Native Amino Group Directed Meta-Selective C–H Arylation of Primary Amines Via Pd/Norbornene Catalysis

The selective functionalization of remote C–H bonds in free primary amines holds significant promise for the late-stage diversification of pharmaceuticals. However, to date, the direct functionalization of the meta position of amine substrates lacking additional directing groups remains underexplored. In this Letter, we present a successful meta-C–H arylation of free primary amine derivatives using aryl iodides, resulting in synthetically valuable yields. This meta-selective C–H functionalization is achieved through a sequence involving native amino-directed Pd-catalyzed seven-membered cyclometalation, followed by the utilization of a norbornene-type transient mediator.