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

Domingo, Luís R.; Emamian, Saeedreza; Salami, M.; Ríos‐Gutiérrez, Mar

doi:10.1002/poc.3544

Cited by 14 publications

(7 citation statements)

References 55 publications

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“…Organic compounds containing an isoxazoline motif as a core unit are known to provide an extensive variety of biological activities such as antibacterial, antifungal, anticancer, anticonvulsant, anti-inflammatory, antiviral, and antidepressant [1,2]. One of the most successful approaches to obtain these valuable skeletons, because of its simplicity, efficiency and high selectivity, is the [3 + 2] cycloaddition (32CA) reaction of nitrile oxides (NOs), participating as the three-atom-component (TAC), with an appropriate alkenes (Scheme 1) [3][4][5].…”

Section: Introductionmentioning

confidence: 99%

The Participation of 3,3,3-Trichloro-1-nitroprop-1-ene in the [3 + 2] Cycloaddition Reaction with Selected Nitrile N-Oxides in the Light of the Experimental and MEDT Quantum Chemical Study

et al. 2021

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The regioselective zw-type [3 + 2] cycloaddition (32CA) reactions of a series of aryl-substituted nitrile N-oxides (NOs) with trichloronitropropene (TNP) have been both experimentally and theoretically studied within the Molecular Electron Density Theory (MEDT). Zwitterionic NOs behave as moderate nucleophiles while TNP acts as a very strong electrophile in these polar 32CA reactions of forward electron density flux, which present moderate activation Gibbs free energies of 22.8–25.6 kcal·mol−1 and an exergonic character of 28.4 kcal·mol−1 that makes them irreversible and kinetically controlled. The most favorable reaction is that involving the most nucleophilic MeO-substituted NO. Despite Parr functions correctly predicting the experimental regioselectivity with the most favorable O-CCCl3 interaction, these reactions follow a two-stage one-step mechanism in which formation of the O-C(CCl3) bond takes place once the C-C(NO2) bond is already formed. The present MEDT concludes that the reactivity differences in the series of NOs come from their different nucleophilic activation and polar character of the reactions, rather than any mechanistic feature.

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Section: Introductionmentioning

confidence: 99%

The Participation of 3,3,3-Trichloro-1-nitroprop-1-ene in the [3 + 2] Cycloaddition Reaction with Selected Nitrile N-Oxides in the Light of the Experimental and MEDT Quantum Chemical Study

et al. 2021

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“…The electronic chemical potential (μ), chemical hardness global (η), global nucleophilicity index ( N ), and electrophilicity index (ω = μ 2 /2η) were calculated in terms of the one‐electron energies of the frontier molecular orbitals HOMO (ε H ) and LUMO (ε L ) in the following form:

normalμ = ((), ε_{H} + ε_{L}) / 2,

normalη = ((), ε_{L} ̶ ε_{H}),

N = ε_{H} ((), Nu) ̶ ε_{H} ((), TCE),

where Nu and TCE denote the given nucleophile and tetracyanoethylene, respectively. Due to its lowest HOMO energy, TCE is taken as the reference in the nucleophilicity scale, providing N with positive values …”

Section: Methodsmentioning

confidence: 99%

A molecular electron density theory study of Diels‐Alder reaction between Danishefsky's diene and (2E)‐3‐phenyl‐2‐(trifluoromethyl) acrylonitrile

Afshari

Mohsen-Nia

2019

J of Physical Organic Chem

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The Diels‐Alder reaction between Danishefsky's diene (DD 4) and (2E)‐3‐phenyl‐2‐(trifluoromethyl) acrylonitrile (EPTA 5) at 393 K in the presence of toluene has been studied using the molecular electron density theory at the M06‐2X/6‐31G(d,p) computational level. The calculated relative Gibbs free energies indicated that the studied reaction takes place in a complete regioselective and stereoselective manner in which the most nucleophilic center of DD 4 is attacked by the most electrophilic center of EPTA 5 passing through the stationary point of TS2n. It was shown that the TS2n affords the corresponding cycloadduct of CA2n as the unique product in excellent agreement with the experimental outcomes. On the other hand, a great destabilizing steric repulsion between methoxy moiety of DD 4 and the trifluoromethyl moiety of EPTA 5 along the exo stereoselective approach is responsible for the predominance of the endo approach over the exo one. The nucleophilic and electrophilic Parr functions at the reactive sites of the DD 4 and EPTA 5 have been used to explain the regioselectivity of the Diels‐Alder reaction. According to the electron localization function analysis of the intrinsic reaction coordinate profile of the energetically most preferred TS2n, a nonconcerted two‐stage one‐step molecular mechanism has been proposed. The mechanism indicated the formation of C1C6 single bond through coupling of C1 to C6 and subsequent C4C5 single bond through coupling of C4 to C5 at cycloadduct CA2n.

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“…The reactions were also inferior in DMSO, DMF, THF and CCl 4 . [42] The B3LYP/6-31G(d) computational level has been applied to successfully understand the selectivity and mechanism of several recent 32CA reactions, [34,[43][44][45][46][47] which justifies its applicability in the present MEDT study.…”

Section: Introductionmentioning

confidence: 99%

Unveiling the high regioselectivity and stereoselectivity within the synthesis of spirooxindolenitropyrrolidine: A molecular electron density theory perspective

Acharjee

Mohammad‐Salim

Chakraborty

et al. 2021

J of Physical Organic Chem

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A molecular electron density theory (MEDT) study for the [3 + 2] cycloaddition (32CA) reaction of indoledione and N-methyl glycine with (E)-1-bromonitrostyrene leading to the spirooxindole-pyrrolidine adduct is presented. Electron localisation function (ELF) study of the in situ generated azomethine ylide classifies a pseudodiradical electronic structure associated with low activation energies. This 32CA reaction is a polar process with electronic flux from the strongly nucleophilic azomethine ylide to the strongly electrophilic nitrostyrene, confirmed from the global electron density transfer (GEDT) above 0.20 e at the transition states (TSs). Parr function analysis predicts the correct regioselectivity from the two-centre interactions. The reaction is kinetically controlled with negative free energy of reaction which makes it irreversible. The activation enthalpy of the favoured TS is lowered by 3.4, 6.3 and 9.3 kcal mol −1 in methanol relative to the other feasible reaction paths,

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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

Cited by 14 publications

References 55 publications

The Participation of 3,3,3-Trichloro-1-nitroprop-1-ene in the [3 + 2] Cycloaddition Reaction with Selected Nitrile N-Oxides in the Light of the Experimental and MEDT Quantum Chemical Study

The Participation of 3,3,3-Trichloro-1-nitroprop-1-ene in the [3 + 2] Cycloaddition Reaction with Selected Nitrile N-Oxides in the Light of the Experimental and MEDT Quantum Chemical Study

A molecular electron density theory study of Diels‐Alder reaction between Danishefsky's diene and (2E)‐3‐phenyl‐2‐(trifluoromethyl) acrylonitrile

Unveiling the high regioselectivity and stereoselectivity within the synthesis of spirooxindolenitropyrrolidine: A molecular electron density theory perspective

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