Nitriles as Solvents in Glycosylation Reactions: Highly Selective β-Glycoside Synthesis¹

The intriguing dual-directing effect of 2-cyanobenzyl ether for a highly stereospecific glycosylation reaction

“…However, we were surprised to observe a complete reversal of anomeric preference when TFE (2,2,2-trifluoroethanol) was used as the acceptor. Under b-optimized condition, a-3h was obtained as the major product with an a:b ratio of 417:1 ( 34 and/or solvent influence [5][6][7] .…”

“…One of the earliest and yet very effective way to acquire the desired anomeric stereoselectivity was through employment of participating solvents, notably nitrile-type 5,6 (for example, acetonitrile) or ether-type 7 (for example, diethyl ether) for the preferential formation of b-D-and a-D-glucosides, respectively. On the other hand, neighbouring hydroxyl groups of the donor could show influence on the anomeric preference through their protecting substituents, many of which were routinely exploited in various glycosylation methods, such as 2-O-ester-type [8][9][10] or 2-O-picolyl-type [11][12][13] for 1,2-trans glycosylation, and several sulfide auxiliaries [14][15][16][17][18] as well as intramolecular aglycon delivery IAD-type 19,20 for 1,2-cis glycosylation reactions.…”

Multi-Component One-Pot Synthesis of the Tumor-Associated Carbohydrate Antigen Globo-H Based on Preactivation of Thioglycosyl Donors

“…The enhancement of stereoselectivity is most likely due to the exclusion of diethyl ether from the reaction and/or the β directing effect of acetonitrile. 45 The disaccharide 12β was then converted to 13 through standard transformations with an 85% overall yield (Scheme 1a). The Troc group was introduced to direct the 1,2-trans linkage in future glycosylation.…”

A highly stereoselective construction of 1,2-trans-β-glycosidic linkages capitalizing on 2-azido-2-deoxy-d-glycosyl diphenyl phosphates as glycosyl donors

“…Although the azido group as a latent amino functionality is incapable of neighboring group participation, modest to high levels of β-selectivity were observed with 2-azido-2-deoxyglycosyl trichloroacetimidates, [6][7][8] Sxanthates, 9 isopropenyl carbonate, 10 2-pyridinecarboxylates, 11 dibutyl phosphates, 12 and phenylthio glycosides. 13 Of these, glycosidation of 2-azido-2-deoxyglycosyl trichloroacetimidates in the presence of BF 3 ·OEt 2 in CH 2 or in the presence of TMSOTf in acetonitrile 8 is the method of choice for a highly stereoselective construction of 2-azido-2-deoxy-β-glycosides. We recently developed glycosyl donors that incorporate various phosphorus-containing leaving groups.…”