Efficient and versatile formation of glycosidic bonds via catalytic strain-release glycosylation with glycosyl ortho−2,2-dimethoxycarbonylcyclopropylbenzoate donors

Abstract

Catalytic glycosylation is a vital transformation in synthetic carbohydrate chemistry due to its ability to expediate the large-scale oligosaccharide synthesis for glycobiology studies with the consumption of minimal amounts of promoters. Herein we introduce a facile and efficient catalytic glycosylation employing glycosyl ortho−2,2-dimethoxycarbonylcyclopropylbenzoates (CCBz) promoted by a readily accessible and non-toxic Sc(III) catalyst system. The glycosylation reaction involves a novel activation mode of glycosyl esters driven by the ring-strain release of an intramolecularly incorporated donor-acceptor cyclopropane (DAC). The versatile glycosyl CCBz donor enables highly efficient construction of O-, S-, and N-glycosidic bonds under mild conditions, as exemplified by the convenient preparation of the synthetically challenging chitooligosaccharide derivatives. Of note, a gram-scale synthesis of tetrasaccharide corresponding to Lipid IV with modifiable handles is achieved using the catalytic strain-release glycosylation. These attractive features promise this donor to be the prototype for developing next generation of catalytic glycosylation.

Efficient O- and S-glycosylation with ortho-2,2-dimethoxycarbonylcyclopropylbenzyl thioglycoside donors by catalytic strain-release

“…of trimethylsilyl trifluoromethanesulfonate (TMSOTf) as the promoter, further underscoring the inherent challenge and complexity in the endeavor to synthesize S -glycosides from thioglycosides. 32 In continuation of our interest in strain-release glycosylation, 33,34 we herein successfully merged the diverse reactivities of thioglycosides and DAC to engender a new genre of thioglycoside, termed ortho -2,2-dimethoxycarbonylcyclopropylbenzyl (CCPB) thioglycoside, for versatile O -, S -, and N -glycosylation (Fig. 1E).…”

Stereoselective strain-release Ferrier rearrangement: the dual role of catalysts

“…Our group is long devoted to the development of novel glycosylation methodologies, 18 and we have developed a novel ortho -2,2-dimethoxycarbonylcyclopropylbenzoate (CCBz) 19 leaving group which can readily be activated by the Sc(OTf) 3 recently (Fig. 1C).…”