Photoredox-Catalyzed Site-Selective Intermolecular C(sp3)-H Alkylation of Tetrahydrofurfuryl Alcohol Derivatives

Org Lett. 2025 Jan 13. doi: 10.1021/acs.orglett.4c04439. Online ahead of print.

Abstract

4'-Selective alkylation of nucleosides has been recognized as one of the ideal and straightforward approaches to chemically modified nucleosides, but such a transformation has been scarce and less explored. In this Letter, we combine a visible-light-mediated photoredox catalysis and hydrogen atom transfer (HAT) auxiliary to achieve β-C(sp3)-H alkylation of alcohol on tetrahydrofurfuryl alcohol scaffolds and exploit it for 4'-selective alkylation of nucleosides. The reaction involves an intramolecular 1,5-HAT process and stereocontrolled Giese addition of the resultant radicals.