Chemoselective Activation of Thioglycosides with Alkyl Trichloroacetimidates

Previously, a method for the activation of thioglycosides and thioimidates using benzyl trichloroacetimidate in the presence of triflic acid has been introduced. Good yields were achieved with highly reactive substrates, whereas the efficiency of reactions with less reactive glycosyl donors and/or acceptors remained modest. Reported herein is the development of a significantly improved method for the activation of thioglycosides using <i>p</i>-methoxybenzyl trichloroacetimidate or diphenylmethyl trichloroacetimidate in the presence of catalytic triflic acid. Excellent yields were achieved with all tested substrates, and the reaction conditions were found to be compatible with chemoselective and selective activation strategies for multistep glycan synthesis.