Substrate-controlled selectivity switch in a three-component reaction: sequential synthesis of spiro-oxazolidinedione-cyclopentenones and hydroxy enaminobarbiturates in water

An efficient eco-friendly catalyst-free three-component domino multicyclization for the synthesis of new spirobicyclic oxazolidinedione containing cyclopentenone moieties has been established by mixing amines, β-dicarbonyl compounds and N,N′-dimethylalloxan in water at room temperature. This domino process involves multiple reactions such as enamination/aldol-like reaction/Stork enamine annulation/intramolecular cyclization under mild conditions.

Spiro-oxazolidinedione-cyclopentenones and hydroxy enaminobarbiturates could be selectively formed from amines, β-dicarbonyl compounds and alloxan derivatives under catalyst-free conditions in water.     

Metal-free cascade synthesis of unsymmetrical 2-aminopyrimidines from imidazolate enaminones

A convenient metal-free synthesis of unsymmetrical 2-aminopyrimidines from imidazolate enaminones has been developed. In this procedure, various structural 2-aminopyrimidines, as well as 4,5-dihydroisoxazol-5-ols and pyrazoles were synthesized in moderate to excellent yields. A plausible mechanism was also proposed for the cascade reaction. This method represents an effective strategy towards the synthesis of unsymmetrical 2-aminopyrimidines.

A convenient metal-free synthesis of unsymmetrical 2-aminopyrimidines from imidazolate enaminones has been developed.     

A novel microwave dielectric ceramic Li2NiZrO4 with rock salt structure

Low loss Li₂NiZrO₄ ceramics with rock salt structure were successfully prepared by the solid-phase reaction method. The relationship between sintering temperature, phase composition and dielectric properties of Li₂NiZrO₄ ceramics was reported for the first time. The grain size gradually increased and the porosity decreased with the sintering temperature increasing. When the sintering temperature exceeds 1300 °C, the grains grow abnormally and some grains begin to melt. The XRD patterns indicated the second phase ZrO₂ appeared due to the volatilization of lithium. The grains grow abnormally and a second phase of ZrO₂ increased the loss of Li₂NiZrO₄ ceramics. The samples sintered at 1300 °C possessed the best dielectric properties: ε_r = 12.3, Q_f = 20000 GHz, τ_f = −23.4 ppm °C⁻¹, which would make the ceramic a possible candidate for millimeter-wave applications.

Low loss Li₂NiZrO₄ ceramics with rock salt structure were successfully prepared by the solid-phase reaction method.     

Convenient construction of tetrahydrochromeno[4′,3′:2,3]indolizino[8,7-b]indoles and tetrahydroindolizino[8,7-b]indoles via one-pot domino reaction

The functionalized tetrahydrochromeno[4′,3′:2,3]indolizino[8,7-b]indoles were conveniently synthesized in high yields by one-pot domino reaction of tryptamines, alkyl propiolates and 2-aryl-3-nitro-2H-chromenes. Under similar conditions, the one-pot reaction of tryptamines, alkyl propiolates and β-nitroalkenes resulted in functionalized tetrahydroindolizino[8,7-b]indoles. The reaction mechanism involved sequential generation of β-enamino ester, Michael addition, Pictet–Spengler reaction and annulation process. The reaction showed high atomic economy and met the goals of sustainable chemistry.

The functionalized tetrahydrochromeno[4′,3′:2,3]indolizino[8,7-b]indoles were conveniently synthesized in high yields by one-pot domino reaction of tryptamines, alkyl propiolates and 2-aryl-3-nitro-2H-chromenes.     

Synthesis of tetrahydro-β-carbolines from 2-indolylmethyl azides and propargylic alcohols

A facile and efficient route to tetrahydro-β-carbolines from 2-indolylmethyl azides and propargylic alcohols via acid-catalyzed dehydrative annulation reactions is described. This reaction proceeds through a cascade sequence of Friedel–Crafts-type alkylation followed by intramolecular “Click” reaction, involving the formation of multiple chemical bonds in a single operation with excellent atom-economy and broad functional group tolerance.

The synthesis of tetrahydro-β-carbolines from 2-indolylmethyl azides and propargylic alcohols via acid-catalyzed dehydrative [4 + 2]-annulation reaction is described.     

Design and synthesis of benzothiazole/thiophene-4H-chromene hybrids

A library of 4H-chromene derivatives with heterocyclic substituent''s at the 3 and 4-positions was synthesized in a convenient DBU catalysed three component synthesis between salicylaldehyde, acetonitrile derivatives and thiazolidinedione to afford 2-amino-3-benzothiazole-4-heterocycle-4H-chromenes and 2-amino-3-thiophenoyl-4-heterocycle-4H-chromenes derivatives in ethanol and a mixture of ethanol and water (1 : 1) at room temperature. The significance of this protocol is the feasibility of incorporating substituents simultaneously at the 3 and 4 positions of 4H-chromenes in an efficient three component reaction.

A library of 4H-chromene derivatives with heterocyclic substituents at 3 and 4-positions was synthesized in a convenient DBU catalysed three component reaction.     

An umpolung reaction of α-iminothioesters possessing a cyclopropyl group

An umpolung N-alkylation reaction of α-cyclopropyl α-iminothioesters with diethylaluminum chloride or ethylmagnesium bromide affords the corresponding N-ethylated α-aminothioesters in good yields. Subsequent oxidation and reaction of the N-ethylated product with a thiolate or a chloride anion proceed effectively to give the ring-opened products in good yields. In contrast, relatively “hard” nucleophiles did not give the ring-opened products but gave the addition products to the iminium carbon.

Tandem N-alkylation/oxidation/second addition reaction to α-cyclopropyl α-imino(thio)esters gave N-alkylated ring-opened products in good yields.     

One-pot,sequential four-component synthesis of novel heterocyclic [3.3.3] propellane derivatives at room temperature

An efficient, one-pot, two-step, four-component reaction for the synthesis of propellane derivatives is described by the condensation reaction between acenaphthenequinone, malono derivatives, primary amines and β-ketoester or β-diketone derivatives in the presence of triethylamine in ethanol at room temperature. Using this procedure, all the products were obtained in good to excellent yields.

An efficient synthesis of propellane derivatives is described by the condensation reaction between acenaphthenequinone, malono derivatives, primary amines and β-ketoesters or β-diketones in the presence of triethylamine in ethanol at room temperature.     

Iron salt-promoted oxidation of steroidal phenols by m-chloroperbenzoic acid: a route to possible antitumor agents

A new oxidant, containing m-chloroperoxybenzoic acid (MCPBA) and an iron salt, was developed and used for oxidation of steroidal phenols to a quinol/epoxyquinol mixture. Reaction was optimized for estrone, by varying initiators (Fe-salts), reaction temperature, time and mode of MCPBA application. A series of five more substrates (17β-estradiol and its hydrophobized derivatives) was subjected to the optimized oxidation, providing corresponding p-quinols and 4β,5β-epoxyquinols in good to moderate yields. The obtained epoxyquinols were additionally transformed by oxidation, as well as the acid-catalyzed oxirane opening. In a preliminary study of the antiproliferative activity against human cancer cell lines, all newly synthesized compounds expressed moderate to high activity.

Iron salt-promoted reaction of estrone and its derivatives with meta-chloroperoxybenzoic acid was developed and epoxyquinols were further transformed. Most compounds showed in vitro antiproliferative activity.     

[3+2] regioselective annulation reaction of 2-arylidene-1,3-indandiones towards synthesis of spirocyclopentenes: understanding the mechanism of γ-attack vs. α-attack using DFT studies

A regioselective [3+2] cyclisation reaction between 2-arylidene-1,3-indanedione and ethyl 2,3-butadienoate catalysed by triphenylphosphine has been demonstrated to synthesize functionalised spirocyclic cyclopentenes. The reaction tolerated various electron-rich and electron-deficient aryl substituted 2-arylidene-1,3-indanediones with high to excellent chemical yields (up to 99%) and moderate to good regioselectivity (up to 5 : 1). DFT studies have also been carried out to understand the regioselective nature of this reaction. The results of Frontier molecular orbital calculations and the activation energy (E_a) favour the formation of compound 3avia γ-attack compared to that of 4avia α-attack.

A [3+2] annulation protocol for the construction of functionalized spirocyclopentenes utilizing 1,3-indanedione derived benzylidene-1,3-indanedione and ethyl-2,3-butadienoate at room temperature was developed.     

The Reformatsky analogous reaction for the synthesis of novel β-thioxoesters via using aroyl isothiocyanates under solvent-free ball milling and conventional conditions

The classical Reformatsky reaction, initially described in 1887, is considered one of the most useful ways of forming C–C bonds. The target of this work includes improving the Reformatsky reaction between aroyl isothiocyanates and α-haloesters using metallic zinc to form β-thioxoesters (3–11). In this procedure, a new metal-mediated carbon–carbon linkage is formed with the formation of an organozinc halide and decomposition due to the presence of dilute acid, affording a good yield of the desired product via conventional techniques and ball milling. The Reformatsky reaction requires no solvent and no inert gases.

The Reformatsky analogous reaction between aroyl isothiocyanates and α-haloesters using metallic zinc to form β-thioxoesters via ball milling and conventional techniques.     

Ferrocenium complex aided O-glycosylation of glycosyl halides

A new strategy for the activation of glycosyl halide donors to be utilized in glycosylation reactions is presented, utilizing the ferrocenium (Fc) complexes [FcB(OH)₂]SbF₆ and FcBF₄ as promoters. The scope of the new system has been investigated using glycosyl chloride and glycosyl fluoride donors in combination with common glycosyl acceptors, such as protected glucose. The corresponding glycosylation products were formed in 95 to 10% isolated yields with α/β ratios ranging from 1/1 to β only (2 to 14 h reaction time at room temperature, 40 to 100% ferrocenium promoter load).

Ferrocenium complexes as a new, tunable platform for O-glycosylation reactions are introduced.     

β-Cyclodextrin: a supramolecular catalyst for metal-free approach towards the synthesis of 2-amino-4,6-diphenylnicotinonitriles and 2,3-dihydroquinazolin-4(1H)-one

β-Cyclodextrin, a green and widespread supramolecular catalyst, has been explored as a highly proficient promoter for the metal-free one-pot multi-component synthesis of a vast range of highly functionalized bioactive heterocyclic moiety, 2-amino-4,6-diphenylnicotinonitriles and 2,3-dihydroquinazolin-4(1H)-one, from easily available precursor aldehydes. The main endeavor of these protocols is to explore this organic supramolecule in one-pot multi-component synthesis. Absence of metal catalyst or toxic acid and harsh reaction conditions, excellent functional group tolerance, inexpensive, greener and environmentally safe protocol are the key advantages of this work.

A vast range of 2-amino-4,6-diphenylnicotinonitrile and 2,3-dihydroquinazolin-4(1H)-one were synthesized through a metal-free one-pot multi-component synthesis using β-cyclodextrin as an efficient supramolecular organocatalyst.     

Revealing the in situ NaF generation balance for user-friendly controlled synthesis of sub-10 nm monodisperse low-level Gd3+-doped β-NaYbF4:Er

Herein, user-friendly control of the synthesis of sub-10 nm hexagonal (β-) NaYbF₄:Er nanocrystals (NCs) with extremely low-level Gd³⁺ doping (0%, 10 mol%) was achieved. We reveal for the first time that the effective sodium/fluoride levels during the formation of cubic (α-) nuclei are not only controlled by the sodium/fluoride to rare-earth precursor ratios used, but also sensitively restricted by the in situ NaF generation reaction in a sodium oleate-based solvothermal system. Excessive in situ NaF generation will lead to a respective sodium- and fluoride-deficient environment, delayed α-to-β transition and larger β-NCs. Based on these effects, sub-10 nm monodisperse low-level Gd³⁺-doped β-NaYbF₄:Er was obtained with a user-friendly low fluoride dosage by finely balancing this NaF generation reaction and achieving an intrinsic optimized sodium-fluoride level for NC nucleation. Notably, our work represents the first example where the focus is on the competing in situ NaF generation reaction and its use for nucleation regulation, as well as for the user-friendly control of the solvothermal synthesis of sub-10 nm β-NaYbF₄:Er.

User-friendly solvothermal controlled synthesis of sub-10 nm monodisperse low-level Gd³⁺-doped β-NaYbF₄:Er was achieved via revealing and balancing the competing in situ NaF generation reaction.     

Decarboxylative aldol reaction of α,α-difluoro-β-ketocarboxylate salt: a facile method for generation of difluoroenolate

We developed a decarboxylative aldol reaction using α,α-difluoro-β-ketocarboxylate salt, carbonyl compounds, and ZnCl₂/N,N,N′,N′-tetramethylethylenediamine. The generation of difluoroenolate proceeded smoothly under mild heating to provide α,α-difluoro-β-hydroxy ketones in good to excellent yield (up to 99%). The α,α-difluoro-β-ketocarboxylate salt was bench stable and easy to handle under air, which realizes a convenient and environmentally friendly methodology for synthesis of difluoromethylene compounds.

A ZnCl₂/N,N,N′,N′-tetramethylethylenediamine complex promoted decarboxylative aldol reaction of α,α-difluoro-β-ketocarboxylate salt with carbonyl compounds has been developed.     

Tailor-made block copolymers of l-, d- and rac-lactides and ε-caprolactone via one-pot sequential ring opening polymerization by pyridylamidozinc(ii) catalysts

Three-coordinated Zn(ii) complexes bearing sterically encumbered bidentate monoanionic [N,N⁻] pyridylamido ligands efficiently catalyze the ring opening polymerization of lactide (LA) and ε-caprolactone (CL). Owing to the polymerization controlled nature and high rate, precise stereodiblock poly(LLA-b-DLA) with different block lengths can be easily produced by one-pot sequential monomer addition at room temperature in short reaction times. NMR, SEC and DSC analyses confirm the production of highly isotactic diblock copolymers which crystallize in the high melting stereocomplex phase. Stereo-triblock and tetrablock copolymers of l-LA, d-LA and rac-LA have been synthesized similarly. Finally, a diblock poly(CL-b-LA) has been easily obtained by sequential addition of ε-caprolactone and lactide under mild conditions.

New 3-coordinated Zn ROP catalysts afford lactide stereo-block copolymers with variable block lengths and steric structures and diblock ε-caprolactone-lactide copolymers at room temperature and in short reaction times.     

Investigation of optical and electrical properties of the semiconducting α-KZnPO4 compound

We used the solid state method to synthesize the α-KZnPO₄ compound. The X-ray diffraction pattern revealed that the sample represents a single hexagonal phase with a P6₃ space group. The chemical composition of the compound was examined by energy dispersive spectroscopy. The optical absorption measurement confirmed the semiconductor nature of the compound with a band gap around 4.52 eV. Furthermore, the electrical properties of the material were analyzed by means of the impedance spectroscopy, in a frequency range from 100 Hz to 1 MHz and a temperature range from 583 K to 673 K. The dependency of s(T) on temperature showed that the overlapping large polaron tunneling model is the mechanism responsible for AC conduction in the compound. A correlation between the crystal structure and the ionic conductivity was established and discussed. Finally, the temperature variation of M′′ peak showed a thermally activated relaxation process and a temperature-dependent stretching exponent β parameter.

We used the solid state method to synthesize the α-KZnPO₄ compound.     

A regioselective C7 bromination and C7 palladium-catalyzed Suzuki–Miyaura cross-coupling arylation of 4-substituted NH-free indazoles

A direct and efficient regioselective C7-bromination of 4-substituted 1H-indazole has been achieved. Subsequently, a successful palladium-mediated Suzuki–Miyaura reaction of C7-bromo-4-substituted-1H-indazoles with boronic acids has been performed under optimized reaction conditions. A series of new C7 arylated 4-substituted 1H-indazoles was obtained in moderate to good yields.

A regioselective C7-bromination of 4-substituted 1H-indazoles followed by a palladium-catalyzed Suzuki–Miyaura reaction with boronic acids is described.     

Catalytic enantioselective Henry reaction of α-keto esters, 2-acylpyridines and 2-acylpyridine N-oxides

A pre-prepared Ni–PyBisulidine complex has been developed for the catalytic asymmetric Henry reaction of α-keto esters, 2-acylpyridines and 2-acylpyridine N-oxides. The corresponding β-nitro-α-hydroxy esters were obtained in good to excellent yields (up to 99%) with a high enantiomeric excess (ee) (up to 94%) with a catalyst loading of 1–2 mol%. The desired products of 2-acylpyridines and 2-acylpyridine N-oxides, which were simple methyl ketones, were obtained in medium to excellent yields (up to 94%) with medium to good ee (up to 86%) by using 2 mol% of catalyst.

Asymmetric Henry reaction of ketones catalyzed by a pre-prepared Ni complex with low catalyst loading.     

Cp2ZrCl2 – Et3Al reagent system in the homo-coupling of trimethylsilyl-substituted alkynes

The reaction of trimethylsilyl-substituted alkynes with 0.5 equivalents of Cp₂ZrCl₂ and 1 equivalent of Et₃Al in toluene at room temperature for 18 hours gives, after hydrolysis/deuterolysis or iodination, functionalized products of the homo-coupling of silyl-substituted alkynes in good yield. Trimethylsilyl-substituted α,ω-diynes react with the Cp₂ZrCl₂ – Et₃Al reagent system to give (1Z,2Z)-1,2-bis(iodo(trimethylsilyl)methylene)cycloalkanes after iodinolysis.

The reaction of trimethylsilyl-substituted alkynes with 0.5 equivalents of Cp₂ZrCl₂ and 1 equivalent of Et₃Al in toluene at room temperature gives products of the homo-coupling in good yield.