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.