Exploration of regiospecificity phenomenon in [2+3] cycloaddition reactions between arylnitrones and trans-substituted nitroethenes on the basis of the reactivity indices theory

Article history: Received May 30, 2012 Received in Revised form July 31, 2012 Accepted 1August 2012 Available online 1 August 2012 Analysis of global electrophilicity and nucleophilicity power of the addends indicate polar character of [2+3] cycloaddition reactions between arylnitrones and trans-substituted nitroethenes. The regioselectivity of these reactions is determined by nucleophilic attack of oxygen atom from nitrone on activated β-position of nitroalkene. Interaction of this type leads to 4-nitroisoxazolidines, which are the only reaction products. © 2012 Growing Science Ltd. All rights reserved.


Results and Discussion
The global (electronic potential μ, electrophilicity power ω, nucleophilicity N) and local (electrophilicity ω k , nucleophilicity N k ) reactivity indices for example reactants (1-2) were estimated according to the equations recommended by Parr 10 and Domingo 8 (for details see next section).Electrophilicity scale was built and validated by Domingo group 11 based on the B3LYP/6-31g(d) calculations.This model was adopted for most reaction systems 9 .Therefore, the quantum chemical calculations were performed using B3LYP/6-31g(d) theoretical level 12 .The results are collected in It has been found, that the nitrones 2-4 show weaker electrophilic character than the nitroethenes 1a-d.Their electronic potential (μ) equals -0.1244÷-0.1256a.u., whereas that of the nitroalkenes 1a-d is only -0.1867÷-0.2147.This indicates, that in the reactions studied, the charge should be transferred from nitrone to nitroalkene.Analysis of global electrophilicity indices (ω) leads to similar conclusion.
The electrophilicity difference (Δω) of the analysed reagent pairs (Scheme 1) is in the range from 0.69 to 1.71 (Table 3).Therefore, the reactions can be considered as polar cycloadditions 8 .According to the Domingo concept 8,13 , the regioselectivity of such reactions may be forecasted using local electrophilicity (ω k ) and nucleophilicity (N k ) indices.According to this approach, most favorable interaction takes place between most nucleophilic and most electrophilic centers.
The values of ω k obtained for the nitroalkenes 1a-d (Table 2) indicate, that β-position of the nitrovinyl moiety is the most electrophilic site, therefore, it should be the preferred position for nucleophilic attack.In particular, for less electrophilic 1-nitroprop-1-ene (1a) ω β =0.23 eV, whereas for more electrophilic 3,3,3-trichloro-1-nitroprop-1-ene (1d) ω β =0.34 eV.On the other hand, the N k indices indicate that in the nitrones 2-4, the oxygen atom of >C=N(O)-moiety is the most nucleophilic site (N O =0.57÷0.63eV).Hence, the reaction course should be controlled by the attack of one of the nucleophilic sites in the nitrone on the electrophilic site localized on the atom C β in nitrovinyl group of the corresponding nitroalkene.(Scheme 1).Interactions of this type lead to 4nitroisoxazolidines.

Conclusions
Analysis of global electronic properties of the addends indicate polar character of [2+3] cycloaddition reactions between arylnitrones and trans-substituted nitroethenes.This is consistent with the kinetic studies 3,7 .The regioselectivity of these reaction is determined by nucleophilic attack of the oxygen atom of >C=N(O)-nitrone moiety on activated β-position of nitroalkene.Interaction of this type leads to 4-nitroisoxazolidines as the only reaction products [3][4][5][6][7] .
According to Contreras observations 14 , Fukui f + k is represented by the square of the suitable LUMO coefficient (C), whereas f - k by the square of the suitable HOMO coefficient: The results are collected in Table 2.

Table 1 .
Experimental conditions and yields for model reactions.

Table 2 .
Global and local electronic properties of nitroalkenes 1a-d and nitrones 2-4