Stereoselectivity of 1,3-dipolar cycloadditions of l-valine-derived nitrones with methyl acrylate

Chiral nitrones derived from l-valine react with methyl acrylate to afford the corresponding diastereomeric 3,5-disubstituted isoxazolidines. The dibenzylsubstituted nitrone gave also 3,4-disubstituted isoxazolidine in 4% yield, additionally. The stereoselectivity was dependent on the steric hindrance of the nitrone and reaction conditions. High pressure decreased the reaction time of the cycloadditions. The major products were found to have the C-3/C-6 erythro and C-3/C-5 trans relative configuration. The major cycloadduct undergoes N-O cleavage and deprotection to a chiral diaminodiol derivative.     

A convenient synthesis of new enantiomerically pure trihydroxypyrrolizidines using l-erythrose glycosylhydroxylamine as a masked acyclic chiral nitrone

A route has been developed for the synthesis of enantiomerically pure trihydroxylated pyrrolizidines starting from l-erythrose glycosylhydroxylamine. The latter acts as a masked acyclic nitrone and reacts diastereoselectively from its Re-face with methyl acrylate to give the corresponding isoxazolidines, which after reductive N-O cleavage are recyclized to trihydroxypyrrolizidines via a Mitsunobu condensation.     

Synthesis of novel 3′-spirocyclic-oxindole derivatives and assessment of their cytostatic activities

The synthesis of some novel 3′-spirocyclic-oxindole compounds, based on the spiro[indole-3,5′-isoxazolidin]-2(1H)-one, the 2′H-spiro[indole-3,6′-[1,3]oxazinane]-2,2′(1H)-dione and the 2′H-spiro[indoline-3,3′-pyrrolo[1,2-c][1,3′]oxazine]-1′,2(1H)-dione heterocyclic structures, is described. These compounds were prepared from methyl α-(2-nitrophenyl)acrylate via [1,3]-dipolar cycloaddition reactions with two acyclic nitrones and one cyclic nitrone followed by reduction of the cycloadducts and then treatment with triphosgene. Two of these compounds showed significant cytostatic activity on three cancer cell lines with GI₅₀ values of 2.6-4.1 μM on the human breast cancer cell line, MCF-7.     

Synthetic transformations of higher terpenoids: XXXII. Synthesis of 16-alkenyl-substituted labdatrienes by oxidative coupling of methyl phlomisoate with alkenes

Reactions of methyl phlomisoate with methyl acrylate, phenyl acrylate, methyl vinyl ketone, phenyl vinyl ketone, or N-substituted acrylamides catalyzed by Pd(OAc)₂ in the presence of Cu(OAc)₂, p-benzoquinone in the mixture of propionic acid and acetonitrile proceed regio- and stereoselectively with the formation of (E)-16-vinyl labdatrienoates. The oxidative coupling under these conditions of the methyl phlomisoate with styrene results in a mixture of 15,16-distyryl-, 16-styryl-, and 16-(1-phenylvinyl)-derivatives of furanolabdanoid.     

Stereoregularity of poly(methyl acrylate)

The stereoregularity of poly(methyl acrylate) and poly(methyl acrylate-αd) was determined from the NMR spectra. A method of quantitative determination of stereoregularity of poly(methyl acrylate) proposed in this paper is based on the fact that in the 100 Mc./sec. NMR spectrum the absorption peaks due to methylene protons in syndiotactic configurations overlap absorptions due to only one of two methylene protons in isotactic configurations. The stereostructure of poly(methy1 acrylates) polymerized with anionic catalysts such as Grignard reagents, n-butyllithium, and LiAlH₄ is generally richer in isotactic diads than in syndiotactic diads. For example, poly(methyl acrylate) polymerized with phenylmagnesium bromide as catalyst at ?20°C. consists of 99% isotactic and 1% syndiotactic diads. In radical polymerization, the isotacticity of poly(methyl acrylate) is independent of polymerization temperature. Poly(methyl acrylates) polymerized with a Ziegler-Natta catalyst consisting of Al(C₂H₅)₂Cl and VCl₄ have configurations similar to those polymerized by radical initiators. The stereoregularity of poly(methyl acrylate-α-d) resembled that of poly(methyl acrylate) polymerized under the same conditions.     

Organometallic gold(III) and gold(I) complexes as catalysts for the 1,3-dipolar cycloaddition to nitrones: synthesis of novel gold-nitrone derivatives

Gold(III) and gold(I) anionic salts mediate the 1,3-dipolar cycloaddition of N-benzyl-C(2-pyridyl)nitrone (2-PyBN) (1) and methyl acrylate (2) (gold 5-10 mol% with respect to the nitrone) decreasing the reaction time and favouring the formation of the exo (cis) isomer. The best catalyst found was Na[AuCl₄] (7) able to perform the addition reaction in 56 h (instead of the 96 h required for the control experiment) and giving an endo/exo relation between isomers of 44/56 (as opposed to 73/27, blank reaction). The catalytic activity of several organometallic gold complexes with the radicals pentafluorophenyl (C₆F₅) or mesityl (2,4,6-(CH₃)₃C₆H₂) has been also investigated. In some cases the activity is very similar to that obtained with inorganic salts. With the aim of identifying possible metallic intermediates in the cycloaddition reaction, novel gold(III) and gold(I) nitrone derivatives such as [Au(C₆F₅)Cl₂(2-PyBN)] (21), [Au(C₆F₅)₂Cl(2-PyBN)] (22) and [Au(C₆F₅)(2-PyBN)] (23) have been prepared and characterized. The reaction between [AuCl₃(tht)] and 2-PyBN unexpectedly affords the ionic compound [2-PyBN-H][AuCl₄] (5) which also displays catalytic activity and moderate regioselectivity and whose crystal structure has been confirmed by X-ray studies.     

Synthesis of a difluorinated carbasugar from d-ribose via intramolecular nitrone cycloaddition reaction

Difluorinated carbasugar 3 has been synthesised from d-ribose via an intramolecular nitrone cycloaddition reaction with an overall yield of 22%.     

Reactions of diazo ketones with activated unsaturated compounds in the presence of gallium trichloride

Diazoacetone reacts with methyl acrylate in the presence of anhydrous GaCl₃ to give isomeric methyl 2-acetylcyclopropanecarboxylates rather than pyrazolines obtained from diazo esters or by noncatalytic reactions. In a similar reaction, diazoacetophenone yields methyl 2-benzoylcyclopropanecarboxylates, benzoylmethyl acrylate, and benzoylmethyl 2-benzoylcyclopropanecarboxylate via partial transesterification. Addition of an equimolar amount of GaCl₃ to diazoacetone in the system CH₂Cl₂-HCl-H₂O unexpectedly produces 4,5-dimethylfuran-3(2H)-one and 1,1′-oxybis(propan-2-one).     

Tetraphenylantimony carboxylates in the cascade Pd-catalyzed C-phenylation reaction of methyl acrylate in the presence of peroxide

Tetraphenylantimony(V) carboxylates have been used in the palladium-catalyzed C-phenylation reaction of methyl acrylate in the presence of (PhCO₂)₂ or t-BuOOH under mild conditions (50 °C). The peroxides promote a cascade participation of the organoantimony compound and result in the transfer of three phenyl groups. Organoantimony intermediates have been isolated from the reaction.     

Effect of monomer/nanoclay interaction on the kinetics of atom transfer radical homo- and copolymerization of styrene and methyl acrylate

Atom transfer radical homo- and copolymerization of styrene and methyl acrylate initiated with CCl₃-terminated poly(vinyl acetate) macroinitiator were performed at 90°C in the presence of nanoclay (Cloisite 30B). Controlled molecular weight characteristics of the reaction products were confirmed by GPC. It was shown that nanoclay slightly decreased the rate of styrene polymerization, while it significantly enhanced the rate of methyl acrylate polymerization and its copolymerization with styrene. The reactivity ratios of the monomers in the presence and in the absence of nanoclay were calculated (r _St = 1.002 ± 0.044, r _MA = 0.161 ± 0.018 by extended Kelen-Tudos method and r _St = 1.001 ± 0.038, r _MA = 0.163 ± 0.016 by Mao-Huglin method), confirming that the presence of nanoclay has no influence on monomer reactivity. The enhancement in the homopolymerization rate of methyl acrylate as well as its copolymerization rate with styrene was attributed to nanoclay effect on the dynamic equilibrium between active (macro)radicals and dormant species. Dipole moments of the monomers were successfully used to predict structure of the polymer/clay nanocomposites prepared via in situ polymerization.     

Interactions of aluminum(III) with the biologically relevant ligand d-ribose

Aluminum(III) can be absorbed when it is appropriately complexed. There are several plasma components which can bind weakly Al(III). Many proteins bind Al(III) in solution quite strongly. Carbohydrates bearing an abundance of electronegative functional groups can interact with metal cations. In solution, d-ribose exists as a mixture at equilibrium of many isomers and only a few of them bear a ‘complexing’ sequence of the hydroxyl groups. The presence of d-ribose in an Al(III) solution experiences a decrease of its Brönsted-acid sites. The lowering of the Brönsted acidity of an Al(III)-d-ribose mixture suggests the existence of attractive interactions (‘association’) between Al(III) ion and the complexing sequence of the hydroxyls of d-ribose. There is enhancement in the stability of the interaction complexes between Al(III) and d-ribose through strong intramolecular hydrogen bonding, which offers the possibility to investigate the kinetics of the subsequent proton release reactions. On the basis of the kinetic results, it may be concluded that proton release reactions, which are associated with the complexation reactions, are associatively activated. The complexes (Al(H₂O)_6−n(d-ribose_−nH)⁽³⁻ⁿ⁾⁺) resulting from the various ‘complexing’ forms of d-ribose are formed at mainly acidic pH. As the pH increases, the values of the activation enthalpy, ΔH^≠, are changing, because of the formation of mixed hydroxo-complexes (Al(H₂O)_6−n−m(OH)_m(d-ribose_−nH)^(3−n−m)+); finally, OH⁻ displaces d-ribose from the coordination sphere of Al(III) in a rather slow process, i.e. with high values of ΔH^≠; the activation enthalpy values, ΔH^≠, decrease with the progression of the displacement, becoming finally very small due to the formation of a precipitate. Chelate coordination of d-ribose with some divalent and trivalent metal ions has been also reported.     

Concise synthesis of zanamivir and its C4-thiocarbamido derivatives utilizing a [3+2]-cycloadduct derived from d-glucono-δ-lactone

A concise synthesis of zanamivir (GG167, 1) has been accomplished utilizing the adduct of a highly diastereoselective 1,3-dipolar cycloaddition between methyl acrylate and the nitrone derived from d-glucono-δ-lactone. Azide-free introduction of C4 nitrogen functionality and one-pot selective O-acetylation followed by straightforward generation of dihydropyran moiety are two advantages in this synthesis. Using the established methodology and common intermediate, two representative C4-thiocarbamido derivatives of zanamivir were also synthesized.     

Preparation,polymerization and copolymerization of some unsaturated dibutyltin carboxylates

Dibutylchlorotin acrylate (DBCTA), dibutylchlorotin methyl maleate (DBCTM) and dibutylchlorotin cinnamate (DBCTC) were prepared by metathesis reactions between equimolar proportions of dibutyltin dichloride and the corresponding dibutyltin dicarboxylate. The acrylate (DBCTA) was the only monomer to undergo free-radical homopolymerization and gave an insoluble cross-linked polymer of poly(dibutyltin diacrylate) with the expulsion of dibutyltin dichloride. Free-radical copolymerization with methyl acrylate (MA) gave copolymers with DBCTA and DBCTC. The reactivity ratios were respectively: MA, r₁ = 0.81 ± 0.05; DBCTA, r₂ = 0.08 ± 0.04 and MA, r₁ = 2.0 ± 0.35 DBCTC, r₂ = 0 ± 0.2. DBCTM did not copolymerize with methyl acrylate.Attempts at free-radical copolymerizations with vinyl chloride (VC) were only partially successful due to severe inhibition. DBCTM and DBCTC formed very low molecular weight copolymers containing approximately equal amounts of the comonomers. DBCTA copolymer with VC formed a copoly(dibutyltin diacrylate) network structure. However, solubility in acetic acid-d₄ due to an exchange equilibrium allowed an estimate of the reactivity ratio $\text{r}{}_{\mathrm{vc}}\text{≌ 0.17}$ to be obtained by NMR analysis.Three new tetrabutyl-1,3-di(carboxy) distannoxanes ([Bu₂SnOCOR]₂O) (R = CHCH₂; C(CH₃)CH₂ and CHCHC₆H₅) were prepared.     

Synthetic route towards (5R,2′S,5′S,6′S)-ribosyl-diazepanone,an analogue core of the liposidomycins

The synthesis of (5R,2′S,5′S,6′S)-ribosyl-diazepanone, an analogue core of liposidomycins is described. The core ribosyl seven-membered heterocycle of nucleoside antibiotic liposidomycins was formed by reductive amination of an α-ribosylamino ester derived from d-ribose, and an amino aldehyde derived from methyl 4-triisopropylsilyloxy-3-oxobutanoate, followed by a peptidic coupling reaction.     

Stereoregularity of radically polymerized poly(alkyl acrylates) and poly(trimethylsilyl acrylates) and the preparation of syndiotactic poly(methyl acrylate)

Nuclear magnetic resonance (NMR) spectroscopy was used to determine the stereoregularity of radically polymerized poly(ethyl acrylates), poly(trimethylsilyl acrylates), and poly(isopropyl acrylate-α,β-d₂). The ethyl acrylate polymers consisted of a random configuration having about 50% of isotactic diads, and their stereoregularities were independent of the polymerization temperature (40 to ?78°C). Poly(trimethylsilyl acrylates) and poly(isopropyl acrylate-α,β-d₂) prepared at low temperatures had a syndiotactic configuration. Syndiotactic poly(methyl acrylate) was derived from syndiotactic poly(trimethylsilyl acrylate). For poly(methyl acrylate), an approximate estimation of the stereoregularity by infrared spectroscopy was proposed.     

Organometallic polymers. XVI. Copolymerization of styrenetricarbonylchromium and the reaction of polystyrene with chromium hexacarbonyl

Styrenetricarbonylchromium (IV) has been synthesized. Monomer IV did not homopolymerize with free-radical initiation but copolymerized with styrene, methyl acrylate, and vinylcymantrene. The copolymerizations were carried out in benzene solutions at 70°C with azobisisobutyronitrile as the initiator. The relative reactivity ratios were determined for the styrene and methyl acrylate copolymerizations. They were (defining M₁ as monomer IV) r₁ ? 0, r₂ ? 1.39 for styrene copolymerizations and r₁ ? 0, r₂ ? 0.75 for methyl acrylate copolymerization. Polystyrene reacted with chromium-hexacarbonyl in refluxing DME to produce a polymer in which about 32% of the benzene rings were complexed with ? Cr(CO)₃ units. The use of a polystyrene of narrow molecular weight distribution in this reaction demonstrated that no decomposition of the polystyrene chains occurred.     

rac-BINAP-PdCl2 catalyzed Heck reactions of 3-formylquinolin-2-yl chlorides with methyl acrylate: synthesis of methyl 3-(3-formylquinolin-2-yl) acrylates

rac-BINAP-PdCl₂ catalytic system catalyzed Heck reaction of 3-formylquinolin-2-yl chlorides with methyl acrylate in DMA is described to the synthesis of methyl 3-(3-formyl-quinolin-2-yl)-acrylates, in good to excellent yields. The reaction could be also extended with other activated alkenes to afford Heck products. Fused-benzene ring in heterocyclic and carbocyclic moieties was found to enhance the yields.     

Effect of excess halide on the palladium‐catalyzed insertion‐triggered radical copolymerization of methyl acrylate and 1‐hexene

[Pd₂(μ‐Cl)₂(C₆F₅)₂(tht)₂] ( 1 ) is a very efficient initiator of the radical polymerization of methyl acrylate, but it is not active in the polymerization of methyl methacrylate or in the copolymerization with 1‐hexene. The addition of an excess of NBu₄Cl to solutions of [Pd₂(μ‐Cl)₂(C₆F₅)₂(tht)₂] ( 1 ) provides an initiator system that copolymerizes methyl acrylate and 1‐hexene by an insertion‐triggered radical mechanism. Random copolymers are obtained with 11% incorporation of 1‐hexene in moderate yields (about 35%). Studies of the decomposition products obtained after the first insertion of methyl acrylate in the Pd? C₆F₅ bond of 1 show that the addition of excess halide in the presence of monomer favors the homolytic cleavage of the Pd? C bond, and the generation of the radicals that are active species in the polymerization, versus alternative evolution pathways. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 5682–5691, 2006     

Bismuth triflate-catalyzed rearrangement of acetates of the Baylis-Hillman adducts into (E)-trisubstituted alkenes

In the presence of a catalytic amount of bismuth triflate, methyl 3-acetoxy-3-aryl-2-methylenepropanoates and 3-acetoxy-3-aryl-2-methylenepropanitriles were smoothly converted into methyl (2E)-2-(acetoxymethyl)-3-arylprop-2-enoates and (2E)-2-(acetoxymethyl)-3-arylprop-2-enenitriles, respectively. A remarkable reversal in stereochemical directions from ester to nitrile was observed. 3-Aryl-3-hydroxy-2-methylenepropanoates and 3-aryl-3-hydroxy-2-methylenepropanitriles could be easily obtained as Baylis-Hillman adducts from methyl acrylate and acrylonitrile, respectively. The overall process is an efficient isomerization of the Baylis-Hillman adducts to the corresponding cinnamyl derivatives. The isomerization reaction proceeded rapidly and afforded smoothly the cinnamyl acetates in moderate to very good yields using catalytic amounts of Bi(OTf)₃·4H₂O (10 mol %).