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A metal- and base-free, robust, and convenient approach for the synthesis of isoxazoline derivatives is reported. This protocol involves 1,3-dipolar cycloaddition between in situ generated nitrile oxides from the corresponding aldoximes using [hydroxy(tosyloxy)iodo]benzene (HTIB, Koser's reagent) and maleimides, styrene and acrylonitrile. The described methodology is very attractive as it is operationally simple, has broad scope, and does not require any base, metal, or other additives. [ABSTRACT FROM AUTHOR]

This Account gives an insight into the selective functionalization of some readily available commercial cyclodienes across simple chemical transformations into functionalized small-molecular scaffolds. The syntheses involved selective cycloadditions, followed by ring-opening metathesis (ROM) of the resulting azetidin-2-one derivatives or isoxazoline frameworks and selective cross metathesis (CM) by discrimination of the C=C bonds on the alkenylated heterocycles. The CM protocols have been described when investigated under various conditions with the purpose on exploring chemodifferentiation of the olefin bonds and a study on the access of the corresponding functionalized β-lactam or isoxazoline derivatives is presented. Due to the expanding importance of organofluorine chemistry in drug research as well as of the high biological potential of β-lactam derivatives several illustrative examples to the access of some fluorine-containing molecular entities is also presented in this synopsis. 1 Introduction 2 Ring C=C Bond Functionalization of Some Cycloalkene β-Amino Acid Derivatives across Chlorosulfonyl Isocyanate Cycloaddition 3 Ring C=C Bond Functionalization of Some Cycloalkene β-Amino Acid Derivatives across Nitrile Oxide Cycloaddition 4 Ring C=C Bond Functionalization of Some Cycloalkene β-Amino Acid Derivatives across Metathesis 5 Functionalization of sSome Cyclodienes across Nitrile Oxide Cycloaddition 6 Selective Synthesis of Functionalized Alicycles across Ring-Opening Metathesis 7 Selective Synthesis of Functionalized Alicycles through Cross Metathesis 8 Summary and Outlook 9 List of Abbreviations [ABSTRACT FROM AUTHOR]

The microwave-assisted 1,3-dipolar cycloaddition of furanyl and benzyl oximes and several methyl acrylates effectively provided several isoxazoline when mediated by diacetoxyiodobenzene. The selected isoxazoline, methyl-5-(3-methoxy-3-oxopropyl)-3-phenyl-4,5-dihydro isoxazole-5-carboxylate, was rapidly transformed to the γ-lactone carboxylic acid, 2-(2-amino-2-phenylethyl)-5-oxotetrahydrofuran-2-carboxylic acid, in reasonable yield. The biological activity of this γ-lactone carboxylic acid increased the growth of E. coli organisms by about 44% and has a potential significance in stem cell research. [ABSTRACT FROM AUTHOR]

Five-membered heterocyclic N -oxides attract special attention due to their significant potential applications in medicinal chemistry and advanced materials science. In this regard, novel methods for their synthesis and functionalization are in constant demand. In this short review, recent state-of-the-art achievements in the chemistry of isoxazoline N -oxides, 1,2,3-triazole 1-oxides and 1,2,5-oxadiazole 2-oxides are summarized. The main routes involving transition-metal-catalyzed and metal-free functionalization protocols along with mechanistic considerations are outlined. The transformations of these hetarene N -oxide rings as precursors to other nitrogen heterocyclic systems are also presented. 1 Introduction 2 Isoxazoline N -Oxides 3 1,2,3-Triazole 1-Oxides 4 1,2,5-Oxadiazole 2-Oxides 5 Conclusion [ABSTRACT FROM AUTHOR]

A copper-catalyzed oxydifluoroalkylation of β,γ-unsaturated oximes has been developed. This reaction proceeded through a cascade of difluoroalkylation of alkene followed by a nucleophilic attack of the hydroxyl group of oximes. This protocol features mild reaction conditions, low-cost catalyst, and broad substrate scope, which provides a facile method to synthesize isoxazolines with a fluorinated side chain [ABSTRACT FROM AUTHOR]

We synthesized [6,6,6]- and [6,6,7]-tricyclic compounds via intramolecular [4+2] cycloaddition by gold or copper catalysts. Substrates for cyclization were prepared by coupling reactions between eight types of diyne and four types of aromatic moieties. We have successfully synthesized eleven tricyclic compounds. [ABSTRACT FROM AUTHOR]

A facile synthesis of novel dispiroheterocycles has been developed through one-pot [3+2] cycloaddition between isatins, amino acids, and aurones. Thirty different dispiroheterocycles were synthesized eusing this method which features mild conditions, convenient operation, and high efficacy. Evaluation of the bioactivity of these dispiroheterocyclic products revealed antiviral activity against tobacco mosaic virus (TMV). [ABSTRACT FROM AUTHOR]

A novel, one-pot reaction for the synthesis of isoxazolines and isoxazoles is developed via a cascade process under metal-free conditions. The approach involves the formation of intramolecular C-N and C-O bonds and intermolecular C-C bonds from aromatic alkenes or alkynes and N-hydroxysulfonamides using hypervalent iodine(VII) and iodine as the oxidant. Activation of C-H and C-C bonds/construction of C-O bonds/elimination of SO2/C-N bond formation is achieved in sequence in the reaction system. [ABSTRACT FROM AUTHOR]

A novel synthetic route for the synthesis of quinolines starting from Δ²-isoxazolines under reductive conditions is reported. The reductive cyclization to quinolines is achieved under both metal and metal-free conditions. The reaction proceeds via an intramolecular N-H···O hydrogen bond intermediate, accelerating the reductive cleavage 1000-fold (DFT calculations) in comparison with non-hydrogen bonded system. [ABSTRACT FROM AUTHOR]

The new chemical cascade reaction was found: the direct formation of substituted 4-oxo-2,7-diaryl-5-oxa-6-azaspiro[2.4]hept-6- ene-1,1-dicarbonitriles from benzylidenemalononitriles and 3-aryl-2- isoxazol-5(4H)-ones. The action of bromine on the equimolar mixture of benzylidenemalononitrile and 3-aryl-2-isoxazol-5(4H)-one in the basic alcohol solution results in stereoselective formation of spirobicycle containing the 2-isoxazolin-5-one and the cyclopropane fragments in 53-92% yields. Thus, the new simple and efficient 'one-pot' approach to substituted (2R*,3R*)-4-oxo-2,7-diaryl-5-oxa-6-azaspiro[2.4]hept-6- ene-1,1-dicarbonitriles was found directly from simple and reasonable starting compounds as benzylidenemalonitriles and 3-aryl-2-isoxazol- 5(4H)-ones. [ABSTRACT FROM AUTHOR]

The room temperature, 1,3-dipolar cycloaddition reactions of the nitrile oxide obtained from (6-piperidin-1-yl-9H-purin-9-yl)acetaldehyde oxime upon phenyliodine(III) bis(trifluoroacetate) treatment with excess unsaturated alcohols as solvent resulted in isoxazoline or isoxazole derivatives in almost quantitative yields. Analogous derivatives were prepared from the reactions of unsaturated phosphates. Preliminary biological tests indicated inhibition of lipid peroxidation for some of the examined compounds. [ABSTRACT FROM AUTHOR]

In this account, we summarize our recent work on the preparation of various N-heterocycles, starting from propargylic alcohols. Our aim was to develop versatile and selective one-pot procedures that would permit the synthesis of large collections of heterocycles, such as di- or tri-substituted isoxazolines and isoxazoles, cis-aziridines, and pyrimidines, by fine changes in the reaction conditions. When needed, mechanistic studies have been performed by combining experimental work with density functional theory calculations. 1 Introduction 2 Synthesis of Disubstituted Isoxazolines 3 Synthesis of Disubstituted Isoxazoles 4 Synthesis of cis-Acylaziridines 5 Trisubstituted Isoxazolines and Isoxazoles 6 β-Enaminones and Pyrimidines 7 Conclusion. [ABSTRACT FROM AUTHOR]

Atisane-type compounds and related natural products are attractive for their molecular skeletons and pharmaceutical bioactivities. This review summarizes total syntheses of atisane-type diterpenoids and related diterpenoid alkaloids. [ABSTRACT FROM AUTHOR]

Heterocyclic compounds are crucial starting reagents and intermediates, or they are direct precursors of target chemicals and/or bio-pharmacological active compounds. Today, they are used in the total synthesis of natural products, in drugs or herbicides, and agrochemical preparation. Developing synthetic strategies targeting isoxazoles is a recurrent aim in preparative chemistry. In particular, five-membered heterocycles such as isoxazoles and isoxazolines are easily formed in a two steps or by a 'one-pot' procedure, by reacting aryl nitrile oxides with a variety of enolates of carbonyl compounds (i.e., aldehydes, ketones, carboxylic acids), followed by aromatization. Such a methodology was found to be selective and versatile allowing the preparation of pharmacologically active isoxazoles in high yields. 1 Introduction 2 Preparation, Synthetic Applications, and Reactivity of 3- Aryl-5-hydroxy-2-isoxazolines and 3-Arylisoxazoles 3 Synthesis of 5-Alkyl-3-aryl-5-hydroxy-2-isoxazolines and 5-Alkyl-3-arylisoxazoles 4 Synthesis and Reactivity of 3,4-Diaryl-5-hydroxy-2-isoxazolines and 3,4-Diarylisoxazoles 5 Synthesis and Reactivity of 3-Aryl-5-hydroxy-5-vinyl-2- isoxazolines and 3-Aryl-5-vinylisoxazoles 6 Synthesis of 3-Aryl-4-phenylisoxazole-5-carboxylic Acid 7 Conclusions 8 Experimental Methodologies [ABSTRACT FROM AUTHOR]

The present account illustrates the syntheses of isoxazoline- based amino acids by the cycloaddition of 1,3-dipolar nitrile oxides to the C-C double bond of unsaturated amino acid derivatives, with focus on the regio- and stereoselectivities of the transformations. Emphasis is also placed on the syntheses of highly functionalized amino acids by means of isoxazoline ring opening. The syntheses of various pharmacologically active compounds and their analogues via the above strategies are described. [ABSTRACT FROM AUTHOR]

A facile one-pot, two-step synthesis of highly substituted pyrazolo[3,4-b]indoles and isoxazolo[5,4-b]indoles was developed via microwave-assisted, copper-catalyzed intramolecular heterocyclization (involving C--N/C--O bond formation) from 3-acetyl-2-chloroindoles in good to excellent yields. [ABSTRACT FROM AUTHOR]

Two highly versatile isoxazoline derivatives, as key intermediates for the synthesis of differently functionalized subtypeselective N-methyl-D-aspartate receptor antagonists, were designed and synthesized. The synthetic strategy is based on an intramolecular nitrile oxide cycloaddition reaction which is a powerful method capable of controlling both the regio- and stereochemistry of the pericyclic reaction. [ABSTRACT FROM AUTHOR]

The enantioseletive alternating copolymerization of CO with styrene derivatives catalyzed by a dicationic palladium(II) complex of tetra isopropyl-substituted spiro bis(isoxazoline) (i-Pr-SPRIX) is developed. This polymerization proceeded efficiently to produce isotactic polyketones with high molecular weights and high molar optical rotation values. [ABSTRACT FROM AUTHOR]

Treatment of N-propargylamides with 5 mol% of silver hexafluoroantimonate results in the rapid formation of oxazolines in essentially quantitative yield. [ABSTRACT FROM AUTHOR]