A Directive Ni Catalyst Overrides Conventional Site-Selectivity in Pyridine C–H Alkenylation

A remote C3–H activation of pyridine-containing substrates can be achieved with a directive Ni catalyst. The bifunctional NHC ligand incorporates an Al-binding side-arm that recruits and orients the substrate leading to the assembly of the requisite macrocyclophane transition state through reversible coordination. This assembly not only induces the reactivity of the otherwise unreactive Ni catalyst, but also overrides the intrinsic C2/C4 electronic bias of the Al-bound pyridine substrate, allowing for the first time, the C3 alkenylation of a variety of pyridine and heteroarene substrates as the limiting reagent.