Mechanisms and Transition States of 1,3-Dipolar Cycloadditions of Phenyl Azide with Enamines: A Computational Analysis

Lopez, Steven A.; Munk, Morton E.; Houk, K. N.

doi:10.1021/jo302695n

Cited by 41 publications

(23 citation statements)

References 35 publications

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“…Thus, the reaction times of enamine 1e with hydroxamoyl chloride 2a (R = Ph) as determined by TLC analysis is 30 h (product 4p ), while those for 2f (R = 6-Cl-2-FC 6 H 3 ) is 18 h (product 4l ) and for 2b (R = 4-MeOC 6 H 4 ) 32 h (products 4i ), respectively. The regio- and stereospecificity and the apparent reaction rate increase by the introduction of electron-withdrawing substituents into the benzonitrile oxide structure, allow to presume that the reaction of enamines with nitrile oxides can be described as 1,3-dipolar cycloadditions with inverse electron demand, similarly to the reaction of enamines with azides [37]. …”

Section: Resultsmentioning

confidence: 99%

Combined experimental and theoretical studies of regio- and stereoselectivity in reactions of β-isoxazolyl- and β-imidazolyl enamines with nitrile oxides

Efimov¹,

Shafikov²,

Беляев³

et al. 2016

Beilstein J. Org. Chem.

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Reactions of β-azolyl enamines and nitrile oxides were studied by both experimental and theoretical methods. (E)-β-(4-Nitroimidazol-5-yl), (5-nitroimidazol-4-yl) and isoxazol-5-yl enamines smoothly react regioselectively at room temperature in dioxane solution with aryl, pyridyl, and cyclohexylhydroxamoyl chlorides without a catalyst or a base to form 4-azolylisoxazoles as the only products in good yields. The intermediate 4,5-dihydroisoxazolines were isolated as trans isomers during the reaction of (E)-β-imidazol-4-yl enamines with aryl and cyclohexylhydroxamoyl chlorides. Stepwise and concerted pathways for the reaction of β-azolyl enamines with hydroxamoyl chlorides were considered and studied at the B3LYP/Def2-TZVP level of theory combined with D3BJ dispersion correction. The reactions of benzonitrile oxide with both E- and Z-imidazolyl enamines have been shown to proceed stereoselectively to form trans- and cis-isoxazolines, respectively. The preference of E-isomers over Z-isomers, driven by the higher stability of the former, apparently controls the stereoselectivity of the investigated cycloaddition reaction with benzonitrilе oxide. Based on the reactivity of azolyl enamines towards hydroxamoyl chlorides, a novel, effective catalyst-free method was elaborated to prepare 4-azolyl-5-substituted isoxazoles that are otherwise difficult to obtain.

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Section: Resultsmentioning

confidence: 99%

Combined experimental and theoretical studies of regio- and stereoselectivity in reactions of β-isoxazolyl- and β-imidazolyl enamines with nitrile oxides

Efimov¹,

Shafikov²,

Беляев³

et al. 2016

Beilstein J. Org. Chem.

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“…After investigating the Diels–Alder reactions of four cycloalkenes with four dienes using the distortion/interaction model, they concluded that the reactivity of the dienes is controlled by both distortion and interaction energies . Other cycloaddition systems were also rationalized using this model . Another similar model is the so‐called activation strain model; when combined with the distortion/interaction model, we can obtain a quantitative comprehension of the physical factors that control the activation energy through different fundamental processes.…”

Section: Introductionmentioning

confidence: 99%

A theoretical study of the mechanisms for 1,3-dipolar cycloadditions of diphenyldiazomethane to C₆₀and C₇₀

Cui

Liu

2014

J. Phys. Org. Chem.

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The 1,3‐dipolar cycloaddition (1,3‐DPCA) reaction plays a crucial role during the functionalization of fullerenes, which have broad applications in the materials and pharmaceutical fields. In concert with previous experiments, we theoretically investigated the mechanisms of 1,3‐DPCA of diphenyldiazomethane (DDMf) to two fullerenes (C60 and C70) using the M06‐2X density functional method under vacuum and in solvents. To understand the influence of the dipolarophile on these reactions, the 1,3‐DPCA of DDMf to three common acceptors, specifically tetracyanoethylene (TCNE), 2,3‐dichloro‐5,6‐dicyano‐1,4‐benzoquinone (DDQ), and chloranil (CA), was also studied at the same computational level. The substituent effects on the five reactions were investigated by modeling 1,3‐DPCA reactions with 12 different substituted DDMf (DDMs) with five dipolarophiles, totaling 60 reactions. Including the five unsubstituted DDMf reactions, 65 1,3‐DPCA reactions were studied. The stereoselectivity, relative reactivity, solvent effects, and distortion/interaction energy model were carefully considered and analyzed based on their corresponding electronic structures, electrostatic potential surfaces, interaction models, solvent models, and thermodynamic data. An intermediate was identified for each of the 65 reactions. A possible biradical pathway for the reactions between DDMf and the two fullerenes was also investigated. The calculated results corroborate and enrich the experimental observations. The conclusion and detailed discussion are generally important for understanding the 1,3‐DPCA reactions to fullerenes. Copyright © 2014 John Wiley & Sons, Ltd.

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“…These reactions are characterized by joining two π systems at their ends to form a ring compound through the formation of two new sigma bonds via the breaking of two π bonds, one from each π system, in a concerted process 55,56 . More recently, a plethora of theoretical tools have been employed, based on the values of the distortion and interaction energies proposed by Houk et al [57][58][59][60] or the analysis of the vibrational modes for the reactants [61][62][63][64] . In this context, we can cite the works of Toro-Labbé et al in which the degrees of synchronicity (or non-synchronicity)…”

Section: On the Reaction Mechanism Of 13-dipolar Cycloadditionsmentioning

confidence: 99%

On the outside looking in: rethinking the molecular mechanism of 1,3-dipolar cycloadditions from the perspective of bonding evolution theory. The reaction between cyclic nitrones and ethyl acrylate

Adjieufack

Ndassa

Patouossa

et al. 2017

Phys. Chem. Chem. Phys.

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In this work we report on the progress that has been made towards gaining an understanding of the molecular mechanism of 1,3-dipolar cycloadditions using the bonding evolution theory (BET). A detailed analysis of the flow of electron density along the reaction pathway of the formal 1,3-dipolar cycloaddition reaction between cyclic nitrones (pyrroline-1-oxide and 2,3,4,5 tetrahydropyridine-1-oxide) and ethyl acrylate, as a case study, allowed the nature of the molecular mechanisms to be characterized.The present study provides a deep insight into the reaction mechanism, based on the electron density rearrangements given by the structural stability domains, and their connection with the bond breaking/forming processes along the reaction pathway.Electron pushing formalism is a powerful tool to describe chemical reactivity. Here, we show how the Lewis structures can be recovered and how curly arrows describe electron density transfers in chemical reaction mechanisms based on the BET results. The reaction mechanism is described by four consecutive events taking place as the reaction progresses: 1) the population of the initial N−C double bond is transferred to the N and C atoms; 2) the population of the initial double C-C bond is transferred to the C atoms.Along the ortho pathway the next steps are: 3) the C−C bond-forming, and 4) the O-C 2 bond-forming process. The order of 3) and 4) is inverted in the meta channel. Based on the sequence of the structural stability domains along the intrinsic reaction coordinate, a new synchronicity index is proposed, allowing us to classify and quantify the (a)synchronicity of the 1,3-DC reactions and, therefore, the nature of the reaction mechanism.3

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Mechanisms and Transition States of 1,3-Dipolar Cycloadditions of Phenyl Azide with Enamines: A Computational Analysis

Cited by 41 publications

References 35 publications

Combined experimental and theoretical studies of regio- and stereoselectivity in reactions of β-isoxazolyl- and β-imidazolyl enamines with nitrile oxides

Combined experimental and theoretical studies of regio- and stereoselectivity in reactions of β-isoxazolyl- and β-imidazolyl enamines with nitrile oxides

A theoretical study of the mechanisms for 1,3-dipolar cycloadditions of diphenyldiazomethane to C₆₀and C₇₀

On the outside looking in: rethinking the molecular mechanism of 1,3-dipolar cycloadditions from the perspective of bonding evolution theory. The reaction between cyclic nitrones and ethyl acrylate

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Mechanisms and Transition States of 1,3-Dipolar Cycloadditions of Phenyl Azide with Enamines: A Computational Analysis

Cited by 41 publications

References 35 publications

Combined experimental and theoretical studies of regio- and stereoselectivity in reactions of β-isoxazolyl- and β-imidazolyl enamines with nitrile oxides

Combined experimental and theoretical studies of regio- and stereoselectivity in reactions of β-isoxazolyl- and β-imidazolyl enamines with nitrile oxides

A theoretical study of the mechanisms for 1,3-dipolar cycloadditions of diphenyldiazomethane to C60and C70

On the outside looking in: rethinking the molecular mechanism of 1,3-dipolar cycloadditions from the perspective of bonding evolution theory. The reaction between cyclic nitrones and ethyl acrylate

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A theoretical study of the mechanisms for 1,3-dipolar cycloadditions of diphenyldiazomethane to C₆₀and C₇₀