Synthesis and Z/E isomerization of 2-imino-1,3-thiaselenolanes via iodocyclization

Article abstract of DOI:10.1016/j.tet.2012.07.083

Selenium-containing heterocycles have been interested because of their unique reactivity and potential biological activity. Recently, several selenium-containing heterocycles bearing an exocyclic imine have been synthesized by isoselenocyanates. Here we r

Full text of DOI:10.1016/j.tet.2012.07.083

Tetrahedron 68 (2012) 10496e10501
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Tetrahedron
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Synthesis and Z/E isomerization of 2-imino-1,3-thiaselenolanes via
iodocyclization
,
,
*
Yosuke Toyoda a y, Mamoru Koketsu b
a Department of Chemistry, Faculty of Engineering, Gifu University, Gifu 501-1193, Japan
b Department of Materials Science and Technology, Faculty of Engineering, Gifu University, Gifu 501-1193, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Selenium-containing heterocycles have been interested because of their unique reactivity and potential
biological activity. Recently, several selenium-containing heterocycles bearing an exocyclic imine have
been synthesized by isoselenocyanates. Here we report the synthesis of 2-imino-1,3-thiaselenolanes. The
reaction of isoselenocyanates with allyl mercaptan afforded S-allyl-selenothiocarbamates. Then 2-imino-
1,3-thiaselenolanes were obtained as Z/E mixture at the imine position via iodocyclization reaction.
Additionally, we also investigated the Z/E isomerization of the related cyclization reactions.
Ó 2012 Elsevier Ltd. All rights reserved.
Received 26 April 2012
Received in revised form 18 July 2012
Accepted 24 July 2012
Available online 31 July 2012
1. Introduction
seven-membered heterocycles 2-imino-1,3-oxaselenepanes were
obtained as Z/E mixture at the imine position.7 As these results, this
The modification of ring system and replacement of heteroatom
in known valuable compounds have been efficient methods in
various fields including organic and pharmaceutical chemistry, and
material science. In recent years, selenium-containing heterocycles
Z/E isomerization is thought to be involved in both the heteroatom
and the ring size in heterocycles.
Iodocyclization has been known a powerful tool for the con-
struction of various heterocycles by the intramolecular cyclization
of unsaturated CeC bond with a variety of nucleophiles such as N,
O, and S atoms.8 In contrast, only a few examples for the synthesis
of selenium-containing heterocycles via electrophilic cyclization
have been reported in the literature.8 Recently, we have described
the synthesis of 2-imino-1,3-selenazines9 and 3-selena-1-
dethiacephems10 via iodocyclization of N-allyl-selenoureas and
synthesis of 2-imino-1,3-oxaselenolanes from O-allyl-seleno-
carbamates.11 And the resulting exocyclic imines in the products
showed Z isomer only. In contrast, 2-imino-1,3-dithiolanes via the
iodocyclization of S-allyl-dithiocarbamates were obtained as Z/E
isomers.12
Therefore, we were interested in the synthesis of selenium/
sulfur-containing heterocycles such as 2-imino-thiaselenolanes,
and their stereochemistry. However, it has never been reported in
the literatures for the synthesis of 2-imino-1,3-thiaselenolanes so
far.13 Herein, we focused on the synthesis of 2-imino-1,3-
thiaselenolanes 3 via iodocyclization of S-allyl-selenothiocarba-
mates 2 (Scheme 1). Additionally, we investigated the Z/E isomer-
ization of exocyclic imines in the related intramolecular cyclization.
1
have been interested because of their unique reactivity and po-
tential biological activity.2 There are some drawbacks for the syn-
thesis of selenium-containing heterocycles due to their instability,
toxicity, and difficulties to introduce selenium element into ring. In
the last decade, isoselenocyanates have been emerged as an effi-
cient building block for the synthesis of selenium-containing het-
erocycles, since they are easy to prepare and store, less-toxic, and
safe to handle.3 Previously, it has been reported that the reactions
of isoselenocyanates with haloamines or haloalcohols gave the
corresponding selenium-containing heterocycles bearing an exo-
cyclic imine. Heimgartner et al. reported the reactions of iso-
selenocyanates with 2-bromoethylamine, 3-chloropropylamine,
and 4-chlorobutylamine, which afforded five- to seven-membered
selenium/nitrogen-containing heterocycles such as 2-imino-1,3-
selenazolidines,4 2-imino-1,3-selenazines,4 and 2-imino-1,3-
selenazepanes.5 We recently described the reaction of iso-
selenocyanates with 2-bromoethanol, which afforded five-mem-
bered selenium/oxygen-containing heterocycles, 2-imino-1,3-
oxaselsenolanes.6 These products were emerged as Z isomers at
the imine position. Notably, when 4-bromobutanol was used,
2. Results and discussion
* Corresponding author. Tel.: þ81 58 293 2619; fax: þ81 58 293 2794; e-mail
Isoselenocyanates
1 were prepared by the reactions of
address: koketsu@gifu-u.ac.jp (M. Koketsu).
y
N-substituted formamides with an excess of triphosgene, selenium
Present address: Department of Pharmacology, Kyoto University Graduate
School of Medicine, Kyoto, 606e8501, Japan.
powder, and triethylamine.14 First, we examined to synthesize
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2012.07.083

Y. Toyoda, M. Koketsu / Tetrahedron 68 (2012) 10496e10501
10497
Scheme 1. Synthetic approach to 2-imino-1,3-thiaselenolanes 3 via iodocyclization.
S-allyl-phenyl-selenothiocarbamate 2a by the reaction with phe-
nylisoselenocyanate 1a and allyl mercaptan under the basic condi-
tions.15,16 In order to determine optimal conditions, several reaction
temperatures (0 ꢀC, ꢁ20 ꢀC, ꢁ40 ꢀC, and ꢁ78 ꢀC) and bases (none,
NaH, Et3N, K2CO3, Cs2CO3, and DBU) were investigated. As a result, 2a
was prepared in the presence of NaH at 0 ꢀC, which is the best result
(79% yield). Then we synthesized various S-allyl-arylselenothio-
carbamates 2be2d from the corresponding isoselenocyanates
1be1d in 73e83% yields (Table 1, entries 2e4). These products 2
were relatively unstable to air, and easy to decompose. Therefore, we
proceeded to the next reaction within a few days.
calculation by the 1H NMR spectrum, the isomeric ratio of 3a was
85:15. Predominant Z form can be explained by hyperconjugation
for the nitrogen lone pair.18
Next, we performed iodocyclization reactions under several
reaction conditions (Table 2). In the case of CH2Cl2 as solvent,
iodocyclization proceeded more efficiently at 0 ꢀC and room tem-
perature, compared with ꢁ40 ꢀC (entries 1e3). Using 1.5 or
2.0 equiv of iodine, the reactions showed similar results (entries 4
and 5). The reactions in other kinds of solvents such as THF, CH3CN,
CHCl3 and toluene gave product 3a in lower yield than the reactions
in CH2Cl2 (entries 6e9) even thermal conditions (entries 10 and 11).
Table 1
Synthesis of S-allyl-selenothiocarbamates 2
Entry
Isoselenocyanate 1
Time (min)
Selenothiocarbamate 2
Product
Yielda (%)
79
1
10
2
3
30
83
30
10
74
73
4
a
Isolated yield.
Next, iodocyclization reaction using selenothiocarbamates 2
were carried out. First, S-allyl-phenylselenothiocarbamate 2a was
reacted with 1 equiv of iodine in CH2Cl2 at room temperature, 5-exo
attack occurred; 2-phenylimino-1,3-thiaselenolane 3a was ob-
tained in 90% yield. The structure of 3a was confirmed by IR, 1H, 13C,
77Se NMR, COSY, HMQC, HMBC, MS, and elemental analysis. In this
reaction, both 5-exo and 6-endo attacks would be allowed.8
According to the NMR spectrum of 3a, selenium coupling was ob-
served at 4.40e4.47 ppm (2J(77See1H)¼39.8 Hz) for methine (CH)
in the 1H NMR spectrum, and 49.2 ppm (1J(77See13C)¼60.7 Hz) in
13C NMR spectrum, respectively. Furthermore, chemical shift of
iodomethyl carbon in 3a is 7.7 ppm in the 13C NMR spectrum.
Therefore, 3a was confirmed to be five-membered ring not six-
membered ring compound.17 Compound 3a was confirmed as Z/E
isomer mixture by 1H, 13C, and 77Se NMR spectra. According to the
In all cases, 3a was observed as isomer mixture, which the Z/E ratio
of 3a was 85:15.
Then, we synthesized four 2-imino-1,3-thiaselenolanes 3 by the
iodocyclization with S-allyl-selenothiocarbamates 2 in CH2Cl2 at
room temperature (Table 3). Phenyl-, p-tolyl-, and o-tolylseleno-
thiocarbamates 2ae2c provided the corresponding 2-imino-
1,3-thiaselenolanes 3ae3c in good yields (75e90%). In contrast, the
reaction of p-chlorophenylselenothiocarbamate 2d bearing electron-
withdrawing substituents afforded 3d in 40% yield. All 2-imino-
1,3-thiaselenolanes 3 were isolated as the inseparable mixture of
Z and E isomers. In the 77Se NMR spectra, 77Se signals were observed
584.6e592.4 ppm for the Z isomers and 606.5e623.0 ppm for the
E isomers, respectively. This tendency was followed to our previous
result, in which 77Se signals of Z isomers showed higher fields than
those of the E isomers in 2-imino-1,3-oxaselenepanes.7

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Y. Toyoda, M. Koketsu / Tetrahedron 68 (2012) 10496e10501
Table 2
thiaselenolane 5 was obtained in 50% yield as an mixture of Z and
E isomers at the imine positions (Scheme 3).
The reaction of S-allyl-phenylselenothiocarbamate 2a with iodine under different
conditions
To date, several selenium- (or sulfur-)containing heterocycles
bearing an exocyclic imine, have been synthesized by iso-
selenocyanates (or isothiocyanates), respectively. These compounds
are summarized in Table 4. The reactions of isoselenocyanates with
nucleophiles such as amines, alcohols, and thiols, generate the
corresponding selenocarbonyl intermediates such as selenoureas,
selenocarbamates, and selenothiocarbamates, respectively. Then
both selenium-containing ring and exocyclic imine are formed by
selenium nucleophilic cyclization from the selenocarbonyl in-
termediates. In the case of amine as a reactant (A¼NH, Y¼Se or S), it
has been reported that intramolecular cyclization afforded the
selenium-containing heterocycles as Z isomer exclusively, despite
Entry
Solvent
I2 (equiv)
Temp
Time (min)
Yielda,b (%)
1
2
3
4
5
6
7
8
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
THF
CH3CN
CHCl3
Toluene
Toluene
Toluene
1.0
1.0
1.0
1.5
2.0
1.0
1.0
1.0
1.0
1.0
1.0
ꢁ40 ꢀC to rt
70c
10
10
10
10
30
30
60
10
10
10
84
90
90
89
88
89
75
77
75
71
75
0 ꢀ
rt
rt
rt
rt
rt
rt
rt
C
any functional groups (halogen,4,5 allyl,9 alkynyl,10,19,20 and allene10
)
and any ring size (five- to seven-membered ring). However, in the
case of the reactions between isoselenocyanates and alcohols (A¼O,
Y¼Se), whereas five-membered heterocycles were obtained as Z
isomers exclusively,6,11,23 Z/E isomerization was observed in six- and
seven-membered ring size.7,24,26 Furthermore, the reactions of
isoselenocyanates with sulfur nucleophiles (A¼S, Y¼Se), the Z/E
isomerization was also observed in five- and six-membered ring size
via intramolecular cyclization of selenothiocarbamates.25 Similarly,
intramolecular cyclization of dithiocarbamates induces the Z/E
isomerization (A¼S, Y¼S).12,26 Taken together, it is shown that Z/E
isomerization of intramolecular cyclization of chalcogen-containing
heterocycles bearing an exocyclic imine depends on both ring size
and nature of heteroatom in the chalcogenocarbonyl intermediates.
In conclusion, we described the synthesis of 2-imino-1,3-
thiaselenolane derivatives using S-allyl-selenothiocarbamates 2.
First, we prepared S-allyl-selenothiocarbamates 2 by the reaction of
isoselenocyanates 1 with allyl mercaptan. Then, intramolecular
9
10
11
40 ꢀC
80 ꢀC
a
Isolated yield.
All product was isolated as isomeric mixture.
ꢁ40 ꢀC (60 min) to rt (10 min).
b
c
Next, we examined further structural modification by using
DBU.11 The reaction of 3a with 1.5 equiv of DBU in CH2Cl2 at room
temperature for 4 h gave 2-phenylimino-4-methylidene-1,3-
thiaselenolane 4a in 80% yield retaining stereochemistry (Z/
E¼85:15). Similarly, 4b was obtained from 3b in 57% yield as iso-
meric mixture (Z/E¼85:15) as shown in Scheme 2.
Previously, we reported the synthesis of 2-imino-5-methyl-1,3-
selenazolidines via acid-induced intramolecular cyclization
from N-allyl-selenoureas.9 In this expansion, S-allyl-phenyl-
selenothiocarbamate 2a was treated with hydrogen chloride under
the reflux conditions for 12 h, 4-methyl-2-phenylimino-1,3-
iodocyclization of
2 gave 2-imino-1,3-thiaselenolanes 3, and
acid-cyclization led to 2-imino-4-methyl-1,3-thiaselenolane 5, re-
spectively. In these cyclizations, we observed the Z/E isomerization
Table 3
Synthesis of 2-imino-1,3-thiaselenolanes 3 via iodocyclization of S-allyl-selenothiocarbamate 2
Entry
S-Allyl-selenothiocarbamate 2
Time
2-Imino-1,3-thiaselenolane 3
Product
Yielda (%)
77Se NMR
d
(ppm)
Z/Eb
Z
E
1
10 min
90
85:15
587.0
584.6
620.6
2
3
1 h
83
83:17
617.7
30 min
1 h
75
40
85:15
86:14
592.4
587.6
606.5
623.0
4
a
Isolated yield.
b
The ratio was calculated by 1H NMR spectra.

Y. Toyoda, M. Koketsu / Tetrahedron 68 (2012) 10496e10501
10499
chromatography. Melting points were measured by a Yanagimoto
micromelting point apparatus (uncorrected). IR spectra were mea-
sured on JASCO FT/IR-410 Fourier Transform Infrared Spectrometer.
The 1H NMR spectra, 13C NMR spectra, and 77Se NMR spectra were
measured on JEOL:JNM ECX-400 P, JEOL:JNM ECA-600 spectrometers
inCDCl3. Chemicalshifts ofprotonsare reported in
TMS as an internal standard. The 77Se chemical shifts were expressed
in values deshielded with respect to neat Me2Se. The mass spectra
d values referredto
d
(MS) and high-resolution mass spectra (HRMS) were measured on a
JEOL JMS-700.
Scheme 2. Synthesis of 2-imino-4-methylidene-1,3-thiaselenolanes 4.
3.2. Typical procedure for the preparation of S-allyl-seleno-
thiocarbamate 2 (2b)
To a stirred suspension of NaH (60%,144 mg, 3.60 mmol) in dry THF
(4.0 ml) was added 4-methylphenylisoselenocyanate 1b (588.2 mg,
3.00 mmol) at 0 ꢀC. After allyl mercaptan (272
ml, 3.30 mmol) was
added dropwise, stirring was continued for 10 min at 0 ꢀC. The re-
action mixture was quenched with saturated aqueous NH4Cl solution,
extracted with diethyl ether, and washed with water and brine. The
combined organic layer was dried over Na2SO4 and evaporated to
dryness. The residue was purified by flash chromatography (SiO2:
hexane/diethyl ether¼10:1) to give 2b (450.5 mg, 83%).
Scheme 3. Synthesis of 4-methyl-2-phenylimino-1,3-thiaselenolane 5 with acid.
at the exocyclic imine position. Further structural modification of 3
with DBU afforded 2-imino-4-methylidene-1,3-thiaselenolanes 4
retaining stereochemistry. In addition, we discussed the Z/E isom-
erization of exocyclic imines, which depends on ring size, and na-
ture of heteroatom in selenocarbonyl intermediates.
3.2.1. S-Allyl-N-phenyl-selenothiocarbamate (2a). Yellow solid; mp:
55e56 ꢀC; IR (KBr): 1334, 1501 cmꢁ1 1H NMR (400 MHz, CDCl3):
;
d
4.03 (2H, d, J¼6.8 Hz, CH2), 5.16 (1H, d, J¼10.0 Hz, CH), 5.30 (1H,
dd, J¼0.9, 16.1 Hz, CH), 5.84e5.96 (1H, m, CH), 7.30e7.44 (5H, m,
Ar), 10.7 (1H, br s, NH); 13C NMR (100 MHz, CDCl3):
42.7, 119.2,
3. Experimental section
3.1. General
d
125.1, 128.0, 129.2, 131.4, 138.3, 201.9; 77Se NMR (95 MHz, CDCl3):
d
571.1; MS (EI): m/z¼257 [M]þ. Anal. Calcd for C10H11NSSe: C,
All solvents and commercially available reagents were purchased
from the suppliers and used without further purification. All reactions
were performed under nitrogen atmosphere. Evaporation and con-
densation were carried out in vacuo. TLC analysis was performed on
Merck TLC (silica gel 60F254 on glass plate). Silica gel (Kanto Chemical
Co. Inc., 60N, spherical, neutral) was used for flash column
46.88; H, 4.33; N, 5.47. Found: C, 47.05; H, 4.40; N, 5.48.
3.2.2. S-Allyl-N-(4-methylphenyl)-selenothiocarbamate (2b). Yellow
oil; IR (KBr): 1504, 1586 cmꢁ1 1H NMR (400 MHz, CDCl3):
; d 2.30
(3H, s, Me), 4.01 (2H, d, J¼7.3 Hz, CH2), 5.12 (1H, d, J¼10.0 Hz, CH),
5.26 (1H, d, J¼16.7 Hz, CH), 5.84e5.94 (1H, m, Ar), 7.01e7.30 (4H, m,
Table 4
Summary of selenium- or sulfur-containing heterocycles bearing an exocyclic imine
A
Y
Z
Ring size
Stereochemistry
References
NH
Se
Br, Cl
Allyl
5, 6, 7
6
Z
Z
4,5
9
Alkynyl
Allene
Br, Cl
Allyl
5, 6
6, 7
5, 6
5, 6
Z
Z
10,19,20
10
4
S
Z
NDa
21,22
O
Se
Br
5
Z
6
Allyl
Alkynyl
Br
5
5
6, 7
Z
Z
11
24
7,23,25
Z and E
S
Se
S
Cl
6
5
5
5
Z and E
Z and E
Z and E
Z and E
25
Allyl
Allyl
Alkynyl
This study
12,b
26,b
a
Not described.
Dithiocarbamates were prepared by carbon disulfide.
b

10500
Y. Toyoda, M. Koketsu / Tetrahedron 68 (2012) 10496e10501
Ar), 10.8 (1H, br s, NH); 13C NMR (100 MHz, CDCl3):
d
20.9, 42.6,
125.8, 126.8, 127.2, 130.5, 150.8, 165.5; 77Se NMR (95 MHz, CDCl3):
118.9, 125.1, 129.5, 129.7, 131.4, 137.0, 201.6; 77Se NMR (95 MHz,
major:
d
592.4; minor:
d
606.5; MS (EI): m/z¼397 [M]þ. Anal. Calcd
CDCl3):
d
564.7; MS (EI): m/z¼271 [M]þ; HRMS (EI): calcd for
for C11H12INSSe: C, 33.35; H, 3.05; N, 3.54. Found: C, 33.46; H, 3.18;
N, 3.19.
C11H13NSSe: 270.9933, found: 270.9954 [M]þ.
3.2.3. S-Allyl-N-(2-methylphenyl)-selenothiocarbamate (2c). Yellow
3.3.4. 2-(4-Chlorophenylimino)-4-(iodomethyl)-1,3-thiaselenolane
oil; IR (KBr): 1589 cmꢁ1
;
1H NMR (400 MHz, CDCl3):
d
2.31 (3H, s,
(3d). Pale yellow oil; IR (KBr): 1580, 1595 cmꢁ1; 1H NMR (600 MHz,
Me), 3.98 (2H, d, J¼7.3 Hz, CH2), 5.12 (1H, d, J¼10.0 Hz, CH), 5.25
CDCl3):
d
3.56 (1H, dd, J¼6.2, 9.9 Hz, CH), 3.68e3.93 (3H, m, CH and
(1H, d, J¼16.7 Hz, CH), 5.80e5.92 (1H, m, CH), 7.19e7.33 (4H, m, Ar),
CH2), 4.32e4.39 (minor 1H, m, CH), 4.42e4.48 (1H, m, CH),
10.7 (1H, br s, NH); 13C NMR (100 MHz, CDCl3):
d 17.7, 42.4, 118.9,
6.84e6.97 (2H, m, Ar), 7.24e7.40 (2H, m, Ar); 13C NMR (150 MHz,
126.6, 127.1, 129.0, 130.9, 131.5, 134.9, 137.1, 202.9; 77Se NMR
CDCl3): major:
d
7.48, 41.4, 49.5 (1J(77See13C)¼60.6 Hz),120.8,129.3,
(95 MHz, CDCl3):
d
543.1; MS (EI): m/z¼271 [M]þ; HRMS (EI): calcd
130.5,151.6,167.11; minor: d 7.74, 44.5, 47.5,121.4,129.2,130.1,150.1,
for C11H13NSSe: 270.9933, found: 270.9953 [M]þ.
167.06; 77Se NMR (114 MHz, CDCl3): major:
d 587.6; minor: d 623.0;
MS (FAB): m/z¼418 [MþH]þ. Anal. Calcd for C10H9ClINSSe: C, 28.83;
3.2.4. S-Allyl-N-(4-chlorophenyl)-selenothiocarbamateꢁ(12d). Yellow
H, 2.18; N, 3.36. Found: C, 28.72; H, 2.30; N, 3.25.
solid; mp: 52 ꢀC; IR (KBr): 1353, 1485, 1514 cm
;
1H NMR
(400 MHz, CDCl3):
d
4.03 (2H, d, J¼6.9 Hz, CH2), 5.18 (1H, d,
3.4. Typical procedure for preparation of 4 (4b)
J¼10.5 Hz, CH), 5.32 (1H, dd, J¼1.3, 15.6 Hz, CH), 5.84e5.96 (1H, m,
CH), 7.28e7.41 (4H, m, Ar), 10.6 (1H, br s, NH); 13C NMR (100 MHz,
To a solution of 3b (198.1 mg, 0.500 mmol) in CH2Cl2 (2 ml) was
added DBU (167.9 ml, 0.750 mmol) and the resulting reaction mix-
CDCl3):
d
42.7, 119.5, 126.5, 129.4, 131.2, 133.7, 136.8, 202.2; 77Se
NMR (95 MHz, CDCl3):
d
586.3; MS (EI): m/z¼291 [M]þ; HRMS (EI):
ture was stirred for 4 h at room temperature. The reaction mixture
was extracted with CH2Cl2, and washed with water and brine. The
combined organic layer was dried over Na2SO4, filtered, and
evaporated in vacuo. The residue was chromatographed on silica
gel using diethyl ether/hexane (1:6) as eluent to give 4b (75.8 mg,
57%, major/minor¼85:15).
calcd for C10H10ClNSSe: 290.9385, found: 290.9396 [M]þ.
3.3. Typical procedure for preparation of 3 (3b)
To a solution of 2b (273.0 mg, 1.01 mmol) in CH2Cl2 (5 ml) was
added I2 (376 mg, 1.00 mmol) at room temperature. After stirring
for 1 h, the reaction mixture was poured to saturated Na2S2O3, then
extracted with CH2Cl2 and washed with water and brine. The
combined organic layer was dried over Na2SO4, filtered, and
evaporated in vacuo. The residue was purified by flash chroma-
tography (SiO2: hexane/diethyl ether¼10:1) to give 3b (331.8 mg,
83%, major/minor¼83:17).
3.4.1. 4-Methylidene-2-phenylimino-1,3-thiaselenolane
(4a). Colo-
d 4.12 (2H, s,
rless oil; IR (KBr): 1583 cmꢁ1; 1H NMR (600 MHz, CDCl3):
CH2), 4.19 (minor 2H, s, CH2), 5.24 (1H, s, CH), 5.33 (minor 1H, s, CH),
5.71(1H,s,CH), 5.73(minor1H, s,CH), 6.93e6.99(2H,m, Ar),7.12e7.19
(1H, m, Ar), 7.32e7.38 (2H, m, Ar); 13C NMR (150 MHz, CDCl3): major:
d
43.3, 115.0 (1J(77See13C)¼19.2 Hz), 119.4, 125.1, 129.2, 142.8, 153.3,
166.6; minor: d
46.8, 114.5, 120.0, 124.8, 129.1, 141.7, 151.1, 166.5; 77Se
3.3.1. 4-(Iodomethyl)-2-phenylimino-1,3-thiaselenolane (3a). White
NMR (114 MHz, CDCl3): major: d 537.1; minor: d 564.2; MS (EI): m/
solid; mp: 85.5e86.5 ꢀC; IR (KBr): 1583 cmꢁ1
;
1H NMR (600 MHz,
z¼255 [M]þ. Anal. Calcd for C10H9NSSe: C, 47.25; H, 3.57; N, 5.51.
CDCl3):
d
3.56 (1H, dd, J¼6.2,10.0 Hz, CH), 3.67e3.92 (3H, m, CH and
Found: C, 47.31; H, 3.67; N, 5.48.
CH2), 4.40e4.47 (1H, m, 2J(77See1H)¼39.8 Hz), 6.90e6.93 (2H, m,
Ar), 6.95e6.98 (minor 2H, m, Ar), 7.12e7.18 (1H, m, Ar), 7.31e7.37
3.4.2. 4-Methylidene-2-(4-methylphenylimino)- 1,3-thiaselenolane
(2H, m, Ar); 13C NMR (150 MHz, CDCl3): major:
d
7.7, 41.3, 49.2
(4b). White solid; mp: 62e63 ꢀC; IR (KBr): 1591 cmꢁ1 1H NMR
;
(1J(77See13C)¼60.7 Hz), 119.4, 125.2, 129.3, 153.3, 166.0; minor:
(600 MHz, CDCl3): d 2.33 (3H, s, CH3), 4.10 (2H, s, CH2), 4.17 (minor 2H,
d
7.9, 44.3, 47.4, 119.9, 124.9, 129.1, 151.8, 165.9; 77Se NMR (114 MHz,
s, CH2), 5.22 (1H, d, J¼1.4 Hz, CH), 5.32 (minor 1H, s, CH), 5.70 (1H, d,
CDCl3): major:
d
587.0; minor:
d
620.6; MS (EI): m/z¼383 [M]þ.
J¼1.4 Hz, CH), 6.85 (2H, d, J¼8.2 Hz, Ar), 7.14 (2H, t, J¼8.2 Hz, Ar); 13C
Anal. Calcd for C10H10INSSe: C, 31.43; H, 2.64; N, 3.67. Found: C,
31.60; H, 2.75; N, 3.67.
NMR (150 MHz, CDCl3): major: d 20.9, 43.2, 114.8, 119.3, 129.8, 134.8,
142.9, 150.8, 165.9; minor: d 20.9, 46.7,114.4,119.9,129.6,134.4,141.6,
148.5, 165.8; 77Se NMR (114 MHz, CDCl3): major:
d
d 536.1; minor:
3.3.2. 4-(Iodomethyl)-2-(4-methylphenylimino)-1,3-thiaselenolane
563.0; MS (EI): m/z¼269 [M]þ. Anal. Calcd for C11H11NSSe: C, 49.25;
(3b). Yellow oil, IR (KBr): 1588 cmꢁ1
;
1H NMR (600 MHz, CDCl3):
H, 4.13; N, 5.22. Found: C, 49.32; H, 4.30; N, 4.94.
d
2.23 (4H, s, Me), 3.38e3.41 (minor 1H, m, CH), 3.43 (1H, dd, J¼6.2,
10.0 Hz, CH), 3.52e3.63 (2H, m, CH2), 3.64e3.72 (1H, m, CH),
4.18e4.22(minor1H, m, CH), 4.26e4.32(1H, m, 2J(77See1H)¼39.9 Hz,
CH), 6.71e6.80 (2H, m, Ar), 7.02e7.07 (2H, m, Ar); 13C NMR (150 MHz,
3.5. Typical procedure for preparation of 5
Hydrogen chloride of 1 M in diethyl ether solution (0.6 ml,
0.6 mmol) was added to an ethyl acetate solution (4 mL) of 2a
(102.5 mg, 0.400 mmol). The reaction mixture was stirred for 12 h
in reflux. The mixture was extracted with ethyl acetate, washed
with water and brine. The organic layer was dried over Na2SO4 and
evaporated to dryness. The residue was purified by flash chroma-
tography on silica gel with hexane/ethyl acetate (5:1) as the eluent
to give 5 (51.2 mg, 50%, major/minor¼84:16).
CDCl3): major:
d
7.99, 20.9, 410, 48.9 (1J(77See13C)¼60.7 Hz), 119.1,
129.6, 134.5, 150.6, 165.0; minor:
d 8.23, 20.9, 44.1, 47.1, 119.7, 129.5,
134.2, 149.0, 164.8; 77Se NMR (114 MHz, CDCl3): major:
d 584.6; mi-
nor:
d
617.7; MS (EI): m/z¼397 [M]þ. Anal. Calcd for C11H12INSSe: C,
33.35; H, 3.05; N, 3.54. Found: C, 33.39; H, 3.17; N, 3.20.
3.3.3. 4-(Iodomethyl)-2-(2-methylphenylimino)-1,3-thiaselenolane
(3c). White solid; mp: 100e101 ꢀC; IR (KBr): 1604 cmꢁ1 1H NMR
(400 MHz, CDCl3): 2.17 (3H, s, Me), 2.37 (minor 3H, s, Me), 3.54
;
d
3.5.1. 4-Methyl-2-phenylimino-1,3-thiaselenolane 5. Colorless oil;
(1H, dd, J¼6.4, 10.0 Hz, CH), 3.62e3.82 (2H, m, CH2), 4.30e4.42 (1H,
m, CH), 4.30e4.42 (1H, m, CH), 6.72e6.77 (1H, m, Ar), 7.02e7.09
(1H, m, Ar), 7.11e7.20 (2H, m, Ar); 13C NMR (100 MHz, CDCl3):
IR (KBr): 1580 cmꢁ1 1H NMR (400 MHz, CDCl3):
; d 1.64 (3H, d,
J¼6.9 Hz, 3J(77See1H)¼19.2 Hz, CH3), 1.70 (minor 3H, d, J¼6.9 Hz,
CH3), 3.26 (1H, dd, J¼8.0, 12.1 Hz, CH2), 3.34 (minor 1H, dd, J¼7.3,
12.4 Hz, CH2), 3.57 (1H, dd, J¼4.6, 11.9 Hz, CH2), 3.66 (1H, dd, J¼4.1,
11.9 Hz, CH2), 4.20e4.30 (1H, m, CH), 6.91e6.99 (2H, m, Ar),
major:
d
7.83, 17.6, 41.5, 48.9 (1J(77See13C)¼62.3 Hz), 117.8, 125.1,
126.6, 128.5, 130.5, 152.6, 165.5; minor: d 7.83, 18.3, 44.1, 48.0, 118.5,

Y. Toyoda, M. Koketsu / Tetrahedron 68 (2012) 10496e10501
10501
7.10e7.18 (1H, m, Ar), 7.31e7.38 (2H, m, Ar); 13C NMR (100 MHz,
8. (a) Frederickson, M.; Grigg, R. Org. Prep. Proced. Int. 1997, 29, 33e62; (b) da Silva,
F. M.; Jones, J.; de Mattos, M. C. S. Curr. Org. Synth. 2005, 2, 393e414; (c)
Mphahlele, M. J. Molecules 2009, 14, 4814e4837; (d) Parvatkar, P. T.; Para-
meswaran, P. S.; Tilve, S. G. Chem.dEur. J. 2012, 18, 5460e5489.
9. Koketsu, M.; Kiyokuni, T.; Sakai, T.; Ando, H.; Ishihara, H. Chem. Lett. 2006, 35,
626e627.
CDCl3): major:
d
20.7, 44.0, 45.6(1J(77See13C)¼56.5 Hz), 47.1, 119.5,
124.8, 129.3, 153.8, 168.5; minor:
d 20.5, 43.8, 48.0, 120.0, 124.5,
129.1, 152.1, 168.1; 77Se NMR (95 MHz, CDCl3): major:
d 546.7, mi-
nor:
d
581.6; MS (FAB): m/z¼258 [MþH]þ; HRMS (FAB): calcd for
10. Garud, D. R.; Koketsu, M. Org. Lett. 2008, 10, 3319e3322.
11. Garud, D. R.; Makimura, M.; Ando, H.; Ishihara, H.; Koketsu, M. Tetrahedron Lett.
C10H12NSSe: 257.9856, found: 257.9878 [MþH]þ.
2007, 48, 7764e7768.
12. Halimehjani, A. Z.; Maleki, H.; Saidi, M. R. Tetrahedron Lett. 2009, 50,
2747e2749.
Acknowledgements
13. Several reports were available about the synthesis of 1,3-thiaselenolanes from
selenium dihalide. See: (a) Amosova, S. V.; Penzik, M. V.; Potapov, V. A.; Al-
banov, A. I. Russ. Chem. Bull. 2008, 57, 1323; (b) Amosova, S. V.; Penzik, M. V.;
Albanov, A. I.; Potapov, V. A. Russ. J. Gen. Chem. 2009, 79, 161; (c) Potapov, V. A.;
Volkova, K. A.; Amosova, S. V. Russ. J. Gen. Chem. 2009, 79, 1758e1759; (d)
Amosova, S. V.; Penzik, M. V.; Albanov, A. I.; Potapov, V. A. Tetrahedron Lett.
2009, 50, 306e308; (e) Amosova, S. V.; Penzik, M. V.; Albanov, A. I.; Potapov, V.
A. J. Organomet. Chem. 2009, 694, 3369e3372; (f) Potapov, V. A.; Kurkutov, E. O.;
Amosova, S. V. Russ. J. Gen. Chem. 2010, 80, 1220e1221; (g) Potapov, V. A.;
Kurkutov, E. O.; Musalov, M. V.; Amosova, S. V. Tetrahedron Lett. 2010, 51,
5258e5261; (h) Potapov, V. A.; Shagun, V. A.; Penzik, M. V.; Amosova, S. V. J.
Organomet. Chem. 2010, 695, 1603e1608; (i) Potapov, V. A.; Kurkutov, E. O.;
Amosova, S. V.; Rusakov, Y. Y. Russ. Chem. Bull. 2011, 60, 196e197.
14. Fernandez-Bolanos, J. G.; Lopez, O.; Ulgar, V.; Maya, I.; Fuentes, J. Tetrahedron
Lett. 2004, 45, 4081e4084.
We thank Masayuki Ninomiya for measurement assistance. This
work was supported by a Grant-in-Aid for Science Research from
the Ministry of Education, Culture, Sports, Science and Technology
of Japan (no. 17550099) to which we are grateful.
Supplementary data
Supplementary data associated with this article can be found in
the online version, at http://dx.doi.org/10.1016/j.tet.2012.07.083.
These data include MOL files and InChiKeys of the most important
compounds described in this article.
15. Previous example of the reaction of isoselenocyanates with thiols. See: (a)
Shafiee, A.; Fanaii, G. Synthesis 1984, 512e514; (b) Zmitrovich, N. I.; Petrov, M.
L.; Petrov, A. A. Zh. Org. Khim. 1990, 26, 179e184; (c) Zmitrovich, N. I.; Petrov, M.
L.; Petrov, A. A. Zh. Org. Khim. 1991, 27, 1394e1398; (d) Sommen, G. L.; Linden,
A.; Heimgartner, H. Heterocycles 2005, 65, 1903e1915.
16. Previous reports about selenothiocarbamates. See: (a) Koketsu, M.; Fukuta, Y.;
Ishihara, H. J. Org. Chem. 2002, 67, 1008e1011; (b) Koketsu, M.; Otsuka, T.;
Ishihara, H. Phosphorus, Sulfur Silicon Relat. Elem. 2004, 179, 443e448; (c) Murai,
T. Organoselenium Chemistry In Synthesis and Reactions; Wirth, T., Ed.;
Wiley-VCH: Weinheim, Germany, 2012; pp 257e285.
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