Does the reaction of nitrone derivatives with allenoates proceed by an initial (3+2) cycloaddition or O-Nucleophilic addition? A quantum chemical investigation

The question of whether the reaction between nitrone derivatives and allenoates proceeds with initial (3 + 2) cycloaddition (32CA) or the oxygen-nucleophilic (O-nucleophilic) addition has been theoretically investigated using density functional theory (DFT) at the M06-2X/6-311G(d,p) level of theory. In all of the reactions considered, the initial 32CA route is kinetically and thermodynamically preferred over the initial O-nucleophilic addition. Increasing the steric bulk of the substituents on the reactants bridges the kinetic and thermodynamic gap between the initial 32CA and O-nucleophilic addition but the 32CA is still energetically preferred, showing that with increasing steric bulk, the O-nucleophilic addition may become competitive with the 32CA route. Within the 32CA reactions, analysis of electrophilic (P-k(+)) and nucleophilic (P-k(-)) Parr functions at the various reaction centers in the allenoate indicates that the three-atom-components (TACs) chemo-selectively add across the olefinic bond bearing the ester functionality (COOMe) with the largest Mulliken spin density coefficients and this observation agrees with the energetic trends and experimental outcomes. The global electron density transfer (GEDT) analysis reveals a high polar character associated with the 32CA reaction of methylbuta-2,3-dienoate with N-methyl-C-phenylnitrone while that of the 32CA reaction of methylpenta-2,3-dienoate with N-cyclo-hexenylnitrone has a low polar character.

Automated summary

The research indicates that the reaction between nitrone derivatives and allenoates tends to proceed through the initial (3+2) cycloaddition route both kinetically and thermodynamically, instead of the initial oxygen-nucleophilic addition. Increasing steric bulk can bridge the gap between the two reactions, but the (3+2) cycloaddition remains energetically preferred.