1,2-trans-Stereoselective Synthesis of C-Glycosides of 2-Deoxy-2-amino-sugars Involving Glycosyl Radicals

Abstract

We report for the first time that the imidate radical can be efficiently added to glycals to generate glycosyl radicals, based on which a general, toxic-reagent-free synthesis of C-glycosides of 2-deoxy-2-amino sugars has been developed. Complementary to previous strategies, the reaction is 1,2-trans-stereoselective and could use aryl alkenes as substrates. The late-stage functionalization and density functional theory calculations are reported.

Visible‐Light‐Promoted Stereoselective C(sp3)−H Glycosylation for the Synthesis of C‐Glycoamino Acids and C‐Glycopeptides

“…The good functional group tolerance renders significant strategies for the chemoselective biomolecule modification. In recent years, a series of C ‐glycosylation strategies have been reported [13a–f] . Notably, in the reactions, the stereoselectivity of the C ‐glycosylation was dominantly determined by the conformation of the glycosyl radical intermediate [13h–k] .…”

Recent Advances and Development in Visible‐Light‐Mediated Glycosylation: An Expanding Research Area in Glycochemistry

“…Same group in 2021, published first time a method for 1,2-trans-stereoselective construction of 2-deoxy-2-amino sugars enabled by iridium catalyst without using toxic reagents (Scheme 18). [68] In this protocol, an excited state of the photocatalyst generated an imidate radical, which intercepts with a double bond of glycal to form a glycosyl radical. Addition of aryl alkenes partners to glycosyl radical forging C-alkyl glycosides of 2-DASs.…”

“…Same group in 2021, published first time a method for 1,2‐ trans ‐stereoselective construction of 2‐deoxy‐2‐amino sugars enabled by iridium catalyst without using toxic reagents (Scheme 18). [68] …”

Catalytic Radical Reactions of Unsaturated Sugars

“…[46] Imidate glycal derivatives 14 were reacted with styrenes or electron-deficient alkenes 15 in the presence of [Ir(dtbpy)(ppy) 2 ](PF 6 ) photocatalyst and an excess of iPr 2 NEt under blue light irradiation to give the C-alkyl 2-amino-2-deoxy glycosides 16 (Scheme 5). [47] This photocatalytic strategy provides a more sustainable alternative to classical radical methods, that generally require the use of stoichiometric toxic tin reagents and glycosyl selenides. [48,49] Under these reaction conditions, d-glucal and d-galactal derived imidates reacted to give the corresponding 1,2-trans glycosides in high yields and exclusive α-selectivity, while β-glycosides were obtained from d-allal derivatives.…”