Multicomponent Cascade Reaction Research Articles

Multicomponent Cascade Reaction by Metal-Free Aerobic Oxidation for Synthesis of Highly Functionalized 2-Amino-4-coumarinyl-5-arylpyrroles.

A novel approach has been constructed for the synthesis of two types of 2-amino-4-coumarinyl-5-arylpyrroles (ACAPs, 5 and 6) through a cascade reaction and a metal-free catalyzed aerobic oxidation reaction of arylglyoxal monohydrates 1, 1,1-enediamines (EDAMs) 2 and 3, and 4-hydroxy-2H-chromen-2-ones 4 via multicomponent reactions to produce the target compounds with good to excellent yields. Specifically, hydroxyl-substituted 2-amino-4-coumarinyl-5-arylpyrroles, that is, 2-amino-4-coumarinyl-5-aryl-6-hydroxylpyrroles (ACAHPs) 6, were obtained by metal-free aerobic oxidation in 1,4-dioxane at simple reflux for approximately 10 h. As a result, ACAHPs 6 have been produced without metal catalysts or traditional oxidizing agents. This method represents a route to obtain the novel ACAPs in an environmentally friendly, concise, rapid, and practical manner with potential biological activity of the product.

Simultaneous Construction of C-Se And C-S Bonds via the Visible-Light-Mediated Multicomponent Cascade Reaction of Diselenides, Alkynes, and SO2.

A visible-light mediated multicomponent cascade reaction of diselenides, alkynes, and sulfur dioxide was developed, in which multiple C-Se and C-S bonds were constructed, and unexpected β-sulfonylvinylselane compounds were generated with high selectivity for E configuration. β-Sulfonylvinylselane transformation into 1,4-oxathiine-4,4-dioxide and sulfonylethyne derivates was then investigated. A plausible mechanism involving a selenium radical-initiated cascade reaction and sulfur dioxide insertion was proposed.

Multicomponent cascade reaction catalyzed by basic alumina

Multicomponent polymerization is gaining popularity because of its high efficiency and ease operation. In this work, commercial basic alumina was used as a solid catalyst to catalyze the Knoevenagel condensation and thiol-ene click reaction. The reaction conditions were mild and the resulting products were easily separated and purified.

Catalytic One-Pot Double Asymmetric Cascade Reaction: Synthesis of Chlorinated Oxindoles and Geminal Diamines

A multicomponent catalytic double asymmetric cascade reaction for obtaining chlorinated oxindoles and C–N aminals simultaneously is described. A calcium VAPOL phosphate complex was shown to catalyze two enantiocontrolled multicomponent reactions utilizing 3-aryloxindoles, N-Boc imines, and N-chlorophthalimide, which afforded two structurally complex and diverse chiral products with high levels of stereocontrol in one pot. This transformation is facile and has a high degree of both step and atom economy.

An unexpected multi-component one-pot cascade reaction to access furanobenzodihydropyran-fused polycyclic heterocycles

An unexpected multi-component one-pot cascade reaction of hydroxyketones with ortho-hydroxychalcones has been developed to afford an array of new furanobenzopyran-fused polycyclic compounds with complex molecular architectures. This reaction not only establishes a new reaction mode of ortho-hydroxychalcones but also provides an expedient and convenient synthetic strategy to access complex furanobenzopyran-fused heterocycles.

Construction of Cyclobutanes by Multicomponent Cascade Reactions in Homogeneous Solution through Visible-Light Catalysis.

[2+2] Photocycloaddition of two olefins is a general method to assemble the core scaffold, cyclobutane, found in numerous bioactive molecules. A new approach to synthesize cyclobutanes through multicomponent cascade reactions by merging aldol reaction and Witting reaction with visible-light-induced [2+2] cycloaddition is reported. An array of cyclobutanes with high selectivity has been achieved from commercially available aldehydes, ketones (or phosphorus ylide), and olefins with visible-light irradiation of a catalytic amount of (fac-tris(2-phenylpyridinato-C2 ,N)iridium) ([Ir(ppy)3 ]) at room temperature. Control experiments and spectroscopic studies revealed that the triplet-triplet energy transfer from the excited [Ir(ppy)3 ]* to enones, generated in situ from aldehyde and ketone or aldehyde and phosphorus ylide, is responsible for these simple and efficient muticomponent transformations.

Multicomponent Reactions and Multicomponent Cascade Reactions for the Synthesis of Sequence-Controlled Polymers.

Control over the monomer sequence during polymerization has attracted great attention in polymer science, but it remains a serious challenge. Recently, multicomponent reactions have been playing a significant role in the synthesis of sequence-controlled polymers due to their inherent advantage of combining three or more starting materials in time-saving, one-pot operations to afford complex microstructures. In this feature article, the recent representative developments in the synthesis of sequence-controlled polymers by multicomponent reactions are highlighted to give insight on the design of novel sequence-controlled polymers with sufficient molecular diversity and complexity. The main part of this article is divided into three sections according to the different polymerization strategies using multicomponent reactions: direct multicomponent polymerization, multicomponent cascade polymerization, and iterative multicomponent reaction, respectively. It is anticipated that this feature article may provide some guidance for the fabrication of sequence-controlled polymers by multicomponent reactions.

Enantioselective Construction of Spiro Thiazol‐4‐one Derivatives with Multiple Stereocenters via an Organocatalyzed Multicomponent Cascade Reaction

AbstractWe have developed an organocatalyzed asymmetric three‐component reaction of thiazol‐4‐ones, acrolein and nitroolefins, which provides an efficient approach to access optically active spiro thiazol‐4‐ones. Under the catalysis of a bifunctional squaramide derived from L‐tert‐leucine, the reactions of a wide range of thiazol‐4‐ones, acrolein and nitroolefins took place smoothly to generate the corresponding spirothiazolone derivatives bearing four contiguous stereogenic centers in good yields with high levels of enantioselectivity. The title chiral spirothiazolones were obtained as a pair of separable epimers, which are formed through a double Michael addition followed by a Henry process.magnified image

Copper-Catalyzed Multicomponent Reaction of DABCO·(SO2)2, Alcohols, and Aryl Diazoniums for the Synthesis of Sulfonic Esters.

A Cu-catalyzed multicomponent cascade reaction of DABCO·(SO2)2 (DABSO), alcohol, and aryl diazonium tetrafluoroborate was developed which afforded sulfonic esters in moderate to good chemical yields. In this reaction, the SO2 surrogate DABSO was used for the first time in the synthesis of sulfonic aliphatic esters. This multicomponent reaction was carried out under mild conditions and tolerated a wide range of substrates, which provides a new and efficient strategy for the synthesis of sulfonic esters.

The mechanism of the triple aryne-tetrazine reaction cascade: theory and experiment.

This article describes an experimental and computational investigation on the possible aryne reactivity modes in the course of the reaction of two highly energetic molecules, an aryne and a 1,2,4,5-tetrazine. Beyond the triple aryne-tetrazine (TAT) reaction, it was observed that combinations of several reactivity modes afford several heterocyclic compounds. Density Functional Theory (DFT) calculations of competition between a second Diels-Alder reaction and the nucleophilic addition pathways indicates the latter to be more favorable. Crossover experiments and computational study of the proton transfer step reveal that the reaction proceeds intermolecularly with the assistance of a water molecule, rather than intramolecularly. The resulting enamine intermediate was found to undergo either a stepwise formal [2 + 2] or [4 + 2] cycloaddition, and their energetic profiles were compared against each other. Isolation of an ene-product and a rearranged product shows the potential competition with oxidation/desaturation. These studies show how multiple arynes react with a highly reactive starting material and provide guidance for future applications of aryne-based multicomponent cascade reactions.

Metal-free multicomponent cascade reactions of homopropargylic amines and acyl chlorides as well as potassium thiocyanate and diiodine: an access to thiazine imides.

A novel metal-free multicomponent cascade reaction was developed for the construction of thiazine imides. This four-component cascade reaction had advantages of mild reaction conditions, wide substrate scope and good atom economy. Four new bonds were formed in one pot via a 6-exo-dig iodothiolation cyclization of homopropargylic amines. The corresponding E-configurational thiazine imide products possess an exocyclic vinyliodide functional group.

Simple Design of an Enzyme-Inspired Supported Catalyst Based on a Catalytic Triad

Summary Enzyme active sites afford an intricate interplay of functional groups to mediate complex organic and inorganic reactions. Many hydrolytic enzymes use a catalytic triad comprising three different functional residues—(Ser(-OH), Hist(-imidazole), Asp(-CO 2 H))—that catalyze the hydrolysis of numerous unique substrates. Inspired by this design, we have developed a simple one-step synthesis for preparing a new supported catalytic system in which the three reactive groups of the catalytic triad (alcohol, imidazole, and carboxylate) are incorporated into a single functional unit. These artificial active sites can be coupled to a solid-phase support (Merrifield resin) by copper(I)-catalyzed azide-alkyne cycloaddition "click chemistry," and their effectiveness as esterolysis catalysts was demonstrated. Furthermore, tuning the local hydrophobicity of the resin particles with an approach analogous to the native enzyme hydrophobic pocket increased the catalytic efficiency. Quantum mechanics and molecular dynamics computational modeling were used to probe the catalytic effect and suggested a concerted two-step mechanism and hydrophobic nanoenvironment similar to that of hydrolytic enzymes.

Recent Advances in Green Synthesis of 3,3′‐Spirooxindoles via Isatin–based One–pot Multicomponent Cascade Reactions in Aqueous Medium

Abstract3,3′‐spirooxindoles are important synthetic target compounds and play special role in organic chemistry because of their extensive biological activities and applications of pharmaceutical lead discovery. In recent years, there has been a significant increase in design of new, atom economical and eco‐friendly isatin‐based one‐pot multicomponent cascade reactions in aqueous medium for the green synthesis of 3,3′‐spirooxindoles. In this review, the recent advances in this area were summarized and classified according to catalyst‐free, organic‐catalyzed, inorganic‐catalyzed, nanometer‐silica‐catalyzed and enzyme‐catalyzed reaction systems. These reviewed methods provide important inspiration for the synthesis of novel 3,3′‐spirooxindoles and design of new pharmaceutical compounds.

An efficient and green synthesis of highly functionalized N-methyl-2-nitro-aryl-1H-benzo[f]chromen-3-amine derivatives under catalyst-free conditions

A highly efficient and environmentally benign protocol has been developed for the construction of various potentially biologically active N-methyl-2-nitro-aryl-1H-benzo[f]chromen-3-amine derivatives using one-pot, multi-component cascade reaction of various naphthalen-2-ol, aldehydes, and (E)-N-methyl-1-(methylthio)-2-nitroethenamine under catalyst-free conditions in the presence of green solvent medium (ethanol–water) is described. The significant features of this protocol are short reaction times, provide excellent yields, avoidance of toxic solvents and catalysts, no column chromatographic purification, atom-economy and uses ethanol–water as a green solvent which is considered to be relatively environmentally benign. This is the first example of the condensation of naphthalen-2-ol, aldehydes, and (E)-N-methyl-1-(methylthio)-2-nitroethenamine to provide a novel series of 1H-benzo[f]chromen-3-amine derivatives.

Brønsted or Lewis Acid Initiated Multicomponent Cascade Reaction: Diastereoselective Synthesis of Imidazolidinyl Spirooxindole Derivatives

AbstractOne peculiar type of aza‐hetero‐imidazolidinyl spirooxindole derivatives was efficiently constructed by the three‐component [2+2+1] cascade reaction of 1,4‐oxazepines with diazo‐oxindoles. Iron(II) trifluoromethanesulfonate [Fe(OTf)2] or p‐toluenesulfonic acid monohydrate (p‐TsOH⋅H2O) proved to be optimal catalysts for this transformation, providing the desired products in high yields (up to 94 %) with excellent diastereoselectivity (up to 99:1 dr). Experimental studies showed that the reaction rate of Brønsted acid catalysis was faster than that of Lewis acids. Furthermore, the mechanism was theoretically investigated for Brønsted acid as the catalyst and a reaction pathway was proposed. DFT calculations suggested that the diazo‐oxindole can act as a 1,3‐dipole to add to a C=N double bond of 1,4‐oxazepine, which forms a 4,5‐dihydro‐1H‐1,2,3‐triazole intermediate. Subsequently, the releasing of N2 is the rate‐limiting step of the whole catalytic cycle.

ChemInform Abstract: Multicomponent Cascade Reaction: Dual Role of Copper in the Synthesis of 1,2,3‐Triazole Tethered Benzimidazo[1,2‐a]quinoline and Their Photophysical Studies.

AbstractThe title compounds are prepared from (azidomethyl)benzimidazoles, acetylenes, and benzaldehydes by domino/cascade reaction including click reaction, N—C bond formation, and Knoevenagel condensation.

ChemInform Abstract: Multicomponent Cascade Reactions of Unprotected Ketoses and Amino Acids — Access to a Defined Configured Quaternary Stereogenic Center.

AbstractIn this stereoselective multicomponent cascade reaction of ketoses with amino acids matched/mismatched situations occur.

Multicomponent cascade reaction: dual role of copper in the synthesis of 1,2,3-triazole tethered benzimidazo[1,2-a]quinoline and their photophysical studies

One-pot synthesis of 1,2,3-triazole tethered benzimidazo[1,2-a]quinolines through a multi-component reaction is demonstrated. Overall one C–C bond and three C–N bonds are formed in a single step.

Cu(i)-catalyzed multicomponent cascade reactions of terminal alkynes, unactivated primary alkyl bromides, CO2 and NaN3

We have developed a mild, robust, and multicomponent cascade reaction for the synthesis of triazolo-fused dihydrooxazinones from terminal alkynes, unactivated primary alkyl bromides, carbon dioxide and sodium azide.

Multicomponent Cascade Synthesis of Trifluoroethyl Isoquinolines from Alkynes and Vinyl Azides.

A multicomponent cascade reaction is described that provides concise access to the trifluoroethyl isoquinolines using a Rh(III)-Cu(II) bimetallic system and readily available Togni's reagent. The system tolerates various vinyl azides and internal alkynes. Experimental results suggest that Togni's reagent might act as a CF3 radical supplier.