Three-component Cyclization Reaction Research Articles

Cu-Catalyzed [3+1+1] Cascade Cyclization of O-Acyl Oximes with Sulfur and Silyl Enol Ethers: Rapid Access to Naphthothiazoles.

A three-component cyclization reaction of O-acyl oximes, silyl enol ethers and elemental sulfur has been developed, in which silyl enol ether acts as a C1 synthon to participate in cyclization reaction and build series of 2-aroylnaphthothiazoles and 2-aroylbenzothienothiazoles. The preliminary exploration of the reaction mechanism indicated that this transformation probably proceeded through a radical process, involving S3•- as a key intermediate, enabling subsequent nucleophilic substitution with O-acyl oximes to afford iminosulfur radical, which undergoes 1,3-H shift to yield sulfur-centered radical intermediate. And then this intermediate undergoes radical addition with silyl enol ether, leading to the formation of the titled products through intramolecular cyclization and oxidation. Moreover, the products obtained exhibit favorable fluorescence properties, which indicates their potential application as functional materials.

Green and clean synthesis of 4-arylideneisoxazol-5-ones using NaCl aqueous solution

The one-pot, three-component cyclization reaction a wide variety of aryl/heteroaryl aldehydes, hydroxylamine hydrochloride, and β-keto ester compounds was performed in a simple manner. The reactions carried out in the presence of sodium chloride (NaCl) as a profitable, green, and efficient catalyst at room temperature. Optimization experiments indicate that the amount of 17 mol% of loaded NaCl is sufficient to catalyze the reaction. Among the advantages of this NaCl-catalyzed method are availability of catalyst, no need for catalyst synthesis in several steps, commercially available reactants, use of aqueous conditions, clean synthesis, non-inflammable reaction medium, no environmental pollution, safety, cost-effectiveness, pot-economy, optimum efficiency, carbon efficiency, and economy of reaction steps. Due to the absence of harmful solvents, the use of sodium chloride as an abundant, low-cost, and useful catalyst, and the use of water as a solvent, this method is considered a green synthesis.

Metal-free three-component tandem cyclization for modular synthesis of 2,3-dihydrobenzothiazin-4-ones

The first three-component cyclization reaction of benzo[c][1,2]dithiol-3-ones based on S–S bond cleavage is disclosed herein.

2-Butyne Biscarbonate as a "Bridge" in Rhodium(III)-Catalyzed [4 + 2] Cyclization and Diels-Alder Reaction.

Described herein is the development of an unprecedented approach to construct multiple heterocycles with high selectivity through Rh(III)-catalyzed two- or three-component cyclization reaction from simple and readily available starting materials: N-methoxybenzamides, 2-butyne biscarbonate, and maleimides. This methodology provides an efficient strategy for the synthesis of diverse and complicated heterocycles in a one-pot manner and displays excellent features of extremely mild reaction conditions, easy operation, excellent regioselectivity, and good functional group compatibility.

An Expeditious Synthesis of Ethyl-2-(4-(arylmethylene)-5-oxo-4,5-dihydroisoxazol-3- yl)acetate Derivatives

Abstract:In this contribution, an operationally simple and efficient synthetic procedure for synthesizing derivatives of 4-(arylmethylene)-5-oxo-4,5-dihydroisoxazol-3-yl)acetate has been developed. This interesting synthetic protocol involves the one-pot cyclocondensation of diethyl 3-oxopentanedioate, aryl or heteroaryl aldehydes, and hydroxylamine hydrochloride catalyzed in an aqueous medium using an azolium salt as a robust organo-catalyst. In this work, for the first time, 1,3-dibenzyl-1H-benzo[d]imidazol-3-ium chloride was used as the catalyst for the synthesis of ethyl-2-(4-(arylmethylene)-5-oxo-4,5-dihydroisoxazol-3-yl)acetate derivatives from the commercially available starting materials. Notably, no by-products were observed during the multicomponent reaction. Optimization studies revealed that 5 mol% of 1,3-dibenzyl-1H-benzo[d]imidazol-3-ium chloride is sufficient to perform the experiment. Furthermore, examining the results of the temperature conditions showed that 70 ºC is the best temperature to carry out the reaction. In an optimization study, H2O was the most effective solvent to perform the three-component cyclization reaction. In this method, using H2O as the environmentally benign and inexpensive reaction medium, so from the point of view of the reaction medium, it can be said that this three-component heterocyclization obeys the principles of green chemistry. This procedure has several advantages, such as good to excellent yields, reasonable reaction times, isolation of heterocyclic products without column chromatography or other chromatographic methods, atom-economy, step-economy, and clean reaction profiles.

Rh(iii)-Catalyzed one-pot three-component cyclization reaction: rapid selective synthesis of monohydroxy polycyclic BINOL derivatives

A Rh(iii)-catalyzed three-component C–H bond functionalization protocol has been successfully applied to access complex polycyclic BINOL derivatives in which the formation of intermediate amides occurred in situ from aldehydes and amines.

A Three-Component Enantioselective Cyclization Reaction Catalyzed by an Unnatural Amino Acid Derivative.

A new diastereo- and enantioselective three-component cyclization reaction is described. The reaction takes place between a ketone, a carboxylic acid, and a nitroalkene to yield a bicyclic octahydro-2H-indol-2-one scaffold possessing three chiral centers. This reaction involves a rearrangement of the nitro group under simple thermal conditions. A plausible mechanism is proposed for this new reaction based on DFT calculations and isotope-labeling experiments. A new concise enantioselective synthesis of the alkaloid (+)-pancracine is presented as an example of the potential of this novel organocatalytic cyclization reaction in the synthesis of natural products.

Microwave Assisted ZrSiO2 Mediated One-Pot Synthesis of Spiro[chromene- 4,3’-indoline] Derivatives

Background: Microwave-assisted organic synthesis has been a powerful and expedient tool for quick organic synthesis which has vital advantages such as simplicity in process, cumulative rate of reaction, high reaction yields, and less amount of side product etc. Multicomponent reactions have developed chemical transformations for powerful bond-forming in organic, combinatorial and medicinal chemistry. The spirooxindole system possesses prominent biological properties and played a very vital role as a core structure of many synthetic pharmaceuticals. Isatin and its derivatives are a leading molecule for designing latent bioactive agents. Isatin and its derivatives are used as precursors due to having numerous applications and great biological characteristics. Fused chromenes derivatives have established more attention because of their high potential biological application. Here, we have described a one-pot synthesis of diverse spiro[chromene-4,3’-indoline] derivatives using ZrSiO2 mediated three-component reactions of substituted phenols with isatin and malononitrile. Methods: We have used microwave assisted method for synthesis. We have taken mixture of phenol derivatives, Isatin, Malononitrile, the catalyst, ZrSiO2 (10 mol %) and 5 ml methanol was placed into a 25 mL round bottomed flask. The reaction mixture was irradiated under microwave radiations at 100 °C, 300 W for 3-7 min. The progress of the reaction was monitored by thin layer chromatographic plate. After consumption of all starting materials the mixture was poured into water and then extracted with ethyl acetate. The organic layer was washed with brine and evaporated under reduced pressure. The combined aqueous layer was filtered to recycle the catalyst. Filtered catalyst washed with methanol two or three times to remove the strains and tars, and then dried in an oven. Compounds were isolated by column chromatography, elution gradient 15% Ethyl acetate: hexane as pure yellow solid with 80-90% of yield. The catalyst was reused up to three cycles with slight decrease of catalytic activity. Antibacterial activity of synthesized compound was carried out on Nutrient- agar plates by well-diffusion assay against test culture. Results: The one pot three-component cyclization reaction of phenol derivatives, isatin and malononitrile in the presence of ZrSiO2 (10 mol %) as catalyst in methanol was performed and the reaction was completed in 3-7 minutes by using microwave irradiation to afford 2-amino-2'-oxospiro [chromene-4,3’-indoline]-3-carbonitrile 4a in good yields. First, we optimized catalyst for finding best catalyst in very short reaction time with high yields. Reactions using ZrSiO2 in methanol give desirable yield with 88 % in very short time. A sensible decrease in the product yield was observed only after the third recycle of the catalyst. The structures of all the newly synthesized compounds were confirmed by various spectroscopy techniques. All the synthesized compounds were screened through antibacterial activity. Most of the synthesized compounds found to be active against Gram negative bacteria and Gram positive bacteria. Conclusion: We have presented a series of 2-amino-2'-oxospiro[chromene-4,3'-indoline]-3-carbonitrile derivatives that have been synthesized by microwave assisted reaction by isatin, malononitrile and various phenol derivatives. We have described a facile, one pot, three component, and environmentally benign protocol using ZrSiO2 as a prompt catalyst which can be reused. Most important of all, the synthesized derivatives can be used for the development of new antibacterial drugs because compounds 4f, 4b and 4d exhibited promising activity as compared to streptomycin. Keywords: Isatin, microwave-assisted synthesis, multi-component reactions, spiro compound, ZrSiO2.

ChemInform Abstract: Sc(OTf)3‐Catalyzed Three‐Component Cyclization of Arylamines, β,γ‐Unsaturated α‐Ketoesters, and 1,3‐Dicarbonyl Compounds for the Synthesis of Highly Substituted 1,4‐Dihydropyridines and Tetrahydropyridines.

A Sc(OTf)3-catalyzed three-component cyclization reaction of arylamines, β,γ-unsaturated α-ketoesters and 1,3-dicarbonyl compounds was developed to synthesize highly substituted 1,4-dihydropyridines and fused bicyclic tetrahydropyridines carrying a quaternary all-carbon center.

Sc(OTf)3-Catalyzed Three-Component Cyclization of Arylamines, β,γ-Unsaturated α-Ketoesters, and 1,3-Dicarbonyl Compounds for the Synthesis of Highly Substituted 1,4-Dihydropyridines and Tetrahydropyridines

A Sc(OTf)3-catalyzed three-component cyclization reaction of arylamines, β,γ-unsaturated α-ketoesters and 1,3-dicarbonyl compounds was developed to synthesize highly substituted 1,4-dihydropyridines and fused bicyclic tetrahydropyridines carrying a quaternary all-carbon center.

Synthesis of functionalized 2-pyridones via Michael addition and cyclization reaction of amines, alkynes and dialkyl acetylene dicarboxylates

The Michael addition and three-component cyclization reaction of amines, alkynes and dialkyl acetylene dicarboxylates to form pyridones has been developed. Aliphatic amines and aromatic amines could selectively be converted into N-alkyl-disubstituted 2-pyridones and N-aryl-trisubstituted 2-pyridones with good yields in the presence of wet ethanol, which means a suitable amount of water is required for this reaction. The Michael addition and cyclization reaction process was confirmed through deuterium-labeling experiments, intermediates isolation and control experiments.

One Approach to Cyclic Carbonates via a Three-Component Cyclization of Phenacyl Bromide, CO2, and Aldehyde

A three-component cyclization reaction was designed for synthesizing cyclic carbonates in a single operation from phenacyl bromide, CO(2), and aldehyde in the presence of lithium diisopropylamide (LDA). These novel reactions were achieved under extremely mild conditions to generate the target products in moderate to good yields within 10 min.

2-Aminobenzimidazole in three-component cyclization reactions with formaldehyde and primary amines

Three-component condensation of 2-aminobenzimidazole and its N-substituted derivatives with formaldehyde and primary amines gave 1,2,3,4-tetrahydro[1,3,5]triazino[1,2-a]benzimidazoles.