Scaffold hopping of furans into 3-cyanopyridines.

Furans are economically accessible bulk chemicals largely derived from lignocellulosic biomass. Although the furan motif is widely found in natural products, it remains underrepresented in FDA-approved therapeutics owing to its metabolic instability. This gap underscores the need for strategies that diversify and functionalize furan scaffolds for drug discovery. Here, we report a scaffold-hopping strategy in which the cyano-sulfenylcarbene selectively cleaves the furan core, generating dienone intermediates bearing an intrinsic thioaryl leaving group. A subsequent reaction with a nitrogen source restores aromaticity and yields pyridines, a privileged and pharmaceutically indispensable heterocycle. This metal-free process exhibits broad functional-group tolerance, enables 15N-incorporation, and provides a conceptually distinct approach to the controlled remodeling of heterocycles. Mechanistic studies, supported by density functional theory calculations, highlight the critical role of the cyano-group in the ring-opening step of furan and uncover an unusual ring-closing pathway that proceeds via a cyclopropane-fused pyrrole, ultimately yielding an unexpected pyridine regioisomer.