Sustainable Access to N‐Heterocycles: One‐Pot Cascade Synthesis of Pyrroles From Bio‐Derived Furans

Abstract

ABSTRACT The synthesis of pyrroles, fundamental nitrogen‐heterocyclic scaffolds in pharmaceuticals and materials science, remains a synthetic challenge, typically requiring pre‐functionalized precursors and multi‐step protocols. Here, we report an efficient cascade synthesis of N‐substituted pyrroles directly from bio‐derived furans and nitroarenes, enabled by a synergistic bifunctional catalyst. The catalyst, featuring highly dispersed platinum (Pt) clusters anchored on a Brønsted acid‐rich zeolite (HY), achieves near‐quantitative yields (up to 97%) under atmospheric H2 pressure. Systematic characterization, including aberration‐corrected transmission electron microscopy and x‐ray absorption spectroscopy, reveals that the Pt clusters provide the necessary moderate hydrogenation activity, thereby selectively reducing nitroarenes to anilines while leaving the furan ring intact. In contrast, Pt nanoparticles, owing to their excessive hydrogenation activity, lead to undesired over‐hydrogenation of both the furan and benzene rings. The zeolite's Brønsted acid sites subsequently facilitate a rapid ring‐opening/condensation sequence, enabling an oxygen‐to‐nitrogen transmutation to form pyrroles. This atom‐economic strategy tolerates a broad range of functional groups (>30 examples) and is further validated by the streamlined synthesis of a potent antimycobacterial drug candidate. Our findings demonstrate how modulating the electronic structure and ensemble configuration of noble metals at the atomic scale can unlock novel, sustainable transformation pathways for biomass‐derived platform chemicals.