Skeletal Editing of Furans into Pyridines

Furans are economically viable bulk chemicals predominantly derived from renewable lignocellulosic biomass, the most abundant source of organic carbon on Earth. The furan motif is commonly found in a wide array of natural products but remains underrepresented among FDA-approved drugs due to their metabolic liability. This disparity highlights the need for new strategies to diversify and functionalize furan scaffolds for therapeutic development. Herein, we report a skeletal editing strategy for furans in which sulfenylcarbenes selectively cleave the furan core to generate ene-one intermediates with a built-in leaving group, which subsequently react with a nitrogen source to restore aromaticity and furnish the most privileged drug scaffold, pyridine. This metal-free approach offers broad functional group tolerance and a conceptually distinct platform for controlled heterocycle remodeling. Mechanistic studies, supported by density functional theory (DFT) calculations, reveal a unique reaction pathway that proceeds via a cyclopropane-fused pyrrole to yield the unexpected pyridine regioisomer.