Structure-reactivity effects on primary deuterium isotope effects on protonation of ring-substituted α-methoxystyrenes

Primary product isotope effects (PIEs) on L⁺ and carboxylic acid catalyzed protonation of ring-substituted α-methoxystyrenes (X-1) to form oxocarbenium ions X-2⁺ in 50/50 (v/v) HOH/DOD were calculated from the yields of the α-CH₃ and α-CH₂D labeled ketone products, determined by ¹H NMR. A plot of PIE against reaction driving force shows a maximum PIE of 8.7 for protonation of 4-MeO-1 by Cl ₂CHCOOH (ΔG° = 1.0 kcal/mol). The PIE decreases to 8.1 for protonation of 4-MeO-1 by L₃O⁺ (ΔG° = -2.8 kcal/mol) and to 5.1 for protonation of 3,5-di-NO₂-1 by MeOCH ₂COOH (ΔG° = 13.1 kcal/mol). The PIE maximum is around ΔG° = 0. Arrhenius-type plots of PIEs on protonation of 4-MeO-1 and 3,5-di-NO₂-1 by L₃O⁺ and on protonation of X-1 by MeOCH₂COOH in 50/50 (v/v) HOH/DOD give similar slopes and intercepts. These were used to calculate values of [(E_a)_H - (E_a)_D] = -1.2 kcal/mol and (A_H/A_D) = 1.0 for the difference in activation energy for reactions of A-H and A-D and for the limiting PIE at infinite temperature, respectively. These parameters are consistent with reaction of the hydron over an energy barrier. There is no evidence for quantum mechanical tunneling of the hydron through the barrier. These PIEs suggest that the transferred hydron at the transition state lies roughly equidistant between the acid donor and base acceptor and contrast with the recently published Brønsted parameters [Richard, J. P.; Williams, K. B. J. Am. Chem. Soc. 2007, 129, 6952-6961], which are consistent with a product-like transition state. An explanation for these seemingly contradictory results is discussed.