Synthesis and reaction of tricyclic tetrathiins and pentathiepins: Novel formation of α-disulfines

Article abstract of DOI:10.1016/j.tet.2012.05.069

Cyclic polysulfanes containing a norbornane skeleton (tetrathiins and pentathiepins) were synthesized by two methods. One is the sulfurization of camphor hydrazone with disulfur dichloride, and the other is the reaction of thiocamphor with disulfur dichloride. The reduction of tetrathiin with LiEt ₃BH gave the corresponding dithiol that further reacted with methyl iodide to afford the corresponding methyl sulfide. Reaction of tetrathiin with (Ph₃P)₂PdCl₂ or NiBr₂ resulted in the formation of the corresponding dithiolene metal complexes. Tetrathiins were stereoselectively oxidized by m-CPBA to afford the corresponding α-disulfines.

Full text of DOI:10.1016/j.tet.2012.05.069

Tetrahedron 68 (2012) 6211e6217
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Synthesis and reaction of tricyclic tetrathiins and pentathiepins: novel formation
of
a-disulfines
,
a
a
a
a
Kentaro Okuma a , Kazunori Munakata , Toshiaki Tsubota , Masayuki Kanto , Noriyoshi Nagahora ,
*
Kosei Shioji a, Yoshinobu Yokomori b
a Department of Chemistry, Fukuoka University, Jonan-ku, Fukuoka 814-0180, Japan
b Department of Applied Chemistry, National Defense Academy, Hashirimizu, Yokosuka 239-8686, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Cyclic polysulfanes containing a norbornane skeleton (tetrathiins and pentathiepins) were synthesized
by two methods. One is the sulfurization of camphor hydrazone with disulfur dichloride, and the other is
the reaction of thiocamphor with disulfur dichloride. The reduction of tetrathiin with LiEt3BH gave the
corresponding dithiol that further reacted with methyl iodide to afford the corresponding methyl sulfide.
Reaction of tetrathiin with (Ph3P)2PdCl2 or NiBr2 resulted in the formation of the corresponding di-
thiolene metal complexes. Tetrathiins were stereoselectively oxidized by m-CPBA to afford the corre-
Received 14 March 2012
Received in revised form 15 May 2012
Accepted 18 May 2012
Available online 26 May 2012
sponding a-disulfines.
Ó 2012 Elsevier Ltd. All rights reserved.
1. Introduction
In this paper, we show the full details of the chemistry of tricyclic
tetrathiins.
The only possible six- and seven-membered ring compounds
containing a carbon-carbon double bond and sulfur atoms are
1,2,3,4-tetrathiins (2) and 1,2,3,4,5-pentathiepins (3). Pentathie-
pins, which are seven-membered cyclic polysulfanes, are very im-
portant compounds because of their pharmacological activity. They
are synthesized by reacting benzodithiols with elemental sulfur in
liquid ammonia,1 by thermolysis of 1,2,3-thia- or selenadiazoles
with elemental sulfur,2 or dioxime with S2Cl2,3 or by reacting
benzyne with elemental sulfur.4 Tetrathiins are novel six-
membered cyclic tetrasulfanes that are synthesized by reacting
sterically hindered alkynes with elemental sulfur,5 alkenes with
S2Cl2,6 or titanocene dithiolene complexes with SO2Cl2.7 Our un-
wavering interest in cyclic polysulfanes has led to the synthesis of
2. Results and discussion
2.1. Synthesis of tricyclic polysulfanes
We first investigated the reaction of thiocamphor 1a with S2Cl2
under several conditions to determine whether the corresponding
cyclic polysulfanes would be formed. The results are shown
in Table 1. When a solution of 1a and triethylamine (1 equiv) in
dichloromethane was added to a solution of S2Cl2 (1 equiv) in
dichloromethane at 0 ꢀC, 1,11,11-trimethyl-3,4,5,6-tetrathia-tricyclo
[6.2.1.02,7]undeca-2(7)-ene (2a) and 1,12,12-trimethyl-3,4,5,6,7-
pentathiatricyclo[7.2.1.02,8]dodeca-2(8)-ene (3a) were obtained in
15% and 12% yields, respectively (entry 1). The yields of 2a and 3a
were improved in the absence of triethylamine (entry 2). The best
yields of 2a (69%) and 3a (12%) were obtained by using 1.5 equiv of
S2Cl2 at rt (entry 3). In contrast to the result of Mloston et al.,13 no
WagnereMeerwein rearranged product was obtained, suggesting
sulfur-containing heterocycles, such as benzothietes,8
a-dithio-
lactones,9 1,2-dithietan-3-ones,10 and 1,2-dithiolane-3-thiones.11
However, relatively little attention has been paid to the synthesis
of sulfur-containing heterocycles by the reaction of bicyclic thiones,
such as thiocamphor (1). The only reported examples are the syn-
thesis of norbornanethiazolines and 6H-[1,3]oxathiin-6-ones from
thiofenchone.12 and the reaction of alkane sulfanyl chlorides with
thiocamphor, which resulted in symmetrical and unsymmetrical
disulfanes.13 We have reported the synthesis and reaction of tet-
rathiin (2) by reacting thiocamphor 1 with sulfur monochloride.14
that the a-proton abstraction proceeds much faster than the rear-
rangement (Scheme 1). When the reaction conditions (tempera-
ture, amount of S2Cl2, and time) were varied, no dithiete was
formed. The reactions of norbornene with active sulfur to afford
cyclic polysulfanes are well known.15 However, there is no report of
the synthesis of tricyclic polysulfanes from thiocamphor 1a.
The present work is the first to provide a method for the syn-
thesis of cyclic polysulfanes with a norbornene skeleton. The re-
action might proceed as follows. Abstraction of a proton from
* Corresponding author. Tel.: þ81 92 871 6631; fax: þ81 92 865 6030; e-mail
address: kokuma@fukuoka-u.ac.jp (K. Okuma).
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2012.05.069

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K. Okuma et al. / Tetrahedron 68 (2012) 6211e6217
Table 1
Reaction of 1a with S2Cl2
O
NH
1a
+ 2
+ 2a + 3a
O
S2Cl2
O
O
N S N
Entry S2Cl2 (equiv) Et3N (equiv) Temp(ꢀC) Product 2a (Yield/%) 3a
CH2Cl2
rt, 1h
10%
4
1
2
3
4
5
1.0
1.0
1.5
1.5
2.0
1.0
0
0
0
0
0
0
15
36
69
35
32
12
15
12
11
16
N S
N
O
S
rt
Reflux
rt
60%
Scheme 3.
2a and 3a or thiocamphor 1a would be formed. Treatment of
camphor hydrazone 5 and triethylamine in dichloromethane with
S2Cl2 in dichloromethane at 0 ꢀC resulted in the formation of
pentathiepin 3a and tetrathiin 2a in 40% and 19% yields, re-
spectively (Scheme 4). In the present case, pentathiepin 3a is the
major product, which is different from that of the reaction of thi-
ocamphor 1a with S2Cl2. Thus, we changed S2Cl2 equivalent under
several conditions. The results are shown in Table 2.
S
S
S
S
S
S
+
S
1a
CH2Cl2
S
S
S
2a
3a
+ S2Cl2
Scheme 1.
initially formed carbocation intermediate a dehydrochlorinated to
give alkenyl trisulfanyl chloride b, which further reacted with S2Cl2
to give alkenyl pentasulfonium chloride c. Intramolecular cycliza-
tion of this chloride followed by proton abstraction afforded tet-
rathiin 2a and SCl2. Intermediate c was further reacted with S2Cl2
followed by the intramolecular cyclization to afford 3a (Scheme 2).
S
S2Cl2/Et3N
CH2Cl2
S
S
S
+
S
S
S
S
S
N
NH2
3a
2a
Scheme 4.
5
Table 2
Reaction of camphor hydrazone 5 with S2Cl2
Cl
H
S2Cl2
Entry S2Cl2 (equiv) Et3N (equiv) Temp (ꢀC) Products 2a (Yields/%) 3a
1a
H
+ HCl
1
2
3
4
5
0.8
1.2
2.4
1.5
2.0
1.6
2.4
4.8
2.0
2.0
0
0
0
rt
0
0
19
16
20
15
8
40
11
11
16
S
S
S Cl
S S
a
b
S Cl
Cl
S
S2Cl2
S
S
Cl
Cl
S
S
c
When 0.8 equiv of S2Cl2 was used, the yield of 3a was only 8%
along with starting hydrazone (25%), whereas 2 equiv of S2Cl2
resulted in the formation of 3a in 16% yield (entries 1 and 5). When
1.2 equiv of S2Cl2 was used, 2a and 3a were obtained in 19 and 40%
yields, respectively (entry 2). Thus, this method is adequate for the
synthesis of pentathiepin 3a. While we did not clearly understand
why pentathiepin is the major product in the present case, we first
thought that S2Cl2 plays a vital role in the selective synthesis of
tetrathiin 2a. When pentathiepin 3a and S2Cl2 in CDCl3 were left to
stand at rt for 3 days, tetrathiin 2a was formed in approximately
10% yield. In contrast, when tetrathiin 2a and S2Cl2 in CDCl3 were
left to stand at rt for 3 days, pentathiepin 3a was formed in 10%
yield (Scheme 5).
Cl
H
2a
+ HCl
S
S
S
S
+ SCl2
Cl
S
- SCl2
S2Cl2
S
Cl
c
3a + HCl
S
S
S
S
Scheme 2.
The formation of SCl2 was easily observed from the emergence
of an orange red color from the original pale yellow solution within
a few minutes. Finally, the reaction of this solution with morpholine
resulted in the formation of thiobismorpholine (4) in 10% yield
along with dithiobismorpholine (60%) (Scheme 3).
As the reaction of ketone hydrazones with S2Cl2 gave thio-
ketones via thiosulfine intermediates,16 there would be a possibility
to synthesize tricyclic polysulfanes such as 2a and 3a. We then
performed the reaction of camphor hydrazone (5) with S2Cl2 in the
presence of triethylamine to determine whether cyclic polysulfanes
S2Cl2
S
2a
3a
+
+
S
S
S
CDCl3
3 days
S
10%
85%
3a
S2Cl2
S
2a
3a
S
CDCl3
3 days
S
S
80%
10%
2a
Scheme 5.

K. Okuma et al. / Tetrahedron 68 (2012) 6211e6217
6213
Although these results partly indicate the interconversion of
tetrathiin 2a and pentathiepin 3a by the use of S2Cl2, they are not
sufficient to explain the mechanism. Okazaki et al. have
explained the formation of thiosulfine intermediate in the re-
action of ketone hydrazone with S2Cl2.16 Thus, the reaction might
proceed as follows: initially afforded thiosulfine or dithiirane
intermediate (d) reacted with S2Cl2, and this was followed by
proton abstraction to afford sulfanyl chloride, intramolecular
cyclization of which gave 2a and HCl. Further addition of sulfur
chloride gave sulfonium intermediate (e). Intramolecular addi-
tion followed by proton abstraction gave pentathiepin 3a
(Scheme 6). The formation of SCl2 was also confirmed by the
reaction with morpholine, which resulted in the formation of
thiobismorpholine.
with lithium triethylborohydride resulted in the formation of
a dithiolate anion. This was further reacted with methyl iodide to
afford 2,3-bis(methylthio)-1,7,7-trimethylbicyclo[2.2.1]hept-2-ene
(6) in 84% yield (Scheme 8).
2a
Li
S
CH3I
S
CH3
THF
+ Li Et3BH
S
CH3
S
Li
6
Scheme 8.
S2Cl2
5
S
2.3. Synthesis of Bornylenedithiolene Pd and Ni complexes
Et3N
S
S
N
S
d
N
Since tetrathiin 2a was obtained, we then tried the reaction with
(Ph3P)2PdCl2 in the hope of thiolate Pd complex. Treatment of
tetrathin 2a with (Ph3P)2PdCl2 followed by the addition of triphe-
nylphosphine in dichloromethane resulted in the formation of
a mixture of dithiolateePd complex (nearly 10:9 ratio) in 57% yield.
The structure was confirmed by its 1H NMR and 13C NMR analysis.
Although the reaction of 2a with (Ph3P)2PdCl2 took place to afford
isomeric mixture of deep purple crystals, single crystals of major
isomer were obtained, which was subjected to X-ray crystallo-
graphic analysis. ORTEP drawing of 7 was shown in Fig. 1. Similarly,
treatment of tetrathiin 2a with triphenylphosphine and NiBr2 in
acetonitrile/CHCl3 (1:1) for 1 h resulted in the formation of 8 in 46%
yield (Scheme 9). Perochon et al. have reported that the reaction of
camphorquinone with P4S10, followed by the addition of NiCl2/
6H2O, afforded bornylenedithiolene Ni complex (7) in its neutral
+ N2
+ 2 Et3NHCl
2a + HCl
Cl
H
S
S2Cl2
Cl
S
Cl
S
H
S
S
S
S2Cl2
S
S
Cl
S
S
Cl
Cl
S
Cl
S
S
3a
+ SCl2 + HCl
S
S
S
form.17 Although the intermediate of the reaction seemed to be
a-
Cl
e
dithione or tetrathiin, they were not able to isolate those in-
termediates. The present reaction offers an alternative route for the
synthesis of Ni complex 8 from tetrathiine. The spectral data was
identical with the reported one.17 Thus, the present reaction pro-
vides another synthetic method for the bornylenedithiolene metal
complexes.
Scheme 6.
As the best result was obtained by reacting thiocamphor 1a with
S2Cl2, we tried to perform the synthesis of other tetrathiins 2 by
using substituted camphor.
As shown in Scheme 7, corresponding tetrathiins 2b and 2c were
obtained in 55% and 37% yields, respectively.
S2Cl2
S
S
CH2Cl2
rt
S
S
S
S
1b
2b
S2Cl2
S
S
CH2Cl2
rt
S
S
Cl
Cl
1c
2c
Scheme 7.
Thus, we have found two different methods for the general
synthesis of tricyclic polysulfanes 2 and 3.
2.2. Reduction of tetrathiin 2a
We then tried to reduce tetrathiin 2a to investigate the chemical
properties of tricyclic polysulfanes. The reaction of tetrathiin 2a
Fig. 1. ORTEP drawing of compound 7 (major).

6214
K. Okuma et al. / Tetrahedron 68 (2012) 6211e6217
S
S
S
S
+ Ph3P
Pd
S
CH2Cl2
rt
S
S
S
+ (Ph3P)4Pd
2a
7
Major
S
S
S
+
Pd
S
Fig. 2. 13C NMR data for compound 10.
7'
Minor
S
S
Ni
S
+ Ph3P
S
S
confirmed from spectroscopic data and elemental analysis data.
Surprisingly, the 13C NMR spectrum of compound 9b shows two
peaks at 192.8 and 194.8 ppm, which clearly indicates that
compound 9b has not the E,E- or Z,Z-form but the E,Z-form.
Thus the structure of 9a has the E,Z-form. Similarly, tetrathiin
CH3CN
CHCl3
rt
S
S
S
+ NiBr2 2H2O
2a
8
Scheme 9.
2c reacted with m-CPBA at rt to afford the E,Z-form of
fine (9c).
a
-disul-
2.4. Oxidation of tetrathiin 2: synthesis of a-disulfine
As the reduction of 2a was carried out successfully, we tried to
perform the oxidation of tetrathiin 2a to investigate whether the
O
S
+
+
S
S
m-CPBA
S
CH2Cl2
rt
corresponding sulfoxide or
of 2a with m-CPBA (2 equiv) at rt resulted in the formation of 1,7,7-
trimethylbicyclo[2.2.1]heptane-2,3-dithione S,S0-dioxide (9a) (
a-disulfine would be formed. Treatment
O
S
S
9b
C=S=O = 192.79
194.82 ppm
2b
a
-
disulfine) as the only isomer in 95% yield, suggesting that the re-
action proceeded stereoselectively (Scheme 10). The structure of
dioxide 9a was confirmed by 1H and 13C NMR spectroscopy, mass
spectrometry, and elemental analysis. The IR spectrum of 9a
showed peaks at 1044 (st), 1058, 1108, and 1124 cmꢁ1 for C]S]O
stretching.
S
O
S
m-CPBA
S
S
CH2Cl2
rt
S
O
S
Cl
Cl
9c
C=S=O = 190.38,
195.45 ppm
2c
Scheme 11.
The E,Z-structure would be also supported by the following
result. When -disulfine 9a was left to stand in EtOH overnight,
a
pale yellow crystals (11) were precipitated (Scheme 12). The 1H
NMR spectrum (CDCl3) of compound 11 shows signals attributable
to the norbornane structure (three methyl signals, two methylene
signals, and one methine signal). In addition, one of the three
methyl signals and one of the two methylene signals in the 1H
NMR spectrum (CDCl3) show broadening, which suggested that
the product would be an equilibrium mixture of conformational
isomers. Its ESI mass spectrum shows a peak at 483 (m/z), which
suggested a dimerized structure (460þNaþ). In addition, the IR
spectrum of this compound shows strong absorptions at 1332 and
1130 cmꢁ1, which are evidence of the existence of an SO2 com-
ponent. Thus, the structure of 11 has a thiosulfonate component.
As very fine single crystals of this compound were obtained, X-ray
crystallographic analysis was performed. Although the R-value
was not sufficient for the elucidation of the precise structure of
this compound, it can be surmised that product 11 has an eight-
membered cyclic thiosulfonate structure (Fig. 3). An oxygen
group was positioned at the less bulky side of the norbornane
skeleton.
Scheme 10.
To investigate the stereochemistry, we compared the 13C NMR
data of 9a with those of bis(tert-butyl)sulfine (9), an aliphatic a-
disulfine. Nakayama et al. reported the synthesis of a mixture of
(E,E)-, (E,Z)-, and (Z,Z)-bis(tert-butyl)sulfines 10 by the oxidation of
1,2-dithietes and 1,2-dithiones (Fig. 2).18 The 13C NMR spectrum of
compound 9a shows peaks at 193.20 and 195.00 ppm for the C]
S]O carbon. The 13C NMR signal of the C]S]O carbon of disul-
fines 10 appears at 192.56 ppm for the E,E-configuration,197.80 and
198.52 ppm for the E,Z-configuration, and 199.69 ppm for the Z,Z-
configuration (in CDCl3).
We initially thought that these data seem to indicate that
sulfine 9a has the E,E-configuration. However, we noted some
ambiguity because the signal at 195.00 ppm of a-disulfine 9a is
relatively close to the reported signals of the E,Z-form of 10
(197.80 and 198.52 ppm). Fortunately, as we had 4-methyl de-
rivative 2b in hand, we tried to oxidize this compound with
m-CPBA. Treatment of tetrathiin 2b with m-CPBA in dichloro-
Thus, the present oxidation would proceed through the fol-
lowing pathway: the oxidation of 2 gave the corresponding dioxide,
stereoselectively. Then, the dioxide cycloreversed to give (E,Z)-
disulfine exclusively (Scheme 13). The stereoselective synthesis of
-disulfine 9 from tetrasulfane 2 was achieved.
a-
methane at 0 ꢀC resulted in the formation of
a
-disulfine (9b) in
55% yield (Scheme 11). The structure of this compound was
a

K. Okuma et al. / Tetrahedron 68 (2012) 6211e6217
6215
column chromatography was performed with silica (Merck,
70e230 mesh). NMR spectra (1H at 400 MHz; 13C at 100 MHz) were
recorded in CDCl3 and chemical shifts are expressed in parts per
O
O
S
O
S
S
million relative to internal TMS (
d¼0.00) and CDCl3
(d¼77.00) for
S
EtOH
1H and 13C NMR. As compounds other than 9 and 11 did not show
characteristic frequencies, their IR spectra were omitted. Melting
points were uncorrected.
O
S
O
S
O
8a
11
Scheme 12.
4.2. Materials
All chemicals were obtained from commercial suppliers and
were used without further purification. Thiocamphor19 and cam-
phor hydrazone were synthesized by a reported method.20
4.3. Synthesis of 10-chlorothiocamphor 1c
To a solution of 10-chlorocamphor (5.10 g, 27.1 mmol) in toluene
(100 mL) were added P4S10 (2.80 g, 12.5 mmol) and hexame-
thyldisiloxane (5.10 g, 31 mmol) in one portion. After refluxing for
12 h, the reaction mixture was evaporated and chromatographed
over silica gel by with hexane as eluent to give 10-
chlorothiocamphor 1c (2.30 g, 11.4 mmol). Pale yellow oil. 1H
NMR (CDCl3)
d
¼0.94 (s, 3H, CH3), 1.20 (s, 3H, CH3), 1.37 (dt, 1H,
J¼6.4, 1.6 Hz, CHH), 1.45 (dt, 1H, J¼2.8, 6.4 Hz, CHH), 2.02e2.34 (m,
3H, CH2, and CH), 2.41 (d, 1H, J¼20 Hz, CHH), 2.79 (br d, 1H,
J¼20 Hz, CHH), 3.76 (d, 1H, J¼12 Hz, CHH), 4.06 (d, 1H, J¼12 Hz,
CHH). 13C NMR (CDCl3)
d
¼20.74 (CH3), 21.17 (CH3), 27.13 (CH2),
30.49 (CH2), 44.08 (CH), 46.36 (CH2), 50.21 (q-C), 55.64 (CH2), 71.36
(q-C), 266.26 (C]S). HRMS (GCEI) (m/z): calcd for C10H15ClS
202.0583. Found 202.0589 (Mþ).
4-Methylthiocamphor 1b: pale yellow oil. 1H NMR (CDCl3)
Fig. 3. ORTEP drawing of compound 11.
d
¼0.66 (s, 3H, CH3), 0.89 (s, 3H, CH3), 1.06 (s, 3H, CH3), 1.12 (s, 3H,
CH3), 1.25e1.31 (m, 1H, CHH), 1.40e1.45 (m, 1H, CHH), 1.65e1.76 (m,
2H, CH2), 2.43 (d, 1H, J¼18 Hz, CHH), 2.50 (br d, 1H, J¼18 Hz, CHH).
13C NMR (CDCl3)
d
¼13.91 (CH3), 14.97 (CH3), 17.00 (CH3), 17.20
O
(CH3), 33.36 (CH2), 34.26 (CH2), 47.17 (q-C), 50.01 (q-C), 61.30 (CH2),
S
S
m-CPBA
S
S
70.89 (q-C), 271.10 (C]S). HRMS (GCEI) (m/z): calcd for C11H18
S
S
O
S
CH2Cl2
S
S
O
182.1129. Found 182.1122 (Mþ).
S
S
O
9b
2b
4.4. Reaction of thiocamphor 1a with S2Cl2
Scheme 13.
To a solution of thiocamphor (0.337 g, 2.05 mmol) in dichloro-
methane (30 mL) was added solution of S2Cl2 (0.405 g,
a
3.00 mmol) in dichloromethane (10 mL) at rt. After stirring for 1 h,
the reaction mixture was washed with water, dried over Na2SO4,
and filtered. The resulting solution was evaporated to yield a yellow
oil, which was chromatographed over silica gel with hexane as
eluent to give a mixture of tetrathiin 2a and pentathiepin 3a. The
mixture was subjected to gel permiation chromatography to fur-
nish 2a (0.364 g, 1.37 mmol) and 3a (0.071 g, 0.23 mmol). Tetrathiin
3. Conclusion
We have synthesized tricyclic polysulfanes 2 and 3 by reacting
thiocamphor 1 or camphor hydrazone 5 with S2Cl2. Reaction of
tetrathiin 2a with lithium triethylborohydride gave the corre-
sponding dithiolate, and this was further reacted with methyl iodide
to give dimethyl derivative. Reaction of 2a with PdCl2 or NiBr2 in the
presence of triphenylphosphine gave the corresponding dithiolene
metal complexes 7 and 8. Oxidation of 2a with m-CPBA proceeded
2a: yellow oil; 1H NMR (400 MHz, CDCl3)
d
¼0.87 (s, 3H, CH3), 0.91
(s, 3H, CH3), 1.11 (s, 3H, CH3), 1.28e1.36 (m, 2H, CH2), 1.64e1.70 (m,
1H, CH2), 1.89e1.95 (m, 1H, CH2), 2.56 (d, J¼3.0 Hz, 1H, CH); 13C
stereoselectively to give (E,Z)-a-disulfines 9a in nearly quantitative
NMR (100 MHz, CDCl3)
d
¼10.53, 18.71, 18.93, 26.30, 33.24, 53.04,
yield. This method affords the first example of tricyclic polysulfanes.
CCDC 870747 and CCDC 866061 contain the supplementary
crystallographic data for compound 7 and 11. These data can be
obtained free of charge from The Cambridge Crystallographic Data
Centre via www.ccdc.cam.ac.uk/data_request/cif.
69.71, 60.02, 129.98, 131.62. MS (EI) m/z: found 262.00 (Mþ). Calcd
for C10H14S4: 261.99. Anal. Calcd for C10H14S4: C, 45.76; H, 5.38.
Found: C, 45.36; H, 5.22. Pentathiepin 3a: yellow oil; 1H NMR
(400 MHz, CDCl3)
d
¼0.74 (s, 3H, CH3), 0.79 (s, 3H, CH3), 1.10 (s, 3H,
CH3), 1.49e1.57 (m, 2H, CH2), 1.76e1.82 (m, 1H, CH2), 2.06e2.12 (m,
1H, CH2), 2.64 (d, J¼3.9 Hz, 1H, CH); 13C NMR (101 MHz, CDCl3)
4. Experimental
4.1. General
d
¼11.95, 18.63, 18.78, 24.99, 31.82, 56.53, 61.54, 61.63, 152.08,
155.86. MS (EI) m/z: found 294.00 (Mþ). Calcd for C10H14S5: 264.02.
Anal. Calcd for C10H14S5: C, 40.78; H, 4.79. Found: C, 40.70; H, 4.94.
Other reactions were carried out in a similar manner.
All solvents were distilled prior to use. Analytical TLC was car-
ried out on precoated plates (Merck silica gel 60, F254) and flash
Tetrathiin 2b: yellow oil, 1H NMR (CDCl3)
d¼0.74 (3H, s, CH3),
0.76 (3H, s, CH3), 1.14 (6H, s, CH3), 1.27e1.31 (2H, m), 1.60e1.64

6216
K. Okuma et al. / Tetrahedron 68 (2012) 6211e6217
(2H, m). 13C NMR (CDCl3)
d
¼11.56 (CH3 ꢂ2), 16.29 (CH3), 17.18 (CH3),
dichloromethane (5 mL) at rt. After being stirred for 1 h, the re-
action mixture was evaporated to give a purple solid, which was
chromatographed over silica gel with hexane: dichloromethane
(2:1) as eluent to give deep reddish purple crystals (74 mg,
0.14 mmol). Recrystallization from methanol/dichloromethane
(1:1) afforded an isomeric mixture of complex 7. Pd complex 7:
isomeric mixture; deep red needles; mp 280 ꢀC (dec). 1H NMR
33.76 (CH2 ꢂ2), 55.49 (C), 61.22 (C ꢂ2),132.315 (CeS ꢂ2). HRMS (m/
z): calcd for C11H16S4: 276.0135. Found: (Mþ) 276.0135.
Tetrathiin 2c: pale yellow oil, 1H NMR (CDCl3)
d
¼0.98 (s, 3H,
CH3), 1.04 (s, 3H, CH3), 1.36 (dt,1H, J¼10.4 and 3.2 Hz, CHH), 1.54 (dt,
1H, J¼10.4 and 3.2 Hz, CHH), 1.80e2.02 (m, 2H, CH2), 2.55 (d, 1H,
J¼3.6 Hz, CH), 3.75 (d, 1H, J¼12.0 Hz, CHH), 3.83 (d, 1H, J¼12.0 Hz,
CHH). 13C NMR (CDCl3)
d
¼19.94 (CH3), 20.02 (CH3), 26.23 (CH2),
(CDCl3)
d
¼0.76 (s, 6H, CH3), 0.79 (s, 6H, CH3), 0.96 (s, 6H, CH3), 1.32
31.21 (CH), 42.87 (CH2), 54.80 (q-C), 60.91 (CH2Cl), 64.74 (q-C),
128.75 (]C), 132.58 (]C). HRMS (EI) m/z: found 295.9589 (Mþ).
Calcd for C10H13ClS4: 295.9583.
(s, 6H, CH3), 1.30e1.43 (m, 8H, CH2), 1.33 (s, 6H, CH3), 1.85e1.91 (m,
4H, CH2), 2.09e2.16 (m, 4H, CH2), 2.98e2.99 (m, 4H, J¼3.6 Hz, CH).
13C NMR (CDCl3)
d¼11.13 (CH3), 11.15 (CH3), 20.26 (CH3), 20.28
(CH3), 20.38 (CH3), 20.40 (CH3), 26.57 (CH2), 26.61 (CH2), 33.52
(CH2), 33.54 (CH2), 60.45 (CH), 60.46 (CH), 61.18 (q-C), 61.35 (q-C),
62.50 (q-C), 62.53 (q-C), 195.63 (C]S), 195.90 (C]S), 200.28 (C]S),
200.43 (C]S). Anal. Calcd for C20H28S4Pd: C, 47.75; H, 5.61. Found C,
4.5. Reaction of thiocamphor 1a with S2Cl2 followed by
addition of morpholine
To a solution of thiocamphor (0.168 g, 1.05 mmol) in dichloro-
methane (30 mL) was added a solution of S2Cl2 (0.270 g, 2.0 mmol)
in dichloromethane (10 mL) at rt. After stirring for 10 min, mor-
pholine (0.350 g, 4.0 mmol) was added and stirring was com-
menced for an additional 1 h. The reaction mixture was washed
with water, dried over Na2SO4, and filtered. The resulting solution
was evaporated to give a yellow oil, the 1H NMR spectrum of which
was compared with those of authentic thiobismorpholine and
dithiobismorpholine. Approximately 10% of thiobismorpholine 4
and 60% of dithiobismorpholine were detected (by NMR).21 Com-
pounds 2a and 3a were also formed.
47.53; H, 5.83. Crystal data for compound 7: MoKa; monoclinic,
ꢀ
ꢀ
ꢀ
M¼503.08, a¼6.9456(7) A, b¼11.902(1) A, c¼13.284(1) A,
3
ꢀ
V¼1090.0(2) A , monoclinic, space group¼P21, Z¼2. Final R and wR
were 0.0607 and 0.1308, respectively.
To a solution of tetrathiin 2a (393 mg, 1.52 mmol) and NiBr2
(645 mg, 3.0 mmol) in dichloromethane/CH3CN (1:1; 10 mL) was
added a solution of triphenylphosphine (1048 mg, 4.0 mmol) in
dichloromethane (10 mL) at rt. After stirring this solution for 1 h,
water (10 mL) was added. The organic layer was dried over mag-
nesium sulfate, filtered, and evaporated to give a purple solid, the
chromatography of which over silica gel with dichloromethane/
hexane (1:1) as eluent gave purple crystals (159 mg, 0.36 mmol).
Recrystallization from methanol/dichloromethane (1:1) afforded
a pure complex of 8. Purple needles: mp 276e278 oC (lit.17 mp
4.6. Reaction of camphor hydrazone 5 with S2Cl2
To a solution of S2Cl2 (275 mg, 2.0 mmol) in dichloromethane
(3 mL) was added a solution of camphor hydrazone 5 (175 mg,
1.07 mmol) and triethylamine (207 mg, 2.0 mmol) at 0 ꢀC. After
stirring for 1 h, water (10 mL) was added and extraction was carried
out with dichloromethane (5 mLꢂ3). The combined extract was
dried over magnesium sulfate, filtered, and evaporated to give
a pale yellow oil, which was chromatographed over silica gel with
hexane as eluent to afford a yellow oil. Gel permiation chroma-
tography of the oil gave tetrathiin 2a (54 mg, 0.21 mmol) and
pentathiepin 3a (104 mg, 0.35 mmol).
278 ꢀC). 1H NMR (CDCl3)
d
¼0.67 (s, 6H, CH3), 0.97 (s, 6H, CH3),
1.20e1.31 (m, 4H, CH2), 1.42 (s, 6H, CH3), 1.80e1.86 (m, 1H, CHH),
2.03e2.14 (m, 1H, CHH), 3.09 (d, 2H, J¼3.6 Hz, CH). 13C NMR (CDCl3)
d
¼11.48 (CH3), 20.22 (CH3), 20.25 (CH3), 25.93 (CH2), 32.98 (CH2),
59.68 (CH), 61.41 (q-C), 61.97 (q-C), 193.73 (C]S), 198.51 (C]S).
4.9. Oxidation of tetrathiin 2a
To a solution of tetrathiin 2a (185 mg, 0.70 mmol) in CH2Cl2
(20 mL) was added a solution of m-CPBA (261 mg, 1.47 mmol) in
dichloromethane (10 mL) at rt. After stirring for 1 h, the reaction
mixture was filtered, washed with satd aq sodium carbonate
(10 mLꢂ3), filtered, dried over magnesium sulfate, and evaporated
to give a yellow solid, the chromatography of which over silica gel
4.7. Reaction of tetrathiin 2a with lithium
triethylborohydride followed by addition of methyl iodide
To a solution of tetrathiin 2a (50 mg, 0.19 mmol) in THF (1 mL)
was added a solution of lithium triethylborohydride (1 Mol solution
in THF, 0.8 mL) at 0 ꢀC. After refluxing for 1 h, methyl iodide
(167 mg, 1.19 mmol) was added. The reaction mixture was washed
with water (10 mL) and extracted with ethyl acetate (3ꢂ5 mL). The
combined extract was dried over magnesium sulfate, filtered, and
evaporated to give a brown oil, which was chromatographed over
silica gel with dichloromethane/hexane as eluent to afford 2,3-
bis(methylthio)-1,7,7-trimethylbicyclo[2.2.1]hept-2-ene 6 (37 mg,
0.16 mmol).
with dichloromethane as eluent furnished yellow leaflets of
disulfine 9a (218 mg, 0.66 mmol). -disulfine 9a: pale yellow
crystals, mp 72 ꢀC (dec) 1H NMR (CDCl3)
a-
a
d
¼0.85 (s, 3H, CH3), 0.94 (s,
3H, CH3), 1.22 (s, 3H, CH3), 1.45 (m, 1H, CHH), 1.53 (m, 1H, CHH), 1.95
(m, 1H, CHH), 2.07 (m, 1H, CHH), 3.89 (d, 1H, J¼4.0 Hz, CH). 13C NMR
(CDCl3)
d
¼12.50 (Me), 18.18 (Me), 20.12 (Me), 25.89 (CH2), 34.82
(CH2), 51.99 (CH), 53.65 (q-C), 57.44 (q-C), 193.20 (C]S]O), 195.30
(C]S]O). IR (
Calcd for C10H14O2S2: C, 52.14; H, 6.13. Found: C, 52.01; H, 6.12%.
The oxidation of 2b was carried out in a similar manner by using
2b (83 mg, 0.30 mmol) and m-CPBA (131 g, 0.74 mmol). Compound
9b (40 mg): pale yellow crystals, mp 74 ꢀC (dec). 1H NMR (CDCl3)
n
C]S]O)/cmꢁ1¼1044 (st),1058,1108, and 1124. Anal.
Compound 6: colorless oil: 1H NMR (CDCl3)
d¼0.82 (s, 3H, CH3),
0.84 (s, 3H, CH3), 1.10 (s, 3H, CH3), 1.06e1.18 (m, 2H, CH2), 1.60e1.62
(m, 1H, CHH), 1.81e1.88 (m, 1H, CHH), 2.23 (s, 3H, CH3), 2.29 (s, 3H,
d
¼0.81 (s, 3H, CH3), 0.83 (s, 3H, CH3), 1.28 (s, 3H, CH3), 1.68 (s, 3H,
CH3), 2.58 (d, 1H, J¼4.0 Hz, CH). 13C NMR (CDCl3)
d
¼12.47 (CH3),
CH3), 2.13e2.23 (m, 2H), 3.73 (m, 2H). 13C NMR (CDCl3)
d
¼12.87
14.84 (CH3), 17.31 (CH3), 19.10 (CH3), 25.53 (CH2), 43.21 (CH), 53.43
(q-C), 55.49 (CH), 59.92 (q-C), 136.00 (]C), 146.04 (]C). HRMS
(GCEI) (m/z): calcd for C12H20S2: 228.1006. Found: (Mþ) 228.1006.
(CH3), 13.90 (CH3), 15.54 (CH3), 18.29 (CH3), 33.61 (CH2), 34.86
(CH2), 43.21 (C), 55.66 (C), 56.46 (C), 63.19 (C), 192.79 (C]S]O),
194.82 (C]S]O). IR (
n
C]S]O)/cmꢁ1¼1056 (st), 1085, 1130, and
1143. Anal. Calcd for C11H16O2S2: C, 54.06; H, 6.60. Found: C, 54.12;
H, 6.97%.
4.8. Synthesis of bornylidene dithiolate complexes
Compound 9c: pale yellow crystals, mp 78 ꢀC (dec). 1H NMR
To
a
solution of tetrathiin 2a (131 mg, 0.5 mmol) and
(CDCl3)
d
¼1.01 (s, 3H, CH3),1.10 (s, 3H, CH3),1.54e1.59 (m,1H, CHH),
(Ph3P)2PdCl2 (210 mg, 0.3 mmol) in dichloromethane (20 mL) was
added a solution of triphenylphosphine (262 mg, 1.0 mmol) in
1.90e1.96 (m, 1H, CHH), 2.13e2.23 (m, 2H, CH2), 3.73 (d, 1H,
J¼12.0 Hz, CHHCl), 3.89 (d, 1H, CHHCl), 4.02 (d, 1H, J¼2.7 Hz, CH).

K. Okuma et al. / Tetrahedron 68 (2012) 6211e6217
6217
13C NMR (CDCl3)
(CH2), 43.21 (CH), 52.69 (CH2Cl), 54.92 (q-C), 63.11 (q-C), 190.38
(C]S]O), 195.45 (C]S]O). IR (
1098, and 1112. Anal. Calcd for C10H13ClO2S2: C, 45.36; H, 4.95.
Found: C, 45.24; H, 4.94.
d
¼19.04 (CH3), 20.70 (CH3), 25.50 (CH2), 32.13
References and notes
C]S]O)/cmꢁ1¼1043 (st), 1065,
1. Sato, R.; Saito, S.; Chiba, H.; Goto, T.; Saito, M. Chem. Lett. 1986, 349e352; (a)
Ogawa, S.; Yomoji, N.; Sato, S.-i.; Sato, R. Chem. Lett. 1994, 507e510.
2. Chenard, B. L.; Miller, T. J. J. Org. Chem. 1984, 49, 1221e1224; (a) Ando, W.;
Tokitoh, N.; Kabe, Y. Phosphorus, Sulfur Silicon Relat. Elem. 1991, 58, 179e205.
3. Macho, S.; Rees, C. W.; Rodríguez, T.; Torroba, T. Chem. Commun. 2001,
403e404.
n
4. Brzostowska, E. M.; Greeer, A. J. Org. Chem. 2004, 69, 5483e5485.
5. Krespan, C. G. J. Am. Chem. Soc. 1961, 83, 3432e3433; (a) Nakayama, J.; Choi, K.
S.; Akiyama, I.; Hoshino, M. Tetrahedron Lett. 1993, 34, 115e118; (b) Choi, K. S.;
Akiyama, I.; Hoshino, M.; Nakayama, J. Bull. Chem. Soc. Jpn. 1993, 66, 623e629.
6. Buddensiek, D.; Dirk, K.; Brigitte, V. J. Chem. Ber. 1987, 120, 575e581.
7. Shimizu, T.; Murakami, M.; Kobayashi, Y.; Iwata, K.; Kamigata, N. J. Org. Chem.
1998, 63, 8192e8199.
8. Okuma, K.; Shiki, K.; Shioji, K. Chem. Lett. 1998, 27, 79e80; (a) Okuma, K.;
Shibata, S.; Shioji, K.; Yokomori, Y. Chem. Commun. 2000, 1535e1536; (b)
Okuma, K.; Shigetomi, T.; Shibata, S.; Shioji, K. Bull. Chem. Soc. Jpn. 2004, 77,
187e188.
9. Okuma, K.; Shigetomi, T.; Nibu, Y.; Shioji, K.; Yoshida, M.; Yokomori, Y. J. Am.
Chem. Soc. 2004, 126, 9508e9509; (a) Shigetomi, T.; Soejima, H.; Nibu, Y.; Shioji,
K.; Okuma, K.; Yokomori, Y. Chem.dEur. J. 2006, 12, 7742e7748.
10. Shigetomi, T.; Okuma, K.; Yokomori, Y. Tetrahedron Lett. 2008, 49, 36e38.
11. Okuma, K.; Nojima, A.; Shigetomi, T.; Yokomori, Y. Tetrahedron 2007, 63,
11748e11753.
12. Martinez, A. G.; Vilar, E. T.; Moreno, F.; Garcia, A. M. A. Tetrahedron: Asymmetry
2006, 17, 2970e2975; (a) Okuma, K.; Mori, Y.; Tabuchi, M.; Shigetomi, T.; Shioji,
K. Tetrahedron Lett. 2007, 48, 8311e8313.
4.10. Synthesis of thiosulfonate 11
A solution of
a-disulfine 9a (45 mg, 0.19 mmol) in ethanol
(10 mL) was left to stand overnight. A colorless solid precipitated
was formed, which was filtered to give colorless fine plates (11). Mp
275 ꢀC (dec). 1H NMR (CDCl3)
d
¼0.90 (s, 3H, CH3), 0.96 (br s, 3H),
1.16 (br s, 3H, CH3), 1.40e1.52 (m, 1H, CHH), 1.52e1.60 (m, 1H, CHH),
1.60e1.83 (CHH), 2.12e2.19 (m, 1H, CHH), 3.20 (d, 1H, J¼4.0 Hz, CH).
13C NMR (CDCl3)
d
¼11.90 (CH3), 18.62 (CH3), 19.73 (CH3), 25.81
(CH2), 30.40 (CH2), 56.82 (CH), 58.75 (q-C), 62.03 (q-C), 140.25 (]
C), 158.04 (]C). MS (ESI) (m/z): calcd for C20H28O4S2þNa: 483.
Found: (MþNaþ) 483. IR (
n
)/cmꢁ1: 1130 and 1332 (SO2). Anal. Calcd
for C20H28O4S2: C, 52.14; H, 6.13. Found: C, 51.86; H, 6.11. Crystal
ꢀ
ꢀ
data for compound 11: M¼460.66, a¼7.422(8) A, b¼12.400(13) A,
3
ꢀ
ꢀ
c¼11.759(12) A, V¼1082(2) A , T¼173(2) K, monoclinic, space
group¼P2(1), Z¼2. The final R and wR were 0.1117 and 0.3099, re-
spectively, using 12,434 reflections.
13. Majchrzak, A.; Mloston, G.; Linded, A.; Heimgartner, H. Helv. Chim. Acta 2004,
790e799.
14. Okuma, K.; Tsubota, T.; Tabuchi, M.; Kanto, M.; Nagahora, N.; Shioji, K.; Yoko-
mori, Y. Chem. Lett. 2010, 39, 648e649; (a) Okuma, K.; Munakata, K. Phosphorus,
Sulfur Silicon Relat. Elem. 2011, 186, 1196e1200.
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2009, 5413e5421.
We thank Mr. Taisuke Matsumoto (Analytical Center, Institute
for Materials Chemistry and Engineering, Kyushu University) for
the X-ray diffraction analysis.
18. Ono, Y.; Sugihara, Y.; Ishii, A.; Nakayama, J. J. Am. Chem. Soc. 2003, 125,
Supplementary data
€
12114e12115; (a) Nakayama, J.; Mizumura, A.; Yokomori, Y.; Krebs, A.; Shutz, K.
Tetrahedron Lett. 1995, 36, 8583e8586.
1H NMR, 13C NMR of compounds 2a, 2b, 7, 9a, 9b, and X-ray
crystallographic data of compound 7 and 11. Supplementary data
associated with this article can be found, in the online version, at
doi:10.1016/j.tet.2012.05.069.
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Okazaki, R. Bull. Chem. Soc. Jpn. 1981, 54, 3541e3545.
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