Stereoselectivity of glycosylations of conformationally restricted mannuronate esters

Glycosidation of conformationally unrestricted mannuronate ester donors proceeds in a highly β-selective fashion, whereas condensations of mannuronate ester donors, which are conformationally constrained by a 3,4-butanedimethylacetal or a 2,3-isopropylidene function, provide α-selective products. We hypothesize that the difference in stereochemical outcome of these condensations results from the different conformations of the product forming oxacarbenium intermediate. The formation of the β-linked products from the flexible mannuronates is thought to originate from the most favorable 3H4 oxacarbenium ion, which is not accessible from the conformationally restrained donors. Although an α-triflate intermediate is formed upon activation of the 3,4-butanedimethylacetal protected mannuronate ester thio donor, this is not the product forming intermediate. The anomeric triflate serves as a reservoir for the 4H3 oxacarbenium ion, which is glycosidated to provide the α-linked mannuronates.