Stereoselective Palladium-Catalyzed O-Glycosylation Using Glycals

Abstract

A highly stereoselective palladium-catalyzed O-glycosylation reaction is described. The reaction of a glycal 3-acetate or carbonate with the zinc(II) alkoxide of acceptors establishes the glycosidic linkage under palladium catalysis to give rise to disaccharides as the product in good yields and with high stereoselectivity. In contrast to the Lewis acid mediated Ferrier procedure, the anomeric stereochemistry of this reaction is controlled by the employed ligand. Whereas the use of a complex of palladium acetate and 2-di(tert-butyl)phosphinobiphenyl as the catalyst results in the exclusive beta-glycoside formation, the same reaction using trimethyl phosphite ligand furnishes an alpha-anomer as the major product. The utility of the 2,3-unsaturation present in the resulting glycoside is demonstrated by the further transformations such as dihydroxylation, hydration, and hydrogenation reactions. Thus, the combination of the glycosylation and subsequent functionalization provides a novel entry to saccharides which are otherwise difficult to prepare. The broad scope of the process, mildness of the reaction conditions, and experimental simplicity should make this method a useful tool in synthetic carbohydrate chemistry.

Scope of AuCl3 in the activation of per-O-acetylglycals

“…To make the b-anomer, only one method is known so far that employs Pd(OAc) 2 and bulky phosphine ligands. 8 In this regard we wished to utilize the oxophilicity and alkynophilicity of AuCl 3 to explore its possible application in making the b-anomer of 2,3-unsaturated glycosides. Further we believed that the bigger size of gold will influence the selectivity.…”

Acid zeolites as efficient catalysts for O- and S-glycosylation

“…Typically the reactions are conducted with glycal derivatives possessing acyloxy groups at the allylic positions and Lewis acids, or occasionally protonic acids as catalysts, promoting the departure of these groups, with the formation of delocalysed oxycarbenium ions, which react then with O-, S-, N-and C-nucleophiles at the anomeric center. A diversity of catalysts have been employed for this reaction leading to O-glycosides, such as BF 3 ·Et 2 O [25], SnCl 4 [26], InCl 3 [27], ZnCl 2 [28], Sc(OTf) 3 [29], Bi(OTf) 3 or SiO 2 -Bi(OTf) 3 [30], BiCl 3 [31], NbCl 5 [32], ZrCl 4 [33], HClO 4 -SiO 2 [34], trifluoroacetic acid [35], potassium dodecatungstocobaltate trihydrate [36], palladium [37], and montmorillonite K10, which catalyzed a microwave-induced Ferrier rearrangement [38]. Rearrangement catalyzed by FeCl 3 based ionic liquid has been described in which the ionic liquid has proved to be an efficient reaction medium, playing a dual role of a catalyst as well as that of a solvent [39].…”

“…The dominant anomeric effect contributes to the ␣-stereoselectivity observed in most of the Ferrier rearrangement reactions. However, the ␣-stereoselective palladium-catalyzed O-glycosylation of glycals was controlled by the reagent, rather than by the anomeric or neighbouring group effects [37].…”

Reactions of N‐, S‐ and O‐Nucleophiles with 3,4,6‐Tri‐O‐benzyl‐D‐glucal Mediated by Triphenylphosphane Hydrobromide versus Those with HY Zeolite

“…Again, the dominant anomeric effect contributes to the α-stereoselectivity observed. However, stereoselective palladium-catalysed O-glycosylation using glycals has also been reported to give Ferrier products [40] in which the anomeric configuration is controlled by the reagent rather than by the anomeric or neighbouringgroup effects. Synthesis of 2,3-unsaturated C-glycosides was recently described by reaction of glycals with either organozinc reagents [41] or catalysed by HClO 4 /SiO 2 .…”