Abstract Although multiple cycloaddition pathways are theoretically accessible, intramolecular cycloadditions of ester-substituted alkenylheptafulvenes experimentally proceed with exclusive 8+2 selectivity. We report a computational investigation of the periselectivity and diastereoselectivity of this reaction using density functional theory (DFT) and frontier molecular orbital (FMO) analysis. The reaction is shown to proceed via an initial 8+2 cycloaddition followed by a 1,5 sigmatropic hydrogen shift. Alternative cycloaddition pathways, including the 6+4, 4+2, and 2+4 modes, are thermodynamically disfavored, accounting for the experimentally observed periselectivity. The stereoselectivity results from favorable secondary interactions of the ester substituent. This study highlights the dual role of the ester carbonyl group as an unfavorable bonding partner but a favorable interacting motif, shaping selectivity through electrostatic and orbital effects rather than through bond formation.
Bianchi et al. (2026) studied this question.