The preparation of intercalating isoxazoles via a nitrile oxide cycloaddition

Pyridinium chlorochromate oxidation of 9-methylacridine (2) affords the corresponding aldehyde 3 in good yield. Conversion of the aldehyde to the hydroximinoyl chloride 5a was accomplished via reaction of the corresponding oxime with N-chlorosuccinimide. Dipolar addition to the enamine of ethylacetoacetate provided the corresponding isoxazoles 1 in good yield.     

Efficient conversion of nitronate into nitrile oxide using cyanuric chloride. One-pot synthesis of bicyclic isoxazolines and isoxazoles from nitroalkenes

Bicyclic isoxazolines and isoxazoles are obtained in good yields by proceeding through a convenient one-pot, two-step procedure utilizing 2,4,6-trichloro-1,3,5-triazine (TCT) as a dehydrating agent.     

Stereocontrolled intramolecular nitrile oxide cycloaddition reaction using a gauche-gauche interaction

A gauche-gauche interaction is proposed as a powerful controlling factor for the stereochemistry in the intramolecular nitrile oxide cycloaddition reaction derived from N-protected 3-(N-allylamino)propionaldehyde and 2-(N-homoallylamino)acetaldehyde oximes. High levels of stereoselectivity (76% de to perfect) were obtained from the reaction involving nitrile oxides with substituents at the adjacent carbon atom to the tether nitrogen.     

Total synthesis of (+)-epilupinine via an intramolecular nitrile oxide-alkene cycloaddition

Total synthesis of (+)-epilupinine was accomplished in nine steps and in 48% overall yield, in which INOC was used as the key step for the construction of the quinolizidine skeleton. We found that it was an extremely difficult task to prepare the key intermediates (R)-N-(3-nitropropyl)-2-vinylpiperidine or (R)-(2-vinylpiperid-1-yl)propanal by routine methods. Thus, by using Fukuyama's oxime synthesis, a general method was developed for highly efficient conversion of 3-(N,N-dialkylamino)propanols into 3-(N,N-dialkylamino)propanal oximes without using the corresponding aldehydes.     

Total synthesis of the sesquiterpene (+/-)-illudin C via an intramolecular nitrile oxide cycloaddition

[reaction: see text] A convergent total synthesis of illudin C is described. The tricyclic ring system of the natural product was quickly assembled from cyclopropane and cyclopentene precursors via a novel oxime dianion coupling reaction and a subsequent intramolecular nitrile oxide-olefin cycloaddition.     

Stereoselective synthesis of azepines through the conjugate addition of formamides to nitroalkenes and subsequent intramolecular nitrile oxide cycloaddition reaction

A concise and stereoselective formation of azepines is achieved through the conjugate addition of formamides to nitroalkenes and the subsequent intramolecular nitrile oxide cycloaddition (INOC) reaction. High cis-selectivity was observed. The one-pot modification of the two reactions provides direct preparation of azepines from nitroalkenes and formamides in moderate yields. The formyl group was readily removed by an acidic treatment without significant epimerization.     

Practical asymmetric synthesis of a gamma-secretase inhibitor exploiting substrate-controlled intramolecular nitrile oxide-olefin cycloaddition

A practical asymmetric synthesis of the gamma-secretase inhibitor (-)-1 is described. As the key transformation, a highly diastereoselective intramolecular nitrile oxide cycloaddition forms the hexahydrobenzisoxazole core of 3 in four operations. Other aspects of the route include a highly stereoselective reduction of an isoxazole to form a cis-gamma-amino alcohol, an efficient chemical resolution, a dianion cyclization to construct a sultam ring, and the alpha-alkylation of a sultam with excellent diastereoselectivity. In each instance, the relative stereochemistry was evolved by way of substrate-based induction with > or = 96% ds. Kilogram quantities of the targeted drug candidate (-)-1 were obtained, without recourse to chromatography, by way of 10 isolated intermediates and in 13% overall yield.     

Steroidal isoxazoles,isoxazolines and isoxazolidines

The present review considers new useful heterocyclosteroids which contain five-membered heterocyclic systems, namely, isoxazoles, isoxazolines and isoxazolidines, condensed to the cyclopentanoperhy-drophenanthrene skeleton, in different positions of the molecule, with changes in their physiological activity and the appearance of new interesting biological properties. Literature coverage for the review includes publications up to the end of 1996.     

Stereoselective intramolecular 1,3-dipolar nitrile oxide cycloaddition reaction of N-formyl-β-nitroamides

The stereoselective intramolecular nitrile oxide cycloaddition (INOC) reaction was achieved from N-formyl-β-nitroamides, which were prepared through the Michael addition of allylic formamides to nitroalkenes, and cis-pyrroroisoxazoles and trans-piperidinoisoxazoles were obtained in a stereoselective manner.     

Synthesis of isoxazoles by hypervalent iodine-induced cycloaddition of nitrile oxides to alkynes

Treatment of oximes with hypervalent iodine leads to substituted isoxazoles via rapid formation of nitrile oxides. Reaction with terminal alkynes led to a series of 3,5-disubstituted isoxazoles with complete regioselectivity and high yield, in a procedure mild enough to prepare a range of nucleoside and peptide conjugates. Exceptionally high reaction rates were found for the formation of 3,4,5-trisubstituted isoxazoles from a cyclic alkyne.     

Synthesis of isoxazolobenzoxepanes via Michael addition of indoles to nitroalkenes and sequential intramolecular nitrile oxide cycloaddition

Nitroalkenes derived from O-propargyl salicylaldehyde undergo facile Michael addition with indoles leading to indole-derived Michael adducts. Intramolecular nitrile oxide cycloaddition (INOC) of the Michael adducts results in isoxazolobenzoxepanes in good to excellent yields.     

Synthesis of pyrano isoxazoline/isoxazole annulated coumarins via intramolecular nitrile oxide cycloaddition and their cytotoxicity

Russian Journal of General Chemistry - An efficient and straight forward procedure for the syntheses of isoxazoline/isoxazole fused coumarin analogues 7a–7g and 8a–8g from the...     

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 and intramolecular nitrile oxide cycloaddition of 3,5'-ether-linked pseudooligosaccharide derivatives: an approach to chiral macrooxacycles

3,5'-ether-linked pseudooligopentose derivatives were synthesized for the first time from readily available carbohydrate precursors. The 1,2-isopropylidene-protected ether-linked oligopentoses are potentially important as precursors of novel RNA analogues. Intramolecular cycloaddition of the nitrile oxides prepared from these derivatives led to the diastereoselective formation of chiral isoxazolines fused to 10-16-membered oxacycles. The stereochemistry of some of these isoxazolines was established by X-ray diffraction and NOESY analysis.     

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.     

A Weinreb nitrile oxide and nitrone for cycloaddition

[reaction: see text] The cycloaddition of Weinreb amide functionalized nitrile oxide/nitrones with a range of dipolarophiles has been explored.     

Intramolecular [3+2] nitrile oxide cycloaddition: synthesis of tetrahydroisoxazoloindazoles

Novel tetrahydroisoxazoloindazoles were synthesized from substituted 1,3-diketones by employing intramolecular [3+2] nitrile oxide cycloaddition [INOC] reaction to alkene as the key step.     

A highly regioselective tandem 1,3-dipolar cycloaddition of cyclopropene 1,1-diesters and nitrile oxides: synthesis of highly functionalized isoxazoles

A highly regioselective tandem 1,3-dipolar cycloaddition of cyclopropene 1,1-diesters with nitrile oxides was described. This reaction supplied a new method for synthesis of polyfunctionalized isoxazole derivatives in moderate to excellent yields under mild conditions.