Catalytic Multicomponent Reaction Research Articles

Enantioselective Allylboration of Acetylene: A Versatile Tool for the Stereodivergent Synthesis of Natural Products.

Efficient catalytic methods that allow the use of simple and abundant chemical feedstocks for the preparation of synthetically versatile compounds are central to modern synthetic chemistry. Acetylene is a basic feedstock with a remarkable production over one million tons per year, although it is underutilized in the stereoselective synthesis of fine chemicals. Here we report a facile catalytic multicomponent reaction that allows for the enantio- and diastereoselective allylboration of acetylene gas. This process is catalyzed by a chiral copper catalyst, operates without specialized equipment or pressurization, and provides chiral skipped dienes bearing stereodefined and orthogonally functionalized olefins with excellent levels of chemo-, regio-, enantio- and diastereoselectivity. The combined stereochemical features and orthogonal functionalization make the products privileged structural scaffolds to access the complete set of stereoisomers of the chiral skipped diene core through simple enantio- and diastereodivergent pathways. The utility of the method is demonstrated with the enantioselective synthesis of three bioactive natural skipped diene products, namely (+)-Nyasol, (+)-Hinokiresinol and Phorbasin C, and other related synthetically relevant chiral molecules.

Anti-proliferative, Morphological and Molecular Docking Studies of New Thiophene Derivatives and their Strategy in Ionic Liquids Immobilized Reactions.

A number of research were conducted on the pyran and thiophene derivatives, which were attributed to have a wide range of biological activities, including anti-plasmodial, as well as acting as caspase, hepatitis C and cancer inhibitors. The multicomponent reactions of the 5-acetyl-2-amino-4-(phenylamino)-thiophene-3-carbonitrile produced biologically active target molecules like pyran and their fused derivatives. Comparison between regular catalytic multi-component reactions and solvent-free ionic liquids immobilized multicomponent was studied. The multicomponent reactions in this work were carried out not only under the reflux conditions using triethylamine as a catalyst but also in solvent-free ionic liquids immobilized magnetic nanoparticles (MNPs) catalysts. Through this work, thirty-one new compounds were synthesized and characterized and were evaluated toward the six cancer cell lines, namely A549, HT-29, MKN-45, U87MG, and SMMC-7721 and H460. The most active compounds were further screened toward seventeen cancer cell lines classified according to the disease. In addition, the effect of compound 11e on the A549 cell line was selected to make further morphological changes in the cell line. The Molecular docking studies of 11e and 11f were carried and promising results were obtained. The synthesis of heterocyclic compounds derived from thiophene derivatives has been receiving significant attention. After a detailed optimizing study, it has been found that the solvent-free ionic liquids immobilized multi-component syntheses afforded a high yield of compounds, opening a greener procedure for this synthetically relevant transformation. Many of the synthesized compounds can be considered anticancer agents, enhancing further studies.

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.

Catalytic multicomponent synthesis, biological evaluation, molecular docking and in silico ADMET studies of some novel 3-alkyl indoles

A series of novel 3-alkylated indoles were synthesized in good yields under mild reaction conditions using inexpensive, readily available, and environmentally benign glycolic acid catalyst. This new catalytic multicomponent reaction is attractive for diversity-oriented synthesis involving C–C bond formation. This strategy has a number of advantages, such as a simple work-up procedure, and short reaction time. Antimicrobial studies were carried out and the para-nitro-substituted compounds were found to be good inhibitors of Aspergillus niger. This activity explained by interacting with active site residues such as MET816, PHE786, and PHE820 of the target fungal protein, phosphodiesterase-5 (PDE5) (PDB:2H44). Furthermore, the SwissADME online application was used to analyses the physicochemical and pharmacokinetic features of the compounds (6–10).

Three-component enantioselective alkenylation of organophosphonates via nickel metallaphotoredox catalysis

•Highly enantioselective synthesis of structurally complex chiral phosphonates •Modular and stereodivergent access to chiral trans- and cis-alkenyl moieties •Asymmetric radical multicomponent reaction via metallaphotoredox catalysis •Enantioselective control of alkyl radicals by guiding the trajectory of radical metalation The development of efficient catalytic multicomponent reactions (MCRs) is highly sought-after in chemical synthesis. However, catalytic asymmetric MCRs, particularly involving radical species, remain largely underdeveloped due to the exceptionally high reactivity of open-shell radical species. Herein, we report a metallaphotoredox-catalyzed asymmetric three-component method to access a diverse array of enantio-enriched α-alkenyl phosphonates from readily available vinyl phosphonates, alkenyl halides, and alkyl trifluoroborates under mild conditions. This operationally simple and redox-neutral protocol exhibits broad substrate scope and excellent chemo-, regio-, stereo-, and enantioselectivity. Furthermore, by simple modification of the triplet energy of the photocatalyst employed, both enantio-enriched trans and cis α-alkenyl phosphonates can be divergently accessed. Detailed computational and experimental studies were undertaken to elucidate the mechanism and origin of the observed reactivity and selectivity, which support a radical cascade sequence with α-phosphonate controlling the trajectory of radical capture by a chiral tetrahedral alkenyl nickel(II) species in the enantioselectivity-determining step. The development of efficient catalytic multicomponent reactions (MCRs) is highly sought-after in chemical synthesis. However, catalytic asymmetric MCRs, particularly involving radical species, remain largely underdeveloped due to the exceptionally high reactivity of open-shell radical species. Herein, we report a metallaphotoredox-catalyzed asymmetric three-component method to access a diverse array of enantio-enriched α-alkenyl phosphonates from readily available vinyl phosphonates, alkenyl halides, and alkyl trifluoroborates under mild conditions. This operationally simple and redox-neutral protocol exhibits broad substrate scope and excellent chemo-, regio-, stereo-, and enantioselectivity. Furthermore, by simple modification of the triplet energy of the photocatalyst employed, both enantio-enriched trans and cis α-alkenyl phosphonates can be divergently accessed. Detailed computational and experimental studies were undertaken to elucidate the mechanism and origin of the observed reactivity and selectivity, which support a radical cascade sequence with α-phosphonate controlling the trajectory of radical capture by a chiral tetrahedral alkenyl nickel(II) species in the enantioselectivity-determining step.

Catalytic multicomponent reaction involving a ketyl-type radical

Catalytic multicomponent reaction involving a ketyl-type radical

Analytical data for Catalytic Multicomponent Reaction Involving a Ketyl-type Radical

Analytical data for Catalytic Multicomponent Reaction Involving a Ketyl-type Radical

Analytical data for Catalytic Multicomponent Reaction Involving a Ketyl-type Radical

Analytical data for Catalytic Multicomponent Reaction Involving a Ketyl-type Radical

Nickel-catalyzed site- and stereoselective reductive alkylalkynylation of alkynes

Nickel-catalyzed site- and stereoselective reductive alkylalkynylation of alkynes

The Catalytic Activity of TiO2 Toward a Multicomponent Reaction Depends on its Morphology, Mechanoactivation and Presence of Visible Light

Aims: Test the hypothesis that the catalytic activity of TiO2 nanoparticles towards a liquidphase or mechanoactivated multicomponent reaction can be tuned by visible light and the shape of nanoparticles. Background: Catalytic multicomponent reactions have been proven to be excellent synthetic approaches to a series of biologically relevant compounds including 2-amino-4H-benzo[b]pyrans. However, the potential photocatalytic activity and structural diversity of nanostructured catalysts remained underutilized in the design of new catalytic systems. Objective: Harness the photocatalytic potential and diverse morphology of TiO2 particles as catalysts for the liquid phase and mechanoactivated multicomponent organic reactions. Results: Catalytic activity of TiO2 nanoparticles towards multicomponent synthesis of 2-amino-4Hbenzo[ b]pyrans is increased by visible light. The nanorod-shaped TiO2 nanoparticles have shown substantially higher catalytic activity towards mechanoactivated multicomponent synthesis of 2- amino-4H-benzo[b]pyrans than their spherically-shaped counterparts. Conclusion: : An efficient methodology for the synthesis of 2-amino-4H-benzo[b]pyrans under ambient light condition has been developed using TiO2 nanorods (high aspect ratio anatase nanocrystals) as photocatalyst. This simple method furnished the corresponding terahydrobenzopyrans in high yields via three component reaction of aldehyde, malononitrile, and dimidone under solvent free reaction conditions at room temperature. The reaction takes 8-10 min at room temperature under ambient light condition and the catalyst can be reused multiple times. Utilization of light and the nanorod morphology of the catalyst through mechanoactivation has been applied for the -first time to the synthetic technique of multicomponent reactions. The synthetic procedures for 2-amino-4Hbenzo[ b]pyrans have been improved.

A catalytic synthesis of dihydrofuran‐3(2H)‐imine skeletons from isocyanides, terminal alkynes, and oxiranes

AbstractIn this catalytic multicomponent reaction, the nucleophilicity of terminal alkynes and isocyanides towards oxiranes has been explored. The reaction outcome depends highly on solvent, bases, and catalysts sources. An array of terminal alkynes, isocyanides, and oxiranes has been examined to explore the of this transformation. The reactions proceeded through SN2 path and in regioselective manner.

N-Methylpiperidine assisted catalytic multicomponent reaction

A catalytic methodology involving terminal alkynes, elemental sulfur, and three-membered heterocycles has been described. This domino transformation serves as a useful method for the synthesis of oxathiolane and thiazolidine derivatives from the readily available starting materials. In situ generated copper acetylides reacted with elemental sulfur and oxiranes or aziridines in the presence of N-methylpiperidine as sulfur activating agent to form synthetically important heterocycles.

A simple route to morpholine derivatives via copper‐acetylide addition to carbodiimide in the presence of oxiranes

AbstractA novel catalytic multicomponent reaction for the synthesis of morpholine derivatives has been reported. The reactions involve terminal alkynes, carbodiimides, and oxiranes using [Cu (CH3CN)4]PF6, tBuOLi, and TBPAc in anhydrous NMP. Aryl and heteroaromatic terminal alkynes were tolerated. Carbodiimides could be symmetrical and unsymmetrical substrates with aryl or alkyl substituents. The reaction exhibited a good regioselectivity when unsymmetrical carbodiimides were employed.

Copper-catalyzed synthesis of thiazolidine derivatives via multicomponent reaction of terminal alkynes, elemental sulfur, and aziridines

An atom-economic catalytic multicomponent reaction between terminal alkynes, elemental sulfur, and aziridines has been reported. In this transformation, alkyne thiolate derived from the reaction of terminal alkynes and elemental sulfur in the presence of CuOTf/DBU reacted with aziridines to afford thiazolidine derivatives.

Asymmetric Synthesis of Tetrahydroindolizines by Bimetallic Relay Catalyzed Cycloaddition of Pyridinium Ylides.

A highly enantioselective synthesis of tetrahydroindolizines by catalytic multicomponent cycloaddition reactions of diazoacetate, pyridine, and alkenyloxindole was developed. Under the relay catalysis, involving an achiral iron(III) catalyst and chiral N,N'-dioxide-scandium(III) complex, a series of tetrahydroindolizines bearing different substituents were obtained in moderate to high yields (up to 99 %) with excellent diastereo- and enantioselectivities (up to >19:1 d.r., 99 % ee).

Asymmetric Synthesis of Tetrahydroindolizines by Bimetallic Relay Catalyzed Cycloaddition of Pyridinium Ylides

AbstractA highly enantioselective synthesis of tetrahydroindolizines by catalytic multicomponent cycloaddition reactions of diazoacetate, pyridine, and alkenyloxindole was developed. Under the relay catalysis, involving an achiral iron(III) catalyst and chiral N,N′‐dioxide‐scandium(III) complex, a series of tetrahydroindolizines bearing different substituents were obtained in moderate to high yields (up to 99 %) with excellent diastereo‐ and enantioselectivities (up to >19:1 d.r., 99 % ee).

PEG/ZnBr2-Assisted Multicomponent Reactions: A Novel Procedure for the Synthesis of Functionalized 5,6-Dihydropyran-2-ones

We report a catalytic multicomponent reaction of isocyanides, oxiranes, and malonates under mild conditions, allowing the transformation of a wide range of substrates into 5,6-dihydropyran-2-one products in acceptable yields. We have also examined the leaving group selectivity using an unsymmetrical malonate. This novel method demonstrates the benefits of combining different activation modes in oxiranes.

Highly Atom Economical Molecular Transformation via Hetero-Nickelacycle

Abstract Nickel is one of the most popular first row transition metals for coupling reactions. For the past two decades, catalytic multi-component coupling reactions via nickelacycles have been developed. Although the formation of nickelacycles has been believed an important key step in the catalytic reactions, the generation of nickelacycles by oxidative cyclization has been less studied. Thus, we have been focusing on the formation of nickelacycles from nickel(0) species and development of catalytic reactions without using coupling reagents to construct highly atom economical nickel-catalyzed multi-component connecting reactions.

An efficient procedure for the synthesis of functionalized 3,4-dihydro-2H-pyrans via catalytic multicomponent reaction

In this transformation, conjugated base of malonitrile was reacted with reactive nitrilium ion derived from the reaction of isocyanides and oxiranes in the presence of lithium salts in PEG-400. The reaction was successfully utilized to synthesize 3,4-dihydro-2H-pyrans in accordance with a simple and environmentally benign procedure. The optimized reaction conditions allowed the selective synthesis of the highly functionalized 3,4-dihydro-2H-pyrans from the commercially available starting materials in acceptable yields.

Catalytic multicomponent reaction between nitroalkanes, elemental sulfur, and oxiranes

An efficient multicomponent reaction of nitroalkanes and elemental sulfur with oxiranes was developed with the aid of silver salt. This reaction procedure provides a novel and practical strategy for the rapid assembly of 1,3-oxathiolane skeletons. The reaction exhibited remarkable functional group tolerability and regio-selectivity so that only one regio-isomer formed during the ring opening of oxiranes.