Elucidating Latent Mechanistic Complexity in Competing Acid-Catalyzed Reactions of Salicylaldehyde-Derived Baylis–Hillman Adducts

1H NMR-based
kinetic studies have revealed the latent
mechanistic complexity of deceptively simple hydrochloric acid-catalyzed
reactions of salicylaldehyde-derived Baylis–Hillman adducts.
Reactions conducted at 0 °C afforded 2-(chloromethyl)­cinnamic
acid derivatives as the major products and the corresponding 3-(chloromethyl)­coumarin
derivatives as the minor products. In reactions conducted in refluxing
acetic acid, however, the 3-(chloromethyl)­coumarin derivatives are
the sole products. Variable-temperature 1H NMR analysis
permitted the determination of the rate constants and kinetic parameters
involved in the pseudo-first-order formation of (Z)-2-(chloromethyl)-3-(2-hydroxyphenyl)-2-propenoic acid. The kinetic
data clearly preclude the operation of classical kinetic versus thermodynamic
control and indicate the operation of three independent reaction pathways.
Theoretical studies of these pathways undertaken at the B3LYP/6-31G­(d)
level permitted rationalization of the experimental data and provided
insights into the possible mechanism of the enzymic E–Z isomerization and cyclization of (E)-cinnamic acid analogues to afford coumarins.