A DFT study on the mechanism and selectivity of [3 + 2] cycloaddition reactions leading to pyrole[2,1-a] phthalazine compounds

Abstract

The mechanism of [3 + 2] cycloaddition (32CA) reactions of phthalazinium-2-dicyanomethanide with electron-deficient and electron-rich ethylenes has been studied using density functional theory (DFT) methods at the M06-2X/cc-pVDZ level of theory. The energy results indicated that the regio- and stereoselectivity of the two 32CA reactions oppose one another, which is in agreement with the experimental report. Accordingly, in the 32CA reaction of phthalazinium-2-dicyanomethanide 1 with methyl vinyl ketone 2a, an electron poor dipolarophile, the meta/endo pathway was more stable than others, while the ortho/exo pathway was the most stable for the 32CA reaction of phthalazinium-2-dicyanomethanide 1 with 1-methoxy-4-vinyl benzene 2b, an electron-rich dipolarophile. Moreover, DFT reactivity indices were studied for the reagents to explain the nucleophilicity and electrophilicity of reagents and selectivity of the reactions. The electron rearrangements along the preferred pathways of these 32CA reactions were studied using the topological analysis of the electron localization function (ELF). The ELF analysis revealed that the reactions proceed through a two-stage one-step mechanism. The noncovalent interactions topological analysis of the possible pathways of the reactions revealed that in addition to strong attractive and repulsive interactions, the weak non-covalent interactions and the steric repulsive interactions have important roles in the determination of the preferred regio- and stereoselective pathway.