Cycloaddition Of Nitrile Oxides Research Articles

Site- and Regioselectivity of Nitrile Oxide-Allene Cycloadditions: DFT-Based Semiquantitative Predictions.

Nitrile oxide 1,3-dipolar cycloaddition to arylsulfonyl- and dialkylaminoallenes have been investigated within the framework of the Kohn-Sham density functional theory (DFT) at the B3LYP/6-31G(d,p) level. The hitherto-unexplained experimental behavior of sulfonylallenes was rationalized by transition-state calculations which enabled a semiquantitative treatment of the cycloaddition site- and regioselectivity. The reliability of DFT computations was further established by predicting the complete selectivity of the nitrile oxide cycloaddition to dialkylaminoallenes according to previous experimental findings.

Base‐Promoted [3+2]‐Annulation of Oxime Esters and Aldehydes for Rapid Isoxazoline Formation

AbstractA base‐promoted [3+2]‐annulation of ketoxime esters and aldehydes is disclosed for the facile and rapid synthesis of 3,5‐disubstituted and 3,4,5‐trisubstituted isoxazolines. The key to our success is the pivalate leaving group of the oxime substrates, combined with cesium carbonate as promoter. This chemistry allows the assembly of a vast array of isoxazoline derivatives under simple base conditions in a method complementary to the classic isoxazoline formation via [3+2]‐dipolar cycloaddition of nitrile oxides and olefins. It also represents a new reaction pattern involving electrophilic amination/N–O bond substitution.magnified image

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

An efficient and straight forward procedure for the syntheses of isoxazoline/isoxazole fused coumarin analogues 7a–7g and 8a–8g from the corresponding 7-O-allyloxy coumarin oximes 5a–5g and 7-O-propargyloxy coumarin oximes 6a–6g is presented. High yields and simple experimental procedures are important features of this methodology. This method is useful for the construction of many biologically active fused heterocycles. The structures of synthesized compounds are established on the basis of IR, NMR, and MS data. The products were tested for in vitro cytotoxic activity against three human cancer cell lines. All tested compounds demonstrated high cytotoxic activity.

Nitrile oxide cycloaddition to 4-hydroxy-2-cyclopentenone: Solvent effect and selectivity

The facial selectivity in the nitrile oxide cycloaddition reactions of 4-hydroxy-2-cyclopentenone and its bulky t-butyloxy derivative is reported. A quantitative evaluation of the solvent effect on the hydrogen bonding directing ability is given, showing the presence of some syn-stereoselectivity even in good H-bond acceptor solvents. The stereoselectivities of the O-t-butyl derivative may serve as reference data for more complex systems and point to the existence of a sole steric effect on the directivity; M(II) ions did not significantly improve the selectivity. The results are also discussed in light of the potential application of these scaffolds in the nucleoside analogue synthesis.

A theoretical investigation on the regioselectivity of the [3+2] cycloaddition of nitrile oxide and N-vinylpyrrole

Theoretical calculations were performed on the [3+2] cycloaddition (32CA) reaction of nitrile oxide and N-vinylpyrrole. The regiochemistry of the reaction has been studied based on potential energy surface analysis and global and local reactivity indices of the reactants. The global electron density transfer (GEDT) calculations at the possible transition states revealed that this cycloaddition has a nearly non-polar character. The ELF topological analyses of the selected structures involved in the intrinsic reaction coordinate (IRC) of TS1a suggests that this 32CA reaction takes place through a two-stage one-step mechanism.

Catalytic Enantioselective [3 + 2] Cycloaddition of α-Keto Ester Enolates and Nitrile Oxides.

An enantioselective [3 + 2] cycloaddition reaction between nitrile oxides and transiently generated enolates of α-keto esters has been developed. The catalyst system was found to be compatible with in situ nitrile oxide-generation conditions. A versatile array of nitrile oxides and α-keto esters could participate in the cycloaddition, providing novel 5-hydroxy-2-isoxazolines in high chemical yield with high levels of diastereo- and enantioselectivity. Notably, the optimal reaction conditions circumvented concurrent reactions via O-imidoylation and hetero-[3 + 2] pathways.

Synthesis of macrocyclic conjugated ψ-disacharides via nitrile oxide cycloaddition: Alkenyl chain length controlled unprecedented formation of di-oxa heterocycles from monosaccharides

Various symmetrical and unsymmetrical isoxazoline embodied chiral macroheterocycles were synthesized from carbohydrate derived oximes. Our result shows that the mode of cycloaddition is dependent on the length and tether present in alkenyl chain of sugar moiety. Thus in some cases inter- and intramolecular cycloaddition of nitrile oxide were observed with high selectivity. The cycloadducts contains two sugar units linked via macrocycles thus they are considered as pseudo-disacharides. The stereochemistry of the newly formed chiral centers was established by 2D-NMR techniques and X-ray crystallographic studies.

The hydrogen bond directing effect in nitrile oxide cycloadditions to allylic substituted cyclopentenes

A quantitative evaluation of the H-bond directing effect on the stereoselectivity in the cycloaddition of nitrile oxides to 2-cyclopenten-1-ol and allylic cyclopentenyl amides is reported. In apolar solvents the H-bond directing effect promotes a high syn stereoselectivity while H-bond acceptor solvents divert the reactions to the anti face of the dipolarophile. Taft's β parameter gives a good description of the solvent effect on the H-bond directing effect. The persistence of some syn stereoselectivity even in good H-bond acceptor solvents points out the existence of some residual hydrogen bond direction. The syn stereoselectivity in the presence of M(II) salts was also investigated and the results discussed in the light of the potential application of these scaffolds in nucleoside synthesis.

Regio- and stereoselective (3 + 2)-cycloaddition of nitrile oxides and nitrones to N-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, the electronic properties and efficient photoinduced electron transfer of new pyrrolidine[60]fullerene- and isoxazoline[60]fullerene-BODIPY dyads: nitrile oxide cycloaddition under mild conditions using PIFA

The first synthesis of fulleroisoxazoline-BODIPY whose electron-accepting ability of the C60 cage is better than its fulleropyrrolidine-BODIPY counterpart.

Facile Regioselective Synthesis and Antimicrobial Activity of Novel 8-Isoxazolinyl Coumarins via Nitrile Oxide Cycloaddition Approach

Facile Regioselective Synthesis and Antimicrobial Activity of Novel 8-Isoxazolinyl Coumarins via Nitrile Oxide Cycloaddition Approach

Synthesis and Biological Evaluation of Pyrazolyl Isoxazolines as Antimicrobial Agents

Pyrazolyl isoxazolines were synthesized by 1,3-dipolar cycloaddition of pyrazolyl nitrile oxide with various activated alkene such as acrylonitrile, methyl acrylate and vinyl acetate in the presence of iodobenzene diacetate in methanol containing a catalytic amount of TFA at room temperature with an aim to explore their effect on in vitro growth of microorganism causing microbial infection. Eleven compounds were tested in vitro for their antibacterial activity against two Gram-positive bacteria namely, Staphylococcus aureus , Bacillus subtilis and two Gram-negative bacteria namely, Escherichia coli and Pseudomonas aeruginosa . All the synthesized compounds were also tested for their inhibitory action against two strains of fungus.

Synthesis of new optically pure isoxazolines via 1,3-dipolar cycloaddition of nitrile oxides with allyl esters derived from eugenol

1,3-dipolar cycloaddition of arylnitrile oxides with allyl ester prepared from eugenol afforded new chiral isoxazolines in good yields. The chemical structure of this compounds was characterized by 1H NMR,13C NMR, 2D NMR and TOF-MS analysis. All the cycloadducts were obtained through a regiospecific and stereospecific pathway and all cases, only one isomer was isolated, as established by unambiguous NMR analysis

ChemInform Abstract: A Simple and Efficient Method for the Synthesis of Novel Pyrazolyl Isoxazoline Derivatives Using Hypervalent Iodine (III) Reagent.

A series of novel pyrazolyl isoxazolines were synthesized by 1,3-dipolar cycloaddition of pyrazolyl nitrile oxide with various activated alkene, such as acrylonitrile, methyl acrylate, and vinyl acetate, in the presence of iodobenzene diacetate in methanol containing a catalytic amount of TFA at room temperature (13 compounds upto 92% yield were isolated).

Corrigendum: Water-Assisted Nitrile Oxide Cycloadditions: Synthesis of Isoxazoles and Stereoselective Syntheses of Isoxazolines and 1,2,4-Oxadiazoles.

Conventional methods generate nitrile oxides from oxime halides in organic solvents under basic conditions. However, the present work revealed that water-assisted generation of nitrile oxides proceeds under mild acidic conditions (pH 4-5). Cycloadditions of nitrile oxides with alkynes and alkenes easily occurred in water without using catalysts, thus yielding isoxazoles and isoxazolines, respectively, with excellent stereoselectivity toward five- and six-membered cyclic alkenes. A double stereoselective cycloaddition of two units of a nitrile oxide with cyclohexene was also achieved, thus yielding 1,2,4-oxadiazole derivatives having a unique hybrid isoxazoline-oxadiazole skeleton. Enantiomerically pure isoxazolines were prepared from monoterpenes with a ring strain. In one case, the isoxazoline with a butterfly-like structure was simply prepared, and it might be used as a ligand in asymmetric catalysis.

Origins of regioselectivity in 1,3-dipolar cycloadditions of nitrile oxides with alkynylboronates

Density functional theory (M06-2X) studies of the regioselectivity of 1,3-dipolar cycloaddition reactions of benzo and mesitonitrile oxides with alkynyl pinacol and MIDA boronates are reported. Calculated relative free energies of activation reproduce the experimentally observed product ratios. The electronic energies of activation are found to be mainly controlled by distortion energies required to achieve the transition states. Both electronic and steric effects influence regioselectivities.

ChemInform Abstract: Water‐Assisted Nitrile Oxide Cycloadditions: Synthesis of Isoxazoles and Stereoselective Syntheses of Isoxazolines and 1,2,4‐Oxadiazoles.

AbstractWater assisted cycloaddition of nitrile oxides with alkenes and alkynes furnish isoxazoline or isoxazole derivatives, resp, in the absence of any catalyst.

A Simple and Efficient Method for the Synthesis of Novel Pyrazolyl Isoxazoline Derivatives Using Hypervalent Iodine (III) Reagent

AbstractA series of novel pyrazolyl isoxazolines were synthesized by 1,3‐dipolar cycloaddition of pyrazolyl nitrile oxide with various activated alkene, such as acrylonitrile, methyl acrylate, and vinyl acetate, in the presence of iodobenzene diacetate in methanol containing a catalytic amount of TFA at room temperature (13 compounds upto 92% yield were isolated).

Pleospdione, A Tricyclic Natural Product with Dense Oxygenation at the A-Ring: Total Synthesis and Incongruity of the Originally Assigned Structure and its C3-Epimer

Abstract Previously we developed a promising synthetic approach to complex polycyclic natural products, including aromatic polyketides derived from the type-II polyketide biosynthesis. The approach consists of three key steps; (1) cycloaddition or cyclocondensation of nitrile oxide for assembling the carbon skeleton having an isoxazole as a 1,3-diketone equivalent, (2) benzoin cyclization for stereoselective ring fusion with an angular hydroxy group, and (3) oxidation of isoxazolium salt for installing an additional angular hydroxy group in stereoselective manner. As a synthetic exercise to highlight the utility of this approach, the first total syntheses of the proposed structure of pleospdione (1) and its C3-epimer (3-epi-1) have been achieved. The synthesis has proved the efficiency of the strategy as an entry into polyketide-derived complex architectures. At the same time, it was revealed that neither 1 nor 3-epi-1 represent the true structure of the natural product by incongruity of the NMR spectra.

ChemInform Abstract: Hypervalent Iodine Mediated Synthesis of Di‐ and Tri‐Substituted Isoxazoles via [3 + 2] Cycloaddition of Nitrile Oxides.

Abstract An efficient and rapid protocol for the synthesis of 3,4-disubstituted and 3,4,5-trisubstituted isoxazoles under catalyst-free conditions is described. This protocol involves pre-oxidation of aldoxime into nitrile oxide using diacetoxyiodobenzene. The in situ generated nitrile oxide was trapped with dipolarophiles for the formation of functionally rich isoxazoles via [3+2] cycloaddition.