A General Strategy to Access Pharmaceutically Relevant Pyridines from Nitroarenes

The incorporation of nitrogen atoms into aromatic systems is a cornerstone of modern drug design, enabling precise modulation of molecular properties and enhanced bioactivity. Here, we report a general and efficient strategy for the first-time conversion of nitroarenes into pharmaceutically relevant pyridine heterocycles via a nitrene-mediated transformation. This process is driven by a bio-inspired iron-porphyrin catalyst that uniquely serves as a singlet oxygen reservoir, enabling the formation of aminopyridines via C5-carbon deletion through a controlled ring-editing cascade. The unprecedented selective C5-carbon deletion provides a powerful new retrosynthetic logic for heterocycle construction. The reaction proceeds under mild conditions, tolerates a wide range of functional groups, and offers broad substrate scope with high regioselectivity. Furthermore, the method's ability to efficiently convert nitroarenes into bioactive pyridine scaffolds via ipso-carbon deletion underscores its practicality and step economy. This modular platform also streamlines the synthesis of drug-like scaffolds from simple building blocks, as demonstrated by the late-stage functionalization of nimesulide derivatives with improved molecular docking and binding profiles. Overall, this work showcases a distinctive catalytic paradigm for heterocycle construction with direct implications for pharmaceutical development and molecular remodeling.