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
SN1 mechanism to afford α-glycosides. We found that
the introduction of a 2,6-lactone bridge can circumvent the competing
SN1 reaction, affording β-glycosides with stereoinversion
via SN2(-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
SN1 mechanism, the corresponding glycosyl cation appears
to present sterically a β-directing nature. Overall, 2,6-lactones
were promising structures for achieving β-mannosylations.