Highly Stereoselective Synthesis of 2-Azido-2-Deoxyglycosides via Gold-Catalyzed SN2 Glycosylation.

Abstract

Highly stereoselective synthesis of 2-azido-2-deoxyglucosides and 2-azido-2-deoxygalactosides is achieved via a gold-catalyzed SN2 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 SN2 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 SN2 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.