Stereoselective C-glycosidation of d-fucose derivatives directed by the protective groups

• Stereoselectivity for the reduction of the lactols can be modulated by the correct choice of protective groups.
• Lactols possessing TBDMS protective groups afford the α-anomer, whereas their benzylated congeners provide the β-anomer.
• This change in stereoselectivity is observed in carbohydrate derivatives possessing 2,3-trans substituents.
• The phenomenon is observed only when the C2 and C3 protective groups are the same (both benzyl or both TBDMS).

Stereoselectivity in the C-glycosidation of lactones derived from d-fucose by following Kishi’s method, which involves the addition of a nucleophile onto a carbohydrate-derived lactone and subsequent reduction of the lactol, was found to be reliant on the nature of the C2 and C3 protective groups. Lactones bearing TBDMS protecting groups selectively afford 1,3-trans products (α anomer), in which the stereoselective outcome is in apparent concordance with Woerpel’s model. On the other hand, their benzylated congeners produce the 1,3-cis products (β anomer) as the major diastereoisomers. The latter results suggest an abnormal behavior during the stereoselective nucleophilic substitution at the anomeric position of the benzylated lactones.

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