Site‐Selective Direct Intermolecular C(sp³)−H Alkylation of Saccharides and Switching of Reaction Sites by Changing Photocatalysts

Abstract

We developed a site‐selective intermolecular C(sp3)−H alkylation of saccharides with electron‐deficient alkenes using photocatalysis by anthraquinone and tetrabutylammonium decatungstate (TBADT). The main reaction site of anthraquinone‐catalyzed C(sp3)−H alkylation is determined by the weakness of the C−H bond. The reaction site can be switched by changing the photocatalyst to TBADT, and the site‐selectivity is controlled by the steric hindrance between the bulkier TBADT photocatalyst and the substituents of the saccharides. The reaction is compatible with several electron‐deficient alkenes and saccharides, and provides C‐saccharides in good yields. Furthermore, the monoalkylated product was obtained in excellent yield, even on the gram scale, under TBADT photocatalysis. Applicability was demonstrated by site‐selective C(sp3)−H alkylation of glycosyl derivatives. The reactions proceed via a site‐selective hydrogen atom transfer between the photocatalyst and saccharide, and the generated carbon radical reacts with an electron‐deficient alkene to give alkylated products.

Transformations of carbohydrate derivatives enabled by photocatalysis and visible light photochemistry

“…A report from Li and Kubinobu documents examples of switching the site of C -alkylation of ketal-protected pyranosides by changing the structure of the hydrogen atom-abstracting photocatalyst ( Scheme 54 ). 123 For example, 6- O -acetylated bis(isopropylidene)galactopyranose underwent C3-selective alkylation upon excitation with UV light (365 nm) in the presence of anthraquinone as photocatalyst, versus C4-selective alkylation in the presence of tetrabutylammonium decatungstate (TBADT). The authors proposed that relative bond dissociation enthalpies play a role in the site-selectivity of HAT to the semiquinone radical, whereas photoexcited decatungstate selectively abstracts the hydrogen atom from the most sterically accessible position.…”

Origin of site-selectivity of hydrogen atom transfer in carbohydrate C–H alkylations via photoredox catalysis

“…3 Because of multiple C–H bonds with similar reactivity in monosaccharide-based molecules, the control of selectivity in C–H modifications to access diverse sugar derivatives is challenging. By employing photoredox catalysis and transition metal catalysis, impressive selective C–H manipulations of carbohydrates, such as epimerization, 4 oxidation, 5 alkylation 6 and alkenylation, 7 have been realized. Recently, the Taylor group developed a site- and stereoselective C–H alkylation of carbohydrates aided by diarylborinic acid and photoredox catalysis (Scheme 1a).…”