Tetramethylethylenediamine Stabilizes Organozinc Surface Intermediates against Chemical Etching but Not against Protodemetalation

<i>N,N,N',N'</i>-Tetramethylethylenediamine (TMEDA) is known to increase yields in Negishi-type cross-coupling reactions in aqueous-surfactant mixtures, presumably by increasing the persistence of the organozinc intermediates toward protodemetalation. The degree to which such stabilization enhances the key surface intermediates, however, is unknown. Here, the persistence of surface organozinc reaction intermediates was examined by fluorescence lifetime imaging microscopy (FLIM). TMEDA did not increase the persistence of these oxidative addition intermediates toward protodemetalation by water in THF or DMF, indicating that its stabilizing effect may be limited to the solution phase. TMEDA, however, enhanced the persistence of these oxidative addition intermediates toward trimethylsilyl chloride (TMSCl) and 1,2-dibromoethane, reagents commonly used in preparative organozinc reagent syntheses that presumably act through zinc surface etching. The data suggest that TMEDA hinders this surface etching. The results pinpoint the elementary steps that result in enhanced water stability of organometallics, for use in developing aqueous-organic reaction systems.