Year: 2025
Type: preprint
Abstract: 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.
Source: ChemRxiv
Authors: Prakash Kafle, Shuhei Yasuda, Daniel Nilson, Deacon Herndon, Rylan Fox, Indrajeet Sharma
Institution: University of Oklahoma
Language: English
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: green
OpenAlex ID: W4414013303