Computational Study of the Magnesium Bonds in Turbo Grignard Reagents

Abstract

High-yielding formation of Grignard reagents from various organic halides is frequently challenging. A two-step process has been developed in which a very inexpensive material can react at low yield to form a Grignard which is then employed in a high-yielding exchange reaction to form the desired Grignard. The second step typically employs lithium chloride to form so called “turbo” Grignards that enable exchange at a temperature which prevents reactions with other functionalities on the organic halide. Most exchanges go from an alkyl Grignard to an aryl Grignard. However, few of these “turbo” Grignards are well characterized and exchanges with other alkyl halides is also desirable. We hypothesize that the predictor of exchange is likely something simple, such as the Mg-halogen or Mg-C bond, and does not rely much on the transition state or solvent employed. To test this hypothesis, various aryl halide compounds from literature known to undergo exchange with isopropyl magnesium chloride (i-PrMgCl) were modelled computationally to compare how the Mg bond lengths changed. Data was generated for these compounds at the given B3LYP level of theory, using GAMESS with a cc-pvtz basis set from ASSIP intern Anh Pham and using TeraChem with a 6-31G basis set from research volunteer Johnny Bui. The Grignard i-PrMgCl and the turbo Grignard i-PrMgCl•LiCl served as controls. The addition of LiCl increased Mg-Cl bonds lengths and decreased bond orders, while the Mg-C bond lengths showed little to no variation. Calculations for the literature Grignard reagents in the absence of LiCl displayed shortened Mg-Cl bond lengths and increased bond orders compared to those for i-PrMgCl. This data suggests an increasing bond distance or decreasing bond order between Mg and Cl will create proper conditions for a “turbo” Grignard. Our data predict that Grignards with electron-withdrawing groups near the C-Mg bond are less suited for exchange. In future work, we plan to collaborate with Dr. Paige’s lab to experimentally test putative “turbo” Grignard designs that could enable exchange with other alkyl halides through attachment of electron releasing groups.