β-Stereoselective Mannosylation Using 2,6-Lactones.

β-Stereoselective mannosylation using donors bearing the 2,6-lactone moiety is described. In general, glycosylation is a nucleophilic substitution reaction between an alcoholic nucleophile and a sugar moiety containing a leaving group at the anomeric position. Owing to stereoelectronic effects, the reaction tends to proceed via an SN 1 mechanism to afford α-glycosides. We found that the introduction of a 2,6-lactone bridge can circumvent the competing SN 1 reaction, affording β-glycosides with stereoinversion via SN 2(-like) mechanisms. Glycosyl trichloroacetimidates are particularly efficient when activated by a combined catalyst of AuCl3 and 3,5-bis(trifluoromethyl)phenyl thiourea. In addition, the product stereoselectivity was highly dependent on the concentration of the reaction. Moreover, even when the reaction proceeds via an SN 1 mechanism, the corresponding glycosyl cation appears to present sterically a β-directing nature. Overall, 2,6-lactones were promising structures for achieving β-mannosylations.