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 deprotonation 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 degrees C was followed by monitoring the incorporation of deuterium by 1H 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 Br?nsted 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 Br?nsted acid to stabilize the transition state for deprotonation of alpha-carbonyl carbon.