An experimental and theoretical study on stereocontrolled glycosylations by a “one-pot” procedure

A generalized strategy for stereocontrolled glycosylation to generate both isomers from a single donor is highly demanded to assemble the desired oligosaccharides. Herein we describe a "one-pot" strategy to install the stereoselectivity of both alpha- and beta-glycosides by changing reaction conditions. Specifically, beta-glycosides were selectively obtained when the perbenzylated trichloroacetimidate was activated by a catalytic amount of SnCl4 at a low temperature of -40 degrees C. On the other hand, using 3.0 equivalents of SnCl4 and/or TiCl4 provided alpha-glycosides as the major products at room temperature via anomerization. The control experiments combined with DFT calculations revealed the mechanistic details of the glycosyl reaction, which elucidated that beta-glycosylation occurred first and anomerization occurred subsequently (glycosidation-anomerization).