Magnesium amide-induced pummerer-type reactions of cyclopropyl sulfoxides. Synthesis of cyclopropanone dithioacetals

Article abstract of DOI:10.1246/bcsj.75.1367

The reaction of cyclopropyl phenyl sulfoxide with a magnesium amide, generated from ethylmagnesium bromide and diisopropylamine, gave 1-(phenylthio)cyclopropanol in 72% yield. When the diisopropylmagnesium reagent was treated with a thiol prior to an interaction with cyclopropyl phenyl sulfoxides, symmetrical and unsymmetrical cyclopropanone dithioacetals were produced in fair yields along with small quantities of the corresponding 1-(phenylthio)cyclopropanols.

Full text of DOI:10.1246/bcsj.75.1367

Bull. Chem.
Soc. Jpn.
75
6
© 2002 The Chemical Society of Japan
Bull. Chem. Soc. Jpn., 75, 1367–1369 (2002) 1367
The Chemical
Society of Ja-
pan
The Chemical
Society of Ja-
pan
OB
Magnesium Amide-Induced Pummerer-Type Reactions of Cyclopropyl
Sulfoxides. Synthesis of Cyclopropanone Dithioacetals
Synthesis of Cyclopropanone Dithioacetals
K. Kobayashi et al.
6
15
Kazuhiro Kobayashi,* Masatoshi Horita, Susumu Irisawa, Akihiro Matsunaga, Osamu Morikawa,
2002
1367
1369
BCSJA8
0009-2673
01441
12
and Hisatoshi Konishi
Department of Materials Science, Faculty of Engineering, Tottori University, Koyama-minami, Tottori 680-8552
(Received December 13, 2001)
13
2001
2
25
2002
The reaction of cyclopropyl phenyl sulfoxide with a magnesium amide, generated from ethylmagnesium bromide
and diisopropylamine, gave 1-(phenylthio)cyclopropanol in 72% yield. When the diisopropylmagnesium reagent was
treated with a thiol prior to an interaction with cyclopropyl phenyl sulfoxides, symmetrical and unsymmetrical cyclopro-
panone dithioacetals were produced in fair yields along with small quantities of the corresponding 1-(phenylthio)cyclo-
propanols.
4.10
In our previous paper we described that the reactions of sul-
foxides bearing α-hydrogens 1 with magnesium amides, gen-
erated in situ by a treatment of ethylmagnesium bromide with
secondary amines, such as diisopropylamine or 2,2,6,6-tetra-
methylpiperidine in diethyl ether, afforded the corresponding
symmetrical dithioacetals 3 via Pummerer-type carbonium ion
intermediates 2 (Scheme 1).1 We have also reported that the
reaction of sulfoxides 1 with various thiols in the presence of a
bis(phenylthio)cyclopropane (7) could be detected (Scheme 2).
It can be assumed that no production of 7 is due to the low sta-
bility of the cyclopropyl carbonium ion intermediate. de Boer
et al. have reported on the preparation of 1-(alkylthio)cyclo-
propanols4 and their transformation into 1-substituted cyclo-
propyl sulfides with a variety of nucleophiles. They synthe-
sized 1-(alkylthio)cyclopropanols using cyclopropanones and
thiols. Although this method appears to be convenient, cyclo-
propanones are unstable and difficult to handle.
magnesium amide gave unsymmetrical dithioacetals
4
(Scheme 1).2 As an extension of these studies, we examined
the reactions of cyclopropyl phenyl sulfoxides with magne-
sium amides. In this paper, we describe the results of our in-
vestigation, which offer simple routes to 1-(phenylthio)cyclo-
propanol and cyclopropanone dithioacetals. Several reports on
Pummerer-type reactions of cyclopropyl sulfoxides have been
recorded previously.3 However, to the best of our knowledge,
no application to the preparation of cyclopropanone dithioace-
tals has been reported.
We began our investigation by first examining the reaction
between cyclopropyl phenyl sulfoxide (5) with magnesium
amides. Sulfoxide 5 was treated with a magnesium amide,
generated from ethylmagnesium bromide (4 molar amounts)
and diisopropylamine (8 molar amounts) overnight at room
temperature.1 After the usual workup, purification of the crude
product by preparative TLC on silica gel afforded 1-(phenyl-
thio)cyclopropanol (6) in good yield, and no trace amounts of
We next found that when the (diisopropylamino)magnesium
reagent was treated with a thiol prior to an interaction with cy-
clopropyl phenyl sulfoxide (5), cyclopropane dithioacetals 8a–
d were obtained in fair yields along with small quantities of 1-
(phenylthio)cyclopropanol (6), as shown in Scheme 3. Reac-
tions of 5 with magnesium amide-thiol reagents, generated
from various ratios of ethylmagnesium bromide, diisopropyl-
amine, and a thiol, were initially examined. The use of 6 molar
amounts each of ethylmagnesium bromide and diisopropyl-
amine, and 4 molar amounts of thiols was found to be most ef-
fective for the production of 8. Cyclopropanone dithioacetals
have been synthesized by, for example, 1) the addition of di-
bromocarbene to olefins, followed by an exchange of the bro-
mines of the resulting dibromocyclopropanes by RS groups;5
2) the base-induced cyclopropanation of 1,1,3-tris(phenyl-
thio)alkanes6 or 3) the reaction of sulfur-stabilized anions with
ketene bis(phenylthio)acetal [1,1-bis(phenylthio)ethylene].7
Scheme 1.

1368 Bull. Chem. Soc. Jpn., 75, No. 6 (2002)
Synthesis of Cyclopropanone Dithioacetals
Scheme 2.
Scheme 3.
Scheme 4.
1
ries FT IR spectrometer. The H NMR spectra were determined
using SiMe4 as an internal reference with a JEOL JNM-GX270 FT
NMR spectrometer operating at 270 MHz in CDCl3. Low-resolu-
tion mass spectra were recorded on a JEOL AUTOMASS 20 spec-
trometer (Center for Joint Research and Development, this Uni-
versity). High-resolution mass spectra were performed on a JEOL
JMS-AX505 HA spectrometer (Faculty of Agriculture, this Uni-
versity). Thin layer chromatography (TLC) was carried out on
Merck Kieselgel 60 PF254. All of the solvents used were dried
over appropriate drying agents and distilled under argon prior to
use.
Transformations of cyclopropanone dithioacetals into other
useful organic compounds have also been reported.5,8
Subsequently, a similar treatment of 2,2-dimethylcyclopro-
pyl phenyl sulfoxide (9) with the magnesium amide in the
presence of 4-methylbenzenethiol under the above-mentioned
conditions gave the expected dithioacetal 12 along with 2,2-
dimethyl-1-(phenylthio)cyclopropanol (13) and 2-methyl-4-(4-
methylphenylthio)-3-phenylthio-2-butene (14), as illustrated in
Scheme 4. The formation of 14 can be explained by a rear-
rangement of the cyclopropyl carbonium ion intermediate 10
to the stable allyl carbonium ion intermediate 11.
In conclusion, the present magnesium amide-mediated
Pummerer-type reactions can provide convenient methods for
preparing 1-(phenylthio)cyclopropanol and cyclopropanone
dithioacetals. The present methods may find some value in or-
ganic synthesis because of simple manipulations as well as the
ready availability of the starting materials.
Starting Materials. Cyclopropyl phenyl sulfoxide (5) and
2,2-dimethylcyclopropyl phenyl sulfoxide (9) were prepared fol-
lowing procedures reported by Oae et al.3b All other chemicals
used in this study were commercially available.
1-(Phenylthio)cyclopropanol 6.4 To a solution of EtMgBr
(4.0 mmol) in Et2O (5 mL) at 0 °C under argon was added i-
Pr2NH (0.81 g, 8.0 mmol); the mixture was heated at reflux tem-
perature for 1 h. The turbid solution was cooled to 0 °C and cy-
clopropyl phenyl sulfoxide (5) (0.17 g, 1.0 mmol) was added. The
temperature was raised to room temperature and the mixture was
stirred overnight. The resulting mixture was quenched by adding
aqueous NH4Cl and extracted with Et2O. The organic layer was
Experimental
General. The melting points were determined on a Laborato-
ry Devices MEL-TEMP Ⅱ melting point apparatus and are uncor-
rected. The IR spectra were recorded on a Perkin-Elmer 1600 Se-

K. Kobayashi et al.
Bull. Chem. Soc. Jpn., 75, No. 6 (2002) 1369
washed with brine and dried over MgSO4. After evaporation of
the solvent, the crude product was purified by preparative TLC on
SiO2 to give 6 (0.12 g, 72%) as a pale-yellow oil: Rf 0.22 (1:5
EtOAc–hexane); bp 120 °C (bath temp)/26.7 Pa (lit.,4 90–93 °C/
1H NMR δ 1.19 (1H, d, J = 5.6 Hz), 1.22 (1H, d, J = 5.6 Hz),
1.49 (3H, s), 1.53 (3H, s), 2.32 (3H, s), and 7.1–7.35 (9H, m); MS
m/z (%) 300 (M+, 7.7), 177 (33), and 135 (100). Found: m/z
300.1009. Calcd for C18H20S2: M, 300.1006. Found: C, 72.00; H,
6.80%. Calcd for C18H20S2: C, 71.95; H, 6.71%.
1
4.0 Pa); IR (neat) 3371 and 3059 cm−1; H NMR δ 1.1–1.3 (4H,
m), 2.30 (1H, s), and 7.2–7.55 (5H, m); MS m/z (%) 166 (M+, 3.0)
and 110 (100).
2,2-Dimethyl-1-(phenylthio)cyclopropanol (13):
a pale-
yellow oil; Rf 0.05 (1:40 EtOAc–hexane); IR (neat) 3422 and
3058 cm−1; 1H NMR δ 0.90 (1H, d, J = 5.6 Hz), 0.94 (1H, d, J =
5.6 Hz), 1.30 (3H, s), 1.36 (3H, s), 2.32 (1H, s), and 7.1–7.45 (5H,
m); MS m/z (%) 194 (M+, 6.8) and 150 (100). Found: m/z
194.0764. Calcd for C11H14OS: M, 194.0765.
1,1-Bis(phenylthio)cyclopropane 8a.6a Typical Procedure
for the Reactions of Cyclopropyl Phenyl Sulfoxides with Thi-
ols in the Presence of a Magnesium Amide.
To a cooled (0
°C) turbid solution of a magnesium amide, generated from EtMg-
Br (6.0 mmol) and i-Pr2NH (0.61 g, 6.0 mmol) in Et2O (8 mL), as
described above, benzenethiol (0.50 g, 4.0 mmol) was added un-
der stirring. After the mixture was stirred for 20 min, cyclopropyl
phenyl sulfoxide (5) (0.17 g, 1.0 mmol) was added. The resulting
mixture was allowed to warm to room temperature, and stirring
was continued overnight. A workup in a similar manner as de-
scribed above gave a residue, which was purified by preparative
TLC on SiO2 (1:40 EtOAc–hexane) to give 8a (0.18 g, 69%) along
with 9% yield of 6 (15 mg). 8a: a pale yellow oil; Rf 0.46; IR
(neat) 3078, 3060, 1583, 1477, 1438, 1024, 889, 737, and 689
cm−1; 1H NMR δ 1.48 (4H, s), 7.27 (2H, t, J = 7.3 Hz), 7.33 (4H,
t, J = 7.3 Hz), and 7.47 (4H, d, J = 7.3 Hz); MS m/z (%) 258
(M+, 12) and 149 (100). Found: m/z 258.0537. Calcd for
C16H16S2: M, 258.0522.
2-Methyl-4-(4-methylphenylthio)-3-phenylthio-2-butene
(14): a pale-yellow oil; Rf 0.25 (1:40 EtOAc–hexane); IR (neat)
1
1625, 1583, 1491, 1478, and 738 cm−1; H NMR δ 1.75 (3H, s),
2.01 (3H, s), 2.30 (3H, s), 3.71 (2H, s), and 7.0–7.35 (9H, m); MS
m/z (%) 300 (M+, 8.1), 176 (33), and 135 (100). Found: m/z
300.1008. Calcd for C18H20S2: M, 300.1006. Found: C, 71.84; H,
6.70%. Calcd for C18H20S2: C, 71.95; H, 6.71%.
We wish to thank Mrs. Miyuki Tanmatsu of this Department
for determining the mass spectra.
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1
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1
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5
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6
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(100). Found: m/z 272.0674. Calcd for C16H16S2: M, 272.0693.
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7
8
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