Differentiation and functionalization of remote C-H bonds in adjacent positions

Site-selective functionalization of C-H bonds will ultimately afford chemists transformative tools for editing and constructing complex molecular architectures. Towards this goal, it is essential to develop strategies to activate C-H bonds that are distal from a functional group. In this context, distinguishing remote C-H bonds on adjacent carbon atoms is an extraordinary challenge due to the lack of electronic or steric bias between the two positions. Herein, we report the design of a catalytic system leveraging a remote directing template and a transient norbornene mediator to selectively activate a previously inaccessible remote C-H bond that is one bond further away. The generality of this approach has been demonstrated with a range of heterocycles, including a complex anti-leukaemia agent and hydrocinnamic acid substrates. Distinguishing remote C-H bonds on adjacent carbon atoms is a fundamental challenge because of a lack of electronic or steric bias. Now, differentiation of distal C-H bonds that are adjacent to each other has been achieved by combining selective remote C-H activation-based on distance and geometry-with a norbornene-assisted palladium migration.