Carbohydrate
RESEARCH
Carbohydrate Research 340 (2005) 2670–2674
Note
Mild one-pot preparation of glycosyl bromides
*
Mo Hunsen, David A. Long, Christopher R. DÕArdenne and Amanda L. Smith
Department of Chemistry, Kenyon College, Gambier, OH 43022, USA
Received 25 May 2005; accepted 15 September 2005
Available online 10 October 2005
Abstract—Mild one-pot protocols for the preparation of glycosyl bromides and alkyl bromides via in situ generation of HBr is
reported here.
Ó 2005 Elsevier Ltd. All rights reserved.
Keywords: Acetyl bromide; Acetobromination; Glycosyl bromides; Carbohydrate; One pot; In situ; HBr
Glycosyl bromides are important intermediates in car-
bohydrate chemistry. For example, a-glycosyl bromides
are used as starting materials in the synthesis of glyco-
sides and oligosaccharides, b-glycosyl halides, glycals,
and 2-acetoxyglycals (Scheme 1). Oligosaccharides are
increasingly becoming important in the pharmaceutical
industry, and the glycals, acetoxyglycals, and a- and b-
glycosyl halides are key intermediates in the synthesis
of oligosaccharides and glycoconjugates.
In the first protocol (Table 1, Scheme 2), free sugars
were directly and effortlessly converted to the corre-
sponding a-glycosyl bromides. First, acetic anhydride
(1.2 equiv per OH group) and a catalytic amount of
HClO were added to the free sugars in acetic acid,
4
and the reaction mixture was stirred for 30 min. Acetyl
bromide (3 equiv) and methanol (3.4 equiv) were then
added, and after 90 min the solvent was removed by a
rotary evaporator to deliver the glycosyl bromides that
were pure enough for further use. As shown in Table
1, glycosyl bromides of monosaccharides (entries 1 and
2), b-linked disaccharides (entries 3 and 4), and a-linked
di- and trisaccharides (entries 5 and 6) were prepared in
near-quantitative yields. It is worth mentioning that our
attempt to use the hydroxyl groups of the free sugar
itself to generate HBr from acetyl bromide resulted in the
partial hydrolysis of the glycosidic bonds of di- and tri-
saccharides. The use of methanol with acetyl bromide
solved this problem. Anhydrous ethanol worked equally
well. Protocol 2 (Table 1, Scheme 3) is another alterna-
tive to protocol 1, and it involves the addition of AcBr
and methanol to acetic acid to generate HBr, followed
Current methods for the preparation of glycosyl bro-
mides include treatment of the free saccharides with
1
,2
3,4
5,6
AcBr,
AcBr–AcOH,
or Ac O–HBr–AcOH,
or
2
treatment of the peracetylated saccharides with HBr–
7
8
AcOH or BiBr –Me SiBr. The above methods involve
3
3
the use of a heavy metal and/or transportation, genera-
tion, and/or use of excess HBr, which is a corrosive gas,
and our experience with the above conditions is not a
pleasant one due to the toxic fumes. In light of the ver-
satility and widespread use of glycosyl bromides as key
intermediates, a milder protocol for their preparation
is still needed.
We report here mild and efficient one-pot protocols
for the preparation of glycosyl bromides from the free
sugars or their peracetates via in situ generation of
HBr from an alcohol and acetyl bromide. We also show
that alkyl bromides can be cleanly prepared from alk-
enes using the same protocol.
by addition of the free sugars and Ac O (1.2 equiv per
2
OH group) to deliver the glycosyl bromides. Protocol
1 was found to be better than protocol 2 for galactose
and maltotriose.
In the third protocol (Table 2, Scheme 4), peracetates
of mono- and disaccharides were cleanly converted to
the corresponding a-glycosyl bromides using a mixture
of acetyl bromide and methanol in acetic acid. The
*
0
008-6215/$ - see front matter Ó 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2005.09.016