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 DPPA-installed glycosyl imidate donors displayed excellent β-selectivities and broad substrate scope, particularly practical to synthesize the challenging β-configured 2-deoxy and 2-azido-2-deoxy glycosides from poor acceptors suffering from electron-deficiency, steric hindrance, and structural rigidity. Chemoselective removal of the DPPA group could be readily achieved under the mild catalysis of Ni(OTf) 2 without affecting acid-or base-labile functional groups, facilitating a rapid conversion to biologically important molecules such as uronic acids and 2,6-deoxy glycosides. The application of this DPPA-directed glycosylation was further highlighted in the complex synthesis toward saponin dioscin using 2,4-O-glycosylated donor in a convergent manner.

The anomeric configuration can greatly affect the biological functions and activities of carbohydrates. Herein, we report that N‐phenyltrifluoroacetimidoyl (PTFAI), a well‐known leaving group for catalytic glycosylation, can act as a stereodirecting group for the challenging 1,2‐cis α‐glycosylation. Utilizing rapidly accessible 1,6‐di‐OPTFAI glycosyl donors, TMSOTf‐catalyzed glycosylation occurred with excellent α‐selectivity and broad substrate scope, and the remaining 6‐OPTFAI group can be cleaved chemoselectively. The remote participation of 6‐OPTFAI is supported by the first characterization of the crucial 1,6‐bridged bicyclic oxazepinium ion intermediates by low‐temperature NMR spectroscopy. These cations were found to be relatively stable and mainly responsible for the present stereoselectivities. Further application is highlighted in glycosylation reactions toward trisaccharide heparins as well as the convergent synthesis of chacotriose derivatives using a bulky 2,4‐di‐O‐glycosylated donor.

Anomeric stereocontrol is usually one of the major issues in the synthesis of complex carbohydrates, particularly those involving β‐configured 2,6‐dideoxyglycoside and d/l‐rhamnoside moieties. Herein, we report that 2‐(diphenylphosphinoyl)acetyl is highly effective as a remote stereodirecting group in the direct synthesis of these challenging β‐glycosides under mild conditions. A deoxy‐trisaccharide as a mimic of the sugar chain of landomycin E was prepared stereospecifically in high yield. The synthetic potential was also highlighted in the synthesis of Citrobacter freundii O‐antigens composed of a [→4)‐α‐d‐Manp‐(1→3)‐β‐d‐Rhap(1→4)‐β‐d‐Rhap‐(1→] repeating unit, wherein the convergent assembly up to a nonasaccharide was realized with a strongly β‐directing trisaccharide donor. Variable‐temperature NMR studies indicate the presence of intermolecular H‐bonding between the donor and the bulky acceptor as direct spectral evidence in support of the concept of hydrogen‐bond‐mediated aglycone delivery.

Anomeric stereocontrol is usually one of the major issues in the synthesis of complex carbohydrates, particularly those involving β-configured 2,6-dideoxyglycoside and D/L-rhamnoside moieties. Herein, we report that 2-(diphenylphosphinoyl)acetyl is highly effective as a remote stereodirecting group in the direct synthesis of these challenging β-glycosides under mild conditions. A deoxy-trisaccharide as a mimic of the sugar chain of landomycin E was prepared stereospecifically in high yield. The synthetic potential was also highlighted in the synthesis of Citrobacter freundii O-antigens composed of a!] repeating unit, wherein the convergent assembly up to a nonasaccharide was realized with a strongly βdirecting trisaccharide donor. Variable-temperature NMR studies indicate the presence of intermolecular Hbonding between the donor and the bulky acceptor as direct spectral evidence in support of the concept of hydrogen-bond-mediated aglycone delivery.

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 β-selectivity and broad substrate scope, particularly applicable to synthesize the challenging β-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.