A novel method for skeletal editing of pyridines through atom-pair swap from CN to CC is reported, enabling the generation of benzenes and naphthalenes in a modular fashion. The process involves sequential dearomatization, [4+2] cycloaddition, and rearomatizing retrocycloaddition reactions in a one-pot sequence. This strategy allows precise substitution or rearrangement of atoms in the pyridine ring, enabling late-stage modification of complex molecules. The method is robust, catalyst-free, and applicable to a broad range of substrates, including various drugs and pharmaceuticals. The approach enables the introduction of diverse functional groups at specific positions on the arene moiety, with excellent regioselectivity. The method was demonstrated on several drug cores, showing its potential for late-stage skeletal diversification. The reaction conditions are mild, and the process is scalable. The strategy provides a general platform for installing pharmacologically relevant functional groups into aromatic compounds. The study also highlights the importance of this method in the field of medicinal chemistry for scaffold-hopping and fragment coupling. The method was validated through experimental and computational studies, showing high regioselectivity and thermodynamic favorability. The results demonstrate the effectiveness of this atom-pair swap strategy for pyridine skeletal editing.A novel method for skeletal editing of pyridines through atom-pair swap from CN to CC is reported, enabling the generation of benzenes and naphthalenes in a modular fashion. The process involves sequential dearomatization, [4+2] cycloaddition, and rearomatizing retrocycloaddition reactions in a one-pot sequence. This strategy allows precise substitution or rearrangement of atoms in the pyridine ring, enabling late-stage modification of complex molecules. The method is robust, catalyst-free, and applicable to a broad range of substrates, including various drugs and pharmaceuticals. The approach enables the introduction of diverse functional groups at specific positions on the arene moiety, with excellent regioselectivity. The method was demonstrated on several drug cores, showing its potential for late-stage skeletal diversification. The reaction conditions are mild, and the process is scalable. The strategy provides a general platform for installing pharmacologically relevant functional groups into aromatic compounds. The study also highlights the importance of this method in the field of medicinal chemistry for scaffold-hopping and fragment coupling. The method was validated through experimental and computational studies, showing high regioselectivity and thermodynamic favorability. The results demonstrate the effectiveness of this atom-pair swap strategy for pyridine skeletal editing.