Direct Access to Alkyl Amide N ‐Glycosides via Transition‐Metal‐Free Visible‐Light Carbonylation of Glycosylamines
Abstract
Amide N ‐glycosides are privileged structural motifs found in glycoproteins, glycoconjugates, and numerous bioactive molecules, yet their preparation remains challenging because existing methods depend on hydrolytically sensitive intermediates or on forcing conditions that erode anomeric integrity. Herein, we report a transition‐metal‐free, visible‐light‐mediated carbonylative coupling of glycosylamines with unactivated alkyl iodides that provides a straightforward and stereoretentive route to structurally diverse alkyl amide N ‐glycosides. The transformation employs 4CzIPN as an inexpensive organic photocatalyst and SilaCOgen as a safer, bench‐stable carbon monoxide surrogate. A broad range of mono‐, di‐, and oligosaccharide‐derived glycosylamines, including anomeric and non‐anomeric glucosamine derivatives and a glycosyl sulfoximine, undergo efficient carbonylation, and the isolated products were assigned with retention of the anomeric configuration. The protocol is compatible with primary, secondary, and tertiary alkyl iodides, tolerates esters, N ‐Boc and N ‐Cbz carbamates, a cyclic ketal, and an aryl ether, and enables the late‐stage functionalization of complex natural‐product‐derived substrates. Its synthetic utility is further demonstrated by the direct incorporation of a 13 C‐labeled carbonyl group, which delivers isotopically labeled amide N ‐glycosides with 99.4% isotopic incorporation. This operationally simple strategy expands the synthetic toolbox for amide N ‐glycoside synthesis and provides access to carbohydrate‐based building blocks for glycochemistry and medicinal chemistry.
Related
- Photocatalytic Direct Desulfurization of Glycosyl Thiols via Glycosyl Radicals for the Synthesis of gem -Difluoroalkene C -Alkyl Glycosides
- Direct halo-/seleno-sulfonylation and diselenylation of ynamides mediated by visible light
- Cobalt Photocatalyzed Carbonylation Reactions in Flow: From Mass-Transfer to Light-Limited Regimes
- Enantioselective synthesis of axially chiral α-ketoamide diaryl ethers via asymmetric double carbonylation of cyclic iodonium salts
- Site-Selective Radical Carbonylation of Aryl Thianthrenium Salts with Gaseous CO in Flow
BibTeX
@article{wang2026direct,
title = {{Direct Access to Alkyl Amide N ‐Glycosides via Transition‐Metal‐Free Visible‐Light Carbonylation of Glycosylamines}},
author = {Gefei Wang and Guillaume Chu and Abdel Aziz Wayzani and Franck Le Bideau and Alexandre Vasseur and Zakaria Halime and Christophe Werlé and Ibrahim Abdellah and Samir Messaoudi},
journal = {ChemistryEurope},
year = {2026},
month = oct,
doi = {10.1002/ceur.70379},
url = {https://hal.science/hal-05826820v1},
note = {CC BY},
}
RIS
TY - JOUR
TI - Direct Access to Alkyl Amide N ‐Glycosides via Transition‐Metal‐Free Visible‐Light Carbonylation of Glycosylamines
AU - Gefei Wang
AU - Guillaume Chu
AU - Abdel Aziz Wayzani
AU - Franck Le Bideau
AU - Alexandre Vasseur
AU - Zakaria Halime
AU - Christophe Werlé
AU - Ibrahim Abdellah
AU - Samir Messaoudi
PY - 2026
DA - 2026/10/20
JO - ChemistryEurope
DO - 10.1002/ceur.70379
UR - https://hal.science/hal-05826820v1
AB - Amide N ‐glycosides are privileged structural motifs found in glycoproteins, glycoconjugates, and numerous bioactive molecules, yet their preparation remains challenging because existing methods depend on hydrolytically sensitive intermediates or on forcing conditions that erode anomeric integrity. Herein, we report a transition‐metal‐free, visible‐light‐mediated carbonylative coupling of glycosylamines with unactivated alkyl iodides that provides a straightforward and stereoretentive route to structurally diverse alkyl amide N ‐glycosides. The transformation employs 4CzIPN as an inexpensive organic photocatalyst and SilaCOgen as a safer, bench‐stable carbon monoxide surrogate. A broad range of mono‐, di‐, and oligosaccharide‐derived glycosylamines, including anomeric and non‐anomeric glucosamine derivatives and a glycosyl sulfoximine, undergo efficient carbonylation, and the isolated products were assigned with retention of the anomeric configuration. The protocol is compatible with primary, secondary, and tertiary alkyl iodides, tolerates esters, N ‐Boc and N ‐Cbz carbamates, a cyclic ketal, and an aryl ether, and enables the late‐stage functionalization of complex natural‐product‐derived substrates. Its synthetic utility is further demonstrated by the direct incorporation of a 13 C‐labeled carbonyl group, which delivers isotopically labeled amide N ‐glycosides with 99.4% isotopic incorporation. This operationally simple strategy expands the synthetic toolbox for amide N ‐glycoside synthesis and provides access to carbohydrate‐based building blocks for glycochemistry and medicinal chemistry.
SN - 2751-4765
ER -