Positional isomerization of pyridine through nitrogen transposition

Positional isomers of pyridines often exhibit distinct biological activities^1,2, yet their direct interconversion remains largely inaccessible, so each isomer is typically prepared through an independent synthesis. Here we report a general strategy for pyridine positional isomerization enabled by controlled reorganization of the heteroaromatic core through sequential nitrogen insertion and deletion. Nitrogen-atom transposition allows predictable translocation of preinstalled substituents without altering substituent identity. The method is broadly applicable to mono-, di- and multisubstituted pyridines and operates across structurally complex molecular environments, providing direct access to positional isomers. This work establishes positional isomerization as a practical synthetic transformation, defining pyridine substitution patterns as mutable variables in retrosynthetic design.