Domino Reactions In Water Research Articles

Catalyst‐free access to substituted pyrano[4,3‐b]pyrrol‐4(1H)‐one derivatives through domino reaction in water

AbstractThus far, domino‐based reactions have received a great deal of attention as a step‐and atom‐economic route toward the synthesis of a plethora of heterocyclic molecules. In this work, we disclose a catalyst‐free domino procedure for rapid synthesis of 3‐substituted 6‐methyl‐1,2‐diarylpyrano[4,3‐b]pyrrol‐4(1H)‐one compound in water at 80°C, accompanied by multiple C‐H/C‐O bond cleavage and C‐C and C‐N bond formation. This approach is characterized by its mild reaction conditions, convenient separation, high tolerance of functional groups, and easily available starting materials, thereby offering a green and efficacious strategy for the design and synthesis of pyrano[4,3‐b]pyrrol‐4(1H)‐one derivatives by domino reaction.

Sustainable access to benzothiophene derivatives bearing a trifluoromethyl group via a three-component domino reaction in water.

A catalyst-free three-component domino reaction was developed for the synthesis of benzothiophene fused pyrrolidones bearing a CF3 group for the first time. The notable advantages of this strategy over the existing methods include the use of water as a solvent at room temperature, transition metal-free conditions, a broad substrate scope, and easy scale-up synthesis. More importantly, the benzothiophene derivatives have been found to show potent anticancer activities using the Cell Counting Kit-8 (CCK-8) assay.

Bis-(5-substituted-2-thiono-1,3,5-thiadiazinan-3-yl) butane as a scaffold of anti-proliferative activity, blended by a multicomponent process

In the search for promising anti-proliferative agents that might be helpful in the treatment of cancer effectively, several compounds in a series (4b–j) comprising 1,4-bis (5-substituted -2-thiono-2H-tetrahydro-1,3,5-thiadiazin-3-yl) butane derivatives have been isolated. The aimed two privileged thiadiazinane pharmacophores were symmetrically assembled in one molecular frame via 1,4-diaminobutane; the endogenous compound produced by the breakdown of some amino acids that’s known as putrescine. The thiadiazinane rings bearing variable substituents at N-5 as well. The structure of the new derivatives, which were obtained by domino-reactions in water are confirmed by NMR and ESI-MS spectra. Data of 1H-NMR and 13C-NMR. NMR-spectra revealed symmetrical structural features. The anti-proliferative activity was evaluated against five different human cancer cell lines. Compounds 4b, 4d, 4e, and 4j (IC50 range 0.11–0.24 µM), were found potent against Hep3B (hepatocellular carcinoma). Compounds 4d and 4e are also potent (IC50 = 0.42 and 0.41 µM) against U-87 MG (Brain (glioblastoma astrocytoma)). Moreover, 4d provided (IC50 = 0.53 µM) against HepG2 (hepatocellular carcinoma), (A549 (lung carcinoma), and HT-29 (human colorectal adenocarcinoma), as well as normal cell line (fibroblast F180). All the derivatives 4b, 4d, 4e, and 4j are not only more potent, but also relatively safer than doxorubicin in the cell-lines mentioned. The anti-proliferative profile indicates that these compounds are good leads as anti-cancer agents and merit further studies to optimize their structure, detect their bio-targets and in vivo activity.

Highly Selective Synergistic Copper(I/II)‐Catalyzed A3 Cross Coupling/Decarboxylative A3 Domino Reactions in Water

AbstractA microwave‐assisted copper‐catalyzed A3 cross‐coupling/decarboxylative A3 domino reaction of a propiolic acid, an aldehyde, a formaldehyde solution and an amine is described. This strategy represents the first one‐pot cross‐coupling reaction for the direct synthesis of trisubstituted unsymmetrical 2‐butynes with a broad functional group tolerance in good yields (up to 91 %) and excellent chemoselectivity. The simultaneous activation of both the C−COOH and C−H bond of propiolic acid is crucial in this approach, and only carbon dioxide and water are generated as byproducts.

Theophylline as the catalyst for the diastereoselective synthesis of trans-1,2-dihydrobenzo[a]furo[2,3-c]phenazines in water

Theophylline-catalyzed efficient and environmentally benign procedure for the diastereoselective synthesis oftrans-1,2-dihydrobenzo[a]furo[2,3-c]phenazines with pyridinium ylide assisted domino reaction in water.

ChemInform Abstract: Catalyst‐Free One‐Pot Four‐Component Domino Reactions in Water—PEG‐400: Highly Efficient and Convergent Approach to Thiazoloquinoline Scaffolds.

AbstractA new and efficient protocol for the synthesis of highly diversified thiazoloquinoline scaffolds by one‐pot four‐component cascade reaction of α‐enolic dithioesters, cysteamine, aldehydes, and cyclic 1,3‐diketones is given.

Catalyst-free one-pot four-component domino reactions in water–PEG-400: highly efficient and convergent approach to thiazoloquinoline scaffolds

Catalyst-free one-pot sustainable synthesis of thiazoloquinoline and thiazolopyridine scaffolds is achievedviafour-component domino reactions in water–PEG.

ChemInform Abstract: Domino Reactions in Water for the Stereoselective Synthesis of Novel Spiro Dihydro‐2′H‐[indene‐2,3′‐thiophen]‐1(3H)‐ones with Three Contiguous Stereocenters.

Abstract The domino reactions of (E)-2-(aryl)-2,3-dihydro-1H-inden-1-ones and 1,4-dithiane-2,5-diol in the presence of triethylamine in water stereoselectively afforded a library of 2′-(aryl)-4′-hydroxy-4′,5′-dihydro-2′H-spiro[indene-2,3′-thiophen]-1(3H)-ones. This transformation presumably proceeds via the generation of 2-mercaptoacetaldehyde from 1,4-dithiane-2,5-diol followed by Michael addition–intramolecular aldol sequence with C–C and C–S bond formations and creation of three contiguous stereocenters in a one-pot operation.

ChemInform Abstract: An Efficient and Mild Synthesis of Tetrahydro‐4H‐indol‐4‐one Derivatives via a Domino Reaction in Water.

An efficient domino approach for the synthesis of tetrahydro-4 H -indol-4-one derivatives has been established. The use of catalytic amount of l -proline in water at 60 °C makes it quite simple, more convenient, and environmentally benign.

Domino reactions in water for the stereoselective synthesis of novel spiro dihydro-2′H-[indene-2,3′-thiophen]-1(3H)-ones with three contiguous stereocenters

The domino reactions of (E)-2-(aryl)-2,3-dihydro-1H-inden-1-ones and 1,4-dithiane-2,5-diol in the presence of triethylamine in water stereoselectively afforded a library of 2′-(aryl)-4′-hydroxy-4′,5′-dihydro-2′H-spiro[indene-2,3′-thiophen]-1(3H)-ones. This transformation presumably proceeds via the generation of 2-mercaptoacetaldehyde from 1,4-dithiane-2,5-diol followed by Michael addition–intramolecular aldol sequence with C–C and C–S bond formations and creation of three contiguous stereocenters in a one-pot operation.

An Efficient and Mild Synthesis of Tetrahydro-4H-indol-4-one Derivatives via a Domino Reaction in Water

An efficient domino approach for the synthesis of tetrahydro-4 H -indol-4-one derivatives has been established. The use of catalytic amount of l -proline in water at 60 °C makes it quite simple, more convenient, and environmentally benign.

ChemInform Abstract: Domino Reactions in Water: Diastereoselective Synthesis of Densely Functionalized Indolyldihydrofuran Derivatives.

AbstractA series of trans‐dihydrofuran derivatives (III) (26 examples) is readily prepared by a triethylamine‐catalyzed domino reaction of chalcones (I) with bromides (II) in aqueous media.

ChemInform Abstract: Synthesis of Functionalized 2,3‐Dihydroisoxazoles by Domino Reactions in Water and Unexpected Ring‐Opening Reactions of 2,3‐Dihydroisoxazoles.

AbstractA convenient synthesis of trisubstituted dihydroisoxazoles (II), (V) and (VIII) is presented, involving the reaction of benzylidenemalononitriles with hydroxylamine in basic medium.

Synthesis of functionalized 2,3-dihydroisoxazoles by domino reactions in water and unexpected ring-opening reactions of 2,3-dihydroisoxazoles

α,α-Dicyanoolefins react with hydroxylamine to afford 2,3-dihydroisoxazoles (2,3-dihydroisoxazoles can be easily isolated by filtration) in excellent yields under mild and environmentally benign conditions. A one-pot reaction in tandem with an unexpected ring-opening of 2,3-dihydroisoxazoles has been developed as well.

Domino reactions in water: diastereoselective synthesis of densely functionalized indolyldihydrofuran derivatives

A library of trans-5-aroyl-2-(indol-3-yl)-4-aryl-4,5-dihydrofuran-3-carbonitriles was diastereoselectively synthesized in excellent yields from the reaction of 2-(3-indolylcarbonyl)-3-aryl-2-propenenitriles with (2-aryl-2-oxoethyl)pyridinium bromides in the presence of triethylamine via a simple, user-friendly domino process carried out in water. Extraction and chromatographic steps were avoided, since the final products could be simply filtered from the aqueous reaction medium and recrystallized. This one-pot transformation generates one C–C and one C–O bond and presumably proceeds by a domino sequence involving the generation of a pyridinium ylide, a Michael addition and a final annulation via intramolecular nucleophilic substitution.

ChemInform Abstract: Efficient and Mild Synthesis of Functionalized 2,3‐Dihydrofuran Derivatives via Domino Reaction in Water.

AbstractThe mild conditions allow the access to a broad spectrum of trans‐substituted furan structures and may thus be of great interest in pharmaceutical chemistry and natural product synthesis.

Efficient and mild synthesis of functionalized 2,3-dihydrofuran derivatives via domino reaction in water

An efficient and mild method for the synthesis of functionalized tricyclic 2,3-dihydrofurans, bicyclic 2,3-dihydrofurans, and other tetrasubstituted 2,3-dihydrofurans by domino reaction of 1,3-dicarbonyl compounds and α-bromonitroalkenes with a large substrate scope and excellent diastereoselectivity (only trans isomers) in moderate to excellent yield (up to 96%) has been reported.

ChemInform Abstract: Fast, Efficient, Mild and Metal‐Free Synthesis of Pyrroles by Domino Reactions in Water.

AbstractReaction of both regioisomers (I) and (IV) of N‐substituted enaminones with β‐bromostyrenes offers novel approaches to trisubstituted pyrroles.

Fast, Efficient, Mild, and Metal-Free Synthesis of Pyrroles by Domino Reactions in Water

(E)-β-Bromonitrostyrenes react with enaminones in water to afford pyrroles in excellent yields. The domino reaction constitutes a new, mild, and environmentally benign process for the fast and efficient synthesis of diverse pyrroles.