Electrochemical Formation of α-Ketoamides from Ketoximes through Non-Beckmann Mechanism Pathway.

α-Ketoamides are highly valued in synthetic chemistry due to their incorporation into diverse natural products and drug molecules. Here, we present an innovative electrochemical approach for constructing α-ketoamides, utilizing a mild and environmentally friendly strategy in a user-friendly undivided cell setup under constant current. The excellent functional-group tolerance, convenient accessibility of reaction instruments and starting materials, and easy scalability collectively enhance the importance of this protocol compared to previous challenging methods. Additionally, mechanistic insight into this reaction is obtained through the investigation of cyclic voltammograms of the reactants.

Scalable Diastereoselective Electrosynthesis of Spiro[benzofuran-2,2'-furan]-3-ones.

Spirobenzofuran scaffolds, because of their three-dimensional structure, are incorporated into several valuable natural products and drug candidate molecules. Herein, with the assistance of electrosynthesis, we introduce a novel electrochemical approach for achieving spirobenzofurans in a user-friendly and operationally simple undivided cell setup under constant current. This metal-catalyst-free electrochemical procedure afforded spiro[benzofuran-2,2'-furan]-3-ones with high diastereoselectivity. Compatibility with gram-scale synthesis along with the convenient accessibility of reaction instruments and starting materials collectively raised the importance of this protocol compared to previous challenging methods. Furthermore, mechanistic cognizance of this reaction is obtained by the investigation of the cyclic voltammetry spectra of reactants.

Isocyanide-based synthesis of spirorhodanine-cyclopentadiene and spirorhodanine-iminobutenolide conjugates from Winterfeldt's zwitterions and 5-ylidene rhodanines.

An ultrasonic-assisted isocyanide-based protocol to access a series of functionalized spirorhodanine-cyclopentadiene and spirorhodanine-iminobutenolide conjugates from alkyl isocyanides and dialkyl acetylenedicarboxylates in the presence of 5-ylidene rhodanines in MeCN, is described. The reaction proceeds via interception of the reactive Winterfeldt's zwitterions by 5-ylidene rhodanine derivatives. The structures of the target compounds were confirmed by X-ray diffraction studies.

Formation of bis-spiropyrrolidines from isatin, secondary amines, and alkylidene Meldrum's acids.

A catalyst-free synthesis of stable bis-spiropyrrolidines from isatin, secondary amines, and alkylidene Meldrum's acids in MeCN in 75-95% yield is described. The antioxidant and antimicrobial properties of the synthesized compounds are investigated. For this purpose, the radical scavenging activities of four derivatives were studied by radical trapping of diphenylpicrylhydrazine and ferric reduction power experiments. Disk diffusion test on Gram-positive and Gram-negative bacteria was employed to investigate antibacterial activities of five derivatives.

Synergistic performance of a new bimetallic complex supported on magnetic nanoparticles for Sonogashira and C-N coupling reactions.

This paper describes the synthesis of a novel Cu-Ni bimetallic system comprising of magnetic nanoparticles, as the core, and 4-amino-3,5-bis(pyridin-2-yl)-1,2,4-triazole (4-ABPT), as a conjugated bridge, between nickel and copper species. With low Cu and Ni loading (0.06 mol% Ni, 0.08 mol% Cu), the resulting Fe3O4@SiO2@4-ABPT/Cu-Ni showed to be a highly efficient catalyst for the Sonogashira and C-N cross-coupling reactions. The developed catalyst was well characterized by FT-IR, XRD, EDX-mapping, FE-SEM, TEM, ICP, VSM, TGA/DTG/DTA, LSV, and XPS techniques. Fe3O4@SiO2@4-ABPT/Cu-Ni nanocatalyst was compatible with a wide range of amines and aryl halides in the Sonogashira and C-N cross-coupling reactions and offered desired coupling products in high to excellent yields under palladium- and solvent-free conditions. Based on the XPS results, the 4-ABPT ligand can adjust electron transfer between Ni and Cu in Fe3O4@SiO2@4-ABPT/Cu-Ni, promoting the formation and stabilization of Cu+ and Ni3+ species. Electronic interactions and the synergistic effect between these metals increased the selectivity and activity of Fe3O4@SiO2@4-ABPT/Cu-Ni catalyst in the Sonogashira and C-N cross-coupling reactions compared with its monometallic counterparts. Additionally, the magnetic properties of Fe3O4@SiO2@4-ABPT/Cu-Ni facilitated its separation from the reaction mixture, promoting its reuse for several times with no significant loss in its catalytic activity or performance.

Synthesis of pyrrolidin-2-ylidenes and pyrrol-2-ylidenes via 1,3-dipolar cycloaddition of H-bond-assisted azomethine ylides to nitrostyrenes.

Hydrogen-bond-assisted azomethine ylides, generated from 2-(benzylamino)-2-(1,3-dioxo-1,3-dihydro-2H-inden-2-ylidene)acetonitriles, undergo a formal Huisgen 1,3-dipolar cycloaddition with ß-bromo-ß-nitrostyrenes to afford a diastereoselective synthesis of highly substituted pyrrolidin-2-ylidene derivatives. When ß-nitrostyrenes were used as the alkene component, 2-(4,5-diaryl-1,5-dihydro-2H-pyrrol-2-ylidene)-1H-indene-1,3(2H)-diones were obtained. Efficient conversion of pyrrolidene-2-ylidenes to the corresponding pyrrol-2-ylidenes takes place in refluxing 1-propanol in the presence of excess Et3N. Also, the structure of the pyrrolidene-2-ylidene derivative was determined by X-ray crystallography.

Migration from Photochemistry to Electrochemistry for [2 + 2] Cycloaddition Reaction.

Cyclobutane scaffolds are incorporated in several valuable natural and bioactive products. However, non-photochemical ways to synthesize cyclobutanes have scarcely been investigated. Herein, based on the principles of the electrosynthesis technique, we introduce a novel electrochemical approach for attaining cyclobutanes by a simple [2 + 2] cycloaddition of two electron-deficient olefins in the absence of photocatalysts or metal catalysts. This electrochemical strategy provides a suitable condition for synthesizing tetrasubstituted cyclobutanes with a variety of functional groups in good to excellent efficiency, compatible with gram-scale synthesis. In contrast to previous challenging methods, this approach strongly focuses on the convenient accessibility of the reaction instruments and starting materials for preparing cyclobutanes. Readily accessible and inexpensive electrode materials are firm evidence to prove the simplicity of this reaction. In addition, mechanistic insight into the reaction is obtained by investigation of the CV spectra of the reactants. Also, the structure of a product is identified by X-ray crystallography.

A one-pot synthesis 3-alkoxycarbonyl-3,4-dihydro-2H-pyran-2-ones from vinylidene melderum's acids, dialkyl acetylenedicarboxylates, and simple alcohols.

A one-pot synthesis of 3-alkoxycarbonyl-3,4-dihydro-2H-pyran-2-ones from intermolecular hetero-Diels-Alder reaction between vinylidene Melderum's acids and dialkyl acetylenedicarboxylates, in the presence of simple alcohols at room temperature, is described. The advantages of this procedure are good yields, short reaction time, and easy workup. Antioxidant properties of four derivatives of these 3,4-dihydro-2H-pyran-2-ones, together with their antimicrobial activities, are investigated.

A consecutive synthesis of spiro[cyclopenta[b]pyrrole-5,2'-indene] derivatives via spirocyclization/annulation reactions.

The reaction between ninhydrin-malononitrile adduct [2-(1,3-dioxo-1,3-dihydro-2H-inden-2-ylidene)malononitrile] and ethyl 2-(alkylamino)-4-aryl-4-oxo-but-2-enoates (prepared from ethyl 2,4-dioxo-4-arylbutanoate and alkylamines) in the presence of Et3N in MeCN at room temperature afforded 3-alkylamino-2-aryloyl-1',3',4-trioxo-1',3'-dihydrospiro[cyclopentane-1,2'-inden]-2-ene-5,5-dicarbonitriles in 78-95% yields. Five derivatives of these NH-acidic compounds are used to intercept the reactive zwitterionic intermediates generated from dimethyl acetylenedicarboxylate and Ph3P to produce dimethyl 4,4-dicyano-6-aryloyl-1-alkyl-1',3'-dioxo-1',2,3',4-tetrahydro-1H-spiro[cyclopenta[b]pyrrole-5,2'-indene]-2,3-dicarboxylates. Radical scavenging activity of four derivatives was investigated by radical trapping of diphenylpicrylhydrazine and ferric reduction power experiments. The antibacterial activities of six derivatives were studied by disk diffusion test on Gram-positive and Gram-negative bacteria.

Benzylic C(sp3)-H Bonds Play the Dual Role of Starting Material and Oxidation Inhibitor for Hydrazides in the Electrochemical Synthesis of Hydrazones.

The electrooxidation of benzylic C(sp3)-H bonds to produce hydrazones as an alternate for conventional pathways has an enormous dignity. Under the aegis of electricity, instead of hazardous metal catalysts and external oxidants, we unveil an electrochemical process for electrooxidation of various benzylic C(sp3)-H bonds in aqueous media in all pH ranges that subsequently produce hydrazones with further reactions. This electrooxidative reaction strategy provides an acceptable condition for synthesizing hydrazones with various functional groups in good efficiency and amenable to gram-scale synthesis. The electrochemical oxidation condition proves an excellent level of compatibility with super cheap electrolyte NaCl for the oxidation of benzylic C(sp3)-H position despite the highly oxidizable hydrazide group remaining intact in the reaction.

A synthesis of functionalized 3-amino-1,2,4-triazoles from nitrile imines and guanidine derivatives.

A regioselective synthesis of trisubstituted 1,2,4-triazoles through reaction of nitrile imines with guanidine derivatives is described. These 1,3-dipolar cycloaddition reactions proceeded smoothly in moderate to good yields and excellent regioselectivity under ambient conditions. This method provides fast access to a range of functionalized 3-amino-1,2,4-triazoles.

A synthesis of fuctionalized 2-amino-3-cyano pyrroles from terminal alkynes, sulfonyl azides and phenacylmalononitriles.

A new strategy for the construction of functionalized 2-amino-3-cyano pyrroles has been developed. The reactions involved a copper-catalyzed azide-alkyne cycloaddtion reaction between terminal alkynes and sulfonyl azides followed by generation of N-sulfonoketenimine intermediates. Interception of these reactive ketenimines by phenacylmalononitriles in the presence of copper(I) iodide and Et3N afforded the expected products. The reaction proceeded smoothly in THF at ambient temperature to afford the target compounds in 70-92% yields and excellent regioselectivity. Evidence for the structure of a typical product is obtained from single-crystal X-ray analyses.

A Molecular Iodine-Mediated Synthesis of Cyclopenta[c]furo[3,2-b]furan-5,6-diones: Assembly of an Angular Dioxatriquinane Core.

A molecular iodine-mediated synthesis of angular oxatriqinane core from 3-acetyl-2H-chromen-2-ones, ß-bromo-ß-nitrostyrenes, and pyridine in the presence of Et3N in MeCN containing a trace amount of water was developed. The reaction proceeds via intermolecular Michael reaction of 2-oxo-2-(2-oxo-2H-chromen-3-yl)-1-(pyridin-1-ium-1-yl)ethan-1-ide with bromonitrostyrene followed by intramolecular Michael reaction and elimination steps. Evidence for the stereochemistry of a typical product is obtained from single-crystal X-ray analyses. The important feature of this strategy is the fact that it forms three stereogenic centers with good selectivity.

TFA-mediated synthesis of functionalized pyrano[2,3-c]pyrazoles from pyrazol-3-ones, active carbonyl compounds and tert-BuOH.

Functionalized pyrano[2,3-c]pyrazoles were synthesized from 2,4-dihydro-3H-pyrazol-3-ones, active carbonyl compounds and tert-BuOH in the presence of trifluoroacetic acid at 65 °C. These reactions are proceeded by acid catalyzed generation of isobutylene from tert-BuOH for LUMOdiene-controlled inverse [4 + 2] cycloaddition reaction with in situ-generated vinylidenepyrazolones.

Reverse orientation in the ultrasound-assisted [3 + 2]-cycloaddition reaction of nitrile imines with 3-formylchromone-Meldrum's acid adducts.

The [3 + 2]-cycloaddition reaction of nitrile imines with 2,2-dimethyl-5-[(4-oxo-4H-chromen-3-yl)methylene]-1,3-dioxane-4,6-dione tends to form the reverse-orientation products under ultrasound irradiation in EtOH in the presence of Et3N. Evidence for the structure of product 5b was obtained from single-crystal X-ray analysis.

Synthesis of thia- and thioxo-tetraazaspiro[4.4]nonenones from nitrile imines and arylidenethiohydantoins.

5-Arylidene-1-methyl-2-thiohydantoins undergo [3+2]-cycloaddition reaction with nitrile imines, generated in situ from hydrazonyl chlorides, at C=C and C=S dipolarophiles in the thiohydantoin moiety to afford thioxo-tetraazaspiro[4.4]nonenones and thia-tetraazaspiro[4.4]nonenones in moderate to good yields. The stereochemistry of these spiroheterocycles has been confirmed by X-ray diffraction studies.

A formal [3+2] cycloaddition reaction of N-methylimidazole as a masked hydrogen cyanide: access to 1,3-disubstitued-1H-1,2,4-triazoles.

N-Methylimidazole (NMI) can act as a masked HCN in the synthesis of 1,3-disubstitued-1H-1,2,4-triazoles via a formal cycloaddition reaction of hydrazonoyl chloride with NMI. The product was proved to be formed via an initial nucleophilic substitution of hydrazonoyl chloride with NMI following cyclization and two sequential C-N bond cleavages.

Electrochemical Synthesis of ß-Ketosulfones from Switchable Starting Materials.

A synthesis of ß-ketosulfones via sulfination of aryl methyl ketones and aryl acetylenes with sodium sulfinates under mild electrochemical conditions, in moderate to good chemical yields, is described. In particular, an electrochemical sulfination reaction of alkynes with sulfinate salts has never been explored. An environmentally friendly characteristic of this reaction is that it uses electricity as a valuable energy source for electrochemical synthesis of ß-ketosulfones. This strategy is more convenient and practical compared to previous approaches.

A synthesis of N-(1H-pyrazol-5-yl)-1,3,4-thiadiazol-2(3H)-imines from nitrile imines and Erlenmeyer thioazlactones.

Erlenmeyer thioazlactones are reacted with hydrazonoyl chlorides in the presence of Et3N to afford functionalized N-(1H-pyrazol-5-yl)-1,3,4-thiadiazol-2(3H)-imines in excellent yields. This strategy is based on a domino double 1,3-dipolar cycloaddition reaction of nitrile imines to Erlenmeyer thioazlactones, followed by the elimination of carbon monoxide and phenylmethanthiol from the initially formed cycloadducts. This method provides fast access to a variety of structurally diverse N-(1H-pyrazol-5-yl)-1,3,4-thiadiazol-2(3H)-imines. The structure of a typical product was established by X-ray crystallography.

A one-pot synthesis of bis(phenylimino)thiazolidines from ketene N,S-acetals and [Formula: see text],[Formula: see text]-diphenyloxalimidoyl dichloride.

A synthesis of functionalized 4,5-bis(phenylimino)-1,3-thiazolidine-2-ylidenes via a simple reaction between ketene [Formula: see text]-acetals (derived from isothiocyanates and acetonitrile derivatives) with N,[Formula: see text]-diphenyloxalimidoyl dichloride in the presence of KOH in DMF is described. When CS[Formula: see text] was used as the heterocumulene component, the reaction led to the formation of 4,5-bis(phenylimino)-1,3-dithiolan-2-ylidene derivatives, in moderate to good yields.