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.     

Regioselective synthesis of novel spiroindane-1,3-diones through 1,3-dipolar cycloaddition reactions

A facile synthesis of novel spiroindane-1,3-diones has been achieved via 1,3-dipolar cycloaddition of an azomethine ylide, generated in situ from ninhydrin and 1,2,3,4-tetrahydroisoquinoline, with the conjugated double bond of chalcone derivatives. The regiochemistry and structures of the cycloadducts were determined with spectroscopic data and by X-ray crystal structure analysis.     

Three-Component Synthesis and 1,3-Dipolar Cycloaddition of Highly Functionalized Pyrans with Nitrile Oxides: Easy Access to 1,2,4-Oxadiazoles

Three-component reaction of 1-[(4-chlorophenyl)sulfanyl]acetone, malononitrile, and substituted aromatic aldehydes in the presence of sodium ethoxide under simple mixing at ambient temperature for 5–8 min afforded highly functionalized 4H-pyrans in good to excellent yields. 1,3-Dipolar cycloaddition of nitrile oxides over the nitrile functionality of the 4H-pyrans furnished 1,2,4-oxadiazoles in moderate yields.

Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications® for full experimental and spectral details.     

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.     

Diastereoselective synthesis of 2,3,4,5-tetrasubstituted isoxazolidines via 1,3-dipolar cycloaddition

The 1,3-dipolar cycloaddition reactions of α-2-methoxyaryl nitrones with nitrostyrenes and chalcones have been investigated. The regiochemistry and stereochemistry of the resultant cycloadducts have been determined with the help of NMR spectroscopy and X-ray analysis. β-Nitrostyrenes add to nitrones to give two geometrical isomers, while the β-methyl-β-nitrostyrene gives a single isomer in relatively low yield. The chalcones give a single cycloadduct upon 1,3-dipolar addition.     

Exploiting microwave-assisted neat procedures: synthesis of N-aryl and N-alkylnitrones and their cycloaddition en route for isoxazolidines

Microwave irradiation allows increasing the speed of several reactions and also offers the possibility of eliminating poisoning organic solvents. In this work we report the microwave-assisted neat synthesis of α-phenyl-tert-butylnitrone (PBN) and other alkyl and aryl nitrones and also the rapid synthesis of isoxazolidines resulting from 1,3-dipolar cycloaddition of nitrones to ethyl trans-crotonate.     

Convenient synthesis of isoxazolines via tandem isomerization of allyl compounds to vinylic derivatives and 1,3-dipolar cycloaddition of nitrile oxides to the vinylic compounds

A novel effective method for the synthesis of new isoxazolines via tandem isomerization of QCH(X)CHCH(Y) to QC(X)CHCH₂(Y) (Q = RO, RS, R₂N, R₃Si, etc.; X = H, R, OR; Y = H, R; R = alkyl, aryl) catalyzed by ruthenium complexes and 1,3-dipolar cycloaddition of the latter compounds to arenenitrile oxides is presented. The cycloaddition of QCH(X)CHCH(Y) to 2,6-dichlorobenzonitrile oxide is also described. The regio- and stereoselectivity of the cycloaddition of nitrile oxide to allyl and 1-propenyl (vinylic in general) compounds is discussed.     

1,3-Dipolar cycloaddition reaction of aryl nitrile oxides with alkenes using imidazole and pyridine containing reusable polymeric base catalysts

Cross-linked poly-1-(4-vinylbenzyl)imidazole and cross-linked poly-4-vinylpyridine have been prepared from respective vinyl monomers using different quantities of divinylbenzene as a cross-linker by radical polymerization. The polymeric bases were characterized by FT-IR, TGA, field emission-scanning electron microscopy (FE-SEM), and Brunauer-Emmett-Teller (BET) surface area analysis. Their swelling behavior was also studied. They were used as base catalysts for 1,3-dipolar cycloaddition reaction of aryl nitrile oxides, generated in situ from N-hydroxyimidoyl chloride, with N-phenylmaleimide and ethyl acrylate, to obtain 3-arylisoxazolines. Both the bases gave excellent results. These polymers were reusable, safe to use, and provided good alternative for organic nonreusable bases like pyridine and triethylamine which are hazardous.     

A stereoselective method for the synthesis of enantiopure 3-substituted 4-hydroxyproline derivatives via 1,3-dipolar cycloadditions

The stereoselective 1,3-dipolar cycloaddition between (Z)-1,4-dichloro-2-butene and a menthone-derived nitrone led to the corresponding isoxazolidine. Regioselective azidation of a single chlorine atom followed by another Cu(I)-catalyzed azide–alkyne 1,3-dipolar cycloaddition (CuAAC) induced enantiopure 1,2,3-triazolyl-functionalized isoxazolidines. The subsequent acidic cleavage of the menthone chiral auxiliary and reductive cleavage of the isoxazolidine N–O bond triggered an intramolecular cyclization through the displacement of the second chlorine. This rapid and stereoselective synthetic strategy provided reliable access to a series of enantiopure 3-substituted 4-hydroxyproline derivatives.     

Regioselective synthesis of 1,5-disubstituted 1,2,3-triazoles by 1,3-dipolar cycloaddition: Role of Er(OTf)3, ionic liquid and water

A simple procedure to obtain 1,5-disubstituted 1,2,3-triazoles, using the Er(OTf)₃/[mpy]OTf/H₂O catalytic system is described. The reaction proceeds through an eliminative azide–olefin cycloaddition (EAOC) offering a highly regioselective approach and good yields (81–94%). The advantages of this method include simple operations of work-up and the ability of the catalytic system to be re-used five times without an evident loss in yield. The role of IL and water were speculated, invoking also a probable ionic self-assembly (ISA) effect.     

Regioselectivity in the 1,3-dipolar cycloaddition of nitrile oxides to 3,3-methylene-5,5-dimethyl-2-pyrrolidinone

Summary Nitrile oxides add regioselectively to the carbon-carbon double bond of 3,3-methylene-5,5-dimethyl-2-pyrrolidinone (1), giving exclusively spiro-isoxazolines: 3-aryl-6-oxo-8,8-dimethyl-1-oxa-2,7-diazaspiro[4.4]non-2-enes3 a–l. The regiochemistry of the 1,3-dipolar cycloaddition to 1 seems to be controlled by the steric effect of the methyl groups at the ring junction and by frontier orbital interactions.Part XXV in the series 1,3-Dipolar Cycloaddition on Heterocycles. Part XXIV Ref. [10]     

Asymmetric 1,3-dipolar cycloaddition of nitrile oxides to chiral acryloyl esters bearing glucofuranose as auxiliary

Asymmetric 1,3-dipolar cydoaddition of nitrite oxides to an acryloyl ester (1) derived from 1,2:5,6-di-O-isopropylidene glucose (6) was studied. Solvent and temperature effect was discussed. The single diastereoisomer was isolated with high diastereoselective excess.     

Regioselective synthesis of 5-trifluoromethyl-1,2,3-triazole nucleoside analogues via TBS-directed 1,3-dipolar cycloaddition reaction

Herein described was a straightforward method for the highly regioselective synthesis of 5-trifluoromethyl-1,2,3-triazole nucleoside analogues, which featured the utilization of tert-butyldimethylsilyl (TBDMS) group as the directing group in the 1,3-dipolar cycloaddition reactions. 4-tert-Butyldimethylsilyl-5-trifluoromethyl-1,2,3-triazole nucleoside analogues were generated as the only cycloaddition products in moderate yields (15-79%) via the treatment of glycosyl azides with 3,3,3-trifluoro-1-tert-butyldimethylsilylpropyne 1 in toluene at 85 °C. Removal of TBS groups in these triazole cycloadducts with tetrabutylammonium fluoride (TBAF) smoothly afforded the various 5-trifluoromethyl-1,5-disubstituted 1,2,3-triazole nucleoside analogues in good yields (40-88%).     

Highly fluoroalkylated amphiphilic triazoles: Regioselective synthesis and evaluation of physicochemical properties

A series of fluoroalkylated amphiphilic 1,2,3-triazoles was synthesised by efficient 1,3-dipolar cycloaddition of 2-perfluoroalkyl-ethyl-azides, prepared from commercial 2-perfluoalkyl-1-iodoethanes, and acetylenic esters or acids. The synthesis was accomplished by heating in acetone or by microwave irradiation. Excellent regioselectivity was observed for dissymmetrical alkynes. Physicochemical study shows surfactant behaviour.     

Chemo- and Regioselective 1,3-Dipolar Cycloaddition of 2-Diazopropane over 1,4-Benzoquinone: Synthesis of New Pyrazoloquinones

Abstract

1,3-Dipolar cycloaddition reaction of 2-diazopropane 1 with 1,4-benzoquinone 2 carried out at ?20 °C led to a minor mono-cycloadduct 4 and mixture of bis-cycloadducts 6 and 7. The same addition realized with 3H-pyrazole 7 at ?60 °C for 2 h yields a mixture of compounds 8 and 9 and results in O-alkylation. The reaction of 3H-pyrazoles 4 and 7 with dimethylsulfoxide and oxalyl chloride under Swern conditions led to pyrazolenines 11 and 12.     

Domino addition of allylzinc bromide to nitrile oxides: synthesis of 5-butenylisoxazolines

Nitrile oxides undergo addition to allylzinc bromide to generate 5-butenylisoxazolines in good yields.     

A facile synthesis and highly atom economic 1,3-dipolar cycloaddition of hexahydropyrido[3,4-c][1,5]benzothiazepines with nitrile oxide: stereoselective formation of hexahydro[1,2,4]oxadiazolo[5,4-d]pyrido[3,4-c][1,5]benzothiazepines

A series of new 2-methyl-11-aryl-4-[(E)-arylmethylidene]-1,2,3,4,11,11a-hexahydropyrido[3,4-c][1,5]benzothiazepines were obtained by the reaction of o-aminothiophenol and (E)-1-methyl-3,5-bis(arylidene)-4-piperidones in the presence of a catalytic amount of acetic acid under solvent-free microwave irradiation. These dipolarophiles undergo a highly atom economic 1,3-dipolar cycloaddition with nitrile oxide to afford a series of novel 6-methyl-1-phenyl-8-aryl-4-[(E)-arylmethylidene]-4,5,6,7,7a,8-hexahydro[1,2,4]oxadiazolo[5,4-d]pyrido[3,4-c][1,5]benzothiazepines stereoselectively.     

1,3-Dipolar cycloadditions of heterocycles 1. Cycloadditions ofC-benzoyl-N-phenylnitrone to furan

A frontier orbital treatment of furan suggests its possible reactivity in 1,3-dipolar cycloadditions with dipoles posessing low lying LUMO's, such as nitrones, especially those with electronwithdrawing substituents. By the reaction ofC-benzoyl-N-phenylnitrone1a with an excess of furan at 60° the monocycloadduct2a, two biscycloadducts4 and5 and further reaction products of nitrone such as azoxybenzene8, diketoamide9a, benzoanilide10a, benzoic acid11a and phenyl glyoxylic acid12 were isolated. The cycloaddition ofC-(4-bromobenzoyl)-N-phenylnitrone1b with furan is also reported.Part CXXXVI in the series Furan Derivatives; Part CXXXV: Coll. Czech. Chem. Commun., in press.     

A facile synthesis of pyrazoles with multi-point structural diversity by 1,3-dipolar cycloaddition

We describe the synthesis of diverse pyrazoles by 1,3-dipolar cycloaddition of ethyl diazoacetate with various acetylenes in refluxing toluene. The product pyrazoles are useful starting points for preparing a diverse collection of trisubstituted pyrazole carboxamides. For aryl and heteroaryl alkynes a single product is obtained while alkyl alkynes afford a ca. 6:1 mixture of regioisomers. The observed regioselectivity for the cycloaddition step and the ease of reaction are consistent with predictions derived from computing the HOMO-LUMO energies of the reactants.     

1,3-Dipolar cycloaddition route to novel isoxazole-type derivatives related to combretastatin A-4

A series of compounds related to combretastatin A-4, containing a five-membered heterocyclic ring interposed between the two phenyl groups have been prepared. Synthetic approach involves 1,3-dipolar cycloaddition of various 3,4,5-trimethoxyphenyl units with an in situ generated nitrile oxide from a suitable aldoxime using sodium hypochlorite. Depending on the nature of the dipolarophile, 3,5-diarylisoxazole derivatives were obtained along with the 3,4-regioisomeric isomers.