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.

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

“…reported the oxidation of a hydroxy group at the C3‐position of protected D‐fructose by Albright‐Goldman Reagent, and successive treatment of the formed carbonyl group with Grignard reagent gave alkylated saccharides (Scheme 1b) [16] . (3) Introduction of a leaving group: Molander's group reported the synthesis of C ‐saccharides from saccharides with a 1,4‐dihydropyridyl (DHP) moiety as a leaving group and aryl bromide under photoredox/nickel dual catalysis (Scheme 1c) [17] …”

StereoselectiveC‐Aryl Glycosylation by Catalytic Cross‐Coupling of Heteroaryl Glycosyl Sulfones

“…Particularly desirable is a set of broadly applicable protocols that harness the power of nonprecious base metal catalysis [3, 18, 19] to transform a readily available glycosyl precursor (donor), the saccharide component which bears a reactive functional group at the C1 position, into the C ‐aryl glycoside product by controlling the stereochemical outcome of C‐aryl bond formation [18] . In this regard, processes that convert glycosyl donors into glycosyl radical intermediates [16, 17, 20–23] en route to C ‐aryl glycosides are highly attractive (Scheme 1b), given that such glycosyl radical cross‐coupling reactions are less susceptible to undesired epimerization and elimination side reactions [16] . In contrast to stereospecific transformations, [24–26] the stereochemical purity of the donor is inconsequential, since both α and β isomers eventually converge to a single diastereomeric product, which means that anomeric mixtures of the substrate can be employed without rigorous purification.…”

Na2S2O8‐Mediated Tandem One‐Pot Construction of 3,3‐Disubsituted 3,4‐Dihydroquinoxalin‐2(1H)‐ones with 4‐Alkyl‐1,4‐dihydropyridines as Alkyl Radical Sources

“…Recent years have witnessed the growing research interest in the application of 1,4‐dihydropyridines as alkyl radical sources due to their stability and easy availability from the abundant aldehydes [7] . With the rapid development of photoredox reactions over the past decade, [8] 4‐alkyl‐1,4‐dihydropyridines have been broadly utilized for the generation of alkyl radicals under light irradiation conditions, and notable contributions came from the groups of Nishibayashi, [9a,b] Molander, [9c–e] Li, [9f] Yu, [9g,h] Melchiorre [9i–k] and others [9l–r] . In contrast, less attention has been devoted to the homolysis of 4‐alkyl‐1,4‐dihydropyridines under thermal conditions [10] .…”