DIBAL-H mediated triple and quadruple debenzylations of perbenzylated cyclodextrins

Abstract

Diisobutylaluminium hydride (DIBAL-H) mediated reductive removal of benzyl groups was investigated for perbenzylated alpha-, beta- and gamma-cyclodextrins using DIBAL-H in hexane as the reagent. It was found that under the new conditions, the debenzylation can be better controlled to provide sequentially tri- and tetra-debenzylated products in moderate yields and in a regioselective manner. In the case of alpha-cyclodextrin, the removal of the third and fourth benzyl groups took a different path involving the secondary rim, compared to beta- and gamma-cyclodextrins which both gave only 6-O-debenzylated products.

Taming of the DIBAL Promoted Debenzylation of α‐Cyclodextrin. Kinetics, Substituent Effects and Efficient Synthesis of Lings Tetrol**

“…The residue was subjected to silica gel flash chromatography in a solvent gradient of heptane‐EtOAc 1:0→3 : 1→1 : 1→0 : 1 gave tetrol 6 (0.45 g, 60 %) as a clear syrup. NMR showed it identical to the compound reported by Lings group [13,14] …”

“… [13] These debenzylations are interesting in that removal of secondary benzyl groups occurs and with a degree of selectivity for the already modified A,D glucose‐residues. It is also interesting that secondary debenzylation is not observed in the similar reaction with β‐cyclodextrin [14] …”

Deoxy sugars. General methods for carbohydrate deoxygenation and glycosidation

“…By mesylation of the primary positions followed by reduction with lithium aluminium hydride, different 6-deoxy cyclodextrines were prepared. 43 Deoxygenation of C-6 of benzyl β-lactoside was accomplished by reduction with sodium borohydride of a mesylated precursor. 44…”

Diisobutylaluminum Hydride Mediated Regioselective O Desilylations: Access to Multisubstituted Cyclodextrins

“…For example, in the cases of α/β CDs, only benzyl group(s) attached to O6 positions of the A and D units (see Scheme for labeling of a CD) are affected. We later found that this methodology could also be used to synthesize triply and quadruply O‐debenzylated products in gram quantities 4b,c. A downside of the methodology is that a large excess (>30 equiv) of DIBAL‐H is required.…”