Prostanoids: LXXXVII. Synthesis of 3-hydroxy-2-phenylsulfonyl-2- cyclopentenone and its ethylene acetal

Article abstract of DOI:10.1023/B:RUJO.0000013142.41402.19

By oxidation of 3-phenylmercapto-2-chloro-4,4-ethylenedioxycyclopet-2-en-1- one with H₂O₂ in AcOH (or with In-ClC₆H ₄CO₃H in CH₂Cl₂) was obtained 2-chloro-3-phenylsulfonyl-4,4-et

Full text of DOI:10.1023/B:RUJO.0000013142.41402.19

Russian Journal of Organic Chemistry, Vol. 39, No. 11, 2003, pp. 1652 1655. Translated from Zhurnal Organicheskoi Khimii, Vol. 39, No. 11, 2003,
pp. 1721 1724.
Original Russian Text Copyright
2003 by Ivanova, Shangiraeva, Miftakhov.
Prostanoids: LXXXVII.*
Synthesis of 3-Hydroxy-2-phenylsulfonyl-2-cyclopentenone
and Its Ethylene Acetal
N. A. Ivanova, F. G. Shangiraeva, and M. S. Miftakhov
Institute of Organic Chemistry, Ufa Scientific Center, Russian Academy of Sciences, Ufa, 450054 Russia
Received July 19, 2002
Abstract By oxidation of 3-phenylmercapto-2-chloro-4,4-ethylenedioxycyclopet-2-en-1-one with H2O2 in
AcOH (or with m-ClC6H4CO3H in CH2Cl2) was obtained 2-chloro-3-phenylsulfonyl-4,4-ethylenedioxycyclo-
pent-2-en-1-one which on reduction with NaBH4 or LiAlH4 afforded respectively 3-hydroxy-2-phenyl-
sulfonylcyclopent-2-en-1-one and its ethyleneketal.
We described formerly a convenient preparation of
phenylmercaptocyclopentenone (I) from hexachloro-
cyclopentadiene [1]. The present paper reports on
conversion of compound I into sulfones II and III.
The latter are aimed to be used as the central cyclo-
pentenone building blocks in designing prostaglandine
structures along the scheme of the triple convergent
coupling [2, 3]. This approach based on a one-pot
addition of the - and -chains of prostaglandine to
appropriate cyclopentenone derivatives is among the
well-known and efficient procedures of prosta-
glandine syntheses [4, 5].
SO2Ph group should be achieved by reduction with
common reagents.
Several common reagents were tested in oxidation
of sulfide I. Sulfoxide IV formed selectively when
heating at reflux with 10 equiv of H2O2, but conver-
sion of the initial compound I did not exceed here
25%. Only traces of sulfoxide were obtained with
Na2WO4 2H2O (TLC). We succeeded in selective
preparation both of the desired sulfone V and the
product of compound I incomplete oxidation, sulf-
oxide IV, applying an oxidative system H2O2 HOAc
and varying the substrate to oxidant ratio and the
reaction time. Sulfoxide IV is also fit for the use in
syntheses because such sulfoxides can be brought into
conjugate addition reaction with organometallic
compounds [6, 7]. The structure of compounds IV
and V was proved by IR and 13C NMR spectra and
on comparison of their Rf on Silufol plates (sulfoxides
are known to be more polar than sulfones). The most
characteristic signals in the 13C NMR spectra of
sulfoxide IV and sulfone V are those of C3 at
165.2 and 156.8 ppm respectively.
The first approach suggested to convert I into the
target compounds II, III by reduction of enone I oxo
function with LiAlH4 or NaBH4 did not result in the
desired products [1]. Therefore it was decided to start
with oxidation of the phenylmercapto group into
phenylsulfonic group hoping that in sulfone V the
elimination of the vinyl chlorine atom activated by
The oxidation of sulfide I with m-ClC6H4CO3H
afforded sulfone V in high yield.
In acetone solution dimethyldioxirane [8] under
mild conditions oxidized sulfide I to the correspond-
ing sulfone V in an almost quantitative yield (95%)
(see table).
After development of an optimum procedure of
sulfone V preparation we started looking for the
method of its conversion into the target sulfones II
and III. The reduction of sulfone V with NaBH4
depending on reaction temperature and workup
*
For preceding communication see [1].
1070-4280/03/3911-1652$25.00 2003 MAIK Nauka/Interperiodica

PROSTANOIDS: LXXXVII.
1653
Oxidation of 3-phenylmercapto-2-chloro-4-ethylenedioxycyclopent-2-en-1-one (I) with various oxidants
Oxidant
solvent
Substrate/
oxidant, mol
Yield, %
Temperature,
C
Time, min (h)
(compounds ratioa IV:V)
H2O2 AcOHc
1: 3
1: 3
1: 5
1: 5
1: 10
1: 15
1: 10
118
118
118
118
118
118
56
10
40
10
80
40
40
(6)
55 (1: 0)
55 (9: 1)
70 (3: 2)
65 (2: 3)
30 (0: 1)
82 (0: 1)
10d (1: 0)
b
H2O2 AcOH
H2O2 AcOH
H2O2 AcOH
H2O2 AcOH
H2O2 AcOH
H2O2 Me2CO
11: 2
20
30
95 (0: 1)
(Me2CO)
H2O2 THF,
Na2WO4.2H2O
ClC6H4CO3H
1: 4: 0.1
1: 3.3
65
20
(10)
90
20d (1: 0)
90 (5: 95)
a
b
c
d
RSO/RSO2 ratio was estimated from 13C NMR spectra.
50% solution of H2O2.
Glacial acetic acid.
Substrate conversion 25%.
procedure provided three different sulfones III, VI,
and VII. The reduction at 0 C followed by quenching
of the reaction mixture with water or acetone afforded
expected alcohol VI, and workup under acid condi-
tions furnished ketoalcohol VII. Sulfone III, the
product of simultaneous reduction, dechlorination,
and removal of the dioxolane protection was obtained
in 75% yield when the reaction was carried out at
room temperature, and the excess of reductant was
quenched with acid. Sulfone V did not undergo
reduction with LiAlH4 at 0 C, and at 20 C a mixture
of alcohol VI and sulfone II was obtained in 2: 3
ratio.
The structure of obtained sulfones II, III, VI, and
VII is well confirmed by spectral data. Their IR
1
spectra contain absorption bands of SO2 (1300 cm )
1
and OH groups (3400 cm ), of C=C C=O moiety
1
(1720 cm ) (III), of a monosubstituted aromatic
1
fragment (700, 760, 1500, 1590, 3080 cm ). The
presence of a vinyl proton in sulfones II and III is
1
evidenced by downfield signals in their H NMR
EXPERIMENTAL
spectra at 6.2 and 6.11 ppm respectively, and also by
doublets at 158.45 and 163.93 ppm in the correspond-
ing 13C NMR spectra.
IR spectra were recorded on spectrophotometeres
UR-20 and Specord M-80 from samples as film or
1
mull in mineral oil. H and 13C NMR spectra were
Thus we developed convenient procedures for
preparation of phenyl cyclopentenyl sulfones II and
III, the key synthons for the planned approach to
prostaglandine synthesis.
registered on spectrometer Bruker AM-300 at operat-
ing frequencies 300.13 and 75.47 MHz respectively
from solutions in CDCl3. The solvent signals were
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 39 No. 11 2003

1654
IVANOVA et al.
77.00 ppm).
used as internal references ( 7.27,
(2H, 2C5H), 4.09 t (2H, CH2O, J 8.5 Hz), 4.44 t
(2H, CH2O, J 8.5 Hz), 7.71 t (2H, J 7.6 Hz, 2Hm),
7.82 t (1H Hz, Hn, J 7.6), 8.02 t (2H, 2Ho, J 7.6 Hz).
13C NMR spectrum, , ppm: 47.68 (C5), 66.35
(2CH2O), 110.45 (C4), 128.41 (Co), 129.16 (Cm),
134.58 (Cp), 140.03 (C2), 143.27 (C3), 156.37 (Ci),
192.37 (C1). Found, %: C 49.32; H 3.78; Cl 11.33;
O 25.33; S 10.24. C13H11ClO5S. Calculated, %:
C 49.61; H 3.52; Cl 11.26; O 25.42; S 10.19.
C
The mass spectra were measured on MKh-1306
device, ionizing electrons energy 20 and 70 eV,
ionizing chamber temperature 75 100 C. The reac-
tion progress was monitored by TLC on Silufol
plates, eluent hexane ethyl acetate. The spots were
visualized with the use of anisaldehyde or alkaline
solution of KMnO4 [9].
Oxidation of sulfide I. (a) With H2O2 in AcOH.
To a solution of 1.1 g (3.85 mmol) of sulfide I in
15 ml of AcOH was added 3.3 ml (58.4 mmol) of
50% solution of H2O2, and the reaction mixture was
heated at reflux (the reaction conditions and products
yield see table). The reaction mixture was evaporated,
diluted with 15 ml of a saturated Na2SO3 solution,
the products were extracted into CHCl3 (3 30 ml).
The combined organic extracts were washed in succes-
sion with saturated solutions of Na2SO3, NaHCO3,
and NaCl, dried over MgSO4, and evaporated.
Sulfone V was obtained by recrystallization of the
residue from ethyl acetate. Sulfoxide IV was isolated
by column chromatography on silica gel (eluent
petroleum ether ethyl acetate, 9: 1) of the residue
after evaporation of the mother liquor.
Reaction of sulfone V with NaBH4. (a) To a
solution of 0.2 g (0.64mmol) of sulfone V in ethanol
THF mixture (1: 1 by volume) was added at 0 C
0.024 g (0.64 mmol) of NaBH4. The reaction mixture
was stirred for 20 min, and then treated as follows.
(1) To the reaction mixture was added 3 ml of
acetone, the reaction products were extracted into
CHCl3 (3 10 ml), the combined organic solutions
were washed with H2O, dried with MgSO4, evaporat-
ed, the residue was subjected to chromatography on
SiO2 (eluent petroleum ether ethyl acetate, 7: 3). We
obtained 0.12 g (60%) of alcohol VI.
(2) To the reaction mixture was added 5 ml of 5%
hydrochloric acid. The mixture was evaporated, the
residue was diluted with 10 ml of H2O, the reaction
product was extracted into CHCl3 (3 10 ml), the
combined extracts were washed with H2O, dried with
MgSO4, evaporated, and subjected to chromato-
graphy (eluent petroleum ether ethyl acetate, 7: 3).
We obtained 0.12 g (70%) of ketoalcohol VII.
(b) With m-chloroperbenzoic acid. To a solution
of 3.92 g (11.33 mmol) of 50% m-chloroperbenzoic
acid in 15 ml of CH2Cl2 at 20 C was added drop-
wise 1.0 g (3.54 mmol) of sulfide I in 15 ml of
CH2Cl2. After stirring for 6 h the reaction mixture
was filtered, diluted with 15 ml of CH2Cl2, and
washed with H2O. The organic products from the
water layer were extracted with 30 ml of CH2Cl2,
and the combined organic solutions were washed with
NaHCO3 till neutral washings, dried over MgSO4,
and evaporated. The recrystallization from ethyl
acetate afforded 0.8 g (72%) of sulfone V.
(b) To a solution of 0.2 g (0.64 mmol) of sulfone
V in ethanol THF mixture (1: 1 by volume) was
added at 20 C 0.024 g (0.64 mmol) of NaBH4. The
reaction mixture was stirred for 20 min, and then
10 ml of 5% hydrochloric acid was added, and the
mixture was evaporated. The residue was diluted with
10 ml of H2O, the reaction product was extracted into
CHCl3 (3 10 ml), the combined extracts were
washed with H2O, dried with MgSO4, evaporated,
and subjected to chromatography (eluent petroleum
ether ethyl acetate, 7: 3). We obtained 0.12 g (75%)
of alcohol III.
3-Phenylsulfinyl-2-chloro-4,4-ethylenedioxy-
cyclopent-2-en-1-one (IV), mp 185 187 C (from
1
ethylacetate). IR spectrum, cm : 1728, 1584, 1216,
1
1148, 1024. H NMR spectrum, , ppm: 2.89 s (2H,
2H5), 4.08 s (2H, CH2O), 4.36 d (2H, CH2O, J
6.98 Hz), 7.55 m (3H arom), 7.86 m (2H arom).
13C NMR spectrum, , ppm: 48.15 (C5), 66.78
(CH2O), 66.95 (CH2O), 110.89 (C4), 125.68 (Co),
129.43 (Cp), 131.91 (Cm), 137.84 (C2), 141.91 (C3),
163.43(Ci), 192.31(C1). Found, %: C 52.41; H 3.83;
Cl12.08; O20.74; S10.94. C13H11ClO4S. Calcd., %:
C 52.27; H 3.71; Cl 11.87; O 21.42; S 10.73.
3-Phenylsulfonyl-2-chloro-4,4-ethylenedioxy-
cyclopent-2-en-1-ol (VI). Colorless oily substance.
1
IR spectrum, cm : 1342, 1615, 3400. 1H NMR spec-
trum, , ppm: 2.11 d.d (1H, H5A, J 4 and 16 Hz),
2.6 d.d (1H, H5B, J 4 and 16 Hz), 3.70 3.90 m (4H,
2CH2O), 4.60 br.s (1H, H4 ), 7.10 7.3 m (5H arom).
13C NMR spectrum, , ppm: 45.22 (C5), 66.13 and
65.76 (2CH2O), 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 49.74; H 4.53;
3-Phenylsulfonyl-2-chloro-4,4-ethylenedioxy-
cyclopent-2-en-1-one (V), mp 165 166 C (from
1
ethyl acetate). IR spectrum, cm : 1012, 1084, 1192,
1320, 1600, 1736. 1H NMR spectrum, , ppm: 2.86 s
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 39 No. 11 2003

PROSTANOIDS: LXXXVII.
1655
1
1
Cl 11.28; O 25.12; S 9.33. C13H13ClO5S. Calculat-
ed, %: C 49.29; H 4.14; Cl 11.19; O 25.25; S 10.12.
cm : 1340, 1590, 3390. H NMR spectrum, , ppm:
2.20 d.d (1H, 2H5A, J 15.4 and 6.3 Hz) and 2.72 d.d
(1H, 2H5ß, J 15.4 and 6.3 Hz), 3.91 4.32 m (5H,
2CH2O, OH), 4.60 m (1H, H1), 6.17 m (1H, H3)
7.01 7.23m (5H arom). 13C NMR spectrum, , ppm:
46.59 (C5), 65.78 (CH2O), 66.32(CH2O), 71.15(C1),
114.74 (C4), 125.26, 127.37, 128.67, 135.46
(C arom), 142.01 (C2), 158.45 (C3). Found, %: C
55.42; H 5.25; O 27.84; S 11.49. C13H14O5S.
Calculated, %: C 55.31; H 5.00; O 28.34; S 11.36.
4-Hydroxy-2-phenylsulfonyl-3-chlorocyclopent-
1
2-en-1-ol (VII). mp 111 113 C. IR spectrum, cm :
1
1344, 1584, 1733, 3400. H NMR spectrum, , ppm:
2.23 m (2H, H5), 4.39 m (1H, H4), 7.50 m (2Ho),
7.57 m (1Hp), 7.96 (2Hm). 13C NMR spectrum, ,
ppm: 45.22 (C5), 78.59 (C4), 129.10 (Cp), 130.39
(Co), 133.92 (Ci), 134.82 (Cm), 148.02 (C2), 176.95
(C3), 195.92 (C1). Found, %: C 48.22; H 3.17;
Cl12.95; O24.18; S 11.48. C11H9ClO4S. Calculated,
%: C 48.45; H 3.33; Cl 13.00; S 11.76.
The study was carried out under financial support
of the Russian Foundation for Basic Research (grant
no. 02-03-32594a).
4-Hydroxy-2-phenylsulfonylcyclopent-2-en-1-ol
1
(III). Yellow oily substance. IR spectrum, cm :
1
REFERENCES
1344, 1696, 1712, 3400. H NMR spectrum, , ppm:
3.0 br.s (1H, OH), 3.15 m (2H, 2H5), 4.32 m (1H,
H4), 6.11 m (1H, H3), 7.7 m (2Ho), 7.77 m (1Hp),
7.88 m (2Hm). 13C NMR spectrum, , ppm: 30.73
(C5), 65.35 (C4), 128.91, 133.1, 134.23, 136.32
(C arom), 138.32 (C2), 163.92 (C3), 197.25 (C1).
Found, %: C 55.02; H 3.92; O 26.53; S 13.41.
C11H10O4S. Calculated, %: C 55.45; H 4.23;
O 26.86; S 13.46.
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Reaction of sulfone V with LiAlH4. To a disper-
sion of 0.03 g (0.78 mmol) of LiAlH4 in 3 ml of
anhydrous ether at room temperature was added in
argon flow dropwise 0.2 g (0.64 mmol) of sulfone V
solution in 6 ml of anhydrous THF. The reaction
mixture was stirred for 6 h at 60 C, cooled to 0 C,
3 ml of water was added, the reaction product was
extracted into chloroform (3 10 ml). The combined
organic solutions were washed with saturated solu-
tion of NaCl, dried over MgSO4, and evaporated.
The residue was subjected to chromatography (eluent
petroleum ether ethyl acetate, 7: 3). We obtained
0.08 g (45%) of sulfone VI and 0.06 g (30%) of
sulfone II.
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3-Phenylsulfonyl-4,4-ethylenedioxycyclopent-2-
en-1-ol (II). Yellow oily substance. IR spectrum,
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 39 No. 11 2003