Synthesis of α-bromoisolevoglucosenone and its cyclopenta annulation

Article abstract of DOI:10.1134/S107042801409140

4,4-Dimethyl-3-nitro-10,11-dioxatricyclo[6.2.1.0^2,6]undec-5-en-7-one possessing a bicyclic iridoid skeleton was synthesized in two steps from isolevoglucosenone which was obtained in turn from levoglucosenone through 4-benzyloxy-2-tosyloxy deri

Full text of DOI:10.1134/S107042801409140

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2014, Vol. 50, No. 9, pp. 1317–1322. © Pleiades Publishing, Ltd., 2014.
Original Russian Text © I.M. Biktagirov, L.Kh. Faizullina, Sh.M. Salikhov, M.G. Safarov, F.A. Valeev, 2014, published in Zhurnal Organicheskoi Khimii,
2014, Vol. 50, No. 9, pp. 1333–1338.
Synthesis of α-Bromoisolevoglucosenone
and Its Cyclopenta Annulation
I. M. Biktagirova, L. Kh. Faizullinab, Sh. M. Salikhovb, M. G. Safarova, and F. A. Valeevb
a Bashkir State University, ul. Zaki Validi 32, Ufa, 450076 Bashkortostan, Russia
b Institute of Organic Chemistry, Ufa Research Center, Russian Academy of Sciences,
pr. Oktyabrya 71, Ufa, 450054 Bashkortostan, Russia
e-mail: sinvmet@anrb.ru
Received April 23, 2014
Abstract—4,4-Dimethyl-3-nitro-10,11-dioxatricyclo[6.2.1.02,6]undec-5-en-7-one possessing a bicyclic iridoid
skeleton was synthesized in two steps from isolevoglucosenone which was obtained in turn from levogluco-
senone through 4-benzyloxy-2-tosyloxy derivative.
DOI: 10.1134/S107042801409140
The presence in the levoglucosenone molecule of
a conjugated enone fragment makes it possible to syn-
thesize in a short way substituted or fused derivatives
at positions C2, C3, and C4 [1–7]. If there is a need of
obtaining regioisomers or compounds with opposite
configuration of the asymmetric centers, isolevogluco-
senone seems to be more appropriate substrate [8–12].
Like levoglucosenone [13], cycloaddition reactions of
isolevoglucosenone, e.g., with cyclopentadiene [11],
show efficient stereocontrol by the substrate structure.
On the other hand, it should be noted that the prop-
erties of isolevoglucosenone have been studied to
a lesser extent than those of levoglucosenone, which is
related to low accessibility of the former. In particular,
there are no published data on the synthesis and prop-
erties of its α-halo derivatives. It is known that such
levoglucosenone derivatives tend to undergo tandem
transformations in reactions with CH acids and binu-
cleophiles [14].
the preparation of carbohydrates, including levogluco-
senone, have been reported. Especially efficient is the
synthesis based on the allylic rearrangement of sele-
nide obtained from hydroxy derivative of levogluco-
senone [16]. Nevertheless, search for alternative paths
of this transformation from simpler levoglucosenone
derivatives remains topical.
We have found that isolevoglucosenone can be syn-
thesized from 2-sulfonyl derivatives of levogluco-
senone and that isolevoglucosenone can be converted
into α-bromo derivative which may be subjected to
cyclopenta annulation according to the procedure de-
scribed by us previously [17].
1,4-Addition of benzyl alcohol to levoglucosenone
(I) gave 4-benzyloxy derivative II [18]; the subsequent
reduction with sodium tetrahydridoborate led to the
formation of a mixture of epimeric alcohols IIIa and
IIIb at a ratio of 1 :0.9. Alcohols IIIa/IIIb were
smoothly converted into sulfonates IVa/IVb and
Va/Vb (Scheme 1).
Isolevoglucosenone attracts interest from the view-
point of development of a short synthetic route to
iridoid compounds [15]. Fairly reliable procedures for
The NOESY spectrum of IVa/IVb displayed a cor-
relation between 6-HB and 4-H, indicating β-orienta-
Scheme 1.
O
O
O
O
PhCH2OH, Et3N
NaBH4
RCl
O
O
O
O
O
O
OH
OR
PhCH2O
II, 92%
PhCH2O
PhCH2O
I
IIIa, IIIb, 90%
β:α = 1:0.9
IVa, IVb, R = Ms, 90%
Va, Vb, R = Ts, 84%
β:α = 1:0.9
1317

BIKTAGIROV et al.
1318
Scheme 2.
O
Bu4NOH, MeCN, 30%
or KOH–DMSO, 75%
O
OCH2Ph
C10H7Li, THF, 0°C
IIIa, IIIb, 70–80%
VI
O
H2, Raney nickel
R = Ms
O
IVa, IVb, Va, Vb
OMs
OH
VIIa, VIIb, 65%
VIIIa, VIIIb, 40%
β:α = 1:0.9
SnCl4, CH2Cl2
VIIa, VIIb, 64%
β:α = 1:0.9
O
O
H2, Raney nickel
R = Ts
O
O
+
OTs
OH
OH
IX, 64%
OH
VIIIa, VIIIb, 28%
β:α = 1:0.9
tion of the latter. The large vicinal coupling constant
3J3A,2 = 10.5 Hz is typical of the R configuration of C2
in β-isomer IVa. The corresponding value for α-epimer
IVb is 4.8 Hz, which corresponds to the S configura-
tion of C2.
SnCl4 in methylene chloride [24] afforded alcohols
VIIa/VIIb and VIIIa/VIIIb in 65 and 40% yield,
respectively (Scheme 2).
The final step, oxidation of VIIa/VIIb and
VIIIa/VIIIb with pyridinium chlorochromate (PCC)
or Collins’ reagent was accompanied by dehydrosul-
fonyloxylation to produce isolevoglucosenone (X)
(Scheme 3). α-Bromoisolevoglucozenone (XI) was
smoothly synthesized according to a procedure analo-
gous to the synthesis of α-bromolevoglucosenone [25].
Treatment of XI with 2,2-dimethyl-1,3-dinitropropane
under conditions of phase-transfer catalysis and ultra-
sonic irradiation afforded cyclopenta-fused adduct XII
in 60% yield (Scheme 4).
The next step of our study implied two transforma-
tion sequences: (1) β-elimination of the sulfonyl group,
debenzylation, and allylic oxidation or (2) debenzyla-
tion, oxidation, and β-elimination of the sulfonyl
group. Unfortunately, treatment of sulfonates IVa/IVb
and Va/Vb with such bases as KOH–EtOH, NaOEt
[19], Et3N–DBU [20], and Zn–i-PrOH [21] or heating
in pyridine or trimethylpyridine [22] led to complex
mixtures of products which were difficult to separate.
An attempt to accomplish debenzylation by the action
of lithium naphthalenide under different conditions
[23] was accompanied (as might be expected) by
simultaneous removal of the sulfonyl group with
formation of initial alcohols IIIa/IIIb. Hydrogenation
of IVa/IVb and Va/Vb over Raney nickel resulted in
debenzylation to alcohols VIIa/VIIb and VIIIa/VIIIb
in moderate yields; however, in the reaction with
Va/Vb the major product was diol IX. β-Elimination
from IVa/IVb and Va/Vb to obtain benzyl ether was
achieved with the aid of tetrabutylammonium hydrox-
ide or potassium tert-butoxide, but the use of KOH–
DMSO was more efficient. Attempted removal of the
benzyl protection by the action of lithium naphtha-
lenide or SnCl4 [24] led to decomposition, presumably,
due to instability of the allylic alcohol thus formed
(Scheme 2). Treatment of IVa/IVb and Va/Vb with
Scheme 3.
PCC (50% and 43%)
or CrO3, pyridine, CH2Cl2
(50% and 27%)
O
O
VIIa, VIIb
VIIIa, VIIIb
O
X
Adduct XII showed in the NOESY spectrum
a cross peak between 9-HB and 2-H, which is possible
if the C2 atom has R configuration. This is also con-
firmed by the NOE observed between 3-H and 1-H.
The coupling constant 3J3,2 = 10.2 Hz is determined by
the anti orientation of 3-H and 2-H. The coupling con-
3
stant J1,2 is equal to zero, presumably because the
torsion angle H1C1C2H2 is close to 90°.
In summary, we have studied the possibility for
“sulfonate” transformation of levoglucosenone into
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 50 No. 9 2014

SYNTHESIS OF α-BROMOISOLEVOGLUCOSENONE
1319
Scheme 4.
O
7
O
O
Me
Br2, pyridine
Me2C(CH2NO2)2
6
2
5
3
8
4
9
O
O
11O
1
Me
O
O
O10
O2N
Br
XI, 68%
X
XII, 60%
1
isolevoglucosenone and thus developed a two-step
procedure for the synthesis of compound XII posses-
sing a bicyclic iridoid fragment.
(2R)-Epimer IVa. H NMR spectrum, δ, ppm:
2
3
3
1.95 d.d.d (1H, 3-HA, J = 14.5, J3A, 2 = 10.5, J3A, 4
=
2
3
4.4 Hz), 2.35 d.d.q (1H, 3-HB, J = 14.5, J3B,2 = 6.2,
3J3B,1 = 1.6, 4J3B,5 = 1.6 Hz), 3.03 s (3H, CH3), 3.58 d.t
3
3
3
EXPERIMENTAL
(1H, 4-H, J4,3A = 4.4, J4,3B = 1.6, J4,5 = 1.6 Hz),
2
3
3.79 d.d (1H, 6-HB, J = 7.8, J6B,5 = 0.6 Hz), 3.84 d.d
2
3
The NMR and IR spectra were obtained using the
equipment of the Khimiya Shared Use Center,
Institute of Organic Chemistry, Ufa Research Center,
(1H, 6-HA, J = 7.8, J6A,5 = 5.4 Hz), 4.63 m (3H, 5-H,
CH2Ph), 4.87 d.d.d (2H, 2-H, 3J2,3A = 10.5, 3J2,3B = 6.2,
3J2,1 = 1.6 Hz), 5.58 d.d (1H, 1-H, J1,2 = 1.6, J1,3B
=
3
4
1
Russian Academy of Sciences. The H and 13C NMR
1.6 Hz), 7.35 m (5H, Ph). 13C NMR spectrum, δC,
ppm: 29.71 (C3), 39.96 (CH3), 68.04 (C6), 71.86
(CH2Ph), 75.42 (C4), 75.83 (C5), 75.49 (C2), 101.53
(C1); 129.17, 129.26, 129.98, 138.93 (Ph).
spectra were recorded on a Bruker AM-300 spectrom-
eter at 300 and 75.47 MHz, respectively, as well as on
a Bruker Avance III spectrometer at 500 MHz (1H);
CDCl3 was used as solvent unless otherwise stated.
The mass spectra were obtained on a Hewlett Packard
HP 5973 mass-selective detector coupled with
an HP 6890 chromatograph. Sorbfil PTSKh-AF-A
plates (Sorbpolimer closed corporation, Krasnodar,
Russia) were used for analytical TLC. The melting
points were measured on a Boetius PHMK 05 hot
stage. The elemental compositions were determined on
a Euro 2000 CHNS(O) analyzer. The optical rotations
were measured on a Perkin Elmer 341 polarimeter.
1
(2S)-Epimer IVb. H NMR spectrum, δ, ppm:
2
3
3
2.09 d.t (1H, 3-HA, J = 16.5, J3A,2 = 4.8, J3A,4
=
=
2
3
4.8 Hz), 2.30 d.quint (1H, 3-HB, J = 16.5, J3B,2
3J3B,4 = J3B,1 = J3B,5 = 1.7 Hz) , 3.08 s (3H, CH3),
4
4
3
3
3
3.40 d.t (1H, 4-H, J4,3A = 4.8, J4,3B = J4,5 = 1.7 Hz),
2
3
3.75 d.d (1H, 6-HB, J = 7.8, J6B,5 = 0.5 Hz), 3.85 d.d
(1H, 6-HA, 2J = 7.8, 3J6A,5 = 5.4 Hz), 4.58 m (1H, 5-H),
3
4.67 s (2H, CH2Ph), 4.89 d.t (1H, 2-H, J2,3A = 4.8,
3J2,3B = J2,1 = 1.7 Hz), 5.55 d.d (1H, 1-H, J1,2
=
3
3
4J1,3B = 1.7 Hz), 7.34 m (5H, Ph). 13C NMR spectrum,
δC, ppm: 26.92 (C3), 40.31 (CH3), 66.95 (C6), 72.19
(CH2Ph), 72.28 (C4), 72.97 (C2), 76.09 (C5), 100.82
(C1); 129.10, 129.39, 129.89, 138.96 (Ph). Mass spec-
trum: m/z 314.1 [M – H]+. Found, %: C 53.43; H 5.70.
C14H18O6S. Calculated, %: C 53.44; H 5.72.
M 314.3551.
1,6-Anhydro-4-O-benzyl-3-deoxy-β-D-erythro-
hexopyranos-2-ulose (II) and 1,6-anhydro-4-O-benzyl-
3-deoxy-β-D-arabino/ribo-hexopyranose (IIIa/IIIb)
were synthesized as described in [10].
1,6-Anhydro-4-O-benzyl-3-deoxy-2-O-(metane-
sulfonyl)-β-D-arabino/ribo-hexopyranose (IVa/IVb).
Triethylamine, 0.4 mL (2.74 mmol), was added to
a solution of 0.32 g (1.37 mmol) of epimeric alcohols
IIIa/IIIb in 7.0 mL of methylene chloride, the mixture
was cooled to 0°C, 0.16 mL (2.05 mmol) of methane-
sulfonyl chloride was added, and the mixture was
stirred for 30 min at room temperature (TLC). The
reaction mixture was treated with water (2×10 mL)
and extracted with methylene chloride (3×10 mL), the
organic phase was washed with 10% aqueous HCl and
saturated aqueous solutions of NaHCO3 and NaCl and
dried over MgSO4, the solvent was distilled off, and
the residue was subjected to chromatography on silica
gel. Yield 0.39 g (90%), colorless crystals, mp 81°C,
Rf 0.5 (petroleum ether–EtOAc, 2:1).
1,6-Anhydro-4-O-benzyl-3-deoxy-2-O-(4-methyl-
benzenesulfonyl)-β-D-arabino/ribo-pyranose
(Va/Vb). A solution of 0.26 g (1.11 mmol) of alcohols
IIIa/IIIb in 7.0 mL of pyridine was cooled to 0°C,
0.21 g (1.11 mmol) of 4-methylbenzenesulfonyl
chloride was added in portions, and the mixture was
stirred at room temperature until the initial compound
disappeared (TLC). The mixture was treated with 10%
aqueous HCl (2×10 mL) and extracted with ethyl
acetate (3×10 mL). The extract was washed with satu-
rated aqueous solutions of NaHCO3 and NaCl, dried
over MgSO4, and concentrated, and the residue was
subjected to chromatography on silica gel. Yield 0.36 g
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 50 No. 9 2014

BIKTAGIROV et al.
1320
(84%), oily substance, Rf 0.4 (petroleum ether–ethyl
concentrated, and the residue was subjected to chro-
matography on silica gel. Yield 0.134 g (75%).
acetate, 2:1).
1
(2R)-Epimer Va. H NMR spectrum, δ, ppm:
c. Epimer mixture IIIa/IIIb, 0.36 g (0.93 mmol),
was added to a solution of 0.31 g (2.80 mmol) of
potassium tert-butoxide in 5.0 mL of tert-butyl alco-
hol, and the mixture was heated under reflux until the
initial compounds disappeared (TLC). The mixture
was treated with 3 mL of water and extracted with
ethyl acetate (3×5 mL), the extract was dried over
MgSO4 and concentrated, and the residue was sub-
jected to chromatography on silica gel. Yield 0.092 g
(46%), oily substance, Rf 0.8 (petroleum ether–EtOAc,
2
3
3
1.87 d.d.d (1H, 3-HA, J = 14.1, J3A,2 = 10.4, J3A,4
=
2
3
4.4 Hz), 2.17 d.d.q (1H, 3-HB, J = 14.1, J3B,2 = 6.2,
3J3B,4 = J3B,1 = J3B,5 = 1.5 Hz), 2.45 s (3H, CH3),
4
4
3
3
3
3.50 d.t (1H, 4-H, J4,3A = 4.4, J4,3B = J4,5 = 1.5 Hz),
2
3
3.72 d.d (1H, 6-HB, J = 7.8, J6B,5 = 0.6 Hz), 3.77 d.d
(1H, 6-HA, 2J = 7.8, 3J6A,5 = 5.6 Hz), 4.54 m (1H, 5-H),
2
4.56 d and 4.58 d (1H each, CH2Ph, J = 12.3 Hz),
3
3
3
4.64 d.d.d (1H, 2-H, J2,3A = 10.4, J2,3B = 6.2, J2,1
=
3
3
1.5 Hz), 5.28 d.d (1H, 1-H, J1,2 = J1,3B = 1.5 Hz),
7.35 m (7H, Harom), 7.78 d (2H, Harom, J = 8.3 Hz).
2:1), [α]D20 = +12.3° (c = 0.5, CHCl3). H NMR spec-
2
1
13C NMR spectrum, δC, ppm: 23.06 (CH3), 29.40 (C3),
67.97 (C6), 72.13 (CH2Ph), 75.38 (C4), 75.92 (C5),
77.14 (C2), 101.32 (C1); 128.36, 129.05, 129.10,
129.25, 129.83, 135.07, 138.89, 146.44 (Carom).
trum, δ, ppm: 3.39 d.d (1H, 6-HB, J = 7.7, J =
2
3
3
2.0 Hz), 3.53 d.t (1H, 4-H, J = 4.2, 1.0 Hz), 3.92 d.d
2
3
(1H, 6-HA, J = 7.7, J = 6.7 Hz), 4.69 s (2H, CH2Ph),
3
4.79 m (1H, 5-H), 5.56 d (1H, 1-H, J = 3.5 Hz),
3
1
5.85 m (1H, 3-H), 6.13 d.d.d (1H, 2-H, J = 9.6, 1.0,
(2S)-Epimer Vb. H NMR spectrum, δ, ppm:
1.0 Hz), 7.40 m (5H, Ph). 13C NMR spectrum, δC,
ppm: 63.13 (CH2Ph), 70.71 (C6), 73.10 (C4), 74.15
(C5), 95.51 (C1), 124.15 (C3); 127.75, 127.86, 128.53
(Ph); 131.40 (C2), 138.11 (Ph). Mass spectrum:
m/z 218.1 [M – H]+. Found, %: C 71.43; H 6.40.
C13H14O3. Calculated, %: C 71.48; H 6.41. M 218.2485.
2
3
3
1.98 d.t (1H, 3-HA, J = 16.4, J3A,2 = J3A,4 = 4.8 Hz),
2
3
3
2.16 d.quint (1H, 3-HB, J = 16.4, J3B,2 = J3B,4
=
4J3B,1 = 4J3B,5 = 1.7 Hz), 2.47 s (3H, CH3), 3.32 d.t (1H,
3
3
3
4-H, J4,3A = 4.8, J4,3B = J4,5 = 1.7 Hz), 3.67 d.d (1H,
2
3
6-HB, J = 7.8, J6B,5 = 0.5 Hz), 3.78 d.d (1H, 6-HA,
2J = 7.8, 3J6A,5 = 5.6 Hz), 4.38 d.t (1H, 2-H, 3J2,3A = 4.8,
3J2,3B = J2,1 = 1.7 Hz), 4.55 d and 4.57 d (1H each,
1,6-Anhydro-3-deoxy-4-hydroxy-2-O-(methane-
sulfonyl)-β-D-arabino/ribo-hexopyranose
(VIIa/VIIb). A solution of 0.27 g (0.28 mmol) of
IVa/IVb in 10.0 mL of ethanol was stirred for 2 days
in a hydrogen atmosphere over Raney nickel (TLC).
The mixture was filtered, the solvent was distilled off
from the filtrate, and the residue was subjected to
chromatography on silica gel. Yield 0.11 g (64%),
colorless crystals, mp 117°C, Rf 0.3 (EtOAc).
3
CH2Ph, 2J = 12.3 Hz), 4.63 m (1H, 5-H), 5.33 d.d (1H,
1-H, 3J1,2 = 3J1,3B = 1.7 Hz), 7.30 m (7H, Harom), 7.79 d
2
13
(2H, Harom, J = 8.3 Hz). C NMR spectrum, δC, ppm:
22.46 (CH3), 26.57 (C3), 66.89 (C6), 71.68 (CH2Ph),
72.22 (C4), 74.04 (C2), 76.13 (C5), 100.75 (C1); 129.16,
129.35, 129.95, 135.36, 139.24, 146.05 (Carom). Mass
spectrum: m/z 390.2 [M – H]+. Found, %: C 61.41;
H 5.62. C20H22O6S. Calculated, %: C 61.47; H 5.63.
M 390.4511.
1,6-Anhydro-4-O-benzyl-2,3-dideoxy-β-D-
erythro-hex-2-enopyranose (VI). a. Tetrabutylammo-
nium hydroxide, 0.25 g (0.97 mmol), was added to
a solution of 0.38 g (0.97 mmol) of sulfonates IVa/IVb
in 10.0 mL of acetonitrile, and the mixture was heated
under reflux until the initial compounds disappeared
(TLC). The solvent was distilled off, and the product
was isolated by chromatography on silica gel. Yield
0.06 g (30%).
b. Potassium hydroxide, 0.05 g (0.83 mmol), was
added to a solution of 0.32 g (0.83 mmol) of epimer
mixture IVa/IVb in 10.0 mL of DMSO, and the mix-
ture was heated under reflux until the initial com-
pounds disappeared (TLC). The mixture was diluted
with 10 mL of water and extracted with ethyl acetate
(3×10 mL), the extract was dried over MgSO4 and
1
(R)-Epimer VIIa. H NMR spectrum, δ, ppm:
2
3
3
2.02 d.d.d (1H, 3-HA, J = 14.1, J3A,2 = 10.6, J3A,4 =
2 3
4.4 Hz), 2.26 d.d.q (1H, 3-HB, J = 14.1, J3B,2 = 6.3,
3J3B,4 = 4J3B,1 = 1.6 Hz), 3.06 s (3H, CH3), 3.84 d.d (1H,
2
3
6-HB, J = 7.8, J6B,5 = 0.9 Hz), 3.89 m (2H, 4-H,
3
6-HA), 4.52 m (1H, 5-H), 4.86 d.d.d (1H, 2-H, J2,3A
=
3
3
10.6, J2,3B = 6.3, J2,1 = 1.6 Hz), 5.57 d.d (1H, 1-H,
3J1,2 = J1,3B = 1.6 Hz). 13C NMR spectrum, δC, ppm:
4
32.67 (C3), 40.09 (CH3), 68.11 (C6), 69.60 (C4), 75.77
(C2), 78.28 (C5), 101.59 (C1).
1
(S)-Epimer VIIb. H NMR spectrum, δ, ppm:
2
3
3
2.10 d.quint (1H, 3-HB, J = 16.3, J3B,2 = J3B,4
=
4J3B,1 = J3B,5 = 1.7 Hz), 2.23 d.t (1H, 3-HA, J = 16.3,
4
2
3J3A,2 = 4.4, J3A,4 = 4.4 Hz), 3.11 s (3H, CH3), 3.68 d.t
3
3
3
3
(1H, 4-H, J4,3A = 4.4, J4,3B = 1.7, J4,5 = 1.7 Hz),
2
3
3.82 d.d (1H, 6-HB, J = 7.8, J6B,5 = 0.9 Hz), 3.89 d.d
2
3
(1H, 6-HA, J = 7.8, J6A,5 = 5.4 Hz), 4.58 m (2H, 2-H,
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 50 No. 9 2014

SYNTHESIS OF α-BROMOISOLEVOGLUCOSENONE
1321
3
3
5-H), 5.54 d.t (1H, 1-H, J1,2 = J1,3B = 1.7 Hz).
13C NMR spectrum, δC, ppm: 30.65 (C3), 40.24 (CH3),
67.03 (C6), 67.19 (C4), 74.79 (C5), 78.59 (C2), 100.83
(C1). Found, %: C 71.43; H 6.40. C13H14O3. Calculat-
ed, %: C 71.48; H 6.41.
Deprotection of sulfonates IVa/IVb and Va/Vb
with lithium naphthalenide was carried out according
to the procedure described in [23].
1,6-Anhydro-2,3-dideoxy-β-D-glycero-hex-2-eno-
pyranos-4-ulose (isolevoglucosenone) (X). a. A mix-
ture of 10 mL of methylene chloride, 0.5 mL
(7.10 mmol) of pyridine, and 0.23 g (2.37 mmol) of
CrO3 was stirred for 1 h, 0.05 g (0.24 mmol) of
alcohols VIIa/VIIb was added to the resulting suspen-
sion, and the mixture was stirred for 15 min (TLC).
The mixture was treated with 10% aqueous HCl and
extracted with methylene chloride (3×10 mL), the
extract was dried over Na2SO4 and concentrated, and
the residue was subjected to chromatography on silica
gel. Yield 0.02 g (50%).
General procedure for the removal of benzyl
protection from compounds IVa/IVb and Va/Vb by
the action of SnCl4. Tin(IV) chloride, 1 mmol, was
added to a solution of 1 mmol of IVa/IVb or Va/Vb in
anhydrous methylene, and the mixture was stirred until
the initial compound disappeared (TLC). The mixture
was treated with a 5% aqueous solution of NaHCO3
and extracted with methylene chloride (3×10 mL).
The extract was washed with brine (2×10 mL), dried
over MgSO4, and concentrated, and the residue was
subjected to chromatography on silica gel. Yield of
VIIa/VIIb 0.69 g (65%) from 1.5 g (4.8 mmol) of
IVa/IVb; yield of VIIIa/VIIIb 0.71 g (40%) from
2.6 g (6.8 mmol) of Va/Vb.
1,6-Anhydro-3-deoxy-4-hydroxy-2-O-(4-methyl-
benzenesulfonyl)-β-D-arabino/ribo-pyranose
(VIIIa/VIIIb) and 1,6-anhydro-3-deoxy-2,4-dihy-
droxy-β-D-arabino/ribo-pyranose (IX) were synthe-
sized as described above for sulfonates VIIa/VIIb.
Yield of VIIIa/VIIIb 28%; yield of IX 65%.
Likewise, 0.07 g (27%) of compound X was
obtained from 0.6 g (2.00 mmol) of VIIIa/VIIIb.
b. Pyridinium chlorochromate, 0.16 g (0.76 mmol),
was added to a solution of 0.06 g (0.25 mmol) of
VIIa/VIIb in 5 mL of methylene chloride, and the
mixture was stirred until the initial compounds disap-
peared (TLC). The mixture was filtered, the solvent
was distilled off from the filtrate, and the residue was
subjected to chromatography on silica gel to isolate
0.015 g (50%) of X. Following a similar procedure,
from 0.29 g (0.95 mmol) of VIIIa/VIIIb we obtained
0.05 g (43%) of X. The physicochemical character-
istics of the product were consistent with published
data [8–12].
Compounds VIIIa/VIIIb. Oily substance, Rf 0.6
1
(ethyl acetate). H NMR spectrum, δ, ppm: 1.97 m
(2H, 3-HA, 3-HB), 2.44 s (3H, CH3), 3.80 m (3H, 6-HA,
6-HB, 4-H), 4.44 m (1H, 5-H), 4.63 d.d.d (1H, 2-H,
3J2,3A = 10.4, J2,3B = 6.4, J2,1 = 1.6 Hz), 5.34 d.d (1H,
1-H, 3J1,2 = 1.6, 4J1,3B = 1.6 Hz), 7.34 d and 7.80 d (2H
each, C6H4, J = 8.0 Hz). 13C NMR spectrum, δC, ppm:
isomer VIIIa: 21.65 (CH3), 30.98 (C3), 66.61 (C6),
68.02 (C2), 75.42 (C4), 76.70 (C5), 100.02 (C1); 127.78,
130.04, 133.56, 145.24 (Carom); isomer VIIIb: 21.46
(CH3), 28.88 (C3), 66.58 (C6), 66.68 (C2), 74.11 (C4),
76.81 (C5), 99.30 (C1); 127.86, 131.01, 133.14, 145.43
(Carom). Found, %: C 51.92; H 5.31. C13H16O6S. Cal-
culated, %: C 51.94; H 5.33.
3
3
1,6-Anhydro-3-bromo-2,3-dideoxy-β-D-glycero-
hex-2-enopyranos-4-ulose (XI). A solution of 0.07 g
(0.5 mmol) of isolevoglucosenone (X) in 5 mL of
methylene chloride was cooled to 0°C, 0.08 g
(0.5 mmol) of bromine and 0.06 mL of pyridine were
slowly added dropwise, and the mixture was stirred for
30 min at 0°C. When the reaction was complete
(TLC), the mixture was treated with 5 mL of
10% aqueous sodium hydroxide and extracted with
methylene chloride (3×20 mL). The combined extracts
were washed with water (3×10 mL) and dried over
MgSO4, the solvent was distilled off, and the residue
was purified by chromatography on silica gel. Yield
0.073 g (68%), colorless crystals, mp 127°C, Rf 0.6
(petroleum ether–EtOAc, 1:1), [α]D20 = +390° (c = 0.8,
CHCl3). 1H NMR spectrum, δ, ppm: 3.69 d (1H, 3-HB,
Diol IX. Colorless crystals, mp 92°C, Rf 0.3 (ethyl
1
acetate). H NMR spectrum, δ, ppm: 1.60 d.d.d (1H,
2
3
3
3-HA, J = 16.4, J3A2,2 = 10.4, J3A,4 = 4.6 Hz),
3
3
2.19 d.d.q (1H, 3-HB, J = 16.4, J3B,2 = 4.2, J3B,4
=
4J3B,1 = 1.6 Hz), 3.68 m (4H, 6-HA, 6-HB, 4-H, 2-H),
3
3
4.50 m (1H, 5-H), 5.37 d.d (1H, 1-H, J1,2 = J1,3B
=
1.6 Hz). 13C NMR spectrum, δC, ppm (CD3OD): 34.67
(C3), 68.05 (C6), 68.16 (C4), 69.54 (C2), 78.76 (C5),
104.95 (C1). Found, %: C 49.26; H 6.80. C6H10O4.
Calculated, %: C 49.27; H 6.84.
2J = 8.4 Hz), 4.13 d.d (1H, 6-HA, J = 16.4, J6A,5
=
2
3
3
6.4 Hz), 5.0 d (1H, 5-H, J5,6A = 6.4 Hz), 5.79 d (1H,
1-H, J1,2 = 3.5 Hz), 7.49 d (1H, 2-H, J2,1 = 3.5 Hz).
13C NMR spectrum, δC, ppm: 62.72 (C6), 79.19 (C5),
3
2
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 50 No. 9 2014

BIKTAGIROV et al.
1322
97.31 (C1), 123.85 (C3), 147.53 (C2), 187.57 (C4).
Mass spectrum: m/z 203.9 [M – H]+. Found, %:
C 35.11; H 2.43. C6H5BrO3. Calculated, %: C 35.12;
H 2.44. M 203.9417.
5. Vasiljeva, L.L. and Pivnitsky, K.K., Russ. Chem. Bull.,
1999, vol. 48, no. 1, p. 157.
6. Samet, A.V., Chernysheva, N.B., Shestopalov, A.M.,
and Semenov, V.V., Russ. Chem. Bull., 1999, vol. 48,
no. 1, p. 210.
(1R,2S,3R,8R)-4,4-Dimethyl-3-nitro-10,11-dioxa-
tricyclo[6.2.1.02,6]undec-5-en-7-one (XII). α-Bromo-
isolevoglucosenone (XI), 0.05 g (0.3 mmol), was dis-
solved in 8 mL of toluene, 0.04 g (0.3 mmol) of 2,2-di-
methyl-1,3-dinitropropane, 0.17 g (1.2 mmol) of
K2CO3, and a catalytic amount of dicyclohexano-18-
crown-6 were added at room temperature, and the mix-
ture was subjected to ultrasonic irradiation (UZDN-2T
generator, 44 Hz, 80 mA) over a period of 10 min
(TLC). The solvent was distilled off, and the residue
was subjected to chromatography. Yield 0.06 g (60%),
colorless crystals, mp 205°C, Rf 0.4 (petroleum ether–
7. Tsypysheva, I.P., Valeev, F.A., and Vasil’eva, E.V., Russ.
Chem. Bull., Int. Ed., 2000, vol. 49, no. 7, p. 1237.
8. Achmatowicz, O., Jr., Bukowski, P., Szechner, B.,
Zwierzchowska, Z., and Zamojsky, A., Tetrahedron,
1971, vol. 27, p. 1973.
9. Koll, P., Schultek, T., and Rennecke, R.-W., Chem. Ber.,
1976, vol. 109, p. 337.
10. Furneaux, R.H., Gainsford, G.J., Shafizadeh, F., and
Stevenson, T.T., Carbohydr. Res., 1986, vol. 146, p. 113.
11. Horton, D., Roski, J.P., and Norris, P., J. Org. Chem.,
1996, vol. 61, p. 3783.
12. Kadota, K., ElAzab, A.S., Taniguchi, T., and Ogasa-
EtOAc, 1:1), [α]D20 = +10° (c = 1.06, CHCl3). H NMR
1
wara, K., Synthesis, 2000, no. 10, p. 1372.
13. Bhate, P. and Horton, D., Carbohydr. Res., 1983,
spectrum, δ, ppm: 1.20 s (3H, CH3), 1.48 s (3H, CH3),
3.79 d.d (1H, 2-H, 3J2,3 = 10.2, 4J2,5 = 2.6 Hz), 3.96 d.d
vol. 122, p. 189.
(1H, 9-HB3, 2J = 8.4, 3J9B,8 = 1.9 Hz), 4.0 d.d (1H, 9-HA,
14. Gorobets, E.V., Miftakhov, M.S., and Valeev, F.A., Russ.
3
2J = 8.4, J9A,8 = 6.4 Hz), 4.59 d.d (1H, 8-H, J8,9A
=
Chem. Rev., 2000, vol. 69, no. 12, p. 1001.
6.4, J8,9B = 1.9 Hz), 4.66 d (1H, 3-H, 3J3,2 = 10.2 Hz),
3
15. Mnatsakanyan, V.A., Iridoidnye glikozidy (Iridoid
4
Glycosides), Erevan: Akad. Nauk Arm. SSR, 1986.
5.67 s (1H, 1-H), 6.42 d (1H, 5-H, J2,5 = 2.6 Hz).
13C NMR spectrum, δC, ppm: 19.68 (CH3), 26.29
(CH3), 49.03 (C4), 50.18 (C2), 65.65 (C9), 78.18 (C8),
94.33 (C3), 101.12 (C1), 132.20 (C6), 146.53 (C5),
194.54 (C7). Mass spectrum: m/z 237.1 [M – H]+.
Found, %: C 55.17; H 5.42. C11H13NO5. Calculated, %:
C 55.18; H 5.43. M 239.0788.
16. Witczak, Z.J., Kaplon, P., and Kolodziej, M., J. Carbo-
hydr. Chem., 2002, vol. 21, p. 143.
17. Tsypysheva, I.P., Valeev, F.A., Kalimullina, L.Kh.,
Spirikhin, L.V., and Safarov, M.G., Russ. J. Org. Chem.,
2003, vol. 39, p. 1055.
18. Kawai, T., Isobe, M., and Peters, S.C., Aust. J. Chem.,
1995, vol. 48, p. 115.
This study was performed under financial support
by the Russian Foundation for Basic Research (project
nos. 14-03-97007-r_povolzh’e_a, 13-00-14056).
19. Cram, D.J., Elhafez, F.A., and Weingartner, H., J. Am.
Chem. Soc., 1953, vol. 20, p. 2293.
20. Baptistella, L.-H.B., Dos Santos, J.F., Ballabio, K.C.,
and Marsaioli, A.J., Synthesis, 1989, no. 6, p. 436.
21. Cruzado, C. and Martin-Lomas, M., Tetrahedron Lett.,
1986, vol. 27, no. 22, p. 2497.
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