Multicomponent Coupling Reaction Research Articles

Unexplored catalytic potency of a magnetic CoFe2O4/Ni-BDC MOF composite for the one-pot sustainable synthesis of 5-substituted 1-H tetrazoles

Within the domain of materials science and engineering, significant progress has led to the emergence of innovative materials based on magnetic MOFs, positioning them as promising candidates in the field of catalysis. This research aims to elaborate on the development of a finely tailored magnetic MOF composite; Ni-BDC (Nickel benzene-1,4-dicarboxylate) microflakes which was synthesized through a straightforward in-situ solvothermal approach. Extensive investigations into the structural properties of the resultant hybrid composite were carried out using various characterization techniques encompassing X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FT-IR), field emission scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), Brunauer-Emmett-Teller (BET) analysis, atomic absorption spectroscopy (AAS), energy-dispersive X-ray spectroscopy (EDX), thermogravimetric analysis (TGA) and vibrating sample magnetometry (VSM). The developed material demonstrated remarkable efficiency in expediting the synthesis of a diverse array of pharmaceutically active 5-substituted 1H-tetrazole derivatives through a multicomponent coupling reaction involving substituted aldehydes, malononitrile, and sodium azide as key components. A noteworthy feature of this approach is its adherence to environmentally friendly reaction conditions, thus making it superior in comparison to previously established methodologies. Furthermore, a plausible mechanistic pathway has been proposed to elucidate the impressive performance of the developed catalytic system in the targeted reaction. It is anticipated that the current research will not only contribute to the purposeful designing of advanced magnetic MOF-based architectures but will also play a pivotal role in promoting sustainable practices in industrial processes, addressing pressing environmental and economic concerns.

Copper-Catalyzed Multicomponent Coupling Reaction of Primary Aromatic Amines, Rongalite, and Alkynes: Access to N-Aryl Propargylamines.

In this work, a practical copper-catalyzed multicomponent coupling reaction of primary aromatic amines, rongalite, and alkynes for the direct synthesis of N-aryl propargylamines has been developed. This method could overcome the substrate limitation in A3 coupling reactions of primary aromatic amines, formaldehyde, and alkynes. Mechanistic studies revealed that rongalite acts as not only the active C1 unit but also the accelerator to activate the in situ-generated N-arylmethanimines for the coupling reaction with alkynes. This coupling reaction is highly efficient and features a broad substrate scope, as well as utility with scale-up synthesis and converting the corresponding product N-aryl propargylamines into useful heterocyclic skeletons.

Organoselenium-Catalyzed C2,3-Diarylation of N-H Indoles.

An organoselenium-catalyzed C2,3-diarylation of unprotected N-H indoles with electron-rich aromatics has been developed. This one-pot multicomponent tandem cross-dehydrogenation coupling reaction allows for the incorporation of two different aromatic groups to indoles. More importantly, this approach offers significant advantages, including a high atom and step economy, eliminating the need for prepreparation of the reaction substrates, streamlining the synthetic process and enhancing its practicality. Overall, this organoselenium-catalyzed C2,3-diarylation reaction presents an efficient and versatile strategy for the functionalization of indole derivatives.

Copper-Assisted (Pseudo-)Halochalcogenation of Arynes.

In this report, we describe the multicomponent coupling reaction between arynes, (pseudo)halides, and an electrophilic chalcogen species. Addition of a copper salt enabled smooth conversion by suppressing side reactions. A variety of different aryne precursors as well as seleno- and thiosulfonates were employed, yielding a broad spectrum of ortho-(pseudo)halogenated chalcogenides. This motif was subjected to different cross-coupling approaches, demonstrating the applicability of these compounds as building blocks for more complex structures.

Organophotocatalytic access to C-glycosides: multicomponent coupling reactions using glycosyl bromides.

Photochemical multi-component coupling reactions initiated by the activation of glycosyl bromides in the presence of 1,4-bis(diphenylamino)benzene (BDB) as an organic photocatalyst were developed. C-glycosides accompanied by olefin (di)functionalization were obtained. This method allows us to access various C-glycosides with alkene, carbonyl, alcohol, ether, and amide functionalities.

Modular synthesis of α-branched secondary alkylamines via visible-light-mediated carbonyl alkylative amination.

The development of methods for the assembly of secondary α-alkyl amines remains a central challenge to chemical synthesis because of their critical importance in modulating the physical properties of biologically active molecules. Despite decades of intensive research, chemists still rely on selective N-alkylation and carbonyl reductive amination to make most amine products. Here we report the further evolution of a carbonyl alkylative amination process that, for the first time, brings together primary amines, aldehydes and alkyl iodides in a visible-light-mediated multicomponent coupling reaction for the synthesis of a wide range of α-branched secondary alkylamines. In addition to exploring the tolerance and limitations in each reaction component, we also report preliminary applications to the telescoped synthesis of α-branched N-heterocycles and an N-alkylation protocol that is selective for primary over cyclic secondary amines. Our data support a mechanism involving addition of an alkyl radical to an uncharged alkyl imine which, to the best of our knowledge, has not previously been described. We believe that this method will enable practitioners of synthetic chemistry in academic and industrial settings to approach the synthesis of these important molecules in a manner that is streamlined compared to established approaches.

Scope and Mechanistic Studies on the Ruthenium-Catalyzed Multicomponent Deaminative C–H Coupling Reaction of Phenols with Aldehydes and Enamines for the Formation of Xanthene and Dioxacyclic Derivatives

The in situ generated catalytic system from the tetranuclear Ru–H complex [(PCy3)(CO)RuH]4(O)(OH)2 (1) with 3,4,5,6-tetrachloro-1,2-benzoquinone (L1) has been found to mediate a multicomponent deaminative coupling reaction of phenols with aldehydes and enamines to form xanthene products. The multicomponent C–H coupling reaction of phenols with 2-hydroxybenzaldehydes and cyclic enamines efficiently installed the tricyclic 1,3-dioxacin derivatives, while the analogous coupling reaction of phenols with 2-hydroxybenzaldehydes and triethylamine selectively formed bicyclic 1,5-dioxacyclic derivatives. The density functional theory (DFT) calculations established two energetically viable mechanistic pathways for the formation of xanthene products, in which both pathways identified the C–O bond cleavage step as the turnover limiting step. A Hammett plot from the coupling reaction of 3,5-dimethoxyphenol with an enamine and para-substituted benzaldehydes p-X-C6H4CHO (X = OMe, Me, H, Cl, CF3) showed a negative slope (ρ = −0.98). The calculated energy analysis showed a similar trend (ρ = −0.59) for the mechanism via the C–O cleavage rate-limiting step. The combined experimental and DFT computational results support a mechanistic path that involves the dehydrative C–H coupling of phenol with aldehyde, followed by the deaminative coupling reaction with an enamine in forming the xanthene product.

Catalytic applications of cobalt/cobalt oxide nanoparticles in heterocyclic compounds

Worldwide interest is growing in the various catalytic uses of cobalt/cobalt oxide nanoparticles in the synthesis of heterocyclic compounds. This review covers the last seven-year (2017–2023) reports on the catalytic applications of cobalt/cobalt oxide nanoparticles in heterocyclic compounds. For several chemical reactions involving N-Heterocycles, we described Co/CoO nanoparticles that were doped with other elements and coordinated with nitrogen in the current work. An excellent performance for reversible hydrogenation-dehydrogenation processes is attributed to a well-designed Co metal catalyst with a reductive N-formylation of N-heterocyclic arenes, an organic pathway for hydrogen storage. There have also been reports of various MCR for heterocycles utilising Co/CoO NPs as the catalyst. In addition to the solvent-free, selective aza-heterocycle synthesis using cobalt described above, intra-molecular ring-closing processes for the synthesis of organic heterocycles have also recently been discovered. In this context numerous studies on a variety of topics, including the oxygenation of alcohols to aldehyde, esters, and nitriles, aryl halide biaryl coupling reactions, radical trans-annulations, multicomponent coupling reactions, cyclization, and cyclo-propanations have been described.

Combining Enantioselective Rh-Catalyzed Conjugate Addition and Ir-Catalyzed Allylic Alkylation in Stereodivergent, Multicomponent Coupling Reactions to Form Three Stereocenters.

Stereodivergent dual catalysis has emerged as a powerful tool to selectively prepare all four stereoisomers in molecules containing two chiral centers from common starting materials. Most processes involve the use of two substrates, and it remains challenging to use dual catalyst approaches to generate molecules having three newly formed stereocenters with high diastereo- and enantioselectivity. Here we report a multicomponent, stereodivergent method for the synthesis of targets containing three contiguous stereocenters by the combination of enantioselective Rh-catalyzed conjugate addition and Ir-catalyzed allylic alkylation methodologies. Both cyclic and acyclic α,β-unsaturated ketones undergo β-arylation using aryl boron reagents to form an enolate nucleophile that can be subsequently allylated at the α-position. The reactions proceed often with >95 % ee and with >90 : 10 dr. Epimerization at the α-carbonyl center enables the preparation of any of the eight possible stereoisomers from common starting materials, as demonstrated for cyclohexanone products.

Cross- and Multi-Coupling Reactions Using Monofluoroalkanes.

Carbon-fluorine bonds are stable and have demonstrated sluggishness against various chemical manipulations. However, selective transformations of C-F bonds can be achieved by developing appropriate conditions as useful synthetic methods in organic chemistry. This review focuses on C-C bond formation at monofluorinated sp3 -hybridized carbons via C-F bond cleavage, including cross-coupling and multi-component coupling reactions. The C-F bond cleavage mechanisms on the sp3 -hybridized carbon centers can be primarily categorized into three types: Lewis acids promoted F atom elimination to generate carbocation intermediates; nucleophilic substitution with metal or carbon nucleophiles supported by the activation of C-F bonds by coordination of Lewis acids; and the cleavage of C-F bonds via a single electron transfer. The characteristic features of alkyl fluorides, in comparison with other (pseudo)halides as promising electrophilic coupling counterparts, are also discussed.

Nickel-Catalyzed Three-Component Tandem Radical Cyclization 1,5-Difunctionalization of 1,3-Enynes and Alkyl Bromide.

A nickel-catalyzed three-component tandem radical cyclization reaction of aryl bromides with 1,3-enynes and aryl boric acids to construct γ-lactam-substituted allene derivatives has been described. This protocol provides lactam alkyl radicals through the free radical cyclization process, which can be effectively used to participate in the subsequent multicomponent coupling reaction so that 1,3-enynes could directly convert into corresponding poly-substituted allene compounds. In addition, this efficient method enjoys a broad substrate scope and provides a series of 1,5-difunctionalized allenes in a one-pot reaction.

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.

A Review on the Syntheses and Applications of the 5H-chromeno[2,3- b]pyridines

Abstract: 5H-Chromeno[2,3-b]pyridine derivatives are a series of the most important compounds of chromenes with industrial, biological, and medicinal properties. These compounds are known as the privileged medicinal scaffold and can be synthesized by different methods such as multicomponent reactions (MCRs), Multicomponent coupling reactions (MCCRs), pot, atom, and step economy (PASE). In this review article, we have focused on the significant reactions for the syntheses and applications of 5H-chromeno[2,3-b] pyridines, including two-component reactions, three-component reactions, four component reactions, and multi-step reactions. This review is expected to serve as a useful conceptual overview and inspire the next generation to develop the different strategies for the preparation of 5H Chromeno[2,3-b] pyridine derivatives

Practical synthesis of allylic amines via nickel-catalysed multicomponent coupling of alkenes, aldehydes, and amides.

Molecules with an allylic amine motif provide access to important building blocks and versatile applications of biologically relevant chemical space. The need for diverse allylic amines requires the development of increasingly general and modular multicomponent reactions for allylic amine synthesis. Herein, we report an efficient catalytic multicomponent coupling reaction of simple alkenes, aldehydes, and amides by combining nickel catalysis and Lewis acid catalysis, thus providing a practical, environmentally friendly, and modular protocol to build architecturally complex and functionally diverse allylic amines in a single step. The method is remarkably simple, shows broad functional-group tolerance, and facilitates the synthesis of drug-like allylic amines that are not readily accessible by other methods. The utilization of accessible starting materials and inexpensive Ni(ii) salt as the alternative precatalyst offers a significant practical advantage. In addition, the practicality of the process was also demonstrated in an efficient, gram-scale preparation of the prostaglandin agonist.

Exploring structural effects in a new class of NRF2 inhibitors.

NRF2 is a transcription factor that controls the cellular response to various stressors, such as reactive oxygen and nitrogen species. As such, it plays a key role in the suppression of carcinogenesis, but constitutive NRF2 expression in cancer cells leads to resistance to chemotherapeutics and promotes metastasis. As a result, inhibition of the NRF2 pathway is a target for new drugs, especially for use in conjunction with established chemotherapeutic agents like carboplatin and 5-fluorouracil. A new class of NRF2 inhibitors has been discovered with substituted nicotinonitriles, such as MSU38225. In this work, the effects on NRF2 inhibition with structural changes were explored. Through these studies, we identified a few compounds with as good or better activity than the initial hit but with greatly improved solubility. The syntheses involved a variety of metal-catalyzed reactions, including titanium multicomponent coupling reactions and various Pd and Cu coupling reactions. In addition to inhibiting NRF2 activity, these new compounds inhibited the proliferation and migration of lung cancer cells in which the NRF2 pathway is constitutively activated.

Photoredox cooperative N-heterocyclic carbene/palladium-catalysed alkylacylation of alkenes

Three-component carboacylation of simple alkenes with readily available reagents is challenging. Transition metal-catalysed intermolecular carboacylation works for alkenes with strained ring or directing groups. Herein, we develop a photoredox cooperative N-heterocyclic carbene/Pd-catalysed alkylacylation of simple alkenes with aldehydes and unactivated alkyl halides to provide ketones in good yields. This multicomponent coupling reaction features a wide scope of alkenes, broad functional group compatibility and free of exogenous photosensitizer or external reductant. In addition, a series of chlorinated cyclopropanes with one or two vicinal quaternary carbons is obtained when chloroform or carbon tetrachloride is used as the alkyl halide. The reaction involves the alkyl radicals from halides and the ketyl radicals from aldehydes under photoredox cooperative N-heterocyclic carbene/Pd catalysis.

CF3SO2Na-Mediated Five-Component Carbonylation of Triarylboroxines with TMSCF3 and THF/LiOH/NaI to Give Aroyloxyalkyl Iodides.

Herein, we developed an efficient and transition-metal-free multicomponent coupling reaction for the synthesis of aroyloxyl alkyl iodides. In the reaction among 2,4,6-triarylboroxines, THF, TMSCF3, LiOH, and NaI, five-component reactions could be precisely controlled by modulating CF3SO2Na, supplying one type of aroyloxyl alkyl iodides in moderate to high yields. The reaction exhibits good functional group tolerance and a wide substrate scope and can be easily transformed into other useful compounds. The mechanism is proposed on the basis of the control experiments.

A Single‐Step Synthesis of Stereodefined Skipped Trienes: Pd‐Catalyzed Cascade Reaction of Terminal Alkynes with Allylic Halides

AbstractA Pd‐catalyzed cascade reaction of terminal alkynes with allylic halides to afford stereodefined skipped trienes was developed. The methodology leads to efficient construction of a series of stereodefined skipped trienes under mild reaction conditions in a single‐step without organometallic alkyne. Preliminary mechanism investigations indicated that the Sonogashira reaction and the radical pathway might not be involved in this novel multicomponent coupling reaction.

Recent Advances in Construction of C(sp2)–O Bonds via Aryne Participated Multicomponent Coupling Reactions

AbstractAryne chemistry is a powerful synthetic technique that forms new bonds to aromatic rings. The recent resurgence of aryne-based multicomponent coupling strategies has led to an influx of methodologies for the mild synthesis of arene derivatives. In particular, these innovative discoveries broaden and streamline approaches toward phenol ether motifs, which are a prevalent structural component across a broad range of chemistry related research fields. Herein, this review aims to provide a comprehensive overview of the recent progress in the construction of C(sp2)–O bonds via aryne-induced multicomponent reactions. Special attention has been paid to reaction design and mechanistic pathways.1 Introduction2 Insertion-Based MCRs3 Nucleophilic-Addition-Based MCRs4 Cycloaddition-Based MCRs5 Summary

From A3/KA2 to AYA/KYA multicomponent coupling reactions with terminal ynamides as alkyne surrogates – a direct, green route to γ-amino-ynamides

A copper-catalysed three-component coupling reaction between a carbonyl derivative, a terminal ynamide and an amine has been developed for the one-pot construction of γ-amino-ynamides under mild and environmentally-friendly conditions.