4’-Selective alkylation of nucleosides has been recognized as one of ideal and straightforward approach to chemically-modified nucleosides, but such transformation has been scarce and less explored. In this manuscript, we combine a visible-light-mediated  photoredox catalysis and HAT auxiliary to achieve  β-C(sp³)–H alkylation of alcohol on tetrahydrofurfuryl alcohol scaffolds and exploit it to 4’-selective alkylation of nucleosides. The reaction involves intramolecular 1,5-HAT process and stereo-controlled Giese addition of the resultant radicals.
DOI: 10.1021/acs.orglett.4c04439