Intramolecular Versus Intermolecular Diels–Alder Reactions: Insights from Molecular Electron Density Theory
The intramolecular Diels–Alder (IMDA) reactions of four substituted deca-1,3,9-trienes and one N-methyleneocta-5,7-dien-1-aminium with different electrophilic/nucleophilic activations have been studied within the Molecular Electron Density Theory (MEDT) and compared to their intermolecular processes...
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2025-05-01
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| author | Luis R. Domingo Patricia Pérez |
| author_facet | Luis R. Domingo Patricia Pérez |
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| description | The intramolecular Diels–Alder (IMDA) reactions of four substituted deca-1,3,9-trienes and one N-methyleneocta-5,7-dien-1-aminium with different electrophilic/nucleophilic activations have been studied within the Molecular Electron Density Theory (MEDT) and compared to their intermolecular processes. The topological analysis of the electron density and DFT-based reactivity indices reveal that substitution does not modify neither the electronic structure nor the reactivity of the reagents relative to those involved in the intermolecular processes. The analysis of the relative energies establishes that the accelerations found in the polar IMDA reactions follow the same trend as those found in the intermolecular processes. The geometries and the electronic structures of the five transition state structures involved in the IMDA reactions are highly similar to those found in the intermolecular processes. A relative interacting atomic energy (RIAE) analysis of Diels–Alder and IMDA reactions allows for the establishment of the substituent effects on the activation energies. Although the nucleophilic frameworks are destabilized, the electrophilic frameworks are further stabilized, resulting in a reduction in the activation energies. The present MEDT study demonstrates the remarkable electronic and energetic similarity between the intermolecular and intramolecular Diels–Alder reactions. Only the lower, unfavorable activation entropy associated with the latter renders it 10<sup>4</sup> times faster than the former. |
| format | Article |
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| language | English |
| publishDate | 2025-05-01 |
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| spelling | doaj-art-3d7240cc3c8d403e9e4b723764d494402025-08-20T02:31:12ZengMDPI AGMolecules1420-30492025-05-01309205210.3390/molecules30092052Intramolecular Versus Intermolecular Diels–Alder Reactions: Insights from Molecular Electron Density TheoryLuis R. Domingo0Patricia Pérez1Independent Researcher, Av. Tirso de Molina 20, 46015 Valencia, SpainFacultad de Ciencias, Universidad San Sebastián, Campus Ciudad Universitaria, Av. del Condor 720, Ciudad Empresarial, Huechuraba, Santiago 8580704, ChileThe intramolecular Diels–Alder (IMDA) reactions of four substituted deca-1,3,9-trienes and one N-methyleneocta-5,7-dien-1-aminium with different electrophilic/nucleophilic activations have been studied within the Molecular Electron Density Theory (MEDT) and compared to their intermolecular processes. The topological analysis of the electron density and DFT-based reactivity indices reveal that substitution does not modify neither the electronic structure nor the reactivity of the reagents relative to those involved in the intermolecular processes. The analysis of the relative energies establishes that the accelerations found in the polar IMDA reactions follow the same trend as those found in the intermolecular processes. The geometries and the electronic structures of the five transition state structures involved in the IMDA reactions are highly similar to those found in the intermolecular processes. A relative interacting atomic energy (RIAE) analysis of Diels–Alder and IMDA reactions allows for the establishment of the substituent effects on the activation energies. Although the nucleophilic frameworks are destabilized, the electrophilic frameworks are further stabilized, resulting in a reduction in the activation energies. The present MEDT study demonstrates the remarkable electronic and energetic similarity between the intermolecular and intramolecular Diels–Alder reactions. Only the lower, unfavorable activation entropy associated with the latter renders it 10<sup>4</sup> times faster than the former.https://www.mdpi.com/1420-3049/30/9/2052intramolecular Diels–Alder reactionsmolecular electron density theorychemical reactivityelectron localization functionDFT-based reactivity indicesrelative interacting atomic energy |
| spellingShingle | Luis R. Domingo Patricia Pérez Intramolecular Versus Intermolecular Diels–Alder Reactions: Insights from Molecular Electron Density Theory Molecules intramolecular Diels–Alder reactions molecular electron density theory chemical reactivity electron localization function DFT-based reactivity indices relative interacting atomic energy |
| title | Intramolecular Versus Intermolecular Diels–Alder Reactions: Insights from Molecular Electron Density Theory |
| title_full | Intramolecular Versus Intermolecular Diels–Alder Reactions: Insights from Molecular Electron Density Theory |
| title_fullStr | Intramolecular Versus Intermolecular Diels–Alder Reactions: Insights from Molecular Electron Density Theory |
| title_full_unstemmed | Intramolecular Versus Intermolecular Diels–Alder Reactions: Insights from Molecular Electron Density Theory |
| title_short | Intramolecular Versus Intermolecular Diels–Alder Reactions: Insights from Molecular Electron Density Theory |
| title_sort | intramolecular versus intermolecular diels alder reactions insights from molecular electron density theory |
| topic | intramolecular Diels–Alder reactions molecular electron density theory chemical reactivity electron localization function DFT-based reactivity indices relative interacting atomic energy |
| url | https://www.mdpi.com/1420-3049/30/9/2052 |
| work_keys_str_mv | AT luisrdomingo intramolecularversusintermoleculardielsalderreactionsinsightsfrommolecularelectrondensitytheory AT patriciaperez intramolecularversusintermoleculardielsalderreactionsinsightsfrommolecularelectrondensitytheory |