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 the “real-world” capabilities of this method. Mechanistic studies show that, in contrast to previous mechanistic proposals, the reaction proceeds via a bis-cyclometallated Ru intermediate, followed by an S_N2-type oxidative addition.

具有 N 基导向基团的芳烃的 C-H 烷基化通常需要高温和/或苛刻的反应条件，这在传统上降低了其官能团兼容性和后期官能化的适用性。我们报告说，环金属化的 Ru 配合物能够在室温和温和的反应条件下，用伯烷基溴对带有各种 N 导向基团的芳烃进行 C-H 烷基化。我们用扩展的底物范围证明了这一点，其中包括药物分子后期烷基化的几个例子，从而展示了这种方法的“现实世界”能力。机理研究表明，与之前的机理建议相反，反应通过双环金属化 Ru 中间体进行，然后是 S _N2型氧化加成。