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

Abstract

The selective functionalization of remote C−H bonds in free primary amines holds significant promise for the latestage 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.