10.1021/ja064927w.s001 Xuyang He Xuyang He J. Jacob Morris J. Jacob Morris Bruce C. Noll Bruce C. Noll Seth N. Brown Seth N. Brown Kenneth W. Henderson Kenneth W. Henderson Kinetics and Mechanism of Ketone Enolization Mediated by Magnesium Bis(hexamethyldisilazide) American Chemical Society 2006 Ketone Enolization Mediated 1 H NMR intramolecular proton transfer deuterium isotope effect rate studies proton transfer isotope effect displays temperature dependence enolate group ambient temperature α carbon HMDS solution NMR studies Mg toluene solution UV characterization substoichiometric amounts data support rate constants enolization proceeding model ketone complexes 295 K IR spectroscopy 2006-10-18 00:00:00 Dataset https://acs.figshare.com/articles/dataset/Kinetics_and_Mechanism_of_Ketone_Enolization_Mediated_by_Magnesium_Bis_hexamethyldisilazide_/3052996 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.