Recent Advances in Decorating the meta-Position of Pyridines through Temporary Dearomatization Strategy

Abstract

The pyridine moiety is a privileged skeleton structure, playing an indispensable role in medicinal, chemical as well as materials science. Site-selective C-H functionalization of pyridines provides a straightforward approach to access valuable substituted pyridines. Compared to the direct orthoand para-functionalization, selective functionalization at meta-position of pyridine has long posed a significant challenge due to the inherent electronic properties. Although lots of methods such as traditional electrophilic aromatic substitution, metalation, and transition metal-catalyzed reactions have been developedfor meta-C-H functionalization, such reactions remain limited and highly challenging. In recent years, innovative strategies based on a dearomatization-rearomatization sequence for meta-selective C-H functionalization of pyridines, involving dihydropyridine, oxazino-pyridine, Zincke imine and radical ion intermediates, were accomplished. This review summarizes the latest advancements in the meta-C-H functionalization of pyridines through temporary dearomatization strategy.According to the types of dearomatized intermediates, we discuss the advantages as well as limitations of these current methods and hope to inspire further progress in this important field.