Beilstein J. Org. Chem.2022,18, 1553–1559, doi:10.3762/bjoc.18.165
Naser-Abdul Yousefi Morten L. Zimmermann Mikael Bols Department of chemistry, University of Copenhagen, Universitetsparken 5, 2100, Copenhagen, Denmark 10.3762/bjoc.18.165 Abstract An α-cyclodextrin protected with 2,4-dichlorobenzyl groups on the primary alcohols and ordinary benzyl groups on the
; cyclodextrin; debenzylation; 2,4-dichlorobenzyl; selective; Introduction
α-Cyclodextrin (1) is a cyclic carbohydrate consisting of six α-1,4-linked ᴅ-glucose molecules (Figure 1). It has a donut-like structure with the glucose residues all aligned with the α-side towards the center of the ring and the polar
electron-poor benzyl groups reacting much more sluggishly. Indeed the per-2,4-dichlorobenzyl (DCB) protected compound 1 was completely resistant to DIBAL even when treated for several days [15]. This led us to wonder if an α-cyclodextrin protected on the primary hydroxy groups with DCB groups and on the
Beilstein J. Org. Chem.2014,10, 1681–1685, doi:10.3762/bjoc.10.176
a mixture of anomers (α:β = 2:3, 93% for two steps). Then, the other two hydroxy groups were protected as 2,4-dichlorobenzyl ether. Compound 8 was isolated in 95% yield after reacting compound 7 with NaH and 2,4-dichlorobenzyl chloride in anhydrous DMF. 2,4-Dichlorobenzyl chloride was used because
it is less irritant than the usually used benzyl bromide.
Regioselective cleavage of the 2-O-(2,4-dichlorobenzyl) group was attempted with anhydrous SnCl4 in DCM by the method reported by Brown [31][32] and our group [16]. To our delight, this approach can afford 3-O-(2,4-dichlorobenzyl)-1-O-methyl-α
correlations of H-1, H-3, 5-CH3 and 2-β-methyl. Then, the remaining 3-(O-2,4-dichlorobenzyl) group was removed under hydrogenation with 20% Pd(OH)2/C as a catalyst to give 12 in 91% yield. As the anomerization of the 1-O-α-methyl glycoside may occur under acidic conditions, the structural characterization may