Reactions of N-, S- and O-nucleophiles with 3,4,6-tri-O-benzyl-D-glucal mediated by triphenylphosphane hydrobromide versus those with HY zeolite

Direct C-N bond formation has been accomplished by reaction of 1,5-anhydro-3,4,6-tri-O-benzyl-2-deOXY-D-arabinohex-l-enitol (3,4,6-tri-O-benzyl-D-glucal) with N-nucleophiles, using triphenylphosphane hydrobromide as catalyst in dichloromethane or THF. 2-Deoxy-S- and -O-glycosides have also been prepared with thiols, sterols, flavonoids, alcohols and sugars as nucleophiles, with alpha-stereoselectivity. Sterically demanding reagents such as sterols, flavonoids, sugars and an indole give only the a-anomer in dichloromethane, while the purine nucleosides in THF were obtained as anomeric mixtures whilst maintaining the alpha-stereoselectivity. This procedure has led to an easy and straightforward synthesis of a variety of biomolecules, in moderate to high yield, with the first use of triphenylphosphane hydrobromide for N- and S-glycosylation. An alternative method for C-O and C-S bond formation uses HY zeohte to promote the Ferrier rearrangement of 3,4,6-tri-O-benzyl-(D)-glucal to give exclusively the corresponding 2,3-unsaturated alpha-O- and alpha-S-glycosides in moderate yields. ((c) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)