Regioselectivity, stereoselectivity, and molecular mechanism of [3 + 2] cycloaddition reactions between 2-methyl-1-nitroprop-1-ene and (Z)-C-aryl-N-phenylnitrones: a DFT computational study

Dresler, Ewa; Kącka‐Zych, Agnieszka; Kwiatkowska, Maria; Jasiński, Radomir

doi:10.1007/s00894-018-3861-y

Cited by 20 publications

(4 citation statements)

References 54 publications

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“…Such molecular complexes have been recently detected for 32CAs of disubstituted nitrones. [42][43][44] The molecular complexes (MCs) for present study were found to be enthalpic in nature with ∆H values of -6.7, -7.4, -4.0 and -1.5 kcal* mol -1 in gas phase and -0. The gas phase activation energy of TSox is lower than that of TSon, TSmx and TSmn by 1.5, 0.8 and 2.3 kcal mol -1 .…”

Section: Study Of the Energy Profile Associated With The 32ca Betweenmentioning

confidence: 64%

Understanding the regio-and diastereoselective synthesis of a potent antinociceptive isoxazolidine from C-(pyridin-3-yl)-N-phenylnitrone in the light of molecular electron density theory

Acharjee

2020

JSCS

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[3+2] cycloaddition reaction of C-(pyridin-3-yl)-N-phenylnitrone and 2-propen-1-ol yields stereochemically defined potent antinociceptive isoxazolidine derivative. Computational quantum calculations (CQC) are performed for this synthesis to predict the polar character, mechanism and selectivity within the framework of molecular electron density theory (MEDT). Topological analysis of the electron localization function (ELF) classifies the nitrone as a zwitter-ionic(zw-) type three atom component (TAC) showing absence of any pseudoradical or carbenoid centre. Four reaction channels corresponding to the possible regio-and stereoselective pathways are studied at DFT/ /B3LYP/6-311G(d,p) level of theory. The reaction follows one-step mechanism with asynchronous transition states and the computed activation energies agree well with experimental data. The reaction can be differentiated into nine ELF topological phases, with faster CC bond formation. Global electron density theory (GEDT) at the favoured transition state and conceptual density functional theory (CDFT) indices at the ground state of the reagents indicate non-polar character. Non-covalent interactions are predicted by atoms-in-molecules (AIM) analysis and non-covalent interaction (NCI) plots at the transition states.

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Section: Study Of the Energy Profile Associated With The 32ca Betweenmentioning

confidence: 64%

Understanding the regio-and diastereoselective synthesis of a potent antinociceptive isoxazolidine from C-(pyridin-3-yl)-N-phenylnitrone in the light of molecular electron density theory

Acharjee

2020

JSCS

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“…The Berny analytical gradient optimization approach was employed to optimize stationary points along the potential energy surface of 32CA reactions at the B3LYP/6-311++G(d,p) level [43,44]. Previous studies have supported the use of the B3LYP functional as a reliable and accurate approach for several 32CA reactions [6,[45][46][47]. Frequency calculations of the optimized TSs established the existence of one imaginary frequency, whereas the absence of an imaginary frequency for the local minimum was confirmed.…”

Section: Methodsmentioning

confidence: 97%

Unveiling the Stereoselectivity and Regioselectivity of the [3+2] Cycloaddition Reaction between N-methyl-C-4-methylphenyl-nitrone and 2-Propynamide from a MEDT Perspective

Salih

Basheer

Julián-Ortiz

et al. 2023

IJMS

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[3+2] cycloaddition reactions play a crucial role in synthesizing complex organic molecules and have significant applications in drug discovery and materials science. In this study, the [3+2] cycloaddition (32CA) reactions of N-methyl-C-4-methyl phenyl-nitrone 1 and 2-propynamide 2, which have not been extensively studied before, were investigated using molecular electron density theory (MEDT) at the B3LYP/6–311++G(d,p) level of theory. According to an electron localization function (ELF) study, N-methyl-C-4-methyl phenyl-nitrone 1 is a zwitterionic species with no pseudoradical or carbenoid centers. Conceptual density functional theory (CDFT) indices were used to predict the global electronic flux from the strong nucleophilic N-methyl-C-4-methyl phenylnitrone 1 to the electrophilic 2-propynamide 2 functions. The 32CA reactions proceeded through two pairs of stereo- and regioisomeric reaction pathways to generate four different products: 3, 4, 5, and 6. The reaction pathways were irreversible owing to their exothermic characters: −136.48, −130.08, −130.99, and −140.81 kJ mol−1, respectively. The enthalpy of the 32CA reaction leading to the formation of cycloadduct 6 was lower compared with the other path owing to a slight increase in its polar character, observed through the global electron density transfer (GEDT) during the transition states and along the reaction path. A bonding evolution theory (BET) analysis showed that these 32CA reactions proceed through the coupling of pseudoradical centers, and the formation of new C-C and C-O covalent bonds did not begin in the transition states.

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“…The Berny analytical gradient optimisation approach was used at the MPWB95/6-311++G (d,p) level for the optimization of the stationary points along the potential energy surface of the 32CA reactions [28,29]. The use of MPWB95 functional in the analysis of 32CA reaction has been shown to be a reliable and accurate approach [20,21,[30][31][32][33][34]. The optimized TSs' frequency computations revealed the existence of a single imaginary frequency, while the disappearance of imaginary frequencies was shown to be the local minimum.…”

Section: Methodsmentioning

confidence: 99%

Unveiling [3 + 2] Cycloaddition Reactions of N-Methyl-C-3-Bromophenyl-Nitrone to Dimethyl Maleate: Molecular Electron Density Theory Perspective

2022

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Abstract. The zwitterionic-type (zw-type) [3+2] cycloaddition (32CA) reactions of N-methyl-C-3-bromophenyl-nitrone 1 with dimethyl maleate 2 with increased electrophilicity were investigated using the Molecular Electron Density Theory (MEDT) at the MPWB95/6-311++G(d,p) computational level. Both reactivity and selectivity are rationalized in relation to the polarity of the reaction. The associated zw-type 32CA reactions are accelerated due to the high nucleophilic character of N-methyl-C-3-bromophenyl-nitrone 1 and the strong electrophilic character of dimethyl maleate 2, which also play a critical part in the mechanism of the reaction, influencing the stereoselectivity, with activation enthalpies in between 34.04 and 38.37 kJ.mol-1 in the gas phase. The CDFT indices are used to anticipate global electron density flux from the nucleophilic N-methyl-C-3-bromophenyl-nitrone 1 to the electrophilic dimethyl maleate 2. These exergonic 32CA reactions have negative Gibbs free energy along the endo and exo stereochemical pathways. The endo stereochemical process is preferred over the exo stereochemical pathway in this kinetically controlled 32CA reaction. The predictions of bonding evolution theory (BET) for the endo and exo pathways indicate a one-step process with early transition states, which is compatible with the ELF topological examination of transition states. Resumen. Las reacciones de cicloadición de tipo zwitteriónico (tipo zw) [3+2] (32CA) de N-metil-C-3-bromofenil-nitrona 1 con maleato de dimetilo 2 con aumento de la electrofilicidad se investigaron utilizando la Teoría de la Densidad Electrónica Molecular (MEDT, por sus siglas en inglés) utilizando el nivel de teoría MPWB95/6-311++G(d,p). Tanto la reactividad como la selectividad se racionalizan en relación con la polaridad de la reacción. Las reacciones asociadas de tipo zw 32CA se aceleran debido al alto carácter nucleofílico de N-metil-C-3-bromofenil-nitrona 1 y al fuerte carácter electrofílico del maleato de dimetilo 2, que también juega un papel crítico en el mecanismo de la reacción, influyendo en la estereoselectividad, con entalpías de activación entre 34.04 y 38.37 kJ.mol-1, en fase gaseosa. Los índices de la Teoría de Funcionales de la Densidad Conceptual (CDFT, por sus siglas en inglés) se utilizan para anticipar el flujo global de densidad de electrones desde el nucleófilo N-metil-C-3-bromofenil-nitrona 1 hasta el maleato de dimetilo electrofílico 2. Estas reacciones exergónicas 32CA tienen energías libres de Gibbs negativa a lo largo de las vías estereoquímicas endo y exo. El proceso estereoquímico endo es preferido sobre la vía estereoquímica exo en esta reacción 32CA controlada cinéticamente. Las predicciones de la teoría de la evolución de enlaces (BET, por sus siglas en inglés) para las vías endo y exo indican un proceso de un paso con estados de transición temprana, que es compatible con el examen topológico de la Función de Localización Electrónica (ELF, por sus siglas en inglés) de los estados de transición.

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Regioselectivity, stereoselectivity, and molecular mechanism of [3 + 2] cycloaddition reactions between 2-methyl-1-nitroprop-1-ene and (Z)-C-aryl-N-phenylnitrones: a DFT computational study

Cited by 20 publications

References 54 publications

Understanding the regio-and diastereoselective synthesis of a potent antinociceptive isoxazolidine from C-(pyridin-3-yl)-N-phenylnitrone in the light of molecular electron density theory

Understanding the regio-and diastereoselective synthesis of a potent antinociceptive isoxazolidine from C-(pyridin-3-yl)-N-phenylnitrone in the light of molecular electron density theory

Unveiling the Stereoselectivity and Regioselectivity of the [3+2] Cycloaddition Reaction between N-methyl-C-4-methylphenyl-nitrone and 2-Propynamide from a MEDT Perspective

Unveiling [3 + 2] Cycloaddition Reactions of N-Methyl-C-3-Bromophenyl-Nitrone to Dimethyl Maleate: Molecular Electron Density Theory Perspective

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