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Photoredox-Catalyzed Site-Selective Intermolecular C(sp<sup>3</sup>)–H Alkylation of Tetrahydrofurfuryl Alcohol Derivatives

R. ABE, Kazunori Nagao, Tomohiro Seki, Dai Hata, Yusuke Sasaki, Hirohisa Ohmiya

2025Organic Letters5 citationsDOIOpen Access PDF

Abstract

High Resolution Image Download MS PowerPoint Slide 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(sp 3 )–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.

Topics & Concepts

AlkylationChemistryCatalysisIntramolecular forceAlcoholIntermolecular forceRadicalCombinatorial chemistryPhotoredox catalysisHydrogen atomMedicinal chemistryOrganic chemistryMoleculeAlkylPhotocatalysisRadical Photochemical ReactionsCatalytic C–H Functionalization MethodsSulfur-Based Synthesis Techniques