Three-component Coupling Reaction Research Articles

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.

Regiocontrol Using Fluoro Substituent on 3,6-Disubstituted Arynes.

The effect of fluoro substituent on the regioselectivity of several reactions of 3,6-disubstituted arynes was studied. These arynes contained another inductively electron-withdrawing substituent other than fluorine. A reasonable degree of regiocontrol was achieved in the (3 + 2) cycloaddition reaction of 3,6-disubstituted aryne containing both fluorine and bromine atoms with benzyl azide. Furthermore, the insertion reaction of aryne into Sn-F σ-bonds and the three-component coupling reaction involving the insertion of aryne into C=O π-bonds also led to the high degree of regiocontrol.

A strategy to develop hydrophobic stainless steel mesh through three-component coupling reaction with presence of sulfur

Metal meshes with controlled surface properties have shown great potential for oil–water separation. However, it is still challenging to prepare cost-effective meshes to satisfy the material requirements under a variety of harsh conditions. In this study, polydopamine was deposited on the surface of stainless steel mesh to provide amine groups as active sites, and a series of modification strategies were constructed through sulfur-based three-component coupling reactions between the amine-functionalized mesh and aliphatic amine, alkyne, isocyanide. The prepared metal meshes showed excellent hydrophobicity with water contact angle in the range of 131–142° and could be used to separate a series of oil–water mixtures with separation efficiency above 99 % and flux higher than 2.3 × 104 L/m2/h. In addition, the separation capabilities of the developed meshes remained stable after 10 cyclic operations. More significantly, the modified meshes could tolerate repeated and prolonged usage and demonstrated excellent stability under various chemical conditions. It was found that the sulfur-based three-component reaction was a versatile way to get functional surface for metal substrate.

CO2 -Based Carbamate Synthesis Utilizing Reusable Polymer-Supported DBU.

The present study highlights a novel and advantageous protocol for accessing carbamates through the well-established three-component coupling reaction involving CO2 , amines, and alkyl halides. By employing an immobilized organic base, operating under mild reaction conditions, an array of alkyl carbamates in yields of up to 95 % could be isolated. This approach offers a broad and versatile product scope, allowing for the facile modification of both the amine and alkyl halide reactants. Notably, the pioneering use of an immobilized organic base, specifically the polymer-supported 1,8-diazabicyclo[5.4.0]undec-7-ene (PS-DBU), in this three-component reaction eliminates the need for classical purification steps, streamlining the process. To ensure practicality and sustainability, extensive studies were conducted to verify the recovery and reusability of the polymer-supported DBU catalyst, which consistently maintained the high chemical yield of the carbamates across multiple cycles. Overall, this innovative protocol represents a significant advancement in carbamate synthesis, combining efficiency, generality, and the potential for DBU recycling.

Visible-Light-Mediated Three-Component Decarboxylative Coupling Reactions to Synthesize 1,4-Diol Monoethers.

An efficient approach for 1,2-difunctionalization of aromatic olefins and the synthesis of functionalized 1,4-diols monoethers has been established via a photoinduced three-component reaction of an α-alkoxycarboxylic acid, an aromatic olefin, and an aldehyde. The reaction proceeds by photoinduced oxidative decarboxylation of the carboxylic acid followed by the addition of the α-alkoxyalkyl radical to the olefin, one-electron reduction of the addition radical, and the nucleophilic attack of the resulting carbanion to the aldehyde. Besides the convenient one-pot protocol of the three-component reaction, this method offers several other advantages, including good functional group tolerance for the three substrates, gentle reaction conditions, and ease of scaling up. The reaction mechanism has been investigated through free radical trapping experiment and isotope labeling experiments.

Synthesis of Pyridin-1(2H)-ylacrylates and the Effects of Different Functional Groups on Their Fluorescence.

While fluorescent organic materials have many potential as well as proven applications and so have attracted significant attention, pyridine-olefin conjugates remain a less studied subset of such systems. Herein, therefore, we report on the development of the straightforward syntheses of pyridin-1(2H)-ylacrylates and the outcomes of a study of the effects of substituents on their fluorescent properties. Such compounds were prepared using a simple, metal-free and three-component coupling reaction involving 2-aminopyridines, sulfonyl azides and propiolates. The fluorescent properties of the ensuing products are significantly affected by the positions of substituents on the cyclic framework, with those located in central positions having the greatest impact. Electron-withdrawing groups tend to induce blue shifts while electron-donating ones cause red shifts. This work highlights the capacity that the micro-modification of fluorescent materials provides for fine-tuning their properties such that they may be usefully applied to, for example, the study of luminescent materials.

Tandem CuI – Zinc dust as a sustainable catalyst for the preparation of propargylamine derivatives via an A3 coupling reaction, under neat conditions

The cooperative activity of two proximal metal ions is well-known to exhibit highly efficient and synergistic catalytic activities in living organisms. Owing to this knowledge, tandem Cu–Zn systems have been widely used to catalyze a diversity of chemical transformations. This report describes the use of CuI and zinc dust as a sustainable tandem catalyst for the preparation of propargylamines via a three-component coupling reaction under neat conditions. This reaction proceeds at low temperature, and produces good yields with a number of aliphatic and aromatic aldehydes. The reactivity of a number of amines and alkynes has also been explored under these reaction conditions, resulting in 33 fully characterized compounds prepared in the process. Among the ketones tested during this study, only cyclohexanone was able to produce the expected product in a decent yield. The catalytic system reported here represents one of the sustainable approaches to the preparation of propargylamines, as it involves the use of naturally abundant metals as a tandem catalyst, at a low temperature and under neat conditions.