Peri-, Chemo-, Regio-, Stereo- and Enantio-Selectivities of 1,3-dipolar cycloaddition reaction of C,N-Disubstituted nitrones with disubstituted 4-methylene-1,3-oxazol-5(4H)- one: A quantum mechanical study

Pipim, George Baffour; Opoku, Ernest; Tia, Richard; Adei, Evans

doi:10.1016/j.jmgm.2020.107542

Cited by 20 publications

(5 citation statements)

References 39 publications

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“…The authors highlight that the dipole, contrary to the mechanism reported by Mekheimer et al [66], adds chemo selectively to the olefinic bond, forming the corresponding spiro cycloadduct 165, rather than to the methylene carbon and the carbonyl oxygen in a [4 + 3] cycloaddition, leading to 166. Furthermore, it was found that the presence of electron-withdrawing groups in the dipole reduces the energy barriers, while it is increased in the presence of electron-donating groups [67] (Scheme 46). The lack of regioselectivity in 1,3-DC of methylenecyclopropane 170, compared to the high regioselectivity of other 1,1-disubstituted alkenes, has been computationally investigated through DFT calculations, to rationalize the experimental finding [68].…”

Section: Conflicts Of Interestmentioning

confidence: 99%

Density Functional Theory Calculations: A Useful Tool to Investigate Mechanisms of 1,3-Dipolar Cycloaddition Reactions

Chiacchio,

Legnani

2024

IJMS

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The present review contains a representative sampling of mechanistic studies, which have appeared in the literature in the last 5 years, on 1,3-dipolar cycloaddition reactions, using DFT calculations. Attention is focused on the mechanistic insights into 1,3-dipoles of propargyl/allenyl type and allyl type such as aza-ylides, nitrile oxides and azomethyne ylides and nitrones, respectively. The important role played by various metal–chiral–ligand complexes and the use of chiral eductors in promoting the site-, regio-, diastereo- and enatioselectivity of the reaction are also outlined.

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Section: Conflicts Of Interestmentioning

confidence: 99%

Density Functional Theory Calculations: A Useful Tool to Investigate Mechanisms of 1,3-Dipolar Cycloaddition Reactions

Chiacchio,

Legnani

2024

IJMS

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“…46 Some recent studies on selected organic reactions have established the M06-2X in conjunction with the 6-311++G(d,p) level of theory as the best choice as it avoids higher energetic barriers associated with, for instance, B3LYP. 7,8,12,[47][48][49]…”

Section: Geometry Optimization and Transition-state Searchmentioning

confidence: 99%

Tandem [4+2]/retro[3+2]/[3+2] cycloaddition reactions of fluorinated‐oxadiazoles with conjugated, unconjugated, cyclic, and acyclic dienes

Atta‐Kumi,

Baffour Pipim,

Opoku

2023

J of Physical Organic Chem

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The tandem reactions of 2,5‐bis(trifluoromethyl)‐1,3,4‐oxadiazole with conjugated, unconjugated, acyclic, and cyclic dienes have been studied at the M06‐2X/6‐311++G(d,p) level of theory. The rate‐determining step is the initial [4+2] cycloaddition in the tandem reaction of 2,5‐bis(trifluoromethyl)‐1,3,4‐oxadiazole with acyclic, cyclic, conjugated, and unconjugated dienes, whereas the stereochemistry of the tandem adduct is determined by the [3+2] step. The exo‐coupling is kinetically favored over the endo‐coupling in the initial [4+2] reaction of 2,5‐(bis‐trifluoromethyl)‐1,3,4‐oxadiazole with all the considered dienes. In the retro [3+2] step (N2 extrusion), higher activation energy is required to furnish the carbonyl ylide in the reaction of 2,5‐(bis‐trifluoromethyl)‐1,3,4‐oxadiazole with conjugated and unconjugated cyclic dienes as compared with the reaction with unconjugated acyclic dienes. At the stereochemistry [3+2] step, the intermolecular addition is kinetically favored over the intramolecular addition in the [3+2] reaction of 2,5‐(bis‐trifluoromethyl)‐1,3,4‐oxadiazole with both conjugated or unconjugated cyclic dienes and unconjugated acyclic dienes. The reaction proceeds with low activation energies when conjugated and unconjugated cyclic dienes are participating, compared with those of unconjugated acyclic dienes. Overall, the tandem process proceeds via an asynchronous one‐step mechanism [4+2] coupling in an exo‐ or endo‐cycloaddition fashion, followed by a retro [3+2], which extrudes the N2, and then the stereo‐determining intermolecular or intramolecular [3+2] cycloaddition step, which leads to the tandem products. The polarity of both inter‐ and intra‐molecular cycloaddition steps can be influenced by two factors: the nature of the heteroatom present on the diene molecule and the size of the cyclic diene. These factors play a role in determining the reactivity and electron distribution within the diene, thereby impacting the overall polarity of the cycloaddition reactions.

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“…Cycloaddition reactions are important synthetic procedures for the transformation of both cyclic and acyclic precursors into complex spirocyclic compounds [14]. The (3 + 2) cycloaddition (32CA) reaction of three-atom components (TACs) and ethylene derivatives presents convenient methods to access spiroheterocyclic compounds of valuable pharmacological and therapeutic properties [1,[15][16][17][18]. The major challenge in the application of the 32CA reaction is to control the regio-, stereo-, and enantio-selectivities [19,20].…”

Section: Introductionmentioning

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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Peri-, Chemo-, Regio-, Stereo- and Enantio-Selectivities of 1,3-dipolar cycloaddition reaction of C,N-Disubstituted nitrones with disubstituted 4-methylene-1,3-oxazol-5(4H)- one: A quantum mechanical study

Cited by 20 publications

References 39 publications

Density Functional Theory Calculations: A Useful Tool to Investigate Mechanisms of 1,3-Dipolar Cycloaddition Reactions

Density Functional Theory Calculations: A Useful Tool to Investigate Mechanisms of 1,3-Dipolar Cycloaddition Reactions

Tandem [4+2]/retro[3+2]/[3+2] cycloaddition reactions of fluorinated‐oxadiazoles with conjugated, unconjugated, cyclic, and acyclic dienes

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

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