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

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posted on 18.10.2006, 00:00 by Xuyang He, J. Jacob Morris, Bruce C. Noll, Seth N. Brown, Kenneth W. Henderson
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.