Regioselective Glycosylation of Unprotected Phenyl 1‐Thioglycopyranosides with Phenylboronic Acid as a Transient Masking Group

A useful protocol is described for the regioselective glycosylation of the secondary alcohols in unprotected glycosyl acceptors. Phenyl 1‐thioglycopyranosides derived from D‐glucose, D‐galactose, D‐glucosamine, L‐rhamnose, and L‐fucose were treated with phenylboronic acid to install a temporary boronic ester, and then submitted to a Koenigs–Knorr glycosylation with perbenzoylated glucopyranosyl or galactopyranosyl bromides. Good yields for coupling to the 3‐position in glucosides and galactosides were achieved, but lower yields were obtained with the other acceptors. With phenyl 1‐thio‐β‐D‐glucopyranoside, the coupling could also be achieved with a superarmed thiogalactoside donor. The product from a glucose–glucose coupling could be subjected to a second regioselective glycosylation at the 6‐position. In the galactose series, a β(1→3)‐linked galactotriose could be prepared in good yield by two consecutive glycosylations in one pot, where a free 2‐hydroxy group ensures neighboring group participation in the second coupling.