Computational studies on [4 + 2] / [3 + 2] tandem sequential cycloaddition reactions of functionalized acetylenes with cyclopentadiene and diazoalkane for the formation of norbornene pyrazolines

Opoku, Ernest; Tia, Richard; Adei, Evans

doi:10.1007/s00894-019-4056-x

Cited by 34 publications

(15 citation statements)

References 33 publications

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“…It is also reported that the use of a larger 6-311G(d,p) basis set did not change the energetic and that the results are comparable to the 6-31G(d) basis set. [59][60][61] Nevertheless, we performed single point energy calculations using the B3LYP/6-311G, B3LYP/cc-pVTZ, B3LYP-D3/6-311 + G(d,p), B3LYP-D3/def2-TZVP, M06-2X/6-311G and M06-2X/cc-pVTZ methods for 45DHP 4 cp [Table S3(b)], show-ing that the results remain qualitatively unchanged. Likewise, on comparing the relative Gibbs free energies of the compounds using the two functionals in the gas phase and solvents, it is observed that the values are comparable and hence, we are reporting only those from the B3LYP/6-31G(d) method.…”

Section: Resultsmentioning

confidence: 99%

Theoretical Studies on the Mechanism of the Formation of Cyclopentadienes and Dihydropyridazines

et al. 2021

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The synthesis of cyclopentadiene derivatives via the domino reaction of norbornadienes with dimethyl 1,2,4,5-tetrazine-3,6dicarboxylate, followed a retro-Diels-Alder reaction, was reported by Dalkılıç few years ago (Tetrahedron 2015;71 : 1966). In some cases, the formation of an unexpected dihydropyridazine (DHP) was observed, and explained by a 1,3-hydrogen shift. A density functional theory study is herein reported giving insights into the proposed mechanisms with different substitu-ents on norbornadiene. Based on the kinetic and thermodynamic data, the retro-Diels-Alder reaction is confirmed to explain the formation of cyclopentadienes plus pyridazines. The intramolecular 1,3-hydrogen shift mechanism was not sufficient to explain the exclusive formation of two DHPs. Thus, an alternative mechanism involving a stepwise tautomerisation is being reported for formation of DHPs.

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Section: Resultsmentioning

confidence: 99%

Theoretical Studies on the Mechanism of the Formation of Cyclopentadienes and Dihydropyridazines

et al. 2021

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“…In the Minnesota hybrid meta-generalized gradient approximations (meta-GGA) set of density functionals, M06-2X is among the best performing in geometry optimizations and energy calculations [32]. Some recent studies on selected organic reactions have established the M06-2X coupled with the 6-311G(d,p) level of theory as the best choice as it avoids higher energetic barriers associated with, for instance, B3LYP [33,34]. To further test the suitability of the level of theory chosen, the parent reactions were also computed (full geometry optimization and energy calculations) at the…”

Section: Computational Details and Methodologymentioning

confidence: 99%

“…Intrinsic reaction coordinate calculations were then performed to ensure that each transition state smoothly connects the reactants and products along the reaction coordinate. [33,34,37,38] The optimized structures were illustrated using CYLview. [39] The global electrophilicity (ω) and maximum electronic charge (ΔNmax) of the various diazomethane derivatives were calculated using equations ( 1) and (2).…”

Section: Computational Details and Methodologymentioning

confidence: 99%

Quantum Chemical Investigation of the Formation of Spiroheterocyclic Compounds Via the (3 + 2) Cycloaddition Reaction of 1-methyl-3-(2,2,2-trifluoroethylidene)pyrrolidin-2-one with Diazomethane and Nitrone Derivatives

Pipim¹,

Tia²,

Adei³

2021

Preprint

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Spirocycles are important structures in drug development due to their inherent biological activity. Their complex architecture usually presents many synthetic difficulties which are efficiently resolved with detailed theoretical studies. The chemo-, regio- and stereoselectivities of the formation of spiroheterocyclic compounds via the (3 + 2) cycloaddition (32CA) reaction of 1-methyl-3-(2,2,2-trifluoroethylidene)pyrrolidin-2-one (A1) derivatives with diazomethane and nitrone derivative have been studied at the M06-2X/6-311G(d,p) level of theory. The reactions of diazomethane (A2) and N-methyl-C-phenyl nitrone (A3) derivatives with 1-methyl-3-(2,2,2-trifluoroethylidene)pyrrolidin-2-one derivatives (A1) occurs chemoselectively along the olefinic bond of A1 via an asynchronous one-step mechanism. Analysis of the electrophilic ( and nucleophilic ( Parr functions at the different reaction sites in A1 shows that A2 and A3 add across the atomic centers with the largest Mulliken and NBO atomic spin densities. Both electron-donating groups (EDGs) and electron-withdrawing groups (EWGs) on the A3 molecule do not affect the observed preferred pathway in its 32CA reaction with A1 whereas the electronic and steric nature of the substituent on the A2 molecule influences the preferred pathway in the 32CA reaction of A1 and A2. The title reaction proceeds via forward electron denisity flux (FEDF), where electron density fluxes from the three-atom components (A2 and A3) to A1. The computed global electron density transfer (GEDT) values suggest that the 32CA of A1 with diazomethane is a polar reaction while the 32CA reaction of A1 with N-methyl-C-phenyl nitrone is a non-polar reaction, and an inverse relationship has been established between the polar character of the reactions and activation barriers. In all the reactions studied, the selectivities are kinetically controlled.

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“…Full harmonic vibrational frequency calculations were carried out to verify that each transition state structure had a Hessian matrix with only a single negative eigen value, characterized by an imaginary vibrational frequency along the respective reaction coordinates. Intrinsic reaction coordinate calculations were then performed to ensure that each transition state smoothly connects the reactants and products along the reaction coordinate 23,24 .…”

Section: Computational Details and Methodologymentioning

confidence: 99%

DFT Mechanistic Study on the Reaction of Benzenesulfonyl Azides with Oxabicyclic Alkenes

Akuamoah¹,

Tia²,

Adei³

2020

Preprint

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The reaction of benzenesulfonyl azides with oxabicyclic alkenes to form aziridines, reported by Chen et al (J. Org. Chem. 2019, 84, 18, 11863-11872), could proceed via initial [3+2] cycloaddition to form triazoline intermediates followed by dinitrogen cleavage or via initial dinitrogen cleavage of the benzenesulfonyl azide to afford a nitrene intermediate followed by insertion of this species into the olefinic bond of the oxabicyclic alkene. Calculations at the DFT M06-2X/6-311G+(d,p) level show that the initial [3+2] cycloaddition has barriers of 17.3 kcal/mol (endo) and 10.2 kcal/mol (exo) while the initial nitrogen extrusion step has a barrier of 38.9 kcal/mol. The rate-determining step along the former pathway is the dinitrogen cleavage from triazoline cycloadducts which has barriers of 32.3 kcal/mol (endo) and 38.6 kcal/mol (exo) and that along the latter pathway is dinitrogen cleavage from benzenesulfonyl azide with an activation of barrier of 38.9 kcal/mol. The [3+2] addition of benzenesulfonyl azide with oxabicyclic alkene to afford endo and exo triazoline intermediates is kinetically favored over the dinitrogen cleavage from benzenesulfonyl azide by 21.6 and 28.1 kcal/mol for endo and exo pathway respectively. Thus, the preferred pathway for the reaction of oxabicyclic alkene with benzenesulfonyl azide is via initial [3+2] addition followed by dinitrogen cleavage, contrary to the proposal by Chen et al. The lower activation barrier for the dinitrogen extrusion step leading to endo aziridine compared to exo isomer means that the endo product will be formed as the major product, confirming the experimental observation. The position of substituents on the benzene group of the benzenesulfonyl azide greatly affects the endo / exo diastereoselectivity.

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Computational studies on [4 + 2] / [3 + 2] tandem sequential cycloaddition reactions of functionalized acetylenes with cyclopentadiene and diazoalkane for the formation of norbornene pyrazolines

Cited by 34 publications

References 33 publications

Theoretical Studies on the Mechanism of the Formation of Cyclopentadienes and Dihydropyridazines

Theoretical Studies on the Mechanism of the Formation of Cyclopentadienes and Dihydropyridazines

Quantum Chemical Investigation of the Formation of Spiroheterocyclic Compounds Via the (3 + 2) Cycloaddition Reaction of 1-methyl-3-(2,2,2-trifluoroethylidene)pyrrolidin-2-one with Diazomethane and Nitrone Derivatives

DFT Mechanistic Study on the Reaction of Benzenesulfonyl Azides with Oxabicyclic Alkenes

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