A Practical Procedure for Iron-Catalyzed Cross-Coupling Reactions of Sterically Hindered Aryl-Grignard Reagents with Primary Alkyl Halides

Although iron-catalyzed cross-coupling reactions of arylmagnesium halides with alkyl halides are well established and proceed effectively under a variety of experimental conditions, they often find limitations when working with sterically hindered aryl-Grignard reagents. Outlined in this paper is a practical solution that allows this gap in coverage to be filled. Specifically, it is shown that bis(diethylphosphino)ethane (depe) crafts an effective coordination environment about Fe(+2). This commercially available ligand is slim enough not to interfere with the loading of the iron center even by ortho,ortho-disubstituted arylmagnesium halides, yet capable of preventing premature reductive coupling of the resulting organoiron species, which seem to be hardly basic either. The reaction is compatible with various polar functional groups as well as with substrates containing beta-heteroatom substituents. Moreover, the procedure even allows encumbered neopentylic electrophiles to be arylated with donors as bulky as mesitylmagnesium bromide, whereas secondary alkyl halides tend to eliminate.