Dual course of bisacetonation of D-xylose in a system Me 2CO-Me2C(OMe)2-H2SO4

Article abstract of DOI:10.1134/S1070428009050194

In the course of formation of a bisisopropylidene protective group by keeping D-xylose in a mixture Me₂CO-(MeO)₂CMe ₂-H₂SO₄ alongside the expected 1,2:4,5-O-diisopropylidene derivative formed minor dimethylacetal, 2,3:4,5-O-diisopropylidene-D-xylose, inseparable from the main product by the chromatography on SiO₂. The conditions were found for the selective formation and isolation of the latter, some its one-pot transformations were studied resulting in synthetically promising orthogonally protected acyclic C⁵-synthons.

Full text of DOI:10.1134/S1070428009050194

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2009, Vol. 45, No. 5, pp. 762−765. © Pleiades Publishing, Ltd., 2009.
Original Russian Text © L.S. Khasanova, N.K. Selezneva, F.A. Gimalova, M.S. Miftakhov, 2009, published in Zhurnal Organicheskoi Khimii, 2009,
Vol. 45, No. 5, pp. 775−778.
Dual Course of Bisacetonation of D-Xylose
in a System Me2CO-Me2C(OMe)2-H2SO4
L. S. Khasanova, N. K. Selezneva, F. A. Gimalova, and M. S. Miftakhov
Institute of Organic Chemistry, Ufa Scientific Center, Russian Academy of Sciences, Ufa, 450054 Russia
e-mail: bioreg@anrb.ru
Received March 13, 2008
Abstract—In the course of formation of a bisisopropylidene protective group by keeping D-xylose in a mixture
Me2CO–(MeO)2CMe2–H2SO4 alongside the expected 1,2:4,5-O-diisopropylidene derivative formed minor
dimethylacetal, 2,3:4,5-O-diisopropylidene-D-xylose, inseparable from the main product by the chromatography
on SiO2. The conditions were found for the selective formation and isolation of the latter, some its one-pot
transformations were studied resulting in synthetically promising orthogonally protected acyclic C5-synthons.
DOI: 10.1134/S1070428009050194
reaction [6] along path a (Scheme 1). Oxetane I can also
be obtained in a good yield by intramolecular substitution
(SN2) of iodine in compound IV by alkoxide.
Anhydro derivatives of sugars are internally protected
compounds convenient for further regio- and
stereoselective transformations (cf., e.g., the structures
of levoglucosan and levoglucosenone, oxetano-,
epoxysugars etc. with the structures of the parent sugars
[1–5]).
Although the preparation of oxetane I by the path a
occurred without complications, still the stage of
bisacetonide II synthesis provided moderate yields and
was time-consuming. Aiming at optimization we carried
out the acetonation of D-xylose by a mixture Me2CO–
We synthesized 3,5-anhydro derivative of a D-xylose
I from diol III by intermolecular ring closure by Mitsunobu
Scheme 1.
DEAD, PPh3,
Py or NaH,
THF
O
R
O
O
O
Me2CO,
H2SO4
(1) H3O
(2) I2, PPh3, Im, THF
O
OH
O
O
O
O
O
O
O
OH
O
OH
III, IV
II
I
a
b
HO
OH
O
D-xylose
O
_
Me2CO_Me2C(OMe)2 H2SO4
CH(OMe)2
+
II
O
O
V
R = OH (III), I (IV).
762

DUAL COURSE OF BISACETONATION OF D-XYLOSE
763
Me2C(OMe)2–H2SO4 (cat.) (path b) [7]. However in
this event alongside the acetonide II formed a significant
amount (~20%) of acyclic bisacetonide V. In various
eluent systems compounds II and V appeared on TLC
plates as a single spot, and we failed to separate them by
column chromatography on SiO2. Therefore the mixture
of compounds II and V was involved into a sequence of
transformations modified compared to procedure a
(stages of preparation of primary iodide from alcohol III
[8] and ring closure effected by NaH instead of
intramolecular cyclization of diol III by Mitsunobu reaction
[9]) and aimed at the preparation of oxetane I (Scheme
2). We hoped that in the course of the progress along the
stages the mixture of compounds II and V would undergo
certain “self-purification”, and the main product I would
be obtained in a plausible purity. In the experiment this
reaction sequence led to the formation of two compounds:
oxetane I and epoxy derivative VI.
dimethoxypropane (the “source” of MεOH) aimed at
quenching water eliminated at the acetalization of xylose
with acetone. The liberated MeOH was involved in the
formation of the dimethyl acetal compound V. In the cyclic
forms of sugars (furanosides, pyranosides) the anomeric
hydroxy group is especially active in the formation of
glycosides catalyzed by acids in the presence of alcohols.
Therefore we believe that the acetalization of D-xylose
along the path leading to acyclic acetonide V started not
by the formation of the dimethyl acetal function at C1,
but the formation of C4,C5- or trans-C2,C3-acetonides
that block further cyclization into furanosides and
pyranosides.
When at the acetonation of D-xylose along path b
(Scheme 1) into the reaction mixture was added MeOH,
then at incomplete conversion of the initial compound at
the beginning of the reaction the TLC test showed a low-
polar main spot corresponding to the acetonides mixture
of II and V. However the spectral data of this compound
showed that it was the individual minor bisacetonide V.
As a result we obtained a sample of bisacetonide V lacking
the impurity of compound II.
We succeeded in the complete purification of oxetane
I after treating the mixture of compounds I and VI with
LiAlH4 (THF, 20°C). The formed alcohol VII due to its
higher polarity was easily separated on SiO2 from the
unreacted oxetane I; alcohol VII was characterized as
acetate VIII.
Thus in the synthesis of oxetane I bisacetonide II
should be used obtained by the H+-catalyzed reaction of
D-xylose with acetone (path a) in the absence of
(MeO)2CMe2. Bisacetonide V, epoxide VI, and acetate
The formation of acyclic derivative V at the preparation
of D-xylose acetal was evidently due to the use of 2,2-
Scheme 2.
(2) H+3O
O
CH(OMe)2
(2) I2, Im, PPh3, THF
(3) NaH, THF
II + V
I +
O
O
VI
OH
OAc
O
CH(OMe)2
CH(OMe)2
(1) SiO2
LiAlH4, THF, 20oC
(2) Ac2O_Py
I +
O
O
O
VII
VIII
O
Me2CO, MeOH,
Me2C(OMe)2, conc. H2SO4,
20oC, 2 h
OH
O
OH
O
CH(OMe)2
+
other compounds
HO
O
O
OH
D-xylose
V (20%)
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 5 2009

KHASANOVA et al.
764
diole III, 4.32 g (18.3 mmol) of PPh3, 1.46 g (21.5 mmol)
of imidazole (Im), and 4.34 g (34.2 mmol) of I2 in 60 ml
of THF was stirred for 4.5 h under an argon atmosphere
at 50–60°C [8]. The workup was the same as in
preparation of compound I, the residue was purified by
column chromatography on SiO2 (eluent ethyl acetate–
petroleum ether, 3:1). Yield 2.27 g (53%), [α]D20 –18.5°
VIII formed in the side reactions are synthetically
promising new chiral C5-block synthons.
EXPERIMENTAL
IR spectra were recorded on spectrophotometers UR-
20 and Specord M-80 from thin films or mulls in mineral
oil. 1H and 13C NMR spectra were registered on a spec-
trometer BrukerAM-300 at operating frequencies 300.13
and 75.47 MHz respectively, internal reference TMS.
The optical rotation was measured on a polarimeter Perkin
Elmer-341. Mass spectra were obtained on an instrument
Thermo Finnigan MAT 95XP, 70 eV, ionizing chamber
temperature 200°C, sample admission at 5–270°C, heating
rate 22 deg/min.
1
(c 0.94, CHCl3). H NMR spectrum, δ, ppm: 1.30 s (3H,
CH3), 1.50 C (3H, CH3), 2.90 br.s (1H, OH), 3.20 m
(2H, CH2I), 4.40 m (2H, C3H, C4H), 4.53 d (1H, C2H,
J 3.6 Hz), 5.96 d (1H, C1H, J 3.6 Hz). 13C NMR
spectrum, δ, ppm: 8.49 (CH2I), 26.13 (CH3), 26.73 (CH3),
74.52 (C4), 80.86 (C3), 85.02 (C2), 105.37 (C1), 111.83
(CMe2).
2,3:4,5-Di-O-isopropylidene-D-xylose dimethyl-
acetal (V). To a solution of 3.5 g (23.95 mmol) of
D-xylose and 6.5 ml (52.69 mmol) of 2,2-dimethoxy-
propane in 20 ml of a mixture acetone–methanol, 1:1,
was added 0.001 ml of concn. H2SO4, and the reaction
mixture was stirred at 20OC till the complete consumption
of the initial compound (~2 h, TLC monitoring). Then
acetone was evaporated, and the residue was subjected
to column chromatography on SiO2 (eluent ethyl acetate–
petroleum ether, 1:1). Yield 1.29 g (~20%), [α]D20 –1.3°
3,5-Anhydro-1,2-O-isopropylidene-α-D-xylo-
furanose (I). To a dispersion of 0.06 g (2.5 mmol) of
NaH in 5 ml of THF under an argon atmosphere was
slowly added dropwise at stirring a solution of 0.3 g
(1.0 mmol) of iodide IV in 10 ml of THF. The reaction
mixture was stirred at room temperature for 2 h, then it
was quenched with a saturated water solution of NH4Cl
(1 ml). THF was distilled off, the reaction product was
extracted from the water layer with CHCl3 (3 × 20 ml),
the combined extracts were washed with the saturated
NaCl solution, dried with MgSO4, evaporated, and the
residue was subjected to chromatography on SiO2. Yield
0.11 g (65%). Oily substance, [α]D20 +11.3° (c 0.5, CHCl3)
{+11.0° (c 1.0, CHCl3) [6], +11.9° (c 0.75, CHCl3) [9]}.
1H NMR spectrum, δ, ppm: 1.37 s (CH3), 1.40 s (CH3),
4.25 d.d (1H, H5A, J4,5A 2.2, J5A,5B 7.7, long range constant
0.5 Hz), 4.72 d (1H, H2, J 3.7 Hz), 4.74 d.d (1H, H5B,
J4,5B 4.3 Hz), 5.13 d.t (1H, H4), 5.20 d (1H, H3, J 4.0 Hz),
6.25 d (1H, H1, J1,2 3.7 Hz). 13C NMR spectrum, δ,
ppm: 27.05 (CH3), 27.75 (CH3), 78.15 (C3), 78.36 (C5),
84.48 (C4), 87.40 (C2), 108.09 (C1), 113.74 (CMe2). Mass
spectrum, m/z: 171 [M – 1]+, 157 [M – CH3]+, 129 [M –
C2H3O]+, 113 [M – C3H7O]+.
1
(c 0.98, CHCl3). H NMR spectrum, δ, ppm: 1.34 s (3H,
CH3), 1.38 s (6H, 2 CH3), 1.40 s (3H, CH3), 3.40 s (3H,
OCH3), 3.41 s (3H, OCH3), 3.75–4.15 m (5H, C3H, C2H,
C4H, CH2), 4.33 d (1H, C1H, J 5.75 Hz). 13C NMR
spectrum, δ, ppm: 25.49 (CH3), 25.94 (CH3), 26.67
(CH3), 26.77 (CH3), 53.55 (OCH3), 55.56 (OCH3), 65.72
(C5), 75.73 (C4), 76.48 (C3), 76.63 (C2), 104.61 (C1),
109.07 (CMe2), 109.69 (CMe2).
Direct transition from D-xylose to oxetane I and
epoxide VI. To a solution of 3.5 g (23.95 mmol) of
D-xylose and 6.5 ml (52.69 mmol) of 2,2-dimethoxy-
propane in 30 ml of acetone was added 0.025 ml of concn.
H2SO4, and the reaction mixture was stirred at 20OC till
the complete consumption of the initial compound
(~10 h, TLC monitoring). Then acetone was evaporated,
and the residue was subjected to column chromatography
on SiO2 (eluent ethyl acetate–petroleum ether, 1:1). Yield
2.73 g (62%) of a mixture of compounds II and V in
a ratio 4:1 (1H NMR data). The spectral characteristics
of compounds II and V measured in the mixture coincided
with the characteristics of individual bisacetonide II [10]
and acetonide V prepared in modified conditions (see
above).
1,2-O-Isopropylidene-α-D-xylofuranose (III)
was obtained by procedure [10]. IR spectrum, cm–1: 3400
(νOH). 1H NMR spectrum, δ, ppm: 1.37 s (3H, CH3),
1.45 s (3H, CH3), 3.70 t (1H, J 5.7 Hz) and 4.13 q (1H,
CH2, J 3.7 Hz), 3.96 d.d (1H, OH, J 3.6 and 5.3 Hz),
4.25 d.t (1H, C4H, J 3.6 Hz), 4.40 d (1H, C3H, J 4.2 Hz),
4.48 d (1H, C2H, J 3.7 Hz), 5.93 d (1H, C1H, J 3.7 Hz).
13C NMR spectrum, δ, ppm: 26.03 (CH3), 26.59 (CH3),
60.58 (C5), 76.17 (C4), 77.42 (C3), 85.41 (C2), 104.67
(C1), 111.64 (CMe2).
To 2.5 g of the mixture of compounds II and V without
purification was added 25 ml of water and 0.025 ml of
5-Deoxy-5-iodo-1,2-O-isopropylidene-α-D-
xylofuranose (IV). A solution of 2.7 g (14.2 mmol) of
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 5 2009

DUAL COURSE OF BISACETONATION OF D-XYLOSE
765
concn. H2SO4, the mixture was stirred for 2 h. Then to
the reaction mixture was added dropwise 5% solution of
NaHCO3 till pH 7, the solvent was evaporated, and the
residue was subjected to column chromatography on SiO2
(eluent ethyl acetate–petroleum ether, 1:1). We obtained
1.8 g of a mixture of diol III and the corresponding
4,5-deprotected derivative of compound V. This mixture
was dissolved in 40 ml of THF, and to the solution 3.07 g
(13.0 mmol) of PPh3, 1.02 g (15.0 mmol) of imidazole,
and 3.17 g (25.0 mmol) of I2 were added, and the mixture
was stirred under argon for 4.5 h while heating at 50–
60°C. The solvent was evaporated, the residue was
dissolved in CHCl3 and washed with a saturated water
solution of Na2S2O3. The organic layer was dried with
MgSO4, the solvent was evaporated, and the residue was
subjected to column chromatography on SiO2 (eluent ethyl
acetate–petroleum ether, 3:1). The mass obtained
(1.0 g) was dissolved in 20 ml of THF, and this solution
was added dropwise to a dispersion of 0.2 g of NaH in
20 ml of THF. After keeping the reaction mixture for 2 h
it was worked up as described for compound I. We
obtained 0.4 g of oily mixture of anhydrosugars I and VI
in the ratio 4:1 (1H NMR data).
acetate, 7:1). We obtained 60 mg of oxetane I and 20 mg
of alcohol VII which was used in the next stage.
(2R,3S,4R)-5-Deoxy-4-acetyl-2,3-O-isopropylid-
ene-D-xylose dimethylacetal (VIII). In 2 ml of a mix-
ture Py–Ac2O, 2:1, was dissolved 20 mg of alcohol VII,
and the reaction mixture was stirred till the disappearance
of the initial compound (TLC monitoring). The reaction
mixture was poured into 2 ml of ice water, and the reaction
product was extracted into CHCl3 (3 × 3 ml), the organic
extracts were washed with water and dried with MgSO4.
Yield 19.5 mg (82%), [α]D20 +6.6° (c 1.0, CHCl3). 1H NMR
spectrum, δ, ppm: 1.40 d (3H, CH3, J 6.5 Hz), 1.42 s (3H,
CH3), 1.43 s (3H, CH3), 2.07 s (CH3), 3.42 s (3H,
OCH3), 3.44 s (3H, OCH3), 3.92 d.d (1H, C2H, J 5.9,
7.0 Hz), 3.98 d.d (1H, C3H, J 3.1, 7.0 Hz), 4.34 d (1H,
C1H, J 5.7 Hz), 4.90 d.d.d.d (1H, C4H, J 3.1, 3.4, 6.5 Hz).
13C NMR spectrum, δ, ppm: 16.06 (CH3), 20.32 (CH3),
25.93 (CH3), 26.42 (CH3), 53.45 (OCH3), 54.96 (OCH3),
68.49 (C4), 75.36 (C3), 79.63 (C2), 104.14 (C1), 109.29
(CMe2), 169.51 (CH3CO).
The study was carried out under the financial support
of the Federal Agency for Science and Innovations and
Council for grants of the President of the Russian
Federation (project NSh-1725.2008.3).
4,5-Anhydro-2,3-O-isopropylidene-D-xylo-
1
furanose dimethylacetal (VI). H NMR spectrum, δ,
ppm: 2.75 d.d (1H, H5a, J 2.7 and 5.3 Hz), 2.81 d.d (1H,
H5b, J 4.2, 5.3 Hz), 3.10 d.d.d (1H, H4, J 2.7, 4.2,
4.9 Hz), 3.45 s (3H, OCH3), 3.46 s (3H, OCH3), 3.83 d.d
(1H, H3, J 4.9, 7.6 Hz), 4.10 d.d (1H, H2, J 6.2, 7.6 Hz),
4.40 d (1H, H1, J 6.2 Hz). 13C NMR spectrum, δ, ppm:
26.44 (CH3), 26.77 (CH3), 44.71 (C5), 51.90 (OCH3),
57.76 (OCH3), 55.49 (C4), 77.84 (C2), 77.21 (C3), 104.49
(C1), 110.41 (CMe2). Mass spectrum, m/z: 218 [M]+, 203
[M – CH3]+, 143 [M – C3H7O2]+, 75 [C3H7O]+.
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