Nickel-Catalyzed Alkylative Cross-Coupling of Anisoles with Grignard Reagents via C-O Bond Activation

We report nickel-catalyzed cross-coupling of methoxyarenes with alkylmagnesium halides, in which a methoxy group is eliminated. A wide range of alkyl groups, including those bearing beta-hydrogens, can be introduced directly at the ipso position of anisole derivatives. We demonstrate that the robustness of a methoxy group allows this alkylation protocol to be used to synthesize elaborate molecules by combining it with traditional cross coupling reactions or oxidative transformation. The success of this method is dependent on the use of alkylmagnesium iodides, but not chlorides or bromides, which highlights the importance of the halide used in developing catalytic reactions using Grignard reagents.