Highly Stereoselective Synthesis of 2-Azido-2-Deoxyglycosides via Gold-Catalyzed S N 2 Glycosylation.

Highly stereoselective synthesis of 2-azido-2-deoxyglucosides and 2-azido-2-deoxygalactosides is achieved via a gold-catalyzed S _N 2 glycosylation. The glycosyl donors feature a designed 1-naphthoate leaving group containing an amide group. Upon gold activation of the leaving group, the amide group is optimally positioned to direct an S _N 2 attack by an acceptor via H-bonding interaction. Both 2-azido-2-deoxyglucosyl/galactosyl donor anomers can undergo stereoinversion at the anomeric position, affording the opposite anomeric glycoside products with excellent levels of stereoselectivity or stereospecificity and in mostly excellent yields. This S _N 2 glycosylation accommodates a broad range of acceptors. The utility of this chemistry is demonstrated in the synthesis of a trisaccharide featuring three 1,2- cis -2-azido-2-deoxyglycosidic linkages.
Competing Interests: Conflict of Interest The authors declare no competing financial interest.