Solvent-controlled regioselective protection of allyl-4,6-benzylidene glucopyranosides

Abstract

We wish to report a simple synthetic procedure, which permits the regiospecific mono-acylation, alkylation and silylation at the 2-position of allyl 4,6-O-benzylidene α-D-glucopyranoside in high yields and which does not require the use of catalysts.

o-Xylylene Protecting Group in Carbohydrate Chemistry: Application to the Regioselective Protection of a Single vic-Diol Segment in Cyclodextrins

“…The acidity depends on the solvent used and is modulated by intramolecular H-bonds while steric effects control the nucleophilicity. The involvement of OH-2 in H-bonding with O-1 in α- d -glucopyranosides renders this hydroxyl group the most acidic in compound 15 , favoring initial benzylation at this position . The next intramolecular etherification at O-3 is then kinetically favored over intermolecular reactions.…”

“…Differences in acidity are less pronounced in the case of the β- gluco anomer 16 , leading to a lower selectivity, whereas it is reversed in favor of OH-3 for the α- manno epimer. In the α- d -galactopyranoside, both OH-2-and OH-3 hydroxyls have similar chemical reactivity as both are involved in cis -H-bonds with vicinal oxygens . Although cyclization through OH-2 must be favored after initial alkylation at O-3, a small proportion of the O-3,O-4 cyclic diether is also formed.…”

“…The involvement of OH-2 in H-bonding with O-1 in α-Dglucopyranosides 44 renders this hydroxyl group the most acidic in compound 15, favoring initial benzylation at this position. 45 The next intramolecular etherification at O-3 is then kinetically…”

“…Differences in acidity are less pronounced in the case of the β-gluco anomer 16, leading to a lower selectivity, whereas it is reversed in favor of OH-3 for the α-manno epimer. In the α-D-galactopyranoside, both OH-2and OH-3 hydroxyls have similar chemical reactivity as both are involved in cis-H-bonds with vicinal oxygens 45. Although cyclization through OH-2 must be favored after initial alkylation at O-3, a small proportion of the O-3,O-4 cyclic diether is also formed.Even though the yields on the selectively o-xylylenated derivatives 17, 19, 20, 23, and 25 are far from optimal, they are remarkable considering that classical benzylation with benzyl chloride under identical reaction conditions led to very complex mixtures of no synthetic utility.…”