Mechanism of an Elusive Solvent Effect in Organozinc Reagent Synthesis

Solvent effects are often difficult to understand in cases where reaction intermediates, and thus their differential behavior in different solvents, are not directly observable by traditional ensemble analytical techniques. Herein, the sensitivity of single-particle fluorescence microscopy uniquely enables direct observation of organozinc intermediates and solvent effects on their build-up and persistence. When combined with NMR spectroscopy, these imaging data pinpoint the previously elusive mechanistic origin of solvent effects in the synthesis of widely used organozinc reagents. These findings characterize the acceleration of oxidative addition of the starting organoiodide to the surface of zinc metal in DMSO relative to THF, but once formed, surface intermediates display similar persistence in either solvent. The current studies are the first demonstration of a highly sensitive, single-particle fluorescence microscopy technique to pinpoint otherwise elusive solvent effects in synthetic chemistry.