The molecular mechanism and stereoselectivity of the BF 3 Lewis acid catalyzed [3+2] cycloaddition (32CA) reaction between C-methoxycarbonyl nitrone and cyclopentene have been theoretically studied using DFT methods at the MPWB1K/6-31G(d) computational level. The BF 3 catalyst accelerates the 32CA reaction by decreasing the activation energy leading to the formation of the trans cycloadduct as the kinetic product, in agreement with the experimental data. Inclusion of solvent effects slightly increases the activation energy and decreases the exothermic character of the 32CA reaction as a consequence of a better solvation of nitrone than the transition state and the cycloadduct.The use of the lithium cation as LA catalyst does not make any remarkable change with respect to the BF 3 catalyzed process. The nature of the mechanism has been also studied using the reactivity indices defined within the conceptual DFT.
The domino retro [3+2] cycloaddition/cyclization reaction of bicyclic isoxazolidines 4 yielding [6.6.5]-tricyclic isoxazolidines 7 and [6.5.5]-tricyclic isoxazolidines 8, experimentally reported by Holmes et al., has been studied in toluene using DFT methods at the MPWB1K/6-311G** level. This domino reaction begins by a reto [3+2] cycloaddition reaction of the bicyclic isoxazolidines 4 forming the cyclic nitrones 5, which undergo a subsequent cyclization reaction yielding [6.6.5]-tricyclic isoxazolidines 7 or [6.5.5]-tricyclic isoxazolidines 8. The [3+2] cycloaddition reactions of cyclic nitrone 12 with ethylene 13, and with (Z)-but-2-enenitrile 15 were also studied in order to explain the role of the tether in the cyclization step. The present study shows that, unlike the [3+2] cycloaddition reaction of cyanoalkene 15, the cyano group in the cyclization step does not have any effect on the selectivity. The present study suggests that the presence of the BF3 catalyst in the domino reaction can change the formation of the [6.5.5]-tricyclic isoxazolidine 7 to the [6.6.5]-tricyclic isoxazolidine 8.
The mechanism of the [3+2] cycloaddition (32CA) reaction of C-phenyl-N-methylnitrone with ethyl trifluoroacetoacetate has been theoretically studied at the MPWB1K/6-311G(d,p) level. This 32CA reaction, in which the enol form of the β-keto ester participates as the ethylene component, takes place with complete ortho regioselectivity and exo stereoselectivity. The presence of the CF3 group in the β-position in the enol acetate accelerates the 32CA reaction, but it does not modify the regioselectivity, which is controlled by the presence of the ester group. While ortho regioselectivity is reproduced by the MPWB1K calculations, the endo selectivity is not. The inclusion of solvent effects slightly decreases the reactivity but does not modify the gas phase selectivities. Analysis of the DFT global reactivity indices and the Parr functions in reagents provide a rationalization for the participation of ethyl trifluoroacetoacetate and the regioselectivity in this zw-type 32CA reaction.
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