Directing Group‐Free Regioselective meta‐C−H Functionalization of Pyridines

Abstract

AbstractThe pyridine core is among the most common motifs found in pharmaceuticals and agrochemicals. Consequently, the C−H functionalization of pyridine is a prized reaction, as it can help access a broad spectrum of valuable chemicals. However, the intrinsic electronic properties of pyridines hinder their meta‐C−H functionalization, requiring drastic conditions affecting functional group compatibility. A synthetic manoeuvre to overcome this challenge involves the temporary conversion of pyridines into electron‐rich intermediates and subsequent regioselective electrophilic functionalization. This was recently accomplished by a ring‐opening ring‐closing sequence via Zincke imine intermediates by McNally and co‐workers, and a dearomatization‐rearomatization sequence via oxazino‐pyridine intermediates by the Studer group. The mildness and simplicity of these protocols enable them to work with complex molecular setups for synthesizing natural products and bioactive molecules.