A highly efficient [3+2] cycloaddition of nitrile oxides and azomethine imines to N-vinylpyrroles

Efremova, Mariia M.; Molchanov, A. P.; Stepakov, A. V.; Kostikov, R. R.; Shcherbakova, V. S.; Иванов, А. В.

doi:10.1016/j.tet.2015.02.058

Cited by 29 publications

(8 citation statements)

References 42 publications

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“…This figure evidently indicates that the considered 32CA reaction in the presence of DCM takes place via a complete regioselective pathway through the most favorable TS1 (ΔΔG activation = 7.0 kcal/mol), affording the most thermodynamically stable CA 4a (ΔΔG reaction = ‐5.9 kcal/mol). These results are in excellent agreement with the experimental outcomes …”

Section: Resultssupporting

confidence: 91%

“…It is interesting to note that the activation enthalpy associated with the most favorable TS1 , 12.5 kcal/mol, is only 0.8 kcal/mol lower than the corresponding value found in the non‐polar 32CA reaction between the simplest nitrile oxide 6 (fulminic acid) and ethylene 7. Moreover, the formation of CA 4a , the unique cycloadduct experimentally observed, is strongly exothermic by 37.2 kcal/mol. In 32CA reactions, because of the bimolecular nature of the reaction, both activation and reaction entropies are very negative, acting as an unfavorable factor in the formation of the TSs and the corresponding CAs.…”

Section: Resultsmentioning

confidence: 84%

“…The most usual method in nitrile oxide generation is a direct oxidation of aldoxime or halogenation of aldoxime to N ‐hydroxyiminoyl halides followed by dehydro‐halogenation . Very recently, Efremova et al experimentally studied a set of 32CA reactions of aryl nitrile oxides 2 , generated in situ by the one‐pot method from oximes 1 under treatment by aqueous NaClO, toward N ‐vinylpyrroles (NVPs) 3a , 3b , 3c in the presence of dichloromethane (DCM) affording isoxazolines 4a , 4b , 4c in a complete regioselective fashion and good yields (Scheme ) …”

Section: Introductionmentioning

confidence: 99%

“…Herein, a density functional theory (DFT) study of the 32CA reaction between the benzonitrile oxide (BNO) 2 and the NVP derivative 3a , ( R 1 = R 2 = (CH 2 ) 4 in Scheme ), experimentally reported by Efremova et al , is performed at the B3LYP/6‐31G(d) level in order to characterize the energetic, the complete regioselectivity experimentally observed and the reaction mechanism of this zw‐type 32CA reaction involving a nitrile oxide (Scheme ). Moreover, an electron localization function (ELF) topological analysis of the most relevant points along the intrinsic reaction coordinate (IRC) curve of the 32CA reaction between BNO 2 and NVP 3a is carried out in order to characterize the bonding changes along the studied 32CA reaction, and thus to establish the molecular mechanism of this reaction in detail.…”

Section: Introductionmentioning

confidence: 99%

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Understanding the molecular mechanism of the [3 + 2] cycloaddition reaction of benzonitrile oxide toward electron‐rich N‐vinylpyrrole: a DFT study

Domingo

Emamian

Salami

et al. 2016

J of Physical Organic Chem

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The [3 + 2] cycloaddition (32CA) reaction of benzonitrile oxide, BNO 2, with an electron‐rich N‐vinylpyrrole derivative, NVP 3a, in the presence of dichloromethane, has been theoretically studied using density functional theory (DFT) methods at the B3LYP/6‐31G(d) level. This 32CA reaction presents a relatively high activation Gibbs free energy as a result of the low polar character of this zwitterionic‐type (zw‐type) reaction. Analyses of the calculated relative Gibbs free energies and transition state geometries indicate that the studied 32CA reaction, in excellent agreement with experimental outcomes, takes place in a complete regioselective manner as a consequence of the steric repulsions that appear at the most unfavorable transition state. An electron localization function (ELF) topological analysis of the bonding changes along this 32CA reaction supports a non‐concerted two‐stage one‐step molecular mechanism in which the formation of the O3‐C5 single bond takes place at the end of the reaction after the complete formation of the C1‐C4 one. Copyright © 2016 John Wiley & Sons, Ltd.

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Section: Resultssupporting

confidence: 91%

Section: Resultsmentioning

confidence: 84%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Understanding the molecular mechanism of the [3 + 2] cycloaddition reaction of benzonitrile oxide toward electron‐rich N‐vinylpyrrole: a DFT study

Domingo

Emamian

Salami

et al. 2016

J of Physical Organic Chem

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“…By intramolecular cyclization of carbonyl ylides at the same bond indole alkaloids (aspidophytine, minovin, vindoline) were synthesized [14][15][16][17]. Previously we have studied the reaction of cycloaddition of N-vinylpyrroles with 1,3-dipoles: nitrones [18,19], nitrile oxides, and azomethine imines [20]. All reactions occur regioselectively involving the N-vinyl group and provide an efficient method for the synthesis of compounds containing ensembles of pyrroloisoxazolidine, pyrroloisoxasoline, or pyrazolopyrazolone fragments.…”

mentioning

confidence: 99%

Regio- and stereoselective (3 + 2)-cycloaddition of nitrile oxides and nitrones to N-vinylindole

et al. 2017

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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.An indole fragment is a structural component of a wide range of natural and pharmacologically active compounds. In this context a search for new synthetic routes to compounds containing an indole fragment, particularly in combination with other heterocyclic groups, was considered in a number of reviews [1][2][3][4]. It is known that indole and its derivatives containing an alkyl substituent at the nitrogen atom enter into a reaction of the 1,3-dipolar cycloaddition with nitrile oxides [5-8], nitrile imines [9, 10], and azomethine ylides [11][12][13] at the bond C 2 -C 3 to form heterocyclic compounds containing oxazoline, pyrrole or pyrazoline fragments fused with the indole ring. By intramolecular cyclization of carbonyl ylides at the same bond indole alkaloids (aspidophytine, minovin, vindoline) were synthesized [14][15][16][17]. Previously we have studied the reaction of cycloaddition of N-vinylpyrroles with 1,3-dipoles: nitrones [18,19], nitrile oxides, and azomethine imines [20]. All reactions occur regioselectively involving the N-vinyl group and provide an efficient method for the synthesis of compounds containing ensembles of pyrroloisoxazolidine, pyrroloisoxasoline, or pyrazolopyrazolone fragments.In this work we investigated the regio-and stereoselective interaction of N-vinylindole 1 with 1,3-dipoles: nitrile oxides and nitrones. The reaction of N-vinylindole 1 with nitrile oxides 2a and 2b, which were generated in situ from chloro oximes 3a and 3b at treating with sodium hydrogen carbonate in toluene, leads to the formation of adducts at the N-vinyl group, 5-indolylisoxazolines 4a and 4b. The yield was 67 and 72%, respectively (Scheme 1). NMR spectra showed that no regioisomeric addition products were present in the reaction mixtures. The structure of the compounds was established proceeding from the spectral data. For example, in the 1 H NMR spectrum of compound 4a along with the aromatic proton signals there were three signals of the isoxazoline ring protons at 3.61 d.d (J 17.8, 4.3 Hz), 3.81 d.d (J 17.8, 9.9 Hz), and of the methine proton in the position 5 at 6.86 d.d (J 9.9, 4.3 Hz). In the 13 C NMR spectrum the corresponding signals of carbon atoms of isoxasoline cycle were located at 40.1 (CH 2 ), 86.3 (CH), and 155.4 (C= N) ppm. Scheme 1. 3a, 3b 4a, 4b 2a, 2b N Cl R OH R N O NaHCO 3 _ + N 1 O N N R R = 4-ClC 6 H 4 (a), COOEt (b).

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[3 + 2] Cycloadditions of Azomethine Imines

Grošelj

Svete

2020

Organic Reactions

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In spite of their late discovery in the middle of 20 th century, the importance of azomethine imines and their [3+2] cycloaddition reactions has grown constantly throughout the decades. Today, [3+2] cycloadditions of azomethine imines have become indispensable in the preparation of pyrazole derivatives with all degrees of saturation. The structural diversity of azomethine imines is wide and comprises acyclic, C , N ‐cyclic, N , N ‐cyclic, and C , N , N ‐cyclic 1,3‐dipoles. Although electron‐deficient dipolarophiles are preferred, electron‐rich dipolarophiles, such as enol ethers and enamines, are also commonly used in these reactions. Compared to cyclocondensation methods and [3+2] cycloadditions with diazoalkanes and nitrile imines, [3+2] cycloadditions with azomethine imines provide access to a greater diversity of pyrazole derivatives with all degrees of saturation. As with other 1,3‐dipolar cycloadditions, a concerted and nearly synchronous mechanism has been proposed for most [3+2] cycloadditions of azomethine imines, although a stepwise mechanism may be viable in some cases. Several examples of asymmetric [3+2] cycloadditions of azomethine imines that afford non‐racemic cycloadducts with high enantioselectivity have been reported. These asymmetric cycloadditions are performed with various types of transition metal catalysts and organocatalysts, and indicate their potential for the asymmetric synthesis of saturated pyrazole derivatives. Finally, many examples of copper‐catalyzed and thermal, strain‐promoted [3+2] cycloadditions of azomethine imines (in particular sydnones) clearly indicate wide applicability of these reactions in bioconjugation, fluorescent labelling, materials functionalization, and other applications outside the realm of pure organic synthesis.

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A highly efficient [3+2] cycloaddition of nitrile oxides and azomethine imines to N-vinylpyrroles

Cited by 29 publications

References 42 publications

Understanding the molecular mechanism of the [3 + 2] cycloaddition reaction of benzonitrile oxide toward electron‐rich N‐vinylpyrrole: a DFT study

Understanding the molecular mechanism of the [3 + 2] cycloaddition reaction of benzonitrile oxide toward electron‐rich N‐vinylpyrrole: a DFT study

Regio- and stereoselective (3 + 2)-cycloaddition of nitrile oxides and nitrones to N-vinylindole

[3 + 2] Cycloadditions of Azomethine Imines

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