Resumen de Ligand-enabled meta-C-H activation using a transient mediator.
Xiao-Chen Wang, Wei Gong, Li-Zhen Fang, Ru-Yi Zhu, Suhua Li, Keary M. Engle, Jin-Quan Yu
Achieving site selectivity in C-H functionalization reactions is a significant challenge, especially when the target C-H bond is distant from existing functional groups 1,2,3,4,5. Coordination of a functional group to a metal is often a key driving force and control element in many important reactions including asymmetric hydrogenation 6, epoxidation 7,8 and lithiation 9. Exploitation of this effect has led to the development of a broad range of directed C-H activation reactions 10,11,12,13,14. However, these C-H activation methods are limited to proximal C-H bonds, which are spatially and geometrically accessible from the directing functional group. The development of meta-selective C-H functionalizations remains a significant challenge 1,2,3,4,5,15,16,17. We recently developed a U-shaped template that can be used to overcome this constraint and have shown that it can be used to selectively activate remote meta-C-H bonds 1,2. Although this approach has proved to be applicable to various substrates and catalytic transformations 3,4,5, the need for a covalently attached, complex template is a substantial drawback for synthetic applications. Here we report an alternative approach employing norbornene as a transient mediator to achieve meta-selective C-H activation with a simple and common ortho-directing group. The use of a newly developed pyridine-based ligand is crucial for relaying the palladium catalyst to the meta position by norbornene after initial ortho-C-H activation. This catalytic reaction demonstrates the feasibility of switching ortho-selectivity to meta-selectivity in C-H activation of the same substrate by catalyst control.
