Understanding the mechanism and regio‐ and stereo selectivity of [3 + 2] cycloaddition reactions between substituted azomethine ylide and 3,3,3‐trifluoro‐1‐nitroprop‐1‐ene, within the molecular electron density theory

Abstract 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.