Electrochemical glycosylation - Carbohydrate Chemistry: Chemical and Biological Approaches - page 174

However, despite the use of sulfides instead of alcohols, the reaction
between 117 and 12 (divided cell, CH 2 Cl 2 , nBu 4 BF 4 , 7.5 mA, 1 h) again
afforded the glycoside 113 in poor yield (20%, 1 : 4 a/b ratio). The use of a
primary carbohydrate alcohol, e.g. the diacetone galactose (17), as a
partner in the coupling with cholesterol derivative 117 allowed the
preparation of the corresponding glycoconjugate via an ether bond for-
mation in satisfactory yield (up to 52%). 38 Therefore, this electrochemical
approach is more suitable for the synthesis of sugar ethers than for the
preparation of sugar acetals (i.e. glycosides).
3 Electroreductive glycosylation
As reported in the previous sections, most of the electrochemical glyco-
sylation approaches are based on the anodic oxidation of aryl O-, S-, Se,
and Te-glycosides in order to generate an anomeric oxycarbenium ion
that reacts with alcohols to give alkyl O-glycosides or disaccharides.
Unfortunately, the oxidative conditions are not compatible with the
use of phenols as the glycosyl acceptors. Therefore, Rondinini and co-
workers 39 envisaged the electroreductive glycosylation of aryl alcohols to
overcome this serious drawback. They explored the cathodic reduction of
some glycosyl bromides and chlorides (reduction peak potential from
1.20 to 2.65 V) and selected the glucosyl bromide 118 to perform 40-42
the coupling with phenol, p-methoxyphenol, 1,2-, 1,3-, and 1,4-dihy-
droxybenzene, p-hydroxybenzyl alcohol, and 2,2 0 -biphenol. In all cases
complex mixtures of products were formed from which the corres-
ponding aryl glucosides were isolated in very low yields (less than 20%),
although the a- D anomers largely predominated in the reaction mixtures.
The latter finding strongly suggested 43,44 the formation of an anomeric
carbon radical that retains the sp 3 hybridization. Then, the more stable
a- D configured radical 120 (DE = 16 kcal/mol) undergoes the coupling
with a latent phenoxy radical (the O-H bond of the adsorbed phenol is
weakened by metal-H interaction) to afford the aryl glycoside 121.
The electrochemical reduction of glycosyl bromides on silver cathode
was also exploited for the synthesis of C-glycosyl compounds. Thus, when
the tri-O-acetyl-a- L -fucopyranosyl bromide 122 and its D -enantiomer were
individually submitted to cathodic reduction to generate the anomeric
radicals, the corresponding dimers, i.e. 1,1 0 -linked C-fucosyl derivatives,
were isolated in modest yield as mixture of anomers (a,a = a,b = 15%,
b,b = 11%). 45 Later on, a similar non-stereoselective dimerization was
carried out by the same authors starting from an O-disaccharide and an
O-trisaccharide anomeric bromide. 46 On the other hand, the reduction of
122 in the presence of the sugar iodide 123 allowed the synthesis 45 of the
1,6-C-disaccharides 124 in a yield slightly higher than that observed in