A molecular electron density theory study on the [3 + 2] cycloaddition reaction of a 2,4-dienone and a nitrone: regioselectivity, diastereoselectivity, energetic aspects, and molecular mechanism

[3 + 2] Cycloaddition reaction of N-methyltrifluoromethylmethylene nitrone (MFN) and 2E,4E-5-(benzo[1,3]dioxol-5-yl)-1-(piperidin-1-yl)penta-2,4-dien-1-one (BPD) is studied using molecular electron density theory. The Parr functions analysis predicted successfully the local reactivities and consequent regioselectivity. The calculation of the reaction and activation Gibbs free energies confirmed that the formation of the reported major product under the experimental conditions is more favorable both kinetically and thermodynamically. The origin of this diastereoselectivity was explained by employing IGMH analysis. ELF analysis suggests that the reaction proceeds via a two-stage one-step mechanism and single bonds are formed via coupling of the pseudoradical centers and polarization of the non-bonding electrons.

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