Reactions of stereocontrolled intramolecular carbocyclization of levoglucosenone adduct with isoprene

Article abstract of DOI:10.1134/S1070428010020144

An intramolecular carbocyclization was found of levoglucosenone adduct with isoprene providing a fused cyclobutane. The intramolecular oxacyclization of the adduct was performed under the treatment with I₂, H ₃PO₄, SOCl₂, and Pd/C leading to 1,4-epoxide. Methods were developed of radical and anionic (by Ferrier method) transformation of the adduct into chiral trans- and cis-decalins.

Full text of DOI:10.1134/S1070428010020144

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2010, Vol. 46, No. 2, pp. 226−235. © Pleiades Publishing, Ltd., 2010.
Original Russian Text © B.T. Sharipov, O.Yu. Krasnoslobodtseva, L.V. Spirikhin, F.A. Valeev, 2009, published in Zhurnal Organicheskoi Khimii,
2010, Vol. 46, No. 2, pp. 232−241.
Reactions of Stereocontrolled Intramolecular Carbocyclization
of Levoglucosenone Adduct with Isoprene
B. T. Sharipov, O. Yu. Krasnoslobodtseva, L. V. Spirikhin, and F.A. Valeev
Institute of Organic Chemistry, Ufa Scientific Center, Russian Academy of Sciences
Ufa, 450054Russia
e-mail: sinvmet@anrb.ru
Received December 3, 2008
Abstract—An intramolecular carbocyclization was found of levoglucosenone adduct with isoprene providing
a fused cyclobutane. The intramolecular oxacyclization of the adduct was performed under the treatment with I2,
H3PO4, SOCl2, and Pd/C leading to 1,4-epoxide. Methods were developed of radical and anionic (by Ferrier
method) transformation of the adduct into chiral trans- and cis-decalins.
DOI: 10.1134/S1070428010020144
The levoglucosenone is known as a highly reactive
dienophile forming in the diene synthesis functionalized
chiral cyclohexanes that have found employment in the
synthesis of natural compounds [1]. The procedures of
transformation of the carbohydrate fragment into
a carbocycle in these adducts is another important stage
in solving the problem of the extension of the synthetic
opportunities of levoglucosenone.
We investigated the possibilities of the radical and
anionic rearrangements of the carbohydrate fragment in
the adducts of the levoglucosenone with isoprene into
the carbocyclic derivatives. The first step in the study of
the radical transformations of the adduct was an attempt
to create a C11-centered radical and to establish the ways
to its stabilization. The rearrangement of the primary
radical might finish with the involvement of the double
Scheme 1.
OH
O
R
H
H
4
6
3
2
5
THF, conc. HCl
H O7
OMe
8
1
10
9
OH
O
H
H
OH
I
V, VI
V, R = I, 50%,
[α]20
_153.8°
D
[α]20
VI, R = OH, 30%,
_71.7°
D
n-TsCl, Py
THF,
conc. HCl
OTs
I
H
O
H
O
H
O
Bu3SnH, AIBN
C6H6
NaI, Ac2O
boiling
OMe
OH
b:a = 5:1
OMe
OMe
O
O
H
H
H
[α]20
III, 86%,
+93.4°
II, 81%
IV, 81%,
D
226

REACTIONS OF STEREOCONTROLLED INTRAMOLECULAR CARBOCYCLIZATION
227
bond; the possibility of its interaction with the α-keto-
aldehyde fragment also could not be completely excluded
in the case of the opening of the pyran ring of the molecule
in the course of the reaction.
group can be the β-orientation. In the 13C NMR spectra
the C8 atom was detected at 111.51 ppm, atoms C1, C9,
and C10 of the cyclobutane ring, at 45.66, 84.94, and 46.55
respectively.
In order to obtain the key radical intermediate
methylacetal I [2] was tosylated, and the nucleophilic
substitution by the treatment with NaI afforded iodide
III.
The alternative and more probable way of obtaining
fused carbocycle would be the transformation of the
carbohydrate part of the molecule into 6-halohexene
fragment for the radical cyclization of this type compounds
is known [3].
The treatment of iodide III with Bu3SnH in the
presence of 1,1'-azobisisobutyronitrile (AIBN) [3] in order
to generate the radical center and to initiate the intra-
molecular cyclization resulted in reductive deiodination
and in the transformation of the carbonyl group into
a carbinol one giving α,β-epimeric alcohols IV
(Scheme 1). Apparently the conditions for the cleavage
of the methoxy group were not attained in the course of
the process, and it impeded the opening of the pyran ring
preceding to the closure of the carbocycle.
The required transformation was sufficiently
effectively performed by boiling the solution of iodoketone
III in a mixture 2-propanol–water in the presence of zinc.
At the opening the pyranose ring the configuration at the
asymmetric center C1 turned to the opposite with the
formation of ketoalcohol VII. The S-configuration of the
C1 atom is indicated by a large coupling constant
(J1,6 9.7 Hz) showing the trans-location of protons H1,
H6.
The attempt on the hydrolysis of the methoxy group
in iodide III by treating its solution in THF with concn.
HCl resulted in the carbocyclization with the formation
of a fused cyclobutane V. The similar treatment of
methoxy derivative I also led to the formation of
cyclobutane VI but in a worse yield.
The subsequent replacement of the hydroxy group by
bromine was performed using CBr4–PPh3. The treatment
of the bromo derivative VIII with Bu3SnH in boiling
benzene resulted in its complete conversion, but bicyclo-
decanone IX was isolated from the reaction mixture in
35% yield.
The structure of compounds V and VI was established
from 1H and 13C NMR spectra. In the 1H NMR spectrum
of compound V a doublet of doublets of H1 is registered
at 2.63 ppm (J1,10 5.7, J1,9 5.2 Hz) indicating the β-syn-
location of protons H1 and H10. The similar value of
coupling constant of protons H10 and H5, 5.0 Hz, also
shows their cis-orientation. At this syn-position of the
rings the only possible orientation of the hemiketal hydroxy
In all likelihood the free keto group initiated competing
side products leading to the decrease in the yield of the
target compound. Therefore the keto group was protected
by transformation into dioxolane X, and the radical
reaction involving Bu3SnH was repeated (Scheme 2).
Already in 2 h compound XI was formed whose
hydrolysis by treatment with cation-exchanger KU-1 in
methanol resulted in bicyclodecanone IX in 92% yield
Scheme 2.
H
H
H
H
H
Zn, i-PrOH_H2O
Br
OH
6
1
CBr4, PPh3
CH2Cl2
Bu3SnH, AIBN
C6H6, boiling
III
boiling
O
H
IX, [α]2D0
O
O
+92.15°
VII, 72%, [α]20
VIII, 90%
D+55.6°
H
H
cation exchanger KU-1,
MeOH
Br
Bu3SnH, AIBN
C6H6, boiling
(CH2OH)2, n-TsOH
C6H6, boiling
H
H
VIII
O
O
O
O
XI
X, 70%
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 2 2010

SHARIPOV et al.
228
Scheme 3.
O
O
O
I2, Et2O_H2O
NaHCO3
H
O
H
H
O
H
O
MeMgI, Et2O
I
O
OH
XIII, 81%
H
H
O
XIV, 90%
XII
H3PO4,
Ac2O
a. SOCl2, Py
H2SO4,
Ac2O
b. 5% Pd/C, EtOAc, H2
c. n-TsOH, C6H6
OAc
O
OAc
H
O
H
O
H
O
H
OAc
H
H
OAc
OH
O
O
XV, 80%
XVI, 70%
XVII, 75 (a), 83 (b), 79% (c)
(with respect to the two last stages). The obtained trans-
junked bicyclodeca-none IX is a chiral matrix for applying
to the synthesis of natural compounds [4, 5].
compound XIII with SOCl2 or hydrogenation on Pd/C
also resulted in the fused tetrahydrofuran ring in
compound XVII.
The obtained tetrahydrofuran derivative XV is a con-
venient object for the study of the opportunities of the
aldol condensation with the prospect of transfer of the
chiral centers into a carbobicyclodecane framework. The
direct acidolysis of diacetates XV or the alkaline
hydrolysis of the anomers of compound XVIII followed
by treating with HCl–MeOH solution led to the formation
of a mixture of methylacetal XIX and a side product,
1,6-anhydro derivative XVII.
In order to study the possibility of the anionic rear-
rangement of the carbohydrate fragment in the
levoglucosenone adduct with isoprene by the type of aldol
intramolecular cyclization the most reasonable way
seemed the preliminary opening of the 1,6-anhydro bridge
and the generation of the aldehyde function. The blocking
of the keto function necessary in this case with
a sufficiently stable protective group may be a problem
for this bicyclic system with a cis-junction. Therefore it
was convenient to carry out these transformations through
a protected hydroxy derivative, and considering that we
had found before an ability to the intramolecular
oxacyclization in a bicyclic system with a cis-junction of
(+)-δ-cadinol [6, 7], we attempted to make analogous
2-hydroxy-5-methyl-5-ene system for its subsequent
cyclization into a tetrahydrofuran ring. The treatment of
compound XII with methylmagnesium iodide furnished
tertiary alcohol XIII whose further iodocyclization [8]
cleanly provided a fused tetrahydrofuran ring in compound
XIV (Scheme 3).
The oxidation of the primary hydroxy group in
compound XIX by Swern method gave aldehyde XX.
The attempt to carry out the theoretically possible aldol
cyclization by treating aldehyde XX with KOH in aqueous
ethanol resulted in a single compound XXI that was more
polar (according to TLC) that initial aldehyde XX (ΔRf
0.05).
Likely the aldol condensation or the completion of ketol
rearrangement was prevented by the methoxy group that
was not eliminated in the course of the reaction. The
hydrolysis of methylacetal XX occurring only at the action
of 85% H3PO4, with the subsequent treatment of
hemiacetal XXII with lithium diisopropylamide (LDA)
led to the formation of a number of intractable products.
The treatment of tertiary alcohol XIII with phosphoric
acid inAc2O also resulted in 1,4-oxacyclization but with
the simultaneous opening of the 1,6-anhydro bridge and
the formation of anomeric diacetates XV. The use in this
reaction of sulfuric acid instead of phosphoric led only to
the opening of the 1,6-anhydro bridge and the formation
of the anomers of compound XVI, and the treatment of
The alternative route consisted of two stages: The
stabilization ot the enol form of aldehyde XX as ethers
followed by their aldolization by Ferrier procedure [9, 10].
Aldehyde XX was treated with LDA–Et3SiCl to obtain
the desired enol ethers XXIII in 30% yield. A simpler
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 2 2010

REACTIONS OF STEREOCONTROLLED INTRAMOLECULAR CARBOCYCLIZATION
229
Scheme 4.
OH
OH
H
O
H
O
H
H
OH
OMe
KOH, EtOH
H2O
HCl
MeOH
HCl
XV
XV
+ XVII
MeOH
O
O
XVIII, 80%
XIX, [α]D20 _127.7°
(COCl)2, DMSO, CH2Cl2, Et3N
CHO
O
CHO
CHO
H
O
H
O
H
H
5
6
KOH, EtOH
H2O
H3PO4
H
OH
OMe
H 7
OMe
3
4
8
2
9
10
1
O
O
O
XX, 81%, [α]D20 _152.1°
XXI, 67%, [α]D20 _47.0°
XXII, 61%
Scheme 5.
OR
O
H
a. LDA, Et3SiCl
H
O
OAc
b. K2CO3, Ac2O,
CH3CN
Hg(OAc)2
H
O
OMe
3
2
H
XX
CH3COCH3
1
OH
O
XXV, 58%, [α]2D0 _0.8°
XXIII, XXIV
procedure was preparation of enol acetates XXIV under
the action of Ac2O in the presence of K2CO3 [11].
EXPERIMENTAL
1H and 13C NMR spectra were registered on a spec-
trometer Bruker AM-300 at operating frequencies 300
(1H) and 75.47 (13C) MHz, solvent CDCl3 The use of
other solvents is indicated in each special case. Melting
points were measured on a Koeffler heating block
S 30A/G (Germany). The analytical TLC was performed
on plates Sorbfil PTCKh-AF-A produced by
“Sorbpolymer” (Krasnodar). The elemental analysis was
carried out on a CHNS(O)-analyzer Euro-2000. IR
spectra were recorded on spectrophotometers UR-20
and Specord M-80 (from films or mulls in mineral oil).
Mass spectra were taken on an GC-MS instrument
Shimadzu 2010EV. The optical rotation was measured
on a polarimeter Perkin Elmer-341.
Ferrier procedure [9, 10] with the use of Hg(OAc)2
completed the stereospecific carbocyclization of the
carbohydrate fragment into tricyclic compound XXV
(Scheme 5) with a cis-junction in the bicyclodecane
system in 58% yield (in the two last stages). In keeping
with the spectral findings the stereochemical result of
the transformation was analogous to that described in
[12], namely, the acetate group is oriented equatorially,
and the hydroxy group axially. The coupling constant
between H2 and H3 equals 4.0 Hz, corresponding to the
coupling constant of the cis-located protons. Compound
XXV is a convenient chiral precursor for the synthesis of
functionalized sesquiterpenoids of the murolan type [4,
5]. One representative of these compounds, (+)-δ-
cardinol, was successfully applied to the synthesis of
eleuthesides [13].
(1S,6R,8R,10S)-4-Methyl-8-methoxy-7-oxo-10-
oxabicyclo[4.4.0]dec-2-en-10-ylmethyl p-toluene-
sulfonate (II). To a solution of 6.0 g (26.55 mmol) of
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 2 2010

SHARIPOV et al.
230
alcohol I in 45 ml of pyridine cooled to 0°C was added
6.30 g (31.8 mmol) of p-TsCl, and the mixture was stirred
at room temperature for 5 h. The reaction mixture was
diluted with water, the reaction product was extracted
into ethyl acetate (3×100 ml). The combined organic solu-
tions were washed with 5% solution of HCl, a saturated
solution of NaCl, with water, dried with MgSO4, and
concentrated. Yield 8.16 g (81%). Oily substance, Rf 0.6
(petroleum ether–EtOAc, 5:1), [α]D20 +94.9° (c 1.0,
CHCl3). 1H NMR spectrum (CCl4 + C6D6), δ, ppm:
1.47 s (3H, CH3), 1.50–2.21 m (5H, CH,CH2), 2.28 s
(3H, PhCH3), 2.40 d.d.d (1H, H6, J 11.3, 9.5, 6.4 Hz),
3.32 s (3H, OCH3), 3.89 m (1H, H10), 3.90 m (1H, H1'),
4.02 m (1H, H1'), 4.24 s (1H, H8), 5.22 m (1H, H3),
7.12 m (2H, Ph), 7.60 d (2H, Ph). 13C NMR spectrum
(CCl4 + C6D6), δ, ppm: 16.52 (PhCH3), 18.26 (C2), 18.41
(CH3), 29.42 (C5), 35.77 (C1), 38.65 (C6), 50.02 (OCH3),
63.70 (C1'), 65.94 (C10), 95.35 (C8), 114.94 (C3), 122.97
(Ph), 124.58 (Ph), 125.79 (C4), 128.63 (Ph), 139.14 (Ph),
195.28 (C7). Found, %: C 60.07; H 6.34. C19H24O6S.
Calculated, %: C 59.98; H 6.36; S 8.43.
within 3 h to a boiling solution of 0.20 g (0.6 mmol) of
iodide III in 10 ml of anhydrous benzene. Afterward the
same amount of Bu3SnH was added to the reaction mix-
ture, and the boiling was continued till the disappearance
of the initial compound. Then the mixture was cooled
and treated with 10% solution of NaOH (10 ml). The
reaction products were extracted into ethyl acetate (3×
30 ml), the organic solutions were combined, washed with
a saturated solution of NaCl, with water, and dried with
MgSO4. The solvent was distilled off, and the residue
was subjected to chromatography on SiO2. Yield 0.10 g
(81%) of a mixture of 7β- and 7α-epimers, 5:1. Oily
substance, Rf 0.4 (petroleum ether–EtOAc, 5:1). 1H NMR
spectrum, δ, ppm: 0.90 d [0.95 d]* (3H, CH3, J 6.8 Hz),
1.15–1.45 m [1.15–1.45 m] (4H, CH2), 1.50 s [1.52 s]
(3H, =CCH3), 1.70 m [1.75 m] (1H, CH), 2.23 m [2.10
m] (1H, CH), 3.04 d.d [3.20 m] (1H, H7, J 10.2, 3.6 Hz),
3.28 s [3.21 s] (3H, OCH3), 3.30 m [3.30 m] (1H, H10),
[4.32 d (1H, H8, J 1.5 Hz)], 4.41 d (1H, H8, J 3.6 Hz),
5.28 d [5.12 d] (1H, H3, J 3.6 Hz). 13C NMR spectrum,
δ, ppm: 18.90 [19.10] (CH3), 24.10 [24.10] (CH3), 29.30
[28.12] (C2), 32.71 [34.64] (C5), 38.07 [36.98] (C1), 42.29
[41.72] (C6), 55.10 [54.82] (OCH3), 69.12 [68.56] (C7),
73.4 [69.6] (C10), 99.8 [101.5] (C8), 121.26 [121.64] (C3),
131.75 [133.62] (C4). Found, %: C 67.94; H 9.63.
C12H20O3. Calculated, %: C 67.89; H 9.50.
(1S,6R,8R,10S)-10-Iodomethyl-4-methyl-8-
methoxy-9-oxabicyclo[4.4.0]dec-2-en-7-one (III). To
a solution of 8.0 g (21.1 mmol) of tosylate II in 35 ml of
acetic anhydride was added 9.45 g (63.22 mmol) of
sodium iodide, and the mixture was heated to boiling and
boiled for 5 min. On cooling to 0°C the reaction mixture
was neutralized with a saturated solution of NaHCO3.
The reaction product was extracted into ethyl acetate
(3 × 100), the organic solutions were combined, washed
with Na2S2O3, a saturated solution of NaCl, with water,
and dried with MgSO4. Yield 6.01 g (86%). Oily
substance, Rf 0.6 (petroleum ether–EtOAc, 10:1),
(1S,5S,6S,8S,9S,10S)-6-Iodomethyl-2-methyl-7-
oxatricyclo[6.1.1.05,10]dec-2-ene-8,9-diol (V). To
a solution of 1.0 g (2.98 mmol) of iodide III in 15 ml of
THF was added 3 ml of water and 5 ml of concn. HCl.
After the disappearance of the initial compound (TLC
monitoring) the reaction mixture was neutralized with
a saturated solution of NaHCO3, the reaction product
was extracted into ethyl acetate (3×50 ml), the extract
was dried with MgSO4. On evaporation of the solvent
the residue was subjected to chromatography. Yield 0.47 g
(50%). Oily substance, Rf 0.5 (petroleum ether–EtOAc,
1
[α]D20 +93.4° (c 1.0, CHCl3). H NMR spectrum
(CD2Cl2), δ, ppm: 1.62 s (3H, CH3), 1.88 m (2H, CH2),
1.91–2.48 m (5H, CH,CH2), 2.70 d.d.d (1H, H6, J 11.6,
9.7, 6.6 Hz), 3.22 d (1H, H1', J 9.9 Hz), 3.26 d (1H, H1', J
9.9 Hz), 3.5 s (3H, OCH3), 3.78 m (1H, H10), 4.57 s (1H,
H8), 5.42 m (1H, H3). 13C NMR spectrum, δ, ppm: 7.46
(C1'), 23.47 (CH3), 23.62 (C2), 32.92 (C5), 43.49 (C1),
45.19 (C6), 55.79 (OCH3), 72.09 (C10), 101.14 (C8),
119.92 (C3), 131.62 (C4), 203.05 (C7). Mass spectrum:
m/z 337 [M + H]+. Found, %: C 42.57; H 5.09. C12H17IO3.
Calculated, %: C 42.87; H 5.10.
1:1), [α]D20 –153.8° (c 1.0, CHCl3). H NMR spectrum,
1
δ, ppm: 1.50 d (1H, H4, J 11.9 Hz), 1.72 s (3H, CH3),
1.72 m (1H, H4), 2.41 m (1H, H5), 2.63 d.d (1H, H1,
J 5.7, 5.2 Hz), 3.15 d.d (1H, H10, J 5.2, 5.0 Hz), 3.32 d.d
(1H, H1', J 9.6, 3.9 Hz), 3.38 d.d (1H, H1', J 9.6, 5.6 Hz),
4.0 d.d (1H, H6, J 9.6, 5.6 Hz), 4.09 d (1H, H9, J 5.7 Hz),
5.30 br.s (1H, H3). 13C NMR spectrum, δ, ppm: 6.64
(C1'), 24.75 (CH3), 26.17 (C4), 44.91 (C5), 45.66 (C1),
46.55 (C10), 84.31 (C6), 84.94 (C9), 111.51 (C8), 120.70
(C3), 141.50 (C2). Mass spectrum: m/z 322 [M]+. Found,
(1S,6R,7SR,8R,10R)-2,8-Dimethyl-4-methoxy-3-
oxabicyclo[4.4.0]dec-8-en-5-ol (IV). The cyclization
was carried out by adding 10 ml of benzene solution of
0.18 g (0.72 mmol) of Bu3SnH and 0.05 equiv of AIBN
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REACTIONS OF STEREOCONTROLLED INTRAMOLECULAR CARBOCYCLIZATION
231
3.92 d (1H, H2', J 12.9 Hz), 3.95 d (1H, H2', J 12.9 Hz),
5.02 d (1H, H2", J 17.2 Hz), 5.07 d (1H, H2", J 10.2 Hz),
5.39 m (1H, H4), 5.67 d.d.d (1H, H1", J 17.1, 10.2,
8.5 Hz). 13C NMR spectrum, δ, ppm: 23.17 (=CCH3),
28.53 (C2), 35.55 (C5), 35.61 (C2'), 41.39 (C6), 44.93 (C1),
116.22 (C2"), 118.63 (C4), 133.18 (C3), 139.77 (C1"),
204.49 (C1'). Found, %: C 54.57; H 6.239. C11H15BrO.
Calculated, %: C 54.34; H 6.22.
%: C 41.21; H 4.66. C11H15IO3. Calculated, %: C 41.01;
H 4.69.
(1S,5S,6S,8S,9S,10S)-6-Hydroxymethyl-2-
methyl-7-oxatricyclo[6.1.1.05,10]dec-2-ene-8,9-diol
(VI) was similarly obtained from 1.0 g (4.42 mmol) of
alcohol I. Yield 0.28 g (30%). Oily substance, Rf 0.3
(petroleum ether–EtOAc, 1:1), [α]D20 –71.7° (c 2.1,
1
CHCl3). H NMR spectrum, δ, ppm: 1.50 d (1H, H4,
(1S,6S)-4-Methylbicyclo[4.4.0]dec-2-en-7-one
(IX). (a) The cyclization was performed as described
for compound IV. From 0.25 g (1.03 mmol) of compound
VIII we obtained 0.062 g (37%) of bicyclodecanone IX.
J 11.8 Hz), 1.70 s (3H, CH3), 1.70 m (1H, H4), 2.42 d
(1H, H5, J 4.2 Hz), 2.65 d.d (1H, H10, J 5.5, 4.2 Hz),
2.78 d.d (1H, H1, J 5.5, 5.2 Hz), 3.0 br.s (1H, OH),
3.30 br.s (1H, OH), 3.68 d.d (1H, H1', J 11.5, 3.5 Hz),
3.78 d.d (1H, H1', J 11.5, 6.9 Hz), 3.86 d.d (1H, H6, J 6.9,
3.5 Hz), 4.11 d (1H, H9, J 5.2 Hz), 5.29 br.s (1H, H3).
13C NMR spectrum, δ, ppm: 24.80 (CH3), 26.05 (C4),
44.17 (C1), 45.08 (C5), 47.19 (C10), 64.23 (C1'), 83.64
(C6), 85.46 (C9), 111.52 (C8), 120.75 (C3), 140.95 (C2).
Found, %: C 62.23; H 7.73. C11H16O4. Calculated, %:
C 62.25; H 7.60.
(b) The cyclization of dioxolane bromide X was carried
out by the procedure used in obtaining compound VIII.
The mixture obtained was dissolved in aqueous methanol,
and cation-exchanger KU-1 was added. On completion
of the reaction the reaction mixture was filtered,
evaporated, and subjected to chromatography. From
0.12 g (0.42 mmol) of dioxolane X 0.06 g (92%) of bi-
cyclodecanone IX was obtained. Oily substance, Rf 0.4
(petroleum ether–EtOAc, 5:1), [α]D20 +92.15° (c 1.1,
1-[(1S,6R)-6-Vinyl-3-methylcyclohex-3-enyl]-2-
hydroxy-1-ethanone (VII). A mixture of 1.00 g
(2.98 mmol) of iodide III, 2.0 g of zinc, 2.5 ml of water,
and 11 ml of 2-propanol was boiled for 5 h. The reaction
mixture was filtered, evaporated, and subjected to
chromatography. Yield 0.39 g (72%). Oily substance, Rf
0.5 (petroleum ether–EtOAc, 4:1), [α]D20 +55.6° (c 1.7,
1
CHCl3). H NMR spectrum, δ, ppm: 1.45 m (1H, CH2),
1.63 s (3H, =CCH3), 1.70 m (2H, CH2), 1.80–1.88 m
(2H, CH2), 1.95–2.18 m (5H, CH, CH2), 2.38 m (1H,
CH2), 2.40 m (1H, CH), 5.40 m (1H, H3). 13C NMR
spectrum, δ, ppm: 23.21 (=CCH3), 24.67 (C9), 26.11 (C5),
32.66 (C2), 38.36 (C10), 40.49 (C1), 42.02 (C8), 50.26 (C6),
119.94 (C3), 132.34 (C4), 212.29 (C7). Mass spectrum:
m/z 165 [M + H]+. Found, %: C 80.40; H 10.03. C11H16O.
Calculated, %: C 80.44; H 9.82.
1
CHCl3). H NMR spectrum, δ, ppm: 1.70 s (3H, =CCH3),
1.83–2.32 m (4H, CH, CH2), 2.50 d.d.d (1H, H1, J 9.7,
9.7, 5.3 Hz), 2.56 d (1H, CH, J 7.3 Hz), 3.14 br.s (1H,
OH), 4.18 m (2H, H2'), 5.0 d (1H, H2", J 10.2 Hz), 5.03 d
(1H, H2", J 17.5 Hz), 5.40 m (1H, H4), 5.61 d.d.d (1H,
H1", J 17.5, 10.2, 7.3 Hz). 13C NMR spectrum, δ, ppm:
23.02 (=CCH3), 27.84 (C5), 35.43 (C2), 40.64 (C6), 47.60
(C1), 66.54 (CH2OH), 115.96 (C2"), 118.40 (C4), 132.83
(C3), 139.56 (C1"), 212.75 (C1'). Mass spectrum: m/z 181
[M + H]+. Found, %: C 73.31; H 9.03. C11H16O2.
Calculated, %: C 73.30; H 8.95.
(1S,6R)-6-Vinyl-1-[2-bromo-1-(2,2-ethylenedi-
oxy)]-3-methylcyclohex-3-ene (X). Asolution of 0.15 g
(0.62 mmol) of ketone VIII in 10 ml of anhydrous benzene
containing a 5-fold excess of ethylene glycol was boiled
at reflux with a Dean-Stark trap in the presence of
a catalytic quantity of p-TsOH till the complete disappear-
ance of the initial compound (TLC monitoring). On
completion of the reaction the reaction mixture was
evaporated, and the residue was subjected to
chromatography. Yield 0.12 g (70%). Oily substance, Rf
0.6 (petroleum ether–EtOAc, 5:1). 1H NMR spectrum,
δ, ppm: 1.68 s (3H, =CCH3), 1.95–2.38 m (5H, CH2,
CH), 2.84 m (1H, H1), 3.49 d (1H, H2', J 12.3 Hz), 3.52
d (1H, H2', J 12.3 Hz), 4.0 m (4H, CH2), 4.90 m (1H,
H2"), 5.02 m (1H, H2"), 5.36 m (1H, H4), 5.80 m (1H,
H1").
1-[(1S,6R)-6-Vinyl-3-methylcyclohex-3-enyl]-2-
bromo-1-ethanone (VIII). To a solution of 0.30 g
(1.66 mmol) of ketoalcohol VII and 0.72 g (2.15 mmol)
of CBr4 in 15 ml of CH2Cl2 at 0°C while stirring was
added 0.65 g (2.49 mmol) of PPh3. The reaction mixture
was kept for 15 min. On evaporation of the solvent the
residue was subjected to chromatography. Yield 0.36 g
(90%). Oily substance, Rf 0.5 (petroleum ether–EtOAc,
10:1). 1H NMR spectrum, δ, ppm: 1.65 s (3H, =CCH3),
1.95 m (2H, CH2), 2.20 m (2H, CH2), 2.57 d.d (1H, CH,
J 10.2, 8.5 Hz), 2.88 d.d.d (1H, CH, J 10.2, 10.2, 6.0 Hz),
(1S,2S,7R,8R,9R)-5,8-Dimethyl-10,12-dioxa-
tricyclo[7.2.1.02,7]dodec-4-en-8-ol (XIII). To 80 ml
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SHARIPOV et al.
232
of 1.0 M MeMgI solution in ethyl ether cooled to 0°C
under an argon atmospher ewas slowly added at stirring
10.0 g (51.6 mmol) of compound XII in 50 ml of THF.
After 5 min (TLC monitoring) a saturated solution was
added to the reaction mixture, and the mixture was
warmed to room temperature. The reaction products
were extracted into ethyl acetate (3×100 ml), the organic
solutions were combined, washed with a saturated solution
of NaCl, and dried with MgSO4, the solvent was evaporat-
ed, and the residue was subjected to chromatography on
SiO2. Yield 8.66 g (80%). Oily substance, [α]D20 –73.41°
(c 1.0, CHCl3), Rf 0.52 (petroleum ether–EtOAc, 5:1).
IR spectrum, ν, cm–1: 3480, 3260, 2920, 1650, 1120, 1080,
dimethyl-6,11-dioxatricyclo[6.2.1.04,9]undec-7-yl
acetate (XV). (a) To a solution of 6.0 g (28.56 mmol) of
alcohol XIII in 50 ml of Ac2O cooled to 0°C was added
dropwise at stirring 6 ml of H3PO4 (86%). The mixture
was stirred for 5 min at 0°C. Then the reaction mixture
was poured into water with ice containing 135 g of
NaHCO3, and the mixture was stirred till the end of gas
liberation. The reaction product was extracted into ethyl
acetate (3×200 ml), the organic solutions were combined,
washed with NaHCO3 solution, with a saturated NaCl
solution, with water, and dried with MgSO4. The solvent
was evaporated, and the residue was subjected to
chromatography. Yield 7.2 g (80%). Oily substance, Rf
1
1000, 960, 920. H NMR spectrum, δ, ppm: 1.12 s (3H,
1
0.5 (petroleum ether–EtOAc, 3:1). H NMR spectrum,
CH3), 1.70 s (3H, CH3), 1.85 d.d (1H, H6, J 12.3, 6.6 Hz),
1.88 m (1H, CH), 2.03 m (1H, CH2), 2.22 m (2H, CH,
CH2), 2.49 (1H, CH2), 3.85 d.d (1H, H11, J 7.1, 4.9 Hz),
3.90 d (1H, H11, J 7.10 Hz), 4.35 d (1H, H1, J 4.9 Hz),
5.02 s (1H, H9), 5.48 br.s (1H, H4). 13C NMR spectrum,
δ, ppm: 22.74 (CH3), 23.38 (C3), 23.71 (CH3), 30.84 (C2),
31.05 (C6), 35.25 (C7), 67.35 (C11), 73.34 (C8), 76.89 (C1),
106.55 (C9), 120.43 (C5), 132.33 (C4). Found, %: C 68.40;
H 8.72. C12H18O3. Calculated, %: C 68.54; H 8.63.
δ, ppm: 1.11 s (3H, CH3), 1.14 s (3H, CH3), 1.46 m (1H,
CH2), 1.62–1.95 m (7H, CH, CH2), 2.06 s (3H, CH3),
2.08 C (3H, CH3), 3.82 d.d (1H, H5, J 7.4, 7.3 Hz),
4.22 d.d (1H, H12 , J 11.3, 7.4 Hz), 4.28 d.d (1H, H1',
J 11.3, 7.3 Hz), 5.62 s (1H, H7). 13C NMR spectrum, δ,
ppm: 20.33 (C3), 20.79 (CH3), 21.37 (COCH3), 22.90
(CH3), 24.32 (COCH3), 26.72 (C4), 31.37 (C9), 31.48
(C2), 38.33 (C10), 65.01 (C1'), 70.22 (C1), 71.30 (C8), 76.66
(C5), 95.13 (C7), 169.46 (COCH3), 170.76 (COCH3).
Found, %: C 61.53; H 7.70. C16H24O6. Calculated, %:
C 61.52; H 7.74.
(1R,2R,3R,5S,6S,8S,9S)-2,5-Dimethyl-6-iodo-
11,12,13-trioxatetracyclo[7.2.1.12,503,8]tridecene
(XIV). In 15 ml of ether and 3 ml of water was dissolved
0.54 g (2.58 mmol) of alcohol XIII, 0.52 g (5.1 mmol) of
NaHCO3 and 1.3 g (5.1 mmol) of I2 was added at 0°C.
The reaction mixture was warmed to room temperature
and stirred for 1 h, then it was diluted with a saturated
NaCl solution, the reaction product was extracted into
ethyl acetate (3×20 ml), the organic solutions were
combined, washed with Na2S2O3 solution, with water, and
dried with MgSO4. The solvent was evaporated, and the
residue was subjected to chromatography. Yield 0.78 g
(1S,6R,7R,8RS,10S)-10-Acetoxymethyl-7-hy-
droxy-4,7-dimethyl-9-oxabicyclo[4.4.0]dec-2-en-8-
yl acetate (XVI). To a solution of 5.0 g (23.8 mmol) of
alcohol XIII in 30 ml of Ac2O cooled to 0°C was added
dropwise at stirring a solution of 2 ml of H2SO4 in 5 ml of
Ac2O. The mixture was stirred for 20 min at 0°C. Then
the reaction mixture was poured into water with ice and
neutralized with a saturated solution of NaHCO3. The
reaction products were extracted into ethyl acetate
(3×150 ml), the organic solutions were combined, washed
with a saturated NaHCO3 solution, with a saturated NaCl
solution, with water, and dried with MgSO4. The solvent
was evaporated, and the residue was subjected to
chromatography. Yield of a mixture of 8β- and 8α-
epimers, 2:1, 5.2 g (70%). Oily substance, Rf 0.51
1
(90%), Rf 0.55 (petroleum ether–EtOAc, 5:1). H NMR
spectrum, δ, ppm: 1.10 s (3H, CH3), 1.33 s (3H, CH3),
1.70–2.0 m (3H, H4, H7, H8), 2.30 d.d.d (1H, H3, J 10.8,
7.3, 1.8 Hz), 2.42 d.d (1H, H4, J 14.0, 10.8 Hz), 2.82 d.d
(1H, H7, J 14.8, 9.9 Hz), 3.73 d.d (1H, H10, J 6.9, 4.5 Hz),
3.79 d (1H, H10, J 6.9 Hz), 4.21 d.d.d (1H, H6, J 9.9, 7.4,
2.3 Hz), 4.27 d.d (1H, H9, J 4.5, 3.1 Hz), 4.86 s (1H, H1).
13C NMR spectrum, δ, ppm: 17.36 (CH3), 27.03 (CH3),
35.50 (C6), 36.65 (C7), 40.33 (C8), 46.00 (C3), 49.33 (C4),
69.46 (C10), 74.26 (C9), 77.43 (C2), 86.24 (C5), 104.32
(C1). Found, %: C 42.64; H 5.14. C12H17IO3. Calculated,
%: C 42.87; H 5.10.
1
(petroleum ether–EtOAc, 5:1). H NMR spectrum, δ,
ppm: 1.32 s [1.36 s] (3H, CH3), 1.62 s [1.65 s] (3H, CH3),
1.70–1.98 m (4H, CH, CH2), 2.0 s [2.05 s] (6H, CH3),
2.05–2.28 m (8H, CH, CH2), 3.78 m (2H, CH), 4.06–
4.24 m (4H, H12 ), 4.96 C [4.88 C] (1H, H8), 5.36 m (2H,
H3). 13C NMR spectrum, δ, ppm: 14.17 [14.15] (CH3),
20.91 (CH3CO), 21.06 (CH3CO), 21.99 [22.46] (C2),
23.44 [23.40] (CH3), 30.69 [31.26] (C5), 33.20 [33.12]
(1R,4S,5S,7RS,8R,9R)-5-Acetoxymethyl-1,8-
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REACTIONS OF STEREOCONTROLLED INTRAMOLECULAR CARBOCYCLIZATION
233
(C1), 41.26 [40.33] (C6), 60.47 [80.57] (C7), 72.33 [66.73]
(C10), 72.42 [71.15] (C12 ), 95.38 [97.57] (C8), 119.35
[120.16] (C3), 130.36 [130.25] (C4), 171.20 (COCH3),
171.22 (COCH3), 171.23 (COCH3), 171.24 (COCH3).
Found, %: C 61.29; H 7.33. C16H24O6. Calculated, %:
C 61.52; H 7.74.
(3×20 ml), the combined organic solutions were washed
with a saturated solution of NaCl and dried with MgSO4,
the solvent was evaporated, and the residue was
subjected to chromatography. Yield 1.17 g (80%), β:α =
3:2, oily substance, Rf 0.55 (methanol–EtOAc, 1:9). 1H
NMR spectrum, δ, ppm: 1.11 s [1.14 s] (3H, CH3), 1.19 s
[1.18 s] (3H, CH3), 1.20–2.00 m (9H, CH, CH2), 3.59 d.d
(1H, H5, J 8.2, 4.2 Hz) [3.49 d.d (1H, H5, J 10.2, 4.0 Hz)],
3.73 d.d (1H, H12 , J 9.0, 4.2 Hz) [3.90 d.d (1H, H12,
J 10.2, 4.0 Hz)], 4.0 d.d (1H, H12 , J 9.0, 8.2 Hz), 4.72 s
[5.22 s] (1H, H7). 13C NMR spectrum, δ, ppm: 20.47
[20.47] (C3), 23.62 [21.69] (CH3), 24.36 [26.66] (CH3),
29.40 [26.79] (C4), 31.63 [31.94] (C2), 32.35 [31.28] (C9),
39.27 [38.36] (C10), 65.45 [61.12] (C1'), 70.28 [70.96]
(C1), 72.81 [72.38] (C8), 80.38 [79.86] (C5), 96.49 [93.36]
(C7). Found, %: C 63.23; H 8.69. C12H20O4. Calculated,
%: C 63.14; H 8.83.
(1R,2R,3R,5R,8S,9S)-2,5-Dimethyl-11,12,13-
trioxatetracyclo[7.2.1.12,503,8]tridecene (XVII). (a)
To a solution of 0.50 g (2.38 mmol) of alcohol XIII in 15
ml of ethyl acetate was added 0.05 g of Pd/C (5%). The
reaction mixture was stirred in an atmosphere of H2 (TLC
monitoring).After 36 h the reaction mixture was filtered,
evaporated, and the residue was subjected to
chromatography. Yield 0.42 g (83%).
(b) A solution of 0.50 g (2.38 mmol) of alcohol XIII,
3 ml of pyridine, and 0.50 ml of thionyl chloride was
maintained at 0°C for 1h. The reaction mixture was diluted
with water, the reaction product was extracted into ethyl
acetate (3 × 20 ml), the organic solutions were combined,
washed with a saturated NaHCO3 solution, with water,
and dried with MgSO4. The solvent was evaporated, and
the residue was subjected to chromatography on SiO2.
Yield 0.38 g (75%).
(1R,2R,3R,5R,8S,9S)-2,5-Dimethyl-11,12,13-
trioxatetracyclo[7.2.1.12,503,8]tridecane (XVII) and
(1R,4S,5S,8R,9R)-1,8-dimethyl-7-methoxy-6,11-
dioxatricyclo[6.2.1.04,9]undec-5-ylmethanol (IX). (a)
To a solution of 4.9 g (15.68 mmol) of epimeric acetates
XV in 17.5 ml of methanol was added at 0°C 17.5 ml of
20% solution of HCl in methanol. Then the cooling was
removed, and the solution was stirred for 3 h. The acid
was neutralized with a saturated solution of NaHCO3 till
pH 7. The reaction products were extracted into ethyl
acetate (3×30 ml), the combined organic solutions were
dried with MgSO4. The reaction mixture was evaporated
on a rotary evaporator, and the residue was subjected to
chromatography. Yield 2.17 g (57%) of methoxyalcohol
XIX and 1.33 g (30%) of compound XVII.
(c)Asolution of 0.25 g (1.19 mmol) of alcohol XIII in
10 ml of benzene was boiled in the presence of a catalytic
quantity of p-TsOH till the initial compound disappeared
(TLC monitoring). On the completion of the reaction the
reaction mixture was evaporated, and the residue was
subjected to chromatography. Yield 0.20 g (79%). Oily
substance, [α]D20 –81.3° (c 1.18, CHCl3), Rf 0.5
(petroleum ether–EtOAc, 5:1). 1H NMR spectrum, δ,
ppm: 1.12 s (3H, CH3), 1.17 s (3H, CH3), 1.10–1.22 m
(2H, CH2), 1.34–2.02 m (6H, CH, CH2), 3.68 d.d (1H,
H10, J 7.1, 4.7 Hz), 3.78 d (1H, H10, J 7.1 Hz), 4.20 d.d
(1H, H9, J 4.7, 3.7 Hz), 4.85 s (1H, H1). 13C NMR
spectrum, δ, ppm: 19.43 (C7), 21.31 (CH3), 26.45 (CH3),
27.01 (C8), 32.17 (C6), 35.35 (C3), 35.46 (C4), 65.75 (C10),
68.99 (C5), 73.91 (C2), 76.17 (C9), 104.43 (C1). Mass
spectrum: m/z 211 [M + H]+. Found, %: C 68.67; H 8.43.
C12H18O3. Calculated, %: C 68.55; H 8.63.
(b) Methanolysis of epimeric alcohols XVIII was
carried out by the procedure for the preparation of
acetates XV. From 1.17 g (5.08 mmol) of epimeric
alcohols XVIII we obtained 0.66 g (54%) of
methoxyalcohol XIX and 0.32 g (30%) of compound
XVII.
Compound XIX. Oily substance, [α]D20 –127.7° (c
1
1.2, CHCl3), Rf 0.4 (petroleum ether–EtOAc, 2:1). H
NMR spectrum, δ, ppm: 1.24 s (3H, CH3), 1.27 s (3H,
CH3), 1.47–1.64 m (2H, CH, CH2), 1.72–1.83 m (2H,
CH, CH2), 1.97 d.d (1H, CH2, J 12.4, 11.8 Hz) 2.05–
2.18 m (3H, CH, CH2), 3.56 s (3H, CH3), 3.72 t (1H, H5,
J 5.2, 5.1 Hz), 3.80 d (1H, H12 , J 5.1 Hz), 3.88 d (1H,
H12 , J 5.2 Hz), 4.27 s (1H, H7). 13C NMR spectrum, δ,
ppm: 20.32 (C3), 23.36 (CH3), 24.48 (CH3), 26.75 (C4),
31.51 (C2), 31.81 (C9), 39.17 (C10), 56.29 (OCH3), 64.71
(C1'), 70.10 (C1), 72.14 (C8), 80.46 (C5), 104.11 (C7).
(1R,4S,5S,7RS,8R,9R)-5-Hydroxymethyl-1,8-
dimethyl-6,11-dioxatricyclo[6.2.1.04,9]undecan-7-ol
(XVIII). To a solution of 2.00 g (6.4 mmol) of epimeric
acetates XV in 20 ml of ethanol was added 20 ml of
a solution of 4.0 g of KOH in a mixture of 20 ml of water
and 40 ml of ethanol. After 1 h (TLC monitoring) the
mixture was neutralized with 10% solution of HCl till pH
7. The reaction products were extracted into ethyl acetate
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SHARIPOV et al.
234
(1R,4S,5S,7RS,8R,9R)-7-Hydroxy-1,8-dimethyl-
6,11-dioxatricyclo[6.2.1.04,9]undec-5-carbaldehyde
(XXII).Asolution of 0.30 g (1.25 mmol) of aldehyde XX
in 3 ml of 86% phosphoric acid was kept at room
temperature for 3 h, The reaction mixture was diluted
with water, the reaction products were extracted into ethyl
acetate (3×10 ml), the organic solutions were combined,
washed with a saturated NaHCO3 solution, with water,
dried with MgSO4. The solvent was evaporated, and the
residue was subjected to chromatography on SiO2. Yield
of a mixture of 7β- and 7α-epimers, 1:1, 0.17 g (61%).
Oily substance, Rf 0.5 (petroleum ether–EtOAc, 1:1).
1H NMR spectrum, δ, ppm: 1.09 s (3H, CH3), 1.16 s
(3H, CH3), 1.32–2.0 m (8H, CH, CH2), [3.80 d (1H, H5,
J 1.8 Hz)], 3.94 d (1H, H5, J 3.1 Hz), 5.21 s [5.02 s] (1H,
H7), 9.88 s (1H, CHO, J 3.1 Hz). 13C NMR spectrum,
δ, ppm: 19.55 [20.30] (C3), 21.41 [24.31] (CH3), 27.58
[26.60] (CH3), 30.03 [29.37] (C4), 31.99 [31.65] (C9),
32.17 [32.17] (C2), 69.89 [70.27] (C1), 73.10 [72.64] (C1),
82.77 [82.70] (C5), 95.07 [105.59] (C7), 202.77 [203.08]
(CHO).
Found, %: C 64.32; H 9.02. C13H22O4. Calculated, %:
C 64.44; H 9.15.
(1R,4S,5S,7R,8R,9R)-1,8-Dimethyl-7-methoxy-
6,11-dioxatricyclo[6.2.1.04,9]undec-5-carbaldehyde
(XX). A solution of 5.19 ml (70.65 mmol) of DMSO in
9.0 ml of CH2Cl2 was slowly added to a solution of 3.21
ml (35.31 mmol) of oxalyl chloride in 60 ml of CH2Cl2
cooled to –60°C. The mixture obtained was for 15 min
stirred at –60°C, then was added dropwise a solution of
3.0 g (11.76 mmol) of alcohol XIX in 15 ml of CH2Cl2.
The reaction mixture was kept for 30 min at –20°C, then
it was cooled again to –60°C, and it was treated with
10.5 ml (70.65 mmol) of Et3N. Afterwards the reaction
mixture was stirred for 1 h at room temperature, diluted
with water, the reaction product was extracted with ethyl
acetate (3×30 ml), the organic solutions were combined,
washed with 5% solution of HCl, with a saturated NaCl
solution, with water, dried with MgSO4, and concentrated.
Yield 2.28 g (81%). Oily substance, [α]D20 –152.1° (c 1.8,
1
CHCl3), Rf 0.65 (petroleum ether–EtOAc, 3:1). H NMR
spectrum, δ, ppm: 1.08 s (3H, CH3), 1.12 s (3H, CH3),
1.47 m (2H, CH2), 1.60 d (1H, H10, J 2.9 Hz), 1.65 d
(1H, H10, J 11.3 Hz), 1.68 d.d.d.d (1H, H4, J 10.6, 2.9,
1.9, 1.5 Hz), 1.84 d (1H, H2, J 12.8 Hz), 1.92 d.d.d (1H,
H3, J 12.2, 10.6, 4.4 Hz), 2.42 d.d.d (1H, H9, J 11.3, 2.9,
2.9 Hz), 3.48 s (3H, OCH3), 3.78 d (1H, H5, J 1.9 Hz),
4.20 s (1H, H7), 9.72 s (1H, CHO). 13C NMR spectrum,
δ, ppm: 20.17 (C3), 23.17 (CH3), 24.87 (C4), 26.81 (CH3),
29.90 (C9), 31.54 (C2), 36.82 (C10), 57.08 (OCH3), 70.06
(C1), 72.11 (C8), 83.22 (C5), 104.71 (C7), 202.82 (CHO).
Mass spectrum: m/z 241 [M + H]+. Found, %: C 65.10;
H 8.31. C13H20O4. Calculated, %: C 64.98; H 8.39.
(1R,4S,7R,8R,9R)-1,8-Dimethyl-7-methoxy-5-
(E,Z-triethylsilyloxy)methylene-6,11-dioxatri-
cyclo[6.2.1.04,9]undecene (XXIII). Under an argon
atmosphere 0.18 ml (1.25 mmol) of anhydrous
diisopropylamine was dissolved in 5 ml of THF, the solution
was cooled to 0°C, and 0.78 ml (0.8 M solution) of BuLi
was added.After 20 min to a solution of LDAwas slowly
added 0.15 g (0.625 mmol) of aldehyde XX, the mixture
obtained was kept for 20 min and then treated with
0.21 ml (1.25 mmol) of Et3SiCl. The reaction mixture
was diluted with water, the reaction products were
extracted into ethyl acetate (3×20 ml). The organic
solutions were combined, washed with a saturated
NaHCO3 solution, with water, dried with MgSO4. The
solvent was evaporated, and the residue was subjected
to chromatography on SiO2. Yield 0.07 g (30%), E:Z =
1:3, oily substance, Rf 0.6 (petroleum ether–EtOAc, 5:1).
1H NMR spectrum, δ, ppm: 0.55–0.70 m (6H, CH2), 0.82–
1.0 m (9H, CH3), 1.16 s [1.18 s] (3H, CH3), 1.23 s
[1.24 s] (3H, CH3), 1.25–1.90 m [1.25–1.90 m] (7H, H4,
CH2), 2.05 m (1H, H9), 3.37 s [3.36 s] (3H, OCH3),
4.21 s [4.32 s] (1H, H7), 5.22 s (1H, =CH), 6.18 s (1H,
=CH). 13C NMR spectrum, δ, ppm: 4.37 [4.37] (SiCH2),
6.72 [6.72] (CH3), 20.53 [20.32] (C3), 23.82 [23.58] (C8),
26.95 [23.17] (C4), 28.62 [28.86] (CH3), 30.65 [32.78]
(C9), 31.85 [31.69] (C2), 37.82 [38.9] (C10), 70.13 [70.04]
(C1), 72.35 [73.01] (C8), 104.19 [104.49] (C7), 125.27
[125.27] (C5), 143.06 [143.06] (=CH).
(1R,4S,5R,7R,8R,9R)-1,8-Dimethyl-7-methoxy-
6,11-dioxatricyclo[6.2.1.04,9]undec-5-carbaldehyde
(XXI) was obtained by the method used in the preparation
of compound XVIII from 0.40 g of aldehyde XX. Yield
0.27 g (67%). Oily substance, [α]D20 –47.0° (c 1.28,
1
CHCl3), Rf 0.35 (petroleum ether–EtOAc, 2:1). H NMR
spectrum, δ, ppm: 1.08 s (3H, CH3), 1.18 s (3H, CH3),
1.45 m (1H, H2), 1.47 m (1H, H3), 1.53 m (1H, H2),
1.60 d.d (1H, H10, J 9.6, 5.4 Hz), 1.67 d.d (1H, H10, J 9.6,
9.4 Hz), 1.78 d.d.d (1H, H4, J 4.5, 2.6, 2.0 Hz), 2.05 d.d
(1H, H3, J 11.2, 4.5 Hz), 2.31 d.d.d (1H, H9, J 9.4, 5.4,
2.6 Hz), 3.38 s (3H, OCH3), 4.23 d (1H, H5, J 2.0 Hz),
4.30 s (1H, H7), 9.67 s (1H, CHO). 13C NMR spectrum,
δ, ppm: 20.49 (C3), 22.90 (CH3), 26.72 (CH3), 29.28 (C4),
31.53 (C2), 32.55 (C9), 33.45 (C10), 55.68 (OCH3), 70.02
(C1), 72.26 (C8), 77.05 (C5), 104.06 (C7), 202.36 (CHO).
Found, %: C 65.07; H 8.45. C13H20O4. Calculated, %:
C 64.98; H 8.39.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 2 2010

REACTIONS OF STEREOCONTROLLED INTRAMOLECULAR CARBOCYCLIZATION
235
(COCH3), 205.30 (C4). Found, %: C 62.42; H 7.57.
C14H20O5. Calculated, %: C 62.67; H 7.51.
(1R,4S,7R,8R,9R)-1,8-Dimethyl-7-methoxy-
6,11-dioxatricyclo[6.2.1.04,9]undec-5E,Z-ylidene-
methyl acetate (XXIV) and (1R,5S,7R,8R,10R)-2-
hydroxy-1,8-dimethyl-4-oxo-11-oxatricyclo-
[6.2.1.05,10]undec-3-yl acetate (XXV). To a solution
of 0.30 g (1.25 mmol) of aldehyde XX in 10 ml of
anhydrous acetonitrile was added 1.0 g of K2CO3 and
1.3 ml (12.5 mmol) of Ac2O. The reaction mixture was
boiled till the initial compound disappeared (TLC
monitoring). Then the reaction mixture was neutralized
with a saturated solution of NaHCO3, the reaction
products were extracted into ethyl acetate (3×20 ml).
The organic solutions were combined, washed with
a saturated NaClsolution, with water, dried with MgSO4.
The study was carried out under a financial support
of the Russian Foundation for Basic Research (grants
08-03-97033-r_povolzhe_a, NSh-1725.2008.3).
REFERENCES
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3. Jasperse, C.P., Curran, D.P., and Fevig, T.L., Chem. Rev.,
1991, vol. 91, p. 1237.
Amixture of Z,E-isomers, 1:1, XXIV. Oily substance,
Rf 0.5 (petroleum ether–EtOAc, 2:1). 1H NMR spectrum,
δ, ppm: 1.18 s [1.17 s] (3H, CH3), [1.19 s (3H, CH3)],
[1.20 s (3H, CH3)], 1.45–1.85 m [1.45–1.85 m] (7H, H4,
CH2), 2.10 s [2.08 s] (3H, CH3), 2.25 m (1H, H9), 2.32 m
(1H, H9), 3.40 s [3.45 s] (3H, OCH3), 4.38 s [4.28 s]
(1H, H7), 6.65 s [7.02 s] (1H, =CH).
4. Semenov, A.A., Ocherk khimii prirodnykh soedinenii
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Novosibirsk: Nauka, 2000, p. 664.
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Perkin Trans. 1, 1985, p. 2413.
On distilling off the solvent the residue was dissolved
in a mixture of 10 ml of acetone and 4 ml of water, 0.70 g
of Hg(OAc)2 was added, the reaction mixture was stirred
till the initial compound disappeared (TLC monitoring)
and it was boiled for 4 h. On the completion of the reaction
the solution was diluted with a saturated NaCl solution,
the reaction products were extracted into ethyl acetate
(3×20 ml). The organic solutions were combined, washed
with a saturated NaCl solution, with water, dried with
MgSO4. The solvent was evaporated, and the residue
was subjected to chromatography. Yield 0.19 g (56%) of
ketone XXV. mp 108–109°C, [α]D20 –0.8° (c 0.78, CHCl3),
10. Ferrier, R.J. and Middleton, S., Chem. Rev., 1993, vol. 93,
p. 2779.
1
Rf 0.4 (petroleum ether–EtOAc, 1 : 1). H NMR spec-
trum, δ, ppm: 1.11–1.21 m (2H, CH2), 1.17 s (3H, H8),
1.39 s (3H, H1), 1.55 m (1H, CH2), 1.82 m (2H, CH2),
2.0 m (1H, CH), 2.05 m (1H, CH2), 2.18 s (3H, CH3),
2.75 d.d.d (1H, H5, J 7.4, 6.4, 3.6 Hz), 4.01 d (1H, H2,
J 4.0 Hz), 5.97 d (1H, H3, J 4.0 Hz). 13C NMR spectrum,
δ, ppm: 19.90 (C6), 20.54 (CH3), 23.99 (CH3), 26.65
(CH3), 31.13 (C10), 31.63 (C7), 33.81 (C9), 46.96 (C5),
70.01 (C1), 74.43 (C2), 76.57 (C8), 78.26 (C3), 169.37
11. Cook, S.L. and Secrist, III, J.A. J. Am. Chem. Soc., 1979,
vol. 106, p. 1554.
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Valeev, F.A., and Tolstikov, G.A., Khimiya v interesakh
ustoichivogo razvitiya (Chemistry in View of Stable
Development), 2007, vol. 15, p. 269.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 2 2010