A Radical Activation Strategy for Versatile and Stereoselective N‐Glycosylation

Previous N‐glycosylation approaches have predominately involved acidic conditions, facing challenges of low stereoselectivity and limited scope. Herein, we introduce a radical activation strategy that enables versatile and stereoselective N‐glycosylation using readily accessible glycosyl sulfinate d...

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Bibliographic Details
Published in:Angewandte Chemie International Edition 2024-09, Vol.63 (36), p.e202409004-n/a
Main Authors: Ding, Wenyan, Chen, Xinyu, Sun, Zuyao, Luo, Jiaxin, Wang, Shiping, Lu, Qingqing, Ma, Jialu, Zhao, Chongxin, Chen, Fen‐Er, Xu, Chunfa
Format: Article
Language:English
Subjects:
Aglycones
Glycosides
glycosyl iodides
glycosyl sulfinates
Glycosylation
Iodides
N-glycosides
N-glycosylation
Nitrogen
radical reactions
Stereoselectivity
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Summary:Previous N‐glycosylation approaches have predominately involved acidic conditions, facing challenges of low stereoselectivity and limited scope. Herein, we introduce a radical activation strategy that enables versatile and stereoselective N‐glycosylation using readily accessible glycosyl sulfinate donors under basic conditions and exhibits exceptional tolerance towards various N‐aglycones containing alkyl, aryl, heteroaryl and nucleobase functionalities. Preliminary mechanistic studies indicate a pivotal role of iodide, which orchestrates the formation of a glycosyl radical from the glycosyl sulfinate and subsequent generation of the key intermediate, a configurationally well‐defined glycosyl iodide, which is subsequently attacked by an N‐aglycone in a stereospecific SN2 manner to give the desired N‐glycosides. An alternative route involving the coupling of a glycosyl radical and a nitrogen‐centered radical is also proposed, affording the exclusive 1,2‐trans product. This novel approach promises to broaden the synthetic landscape of N‐glycosides, offering a powerful tool for the construction of complex glycosidic structures under mild conditions. A versatile and stereoselective N‐glycosylation has been developed using glycosyl sulfinates under basic conditions. Mechanistic studies indicate the transformation involves a key glycosyl radical species, which can directly couple with a nitrogen‐centered radical. An alternative route involving the coupling of glycosyl and iodine radicals, followed by an SN2 reaction with the resultant glycosyl iodide to give the N‐glycoside, is also demonstrated.
ISSN:1433-7851
1521-3773
1521-3773
DOI:10.1002/anie.202409004