Cycloaddition Reactions Of Nitrones Research Articles

ChemInform Abstract: Synthesis of Some Novel Bisisoxazolidine Derivatives from Glyoxal‐Derived Bisnitrones via Simultaneous Double Cycloaddition Reactions in Water.

AbstractA new methodology for the synthesis of bisisoxazolidines from one‐pot double cycloaddition reactions of bifunctional nitrones (I) with maleimides and other activated alkenes is given.

Diastereoselective construction of highly functionalized tetrahydroquinolinoisoxazole scaffolds via intramolecular nitrone cycloaddition

A novel strategy towards the construction of highly diversified tetrahydroquinolinoisoxazole frameworks with high diastereoselectivity via intramolecular 1,3-dipolar nitrone cycloaddition reaction is described for the first time. All the synthesized tetrahydroquinolinoisoxazoles are new and obtained in excellent yields under catalyst free condition.

Chemistry of unsaturated arenetricarbonylchromium compounds

1,3-Dipolar cycloaddition reactions of nitrones of a general formula RCH=N+(O–)R´, where R = Ph, Ph[Cr(CO)3], R´ = Me, Ph, But, with acrylonitrile were studied. The isoxazolidines obtained by these reactions were isolated and identified. The introduction in the nitrone molecule of a tricarbonylchromium group led to the increase in the regioand stereoselectivity of cycloaddition. The influence of deuterated solvents on chemical shifts of protons in the isoxazolidine ring was studied.

Cycloaddition Reactions of Alkyl Cyclopropenecarboxylates Generated in situ with Nitrones: Construction of Substituted Pyrroles and 1,2‐Oxazinanes

AbstractA highly regioselective [3+2] cycloaddition reaction of nitrones 1 with alkyl 2‐aroylcyclopropenecarboxylates generated in situ from alkyl 2‐aroyl‐1‐chlorocyclopropanecarboxylates 2 under basic conditions is described. The reaction proceeded readily to afford ring‐fused isoxazolidines 3 in moderate‐to‐high yields. The strained ring‐fused cycloaddition products were selectively transformed into the corresponding polysubstituted pyrroles, for example, pyrrolizine derivatives, through N–O bond cleavage or 1,2‐oxazinane derivatives through ring‐opening by treatment with HCl·pyridine in alcoholic solvents.

A bonding evolution theory study of the mechanism of [3+2] cycloaddition reactions of nitrones with electron-deficient ethylenes

BET study of the mechanism of zw-type [3+2] cycloaddition reactions of nitrones with electron-deficient ethylenes.

Exploitation of in situ generated sugar-based olefin keto-nitrones: synthesis of carbocycles, heterocycles, and nucleoside derivatives.

Application of intramolecular 1,3-dipolar nitrone cycloaddition reaction on carbohydrate-derived precursors containing an olefin functionality at C-1 or C-3 or C-5 and a nitrone moiety at C-2 or C-3 as appropriate has resulted in the formation of structurally new cycloaddition products containing furanose-fused oxepane, thiepane, azepane, cyclopentane, cycloheptane, tetrahydrofuran, and pyranose-fused tetrahydrofuran rings. The structure and stereochemistry of these products have been characterized by spectral as well as single-crystal X-ray analyses. Two of the compounds have been transformed to the bicyclic nucleoside derivatives applying Vorbrüggen reaction conditions.

Acyclic and cyclic nitrone cycloadditions to 1-cinnamoyl-1-piperidine: A DFT study

DFT studies have been carried out for the cycloaddition reactions of a cyclic nitrone, 1-pyrroline-1-oxide and an acyclic nitrone, C,N-diphenyl nitrone to an unsymmetrically disubstituted dipolarophile, 1-cinnamoyl-1-piperidine. These reactions proved to be opposite to each other with respect to the electron demand character predicted by the electronic chemical potentials, electrophilicities and charge transfer at the transition states. The regio- and stereoselectivities have been predicted from DFT based reactivity indices, interaction energy calculations using a perturbative orbital independent theoretical model and the activation parameters of the located transition states. Two different concepts have been used for the evaluation of interaction energies. The selectivities were found to be in conformity with the experimental findings. The time gaps between the formations of C – C and C – O bonds were evaluated from single trajectory simulations. The asynchronicity of bond formation process was analyzed from the wiberg bond indices, atom–atom overlap weighted NAO bond orders and the calculated asymmetry indices of the transition states.

ChemInform Abstract: [3 + 2] Cycloaddition Reactions of Arylallenes with C‐(N‐Arylcarbamoyl)‐ and C,C‐Bis(methoxycarbonyl)nitrones and Subsequent Rearrangements.

The first example of 1,3-dipolar cycloaddition reactions of nitrones with arylallenes is described. C-Carbamoylnitrones react with the C1C2 double bond of arylallenes affording the corresponding 4-methyleneisoxazolidines in good yields. N-Aryl-C,C-bis(methoxycarbonyl)nitrones usually gave rearranged products: mixtures of 4,5-dihydro-4-oxo-1H-benzo[b]azepine-2,2(3H)dicarboxylates and 4-oxo-1,5-diarylpyrrolidine-2,2-dicarboxylates.

Understanding the domino retro [3+2] cycloaddition/cyclization reaction of bicyclic isoxazolidines in the synthesis of spirocyclic alkaloids. A DFT study.

The domino retro [3+2] cycloaddition/cyclization reaction of bicyclic isoxazolidines 4 yielding [6.6.5]-tricyclic isoxazolidines 7 and [6.5.5]-tricyclic isoxazolidines 8, experimentally reported by Holmes et al., has been studied in toluene using DFT methods at the MPWB1K/6-311G** level. This domino reaction begins by a reto [3+2] cycloaddition reaction of the bicyclic isoxazolidines 4 forming the cyclic nitrones 5, which undergo a subsequent cyclization reaction yielding [6.6.5]-tricyclic isoxazolidines 7 or [6.5.5]-tricyclic isoxazolidines 8. The [3+2] cycloaddition reactions of cyclic nitrone 12 with ethylene 13, and with (Z)-but-2-enenitrile 15 were also studied in order to explain the role of the tether in the cyclization step. The present study shows that, unlike the [3+2] cycloaddition reaction of cyanoalkene 15, the cyano group in the cyclization step does not have any effect on the selectivity. The present study suggests that the presence of the BF3 catalyst in the domino reaction can change the formation of the [6.5.5]-tricyclic isoxazolidine 7 to the [6.6.5]-tricyclic isoxazolidine 8.

ChemInform Abstract: A Tactical Approach for the Synthesis of Novel β‐Lactam‐Substituted, Polycyclic‐Fused Isoxazolidine Derivatives via an Intramolecular [3 + 2] Cycloaddition Reaction.

Abstract The synthesis of functionalized β-lactam-substituted, tricyclic chromenoisoxazolidine and tetracyclic naphthopyranoisoxazolidine derivatives by intramolecular nitrone cycloaddition reaction is described. The O-allyl hydroxyaldehyde derivatives, obtained from Baylis–Hillman adducts (BHA) derived from β-lactam aldehyde underwent intramolecular cycloaddition reaction to give β-lactam-substituted, polycyclic isoxazolidine derivatives in good yield. All the products were confirmed by spectral analysis. The products with a β-lactam substituent may find good applications in biological chemistry.

3+2] Cycloaddition reactions of arylallenes with C-(N-arylcarbamoyl)- and C,C-bis(methoxycarbonyl)nitrones and subsequent rearrangements

The first example of 1,3-dipolar cycloaddition reactions of nitrones with arylallenes is described. C-Carbamoylnitrones react with the C1C2 double bond of arylallenes affording the corresponding 4-methyleneisoxazolidines in good yields. N-Aryl-C,C-bis(methoxycarbonyl)nitrones usually gave rearranged products: mixtures of 4,5-dihydro-4-oxo-1H-benzo[b]azepine-2,2(3H)dicarboxylates and 4-oxo-1,5-diarylpyrrolidine-2,2-dicarboxylates.

ChemInform Abstract: Design, Synthesis, Antiviral, and Cytostatic Evaluation of Novel Isoxazolidine Analogues of C‐Nucleotides.

AbstractA series of novel isoxazolidines (III) (25 examples), are prepared by a catalyst‐free 1,3‐dipolar cycloaddition reaction of nitrones (I) with styrenes (II).

Kinetics studies of rapid strain-promoted [3+2] cycloadditions of nitrones with bicyclo[6.1.0]nonyne

Strain-promoted alkyne−nitrone cycloaddition (SPANC) reactions represent a bioorthogonal labeling strategy that is both very rapid and at the same time efficient and selective. Nitrones provide increased reaction rates as well as greater susceptibility toward stereoelectronic modification when compared with organic azides. We find that strain-promoted cycloadditions of cyclic nitrones with bicyclo[6.1.0]nonyne react with second-order rate constants as large as 1.49 L mol−1 s−1 at 25 °C. These reactions display rate constants that are up to 37-fold greater than those of the analogous reactions of benzyl azide with bicyclo[6.1.0]nonyne. We observed that reactions of nitrones with bicyclo[6.1.0]nonyne showed a stronger dependence on substituent effect for the reaction, as evidenced by a larger Hammett ρ value, than that for biaryl-aza-cyclooctanone. We demonstrate the ability to stereoelectronically tune the reactivity of nitrones towards different cyclooctynes in SPANC reactions. This ability to introduce selectivity into different SPANC reactions through substituent provides the opportunity to perform multiple SPANC reactions in one reaction vessel and opens up potential applications in multiplex labeling.

ChemInform Abstract: Microwave Assisted One Pot Green Synthesis of Novel Isoxazoline Derivatives Using N‐Methyl‐α‐chloro Nitrone and Their Antibacterial Activities.

AbstractThe title compounds are obtained as diastereomeric mixture in a 1,3‐dipolar cycloaddition reaction of nitrone (I) with different alkynes (II).

ChemInform Abstract: Synthesis of Some Novel Fluoro Isoxazolidine and Isoxazoline Derivatives Using N‐Benzyl Fluoro Nitrone via Cycloaddition Reaction in Ionic Liquid.

Abstract1,3‐Dipolar cycloaddition reactions of fluoro nitrone (I) with activated alkenes (II) and electron‐deficient alkynes (V) can be efficiently and conveniently proceed in ionic liquids to furnish isoxazolidines or isoxazolines, resp., in short reaction times and high product yields.

ChemInform Abstract: Urea‐Catalyzed Construction of Oxazinanes

Abstractby cycloaddition reaction of nitrocyclopropane carboxylates and nitrones

A tactical approach for the synthesis of novel β-lactam-substituted, polycyclic-fused isoxazolidine derivatives via an intramolecular [3+2] cycloaddition reaction

The synthesis of functionalized β-lactam-substituted, tricyclic chromenoisoxazolidine and tetracyclic naphthopyranoisoxazolidine derivatives by intramolecular nitrone cycloaddition reaction is described. The O-allyl hydroxyaldehyde derivatives, obtained from Baylis–Hillman adducts (BHA) derived from β-lactam aldehyde underwent intramolecular cycloaddition reaction to give β-lactam-substituted, polycyclic isoxazolidine derivatives in good yield. All the products were confirmed by spectral analysis. The products with a β-lactam substituent may find good applications in biological chemistry.

The 1,3-dipolar cycloaddition reaction of chiral carbohydrate-derived nitrone and olefin: towards long-chain sugars

The thermal and microwave-activated 1,3-dipolar cycloadditions of several α,β-unsaturated esters derived from d-mannose and chiral nitrones derived from threitol have been studied as a model reaction en route to eleven carbon long chain carbohydrates. Very high facial selectivity is observed for the chiral nitrones whereas the olefin facial selectivity varies with the substrate. The presence of a dioxolane ring α to the olefinic bond is beneficial to the facial selectivity of the olefin whereas a pyranose ring is not. The combination of a d-mannose derivative and a l-threitol-derived nitrone is a matched pair suitable for the synthesis of long chain sugars with nine contiguous chiral centres. Finally complete facial selectivity was observed with exo-glycals which gave a single cycloadduct.

Diastereoselective synthesis of deprotectable isoxazolidines

Isoxazolidines are important synthetic targets due to their ability to act as nucleoside analogs. The 1,3-dipolar cycloaddition reaction of nitrones with alkenes is a powerful approach to the synthesis of isoxazolidines with the potential for control over absolute and relative stereoselectivity. However, removal of the most commonly used protecting groups without cleavage of the N–O bond is a significant challenge. The diastereoselective synthesis of benzhydryl protected isoxazolidines and the reductive cleavage of the benzhydryl protecting group with retention of the isoxazolidine ring are reported.

Thermal and Sc(OTf)3 catalyzed 1,3-dipolar cycloaddition of open-chain nitrones to α,β-unsaturated lactones: combined experimental and computational studies

The stereoselectivity of 1,3-dipolar cycloaddition reactions of C-phenyl open-chain nitrones and α,β-unsaturated γ- and δ-lactones was investigated under thermal and catalytic conditions. It was found that under thermal conditions, the endo approach of the reactants was preferred leading to the thermodynamic product. In the presence of Sc(OTf)3 the exo adduct was obtained in high yield and selectivity. The energies of the cycloaddition reactions were investigated by means of molecular orbital calculations at the B3LYP/6-31+G(d,p) and MP3/6-31+G(d,p) theory level. Different reaction channels and reactant approaches, fitting the individual regio- and stereochemical preferences, are discussed. The computational results were compared with the corresponding experimental data and found to be in good agreement.