reaction conditions. The desired products were obtained in high yields over this environmentally safe catalyst under optimized reaction conditions. Remarkably high specific surface area of Ag-NPs@PDVTA-1 (694 m2g−1) and its highly accessible catalytically active Ag-sites in the nano-architecture potentially makes it an efficient catalyst as reflected from the respective turn over numbers. The catalyst was collected and reused for several reaction cycles without any noticeable decline in its catalytic activity, suggesting its high merit in heterogeneous catalysis for the synthesis of value added CC/CN coupling products via one pot coupling reaction.

Clean Synthesis of Propargylamines Using Novel Magnetically Recyclable Silver Nanocatalyst (AgMNPs)

A novel and green magnetic nanocatalyst were synthesized by anchoring silver (I) to (2-iminomethyl)pyridine moiety. The prepared nanocatalyst was identified by different techniques, such as FT-IR, XRD, SEM, EDX, VSM, and TGA analyses. The nanocatalyst exhibited significant catalytic activity and recoverability in a three-component coupling reaction of aldehyde, amine, and terminal alkyne to produce a variety of propargylmines. This impactful method furnished the desired products under mild reaction conditions, in excellent yield (91–98%) and lower reaction time (25–45 min). The nanocatalyst was easily recovered by an external magnet and reused in10 consecutive cycles without a considerable decrease in its activity and selectivity.

Synthesis of N-protected 1-aminoalkylphosphonium salts—a new perspective

The current study presents two novel and efficient strategies for the synthesis of N-protected 1-aminoalkylphosphonium salts from readily available substrates. The first one is a one-pot methodology which is based on the three-component coupling reaction of aldehydes with amides, carbamates, lactams, imides, or urea in the presence of triarylphosphonium salt. This approach results in the production of a wide range of structurally diverse N-protected 1-aminoalkylphosphonium salts. The second one is a step-by-step procedure which results in the synthesis of N-protected 1-aminomethylphosphonium salts only, and hence has a limited scope of application. This method is performed in two steps: transformation of amide-type substrates to the corresponding hydroxymethyl derivatives and substitution of the hydroxyl group with triarylphosphine. Both protocols are promising alternatives and complement the hitherto described methodologies.

Dinuclear silver-bis(N-heterocyclic carbene) complexes: Synthesis, catalytic activity in propargylamine formation and computational studies

Preparation of a series of 1,1′-dialkyl-3,3′-(2-methylenepropane-1,3-diyl)dibenzimidazolium salts (alkyl = ethyl, propyl, butyl) (2a-2c) and their dinuclear bis(N-heterocyclic carbene) silver complexes (3a-3c) is reported. The silver complexes were synthesized via in situ deprotonation with Ag2O in 67-74% yields. The structural definitions of the synthesized compounds were performed by 1H NMR, 13C NMR, elemental analysis, FT-IR and also LC-MSMS techniques (only for 3a-3c). The silver complexes were utilized for three-component coupling reactions of aldehydes, amines and alkynes (A3-coupling). It was found that increasing the chain length of the alkyl substituent on the N-heterocyclic carbene ligand led to increase in catalytic performance. 3c showed the highest activity with 81% yield and with TON of 27 for N,N-diethyl-3-phenylprop-2-yn-1-amine formation. Geometry optimization was performed and geometric parameters were calculated for the compounds. The theoretical harmonic vibration frequencies of molecules were computed by DFT/B3LYP methods for their optimized geometries.

Silver–N‐heterocyclic carbene complexes‐catalyzed multicomponent reactions: Synthesis, spectroscopic characterization, density functional theory calculations, and antibacterial study

Nowadays, silver-N-heterocyclic carbene (silver-NHCs) complexes are widely used in medicinal chemistry due to their low toxic nature toward humans. Due to the success of silver-NHCs in medicinal applications, interest in these compounds is rapidly increasing. Therefore, the interaction of N,N-disubstituted benzimidazolium salts with Ag2 O in dichloromethane to prepare novel Ag(I)-NHCs complexes was carried out at room temperature for 120 h in the absence of light. The obtained complexes were identified and characterized by 1 H and 13 C nuclear magnetic resonance, Fourier-transform infrared, UV-Vis, and elemental analysis techniques. Then, the silver complexes were applied for three-component coupling reactions of aldehydes, amines, and alkynes. The effect of changing the alkyl substituent on the NHCs ligand on the catalytic performance was investigated. In addition, it has been found that the complexes are antimicrobially active and show higher activity than the free ligand. The silver-carbene complexes showed antimicrobial activity against specified microorganisms with MIC values between 0.24 and 62.5 μg/ml. These results showed that the silver-NHC complexes exhibit an effective antimicrobial activity against bacterial and fungal strains. A density functional theory calculation study was performed to identify the stability of the obtained complexes. All geometries were optimized employing an effective core potential basis, such as LANL2DZ for the Ag atom and 6-311+G(d,p) for all the other atoms in the gas phase. Electrostatic potential surfaces and LUMO-HOMO energy were computed. Transition energies and excited-state structures were obtained from the time-dependent density functional theory calculations.

Bioinspired AgNPs: Effective and Recyclable Catalysts towards the One‐Pot Synthesis of Hexahydroquinoline Derivatives via Three‐Component Coupling Reaction

AbstractGreen synthesis of silver nanoparticles (AgNPs) was carried out using aqueous bark extract of Shorea robusta(Sal tree) as the reducing and capping agent. AgNPs were characterized using modern characterization tools like UV‐Vis, PXRD, FT‐IR, SEM, and HR‐TEM. The catalytic application of the prepared AgNPs in three‐component coupling reaction of aldehyde, malononitrile, and cyclic enamino ketone resulted in good to excellent yields of hexahydroquinoline derivatives. Moreover, the catalyst can be recycled up to 5 times without compromising too much yield. The mechanistic pathway was investigated employing GC‐Mass spectroscopy and supported through the Density Functional Theory (DFT) calculations. A two‐step mechanism has been proposed for the coupling reaction, and the presence of electron‐withdrawing group in the aldehyde component is found to be more favorable than electron‐releasing one in terms of yield with lesser time.

Nickel-Catalyzed Carboalkenylation of 1,3-Dienes with Aldehydes and Alkenylzirconium Reagents: Access to Skipped Dienes.

A regio- and stereoselective nickel-catalyzed three-component coupling reaction of aldehydes, 1,3-dienes, and alkenylzirconium reagents was realized. The ligand- and additive-free protocol afforded a convenient approach to the synthesis of skipped diene compounds bearing various functionals (e.g., hydroxyl, carbonyl, halide) and heterocyclic groups. The products were readily transformed into structurally diverse polyenes. The utility of this reaction was also demonstrated by the one-pot operation and scale-up preparation.

Zinc Complexes of β‐Ketoiminato Ligands as Efficient Catalysts for the Synthesis of α‐Amino Nitriles via Strecker Reaction

AbstractWe report the synthesis of α‐aminonitriles by one‐pot coupling reaction of aldehyde, amines and trimethylsilyl cyanide (TMSCN) using β‐ketoiminato zinc complexes as a pre‐catalyst in very good yield under mild reaction condition. Homoleptic zinc complex [{κ2‐(2,4,6‐Me3C6H2NC(Me)=CHC(Me)=O)}2Zn] (1 a) was synthesized by the treatment of protic ligand [(2,4,6‐Me3C6H2NHC(Me)=CHC(Me)=O)] (L1H) with potassium hydride and anhydrous zinc diiodide in 2 : 2 : 1 molar ratio in THF. Analogous reactions using [(2,6‐iPr2C6H3NHC(Me)=CHC(Me)=O)] (L2H) and [(Ph2CHNHC(Me)=CHC(Me)=O)] (L3H) as protic ligands, dinuclear zinc complexes [{κ3‐(2,6‐iPr2C6H3NC(Me)=CHC(Me)=O)}ZnI]2 (1 b) and [Zn(Ph2CHNHC−(Me)=CHC(Me)=O)ZnI2] (1 c) were obtained in good yield. Molecular structures of ligands L1H, L3H, and zinc complexes 1 a, 1 b, and 1 c were established by single‐crystal x‐ray diffraction analysis. Dinuclear zinc complexes 1 b, and 1 c exhibited high transformation, greater selectivity and broad substrate scope for the synthesis of α‐aminonitrile under mild condition. A most plausible mechanism for synthesis α‐aminonitrile is proposed based on several controlled reactions.

Nickel‐Catalyzed Reductive Coupling of Aldehydes with Alkynes Mediated by Alcohol†

Summary of main observation and conclusionA nickel‐catalyzed reductive coupling of aldehydes with alkynes using 1‐phenylethanol as reducing agent has been developed. The key achievement of this work is that we demonstrate environmentally benign 1‐phenylethanol can serve as a viable alternative reducing agent to Et3B, ZnEt2 and R3SiH for the nickel‐catalyzed reductive coupling reaction of aldehyde and alkynes.