Density functional theory study of the mechanisms of iron-catalyzed cross-coupling reactions of alkyl grignard reagents.

When compared with the established palladium and nickel catalyst systems, simple iron salts turn out to be highly efficient, cheap, toxicologically benign, and environmentally friendly precatalysts for a host of cross-coupling reactions of alkyl or aryl Grignard reagents. The inorganic Grignard reagent [Fe(MgX)(2)], where X corresponds to Br or I, is a good catalyst for cross-coupling reactions. The present study reports a thorough theoretical analysis of the mechanisms of the [Fe(MgBr)(2)] catalyzed cross-coupling reaction between 4-chlorobenzoic acid methyl ester and n-hexylicmagnesium bromide using density functional theory (DFT) calculations. Our calculations show that the overall catalytic cycle includes three basic steps: oxidation of [Fe(MgBr)(2)] to obtain [Ar-Fe(MgBr)], addition to yield [Ar-(n-hexyl)-Fe(MgBr)(2)], and reductive elimination to return to [Fe(MgBr)(2)]. The energy barrier is lower if n-hexylicmagnesium bromide attacks the intermediate of the oxidative addition directly before [Cl-Mg-Br] dissociates to form the middle product [Ar-Fe(MgBr)] than if the attack occurs after the dissociation of [Cl-Mg-Br]. The solvation effect in this step dearly leads to a lowering of the energy barrier. The rate-limiting step in the whole catalytic cycle is the reductive elimination of [Ar-(n-hexyl)-Fe(MgBr)(2)] to regenerate the catalyst [Fe(MgBr)(2)], where the electronic energy barrier Delta E is 29.74 kcal/mol in the gas phase and the Gibb's free energy in solvent THF Delta G(sol) is 28.13 kcal/mol computed using the C-PCM method.