Stereoselective Michael addition of carbon-, nitrogen-, oxygen-, and sulfur-centered nucleophiles on enantiopure hydroxylated 6,7-dehydro-5-oxoindolizidine. Synthesis of carbon- or hetero-7-substituted swainsonine analogues

Enantiopure alpha,beta-unsaturated delta-lactams 1 and 2 react stereoselectively with carbon-, nitrogen-, sulfur-, and oxygen-centered nucleophiles. The synthetic potential of these conjugate additions is demonstrated through the synthesis of two new substituted indolizidines: (7R)-7-amino-8-deoxyswainsonine 3 and (7R)-7-acetylaminoswainsonine 4.     

Synthesis and reactions of a monosubstituted dithiirane 1-oxide, 3-(9-triptycyl)dithiirane 1-oxide

A 3-monosubstituted dithiirane 1-oxide, 3-(9-triptycyl)dithiirane 1-oxide, was prepared for the first time, by the reaction of (9-triptycyl)diazomethane and S₈O. The dithiirane 1-oxide was obtained as cis- and trans-isomers, and the structure of the trans-isomer was verified by X-ray crystallography. The cis-isomer isomerized gradually to the trans-isomer in solution. The divalent sulfur atom of the cis- and trans-dithiirane 1-oxides were removed on treatment with triphenylphosphine to give the corresponding Z- and E-sulfines, respectively. The reaction of the trans-dithiirane 1-oxide with (Ph₃P)₂Pt(C₂H₄) provided the (sulfenato-thiolato)Pt^II complex, and that with Lawesson's reagent yielded the 1,3,4,2-trithiaphospholane and 1,2,4,5,3-tetrathiaphosphorinane derivatives.     

Synthesis of 9-alkylidene-9H-fluorenes by a novel, palladium-catalyzed cascade reaction of aryl halides and 1-aryl-1-alkynes.

In the presence of a palladium catalyst and NaOAc, aryl iodides react with 1-aryl-1-alkynes to afford 9-alkylidene-9H-fluorenes in good yields. The products from this reaction are highly dependent on the base employed. This process appears to involve (1) oxidative addition of the aryl iodide to Pd(0), (2) alkyne insertion, (3) rearrangement of the resulting vinylic palladium intermediate to an arylpalladium species, and (4) aryl-aryl coupling with simultaneous regeneration of the Pd(0) catalyst. Consistent with this mechanism is the fact that 9-alkylidene-9H-fluorenes can also be prepared by the Pd-catalyzed rearrangement of 1,1-diaryl-2-iodo-1-alkenes.     

Synthesis of 3-substituted isoindolin-1-ones via a palladium-catalysed 3-component carbonylation/amination/Michael addition process

A novel palladium-catalysed three component cascade process is described involving carbonylation of an aryl iodide to generate an acyl palladium species which is intercepted by a primary aliphatic/aromatic amine, amide or sulfonamide followed by intramolecular Michael addition to afford 3-substituted isoindolin-1-ones in good yield.     

Synthesis of a novel crown ether derived from chiro-inositol and its catalytic activity on the asymmetric Michael addition

A novel 18-membered chiral crown ether was prepared in four steps starting from L-quebrachitol, a chiro-inositol, and its catalytic activity in the Michael addition reaction of glycine imine with several Michael acceptors was studied.     

Synthesis and characterization of a novel quercetin magnetic molecularly imprinted polymer via reversible addition fragmentation chain transfer strategy

Molecularly imprinted polymer (MIP) will be modified on the surface of the core-shell structure silica magnetic nanoparticles, during which quercetin is used as a template molecule, acrylamide as a functional monomer, azo-bisisobutyronitrile as an initiator and ethylene glycol dimethacrylate as a cross-linker, to synthesize highly efficient and selective quercetin magnetic molecularly imprinted nanoparticles via Reversible Addition-Fragmentation chain Transfer (RAFT) polymerization. FT-IR and X-ray diffraction (XRD) patterns are used to monitor the reaction and show the characteristic groups of each reaction step. Compared with the conventional bulk polymerization (2.7029 mg/g), the adsorption test showed that the MMIP by RAFT activity controlled polymerization had better absorption capacity for quercetin which the saturated adsorption amount was 4.8471 mg/g. Kinetic studies indicate that pseudo first order model is suitable to describe the adsorption mechanism. Thermodynamics experiment revealed that Langmuir model was more applied for explains the adsorption of quercetin onto magnetic molecularly imprinted polymer.     

Synthesis,characterization, and antimicrobial activity of novel heterocyclic compounds containing a ferrocene unit via Michael addition reaction

Research on Chemical Intermediates - A series of novel heterocyclic compounds containing a ferrocene unit were synthesized by reacting ferrocenylchalcone with pyrazolyl amine or triazolyl amine via...     

Synthesis of the aziridinomitosene skeleton by intramolecular Michael addition of alpha-lithioaziridines: an aromatic route featuring deuterium as a removable blocking group

A convergent synthetic route to the 1,2-aziridinopyrrolo(1,2-a)indole 34 has been developed. Key features of this route include the deuterium kinetic isotope effect to block undesired indole lithiation during tin-lithium exchange from 27a to 30a, the intramolecular Michael addition to generate the enolate 31a, and conversion into 34 by trapping with phenylselenenyl chloride. Reductive cleavage of the N-trityl group in 34 allows access to tetracyclic aziridinomitosenes containing the aziridine N-H subunit. Reduction of the C(9) ester in 34 with LAH gives the primary alcohol 35 with the correct C(9), C(9a), C(10) oxidation state corresponding to the aziridinomitosenes, and deprotection of 34 affords 37.     

Michael addition of phenylacetonitrile to the acrylonitrile group leading to diphenylpentanedinitrile. Structural data and theoretical calculations

Knoevenagel condensation of phenylacetonitrile with 4-diphenylaminophenylacetonitrile in the presence of piperidine was carried out to obtain a novel conjugated compound. In addition to the expected compound 2-(phenyl)-3-(4-diphenylaminophenyl)acrylonitrile (I), the 3-((4-diphenylamino)phenyl)-2,4-diphenylpentanedinitrile (II) was also obtained with a good yield. Compound II was obtained as a result of the Michael addition of phenylacetonitrile with 2-(phenyl)-3-(4-diphenylaminophenyl)acrylonitrile (I). Conversely, when the same reaction was performed in the presence of KOH as catalyst, only the α,β-unsaturated nitrile (I) was afforded with a 92 % yield. The structures were confirmed with IR, EI-MS and NMR spectroscopy. Single crystals I and II were formed and their structures were determined by X-ray single-crystal diffraction analysis. Crystal I belongs to the monoclinic system with space group P2₁/n having unit cell parameters of a = 16.8589(5) Å, b = 6.68223(17) Å, c = 19.8289(7) Å, β = 111.133(4)○ and Z = 4. Crystal II belongs to the same monoclinic system with space group P2₁/c, having unit cell parameters of a = 10.8597(4) Å, b = 24.7533(10) Å, c = 9.7832(4) Å, β = 91.297(3)○ and Z = 4. In addition to the structural data analysis, some theoretical calculations that reveal the nature of relevant structure-property relationships are also reported.     

Probing the reactivity of nebularine N1-oxide. A novel approach to C-6 C-substituted purine nucleosides

A novel approach to the synthesis of purine nucleoside analogues, featuring the reaction of the C6-N1-O⁻ aldonitrone moiety of 9-ribosyl-purine (nebularine) N1-oxide with some representative dipolarophiles, as well as Grignard reagents, is reported. Addition of Grignard reagents to the electrophilic C-6 carbon of the substrate allows a facile access to C-6 C-substituted purine nucleosides without using metal catalysts. 1,3-Dipolar cycloaddition processes lead to novel nucleoside analogues via opening, degradation or ring-enlargement of the pyrimidine ring of the base system of the first-formed isoxazoline or isoxazolidine cycloadduct.     

Synthesis and properties of the first representatives of terminal acetylenes in 3-imidazoline-1-oxyl 3-oxide series

Method for the synthesis of m-and p-isomers of 4-[2-(ethynylphenyl)vinyl]-2,2,5,5-tetramethyl-3-imidazoline-1-oxyl 3-oxides by the cross-coupling of 4-[2-(3-iodophenyl)vinyl]-and 4-[2-(4-iodophenyl)vinyl]-2,2,5,5-tetramethyl-3-imidazoline-1-oxyl 3-oxides with (trimethylsilyl)acetylene followed by desilylation was elaborated. The reactions at the CH-fragment of the ethynyl group were performed. The Mannich reaction proceeds with the loss of a spin label, whereas the oxidative homocoupling, with its retention. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 10, pp. 2051–2054, October, 2007.     

Synthesis and reactivity of 3-aralkoxy-4-imino-imidazolidin-2-ones: a novel class of 4-iminohydantoins

Reactions of diethylphosphonoalkyl α-aminonitriles with 1,1′-carbonyl-diimidazole or 1,1′-carbonyl-di-(1,2,4-triazole) and O-substituted hydroxylamines under acidic conditions gave 3-alkoxy-4-imino-imidazolidin-2-ones, whereas in presence of triethylamine 4-alkoxy(aralkoxy)imino-imidazolidin-2-ones were formed.     

A novel and practical method for the synthesis of dinotefuran through Michael addition of nitromethane to diethyl maleate

A novel and practical synthesis of dinotefuran 1, featuring a new access to it from known key intermediate (tetrahydrofuran-3-yl)-methanamine 5, has been achieved through Michael addition reaction of nitromethane to diethyl maleate in 6 steps with 45.5% total yield. This synthesis is scalable and hence has high potential for application to further synthetic elaboration on such new neonicotinoid insecticide dinotefuran 1.     

Synthesis and liquid crystalline properties of novel compounds containing a 3-fluoro-4-cyanophenoxy group

A series of novel compounds containing a 3-fluoro-4-cyanophenoxy group were synthesized and fully characterized by IR and ¹H NMR, and their mesomorphic properties were studied. Seven compounds exhibited enantiotropic nematic phases and three compounds exhibited monotropic nematic phases, as confirmed by differential scanning calorimetry and polarizing optical microscopy. Selected properties of the liquid crystalline compounds synthesized were calculated by ab initio methods at a HF/6-31G level. The bond lengths, bond angles and dihedral angles of the fragments with the same structure change little between the compounds. All the compounds with a terminal alkoxy chain approached a planar structure.     

Synthesis, reactivity and applications of 1-fluoroalkyl carboxylates: novel synthetic substrates for esterases and lipases

A series of 1-fluoroalkyl carboxylate derivatives was synthesised by reacting a carboxylic acid and a ketone or aldehyde with (diethylamino)sulfur trifluoride (DAST). The reactivity of these compounds towards the nucleophiles benzylamine and water was investigated. The hydrolysis of the 1-fluoroalkyl carboxylates by an esterase was observed, along with the concomitant release of the fluoride ion, demonstrating the potential for a new esterase assay platform. Other applications may include a detectable in situ inhibitor synthesis protocol.     

Synthesis and chemical reactivity of the novel 3-chloro-3-(4-chlorocoumarin-3-yl)prop-2-enal

Vilsmeier-Haack formylation of 3-acetyl-4-hydroxycoumarin (1) afforded the unexpected 3-chloro-3-(4-chlorocoumarin-3-yl)prop-2-enal (3). Compound 3 reacted with p-toluidine and benzylamine producing Schiff base 4 and enamine 6, respectively. Treatment of compound 3 with hydrazine hydrate produced bis-coumarin 15 which upon treating with hydrazine hydrate afforded bis chromeno[4,3-c]pyrazole derivative 16. Compound 3 reacted with cyanoacetohydrazide under different conditions. Condensation of compound 3 with some heterocyclic amines and 1,2-N,N-binucleophiles was studied. Structures of the new synthesized products were deduced on the basis of their analytical and spectral data.     

Synthesis and reactivity of some 6-substituted-2,4-dimethyl-3-pyridinols, a novel class of chain-breaking antioxidants

The synthesis and study of a series of 6-substituted-2,4-dimethyl-3-pyridinols having interesting antioxidant properties is reported. The general synthetic strategy leading to the compounds involved a low-temperature aryl bromide-to-alcohol conversion as the last step. 2,4-dimethyl-3-pyridinol (1a), 2,4,6-trimethyl-3-pyridinol (1b), and 2,4-dimethyl-6-(dimethylamino)-3-pyridinol (1d) were thus prepared from the corresponding 3-bromopyridine precursor. The methoxy derivative 2,4-dimethyl-6-(methoxy)-3-pyridinol (1c) was also prepared by an alternate route via a Baeyer-Villiger reaction on the substituted benzaldehyde precursor. Novel bicyclic pyridinols 2 and 3 required prior construction of the ring structure. Thus, 2 was prepared by the use of a 6-step intramolecular Friedel-Crafts strategy, and 3 required an 11-step sequence with a thermolytic intramolecular inverse-demand Diels-Alder reaction between a pyrimidine ring and an alkyne as the key step. Basicities of the pyridinols approached physiological pH with increasing electron density in the ring. Pyridinols 1a-d were found to be indefinitely stable to air oxidation while 2 and 3 decomposed upon extended exposure to the atmosphere. The reactivities of the pyridinols toward chain-carrying peroxyl radicals in homogeneous organic solution were examined by studying the kinetics of radical-initiated styrene autoxidations under controlled conditions. These experiments revealed that some of the newly synthesized pyridinols are the most effective phenolic chain-breaking antioxidants reported to date.     

Semicarbazones from N-hydroxyureas and amines: a novel entry in the reactivity of the acyl nitroso group

The condensation of carbamoyl nitroso compounds, obtained by oxidation of N-hydroxyureas, with amines unexpectedly afforded semicarbazones (aka carbamoyl hydrazones). Although the substitution of the nitrosyl moiety might compete to afford the corresponding urea, an excess of amine led to the semicarbazone as the major product, which is presumably formed via isomerization of an initially generated acyl azo compound.     

Michael addition of dimedone with α,β‐unsaturated ketones: Synthesis of quinoline and chromene derivatives

A series of quinoline and chromene derivatives has been synthesized by Michael addition of dimedone 1 with 2‐aroyl‐3‐arylacrylonitrile 2 and study of absorption and fluorescence maxima of quinolines.