Kinetics and Mechanism of Ketone Enolization Mediated by Magnesium Bis(hexamethyldisilazide)

Magnesium bis(hexamethyldisilazide), Mg(HMDS)<sub>2</sub>, reacts with substoichiometric amounts of propiophenone in toluene solution at ambient temperature to form a 74:26 mixture of the enolates (<i>E</i>)- and (<i>Z</i>)-[(HMDS)<sub>2</sub>Mg<sub>2</sub>(μ-HMDS){μ-OC(Ph)CHCH<sub>3</sub>}], (<i>E</i>)-<b>1</b> and (<i>Z</i>)-<b>1</b>, which contain a pair of three-coordinate metal centers bridged by an amide and an enolate group. The compositions of (<i>E</i>)-<b>1</b> and (<i>Z</i>)-<b>1</b> were confirmed by solution NMR studies and also by crystallographic characterization in the solid state. Rate studies using UV−vis spectroscopy reveal the rapid and complete formation of a reaction intermediate, <b>2</b>, between the ketone and magnesium, which undergoes first-order decay with rate constants independent of the concentration of excess Mg(HMDS)<sub>2</sub> (Δ<i>H</i><sup>⧧</sup> = 17.2 ± 0.8 kcal/mol, Δ<i>S</i><sup>⧧</sup> = −11 ± 3 cal/mol·K). The intermediate <b>2</b> has been characterized by low-temperature <sup>1</sup>H NMR, diffusion-ordered NMR, and IR spectroscopy and investigated by computational studies, all of which are consistent with the formulation of <b>2</b> as a three-coordinate monomer, (HMDS)<sub>2</sub>Mg{η<sup>1</sup>-OC(Ph)CH<sub>2</sub>CH<sub>3</sub>}. Further support for this structure is provided by the synthesis and structural characterization of two model ketone complexes, (HMDS)<sub>2</sub>Mg(η<sup>1</sup>-OC<i><sup>t</sup></i><sup></sup>Bu<sub>2</sub>) (<b>3</b>) and (HMDS)<sub>2</sub>Mg{η<sup>1</sup>-OC(<i><sup>t</sup></i><sup></sup>Bu)Ph} (<b>4</b>). A large primary deuterium isotope effect (<i>k</i><sub>H</sub>/<i>k</i><sub>D</sub> = 18.9 at 295 K) indicates that proton transfer is the rate-limiting step of the reaction. The isotope effect displays a strong temperature dependence, indicative of tunneling. In combination, these data support the mechanism of enolization proceeding through the single intermediate <b>2</b> via intramolecular proton transfer from the α carbon of the bound ketone to the nitrogen of a bound hexamethyldisilazide.