Dedicated to Prof. Shinji Murai
Abstract
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.
1 Introduction
2 Stoichiometric Remote C–H Functionalizations
3 meta-C–H Functionalizations
4 para-C–H Functionalizations
5 meta-/ortho-C–H Difunctionalizations
6 Conclusions
Key words
ruthenium catalysis -
meta-selectivity -
para-selectivity - remote functionalization - C–H activation - DFT calculation - sequential functionalization
