RESUMO
The selectivity and the nature of the molecular mechanism of the [3 + 2] cycloaddition (32CA) reaction between 2-(dimethylamino)-1H-indene-1,3(2H)-dione (AY11) and trans(E)-3,3,3-trifluoro-1-nitroprop-1-ene(FNP10) has been studied, in which the molecular electron density theory using density functional theory methods at the MPWB1K/6-31G(d) computational level was used. Analysis of the global reactivity indices permits us to characterize FNP10 as a strong electrophile and AY11 as a strong nucleophile. Four reactive pathways associated with the ortho/meta regioselective channels and endo/exo stereoselective approaches modes have been explored and characterized in the gas phase and in the benzene solvent. The analysis of the relative energies associated with the different reaction pathways indicates that the 32CA reactions of the azomethine ylide (AY) with the nitroalkene (FNP) is meta regioselective with high endo stereoselectivity. This result is in good agreement with the experimental observations. electron localization function topological analysis of the most favored reactive pathways allows for characterizing the mechanism of this 32CA reactions as a non-concerted two-stage one-step mechanism. Finally, non-covalent interactions and quantum theory of atoms in molecule analyses at the meta/endo transition state structure indicate that the presence of different several weak interactions, namely, CF and NH contributed in favoring the formation of a meta-endo cycloadduct.
RESUMO
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 ß-keto ester participates as the ethylene component, takes place with complete ortho regioselectivity and exo stereoselectivity. The presence of the CF3 group in the ß-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.
RESUMO
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.
