Three-component coupling reactions in ionic liquids: One-pot synthesis of isoxazolidines

1-Butyl-3-methylimidazolium based ionic liquids are found to accelerate significantly the intermolecular 1,3-dipolar cycloaddition of nitrones derived in situ from aldehydes and phenyl hydroxylamine, with electron deficient olefins to afford enhanced rates and improved yields of isoxazolidines with high regio- and diastereoselectivity.     

Regio- and diastereoselective synthesis of anticancer spirooxindoles derived from tryptophan and histidine via three-component 1,3-dipolar cycloadditions in an ionic liquid

A small library of novel hybrid spiroheterocycles containing spirooxindole, pyrrolidine and indole/imidazole moieties were synthesized with complete regio- and diastereoselectively in good to excellent yields from a three-component process starting from a series of variously substituted (E)-(2-nitrovinyl)benzenes, indoline-2,3-dione derivatives and l-tryptophan or l-histidine in an ionic liquid. The key step of this transformation is a 1,3-dipolar cycloaddition reaction involving a rare class of in situ-generated azomethine ylides derived from aromatic amino acids. The compounds thus synthesized were evaluated for their anticancer activity and were shown to inhibit the proliferation of FaDu cells, a human epithelial cell line isolated from a squamous cell carcinoma of the hypopharynx, via apoptotic cell death.     

Application of ionic liquids in palladium(II) catalyzed homogenous transfer hydrogenation

The first application of palladium(II) catalyzed homogenous transfer hydrogenations in ionic liquids is described. Cinnamic acid and its derivatives were reduced in high yields under mild conditions using ammonium formate as hydrogen donor.     

Palladium catalyzed cycloisomerization of 2,2-diallylmalonates in imidazolium ionic liquids

A series of palladium salts and complexes, including PdCl₂, PdCl₂/AgPF₆, PdCl₂(PhCN)₂, PdBr₂ and Pd₂(dba)₃ were used in imidazolium ionic liquids as catalysts for the cycloisomerization of diethyl 2,2-diallylmalonate. The order of reactivity follows the expected Pd atom hardness and, therefore, “naked” Pd²⁺ generated from PdCl₂ + AgPF₆ gives the highest turnover frequencies. The system comprising Pd species dissolved in ionic liquid can be reused with minor decrease in conversion, but with an apparent variation in the product distribution. The latter comes from a diminished catalytic activity and from formation of Brönsted acid sites. Finally, by using 1,10-undecadiene derivative we have observed that this Lewis acid induced cycloisomerization is specific for the formation of five-member rings.     

Asymmetric Mannich-type reactions catalyzed by indium(III) complexes in ionic liquids

In(III) complexes efficiently catalyse asymmetric Mannich-type reactions in ionic liquids with high diastereoselectivity and good yield.     

Indium(III) triflate catalyzed tandem azidation/1,3-dipolar cycloaddition reaction of ω,ω-dialkoxyalkyne derivatives with trimethylsilyl azide

The azidation reaction of dialkyl acetal derivatives with trimethylsilyl azide (TMSN₃) was efficiently catalyzed by 1-5 mol % of In(OTf)₃. The major product differed depending on the substrate structure and molar ratio of TMSN₃, that is, aliphatic acetals provided α-azido ether derivatives, while aromatic acetal (benzaldehyde dimethyl acetal) provided gem-diazide, respectively. Furthermore, novel tandem azidation/1,3-dipolar cycloaddition reaction using alkynyl acetal derivatives gave bicyclic triazolo-heterocyclic compounds, recognized as chemically modified aza-sugar analogues, in high yields under mild conditions.     

Mononuclear rearrangement of heterocycles in ionic liquids catalyzed by copper(II) salts

The reactivity of E- and Z-phenylhydrazones of 3-benzoyl-5-phenyl-1,2,4-oxadiazole in the presence of CuCl₂ and Cu(ClO₄)₂·6H₂O has been studied in four imidazolium ionic liquids [bmim][X] (X=BF₄⁻, PF₆⁻, SbF₆⁻ and CF₃SO₃⁻). The reaction may follow different mechanistic patterns, depending on the nature of the ionic liquid anion, accounting for both qualitative and kinetic data. In the presence of CuCl₂, two processes take place at the same time, i.e., the E?Z isomerization and the rearrangement of Z-isomer into the relevant 4-benzoylamino-2,5-diphenyl-1,2,3-triazole. In contrast, in the presence of Cu(ClO₄)₂·6H₂O, the rearrangement occurs only in solution of [bmim][BF₄] and [bmim][CF₃SO₃]. Collected data show that the effect of the ionic liquid on the isomerization and the rearrangement is different. In particular, a higher cross-linking degree seems to favour the triazole, but disfavour the E?Z isomerization.     

Laser-induced fluorescence and infrared spectroscopic studies on the specific solvation of tris(1-(2-thienyl)-4,4,4-trifluoro-1,3-butanedionato)europium(III) in an ionic liquid

The extraction constant and the two-phase stability constant (K_D,Mβ₃) of tris(2-thenoyltrifluoroacetonato)europium(III) between 1-butyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide ([C₄mim][Tf₂N]) as an ionic liquid and an aqueous phase were determined by considering the extraction equilibria including anionic tetrakis(2-thenoyltrifluoroacetonato)europate(III). Specific solute-solvent interactions between the neutral Eu(III) chelate and [C₄mim][Tf₂N] molecules were revealed from the relationships between the distribution constant of the enol form of 2-thenoyltrifluoroacetone (Htta) as a proton chelate and the distribution constant (K_D,M) of the neutral Eu(III) chelate because the [C₄mim][Tf₂N] system gave the high K_D,Mβ₃ value compared with those in conventional molecular solvents such as benzene and 1,2-dichloroethane. The coordination environment of Eu³⁺ in the neutral Eu(III) chelate in [C₄mim][Tf₂N] was investigated by time-resolved laser-induced fluorescence spectroscopy and infrared absorption spectroscopy. Both methods consistently indicated that not only the Eu(III) chelate extracted but also Eu(tta)₃(H₂O)₃ synthesized as a solid crystal were almost completely dehydrated in [C₄mim][Tf₂N] saturated with water. Consequently, the higher K_D,M or extractability of the neutral Eu(III) chelate in the [C₄mim][Tf₂N] system can be ascribed to the dehydration of the Eu(III) chelate, which is caused by the specific solvation with [C₄mim][Tf₂N] molecules.     

Glaser oxidative coupling in ionic liquids: an improved synthesis of conjugated 1,3-diynes

Terminal alkynes undergo oxidative-coupling smoothly in the presence of the CuCl-TMEDA catalytic system in hydrophobic [bmim]PF₆ ionic liquid under aerobic conditions to produce 1,3-diynes in excellent yields under mild conditions. The substrates, alkynes, show enhanced reactivity and selectivity in ionic liquids (ILs). The recovery of the catalyst is facilitated by the hydrophobic nature of the [bmim]PF₆ ionic liquid.     

Iron(III) porphyrin catalyzed ionic liquid mediated polymerization of methylmethacrylate

A novel application of iron(III)porphyrin catalyst, 5,10,15,20 ? tetrakis ? (2′,6′‐dichlorophenyl)porphyrinatoiron(III) chloride is reported for the reaction of methyl methacrylate with hydrogen peroxide in imidazolium ionic liquids at ambient temperature. The reaction furnished polymethyl methacrylate in 75–94% yields. The yield of the polymer was optimized upon changing the reaction media, ratio of catalyst, oxidant and substrate, reaction time and quenchers. The polymethyl methacrylate was secured as highly stereoregular with predominantly syndiotactic sequences as analyzed with the aid of NMR (¹H and ¹³C) and infrared spectroscopy. Besides, the number‐average molecular weights (Mn) were attained in the range of 15,000 to 55,000 with narrow polydispersity (~1.1–1.9) as calculated using gel permeable chromatography (GPC).     

Investigations on synthesis of indole based constrained mimetic scaffolds through 1,3-dipolar cycloadditions of the C-(3-indolyl)-N-phenylnitrone with a variety of olefinic and allenic dipolarophiles under microwave irradiation

Monomode microwave assisted regio- and stereo-selective 1,3-dipolar cycloadditions of C-(3-indolyl)-N-phenylnitrone (19) with a number of olefinic dipolarophiles (20a-f) afford isoxazolidines (21-26) in high yields, which are conformationally constrained mimetics of indole-3-propionic acid of biological significance. Similar cycloadducts derived from addition of nitrone (19) to allenic esters (27a-c) undergo domino reorganization to afford potentially biologically active bis-indole derivatives (28, 29). The observed regio- and stereo-selectivities are analysed, inter alia, in terms of HOMO-dipole-LUMO-dipolarophile and involved secondary orbital/steric interactions in the transition states intervening these cycloadditions.     

1,3-Addition of silyl enol ethers to nitrones catalyzed by mesoporous aluminosilicate

Mesoporous aluminosilicate (Al-MCM-41) was found to be an effective and reusable catalyst for 1,3-addition of silyl enol ethers to nitrones. The reaction proceeded under mild reaction conditions to afford the corresponding β-(siloxyamino)ketones in high yields. Furthermore, a unique chemoselectivity of a nitrone over an aldehyde and an acetal, which are more reactive toward silyl enol ether in the presence of Al-MCM-41 than a nitrone, was observed.     

Alkylation of toluene with 1,3-pentadiene catalyzed by [bupy]BF4-AlCl3 and [bupy]BF4-FeCl3 ionic liquids

A new application of ionic liquids is developed for a novel process of synthesizing pentyltoluene from toluene and a C5 diolefin (1,3-pentadiene). The catalyst [bupy]BF₄-AlCl₃ behaves better than [bupy]BF₄-FeCl₃.     

The preparation of sol-gel materials doped with ionic liquids and trialkyl phosphine oxides for yttrium(III) uptake

A new material (IL923SGs) composed of ionic liquids and trialkyl phosphine oxides (Cyanex 923) for Y(III) uptake was prepared via a sol-gel method. The hydrophobic ionic liquid 1-octyl-3-methylimidazolium hexafluorophosphate (C₈mim⁺PF₆⁻) was used as solvent medium and pore templating material. The extraction of Y(III) by IL923SGs was mainly due to the complexation of metal ions with Cyanex 923 doped in the solid silica. Ionic liquid was stably doped into the silica gel matrix providing a diffusion medium for Cyanex 923, and this will result in higher removal efficiencies and excellent stability for metal ions separation. IL923SGs were also easily regenerated and reused in the subsequent removal of Y(III) in four cycles.     

Ionic liquids as a convenient recyclable medium for the generation of transient carbonyl ylides: syntheses of oxa and dioxa-bridged polycyclic systems

The tandem cyclization-cycloaddition reactions of α-diazo ketones in the presence of rhodium(II) acetate, rhodium(II) octanoate or copper(II) acetyl acetonate as catalyst were performed in different imidazole based ionic liquids as solvent. A successful generation of the transient five- or six-membered-ring carbonyl ylides, followed by the 1,3-dipolar cycloaddition with olefin or carbonyl functional groups in ionic liquid is described to furnish the oxa and dioxa-bridged polycyclic systems with high stereoselectivity. Significant advantages of this process are the recovery of rhodium catalyst, the re-use of ionic liquid, replacement of hazardous organic solvents and the resulting high stereoselectivity.     

Condensation of propargylic alcohols with 1,3-dicarbonyl compounds and 4-hydroxycoumarins in ionic liquids (ILs)

Propargylic alcohols are activated toward 1,3-diketones by Lewis or Brønsted acidic ionic liquids (ILs) without an added catalyst, but significantly better conversions are achieved with metallic triflates [in particular Sc(OTf)₃ and Ln(OTf)₃] and bismuth nitrate in imidazolium ILs. The scope of this condensation reaction was investigated with a variety of propargylic alcohols and a host of acyclic and cyclic dicarbonyl compounds. Concomitant cycloisomerization leading to tetrasubstituted furans was observed with the propargylic alcohols 1b and 1c in reaction with 1,3-diketone 2b and the β-ketoester 2c. With propargylic alcohol 1c, propargylation, cycloisomerization, or dienone formation were observed, depending on the structure of the 1,3-dicarbonyl compound. The [BMIM][PF₆]/Bi(NO₃)₃·5H₂O system proved efficient for propargylation, vinylation, and alkylation of 4-hydroxycoumarins. The recycling and reuse of the IL are added advantages of this method.     

Glycolysis of poly(ethylene terephthalate) catalyzed by ionic liquids

Poly(ethylene terephthalate) (PET) from an industrial manufacturer was depolymerized by ethylene glycol in the presence of a novel catalyst: ionic liquids. It was found that the purification process of the products in the glycolysis catalyzed by ionic liquids was simpler than that catalyzed by traditional compounds, such as metal acetate. Qualitative analysis showed that the main product in the glycolysis process was the bis(hydroxyethyl) terephthalate (BHET) monomer. Thermal analysis of the glycolysis products was carried out by differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). The influences of experimental parameters, such as the amount of catalyst, glycolysis time, reaction temperature, and water content in the catalyst on the conversion of PET, selectivity of BHET, and distribution of the products were investigated. Results show that reaction temperature is a critical factor in this process. In addition, a detailed reaction mechanism of the glycolysis of PET was proposed.     

Synthesis of glucose-tagged triazolium ionic liquids and their application as solvent and ligand for copper(I) catalyzed amination

Glucose-linked 1,2,3-triazolium ionic liquids have been synthesized as a new class of chiral solvents by copper(I) catalyzed regioselective cycloaddition of a glucose azide with a glucose alkyne followed by quaternization with methyl iodide. The tagging of glucose to triazolium core makes these molecules act as reusable ligand and solvent in copper(I) catalyzed amination of aryl halides with aqueous ammonia. While the free hydroxyl groups of sugar help in stabilizing copper(I) species during the reaction thus acting as a ligand, the triazolium salt which makes it a liquid at room temperature serves as a reusable solvent. These chiral ionic liquids derived from low-cost natural sources can find utility in various transition-metal catalyzed reactions, and can be explored for asymmetric synthesis in future.     

The highly enantioselective 1,3-dipolar cycloaddition of alkyl glyoxylate-derived nitrones to E-crotonaldehyde catalyzed by hybrid diamines

1,3-Dipolar cycloaddition of alkyl glyoxylate-derived nitrones to E-crotonaldehyde can be catalyzed by hybrid diamines, obtained from (S)-BINAM and l-α-amino acids. The hybrid of (S)-BINAM and l-Phe was found to be the best organocatalyst. Products were obtained in good yield and diastereoselectivity as well as high enantioselectivity (82-91% ee). Subsequent transformations into functionalized pyrrolidinones have been demonstrated.     

New ionic liquids with tris(perfluoroalkyl)trifluorophosphate (FAP) anions

The synthesis of new ionic liquids with tris(perfluoroalkyl)trifluorophosphate (FAP) anions is described. The physico-chemical properties (conductivity, viscosity, electrochemical and thermal stability) of this new generation of ionic liquids (molten salts) are discussed. FAP-ionic liquids show an excellent hydrolytic stability, low viscosity and high electrochemical and thermal stability that makes them attractive for use in electrochemical devices and as a new media for application in modern technologies and chemical synthesis.