In 2012, Yu and co-workers reported a pioneering meta-selective C-H olefination using nitrile-containing templates to deliver the palladium to the meta-position via a macrocyclic cyclophane-like pre-transition state. The nitrile group is tethered to the aromatic ring by a removable linker. It coordinates weakly to palladium in an "end-on" fashion, which refers to the linear structure of C–CN–Pd bonds. The linear coordination is proposed to help overcome the high strain in the cyclophane-like pre-transition state that brings palladium to the vicinity of the meta-hydrogen. The template is designed as such that the flat arene linker keeps the substrate aromatic ring and the nitrile group coplanar. Bulky substituents on the arene linker "lock" the nitrile tether in the desired position. The delicate design results in high regioselectivity towards the meta-C-H bond. The templates can be removed easily to give toluene derivatives or hydrocinnamic acid derivatives in high yield.
In their subsequent works, Yu and co-workers report the application of the same strategy in meta-selective C-H cross-coupling, meta-C-H acetoxylation and meta-C–H olefination in a broad substrate scope. It is demonstrated that the "end-on" template not only work with the Pd(0)/Pd(II) catalytic cycle but is also compatible with the Pd(II)/Pd(IV) cycle. In all three works, addition of mono-N-protected amino acid (MPAA) such as N-acetyl glycine improves the reaction yields and enhances the regioselectivity.