UC Santa Barbara

Highly stereoselective synthesis of 2-azido-2-deoxyglucosides and 2-azido-2-deoxygalactosides is achieved via a gold-catalyzed S_N2 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_N2 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_N2 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.