A Comparison of the Electrophilic Reactivities of Zn2+and Acetic Acid as Catalysts of Enolization: Imperatives for Enzymatic Catalysis of Proton Transfer at Carbon

Abstract

The deprotonation of the α-CH₃ and α-CH₂OD groups of hydroxyacetone and the α-CH₃ groups of acetone in the presence of acetate buffer and zinc chloride in D₂O at 25 °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 α-CH₂OD and α-CH₃ groups of hydroxyacetone by acetate anion, and a smaller 3.3 kcal/mol stabilization of the transition state for deprotonation of the α-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 Brønsted 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 Brønsted acid to stabilize the transition state for deprotonation of α-carbonyl carbon.