Prostanoids: LXXXVI. Synthesis and reductive transformations of 2-chloro-4,4-ethylenedioxy-3-phenyl-sulfanyl-2-cyclopentenone

Article abstract of DOI:10.1023/B:RUJO.0000010567.22691.a5

The reduction of 2-chloro-4,4-ethylenedioxy-3-phenylsulfanyl-2- cyclopentenone with sodium tetrahydridoborate in ethanol yields 3-chloro-4-hydroxy-2-phenylsulfanyl-2-cyclopentenone, while with the use of lithium aluminum hydride in tetrahydrofuran or the

Full text of DOI:10.1023/B:RUJO.0000010567.22691.a5

Russian Journal of Organic Chemistry, Vol. 39, No. 10, 2003, pp. 1489 1492. Translated from Zhurnal Organicheskoi Khimii, Vol. 39, No. 10, 2003,
pp. 1558 1560.
Original Russian Text Copyright
2003 by Ivanova, Khusainova, Shangiraeva, Akhmetvaleev, Miftakhov.
Prostanoids: LXXXVI.* Synthesis and Reductive
Transformations of 2-Chloro-4,4-ethylenedioxy-3-phenyl-
sulfanyl-2-cyclopentenone
N. A. Ivanova, A. A. Khusainova, F. G. Shangiraeva,
R. R. Akhmetvaleev, and M. S. Miftakhov
Institute of Organic Chemistry, Ufa Research Center, Russian Academy of Sciences,
pr. Oktyabrya 71, Ufa, 450054 Bashkortostan, Russia
e-mail: bioreg@anrb.ru
Received April 17, 2002
Abstract The reduction of 2-chloro-4,4-ethylenedioxy-3-phenylsulfanyl-2-cyclopentenone with sodium tetra-
hydridoborate in ethanol yields 3-chloro-4-hydroxy-2-phenylsulfanyl-2-cyclopentenone, while with the use
of lithium aluminum hydride in tetrahydrofuran or the system Zn/NH4Cl in methanol products of more
profound reduction are obtained.
Oxygenated cyclopentenes having a phenyl vinyl
sulfone fragment attract interest as central cyclopen-
tenone building blocks in the synthesis of prostanoids
according to the triple convergent coupling scheme
[2 4]. With the goal of developing approaches to such
compounds on the basis of hexachloropentadiene
derivatives, in the present work we examined the
reduction of phenylsulfanylcyclopentenone II under
various conditions. Compound II was synthesized
in more than 80% yield by reaction of previously
reported 2,3-dichloro-4,4-ethylenedioxy-2-cyclopente-
none (I) [5] with sodium benzenethiolate in methanol
(Scheme 1). The minor product of this reaction was
2,3-bis(phenylsulfanyl) derivative III ( 10%) which
can readily be converted into symmetric diketone IV
by acid hydrolysis (yield (87%).
We examined the reduction of cyclopentenone II
with the use of NaBH4 in ethanol, LiAlH4 in THF,
Scheme 2.
Scheme 1.
III, R = OCH2CH2O; IV, RR = O.
____________
*
For communication LXXXV, see [1].
1070-4280/03/3910-1489$25.00 2003 MAIK Nauka/Interperiodica

1490
IVANOVA et al.
likely to result from successive reduction of the
Scheme 3.
ketone group in II to hydroxy, saturation of the
double bond in V via hydride transfer, and stabiliza-
tion of anion IX by opening of the dioxolane ring.
Reductive elimination of the chlorine atom and sub-
sequent protonation of enolate X lead to formation
of final product VII (Scheme 3).
Presumably, the initial stage in the reaction of
sulfide II with Zn/NH4Cl in MeOH is reductive
elimination of the phenylsulfanyl group. Next follows
Michael addition of methanol to enone XI and syn-
chronous elimination of the chlorine atom from sp2-
hybridized carbon atom and opening of the dioxolane
ring. Transetherification of enol ether XII with MeOH
yields 3,4-dimethoxycyclopentenone VIII (Scheme 4).
3-Chloro-4-hydroxy-2-phenylsulfanyl-2-cyclopente-
none (VI) obtained by reduction of ketone II with
sodium tetrahydridoborate is promising as inter-
mediate product in the syntheses of prostanoids,
which we plan to perform.
and Zn/NH4Cl in MeOH. The hydride reducing agents
were found to afford different reduction products.
In the reduction with sodium tetrahydridoborate,
followed by treatment of the reaction mixture with
acetone, we isolated expected alcohol V and hydroxy-
cyclopentenone VI (Scheme 2). The latter was the
only product when the reaction mixture was subjected
to acid hydrolysis. Ready hydrolysis of related acetals
in neutral media was also observed by us previously
[6, 7]; this process is favored by intramolecular assist-
ance by the existing hydroxy group.
The reduction of compound II with LiAlH4 in
tetrahydrofuran gave an anomalous product, hydroxy-
cyclopentene VII. Unusual reduction product, di-
methoxy derivative VIII, was also obtained by
heating of cyclopentenone II with Zn/NH4Cl in
MeOH (Scheme 2). Probable mechanisms of forma-
tion of anomalous reduction products VII and VIII
are of undoubted interest. The transformation II VII
was presumed to involve intermediate X which is
EXPERIMENTAL
The IR spectra were recorded on UR-20 and
Specord M-80 spectrometers from samples prepared
as thin films or suspensions in mineral oil. The 1H and
13C NMR spectra were obtained on a Bruker AM-300
spectrometer (300.13 and 75.47 MHz, respectively)
using CDCl3 as solvent and reference ( 7.27 ppm,
77.00 ppm). The mass spectra (electron impact,
2C0 and 70 eV) were run on an MKh-1306 instrument
(ion source temperature 75 100 C). The progress of
reactions was monitored by TLC using Silufol plates
(eluent hexane ethyl acetate); spots were visualized
by treatment with an alkaline solution of potassium
permanganate [8].
Reaction of 2,3-dichloro-2-cyclopentenone (I)
with sodium benzenethiolate. Benzenethiol, 1.1 g
(10 mmol), was added with stirring to a solution of
0.54 g (10 mmol) of sodium methoxide in 10 ml of
methanol, and a solution of 1.4 g (6.7 mmol) of
ketone I in 15 ml of methanol was added dropwise.
The mixture was stirred for 1 h, an equal volume of
water was added, and the mixture was extracted with
chloroform (3 30 ml). The combined extracts were
washed with a saturated aqueous solution of sodium
chloride (3 10 ml) and dried over MgSO4, and the
solvent was distilled off. Recrystallization of the
residue from petroleum ether ethyl acetate (1 :1)
gave 1.71 g (85%) of sulfide II. The mother liquor
was evaporated, and the residue was subjected to
chromatography to isolate 0.2 g (10%) of bis-sulfide
III. Compound III was kept for 2 h in a 1:1 mixture
Scheme 4.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 39 No. 10 2003

PROSTANOIDS: LXXXVI.
1491
of methanol with 10% hydrochloric acid at room tem-
perature. We thus isolated diketone IV in 87% yield.
4.60 br.s (1H, 4-H), 7.10 7.3 m (5H, C6H5). 13C
NMR spectrum, C, ppm: 45.22 (C5), 66.13 and 65.76
(CH2O), 70.96 (C1), 115.20 (C4), 146.88 (C2), 130.14
(C3), 128.01 (Cp), 129.09 (Co), 129.95 (Cm), 132.19
(Ci). Found, %: C 54.74; H 4.53; Cl 12.28; S 11.18.
C13H13ClO3S. Calculated, %: C 54.83; H 4.61;
Cl 12.45; S 11.26.
2-Chloro-4,4-ethylenedioxy-3-phenylsulfanyl-2-
1
cyclopentenone (II). mp 65 C. IR spectrum, , cm :
1
1580, 1732. H NMR spectrum, , ppm: 2.75 s (2H,
5-H), 3.72 m (2H, CH2O), 3.91 m (2H, CH2O), 7.35
7.58 m (5H, C6H5). 13C NMR spectrum, C, ppm:
47.02 (C5), 65.74 (CH2O), 110.54 (C4), 126.82 (C2),
128.79 (Co), 129.50 (Cp), 132.14 (Ci), 135.18 (Cm),
163.43 (C3), 192.19 (C1). Mass spectrum: m/z 282.
Found, %: C 55.41; H 3.83; Cl 12.38; S 11.24.
C13H11ClO3S. Calculated, %: C 55.22; H 3.92;
Cl 12.54; S 11.34.
3-Chloro-4-hydroxy-2-phenylsulfanyl-2-cyclo-
penten-1-one (VI). Yellow oily substance. IR spec-
1
1
trum, , cm : 1590, 1630, 3400. H NMR spectrum,
, ppm: 2.50 d.d (1H, 5-H, J = 3, 18 Hz), 2.90 d.d
(1H, 5-H, J = 6, 18 Hz), 3.44 br.s (1H, OH), 4.77 br.s
(1H, 4-H), 7.10 7.40 m (5H, C6H5). 13C NMR spec-
trum, C, ppm: 44.42 (C5), 73.50 (C4), 126.83 (Cp),
128.09 (Co), 131.81 (Ci), 134.82 (Cm), 146.88 (C2),
167.31 (C3), 197.36 (C1). Found, %: C 55.02; H 3.92;
Cl 14.95; S 13.41. C11H9ClO2S. Calculated, %:
C 54.89; H 3.77; Cl 14.73; S 13.32.
4,4-Ethylenedioxy-2,3-bis(phenylsulfanyl)-2-
cyclopentenone (III). Colorless oily substance. IR
1
1
spectrum, , cm : 1575, 1730. H NMR spectrum,
, ppm: 2.70 s (2H, CH2), 3.61 m (2H, CH2O),
3.75 m (2H, CH2O), 7.10 7.40 m (10H, C6H5). 13C
3-(2-Hydroxyethoxy)-4-phenylsulfanyl-3-cyclo-
penten-1-ol (VII). A solution of 0.2 g (0.7 mmol) of
ketone II in 2 ml of anhydrous THF was added drop-
wise to a suspension of 0.03 g (0.84 mmol) of LiAlH4
in 5 ml of anhydrous diethyl ether, while stirring at
room temperature under argon. The mixture was
stirred for 3 h, 3 ml of water was added, and the
product was extracted into chloroform (3 10 ml).
The combined organic extracts were washed with
a saturated solution of sodium chloride, dried over
MgSO4, and evaporated. The residue was subjected
to chromatography on silica gel using chloroform
methanol (40:1) as eluent. Yield 0.10 g (56%). Color-
NMR spectrum, C, ppm: 47.77 (C5), 65.58 (CH2O),
111.17 (C4), 126.64 and 128.88 (Cp), 128.29 and
129.49 (Ci), 128.68 and 128.79 (Co), 129.49 and
132.12 (Cm), 132.10 (C2), 169.52 (C3), 195.53 (C1).
Found, %: C 64.10; H 4.69; S 18.17. C19H16O3S2.
Calculated, %: C 64.02; H 4.52; S 17.99.
2,3-Bis(phenylsulfanyl)-2-cyclopentene-1,4-dione
1
(IV). Colorless oily substance. IR spectrum, , cm :
1
1745. H NMR spectrum, , ppm: 3.05 s (2H, CH2),
7.22 7.35 m (10H, C6H5). 13C NMR spectrum,
,
C
ppm: 42.64 (C5), 128.45 (Ci), 128.65 (Ci), 128.68
(Cp), 128.91 (Co), 132.51 (Cm), 152.54 (C2, C3),
192.43 (C1, C4). Found, %: C 65.12; H 3.79; S 20.63.
C17H12O2S2. Calculated, %: C 65.25; H 3.87; S 20.52.
1
less oily substance. IR spectrum, , cm : 1590, 1740.
1H NMR spectrum, , ppm: 2.20 d (1H, 2-H, J =
15.4 Hz), 2.72 d.d (1H, 2-H, J = 15.4, 6.3 Hz), 2.43 d
(1H, 4-H, J = 16.7 Hz), 2.75 d.d (1H, 4-H, J = 16.7,
6.6 Hz), 3.60 br.s (4H, CH2O, OH), 3.91 br.s (2H,
CH2O), 4.30 m (1H, 1-H), 7.01 7.23 m (5H, C6H5).
Reduction of ketone II with NaBH4. Sodium
tetrahydridoborate, 0.03 g (0.8 mmol) was added at
0 C to a solution of 0.56 g (2 mmol) of ketone II in
10 ml of methanol. The mixture was stirred for 1 h,
3 ml of acetone was added, and the mixture was
evaporated. Water, 10 ml, was added to the residue,
the product was extracted into methylene chloride,
the extract was dried over MgSO4 and evaporated, and
the residue was subjected to chromatography on silica
gel using petroleum ether ethyl acetate (8:2) as
eluent. We isolated 0.47 g (82%) of hydroxy acetal V
and 0.06 g (13%) of enone VI. Compound VI was
obtained in 89% yield when the reaction mixture was
treated with 5 ml of 5% hydrochloric acid.
13C NMR spectrum, C, ppm: 40.51 (C2); 42.90 (C5);
60.24 (CH2OH); 67.15 (C1); 71.15 (CH2O); 97.79
(C3); 125.26, 127.37, 128.67, 135.46 (C6H5); 158.45
(C4). Found, %: C 62.01; H 6.55. C13H16O3S. Calcu-
lated, %: C 61.89; H 6.39; S 12.71.
3,4-Dimethoxy-2-cyclopentenone (VIII). A mix-
ture of 0.20 g (0.7 mmol) of ketone II and 0.5 g
(7.7 mmol) of zinc dust in 5 ml of anhydrous MeOH
was heated under reflux until the conversion of the
initial ketone was complete (3 h, TLC). The mixture
was diluted with chloroform, filtered from zinc,
washed with a saturated solution of sodium chloride,
dried over MgSO4, and evaporated. The residue was
subjected to chromatography on silica gel using
2-Chloro-4,4-ethylenedioxy-3-phenylsulfanyl-2-
cyclopenten-1-ol (V). Yellow oily substance. IR spec-
1
1
trum, , cm : 1615, 3400. H NMR spectrum,
,
ppm: 2.11 d (1H, 5-HA, J = 4, 16 Hz), 2.6 d.d (1H,
5-HB, J = 4, 16 Hz), 3.70 3.90 m (4H, CH2O),
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 39 No. 10 2003

1492
IVANOVA et al.
benzene methanol (9:1) as eluent. Yield 0.11 g
2. Donaldson, R.E. and Fuchs, P., J. Am. Chem. Soc.,
1
1
1981, vol. 103, no. 8, p. 2108.
(59%). IR spectrum, , cm : 1605, 1740. H NMR
spectrum, , ppm: 2.40 d.d (1H, 5-H, J = 2.4,
17.7 Hz), 2.72 d.d (1H, 5-H, J = 6.6, 17.7 Hz), 3.47 s
(3H, OMe), 3.92 s (3H, OMe), 4.45 d.d (1H, 4-H, J =
2.4, 6.6 Hz), 5.37 s (1H, 2-H). 13C NMR spectrum,
C, ppm: 41.35 (C5), 57.74 (OMe), 59.02 (OMe),
77.04 (C4), 105.77 (C2), 186.95 (C3), 201.12 (C1).
Found, %: C 88.67; H 11.33. C8H12. Calculated, %:
C 88.82; H 11.18.
This study was financially supported by the Rus-
sian Foundation for Basic Research (project no. 99-
03-32915a) and by the Integration Federal Special-
Purpose Program (project no. 30344).
3. Saddler, J.C. and Fuchs, P.L., J. Am. Chem. Soc.,
1981, vol. 103, no. 8, p. 2112.
4. Donaldson, R.E., Saddler, J.C., Burn, S., Mcken-
zie, A.T., and Fuchs, P.L., J. Org. Chem., 1983,
vol. 48, no. 13, p. 2167.
5. Akhmetvaleev, R.R., Imaeva, L.R., Belogaeva, T.A.,
and Miftakhov, M.S., Izv. Ross. Akad. Nauk, Ser.
Khim., 1997, no. 9, p. 1699.
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