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

Magnesium bis(hexamethyldisilazide), Mg(HMDS)2, reacts with substoichiometric amounts of propiophenone in toluene solution at ambient temperature to form a 74:26 mixture of the enolates (E)- and (Z)-[(HMDS)2Mg2(μ-HMDS){μ-OC(Ph)CHCH3}], (E)-1 and (Z)-1, which contain a pair of three-coordinate metal centers bridged by an amide and an enolate group. The compositions of (E)-1 and (Z)-1 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, 2, between the ketone and magnesium, which undergoes first-order decay with rate constants independent of the concentration of excess Mg(HMDS)2H = 17.2 ± 0.8 kcal/mol, ΔS = −11 ± 3 cal/mol·K). The intermediate 2 has been characterized by low-temperature 1H NMR, diffusion-ordered NMR, and IR spectroscopy and investigated by computational studies, all of which are consistent with the formulation of 2 as a three-coordinate monomer, (HMDS)2Mg{η1-OC(Ph)CH2CH3}. Further support for this structure is provided by the synthesis and structural characterization of two model ketone complexes, (HMDS)2Mg(η1-OCtBu2) (3) and (HMDS)2Mg{η1-OC(tBu)Ph} (4). A large primary deuterium isotope effect (kH/kD = 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 2 via intramolecular proton transfer from the α carbon of the bound ketone to the nitrogen of a bound hexamethyldisilazide.