Stereoconvergent and stepwise 1,3-dipolar cycloadditions of nitrile oxides and nitrile imines

The first example of stereoconvergent 1,3-dipolar cycloaddition of nitrile oxides and nitrile imines with E/Z isomeric mixture of electron-deficient olefins is reported, delivering isoxazolines and pyrazolines bearing two vicinal stereogenic tertiary and trifluoromethylated quaternary carbon centers with perfect regioand diastereoselectivities. The possibility of concerted cycloaddition/epimerization sequence under basic condition to form the thermodynamically stable diastereomers is excluded th...     

Synthesis of novel pyrano[2,3-b]quinolines from simple acetanilides via intramolecular 1,3-dipolar cycloaddition

Some novel isoxazole and pyrazole fused pyrano[2,3-b]quinolines were synthesized from simple acetanilides via intramolecular 1,3-dipolar cycloaddition reactions involving nitrones, nitrile oxides and nitrile imines as 1,3-dipoles, in a regioselective manner.     

An environmentally benign synthesis of isoxazolines and isoxazoles mediated by potassium chloride in water

An effective and environmentally benign procedure for the synthesis of isoxazolines and isoxazoles has been developed by a cycloaddition of nitrile oxides with alkenes or alkynes in water. In this approach, potassium chloride is first oxidized into chlorine in water by the environmentally friendly oxidant Oxone®, then aldoximes are oxidized into nitrile oxides by the in situ generated hypochlorous acid, finally a 1,3-dipolar cycloaddition between nitrile oxides and alkenes or alkynes occurs to provide the corresponding isoxazolines and isoxazoles in good yields.     

One-pot Synthesis of Isoxazolines Using Soluble Polymer-supported Acrylate

An eficient liquid-phase synthesis of isoxazolines through a 1,3-dipolar cycloaddition is described.Soluble polymer-supported acrylate reacted with nitrile oxides generated in-situ,followed by cleavage from the support giving corresponding isoxazolines in high yields and excellent purities.     

One step regioselective synthesis of 5-aminoisoxazoles from nitrile oxides and alpha-cyanoenamines

The 1,3-dipolar cycloaddition of nitrile oxides to 1-cyanoenamines gives 5-aminoisoxazoles regioselectively. Moderate to good yields could be obtained depending on the method used to generate the nitrile oxides. The intermediate isoxazolines could not be isolated.     

聚乙二醇支持的2,5-二取代异噁唑啉衍生物的液相合成

介绍了通过1,3-偶极环加成合成2,5-二取代异噁唑啉衍生物的液相合成方法, 利用聚乙二醇(PEG)支持的烯烃与由醛肟制得的腈氧化物反应制备了多种异噁唑啉衍生物, PEG解脱后产物的产率和纯度均很高.     

Hypervalent Iodine–Catalyzed Cycloaddition of Nitrile Oxides to Alkenes

A new and convenient method for preparation of isoxazolines was developed by a catalytic cycloaddition of nitrile oxides generated in situ from aldoximes to alkenes in the presence of a catalytic amount of iodobenzene. In this protocol, iodobenzene was first oxidized into the hypervalent iodine intermediate by m-chloroperbenzoic acid, which then transformed aldoximes into nitrile oxides, and a 1,3-dipolar cycloaddition of nitrile oxides to alkenes to provide the isoxazolines in moderate to good yields.

[Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications® for the following free supplemental resource(s): Full experimental and spectral details.]     

Stereoselective synthesis of novel annulated thiopyrano indole derivatives from simple oxindole via intramolecular 1,3-dipolar cycloaddition reactions of nitrone and nitrile oxide

Synthesis of some novel isoxazolidine/dihydroisoxazole annulated thiopyrano[2,3-b]indole derivatives from simple oxindole via 1,3-dipolar cycloaddition reaction involving nitrone and nitrile oxide as 1,3-dipole is reported.     

Synthesis of multivalent neoglycoconjugates by 1,3 dipolar cycloaddition of nitrile oxides and alkynes and evaluation of their lectin-binding affinities

The synthesis of multivalent neoglycoconjugates by 1,3-dipolar cycloaddition of nitrile oxides and alkynes is reported. The nitrile oxides are generated in situ in the presence of alkynyl derivatives allowing the access to homo and hetero multivalent systems containing O- and C-linked glycosides and isoxazole bridges. The concanavalin A binding affinities of some of these neoglyconjugates bearing mannose residues were evaluated by enzyme-linked lectin essay (ELLA).     

Synthesis of new aza-bicyclic 2-isoxazolines by 1,3-dipolar cycloaddition of endocyclic enecarbamates and enamides with nitrile oxides

Novel aza-bicyclic 2-isoxazolines, 4,5-dihydroisoxazole[5,4-b]pyrrolidines, and 4,5-dihydroisoxazole[5,4-b]piperidines were synthesized in a highly regioselective manner through a 1,3-dipolar cycloaddition reaction of 5- and 6-membered endocyclic enecarbamates and enamides with several nitrile oxides in good to excellent yields. Hydrogenolysis of 5- and 6-membered Cbz-cycloadducts led to secondary amines, which presented distinctive stabilities. 2-Isoxazoline bisamides were obtained in good yields through a N-benzoylation, followed by ammonolysis of the secondary amine, or directly from ammonolysis of the cycloadducts.     

Synthesis of 5-aminoisoxazolines from N-allyl compounds and nitrile oxides via tandem isomerization-1,3-dipolar cycloaddition

A new strategy for the synthesis of derivatives of 5-aminoisoxazolines via tandem catalytic isomerization (of N-allyl systems to N-(1-propenyl) systems)—1,3-dipolar cycloaddition (of a stable nitrile oxide to N-(1-propenyl) systems) is presented. Rhodium and ruthenium complexes, Verkade’s superbase, and 18-crown-6/KOH system were used for the syntheses of the N-(1-propenyl) systems. 4-P-substituted isoxazoline was also synthesized via cycloaddition of diphenyl(1-propenyl)phosphine (prepared via isomerization of allyldiphenylphosphine) to 2,6-dichlorobenzonitrile oxide. All cycloadditions were regioselective but not stereoselective and not concerted. Cycloaddition to all N-(1-propenyl) systems yielded 5-N-substituted isoxazolines, but cycloaddition to P-(1-propenyl) system lead to the formation of a 4-P-regioisomer. This difference in regioselectivity is predicted by opposite FMO reactivity indices calculated for model compounds: N-(1-propenyl)amine and N-(1-propenyl)phosphine.     

Solid Phase Synthesis of Isoxazole and Isoxazoline-carboxamides via [2+3]-Dipolar Cycloaddition Using Resin-bound Alkynes or Alkenes

An efficient approach for the parallel solid phase synthesis of isoxazole and isoxazoline derivatives has been developed. The isoxazoles and isoxazolines were constructed through a 1,3-dipolar cycloaddition reaction of nitrile oxides, with resin-bound alkynes or alkenes. The cycloaddition reaction conditions performed on solid phase supports was optimized, and an array of resin bound carboxylic acid building blocks were utilized for distinct conversions. This methodology presents a new alternative to the diversity oriented synthesis of disubstituted isoxazoles and isoxazolines different from existing routes which are limited in structural diversity.     

Multicomponent cascade reactions: sequential [1 + 4] and [2 + 3] cycloadditions for the generation of heterocyclic ring systems

[reaction: see text]. A novel intermolecular nitrile oxide cycloaddition sequence has been developed for the formation of highly substituted heterocyclic rings. Reaction of trimethylsilyl cyanide with epoxides generates isonitriles which can react with nitroalkenes to form N-(isoxazolylidene)alkylamines. After fragmentation to nitrile oxides, the dipoles can undergo intermolecular 1,3-dipolar cycloadditions with electron deficient dipolarophiles to generate substituted isoxazolines in one synthetic operation.     

Regio- and stereoselective (3 + 2)-cycloaddition of nitrile oxides and nitrones to <Emphasis Type="Italic">N</Emphasis>-vinylindole

1,3-Dipolar cycloaddition of nitrile oxides and nitrones to N-vinylindole proceeds regioselectively at the exocyclic multiple bond to form 5-indolyl-substituted isoxazolines and isoxazolidines in good yields.     

Synthesis and pharmacological activity of silyl isoxazolines 2

Silyl isoxazolines have been synthesized by [2+3] cycloaddition reaction of nitrile oxides to vinyl- and allylsilanes. The addition of 3-pyridylnitrile oxide to 1,3-divinyl-1,1,3,3-tetraphenyldisiloxane affords 1,3-bis{5-[3-(3-pyridyl)isoxazolin-2-yl]}-1,1,3,3-tetraphenyldisiloxane; the latter exists as a mixture of trans- and cis-isomers.The bond angle of the Si–O–Si fragment in thetrans-isomer equals 180(3)° and in the cis-isomer it is 162(3)°.The pharmacological properties of 4-[3-(5-trimethylsilylisoxazolin-2-yl)]pyridinium-chloride have been studied.     

Asymmetric 1,3-dipolar cycloaddition of nitrile oxides with optically active vinylboronic ester

Pinanyldioxy styrylboronic ester (1) was employed for asymmetric 1,3-dipolar cycloaddition with nitrile oxides, optically active △2-isoxazolines (3) or 4-hydroxy-△2-isoxazolines (4) were obtained. The effect of different bases on the selectivity of the cycloaddition reaction was studied.     

1,3-Dipolar cycloaddition approach to isoxazole, isoxazoline and isoxazolidine analogues of C-nucleosides related to pseudouridine

Isoxazole, isoxazoline and isoxazolidine analogues of C-nucleosides related to pseudouridine have been synthesized by 1,3-dipolar cycloaddition reactions of nitrile oxides and nitrones derived from mono and disubstituted uracil-5-carbaldehydes and 2,4-dimethoxypyrimidine-5-carbaldehyde. The dimethoxy derivatives have been easily deprotected to the corresponding uracils bearing the heterocyclic ring instead of a sugar moiety. The regio and stereoselectivity of the reactions are discussed.     

1,3-Dipolar cycloaddition of nitrile oxides to (R)-1-(1-phenylethyl)-3-[(E)-arylmethylidene]tetrahydro-4(1H)-pyridinones: synthesis of enantiomerically pure spiro heterocycles

The 1,3-dipolar cycloaddition of (R)-1-(1-phenylethyl)-3-[(E)-arylmethylidene]tetrahydro-4(1H)-pyridinones to nitrile oxides proceeds chemo-, regio-, and stereoselectively affording moderate yields of enantiomerically pure spiro heterocycles comprising piperidine and isoxazoline/dioxazole rings.     

Base-promoted 1,3-dipolar cycloaddition reaction of nitrile oxides with methyl 1,4-dioxo-1,4-dihydronaphthalene-2-carboxylate for the construction of naphtho[2,3-d]isoxazole-4,9(3aH,9aH)-diones

A base mediated 1,3-dipolar cycloaddition reaction of methyl 1,4-dioxo-1,4-dihydronaphthalene-2-carboxylate with nitrile oxides in situ generated from N-hydroximoyl chlorides was achieved. With this developed protocol, a range of structurally diverse naphtho[2,3-d]isoxazole-4,9(3aH,9aH)-dione derivatives were smoothly obtained in high yields (up to 95%) with up to >20:1 regioselectivities and >20:1 diastereoselectivities under mild conditions. The promising applicability of the protocol was also demonstrated by the further transformations.     

1,3-Dipolar Cycloaddition of Dipolar Reagents to Bifunctional Olefins with Chloramine-T --- Part-II

A one pot synthesis of pyrazoles and isoxazoles was achieved by 1,3-dipolar cycloaddition of nitrile imines and nitrile oxides to an activated olefins in the presence of chloramine-T.