Ru-Catalyzed Room Temperature Alkylation and Late-Stage Alkylation of Arenes with Primary Alkyl Bromides

The C–H alkylation of arenes with N-based directing groups typically requires high temperatures and/or harsh reaction conditions, which has traditionally reduced its functional group compatibility and applicability for late stage-functionalization. We report that a cyclometallated Ru complex is able to perform the C–H alkylation of arenes bearing a variety of N-directing groups with primary alkyl bromides at room temperature and under mild reaction conditions. We demonstrate this with an extended substrate scope, which includes several examples of late-stage alkylation of drug molecules, thus showcasing “real world” capabilities of this method. Mechanistic studies show that, contrary to previous mechanistic proposals, the reaction proceeds via a bis-cyclometallated Ru intermediate, followed by an SN2-type oxidative addition.