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

Domingo, Luís R.; Ríos‐Gutiérrez, Mar; Acharjee, Nivedita

doi:10.3390/chemistry3010006

Cited by 9 publications

(8 citation statements)

References 69 publications

(105 reference statements)

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“…This behavior contrasts with the analyses of the geometrical parameters, which indicate that at the two TSs, the N1‐C5 distances are shorter than the C3−C4 ones. This finding, which has been observed in recent MEDT studies of 32CA reactions, allows rejecting any analysis of the asynchronicity in the single bond formation based on geometrical parameters [29,53,54] …”

Section: Resultsmentioning

confidence: 55%

“…This finding, which has been observed in recent MEDT studies of 32CA reactions, allows rejecting any analysis of the asynchronicity in the single bond formation based on geometrical parameters. [29,53,54] ELF and AIM comparative analysis of the TSs associated with the 32CA reactions of NBD 9 with SDAPs 10-14…”

Section: Bet Study For the Syn/endo Reaction Path Associated With The 32ca Reaction Of Nbd 9 With Dat 13mentioning

confidence: 99%

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Unveiling the Substituent Effects in the Stereochemistry of [3+2] Cycloaddition Reactions of Aryl‐ and Alkyldiazomethylphosphonates with Norbornadiene within a MEDT Perspective

Domingo

Acharjee

2021

ChemistrySelect

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The [3 + 2] cycloaddition (32CA) reactions of norbornadiene with aryl and alkyl substituted diazomethylphosphonates (SDAPs) have been studied within the molecular electron density theory (MEDT). Electron localization function (ELF) shows the presence of a pseudoradical C3 center at the alkyl SDAPs, classifying them as pseudo(mono)radical species, while the aryl SDAP is classified as a zwitterionic one, owing to the delocalization of the C3 electron density on the C3-P bond. These 32CA reactions present high activation enthalpies in dichloromethane, between 17.3 and 21.6 kcal mol À 1 , being strongly exothermic by more than 33.8 kcal mol À 1 . While these 32CA reactions present a total syn facial selectivity, the endo/ exo stereoselectivity depends on the steric hindrance caused by the bulk substituents present in these SDAPs along the approach to norbornadiene. Interestingly the phenyl group provokes a lesser hindrance than that of the small methyl group, justifying the 95 % of exo stereoselectivity experimentally observed. ELF and the AIM (Atoms-in-Molecules) analyses account for the bonding changes along these 32CA reactions. The energy cost for the rupture of the norbornadiene CÀ C and that of the SDAPs NÀ N double bonds are the major contributors to the activation energies of these non-polar 32CA reactions.

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Section: Resultsmentioning

confidence: 55%

Section: Bet Study For the Syn/endo Reaction Path Associated With The 32ca Reaction Of Nbd 9 With Dat 13mentioning

confidence: 99%

Unveiling the Substituent Effects in the Stereochemistry of [3+2] Cycloaddition Reactions of Aryl‐ and Alkyldiazomethylphosphonates with Norbornadiene within a MEDT Perspective

Domingo

Acharjee

2021

ChemistrySelect

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“…diazoalkanes 23 , 32CA reactions of strained allenes 21 , competitiveness of Diels Alder and Alder ene reactions 21 etc.…”

Section: A N U S C R I P Tmentioning

confidence: 99%

Unveiling the regioselective synthesis of antiviral 5-isoxazol-5-yl-2´-deoxyuridines from the perspective of a molecular electron density theory

Acharjee

Mohammad‐Salim

Chakraborty³

2022

JSCS

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The regioselective synthesis of a potent antiviral sugar nucleoside isoxazole analogue from the [3+2] cycloaddition (32CA) reaction of aceto-nitrile-N-oxide (ANO) and acetyl-protected 5-ethynyl-2?-deoxyuridine (EDU) has been studied at MPWB1K/6-311G(d,p) level within the molecular electron density theory (MEDT) perspective. ANO is classified as a zwitterionic species devoid of any pseudoradical or carbenoid center from the electron localization function (ELF) analysis. The ortho regioisomer is energetically preferred over the meta one by the activation enthalpy of 21.7-24.3 kJ mol-1, suggesting complete regioselectivity in agreement with the experiment. The activation enthalpy increases from 53.9 kJ mol-1 in gas phase to 71.5 kJ mol-1 in water suggesting more facile reaction in low polar solvents. The minimal global electron density transfer (GEDT) at the TSs suggests non-polar character and the formation of new covalent bonds has not been started at the located TSs showing non-covalent intermolecular interactions from Atoms-in-Molecules (AIM) study and in the Independent Gradient Model (IGM) isosurfaces. The AIM analysis shows more accumulation of electron density at the C-C interacting region relative to the C-O one, and earlier C-C bond formation is predicted from the bonding evolution theory (BET) study.

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“…Cycloaddition reactions have been widely analyzed within the Frontier Molecular Orbital [14] (FMO) theory until the establishment of MEDT in 2016, [6] which states the decisive role of the changes of electron density in the feasibility of an organic reaction [6,7] . Several aspects of 32CA reactions such as the regio‐, [8,15] stereo‐ [8,16] and chemoselectivity, [15,17] catalysis, [18] strain promotion, [19] substituent effects, [20] and other aspects [21,22] have been successfully analyzed within MEDT.…”

Section: Introductionmentioning

confidence: 99%

A Molecular Electron Density Theory Study of the Lewis Acid Catalyzed [3+2] Cycloaddition Reactions of Nitrones with Nucleophilic Ethylenes

Domingo

Ríos‐Gutiérrez

Acharjee³

2022

Eur J Org Chem

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The BF 3 Lewis acid (LA) catalyzed [3 + 2] cycloaddition (32CA) reaction of 1-pyrroline-1-oxide (PNO) with 2,3-dihydrofuran (DHF) has been studied within the molecular electron density theory (MEDT) at the ωB97X-D/6-311G(d,p) computational level. Electron localization function (ELF) characterizes PNO and the corresponding PNO : BF 3 complex as zwitterionic species. Conceptual DFT indices allow classifying PNO and DHF as marginal electrophiles and strong nucleophiles, while the PNO : BF 3 complex is a strong electrophile. Consequently, while the noncatalyzed 32CA reaction is non-polar, the BF 3 catalyzed one has a high polar character, revealed by the analysis of the global electron density transfer (GEDT) at the transition state structures. The BF 3 catalyzed 32CA reaction, which is classified as of reverse electron density flux (REDF), presents high exo stereoselectivity, and total ortho regioselectivity. The presence of the BF 3 catalyst decreases the activation enthalpy of the 32CA reaction in dichloromethane by 7.5 kcal mol À 1 , as a consequence of the increase of the polar character of the reaction, in complete agreement with the experimentally observed acceleration.

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

Cited by 9 publications

References 69 publications

Unveiling the Substituent Effects in the Stereochemistry of [3+2] Cycloaddition Reactions of Aryl‐ and Alkyldiazomethylphosphonates with Norbornadiene within a MEDT Perspective

Unveiling the Substituent Effects in the Stereochemistry of [3+2] Cycloaddition Reactions of Aryl‐ and Alkyldiazomethylphosphonates with Norbornadiene within a MEDT Perspective

Unveiling the regioselective synthesis of antiviral 5-isoxazol-5-yl-2´-deoxyuridines from the perspective of a molecular electron density theory

A Molecular Electron Density Theory Study of the Lewis Acid Catalyzed [3+2] Cycloaddition Reactions of Nitrones with Nucleophilic Ethylenes

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