A 3,4-trans-fused cyclic protecting group facilitates α-selective catalytic synthesis of 2-deoxyglycosides

Abstract

A practical approach has been developed to convert glucals and rhamnals into disaccharides or glycoconjugates with high α-selectivity and yields (77-97%) using a trans-fused cyclic 3,4-O-disiloxane protecting group and TsOH⋅H2O (1 mol%) as a catalyst. Control of the anomeric selectivity arises from conformational locking of the intermediate oxacarbenium cation. Glucals outperform rhamnals because the C6 side-chain conformation augments the selectivity.

Keywords: conformation analysis; glycosides; homogeneous catalysis; protecting groups; synthetic methods.

Scheme 1

Thiourea-catalyzed synthesis of deoxyglycosides. a) Galactal series.[5] b) Glucal series.

Scheme 2

Diastereomeric half-chair conformers of glucal oxacarbenium ions and preferred nucleophilic attack to yield the corresponding glycosides.

Scheme 3

Mechanistic investigation.

Figure 1

a) Chair and twist-boat products formed by axial α and β attack on a half-chair oxacarbenium ion. b) Staggered conformations about the exocyclic C5=C6 bond. The stereochemical relationship (gauche or anti) between O6 and O1 and C4 is described. c) Favored gauche-gauche conformation for the glucal oxacarbenium ion (15) with the O-C-CH₂-OR torsion angle at −64°.