How Solvent Dynamics Controls the Schlenk Equilibrium of Grignard Reagents: A Computational Study of CH3MgCl in Tetrahydrofuran.

The Schlenk equilibrium is a complex reaction governing the presence of multiple chemical species in solution of Grignard reagents. The full characterization at the molecular level of the transformation of CH3MgCl into MgCl2 and Mg(CH3)2 in tetrahydrofuran (THF) by means of ab initio molecular dynamics simulations with enhanced-sampling metadynamics is presented. The reaction occurs via formation of dinuclear species bridged by chlorine atoms. At room temperature, the different chemical species involved in the reaction accept multiple solvation structures, with two to four THF molecules that can coordinate the Mg atoms. The energy difference between all dinuclear solvated structures is lower than 5 kcal mol-1. The solvent is shown to be a direct key player driving the Schlenk mechanism. In particular, this study illustrates how the most stable symmetrically solvated dinuclear species, (THF)CH3Mg(μ-Cl)2MgCH3(THF) and (THF)CH3Mg(μ-Cl)(μ-CH3)MgCl(THF), need to evolve to less stable asymmetrically solvated species, (THF)CH3Mg(μ-Cl)2MgCH3(THF)2 and (THF)CH3Mg(μ-Cl)(μ-CH3)MgCl(THF)2, in order to yield ligand exchange or product dissociation. In addition, the transferred ligands are always departing from an axial position of a pentacoordinated Mg atom. Thus, solvent dynamics is key to successive Mg-Cl and Mg-CH3 bond cleavages because bond breaking occurs at the most solvated Mg atom and the formation of bonds takes place at the least solvated one. The dynamics of the solvent also contributes to keep relatively flat the free energy profile of the Schlenk equilibrium. These results shed light on one of the most used organometallic reagents whose structure in solvent remains experimentally unresolved. These results may also help to develop a more efficient catalyst for reactions involving these species.