Preparation of acetylated pyranoid glycals from glycosyl halides by chromium(II) complexes under aqueous biphasic conditions

Article abstract of DOI:10.1016/S0008-6215(01)00254-3

Reactions of chromium(II) aminocarboxylate complexes (ethylenediamine-tetraacetate, nitrilo-triacetate, imino-diacetate) with acetylated glycopyranosyl chlorides or bromides in liquid-liquid or solid-liquid biphasic media (such as water-diethylether, water-ethyl acetate or halosugar-water) give the corresponding glycals in 75-97% yield.

Full text of DOI:10.1016/S0008-6215(01)00254-3

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Carbohydrate Research 336 (2001) 225–228
Note
Preparation of acetylated pyranoid glycals from glycosyl
halides by chromium(II) complexes under aqueous
biphasic conditions
Gyo¨ngyve´r Kova´cs,a Ka´roly Micskei,a,* La´szlo´ Somsa´kb,*
aDepartment of Inorganic and Analytical Chemistry, Faculty of Natural Sciences, Uni6ersity of Debrecen,
Egyetem te´r 1, H-4010 Debrecen, Hungary
bDepartment of Organic Chemistry, Faculty of Natural Sciences, Uni6ersity of Debrecen, Egyetem te´r 1,
H-4010 Debrecen, Hungary
Received 1 August 2001; accepted 19 September 2001
Abstract
Reactions of chromium(II) aminocarboxylate complexes (ethylenediamine-tetraacetate, nitrilo-triacetate, imino-di-
acetate) with acetylated glycopyranosyl chlorides or bromides in liquid–liquid or solid–liquid biphasic media (such
as water–diethylether, water–ethyl acetate or halosugar–water) give the corresponding glycals in 75–97% yield.
© 2001 Elsevier Science Ltd. All rights reserved.
Keywords: Chromium(II) complexes; Biphasic reactions; Glycals
Glycals (1,4- or 1,5-anhydro-2-deoxy-1-eni-
tols) are widely used in carbohydrate and
natural product syntheses as starting materi-
als. A recent review1 covering the synthetic
methods for glycals revealed that despite of
several existing procedures, further innova-
tions and amendments of known protocols
can improve the availability of this important
class of compounds.
corresponding glycosyl chlorides or bromides
mediated by Cr(II) aminopolycarboxylate
complexes in aqueous DMF as the reaction
medium. It was demonstrated in our previous
study that under the above conditions, com-
peting reactions at the anomeric centre (nucle-
ophilic attack by water or acetate ions to give
by-products versus electrontransfer leading to
glycals) had comparable rates if less reactive
Cr(II)L complexes (L=malonate, glycine,
imino-diacetate (IDA)) were used. This re-
sulted in less clean transformations which
could be avoided by using complexes of Cr(II)
with nitrilo-triacetate (NTA), or ethylenedi-
amine-tetraacetate (EDTA) as ligands.
In this note, we disclose a modification of
our recently published method2 for the prepa-
ration of acylated pyranoid glycals from the
* Corresponding authors. Tel.: +36-52-512900/2757; fax:
+36-52-489667 (K.M.); tel.: +36-52-512900/2453; fax: +36-
52-453836 (L.S.).
E-mail addresses: kmicskei@delfin.klte.hu (K. Micskei),
somsak@tigris.klte.hu (L. Somsa´k).
We reasoned that protection of the glycosyl
halides from the non-desirable nucleophilic
attack can also be achieved if these sensitive
0008-6215/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0008-6215(01)00254-3

226
G. Ko6a´cs et al. / Carbohydrate Research 336 (2001) 225–228
substrates and the reagents are placed into
separate phases. Following this hypothesis,
the chromium(II) complexes were prepared in
water and a solution of a glycosyl halide in
either diethyl ether (Table 1, Entries 1–7) or
ethyl acetate (Table 1, Entries 8–16) was
added and the mixture was vigorously stirred.
Yields and purities of the product glycals were
comparable with or better than those obtained
in the water–DMF homogeneous medium.2
Under these conditions Cr(II)(IDA) gave re-
sults comparable to the ones obtained with the
best complexes of NTA and EDTA.
added in pure water. These two-phase reac-
tions also offered an easier work-up procedure
as compared to the water–DMF variants for
each glycosyl halide.
Although this was not investigated, we spec-
ulate that under the biphasic conditions the
reaction may take place at the phase
boundary. Another possibility is that the
acetylated sugar derivatives which are not
completely insoluble in water can be present
in a limited concentration in the aqueous
phase containing the reagent. This latter as-
sumption is supported by the failure of the
biphasic transformations of 8 and 9 (Table 1,
Entries 17 and 18) which must be much less
soluble in water than their acetylated
analogues.
Another version of the biphasic reaction is
represented by Entries 19 and 20 in Table 1,
where the substrates 1 and 3 remained in the
solid phase and the reagent complex was
Table 1
Preparation of glycals in various biphasic systems
Entry
Solvent
Starting compound
Ligand (L)
pH
Product
Yield a,b (%)
1
2
3
4
5
6
7
water–Et2O
water–Et2O
water–Et2O
water–Et2O
water–Et2O
water–Et2O
water–Et2O
1
1
1
2
2
2
6
IDA
6.2
6.0
5.0
6.2
6.0
5.0
5.0
10
10
10
10
10
10
13
84
78
80
87
79
90
85
NTA
EDTA
IDA
NTA
EDTA
EDTA
8
9
water–EtOAc
water–EtOAc
water–EtOAc
water–EtOAc
water–EtOAc
water–EtOAc
water–EtOAc
water–EtOAc
water–EtOAc
1
2
2
2
3
4
5
6
7
EDTA
IDA
NTA
EDTA
EDTA
EDTA
EDTA
EDTA
EDTA
5.0
5.8
6.2
5.0
5.0
5.0
5.0
5.0
5.0
10
10
10
10
11
11
12
13
14
90
76
91
91
84
97
44 c
75
95
10
11
12
13
14
15
16
17
18
water–EtOAc
water–EtOAc
8
9
EDTA
EDTA
5.0
5.0
no reaction
no reaction
19
20
water
water
1
3
EDTA
EDTA
5.0
5.0
10
11
80
83
a The isolated products had NMR characteristics identical with those of authentic samples 10, 11, 13, 143, 12.4
1
b The purity of the isolated products was higher than 95% based on H NMR spectra of the worked-up reaction mixtures and
this means that no resonance other than those of 10–14 could be observed in the spectrum.
c For the -xylo configurated compounds, lower yields were obtained also under homogeneous conditions.2 For this behaviour,
D
the probably higher hydrolytic lability of these compounds may be responsible.

G. Ko6a´cs et al. / Carbohydrate Research 336 (2001) 225–228
227
In conclusion, we have elaborated a simple
procedure for the preparation of acetylated
pyranoid glycals of high purity in which both
glycosyl chlorides and bromides can be ap-
plied as starting compounds.
Organic solutions were dried over anhyd
MgSO4 and concentrated under diminished
pressure at 40–50 °C (water bath).
Aqueous solutions of the Cr(II)L complexes
and the glycosyl halides were prepared accord-
ing to literature protocols described and refer-
enced in detail in our previous paper.2
General procedure I for the reaction of
acetylated glycosyl halides 1–7 with chromium-
(II) complexes in liquid–liquid biphasic
medium.—Na2EDTA·H2O (0.893g, 2.4 mmol)
was dissolved in water (48.9 cm3) and KOH
(2.42 mol dm−3, 1.1 cm3, 2.66 mmol) was
added. Argon was bubbled into the solution
for 15 min. [Cr(OAc)2·H2O]2 (0.750 g, 2.2
mmol Cr(II)) was then added and the colour
of the solution turned immediately to sky-
blue. A solution of a glycosyl halide (1 mmol)
in Et2O or EtOAc (30 cm3) was deoxygenated
with argon and then added to the complex.
1. Experimental
Melting points were measured on a Kofler
hot-stage and are uncorrected. Optical rota-
tions were determined with a Perkin–Elmer
241 polarimeter at rt. NMR spectra were
recorded with a Bruker WP 200 SY spectrom-
13
eter (1H, 200 MHz; C, 50.3 MHz). TLC was
performed on DC-Alurolle, Kieselgel 60 F254
(E. Merck), (eluent: 1:1 EtOAc–hexane); the
plates were visualised by gentle heating. For
column chromatography Kieselgel 60 (E.
Merck) was used (eluent: 1:3 EtOAc–hexane).

228
G. Ko6a´cs et al. / Carbohydrate Research 336 (2001) 225–228
was continued as described in General proce-
dure I.
The colour of the aqueous phase turned
slowly to blue–violet indicating the formation
of Cr(III)EDTA. Intensive stirring was contin-
ued for 18 h. The aqueous phase was then
saturated with NH4Cl, then the two phases
were separated, and extracted with ether
(5×). The ethereal phase was washed with
water (3×), dried and the solvent removed
under diminished pressure. The residue was of
Acknowledgements
This work was supported by the Hungarian
Scientific Research Foundation (Grant No.:
OTKA T33130) and the Ministry of Educa-
tion (Grant No.: FKFP 0614/2000).
1
\95% purity as shown by H NMR spec-
troscopy.
General procedure II for the reaction of
acetylated glycosyl chlorides 1 and 3 with
[Cr(II)(EDTA)]2− complex in solid–liquid
biphasic medium.—Solutions of the complexes
were prepared in water (50 cm3) under argon
(General procedure I). A solid glycosyl halide
(1 mmol) was added to the solution in one
portion. After stirring for 18 h, the work-up
References
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Tetrahedron 1999, 55, 5253–5264.
3. Somsa´k, L.; Ne´meth, I. J. Carbohydr. Chem. 1993, 12,
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4. Weygand, F. Methods Carbohydr. Chem. 1962, 1, 182–
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