A General Strategy to Access Pharmaceutically Relevant Pyridines from Nitroarenes
Argha Saha, Avishek Pan, Devika Ghosh, Anirban Pal, Srimanta Guin, Archana Kumari Redhu, Vikram Gota, Debabrata Maiti
Abstract
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.