Emerging Strategies for meta-Heteroatom Functionalization of Pyridines.

Pyridine is a highly important nitrogen heterocycle that serves as a core structural motif in a wide range of drugs, catalysts, functional materials and agrochemicals. The direct functionalization of pyridines via C-H activation provides a straightforward approach to access valuable substitution patterns and functional groups. While ortho- and para-functionalizations are well developed, meta-selective functionalization is far more challenging, owing to the inherent electronic properties of the pyridine ring. When it comes to meta-selective functionalization of pyridine, much has been accomplished, particularly in C-C bond formation. On the other hand, when a C-heteroatom (N, O, S and halogen) bond is envisioned, there remains significant room for development. In the last two to three years, considerable progress has been made in this topic, with a variety of approaches being reported. In this Perspective, we outline a selection of the most recent advances in pyridine meta-functionalization featuring amination, hydroxylation, thiolation and halogenation by means of emerging strategies that offer elegant approaches to otherwise elusive bond formations.