Solid-Phase Synthesis of Oligosaccharides. II. Steric Control by C-6 Substituents in Glucoside Syntheses

A number of 2,3,4-tri-O-benzyl-α-D-glucopyranosyl bromides containing various acid residues on C-6 were prepared and tested in glycoside-forming reactions. The fraction of anomeric glucosides produced varied from over 90% α to over 90% β depending on the nature of the C-6 acyl group. In the para-substituted benzoic acid series the proportion of α-glucoside formed was shown to increase with increasing σ Hammett substituent constant value. This degree of steric control should be sufficient for the synthesis of lower 1→6 linked oligosaccharides and is probably due primarily to orbital overlap of the carbonyl function in the transition state. Reaction rates were measured polarimetrically and product composition was estimated by nmr spectrometry with the help of deuterated samples. A few glucopyranosyl chlorides tested were shown to react by a different mechanism. The difference between the chlorides and bromides may be due to the relative tightness of the intermediate ion pairs.