Remote C-H Functionalizations by Ruthenium Catalysis

Synthetic transformations of otherwise inert C-H bonds have emerged as a powerful tool for molecular modifications during the last decades, with broad applications towards pharmaceuticals, material sciences, and crop protection. Consistently, a key challenge in C-H activation chemistry is the full control of site-selectivity. In addition to substrate control through steric hindrance or kinetic acidity of C-H bonds, one important approach for the site-selective C-H transformation of arenes is the use of chelation-assistance through directing groups, therefore leading to proximity-induced ortho-C-H metalation. In contrast, more challenging remote C-H activations at the meta- or para-positions continue to be scarce. Within this review, we demonstrate the distinct character of ruthenium catalysis for remote C-H activations until March 2021, highlighting among others late-stage modifications of bio-relevant molecules. Moreover, we discuss important mechanistic insights by experiments and computation, illustrating the key importance of carboxylate-assisted C-H activation with ruthenium(II) complexes.