Arylnitrile Oxides Research Articles

Carbohydrate-based spiro bis(isoxazolines): synthesis and evaluation in asymmetric catalysis

Two carbohydrate-based spiro bis(isoxazolines) were synthesized via 1,3-dipolar cycloaddition from peracetylated methylene exo-glucal and the corresponding bis(arylnitrile oxide). The bis(cycloadducts) were then evaluated as ligands for enantioselective catalytic reactions. The Pd-catalyzed Tsuji–Trost reaction between a malonate and an allylic acetate did not provide good results. The poor conversion observed can be attributed to the rearrangement of the ligand in the reaction mixture to afford the corresponding ring-opened isoxazole which has been characterized. Both ligands were also evaluated in Cu(I)-catalyzed asymmetric imine alkynylation and afforded the product in good yield and modest enantioselectivity.

Reactivity of Arylnitrile Oxides and C-Aroyl-N-phenylnitrones with 3-Methylenedihydro-(3H)-furan-2-one and Itaconic Anhydride

1,3-dipolar cycloaddition is a powerful route for the synthesis of five-membered heterocycles. The [3+2] cycloadditions of some alpha-methylene-gamma-buryrolactones, namely 3-methylenedihydro-(3H)-furan-2-one (1) and itaconic anhydride (2) were Studied. Their reactions with arylnitrile oxides (3) and Caroyl-N-phenylnitrones (7) proceed with complete regioselectivity. From a stereochemical point of view, the addition of arylnitrile oxides (3) leads to the unique spiroheterocycles (4-5). Actually, a single stereocenter is generated during the reaction. In the particular case of p-nitrophenylnitrile oxide (3d), only the diacidic form (10d) of the spiroheterocyle (5d) was isolated. In contrast, the addition of C-aroyl-N-phenylnitrones (7) produces a couple of diastereoisomers. since two stereocenters are generated simultaneously. Nevertheless, the reaction is regioselective and stereospecific leading also to the single spiroheterocycles (1920). The proposed stereochemistry of spiranic compounds (19d) and (20d) has been corroborated by two single crystal X-ray crystallographic analysis.

3-Arylisoxazolyl-5-carboxylic acid and 5-(Hydroxymethyl)-3-aryl-2-isoxazoline as molecular platforms for liquid-crystalline materials

The synthesis of the molecular platform for liquid-crystalline materials based on 3-arylisoxazolyl-5-carboxylic acid (1) and 5-(hydroxymethyl)-3-aryl-2-isoxazoline (2) is described. The key intermediates 1 and 2 are obtained by [3+2] 1,3-dipolar cycloaddition reaction between an arylnitrile oxide and an acrylic acid and allylic alcohol as the dipolarophile. The liquid crystals (LC) compounds are synthesized through a "molecular elongation strategy" from the initial isoxazolinic core by connecting the arylacetylene moiety obtained from the Sonogashira reaction. Under these conditions, the series of liquid crystals 5a-c, 6, 7a-g and 8a-d have been successfully synthesized in fair to good yields. The final compounds display nematic and smectic liquid-crystalline properties. The structural properties of the series of the liquid crystals has been studied using DFT methods at level B3LYP/6-31G(d,p). The equilibrium geometries in the gas phase are presented and analyzed.

Synthesis and structure characterization of new 1,2,4-oxadiazolo[4,5-d]-1,5-benzothiazepines derivatives containing 2-phenyl-1,2,3-triazole through 1,3-dipolar cycloaddition reaction

Reaction of 1,5-benzothiazepines, containing 2-phenyl-1,2,3-triazole 2a-d, with aryl nitrile oxides in CH2 Cl2 at room temperature leads to a series of novel 1,2,4-oxadiazolo[4,5-d]-1,5-benzothiazepine derivatives 3a-l in good yields. The products were characterized by IR, 1H NMR, MS, elemental analyses, X-ray and their spectrum characters were discussed.

Asymmetric Lewis acid-catalyzed 1,3-dipolar cycloadditions

Abstract Highly tuned, one-point binding chiral iron and ruthenium complexes selectively coordinate and activate α,β-unsaturated aldehydes and ketones toward asymmetric catalytic Diels-Alder cycloaddition reactions. Here we focus on the application of these transition-metal Lewis acids to asymmetric catalytic 1,3-dipolar cycloaddition reaction between enals and cyclic and acyclic nitrones as well as aryl nitrile oxides to give isoxazolidines and isoxazolines, respectively.

Synthesis of Isoxazolinylxanthines

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Spiroheterocycles from the Reaction of Arylnitrile Oxides with Some (Z)‐3‐Arylidene‐2(3H)‐benzofuranones. New Access to Orthohydroxyphenylisoxazoline Esters.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Chiral ruthenium Lewis acid-catalyzed nitrile oxide cycloadditions

The synthesis of the chiral ligand ( R, R)-BIPHOP-F is detailed. Its coordination to a cationic cyclopentadienyl ruthenium fragment generates [Ru (acetone)( R, R)-BIPHOP-F)Cp][SbF 6], a transition metal Lewis acid that catalyzes the [3+2] dipolar cycloaddition reaction between aryl nitrile oxides and α,β-unsaturated aldehydes to give chiral 2-isoxazolines with yields of 43–98% and asymmetric purity of 60–93% ee. The stereochemistry of the major enantiomer is S, consistent with an approach of the nitrile oxide to the C α- Si face of the enal in the anti- s- trans conformation in the catalyst site.

Synthesis of isoxazolinylxanthines

1-[5-(3-Arylisoxazolin-2-yl)methyl]-3,7-dimethylxanthines have been synthesized by the [2+3] cycloaddition of arylnitrile oxides to allyltheobromine. 7-{5-[3-(2,4-Dichlorophenyl)isoxazolin-2-yl]methyl}-1,3-dimethylxanthine was obtained by the addition of 2,4-dichlorobenzonitrile oxide to allyltheobromine. The addition of arylnitrile oxides to structural isomers of methylxanthines proceeds regioselectively with the formation of 3,5-disubstituted isoxazolines.

Spiroheterocycles from the Reaction of Arylnitrile Oxides with Some (Z)-3-Arylidene-2(3H)-benzofuranones. New Access to Orthohydroxyphenylisoxazoline Esters

Some 4-substituted arylnitrile oxides and (Z)-3-arylidene-2(3H)-benzo-furanones undergo 1,3-dipolar cycloaddition reactions to give exclusively spirodihydroisoxazoles. These spiroadducts have be opened to the corresponding ethyl 3,4-diaryl-5-(orthohydroxyphenyl)-4,5-dihydroisoxazoline-5-carboxylates by the action of concentrated hydrochloric acid at reflux in ethanol.

An efficient one-step regiospecific synthesis of novel isoxazolines and isoxazoles of N-substituted saccharin derivatives through solvent-free microwave-assisted [3+2] cycloaddition

Novel isoxazolines and isoxazoles of N-substituted saccharin derivatives are synthesized in good yields by 1,3-dipolar cycloaddition of N-allyl or propargyl N-substituted saccharin with arylnitrile oxide under solvent-free microwave irradiation. In this process, the yields were significantly improved over conventional heating, without alteration of the selectivity. The regioselectivity as well as the nonthermal specific microwave effect are discussed.

1,3-Dipolar cycloaddition reactions on carbohydrate-based templates: synthesis of spiro-isoxazolines and 1,2,4-oxadiazoles as glycogen phosphorylase inhibitors

1,3-Dipolar cycloaddition of aryl nitrile oxides to benzyl/acetyl-protected exo-glucals and to a benzoylated glucosyl cyanide led in high yield to spiro-isoxazolines and to 3-aryl-5-glucosyl-1,2,4-oxadiazoles, respectively. The choice of the protective groups was important to the outcome of the cycloaddition and for the deprotection of the adducts. Cleavage of the ester protecting groups (acetyl, benzoyl) provided water-soluble spiro-isoxazolines and 3-aryl-5-glucosyl-1,2,4-oxadiazoles, evaluated as glycogen phosphorylase inhibitors. Preliminary tests showed IC 50 values in the μM range.

Novel synthesis of 3,4-diarylisoxazole analogues of valdecoxib: reversal cyclooxygenase-2 selectivity by sulfonamide group removal.

3,4-Diarylisoxazole analogues of valdecoxib [4-(5-methyl-3-phenylisoxazol-4-yl)-benzensulfonamide], a selective cyclooxygenase-2 (COX-2) inhibitor, were synthesized by 1,3-dipolar cycloaddition of arylnitrile oxides to the enolate ion of phenylacetone regioselectively prepared in situ with lithium diisopropylamide at 0 degrees C. The corresponding 3-aryl-5-methyl-4-phenylisoxazoles were easily generated by a dehydration/aromatization reaction under basic conditions of 3-aryl-5-hydroxy-5-methyl-4-phenyl-2-isoxazolines and further transformed into their benzenesulfonamide derivatives. The biochemical COX-1/COX-2 selectivity was evaluated in vitro by using the human whole blood assays of COX isozyme activity. Three compounds not bearing the sulfonamide group present in valdecoxib were selective COX-1 inhibitors.

Synthesis and Binding Properties of Chiral Macrocyclic Barbiturate Receptors: Application to Nitrile Oxide Cyclizations.

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Synthesis and binding properties of chiral macrocyclic barbiturate receptors: application to nitrile oxide cyclizations

A series of chiral macrocyclic receptors containing a barbiturate binding domain based on two 2,6-diaminopyridine groups has been synthesized with the purpose of exploiting these for asymmetric 1,3-dipolar cycloadditions. Each macrocyclic host was built possessing an (R)-BINOL or a modified deoxycholate moiety as the chiral unit connected to the barbiturate binding domain with varying lengths of spacer. All the hosts with the exception of one were found to effectively bind a barbiturate–cinnamic acid conjugate with association constants in the order of 104 M−1 in CDCl3. The 1,3-dipolar cycloaddition between several arylnitrile oxides and the cinnamate conjugates were examined in the presence of stoichiometric amounts of a chiral receptor affording two regioisomeric isoxazolines. Enantiomeric excesses of up to 30% were obtained in one case for the major regioisomer. In most cases, the enantiomeric excesses could be measured directly from the crude 1H-NMR spectra owing to the diastereomeric interaction between the isoxazoline cycloadduct and the chiral receptor. The relatively low enantiofacial selectivities at the CC double bond of the cinnamate were attributed to the non-planar orientation of the barbiturate–cinnamate conjugate with respect to the receptor, as previously noted for the binding of barbital to an achiral macrocyclic host (S.-K., Chang, E. Fan, D. Van Engen and A. D. Hamilton, J. Am. Chem. Soc., 1991, 113, 7640), directing the cinnamate unit away from the chiral unit.

Regioselective synthesis and side-chain metallation and elaboration of 3-aryl-5-alkylisoxazoles

A number of 3-aryl-5-alkylisoxazoles have been synthesized in high yields by reacting arylnitrile oxides with free enolate ions regioselectively obtained by metallation of various alkyl methyl ketones with LDA in THF at −78°C followed by dehydration. Investigations concerning regioselective side-chain metallation and elaboration of one of them (3-phenyl-5-ethylisoxazole) have also been carried out.

A new route to C-aryl glycosides.

[reaction: see text] A six-step route for de novo synthesis of C-aryl glycosides based on cycloaddition of an aryl nitrile oxide with 4-pentyn-2-ol has been developed.

A novel resin-bound CF 3-containing building block: application to the solid-phase synthesis of CF 3-containing acrylates and 4-isoxazolecarboxylates

A novel resin-bound CF 3-containing building block ( 3) was prepared. Stereospecific Suzuki cross-coupling of compound 3 with a variety of aryl boronic acids gave the corresponding resin-bound coupling products ( 4), which can be cleaved with sodium methoxide to afford methyl ( E)-3-aryl-4,4,4-trifluoro-2-butenoate ( 5). 1,3-Dipolar cycloaddition of compound 3 with aryl nitrile oxides followed by cleavage with TFA led to methyl 3-aryl-5-trifluoromethyl-4-isoxazolecarboxylate regioselectively, which was determined by 19 F NMR analysis.

1,3-Dipolar Cycloaddition Reaction of Nitrile N-Oxides to 6-(2-Phenylethenyl)fulvene

Dipolar cycloaddition reactions of aryl nitrile oxides to 6-(2-phenylethenyl)fulvene leading to isoxazolines are described.

A novel approach to bis-isoxazolines using a latent form of cyclopentadienone

We describe the synthesis of a range of both racemic and homochiral 4-alkyl- and 4-aryl-8-hydroxy-2-oxa-3-azabicyclo[3.3.0]oct-3-en-6-ones (isoxazolines) from the 1,3-dipolar cycloaddition reactions between alky- and aryl-nitrile oxides and 4-alkoxycyclopent-2-enones. Elimination of the 8-hydroxy group and subsequent additional cycloaddition reactions provided 5,9-disubstituted-3,11-dioxa-4,10-diazatricyclo[6.3.01,8.02,6]undeca-4,9-dien-7-ones (bis-isoxazolines) formally derived from cyclopentadienone.