Organozinc Reagents in Solution: Insights from Ab Initio Molecular Dynamics and X-ray Absorption Spectroscopy

Organozinc reagents are widely used in synthesis; however, their solution-phase structures and the resulting effects on reactivity remain insufficiently understood. Here, we present a computational workflow, validated by X-ray absorption spectroscopy, to characterize the solvation dynamics of ZnCl₂, ZnMeCl, and ZnMe₂ in tetrahydrofuran (THF) solution. Ab initio molecular dynamics (metadynamics and Blue Moon sampling) in explicit solvent cage reveal a distribution of solvation states at room temperature, resolving the long-standing ambiguity surrounding the solvation environment of ZnMe₂. Spectral signatures derived from molecular dynamic trajectories and time-dependent DFT closely match the experimental XANES and IR data collected from the literature. We apply this framework to evaluate the effects of solvation on the transmetalation between ZnMe₂ and PdMeCl(PPh₂Me)₂. Although THF coordination to ZnMe₂ has a limited influence on activation barriers, changes in solvation state along the reaction coordinate emerge as key thermodynamic drivers. These findings underscore the need to account for solvation equilibria when modeling organozinc-mediated catalytic processes.