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

Abstract

Direct C–N bond formation has been accomplished by reaction of 1,5‐anhydro‐3,4,6‐tri‐O‐benzyl‐2‐deoxy‐D‐arabino‐hex‐1‐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 α‐stereoselectivity. Sterically demanding reagents such as sterols, flavonoids, sugars and an indole give only the α‐anomer in dichloromethane, while the purine nucleosides in THF were obtained as anomeric mixtures whilst maintaining the α‐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 zeolite to promote theFerrier rearrangement of 3,4,6‐tri‐O‐benzyl‐D‐glucal to give exclusively the corresponding 2,3‐unsaturated α‐O‐ and α‐S‐glycosides in moderate yields. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)

Recent Developments in the Ferrier Rearrangement

“…The well‐documented effect of triphenylphosphane hydrogen bromide (TPHB) in favoring 1,2‐addition of alcohols to glycals (rather than Ferrier rearrangement) has also been demonstrated for 1,2‐addition of thiols to glycals leading to 2‐deoxythioglycosides 118a. The same effect, favoring 1,2‐addition over Ferrier rearrangement, has also been reported for ceric(IV) ammonium nitrate (CAN),221 and GaCl 3 222…”

“…However, the current tendency in Ferrier rearrangement with thiols and glycals seems to be toward the use of heterogeneous or supported catalysts. Heterogeneous catalysts such as zeolites,119,118a heteropoly acids,111 Amberlyst‐15,110 silica gel under microwave irradiation conditions,100 and the supported acids ZnCl 2 /alumina,109 PMA on silica gel,106 and perchloric acid on silica gel101,102 have thus been reported recently.…”

Tuning the Bioactivity of Tensioactive Deoxy Glycosides to Structure: Antibacterial Activity Versus Selective Cholinesterase Inhibition Rationalized by Molecular Docking

“…The 2‐deoxy glycosides were synthesized in good yields by the reaction of glycals with fatty alcohols in the presence of triphenylphosphane hydrobromide (TPHB) 9,18. With this catalyst, the Ferrier products, which result from reaction of acetylated glycals with alcohols catalysed by Lewis acids, are absent or can be isolated as secondary products in very low yields.…”

Acid zeolites as efficient catalysts for O- and S-glycosylation

“…We have previously described the efficacy of the HY zeolite (Si/Al ratio of 2.7) to promote the Ferrier rearrangement of 1,5-anhydro-3,4,6-tri-O-benzyl-2-deoxy-d-arabinohex-1-enitol (6) (3,4,6-tri-O-benzyl-d-glucal), affording only 2,3-unsaturated ␣-O-and ␣-S-glycosides in reasonable yields, by reaction with alcohols and thiols [44]. In this paper we report on the efficiency of various acid zeolites differing in their pore dimensions, hydrophilicity/hydrophobicity characteristics and density of acid sites on the reaction of O-and S-nucleophiles with 6.…”