Eleuthesides and their analogs: VIII. Preparation of menthane derivatives from levoglucosenone and (2E,4E)-6-methylhepta-2,4-dienyl acetate by Diels-Alder reaction

Article abstract of DOI:10.1134/S1070428014110153

Synthesis of chiral functionalized menthane derivatives was carried out by Diels-Alder reaction from levoglucosenone and (2E,4E)-6-methylhepta-2,4-dienyl acetate.In extension of research [1] on development of preparation methods for polyfunctional menthan

Full text of DOI:10.1134/S1070428014110153

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2014, Vol. 50, No. 11, pp. 1628–1635. © Pleiades Publishing, Ltd., 2014.
Original Russian Text © B.T. Sharipov, A.N. Pilipenko, F.A. Valeev, 2014, published in Zhurnal Organicheskoi Khimii, 2014, Vol. 50, No. 11,
pp. 1642–1648.
Eleuthesides and Their Analogs:
VIII.* Preparation of Menthane Derivatives
from Levoglucosenone
and (2E,4E)-6-Methylhepta-2,4-dienyl Acetate
by Diels—Alder Reaction
B. T. Sharipov, A. N. Pilipenko, and F. A. Valeev
Institute of Organic Chemistry, Ufa Scientific Center, Russian Academy of Sciences, pr. Octyabrya 71, Ufa, 450054 Russia
e-mail: sinvmet@anrb.ru
Received April 9, 2014
Abstract—Synthesis of chiral functionalized menthane derivatives was carried out by Diels–Alder reaction
from levoglucosenone and (2E,4E)-6-methylhepta-2,4-dienyl acetate.In extension of research [1] on develop-
ment of preparation methods for polyfunctional menthane derivatives we explored the possibility of an isopro-
pyl group direct introduction in the course of Diels–Alder reaction.
DOI: 10.1134/S1070428014110153
For the preparation of the corresponding diene we
studied the condensation conditions of isobutyric alde-
hyde (I) and siloxybutadiene (II) [2] leading to the for-
mation of 5-hydroxy-6-methylhept-2-enal (III). The
use of TiCl4 as catalyst resulted in the formation of
trace amounts of aldehyde III, but its yields were
increased at the addition of Et3N [3]. More appropriate
catalyst for siloxybutadiene (II) condensation proved
to be BF3·Et2O [4]. However in the reaction of equi-
molar quantities of reagents compound IV formed in
30% yield, a product of repeated addition of siloxy-
butadiene to adduct III. Utilization of the triple excess
of isobutyric aldehyde allowed increasing the yield of
aldehyde III up to 67% and reducing the yield of
compound IV to 7% (Table 1, Scheme 1).
DMF [6]. The most efficient procedure resulting in the
predominant formation of trans, trans-diene V (4E/4Z
94 : 6) was boiling of alcohol III in the system Py·HCl–
toluene–DMF. The reduction of the carbonyl group in
aldehyde V was performed by treating with (i-Bu)2AlH,
and the subsequent acetylation of the hydroxy group
to obtain acetate VI was carried out with a mixture
Ac2O–Py (Scheme 2).
Diene VI whose reactivity was tested in the
reaction with maleic anhydride turned out to be
sufficiently active. At boiling in toluene for 4 h the
cycloaddition proceeded stereospecifically affording
the only product VII (Scheme 3) in 74% yield; the
relative configuration of compound VII was establi-
shed from 1Н and 13С NMR spectra.
The dehydration of alcohol III to obtain dienal V
was carried out in the systems 10% solution of HCl–
dichloroethane [5], TsOH–CH2Cl2, Py·HCl–toluene–
Adduct VII possesses a cis-junction of the rings.
The vicinal constants 3J3а,4 6.4, 3J3а,7а 9.5, and 3J7а,7 5.9 Hz
Scheme 1.
catalyst
+
+
CHO
OSiMe3
CHO
CHO
CH2Cl2, Et2O
OH
OH
OH
III
I
II
IV
* For communication VII, see [1].
1628

ELEUTHESIDES AND THEIR ANALOGS: VIII.
1629
Table 1. Yields of condensation products of isobutyric aldehyde (I) and siloxybutadiene (II) depending on reaction
conditions
Yield, %
Run
no.
Ratio
I/II (equiv.)
Catalyst (equiv.)
T, °C
Time, h
III
32
44
56
67
IV
–
30
11
7
1
2
3
4
TiCl4, Et3N (1.1)
BF3·Et2O (1)
BF3·Et2O (1.5)
BF3·Et2O (1.5)
1.5
1.1
2
–40
–78
–78
–78
5
2
1
1
3
3
show the syn-position of protons Н4, Н3а, Н7 , and Н7а.
Correlation peaks Н4/Н7, Н4/Н7а, and Н7/Н3а in the
NOESY spectrum indicate the 3аS,4S,7R,7аR-coordi-
nation of the centers.
in the NOESY spectra. The vicinal constants J2,3 8.0
and 3J2,7 7.0 Hz indicate the syn-location of protons Н3
and Н7 with respect to Н2. The absence of a constant
3J7,6 permits a conclusion that the torsion angle
Н7С7С6Н6 is close to 90° which is possible at the S-
configuration of the center С6. Besides in the NOESY
spectrum the correlation peaks appear between Н14/Н7,
Н14/Н2, and Н13/Н1 proving the 2S,3S,6S,7R-configu-
ration of these centers.
6-Methylheptа-2,4-dienyl acetate (VI) unlike hexa-
2,4-dienyl acetate [1] was as expected less reactive in
the cycloaddition with levoglucosenone (VIII). This
process was carried out at heating either in toluene or
without solvent. The reaction proceeded regiospecifi-
cally and stereoselectively affording two diastereome-
ric acetates. To isolate from the mixture the diastereo-
meric acetates possessing chromatographic mobility
close to that of levoglucosenone we subjected them to
hydrolysis into alcohols IX and X (Scheme 4), whose
ratio measured by 1Н NMR spectra varied in the range
1 : 4–1 : 5 (Table 2).
In compounds X the S-configuration of С2 center is
confirmed by the correlation peak Н11endo/Н2 in the
3
NOESY spectra. The vicinal constants J7,2 11.7 and
3J7,6 10.2 Hz show the anti-location of protons Н2 and
Н6 with respect to Н7, and the constant J2,3 4.6 Hz
3
indicates the syn-location of atoms Н2 and Н3. The
NOESY spectrum contains the correlation peaks Н2/Н6,
Н7/Н1, Н7/Н13, and Н7/Н14, proving the 2S,3S,6R,7S-
configuration of these centers.
The increased reaction time led to levoglucosenone
consumption, but did not affect the ratio of adducts IX
and X (Table 2, runs nos. 1, 2, 7, 8). Increased diene
quantity resulted in growing conversion and yield of
the adducts. At the temperature increase to 200°С the
yield decreased. In the absence of solvents the same
trend was observed, but the reaction time was shorter.
The best results were obtained at the use in the Diels–
Alder reaction of the five-fold excess of acetoxydiene
VI with respect to levoglucosenone (VIII).
In order to optimize the conditions of the Diels–
Alder reaction between levoglucosenone (VIII) and
diene VI we studied this process at superhigh pressure.
The cycloaddition at 10000 at and 100°С in toluene
(Scheme 5) resulted in total consumption of levogluco-
senone within 6 h, but the selectivity of the cycloaddi-
tion reduced: we isolated from the reaction mixture five
adducts XI–XV. At the pressure decreased to 6000 at
the yields of adducts XI–XV grew, and the side
product, dimer XVI, was detected in trace quantity.
The reaction performed without solvent unexpectedly
gave two adducts XI and XV having a trans-junction
of the six-membered rings; levoglucosenone dimer
(XVI) proved to be the main product [7] (Table 3).
1
The structure of adducts was established from Н
and 13С NMR spectra. The signal positions of the
protonated carbon atoms in compound IX were
established from the analysis of spectra COSY and
HSQC. The 2S- and 7R-configurations are demons-
trated by the correlation peaks Н11endo/Н2 and Н11endo/Н7
Scheme 2.
1. (i-Bu)2AlH, Et2O, _78oC
a_c
2. Ac2O, Py
OAc
III
CHO
V
VI
а. 10% HCl, C2H4Cl2, 55oC; b. TsOH, CH2Cl2, boiling; c. Py·HCl, toluene, DMF, boiling.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 50 No. 11 2014

SHARIPOV et al.
1630
Table 2. Yield and the ratio of adducts IX and X depending
on reaction conditions
The 3S-configuration is suggested by the presence of NOE
Н14/ Н1. The presence of NOE Н11endo/Н2, Н11endo/Н7
and Н7/Н13 confirms the 6S,7R-configuration.
Overall
Ratio
VI/VIII
(equiv.)
yield, %
(ratio IX–
X)
Run
no.
HMBC spectra of compound XIII contain cross-
peaks H2/С13, H7/С14, H14/С7, and H13/С2. The vicinal
constant 3J7,2 7.0 Hz indicates the syn-location of atoms
Н2 and Н7. The anti-position of Н2 and Н3 is confirmed
Conditions
1
2
3
4
5
6
7
8
9
1.3
1.3
2
160°C, toluene, 100 h
160°C, toluene, 150 h
160°C, toluene, 50 h
160°C, toluene, 75 h
200°C, toluene, 15 h
160°C, 75 h
72
86
49
73
100
91
63
82
90
24 (1 : 4)
23 (1 : 4)
29 (1 : 4)
47 (1 : 4)
18
3
by the constant J2,3 9.1 Hz. The presence of NOE
Н13B/Н7, Н1/Н3, Н2/Н14, and Н2 with the protons of the
methyl group proves the 2S,3R,6S,7R-configuration.
5
Hence a method was developed for the preparation
of menthane derivatives fused with carbohydrate frag-
ment based on Diels–Alder reaction between levogluco-
senone and (2E,4E)-6-methylhepta-2,4-dienyl acetate.
5
1.3
2
27 (1 : 5)
33 (1 : 5)
20 (1 : 5)
54 (1 : 5)
160°C, 24 h
2
160°C, 36 h
EXPERIMENTAL
5
160°C, 24 h
1Н and 13С NMR spectra were registered on a
spectrometer Bruker AM-300 at operating frequencies
300 (1Н) and 75.47 (13С) MHz and on a spectrometer
Bruker Avance III, 500 MHz, solvent CDCl3 if not
indicated otherwise. IR spectra were recorded on spectro-
photometers Shimadzu IRPrestige-21 or Bruker Tensor
27 (from films or mulls in mineral oil). Mass spectra were
measured on a GC-MS instrument Hewlett Packard,
chromatograph HP 6890 with a mass-selective detector
HP 5973. Optical rotation was determined on a polari-
meter Perkin Elmer-341. Analytic TLC was carried out
on Sorbfil plates of the grade PTSKh-AF-A (”Sorbpo-
lymer” Co., Krasnodar). The melting points were mea-
sured on a Boёtius 05 heating block.
The structure of adducts was established from the
1Н and 13С NMR spectra, the structure of compounds
XIV and XV was additionally confirmed by hydrolysis
into alcohols IX and X.
The position of isopropyl group at С3 and aceto-
xymethyl group at С6 in compound XI is indicated by
cross-peaks H2/С14, H7/С13, H13А/С7, and H13В/С7 in
3
HMBC spectra. The vicinal constants J7,2 12.0 and
3J7,6 10.2 Hz show the anti-location of protons Н2 and
Н6 with respect to Н7. The presence of NOE was infor-
mative for confirming the 6R-configuration. The signal
of Н6 at 2.71 ppm has a NOE with Н2 (1.82 ppm)
which in its turn interacts with Н11endo. The β-orienta-
tion of Н3 proton is indicated by the presence of NOE
Н14/Н1, and also by the interaction between the protons
of the methyl group and Н1, Н7.
(E)-5-Hydroxy-6-methylhept-2-enal (III) and
(2E,6E)-5,9-dihydroxy-10-methylundeca-2,6-di-
Scheme 4.
O
The HMBC of compound XII contained cross-
peaks H2/С14, H7/С13, H13А/С7, and H13В/С7 analogously
to the spectra of compound XI. The vicinal constant
3J7,2 6.9 Hz indicates the syn-location of atoms Н2 and Н7.
O
VI
+
O
VIII
10O
O
O
Scheme 3.
11
13
4
HO
H
O
HO
+
H
O
1
AcO
12
1. see Table 2
2
7
8
9
O
O
3
H
2. KOH, EtOH, H2O
8
4
3
1
3a
7a
5
6
5
6
reflux
toluene
H
O
H
O
O
VI
+
7
14
H
O
O
IX
[a]D20_18.1o
X
9
VII
[a]D20+36.7o
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 50 No. 11 2014

ELEUTHESIDES AND THEIR ANALOGS: VIII.
1631
Scheme 5.
O
O
14
H
H
11
O
3
6
1
8
O
12O
pressure
100oC
4
5
2
7
10O
+
OAc
O
+
9
H
H
O
13
O
AcO
AcO
VIII
AcO
XI
VI
XII
AcO
AcO
O
O
O
H
H
H
O
O
O
O
O
O
O
O
+
+
+
O
+
H
H
H
O
O
O
XIII
XIV
XVI
XV
eneal (IV). а. To a solution of 4.25 mL (38.7 mmol) of
TiCl4 in 50 mL of CH2Cl2 at –78°С was added
dropwise 5.44 mL (38.7 mmol) of Et3N. The mixture
was stirred for 5 min, 5.00 g (35.2 mmol) of siloxybu-
tadiene (II) was added, and the stirring at –78°С was
continued for 30 min 4.78 mL (52.8 mmol) of
isobutyric aldehyde (I) was added, the reaction mixture
was warmed to –40°С, and it was stirred for 5 h. The
reaction mixture was diluted with 20 mL of saturated
NH4Cl solution. The reaction products were extracted
into dichloromethane (3 × 50 mL), the combined organic
solutions were washed with saturated solution of
NaHCO3, with water, and dried with MgSO4. The
solvent was distilled off, the residue was chromato-
graphed on SiO2. Yield of compound III 1.60 g (32%).
(3 × 50 mL). The combined organic solutions were dried
with MgSO4. The solvent was distilled off, the residue
was chromatographed to obtain 2.01 g (67%) of alco-
hol III and 0.157 g (7%) of diol IV. The reaction was
similarly carried out at the other reagents ratios (Table 1).
Compound III. Oily substance. Rf 0.3 (petroleum
ether–EtOAc, 3 : 1). IR spectrum, cm–1: 2962, 1691, 1469,
1386, 1145, 1033, 975. 1Н NMR spectrum, δ, ppm: 0.81
d (3Н, СН3, J 6.7 Hz), 0.82 d (3Н, СН3, J 6.8 Hz), 1.58
m (1Н, Н6), 2.31 d.d.d (1Н, Н4, J 16.0, 8.9, 7.2 Hz),
2.37 d.d.d (1Н, Н4, J 16.0, 7.2, 3.7 Hz), 3.57 d.d.d (1Н,
Н5, J 8.9, 5.5, 3.7 Hz), 6.20 d.d (1Н, Н2, J 15.6, 7.9 Hz),
6.95 t.d (1Н, Н3, J 15.6, 7.2 Hz), 9.55 d (1Н, Н1, J 7.9 Hz).
13С NMR spectrum, δ, ppm: 17.32 (CH3), 18.81 (CH3),
33.71 (C6), 37.52 (C4), 76.79 (C5), 134.71 (C2), 155.72
(C3), 194.06 (C1). Mass spectrum: m/z 143.1 [M + Н]+.
С8Н14О2. Mcalc 142.0994.
b. To a solution of 3.00 g (21.12 mmol) of siloxy-
butadiene (II) in 50 mL of a mixture CH2Cl2–Et2O, 9 : 1,
was added at –78°С 5.6 mL (63.4 mmol) of isobutyric
aldehyde (I) and 4.0 mL (31.6 mmol) of BF3·Et2O. The
mixture was stirred for 1 h at –78°С, then diluted with
10 mL of 1 M HCl solution and was left standing till it
warmed to 0°С, then it was treated with saturated
NaHCO3 solution and water. The organic layer was
separated and washed with water. The product was
extracted from the water layer with dichloromethane
Compound IV. Oily substance. Rf 0.3 (petroleum
ether–EtOAc, 1 : 1). Mixture of diastereomers. IR spec-
trum, cm–1: 3402, 2956, 1693, 1417, 1139, 1029, 972.
1Н NMR spectrum, δ, ppm: 0.75–0.86 m (6Н, СН3), 0.81
d (3Н, СН3, J 6.7 Hz), 1.57 m (1Н, Н9), 1.94 m (1Н,
Н8А), 2.15 m (1Н, Н8В), 2.47 m (2Н, С4Н2), 3.27 m
(1Н, Н9), 4.70 m (1Н, Н5), 5.50 t.d (1Н, Н7, J 15.4,
Table 3. Yields of adducts XI–XV depending on reaction conditions
Ratio
Yield, %
Run no.
VI/VIII
(equiv.)
Time, h
Pressure, at
Solvent
XII + XIII
XIV + XV
(ratio)
30 (1:2)
16 (XV)
47 (1:2)
XI
XVI
(ratio)
5 (2:5)
–
1
2
3
2
2
2
6
5
9
10 000
10 000
6 000
Toluene
Without solvent
Toluene
13
5
7
19
37
1
8 (3:8)
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 50 No. 11 2014

SHARIPOV et al.
1632
6.7 Hz), 5.61 d.d 1Н, Н6′, J 15.4, 7.7 Hz) 5.65 d.d (1Н,
Н6′′, J 15.4, 7.4 Hz), 6.08 d.d (1Н, Н2, J 15.6, 7.9 Hz),
6.80 t.d (1Н, Н3, J 15.6, 7.2 Hz), 9.40 d (1Н, Н1, J
7.9 Hz). 13С NMR spectrum, δ, ppm: 17.65 (CH3),
17.80 (CH3), 18.55 (CH3), 18.68 (CH3), 33.11 (C10),
33.39 (C10), 36.72 (C8), 36.89 (C8), 40.19 (C4), 40.25
(C4), 70.90 (C5), 71.20 (C5), 75.81 (C9), 75.98 (C9),
129.13 (C7), 129.95 (C7), 134.49 (C6), 134.62 (C2),
134.72 (C2), 154.85 (C3), 194.23 (C1). Mass spectrum:
m/z 212.1 [M]+. С12Н20О3. Mcalc 212.1412.
was slowly added 21.6 mL (88.7 mmol) of 73%
solution of (i-Bu)2AlH in toluene. The mixture was
stirred for 1 h at –78°С, then 20 mL (241.8 mmol) of
pyridine and 23 mL (241.8 mmol) of Ac2O was added.
The reaction mixture was left to warm to 0оС and it
was stirred for another 2 h. 30 mL of EtOH was
added dropwise, and the mixture was neutralized with
10% solution of HCl. The reaction products were
extracted from the water phase with petroleum ether
(2 × 100 mL), the combined organic solutions were
dried with MgSO4. The solvent was distilled off, the
residue was distilled in a vacuum collecting the
fraction of bp 80–90°С (5 mmHg). Yield 10.84 g
(80%). Crystalline substance, mp 50–53°С, Rf 0.5
(petroleum ether–EtOAc, 5 : 1). IR spectrum, cm–1:
(2E,4E)-6-Methylheptа-2,4-dieneal (V). а. To a
solution of 2.00 g (14.1 mmol) of alcohol III in 40 mL
of 1,2-dichloroethane was added 40 mL of 10% НCl
solution, then the two-phase system at vigorous stir-
ring was heated at 55°С and stirred for 6 h. On cooling
to room temperature the mixture was cautiously neut-
ralized with a saturated solution of NaHCО3. The orga-
nic layer was separated, the reaction products were
extracted from the water phase with dichloromethane
(2 × 30 mL). The combined organic solutions were was-
hed with water and dried with MgSO4. The solvent was
distilled off, the residue was chromatographed. Yield
1.01 g (58%).
1
2960, 1734, 1471, 1377, 1232, 1099, 1024, 746. Н
NMR spectrum, δ, ppm: 0.98 d (6Н, СН3, J 6.7 Hz),
2.03 s (3Н, СН3), 2.31 m (1Н, Н6), 4.55 d (2Н, Н1, J
6.7 Hz), 5.61 d.d (1Н, Н5, J 15.3, 6.8 Hz), 5.67 t.d
(1Н, Н2, J 15.3, 6.7 Hz), 5.95 d.d (1Н, Н4, J 15.3,
10.4 Hz), 6.21 d.d (1Н, Н3, J 15.3, 10.4 Hz). 13С NMR
spectrum, δ, ppm: 20.89 (CH3), 22.09 (CH3), 22.09
(CH3), 31.03 (C6), 64.91 (C1), 123.98 (C2), 126.08
(C4), 135.17 (C3), 143.59 (C5), 170.75 (Аc). Mass
spectrum: m/z 111.1 [M – ОАc]+. С10Н16О2. Mcalc
168.1150.
b. A mixture of 1.36 g (9.58 mmol) of alcohol III
with 0.04 g (3 mol%) of TsOH in 10 mL of
dichloromethane was boiled with a Dean–Stark trap
for 5 h. The solvent was distilled off, the residue was
chromatographed. Yield 0.70 g (59%).
(±)-[(3aS,4S,7R,7aR)-7-Isopropyl-1,3-dioxo-
1,3,3a,4,7,7a-hexahydroisobenzofuran-4-yl]-methyl
acetate (VII). A mixture of 0.030 g (0.31 mmol) of
maleic anhydride and 0.077 g (0.46 mmol) of diene VI
in 10 mL of anhydrous toluene was boiled for 4 h. The
reaction mixture was evaporated, the residue was
chromatographed on SiO2. Yield 0.060 g (74%).
Crystalline substance, mp 80–82°С, Rf 0.24 (petroleum
ether–AcOEt, 5 : 1). IR spectrum, cm–1: 1842, 1774,
c. A mixture of 13.60 g (95.8 mmol) of alcohol III
with 0.11 g (1 mol%) of Py·HCl in 50 mL of a mixture
toluene–DMF, 4 : 1, was boiled for 30 min. The sol-
vent was distilled off, the residue was distilled in a
vacuum collecting the fraction boiling at 55–65°С
(5 mmHg). Yield 8.91 g (75%). A mixture of 4E- and
4Z-isomers, 94 : 6. Crystalline substance, mp 50–52°С,
Rf 0.7 (petroleum ether–EtOAc, 10 : 1). IR spectrum,
cm–1: 2960, 1734, 1683, 1265, 1114, 1045, 738. 1Н NMR
spectrum (4E), δ, ppm: 0.93 d (3Н, СН3, J 6.8 Hz),
0.94 d (3Н, СН3, J 6.8 Hz), 1.83 m (1Н, Н6), 6.07 d.d
(1Н, Н2, J 15.3, 8.1 Hz), 6.24 d.d (1Н, Н5, J 15.3,
6.3 Hz), 6.27 d.d (1Н, Н4, J 15.3, 8.9 Hz), 7.07 d.d
(1Н, Н3, J 15.3, 8.1 Hz), 9.53 d (1Н, Н1, J 8.1 Hz). 13С
NMR spectrum, δ, ppm: 20.93 (CH3), 20.93 (CH3),
31.68 (C6), 125.77 (C4), 130.18 (C2), 153.19 (C3),
153.67 (C5), 193.86 (C1). Mass spectrum: m/z 124.1
[M]+. С8Н12О. Mcalc 124.0888.
1
1739, 1473, 1369, 1249, 1037, 979, 932. Н NMR
3
spectrum, δ, ppm: 1.03 d (3Н, C11Н3, J11,9 6.6 Hz),
1.14 d (3Н, C10Н3, 3J10,9 6.4 Hz), 1.80 m (1Н, Н7), 2.08
s (3Н, Аc), 2.21 m (1Н, Н9), 2.63 m (1Н, Н4), 3.54 d.d
3
3
(1Н, Н3a, J3a,7a 9.5, J3a,4 6.4 Hz), 3.61 d.d (1Н, Н7a,
3J7a,3a 9.5, 3J7a,7 5.9 Hz), 4.45 d.d (1Н, Н8А, 2J8А,8В 11.2,
3J8А,4 7.6 Hz), 4.56 d.d (1Н, Н8В, J8В,8А 11.2, J8В,4
2
3
7.7 Hz), 5.86 d.d.d (1Н, Н5, J5,6 9.2, J5,4 3.3, J5,7
3
3
4
3.3 Hz), 6.03 d.d.d (1Н, Н6, J6,5 9.2, J6,7 3.4, J6,4
3.4 Hz). 13С NMR spectrum, δ, ppm: 20.82 (С10H3),
20.87 (Аc), 21.94 (С11H3), 27.81 (С9), 35.30 (C4),
42.90 (С7a), 43.22 (С3a), 44.25 (С7), 63.39 (С8), 129.36
(С5), 134.47 (С6), 170.78 (СO), 170.95 (СO), 171.25
(СO). Mass spectrum: m/z 224.1 [M – Аc + Н]+.
С14Н18О5. Mcalc 266.1154.
3
3
4
(2E,4E)-6-Methylheptа-2,4-dienyl acetate (VI).
In an argon atmosphere to a solution of 10.00 g
(80.6 mmol) of aldehyde V in 300 mL of Et2O at –78°С
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ELEUTHESIDES AND THEIR ANALOGS: VIII.
1633
Reaction of levoglucosenone (VIII) and diene VI.
а. A solution of 0.550 g (1.3 equiv.) [0.840 g (2 equiv.)
or 2.1 g (5 equiv.)] of diene VI, 0.315 g (2.5 mol) of
levoglucosenone (VIII), and several crystals of ionol
in 10 mL of anhydrous toluene was heated in a
pressure reactor (reaction time and temperature are
listed in Table 2). The reaction mixture was
evaporated, the residue was dissolved in 5 mL of
ethanol and hydrolyzed with a mixture of 4 g of KOH,
40 mL of EtOH, 20 mL of H2O. On completion of the
reaction (TLC monitoring) the mixture was neutralized
with 3% HCl solution. The reaction product was
extracted from the water layer with ethyl acetate
(3 × 30 mL). The combined organic solutions were
dried with MgSO4 and evaporated on a rotary
evaporator. The residue was chromatographed on SiO2.
Compounds IX and X were isolated.
e. A solution of 0.314 g (2.49 mmol) of levoglu-
cosenone (VIII), 0.830 g (4.98 mmol) of diene VI, and
some ionol crystals in 3 mL of anhydrous toluene was
heated in a pressure reactor at 100°С and a pressure of
6000 at for 9 h. The reaction mixture was evaporated,
the residue was chromatographed on SiO2. We
obtained 0.051 g (7%) of adduct XI, 0.058 g (8%) of a
mixture of adducts XII and XIII, 0.344 g (47%) of a
mixture of adducts XIV and XV, 0.003 g (1%) of
dimer XVI. The ratio of adducts XII–XIII is 3 : 8, of
XIV–XV 1 : 2, according to 1Н NMR data.
(1S,2S,3S,6S,7R,9R)-3-(Hydroxymethyl)-6-iso-
propyl-10,12-dioxatricyclo[7.2.1.02,7]dodec-4-en-8-
one (IX). Oily substance, [α]D20 –18.1° (c 1.0, CHCl3),
1
Rf 0.3 (petroleum ether–AcOEt, 3 : 1). Н NMR spec-
trum, δ, ppm: 0.90 d (3Н, C16Н3, 3J16,14 6.7 Hz), 0.92 d
3
(3Н, C15Н3, J15,14 6.7 Hz), 1.61 m (1Н, Н14), 2.44
3
3
3
d.d.d (1Н, Н2, J2,3 8.0, J2,7 7.0, J2,1 1.3 Hz), 2.59 m
b. A mixture of 0.550 g (1.3 equiv.) [0.840 g
(2 equiv.) or 2.1 g (5 equiv.)] of diene VI, 0.315 g
(2.5 mol) of levoglucosenone (VIII), and several
crystals of ionol was heated in a pressure reactor
(reaction time is listed in Table 2). The reaction mixture
was dissolved in 5 mL of ethanol and hydrolyzed with
a mixture of 4 g of KOH, 40 mL of EtOH, 20 mL of
H2O. On completion of the reaction (TLC monitoring)
the mixture was neutralized with 3% HCl solution. The
reaction product was extracted from the water layer
with ethyl acetate (3 × 30 mL). The combined organic
solutions were dried with MgSO4 and evaporated on a
rotary evaporator. The residue was chromatographed
on SiO2. Compounds IX and X were isolated.
(2Н, Н3, Н6), 3.04 d (1Н, Н7, J7,2 7.0 Hz), 3.66 d.d
3
(1Н, Н13В, J13В,13А 11.0, J13В,3 3.4 Hz), 3.74 d.d (1Н,
2
3
Н13А, J13А,13В 11.0, J133А,3 4.4 Hz), 4.08 d.d (1Н,
2
3
Н11endo, J11endo,11exo 7.5, J11endo,1 5.2 Hz), 4.19 d (1Н,
2
Н11exo, J11exo,11endo 7.5 Hz), 4.81 d.d (1Н, Н1, J1,11endo
2
3
5.2, J1,2 1.4 Hz), 5.12 s (1Н, Н9), 5.56 d.d.d (1Н, Н4,
3
3J4,5 10.3, J4,3 1.7, J4,6 1.7 Hz), 5.88 d.d.d (1Н, Н5,
3J5,4 10.3, 3J5,6 4.7, 4J5,3 2.3 Hz). 13С NMR spectrum, δ,
ppm: 20.27 (С16H3), 20.60 (С15H3), 32.44 (С14), 35.99
(C6), 36.49 (С3), 41.26 (С7), 41.99 (С2), 64.99 (С13),
69.71 (С11), 75.69 (С1), 101.61 (С9), 126.52 (С4),
130.87 (С5), 202.26 (С=O). Mass spectrum: m/z 252.1
[M]+. С14Н20О4. Mcalc 252.1362.
3
4
(1S,2S,3S,6R,7S,9R)-3-(Hydroxymethyl)-6-iso-
propyl-10,12-dioxatricyclo[7.2.1.02,7]dodec-4-en-8-
one (X). Oily substance, [α]D20 +36.7° (c 1.0, CHCl3),
Rf 0.28 (petroleum ether–AcOEt, 3 : 1). 1Н NMR spec-
trum, δ, ppm: 0.65 d (3Н, C16Н3, 3J16,14 7.0 Hz), 1.04 d
c. A solution of 0.118 g (0.94 mmol) of levogluco-
senone (VIII), 0.310 g (1.87 mmol) of diene VI, and
several crystal of ionol in 1.5 mL of anhydrous toluene
were heated in a pressure reactor at 100°С and a
pressure of 10000 at for 6 h. The reaction mixture was
evaporated, the residue was chromatographed on SiO2.
We obtained 0.036 g (13%) of adduct XI, 0.014 g (5%)
of a mixture of adducts XII and XIII, 0.083 g (30%)
of a mixture of adducts XIV and XV, 0.022 g (19%) of
dimer XVI. The ratio of adducts XII–XIII is 2 : 5, of
adducts XIV–XV is 1 : 2, according to 1Н NMR data.
3
3
(3Н, C15Н3, J153,14 7.0 Hz), 1.79 d.d.d (1Н, Н2, J2,7
3
11.7, J2,3 4.6, J2,1 1.2 Hz), 2.20 m (1Н, Н14), 2.43
d.d.d (1Н, Н6, 3J6,7 10.2, 3J6,14 4.4, 3J6,5 4.4 Hz), 2.58 m
3
3
(1Н, Н3), 2.78 d.d (1Н, Н7, J7,2 11.7, J7,6 10.2 Hz),
3.57 d (1Н, Н11exo, J11exo,11endo 7.1 Hz), 3.79 d.d (1Н,
2
Н11endo, J11endo,11exo 7.1, J11endo,1 5.0 Hz), 3.83 d.d (1Н,
2
3
Н13В, J13В,13А 11.3, J13В,3 4.4 Hz), 3.93 d.d (1Н, Н13А
,
2
3
2J13А,13В 11.3, 3J13А,3 6.7 Hz), 5.06 d.d (1Н, Н1, 3J1,11endo
d. A mixture of 0.236 g (1.87 mmol) of levogluco-
senone (VIII), 0.620 g (3.71 mmol) of diene VI, and
several crystals of ionol were heated in a pressure
reactor at 100°С and 10000 at for 5 h. The reaction
mixture was chromatographed on SiO2 to obtain
0.028 g (5%) of adduct XI, 0.088 g (16%) of adduct
XV, and 0.087 g (37%) of dimer XVI.
5.0, J1,2 1.2 Hz), 5.14 s (1Н, Н9), 5.69 d.d (1Н, Н4,
3
3J4,5 10.2, J4,6 2.2 Hz), 5.80 d.d.d (1Н, Н5, J5,4 10.2,
4
3
3J5,6 4.4, J5,3 2.2 Hz). 13С NMR spectrum, δ, ppm:
4
14.59 (С16H3), 21.23 (С15H3), 28.45 (С14), 38.75 (C7),
40.85 (С3), 41.37 (С2), 41.74 (С6), 62.72 (С13), 71.23
(С11), 73.85 (С1), 99.08 (С9), 127.94 (С4), 129.39 (С5),
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 50 No. 11 2014

SHARIPOV et al.
1634
208.17 (С=O). Mass spectrum: m/z 252.1 [M]+.
С14Н20О4. Mcalc 252.1362.
3J2,3 9.1, 3J2,7 7.0, 3J2,1 1.6 Hz), 2.61 m (1Н, Н6), 2.71 m
(1Н, Н3), 3.01 d (1Н, Н7, 3J7,2 7.0 Hz), 4.05 d (1Н, Н11endo
,
2
2J11endo,11exo 7.7 Hz), 4.05 d.d (1Н, Н11exo, J11exo,11endo
{(1S,2S,3S,6R,7S,9R)-3-Isopropyl-8-oxo-10,12-di-
oxatricyclo[7.2.1.02,7]dodec-4-en-6-yl}methyl acetate
(XI). Oily substance, Rf 0.3 (petroleum ether–AcOEt,
3 : 1), [α]D20 +10.6° (c 1.0, CHCl3). IR spectrum, cm–1:
2960, 1735, 1467, 1368, 1247, 1101, 1036, 904. 1Н NMR
3
2
7.7, J11exo,1 5.1 Hz), 4.16 d.d (1Н, Н13А, J13А,13В 11.2,
3J13А,3 6.4 Hz), 4.19 d.d (1Н, Н13В, J13В,13А 11.2, J13В,3
2
3
4.8 Hz), 4.75 d.d (1Н, Н1, 3J1,11exo 5.1, 3J1,2 1.6 Hz), 5.12
s (1Н, Н9), 5.56 d.d.d (1Н, Н4, J4,5 10.3, J4,3 2.1, 4J4,6
3
3
2.1 Hz), 5.79 d.d.d (1Н, Н5, J5,4 10.3, J5,6 4.8, J5,3
2.5 Hz). 13С NMR spectrum, δ, ppm: 20.08 (С15H3),
20.43 (С16H3), 20.81 (Ас), 32.36 (С14), 33.70 (C3),
35.63 (С6), 41.15 (С7), 42.39 (С2), 65.93 (С13), 67.31
(С11), 75.23 (С1), 101.59 (С9), 126.27 (С4), 129.60 (С5),
170.99 (Ас), 201.57 (С=O). Mass spectrum: m/z 206.1
[M – ОАс – Et]+. С16Н22О5. Mcalc 294.1467.
3
3
3
3
spectrum, δ, ppm: 1.00 d (3Н, C16Н3, J16,14 6.7 Hz),
3
1.13 d (3Н, C15Н3, J15,14 6.8 Hz), 1.82 d.d.d (1Н, Н2,
3
3
3J2,7 12.0, J2,3 5.3, J2,1 1.6 Hz), 2.00 s (3Н, Ас), 2.21
m (1Н, Н14), 2.27 m (1Н, Н3), 2.71 m (1Н, Н6), 2.82
d.d (1Н, Н7, J7,2 12.0, J7,6 10.2 Hz), 3.62 d (1Н,
3
3
Н11endo
,
2J11endo,11exo 7.0 Hz), 3.81 d.d (1Н, Н11exo
,
,
,
2J11exo,11endo 7.0, J11exo,1 4.9 Hz), 4.19 d.d (1Н, Н13А
3
2J13А,13В 10.9, J13А,6 4.9 Hz), 4.38 d.d (1Н, Н13В
3
{(1S,2S,3S,6S,7R,9R)-6-Isopropyl-8-oxo-10,12-di-
oxatricyclo[7.2.1.02,7]dodec-4-en-3-yl}methyl acetate
(XIV). Oily substance, Rf 0.4 (petroleum ether–
AcOEt, 1 : 1). IR spectrum, cm–1: 2960, 1733, 1464,
1368, 1242, 1037, 895. 1Н NMR spectrum, δ, ppm: 0.87 d
(3Н, C16Н3, 3J16,14 6.6 Hz), 0.97 d (3Н, C15Н3, 3J15,14 6.5
Hz), 1.53 m (1Н, Н14), 2.06 s (3Н, Ас), 2.44 m (1Н, Н2),
2.65 m (2Н, Н3, Н6), 3.20 d.d (1Н, Н7, 3J7,2 6.6, 3J7,6 3.7
2J13В,13А 10.9, J13В,6 3.3 Hz), 4.78 d.d (1Н, Н1, J1,11exo
3
3
4.9, 3J1,2 1.6 Hz), 5.17 s (1Н, Н9), 5.65 d (1Н, Н5, 3J5,4
10.1 Hz), 5.85 d.d.d (1Н, Н4, J4,5 10.1, J4,3 5.5, J4,6
2.2 Hz). 13С NMR spectrum, δ, ppm: 20.46 (С16H3),
20.99 (Ас), 24.12 (С15H3), 28.52 (С14), 36.53 (C6),
37.82 (С7), 42.27 (С2), 43.43 (С3), 65.94 (С13), 71.55
(С11), 73.78 (С1), 99.13 (С9), 129.09 (С5), 129.44 (С4),
171.06 (Ас), 207.13 (С=O). Mass spectrum: m/z 266.1
[M – С2Н5 + H]+. С16Н22О5. Mcalc 294.1467.
3
3
4
2
3
Hz), 3.59 d.d (1Н, Н11endo, J11endo,11exo 7.4, J11endo,1 5.1
Hz), 4.06 d (1Н, Н11exo, J11exo,11endo 7.4 Hz), 4.27 d.d
2
(1Н, Н13В, J13В,13А 11.0, J13В,3 5.9 Hz), 4.39 m (1Н,
2
3
{(1S,2S,3S,6S,7R,9R)-3-Isopropyl-8-oxo-10,12-
dioxatricyclo[7.2.1.02,7]dodec-4-en-6-yl}methyl ace-
tate (XII). Oily substance, Rf 0.37 (petroleum ether–
AcOEt, 3 : 1). IR spectrum, cm–1: 2960, 1738, 1465,
Н13А), 4.82 d.d (1Н, Н1, J1,11endo 5.3, J1,2 1.4 Hz), 4.94
3
3
s (1Н, Н9), 5.62 d.d.d (1Н, Н4, J4,5 9.6, J4,3 2.7, J4,6
3
3
4
2.7 Hz), 6.00 d.d.d (1Н, Н5, J5,4 9.6, J5,6 2.9, J5,3 2.9
Hz). Mass spectrum: m/z 266.1 [M – С2Н5 + H]+.
С16Н22О5. Mcalc 294.1467.
3
3
4
1
1387, 1231, 1107, 1037, 896. Н NMR spectrum, δ,
ppm: 0.75 d (3Н, CН3, J 6.8 Hz), 1.03 d (3Н, CН3, J
6.9 Hz), 1.91 m (1Н, Н14), 2.04 s (3Н, Ас), 2.29 m
(1Н, Н2), 2.43 m (1Н, Н3), 2.71 m (1Н, Н6), 3.05 d
(1Н, Н7, J 6.9 Hz), 3.91 d.d (1Н, Н13А, J 9.8, 8.7 Hz),
4.19 d.d (1Н, Н13В, J 9.8, 4.8 Hz), 4.07 m (2Н, Н11),
4.68 d (1Н, Н1, J 4.9 Hz), 5.11 s (1Н, Н9), 5.68 m (2Н,
Н4, Н5). 13С NMR spectrum, δ, ppm: 16.72 (С15H3),
20.94 (Ас), 21.14 (С16H3), 28.33 (С14), 30.40 (C6),
38.78 (С3), 40.68 (С7), 41.70 (С2), 65.33 (С13), 67.29
(С11), 75.30 40.68 (С7), 41.70 (С2), 65.33 (С13), 67.29
(С11), 75.30 (С1), 101.52 (С9), 124.52 (С4), 128.58
(С5), 171.14 (Ас), 201.30 (С=O). Mass spectrum: m/z
294.1 [M]+. С16Н22О5. Mcalc 294.1467.
{(1S,2S,3S,6R,7S,9R)-6-Isopropyl-8-oxo-10,12-
dioxatricyclo[7.2.1.02,7]dodec-4-en-3-yl}methyl ace-
tate (XV). Oily substance, Rf 0.4 (petroleum ether–
AcOEt, 1 : 1), [α]D20 +48.4° (c 1.0, CHCl3). IR spec-
trum, cm–1: 2960, 1733, 1464, 1368, 1242, 1037, 895. 1Н
NMR spectrum, δ, ppm: 0.63 d (3Н, C16Н3, 3J16,14 6.8 Hz),
1.02 d (3Н, C15Н3, 3J15,14 6.8 Hz), 1.76 d.d.d (1Н, Н2, 3J2,7
11.9, 3J2,3 4.7, 3J2,1 1.3 Hz), 2.08 s (3Н, Ас), 2.17 m (1Н,
3
3
Н14), 2.40 m (1Н, Н6), 2.60 d.d (1Н, Н7, J7,2 11.9, J7,6
10.4 Hz), 2.67 m (1Н, Н3), 3.56 d (1Н, Н11endo
,
2J11endo,11exo 7.2 Hz), 3.77 d.d (1Н, Н11exo, 2J11exo,11endo 7.2,
2
3J11exo,1 4.8 Hz), 4.15 d.d (1Н, Н13А, J13А,13В 11.6,
2
3
3J13А,3 5.1 Hz), 4.34 d.d (1Н, Н13В, J13В,13А 11.6, J13В,3
7.0 Hz), 4.87 d.d (1Н, Н1, 3J1,11exo 4.8, 3J1,2 1.3 Hz), 5.11 s
(1Н, Н9), 5.67 d (1Н, Н5, 3J5,4 10.1 Hz), 5.76 d.d.d (1Н, Н4,
3J4,5 10.1, 3J4,3 5.6, 4J4,6 2.1 Hz). 13С NMR spectrum, δ,
ppm: 16.28 (С16H3), 21.08 (Ас), 21.26 (С15H3), 28.57
(С14), 37.96 (C3), 38.49 (С7), 41.36 (С2), 41.88 (С6), 64.15
(С13), 71.29 (С11), 73.83 (С1), 99.17 (С9), 127.58 (С4),
{(1S,2S,3R,6S,7R,9R)-6-Isopropyl-8-oxo-10,12-di-
oxatricyclo[7.2.1.02,7]dodec-4-en-3-yl}methyl acetate
(XIII). Oily substance, Rf 0.37 (petroleum ether–AcOEt,
3 : 1). IR spectrum, cm–1: 2960, 1738, 1465, 1387, 1231,
1107, 1037, 896. 1НNMR spectrum, δ, ppm: 0.89 d (3Н,
C16Н3, 3J16,14 6.8 Hz), 0.90 d (3Н, C15Н3, 3J15,14 6.7 Hz),
1.62 m (1Н, Н14), 2.04 s (3Н, Ас), 2.24 d.d.d (1Н, Н2,
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 50 No. 11 2014

ELEUTHESIDES AND THEIR ANALOGS: VIII.
1635
129.62 (С5), 170.90 (Ас), 207.64 (С=O). Mass spectrum:
m/z 266.1 [M – С2Н5 + H]+. С16Н22О5. Mcalc 294.1467.
Foundation for Basic Research (grants nos. 14-03-
31367mol_а, 14-03-97007-р_povolzh’e_а).
REFERENCES
(1S,5R)-3-{(1S,2R,5R)-4-Oxo-6,8-dioxabicyclo-
[3.2.1]octan-2-yl}-6,8-dioxabicyclo[3.2.1]oct-2-en-4-
one (XVI). 1Н NMR spectrum, δ, ppm: 2.23 d (1Н, Н3′,
J 16.92 Hz), 2.97 d.d (1Н, Н3′, J 16.92, 8.82 Hz), 3.43 d
(1Н, Н2′, J 8.82 Hz), 3.72 d (1Н, Н7, J 6.62 Hz), 3.90
d.d (1Н, Н7, J 6.62, 4.41 Hz), 4.05 d.d (1Н, Н7′, J 8.09,
5.15 Hz), 4.10 d (1Н, Н7′, J 8.09 Hz), 4.53 d (1Н, Н1′, J
5.15 Hz), 5.01 d.d (1Н, Н1, J 5.14, 4.41 Hz), 7.11 d
(1Н, Н2, J 5.14 Hz).
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The analysis were carried out on the equipment of
the Center of the joint use “Khimiya” of the Institute of
Organic Chemistry, Ufa Scientific Center. The study
was performed under a financial support of the Russian
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 50 No. 11 2014