Full Regio- and Stereoselective Protocol for the Synthesis of New Nicotinoids via Cycloaddition Processes with the Participation of Trans-Substituted Nitroethenes: Comprehensive Experimental and MEDT Study
Abstract
:1. Introduction
2. Results
2.1. Analysis of the Conceptual DFT Reactivity Descriptors
2.2. BET Mechanistic Investigations
- From phase I to phase IV, the topological changes leading to the creation of the pseudoradical center [33] on C10 are taking place. In structures P1 and P2, the V(N13) and V’(N13) monosynaptic basins respectively vanish, increasing the population in the V(C4,N13) disynaptic basin. Then, the V’(C4,C5) disynaptic basin of the double bond merges with V(C4,C5), increasing its integration in P3. At the same time, the N2-O1 bond becomes depopulated, transferring 0.12 e to the V(C3,N2) disynaptic basin. These changes contribute most to the energetic cost, 11.0 kcal∙mol−1, which is only 1.1 kcal∙mol−1 lower than the TS (coincidentally being the P7 structure);
- At the start of phase V, the pseudoradical center at C4 is created from the electron density of the C4-C5 bond, with an initial population of 0.44 e, after which the V(C4,C5) disynaptic basin is further depopulated, increasing the V(C4) monosynaptic basins integration;
- Then, the V(N2) monosynaptic basin representing nonbonding electron density is created at P5 with an initial population of 0.90 e originating from the V(C3,N2) basin. The V(N2) starts with only 39% of its final population, to which the V(C3,N2) disynaptic basin contributes further in the leading phases, becoming an underpopulated double bond;
- At P6, the V(C5) monosynaptic basin is created from the population of disynaptic basin V(C4,C5), only integrating 0.07 e for a duration of a short phase VII, after which it disappears. At P8, a new bond is created, at an O-C distance of 1.658 Å, by the donation of nonbonding electron density of O1. The new V(O1,C5) disynaptic basin starts with a population of 0.76 e, ultimately increasing to 1.29 e at the cost of the nonbonding electron density of O1 and the V(N2,O1) disynaptic basins integration. The N2-O1 single bond becomes strongly underpopulated with its final integration of 0.94 e;
- Phase X starts with the creation of a pseudoradical center at C3 with a population of 0.12 e originating from the disynaptic basin V(C3,N2). Then, at P10, the C3-C4 single bond is created by the coupling of C3 and C4 pseudoradical centers, integrating 0.31 and 0.93 e, respectively, just before the event.
- The formation of the second C3-C4 single bond begins while the first O1-C5 single bond has reached 81% of its final population. Therefore, the mechanism of 32CA of nitrone 1 and nitroalkene 2a proceeds by a two-stage one-step mechanism [34].
3. Materials and Methods
3.1. Materials
3.2. Analytical Techniques
3.3. Cycloaddition between Z-C-(3-pyridyl)-N-methylnitrone and Nitroalkenes–General Procedure
3.4. ELF Computational Study
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Sample Availability
References
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μ | η | ω | N | |
---|---|---|---|---|
3,3,3-trichloro-1-nitropropene 2a | −5.74 | 5.35 | 3.07 | 0.69 |
3,3,3-tribromo-1-nitropropene 2b | −5.50 | 5.03 | 3.00 | 1.09 |
1-nitropropene 2c | −5.00 | 5.59 | 2.23 | 1.32 |
N-methyl-C-3-pyridylnitrone 1 | −3.65 | 4.33 | 1.53 | 3.29 |
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Kras, J.; Woliński, P.; Nagatsky, R.; Demchuk, O.M.; Jasiński, R. Full Regio- and Stereoselective Protocol for the Synthesis of New Nicotinoids via Cycloaddition Processes with the Participation of Trans-Substituted Nitroethenes: Comprehensive Experimental and MEDT Study. Molecules 2023, 28, 3535. https://doi.org/10.3390/molecules28083535
Kras J, Woliński P, Nagatsky R, Demchuk OM, Jasiński R. Full Regio- and Stereoselective Protocol for the Synthesis of New Nicotinoids via Cycloaddition Processes with the Participation of Trans-Substituted Nitroethenes: Comprehensive Experimental and MEDT Study. Molecules. 2023; 28(8):3535. https://doi.org/10.3390/molecules28083535
Chicago/Turabian StyleKras, Jowita, Przemysław Woliński, Roman Nagatsky, Oleg M. Demchuk, and Radomir Jasiński. 2023. "Full Regio- and Stereoselective Protocol for the Synthesis of New Nicotinoids via Cycloaddition Processes with the Participation of Trans-Substituted Nitroethenes: Comprehensive Experimental and MEDT Study" Molecules 28, no. 8: 3535. https://doi.org/10.3390/molecules28083535