Synthesis of Non‐Classical Arylated C‐Saccharides through Nickel/Photoredox Dual Catalysis

Abstract

The development of synthetic tools to introduce saccharide derivatives into functionally complex molecules is of great interest, particularly in the field of drug discovery. Herein, we report a new route toward highly functionalized, arylated saccharides, which involves nickel-catalyzed cross-coupling of photoredox-generated saccharyl radicals with a range of aryl- and heteroaryl bromides, triggered by an organic photocatalyst. In contrast to existing methods, the mild reaction conditions achieve arylation of saccharide motifs while leaving the anomeric carbon available, thus providing access to a class of arylated glycosides that has been underexplored until now. To demonstrate the potential of this strategy in late-stage functionalization, a variety of structurally complex molecules incorporating saccharide moieties were synthesized.

Alkyl Carbon–Carbon Bond Formation by Nickel/Photoredox Cross‐Coupling

“…Both sets of conditions allow the cross-coupling of various alkyl radicals with either aryl bromides or iodides.S accharide-derived DHPs can also be used in the Ni/photoredox cross-coupling cycle to afford reversed C-aryl glycosides such as 53 (Scheme 4B). [56] The latter substrate would be prone to b-elimination using traditional cross-coupling methods.Arecent report indicated the possibility of direct photoexcitation of DHPs to trigger the formation of alkyl radicals in the absence of ap hotocatalyst with 400 nm light (Scheme 4C). [57] 2.5.…”

Photoredox/Nickel‐Catalyzed Single‐Electron Tsuji–Trost Reaction: Development and Mechanistic Insights

“…A desire to integrate greater functional density within the radical precursor led to the exploration of monosaccharide moieties that were recently highlighted in publications from our group. 28 Pleasingly, pyranose DHP afforded the allylated products 2i-j in high E/Z ratios and diastereoselectivity.…”

Design and synthesis of glycomimetics: Recent advances

“…An organic dye (4CzIPN) was used as the photocatalyst in the presence of blue light to achieve oxidative cleavage of the DHP group, thus generating the alkyl radical that enters the Ni‐catalyzed cross coupling process. By replacing the activated acid with arylhalogenides, similar conditions lead to the synthesis of 5‐arylmonosaccharides . The mild conditions required for the process and the high tolerance for functional groups are attractive for late stage functionalization of complex bioactive molecules.…”