2-Diphenylphosphinoyl-acetyl as a remote directing group for the highly stereoselective synthesis of β-glycosides

Abstract

The configuration of the anomeric glycosidic linkages is crucial for maintaining the biological functions and activities of carbohydrate molecules. However, their stereochemistry control in glycosylation represents one of the most challenging tasks in carbohydrate chemistry. In this report, the easily accessible 2-diphenylphosphinoyl-acetyl (DPPA) group was developed as a highly stereodirecting group for catalytic glycosylation via hydrogen-bond mediated delivery of the alcoholic acceptors. TMSOTf-catalyzed glycosylation with 6-O-DPPA glycosyl imidate donors displayed excellent -selectivity and broad substrate scope, particularly applicable to synthesize the challenging -configured 2-deoxy-and 2-azido-2-deoxy-glycosides from electron-deficient or bulky acceptors. Chemoselective removal of the DPPA group could be readily achieved under the mild catalysis of Ni(OTf)2, and further application was demonstrated in the synthesis of biologically important oligosaccharides, uronic acids, and 2,6-dideoxy-glycosides.