From conventional to greener catalytic approaches for carbohydrates etherification - Carbohydrate Chemistry: Chemical and Biological Approaches - page 75

Br Br

O

HO

HO O

O

O

OH

OH

NaH, DMF

O

O

yield: 60% O

O

Scheme 1 Xylylenation of an isopropylidene glucofuranoside derivative.

OTBS
OH

OTBS
OH

BnBr (1.5 eq.)
Catalyst (10%)
Ag 2 O (1.1 eq.)
MeCN, 40 °C

HO
HO

HO
BnO

P h OTBS

OMe

OMe

Ph

B

yield: 90% Intermediate: O

HO
O

OMe

O

catalyst:

B

The more nucleophilic
oxygen

N

H

H

Scheme 2 Regioselective alkylation of carbohydrate derivatives catalyzed by a diaryl-
borinic acid derivative.

As an example, the particular structure of the o-xylylene group allows
the selective synthesis of the corresponding 5,6-di-O-cyclic diether thus
retaining the 3-hydroxyl group untouched.
Interestingly, borinic acids have been used as catalysts to regio-
selectively alkylate carbohydrate derivatives bearing multiple secondary
hydroxyl groups with benzyl halides (Scheme 2). 5 It was proposed that
borinate esters formed from the carbohydrate and the catalyst are key
intermediates. On the basis of computational studies, it was shown that
the high selectivity arises from the favored substitution of the more
nucleophilic oxygen in the intermediate borinate ester. The procedure
allowed the protection of a broad scope of carbohydrates with benzyl,
4-bromobenzyl, 2-naphthylmethyl and (benzyloxy)methyl ether protect-
ing groups with high yields.
2-O-Picolinyl (2 0 -pyridylmethyl, Pic) units have been used as directing
groups in the stereoselective glycosylation for the synthesis of
oligosaccharides with 1,2-trans stereoselectivity. 6 Controlling the stereo-
selectivity of the glycosylation is an important issue to synthesize well
defined oligosaccharides that are known to play major roles in biological
processes. 7 The picolinyl group is introduced according to a Williamson
reaction between a free hydroxyl group of a polysubstituted carbohydrate
and picolyl bromide in the presence of a strong base (Scheme 3). The
reaction of a thus obtained S-thiazolinyl glycosyl donor with a glycosyl
acceptor leads to the formation of a disaccharide with a high yield and
b-stereoselectivity. This selectivity was explained by the formation of a
transient six membered cyclic intermediate which involves the pyridyl
moiety.
Interestingly, the substitution of other hydroxyl groups of the
carbohydrate leads to the formation of cis or trans glycosidic linkages
depending on the absolute configuration of the carbon center that bears
the picolinyl group. The selective formation of cis or trans linkage is in