scholarly journals A Molecular Electron Density Theory Study of the Chemoselectivity, Regioselectivity, and Diastereofacial Selectivity in the Synthesis of an Anticancer Spiroisoxazoline derived from α-Santonin

Molecules ◽  
2019 ◽  
Vol 24 (5) ◽  
pp. 832 ◽  
Author(s):  
Luis Domingo ◽  
Mar Ríos-Gutiérrez ◽  
Nivedita Acharjee
Keyword(s):  
Double Bond ◽  
Electron Density ◽  
Density Functional ◽  
Nitrile Oxide ◽  
Complete Agreement ◽  
Hydrogen Atoms ◽  
Conceptual Density Functional Theory ◽  
Electronic Interactions ◽  
Molecular Electron ◽  
Molecular Electron Density Theory

The [3 + 2] cycloaddition (32CA) reaction of an α-santonin derivative, which has an exocyclic C–C double bond, with p-bromophenyl nitrile oxide yielding only one spiroisoxazoline, has been studied within the molecular electron density theory (MEDT) at the MPWB1K/6-311G(d,p) computational level. Analysis of the conceptual density functional theory (CDFT) reactivity indices and the global electron density transfer (GEDT) account for the non-polar character of this zwitterionic-type 32CA reaction, which presents an activation enthalpy of 13.3 kcal·mol−1. This 32CA reaction takes place with total ortho regioselectivity and syn diastereofacial selectivity involving the exocyclic C–C double bond, which is in complete agreement with the experimental outcomes. While the C–C bond formation involving the β-conjugated carbon of α-santonin derivative is more favorable than the C–O one, which is responsible for the ortho regioselectivity, the favorable electronic interactions taking place between the oxygen of the nitrile oxide and two axial hydrogen atoms of the α-santonin derivative are responsible for the syn diastereofacial selectivity.

scholarly journals Unveiling the Different Chemical Reactivity of Diphenyl Nitrilimine and Phenyl Nitrile Oxide in [3+2] Cycloaddition Reactions with (R)-Carvone through the Molecular Electron Density Theory

Molecules ◽  
2020 ◽  
Vol 25 (5) ◽  
pp. 1085 ◽  
Author(s):  
Mar Ríos-Gutiérrez ◽  
Luis R. Domingo ◽  
M’hamed Esseffar ◽  
Ali Oubella ◽  
My Youssef Ait Itto
Keyword(s):  
Electron Density ◽  
Density Functional ◽  
Chemical Reactivity ◽  
Topological Analysis ◽  
Nitrile Oxide ◽  
Conceptual Density Functional Theory ◽  
Functional Theory ◽  
Molecular Electron ◽  
Molecular Electron Density Theory

The [3+2] cycloaddition (32CA) reactions of diphenyl nitrilimine and phenyl nitrile oxide with (R)-carvone have been studied within the Molecular Electron Density Theory (MEDT). Electron localisation function (ELF) analysis of these three-atom-components (TACs) permits its characterisation as carbenoid and zwitterionic TACs, thus having a different reactivity. The analysis of the conceptual Density Functional Theory (DFT) indices accounts for the very low polar character of these 32CA reactions, while analysis of the DFT energies accounts for the opposite chemoselectivity experimentally observed. Topological analysis of the ELF along the single bond formation makes it possible to characterise the mechanisms of these 32CA reactions as cb- and zw-type. The present MEDT study supports the proposed classification of 32CA reactions into pdr-, pmr-, cb- and zw-type, thus asserting MEDT as the theory able to explain chemical reactivity in Organic Chemistry.

scholarly journals Unveiling the Different Reactivity of Bent and Linear Three-Atom-Components Participating in [3 + 2] Cycloaddition Reactions

Organics ◽  
2021 ◽  
Vol 2 (3) ◽  
pp. 274-286
Author(s):  
Mar Ríos-Gutiérrez ◽  
Luis R. Domingo ◽  
Fatemeh Ghodsi
Keyword(s):  
Density Functional Theory ◽  
Transition State ◽  
Electron Density ◽  
Density Functional ◽  
Geometrical Parameters ◽  
Single Bond ◽  
Conceptual Density Functional Theory ◽  
Functional Theory ◽  
Molecular Electron ◽  
Molecular Electron Density Theory

The reactivity of a series of pairs of bent and linear three-atom-component (B-TACs and L-TACs) participating in [3 + 2] cycloaddition (32CA) reactions towards ethylene and electrophilic dicyanoethylene (DCE) have been studied within the Molecular Electron Density Theory. While the pseudodiradical structure of B-TACs changes to that of pseudoradical or carbenoid L-TACs upon dehydrogenation, zwitterionic B-TACs remain unchanged. Conceptual Density Functional Theory (CDFT) indices characterize five of the nine TACs as strong nucleophiles participating in polar reactions towards electrophilic ethylenes. The activation energies of the 32CA reactions with electrophilic DCE range from 0.5 to 22.0 kcal·mol−1, being between 4.3 and 9.1 kcal·mol−1 lower than those with ethylene. In general, B-TACs are more reactive than their L-TAC counterparts. A change in the regioselectivity is found in these polar 32CA reactions; in general, while B-TACs are meta regioselective, L-TACs are ortho regioselective. The geometrical parameters of the transition state structures suggest that the formation of the single bond involving the most electrophilic carbon of DCE is more advanced. A change in the asynchronicity in the reactions involving B-TACs and L-TACs is also found.

scholarly journals Participation of Phosphorylated Analogues of Nitroethene in Diels–Alder Reactions with Anthracene: A Molecular Electron Density Theory Study and Mechanistic Aspect

Organics ◽  
2020 ◽  
Vol 1 (1) ◽  
pp. 36-48
Author(s):  
Agnieszka Kącka-Zych
Keyword(s):  
Electron Density ◽  
Density Functional ◽  
Diels Alder ◽  
Single Bond ◽  
Conceptual Density Functional Theory ◽  
Molecular Electron ◽  
Bet Analysis ◽  
One Step ◽  
Molecular Electron Density Theory ◽  
Step Mechanism

The structure and the contribution of the bis(2-chloroethyl) 2-nitro 1a and 2-bromo-2-nitroethenylphosphonates 1b with anthracene 2 in the Diels–Alder (DA) reactions have been studied within the Molecular Electron Density Theory (MEDT) at the B3LYP functional together with 6-31G(d), 6-31+G(d) and 6-31+G(d,p) basic sets. Analysis of the Conceptual Density Functional Theory (CDFT) reactivity indices indicates that 1a and 1b can be classified as a strong electrophile and marginal nucleophile, while 2 is classified as a strong electrophile and strong nucleophile. The studied DA reactions take place through a one-step mechanism. A Bonding Evolution Theory (BET) of the one path associated with the DA reaction of 1a with 2 indicates that it is associated with non-concerted two-stage one-step mechanism. BET analysis shows that the first C2-C3 single bond is formed in Phase VI, while the second C1-C6 single bond is formed in the Phase VIII. The formation of both single bonds occurs through the merging of two C2 and C3, C1 and C6 pseudoradical centers, respectively.

scholarly journals Understanding the Reactivity of C-Cyclopropyl-N-Methylnitrone Participating in [3+2] Cycloaddition Reactions Towards Styrene with a Molecular Electron Density Theory Perspective

2021 ◽  
Vol 65 (1) ◽  
Author(s):  
Haydar A. Mohammad-Salim
Keyword(s):  
Electron Density ◽  
Density Functional ◽  
Transition States ◽  
Free Energies ◽  
Conceptual Density Functional Theory ◽  
Covalent Bonds ◽  
Functional Theory ◽  
Molecular Electron ◽  
One Step ◽  
Molecular Electron Density Theory

Abstract. The [3+2] cycloaddition (32CA) reactions of C-cyclopropyl-N-methylnitrone 1 with styrene 2 have been studied within molecular electron density theory (MEDT) at the B3LYP/6-311++G(d,p) level of theory. These zwitterionic type 32CA reactions occur through a one-step mechanism. The 32CA reactions undergo four stereo- and regioisomeric reaction paths to form four different products, 3, 4, 5 and 6.  Analysis of the conceptual density functional theory (CDFT) indices predict the global electronic flux from the strong nucleophilic nitrone 1 to the styrene 2. These 32CA reactions are endergonic with reactions Gibbs free energies between 2.83 and 7.39 kcal.mol-1 in the gas phase. The 32CA reaction leading to the formation of cycloadduct 3 presents the lowest activation enthalpy than the other paths due to a slightly increase in polar character evident from the global electron density transfer (GEDT) at the transition states and along the reaction path. The bonding evolution theory (BET) study suggests that these 32CA reactions occur through the coupling of pseudoradical centers and the formation of new C-C and C-O covalent bonds has not been started in the transition states.   Resumen.

scholarly journals 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

2020 ◽  
Vol 85 (6) ◽  
pp. 765-779
Author(s):  
Nivedita Acharjee
Keyword(s):  
Electron Density ◽  
Density Functional ◽  
Topological Analysis ◽  
Transition States ◽  
Cycloaddition Reaction ◽  
Aim Analysis ◽  
Conceptual Density Functional Theory ◽  
Covalent Interaction ◽  
Molecular Electron ◽  
Molecular Electron Density Theory

[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 C?C 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.

scholarly journals A regio- and stereoselectivity and molecular mechanism study on the addition reactions of morpholine and m-CPBA to 9α-hydroxyparthenolide using DFT calculations

2020 ◽  
Vol 10 (5) ◽  
Author(s):  
Sanaa Elhamidi ◽  
Wafaa Boumya ◽  
Redouan Hammal ◽  
Mohamed Moumou ◽  
Asmaa Ben Naji ◽  
...  
Keyword(s):  
Double Bond ◽  
Dft Calculations ◽  
Electron Density ◽  
Density Functional ◽  
Major Product ◽  
Mechanism Study ◽  
Epoxidation Reaction ◽  
Molecular Electron ◽  
Molecular Electron Density Theory

<p class="Mabstract"><span lang="EN-US">The chemoselectivity and stereospecificity of the addition of the morpholine and the meta-chloroperoxybenzoic acid</span><span lang="EN-US"> (</span><span lang="EN-US">m-CPBA) onto 9α-hydroxyparthenolide were studied using Density Functional Theory (DFT) calculations with the B3LYP/6-311+G(d,p) computational level within the Molecular Electron Density Theory (MEDT), to demonstrate the key role of the Global Electron Density Transfer (GEDT) and to examine the polar character of these reactions. This work is divided into two parts; the first part concerns the reaction between the morpholine and the 9α-hydroxyparthenolide. The second part deals with the epoxidation of the 9α-hydroxyparthenolide by m-CPBA followed by the addition of the morpholine to the major product resulting from the epoxidation step. The obtained results show that the reaction between the morpholine and the 9α-hydroxyparthenolide takes place on the double bond C<sub>3</sub>=C<sub>4</sub>. On the other hand, when 9α-hydroxyparthenolide is attacked by m-CPBA, the epoxidation reaction is carried out on the double bond C<sub>1</sub>=C<sub>2</sub>.</span></p>

Understanding the molecular mechanism of the stereoselective conversion of N-trialkylsilyloxy nitronates into bicyclic isoxazoline derivatives

2021 ◽  
Author(s):  
Agnieszka Kącka-Zych ◽  
Radomir Jasinski
Keyword(s):  
Density Functional Theory ◽  
Molecular Mechanism ◽  
Electron Density ◽  
Density Functional ◽  
Dft Method ◽  
Functional Theory ◽  
Molecular Electron ◽  
Molecular Electron Density Theory

Conversion of N-trialkylsilyloxy nitronates into bicyclic isoxazoline derivatives has been explored using Density Functional Theory (DFT) method within the context of the Molecular Electron Density Theory (MEDT) at the B97XD(PCM)/6-311G(d,p)...

scholarly journals Unveiling the Unexpected Reactivity of Electrophilic Diazoalkanes in [3+2] Cycloaddition Reactions within Molecular Electron Density Theory

2020 ◽  
Author(s):  
Luis R. Domingo ◽  
Mar Ríos-Gutiérrez ◽  
Nivedita Acharjee
Keyword(s):  
Electron Density ◽  
Complete Agreement ◽  
Slowing Down ◽  
Molecular Electron ◽  
One Step ◽  
Molecular Electron Density Theory ◽  
Electrophilic Character ◽  
Step Mechanism ◽  
Computational Level ◽  
Density Transfer

The [3+2] cycloaddition (32CA) reactions of strongly nucleophilic norbornadiene (NBD) with simplest diazoalkane (DAA) and three DAAs of increased electrophilicity have been studied within the Molecular Electron Density Theory (MEDT) at the MPWB1K/6-311G(d,p) computational level. These pmr-type 32CA reactions follow an asynchronous one-step mechanism with activation enthalpies ranging from 17.7 to 27.9 kcal&middot;mol-1 in acetonitrile. The high exergonic character of these reactions makes them irreversible. The presence of electron-withdrawing (EW) substituents in the DAA increases the activation enthalpies, in complete agreement with the experimental slowing-down of the reactions, but contrary to the Conceptual DFT prediction. Despite the nucleophilic and electrophilic character of the reagents, the global electron density transfer at the TSs indicates rather non-polar 32CA reactions. The present MEDT study allows establishing that the depopulation of the NNC core in this series of DAAs with the increase of the EW character of the substituents present at the carbon center is responsible for the experimentally found deceleration.

scholarly journals Unveiling the Unexpected Reactivity of Electrophilic Diazoalkanes in [3+2] Cycloaddition Reactions within Molecular Electron Density Theory

Chemistry ◽  
2021 ◽  
Vol 3 (1) ◽  
pp. 74-93
Author(s):  
Luis R. Domingo ◽  
Mar Ríos-Gutiérrez ◽  
Nivedita Acharjee
Keyword(s):  
Electron Density ◽  
Complete Agreement ◽  
Slowing Down ◽  
Molecular Electron ◽  
One Step ◽  
Molecular Electron Density Theory ◽  
Electrophilic Character ◽  
Step Mechanism ◽  
Computational Level ◽  
Density Transfer

The [3+2] cycloaddition (32CA) reactions of strongly nucleophilic norbornadiene (NBD), with simplest diazoalkane (DAA) and three DAAs of increased electrophilicity, have been studied within the Molecular Electron Density Theory (MEDT) at the MPWB1K/6-311G (d,p) computational level. These pmr-type 32CA reactions follow an asynchronous one-step mechanism with activation enthalpies ranging from 17.7 to 27.9 kcal·mol−1 in acetonitrile. The high exergonic character of these reactions makes them irreversible. The presence of electron-withdrawing (EW) substituents in the DAA increases the activation enthalpies, in complete agreement with the experimental slowing-down of the reactions, but contrary to the Conceptual DFT prediction. Despite the nucleophilic and electrophilic character of the reagents, the global electron density transfer at the TSs indicates rather non-polar 32CA reactions. The present MEDT study establishes the depopulation of the N–N–C core in this series of DAAs with the increase of the EW character of the substituents present at the carbon center is responsible for the experimentally found deceleration.

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