A comparison of the electrophilic reactivities of Zn2+ and acetic acid as catalysts of enolization:: Imperatives for enzymatic catalysis of proton transfer at carbon

The deprotonalion of the alpha-CH3 and alpha-CH2OD groups of hydroxyacetone and the alpha-CH3 groups of acetone in the presence of acetate buffer and zinc chloride in D2O at 25 degreesC was followed by monitoring the incorporation of deuterium by H-1 NMR spectroscopy, and the rate laws for catalysis of these reactions by acetate anion and zinc dication were evaluated. Relative to solvent water at a common standard state of 1 M, Zn2+ provides 6.3 and 4.4 kcal/mol stabilizations, respectively, of the transition states for deprotonation of the alpha-CH2OD and alpha-CH3 groups of hydroxyacetone by acetate anion, and a smaller 3.3 kcal/mol stabilization of the transition state for deprotonation of the alpha-CH3 group of acetone. There is only a 1.4 kcal/mol smaller stabilization of the transition state for the acetate-ion-promoted deprotonation of acetone by the Bronsted acid acetic acid than by Zn2+, which shows that, in the absence of a chelate effect, there is no large advantage to the use of a metal dication rather than a Bronsted acid to stabilize the transition state for deprotonation of alpha-carbonyl carbon.