Origin of Substituent-Modulated Regioselectivity in Phosphine-Catalyzed [3 + 2] Cyclization of Allenoates and Enones: A Kinetic Shift toward Curtin–Hammett Control

The phosphine-catalyzed [3 + 2] cycloaddition of allenoates with enones provides an efficient route to five-membered carbocycles and exhibits regioselectivity that depends on the substituents of the substrates. To elucidate the origin of the substituent effects, density functional theory calculations and kinetic modeling are performed on the reactions of unsubstituted/substituted allenoates (2/8) with arylideneoxindoles (e-iii). Nucleophilic attack of PPh₃ on the allenoate generates interconvertible Z-, E-, and twisted adducts: the former two participate in regioselective [3 + 2] cyclization. For 2, the major γ-regioisomeric product forms via the E-adduct. Kinetic modeling predicts an α:γ ratio of 1:99, consistent with the experimentally observed 10:90 selectivity. By contrast, the reaction of 8 yields the α-regioisomer via the Z-adduct. The computed isomer ratio of 99:1 agrees with the experimental value of >95:5. The switch in regioselectivity is attributed to the interplay between electronic and steric effects. Secondary orbital interactions favor the γ-[3 + 2] pathway. Substituent-induced steric hindrance is found to elevate the activation barriers to cyclization, thereby shifting the kinetic regime toward Curtin–Hammett control and modulating regioselectivity. These findings highlight the pivotal role of adduct dynamics in phosphine catalysis and clarify the conditions under which Curtin–Hammett control governs product selectivity.