Origins of Steric Effects in General-Base-Catalyzed Enolization: Solvation and Electrostatic Attraction

Bronsted plots for general-base-catalyzed enolization of aldehydes and ketones show significant negative deviations for the rates of proton removal by sterically hindered amine bases. The origins of the deviations are not apparent from considerations of interactions at the site of the proton transfer. Contrasting behavior is observed in general-base-catalyzed proton removal from an iminium derivative, N1'-methyl-2-(1-hydroxybenzyl)thiamin (NMHBnT), which shows no deviations from the Bronsted correlation for sterically hindered amine bases. The difference in behavior for these two systems suggests that the steric effects arise from disruption of solvation of the enolate enforced by the electrostatic requirements of the overall process. This interpretation also can account for reduced steric effects for enolization in the presence of metal ions.