Unveiling the intramolecular [3 + 2] cycloaddition reactions of<i>C</i>,<i>N</i>-disubstituted nitrones from the molecular electron density theory perspective

Acharjee, Nivedita; Mondal, Asmita; Chakraborty, Mrinmoy

doi:10.1039/d2nj00888b

Cited by 10 publications

(4 citation statements)

References 71 publications

(147 reference statements)

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“…Consequently, the absence of pseudoradical and carbenoid centers in N‐benzyl fluoro nitrone ( a ) justifies its classification as a zwitterionic TAC, 61 which participates in zw‐type reactions associated with high energy barriers 16 . This ELF analysis of N‐benzyl fluoro nitrone ( a ) is identical to that found for C,N‐disubstituted nitrones by Acharjee et al 62 For isolated maleimide derivatives 1b , 2b , and 3b , the most important valence basins are the two disynaptic basins V(C4C5) with a total population of 3.33 e, associated with the C4C5 double bonds.…”

Section: Resultssupporting

confidence: 80%

Insights into the mechanism of [3+2] cycloaddition reactions between N‐benzyl fluoro nitrone and maleimides, its selectivity and solvent effects

Boutiddar,

Abbiche,

Mellaoui

et al. 2023

J Comput Chem

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We present a theoretical study of the [3+2] cycloaddition (32CA) reactions of N‐benzyl fluoro nitrone with a series of maleimides producing isoxazolidines. We use the Molecular Electron Density Theory at the MPWB1K/6‐311G(d) level. We focus on the reaction mechanism, selectivity, solvent, and temperature effects. In addition, we perform topological analyses at the minimal and transition states to identify the intermolecular interactions. Electron Localization Function approach classifies the N‐benzyl fluoro nitrone as zwitterionic (zw‐) three‐atom components (TACs), associated with a high energy barrier. The low polar character of the reaction is evaluated using the Conceptual Density Functional Theory analysis of the reactants, confirmed by the low global electron density transfer computed at the transition states. Computations show that these 32CA reactions follow a one‐step mechanism under kinetic control, with highly asynchronous bond formation and no new covalent bond is formed at the TS. Besides, the potential energy surfaces along the reaction pathways in gas phase and in solvent are mapped. The corresponding Gibbs free energy profiles reveal that the exo‐cycloadducts are kinetically and thermodynamically more favored than endo‐cycloadducts, in agreement with the exo‐selectivity observed experimentally. In particular, we found that solvent and temperature did not affect this selectivity and mainly influence the activation energies and the exothermic character of these 32CA reactions.

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Section: Resultssupporting

confidence: 80%

Insights into the mechanism of [3+2] cycloaddition reactions between N‐benzyl fluoro nitrone and maleimides, its selectivity and solvent effects

Boutiddar,

Abbiche,

Mellaoui

et al. 2023

J Comput Chem

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“…The CDFT [33,34] analysis has been applied in numerous 32CA reactions [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26] to assess the electronic behavior at the GS of the reagents and accordingly predict the polar character of the reactions. The electronic chemical potential µ, global electrophilicity ω, chemical hardness η and global nucleophilicity N calculated at the GS of the reagents at the B3LYP/6-31G(d) computational level are given in Table 1.…”

Section: Analysis Of the Ground State (Gs) Electronic Structures Of T...mentioning

confidence: 99%

“…In 2016, Domingo proposed the molecular electron density theory [8] (MEDT) to establish the role of electron density changes on molecular reactivity. Since last seven years, the MEDT perspective has been successfully applied to analyse the experimentally observed region [9,10], stereo- [9][10][11][12] and chemoselectivity [13,14], reactivity [15][16][17], substituent effects [18,19], catalysis [20,21], strain promotion [22,23] and several other aspects of 32CA reactions [24,25]. Recently, we have reported the MEDT analysis of the chemo and regioselectivity observed in the 32CA reaction of 4-chlorobenzonitrile N-oxide and β-aminocinnamonitrile for construction of 1,2,4oxadiazoles [26].…”

Section: Introductionmentioning

confidence: 99%

Unveiling substituent effects in [3+2] cycloaddition reactions of benzonitrile N-oxide and benzylideneanilines from the molecular electron density theory perspective

Mondal¹,

Mohammad‐Salim²,

Acharjee³

2023

Sci. Rad

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The zw- type [3+2] cycloaddition (32CA) reactions of benzonitrile N-oxide with a series of substituted benzylideneanilines have been studied within the Molecular Electron Density Theory (MEDT) at the B3LYP/6-31G(d) computational level. The presence of dimethylamino and methoxy substituents in the aromatic rings of benzylideneaniline makes the reaction more facile relative to the unsubstituted one, while the electron withdrawing nitro substituents relatively induce minimal changes in the energy profile complying with the experimentally observed reaction rates. The presence of non-bonding electron density at the nitrogen atom and the formation of pseudoradical centre at the carbon atom of benzonitrile N-oxide characterise the difference in electronic structure of the TSs relative to the reagents, while the topological analysis of the electron localization function (ELF) and the atoms-in-molecules (AIM) reveal no covalent bond formation at the early TSs. The present MEDT study analyses the experimentally observed substituent effects and complete regioselectivity in the studied 32CA reactions.

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“…diastereo- [33,34] and chemoselectivity [35,36], reactivity [37,38], steric effects [32] and substituent effects [39][40][41][42].…”

Section: Introductionmentioning

confidence: 99%

Diastereoselective green synthesis of pyrrolo[1,2-a]quinolines via [3+2] cycloaddition reaction: insights from molecular electron density theory

Mohammad-Salim,

Mondal,

de Julián-Ortiz

et al. 2023

Theor Chem Acc

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The [3 + 2] cycloaddition (32CA) reaction between cyclic azomethine ylide (generated from Nphenacylquinolinium bromide) and N-arylmaleimide, leading to pyrrolo[1,2-a]quinolone, has been investigated using the Molecular Electron Density Theory (MEDT) at the B3LYP/6-311 + + G(d,p) computational level. This study focuses on the zwitter-ionic type 32CA reaction, highlighting its polar character with the electronic ux from the azomethine ylide to the alkene. The reaction proceeds with complete endo-stereoselectivity, and the activation parameters show minimal variations in different solvents, consistent with experimental observations. The activation energy is associated with the depopulation of the N2-C1 and C4-C5 bonding regions, formation of non-bonding electron density at N2 nitrogen and creation of pseudoradical centers at C3, C4 and C5. These ndings suggest that the formation of new covalent bonds does not occur at the transition states, in line with the presence of noncovalent interactions at the interatomic bonding regions, as revealed by the topological analysis of the Quantum Theory of Atoms-in-Molecules (QTAIM).

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Unveiling the intramolecular [3 + 2] cycloaddition reactions ofC,N-disubstituted nitrones from the molecular electron density theory perspective

Abstract: The zwitterionic type intramolecular [3 + 2] cycloaddition reactions of nitrones show remarkable substituent effects and varying reactivities in the cases of cyclic and acyclic alkenes.

Cited by 10 publications

References 71 publications

Insights into the mechanism of [3+2] cycloaddition reactions between N‐benzyl fluoro nitrone and maleimides, its selectivity and solvent effects

Insights into the mechanism of [3+2] cycloaddition reactions between N‐benzyl fluoro nitrone and maleimides, its selectivity and solvent effects

Unveiling substituent effects in [3+2] cycloaddition reactions of benzonitrile N-oxide and benzylideneanilines from the molecular electron density theory perspective

Diastereoselective green synthesis of pyrrolo[1,2-a]quinolines via [3+2] cycloaddition reaction: insights from molecular electron density theory

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