One-pot synthesis of 2-sulfanyl-3-sulfinyl(or sulfonyl)-1H-indoles via cyclization of 1-isothiocyanato-2-[sulfinyl(or sulfonyl)methyl]benzenes with sodium hydride

Article abstract of DOI:10.1016/j.tet.2013.07.011

An efficient one-pot method for the synthesis of 2-sulfanyl-3-sulfinyl(or sulfonyl)-1H-indoles from 1-isothiocyanato-2-[sulfinyl(or sulfonyl)methyl] benzenes, derived from N-[2-(chloromethyl)phenyl]formamide by an easy four-step sequence, has been develop

Full text of DOI:10.1016/j.tet.2013.07.011

Tetrahedron 69 (2013) 7936e7942
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Tetrahedron
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One-pot synthesis of 2-sulfanyl-3-sulfinyl(or sulfonyl)-1H-indoles
via cyclization of 1-isothiocyanato-2-[sulfinyl(or sulfonyl)methyl]
benzenes with sodium hydride
*
Kazuhiro Kobayashi , Akihiro Kobayashi, Kosuke Ezaki
Division of Applied Chemistry, Department of Chemistry and Biotechnology, Graduate School of Engineering, Tottori University, 4-101 Koyama-minami,
Tottori 680-8552, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 13 May 2013
Received in revised form 3 July 2013
Accepted 5 July 2013
Available online 12 July 2013
An efficient one-pot method for the synthesis of 2-sulfanyl-3-sulfinyl(or sulfonyl)-1H-indoles from 1-
isothiocyanato-2-[sulfinyl(or sulfonyl)methyl]benzenes, derived from N-[2-(chloromethyl)phenyl]form-
amide by an easy four-step sequence, has been developed. The products are formed via cyclization of the
precursor isothiocyanates using 2 equiv of sodium hydride followed by S- and/or N-alkylation of the
resulting 1-sodio-2-sodiosulfanyl-1H-indole intermediates.
Ó 2013 Elsevier Ltd. All rights reserved.
Keywords:
2-Sulfanyl-3-sulfinylindoles
2-Sulfanyl-3-sulfonylindoles
Isothiocyanate
Sodium hydride
Alkylation
1. Introduction
2. Results and discussion
2-Sulfanyl-3-sulfinyl(or sulfonyl)-1H-indoles are of potentially
biological importance1 and some of them have been found in na-
ture.2 However, their general synthesis has been relatively un-
explored so far,3 although quite a number of methods for the
preparation of 1H-indole derivatives have been reported.4 1-
Methyl-2-methylsulfanyl-3-methylsulfinyl-1H-indole has been
prepared by the acid-catalyzed reaction of 1-methyl-1H-indole
with 4-(methylsulfanyl)morpholine followed by oxidation of the
resulting 1-methyl-2,3-bis(methylsulfanyl)-1H-indole.3 In this pa-
per, we wish to describe the results of our investigation, which
provide a convenient method to prepare 3-sulfinyl(or sulfonyl)-1H-
indoles carrying a 2-alkylsulfanyl substituent 7 and those carrying
2-alkylsulfanyl and 1-alkyl substituents 8 and 9 utilizing cyclization
of 1-isothiocyanato-2-[sulfinyl(or sulfonyl)methyl]benzenes 5 us-
ing 2 equiv of sodium hydride followed by S- and/or N-alkylation of
the resulting 1-sodio-2-sodiosulfanyl-3-sulfinyl(or sulfonyl)-1H-
indole intermediates 6 under mild reaction conditions. In addition,
we present an application of this procedure to the synthesis of
tricyclic compounds including the 3-sulfinyl(or sulfonyl)-1H-indole
moiety 10.
We initiated our investigation by preparing 2-(sulfinyl(or sul-
fonyl)methyl)phenyl isothiocyanates 5, the key precursors for our
synthesis. The synthesis of these compounds was readily accom-
plished from N-[2-(chloromethyl)phenyl]formamide (1) according
to the process illustrated in Scheme 1. Substitution of the chloro
group with sodium thiolates in DMF provided N-[2-(sulfanyl
methyl)phenyl]formamides 2 in excellent yields, which were then
oxidized with 1 or 2 equiv of sodium metaperiodate in aqueous
methanol to furnish N-[2-(sulfinyl(or sulfonyl)methyl)phenyl]
formamides 3 in good yields. These sulfinyl or sulfonyl formamides
3 were dehydrated with phosphorous oxychloride in the presence
of triethylamine in THF to afford 1-isocyano-2-[sulfinyl(or sulfinyl)
methyl]benzene 4 in good yields. Finally, these isocyano sulfoxides
or sulfones were converted into the corresponding isothiocyanates
5 on treatment with sulfur in the presence of a catalytic amount of
selenium and excess triethylamine under Fujiwara’s conditions.5
First, we tried to prepare 2-methylsulfanyl-3-phenylsulfinyl-1H-
indole (7a) from 1-isothiocyanato-2-[(phenylsulfinyl)methyl]ben-
zene (5a) and iodomethane. Thus, compound 5a was treated with
1 equiv of sodium hydride in THF/DMSO (2:1, v/v) at 0 ꢀC. Vigorous
evolution of hydrogen gas revealed the deprotonation from the
benzyl hydrogen of 5a, and TLC analyses on silica gel after 5 min
showed complete consumption of the starting materials. However,
after addition of iodomethane and the subsequent usual aqueous
* Corresponding author. Tel./fax: þ81 857 31 5263; e-mail address: kkoba@
chem.tottori-u.ac.jp (K. Kobayashi).
0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.07.011

K. Kobayashi et al. / Tetrahedron 69 (2013) 7936e7942
7937
1H-indole 6a (n¼1, R1¼Ph), then an equivalent of iodomethane was
added. The reaction proceeded immediately at 0 ꢀC and the desired
product 7a was obtained in 78% yield. Using four isothiocyanato
sulfoxides and sulfones including 5a, and three haloalkanes in-
cluding iodomethane, the other five 2-alkylsulfanyl-3-sulfinyl(or
sulfonyl)-1H-indoles 7bef could be obtained under the same re-
action conditions in comparable yields to that of 7a, as summarized
in Table 1. The use of DMSO as a co-solvent had a detrimental effect
upon the smooth progress of the cyclization forming a pyrrole ring
and the subsequent alkylation. The reactions without DMSO both of
the cyclization and the alkylation proceeded sluggishly and un-
cleanly to result in the formation of considerably complex mixtures
of products, from which only low yields (<10%) of the desired
products contaminated with structurally undefined products were
isolated.
CH2Cl
CH2SR1
NHCHO
R1SH, NaH
DMF, 0 ˚C
NHCHO
2a R1 = Ph 93%
1
2b R1 = 4-ClC6H4 93%
2c R1 = Et 99%
CH2S(O)nR1
NHCHO
1 or 2 eq.NaIO4
aq. MeOH, r. t.
3a n = 1, R1 = Ph 81%
3b n = 1, R1 = 4-ClC6H4 80%
3c n = 2, R1 = Ph 79%
3d n = 2, R1 = Et 80%
Table 1
Preparation of 2-sulfanyl-3-sulfinyl(or sulfonyl)-1H-indoles 7
Entry
5
R2X
7
Yielda/%
CH2S(O)nR1
POCl3, Et3N
THF, 0 ˚C
1
2
3
4
5
6
5a (n¼1, R1¼Ph)
MeI
EtI
BnBr
MeI
MeI
EtI
7a
7b
7c
7d
7e
7f
78
75
71
71
73
83
5a
5a
NC
5b (n¼1, R1¼4-ClC6H4)
5c (n¼2, R1¼Ph)
5d (n¼2, R1¼Et)
4a n = 1, R1 = Ph 84%
4b n = 1, R1 = 4-ClC6H4 86%
4c n = 2, R1 = Ph 78%
4d n = 2, R1 = Et 88%
a
Isolated yields.
When 2 M amounts of haloalkanes were added after generation
of 1-sodio-2-sodiosulfanyl-1H-indole intermediates 6, 1-alkyl-2-
alkylsulfanyl-3-sulfinyl(or sulfonyl)-1H-indoles 8 were obtained
in good yields in general, as summarized in Table 2. However, after
addition of haloalkanes, the reaction temperature was raised to
room temperature, because N-alkylation did proceed very slug-
gishly at 0 ꢀC. It is important to note that only iodomethane was
usable in the reactions using 6c and 6d (n¼2). For example, the
reaction of 6d with 2 equiv of iodoethane resulted in the exclusive
formation of only S-ethylated product 7f. This result implies that
the reactivity of 2-ethylsulfanyl-3-ethylsulfonyl-1-sodio-1H-indole
intermediate is not enough efficient to achieve ethylation with
iodoethane.
CH2S(O)nR1
NCS
5a n = 1, R1 = Ph 98%
5b n = 1, R1 = 4-ClC6H4 92%
5c n = 2, R1 = Ph 83%
5d n = 2, R1 = Et 79%
S8, cat. Se, Et3N
THF, r. t.
Scheme 1.
workup, a rather complicated mixture, which proved to contain
a small amount of 7a on the basis of its 1H NMR spectrum. So, as
shown in Scheme 2, compound 5a was treated with 2 equiv of
sodium hydride to form 3-phenylsulfinyl-1-sodio-2-sodiosulfanyl-
Table 2
Preparation of 1-alkyl-2-sulfanyl-3-sulfinyl(or sulfonyl)-1H-indoles 8
Entry
5
R2X
8
Yield/%a
1
2
3
4
5
6
7
5a (n¼1, R1¼Ph)
MeI
EtI
BnBr
MeI
CH2]CHCH2Br
MeI
MeI
8a
8b
8c
8d
8e
8f
86
80
68
74
77
66
78
5a
5a
5b (n¼1, R1¼4-ClC6H4)
5b
5c (n¼2, R1¼Ph)
5d (n¼2, R1¼Et)
8g
a
Isolated yields.
Different haloalkanes proved to be usable in S-alkylation and N-
alkylation of 6a and 6b (n¼1). The reaction of these dianionic in-
termediates with an equivalent each of the first haloalkane fol-
lowed by second electrophile afforded 1-alkyl-2-alkylsulfanyl-3-
sulfinyl-1H-indoles 9 in fair yields, as summarized in Table 3. For
example, after intermediate 6a was first treated with iodomethane
at 0 ꢀC, (bromomethyl)benzene was added at the same temperature
and temperature was raised to room temperature to provide 2-
methylsulfanyl-1-phenylmethyl-3-phenylsulfinyl-1H-indole (9a)
(entry 1). The second electrophile was not limited to only hal-
oalkanes, as benzoyl chloride worked equally well. Unfortunately,
Scheme 2.

7938
K. Kobayashi et al. / Tetrahedron 69 (2013) 7936e7942
Table 3
Low-resolution MS spectra (EI, 70 eV) were measured by a JEOL JMS
AX505 HA spectrometer. High-resolution MS spectra (DART, posi-
tive) were measured by a Thermo Scientific Exactive spectrometer.
TLC was carried out on Merck Kieselgel 60 PF254. Column chro-
matography was performed using WAKO GEL C-200E. All of the
organic solvents used in this study were dried over appropriate
drying agents and distilled prior to use.
Preparation of 1-substituted 2-sulfanyl-3-sulfinyl-1H-indoles 9
Entry
5
R2X
R3X
9
Yielda/%
1
2
3
4
5
5a (n¼1, R1¼Ph)
MeI
BnBr
MeI
MeI
BnBr
MeI
BzCl
BnBr
MeI
9a
9b
9c
9d
9e
57
76
57
64
63
5a
5a
5b (n¼1, R1¼4-ClC6H4)
5b
CH2]CHCH2Br
a
Isolated yields.
3.2. Starting materials
N-[2-(Chloromethyl)phenyl]formamide (1) was prepared accor
ding to the reported method.6 All other chemicals used in this study
were commercially available.
however, similar attempts via 6c and 6d (n¼2) all resulted in fail-
ure; the second alkylation at the 1-position did not occur at all.
In order to demonstrate the utility of the present procedure by
preparing tricyclic compounds with the 3-sulfinyl(or sulfonyl)-1H-
indole moiety 10,1-sodium-2-sodiosulfanyl-1H-indole intermediates
6 were reacted with 1,3-dibromopropane and 1,2-dibromoethane.
Not only S-alkylation but also N-alkylation of 6a and 6b with these
dibromides smoothly occurred at 0 ꢀC to afford the corresponding
tricyclic compounds 10aec as illustrated in Scheme 3. The yields of
these products were good as can be seen from Table 4, entries 1e3.
The reactions of 6c and 6d with 1,3-dibromopropane also proceeded
under the same conditions to afford 10d and 10e, respectively, but in
somewhat lower yields (entries 4 and 5) than those of 10aec.
3.2.1. N-[2-(Sulfanylmethyl)phenyl]formamides 2. These compounds
were prepared by treating 1 with sodium thiolates, generated from
thiols and NaH, in DMF at 0 ꢀC.7
3.2.1.1. N-[2-(Phenylsulfanylmethyl)phenyl]formamide (2a). A
colorless oil; Rf 0.16 (AcOEt/hexane 1:3); IR (neat) 3275,
1681 cmꢁ1
;
1H NMR (500 MHz, CDCl3)
d
4.08 and 4.10 (2s, com-
bined 2H), 7.02e7.31 (m, 9H), 7.82e8.54 (m, 2H); 13C NMR
(125 MHz, CDCl3) 36.62, 36.81, 121.84, 124.24, 125.43, 126.08,
d
127.45, 127.57, 128.59, 128.89, 129.03, 129.06, 130.68, 131.13, 131.25,
131.60, 134.88, 135.32, 159.20, 162.73. Anal. Calcd for C14H13NOS: C,
69.11; H, 5.39; N, 5.76. Found: C, 69.03; H, 5.45; N, 5.71.
3.2.1.2. N-{2-[(4-Chlorophenyl)sulfanylmethyl]phenyl}formamide
(2b). A white solid; mp 92e93 ꢀC (hexane/CH2Cl2); IR (KBr) 3292,
1693, 1661 cmꢁ1 1H NMR (500 MHz, CDCl3)
; d 4.05 and 4.06 (2s,
combined 2H), 7.00e7.13 (m, 2H), 7.18e7.32 (m, 6H), 7.83e8.56 (m,
2H). Anal. Calcd for C14H12ClNOS: C, 60.54; H, 4.35; N, 5.04. Found:
C, 60.31; H, 4.35; N, 4.75.
Scheme 3.
3.2.1.3. N-[2-(Ethylsulfanylmethyl)phenyl]formamide
pale-yellow oil; Rf 0.32 (AcOEt/hexane 1:2); IR (neat) 3307,
1688 cmꢁ1; 1H NMR (500 MHz, CDCl3)
each, combined 3H), 2.41 and 2.43 (2q, J¼7.4 Hz each, combined
2H), 3.75 and 3.76 (2s, combined 2H), 7.08e7.33 (m, 4H),
8.00e8.69 (m, 2H). Anal. Calcd for C10H13NOS: C, 61.50; H, 5.71; N,
7.17. Found: C, 61.49; H, 5.82; N, 7.06.
(2c). A
Table 4
Preparation of tricyclic 1H-indole derivatives 10
d
1.23 and 1.24 (2t, J¼7.4 Hz
Entry
5
m
10
Yield/%a
1
2
3
4
5
5a (n¼1, R1¼Ph)
5b (n¼1, R1¼4-ClC6H4)
5b
1
1
0
1
1
10a
10b
10c
10d
10e
83
72
75
50
64
5c (n¼2, R1¼Ph)
5d (n¼2, R1¼Et)
3.2.2. N-[2-(Sulfinylmethyl)phenyl]formamides 3a and 3b. These
compounds were prepared by treating 2a and 2b with an equimolar
amount of NaIO4 in aqueous MeOH at room temperature.8
a
Isolated yields.
In conclusion, we have demonstrated that 1-isocyanato-2-
sulfinyl(or sulfonyl)methylbenzenes can serve as versatile pre-
cursors for the preparation of 2-sulfanyl-3-sulfinyl(or sulfonyl)-1H-
indoles, which are hard to obtain by previous methods. Since the
method employs readily available starting materials and is opera-
tionally simple, it may be of value in organic synthesis.
3.2.2.1. N-[2-(Phenylsulfinylmethyl)phenyl]formamide (3a). A
pale-yellow oil; Rf 0.40 (1:4 THF/hexane); IR (neat) 3256, 1684,
1020 cmꢁ1 1H NMR (500 MHz, CDCl3)
; d 3.86 and 3.90 (2d,
J¼17.5 Hz each, combined 1H), 4.34 and 4.40 (2d, J¼17.5 Hz each,
combined 1H), 6.58e7.29 (m, 4H), 7.44e7.51 (m, 5H), 7.86e9.81
(m, 2H); 13C NMR (125 MHz, CDCl3)
d 56.51, 59.07, 120.96, 124.09,
125.29, 125.37, 126.38, 126.45, 129.22, 130.22, 131.51, 131.65,
131.77, 132.27, 133.72, 136.04, 140.61, 145.09, 159.70, 163.11. Anal.
Calcd for C14H13NO2S: C, 64.84; H, 5.05; N, 5.40. Found: C, 64.66;
H, 5.08; N, 5.31.
3. Experimental
3.1. General
All melting points were obtained on a Laboratory Devices MEL-
TEMP II melting apparatus and are uncorrected. IR spectra were
recorded with a PerkineElmer Spectrum65 FTIR spectrophotome-
ter. 1H NMR spectra were recorded using TMS as an internal ref-
erence with a JEOL ECP500 FT NMR spectrometer operating at
500 MHz or JEOL LA400FTNMR spectrometer operating at
400 MHz. 13C NMR spectra were recorded using TMS as an internal
reference with a JEOL ECP500 FT NMR spectrometer operating at
125 MHz or JEOL LA400FTNMR spectrometer operating at 100 MHz.
3.2.2.2. N-{2-[(4-Chlorophenyl)sulfinylmethyl]phenyl}formamide
(3b). A reddish-white solid; mp 119e121 ꢀC (hexane/Et2O); IR
(KBr) 3260, 1690, 1030 cmꢁ1; 1H NMR (500 MHz, CDCl3)
d 3.82 and
3.85 (2d, J¼13.7 Hz each, combined 1H), 4.40 and 4.42 (2d,
J¼13.7 Hz, each, combined 1H), 6.56 and 6.67 (2dd, J¼7.8, 1.5 Hz
each, combined 1H), 6.96 and 7.06 (2ddd, J¼7.8, 7.3, 1.5 Hz each,
combined 1H), 7.21e7.39 (m, 4H), 7.45 (d, J¼8.3 Hz, 2H), 7.86e9.71
(m, 2H). Anal. Calcd for C14H12ClNO2S: C, 57.24; H, 4.12; N, 4.77.
Found: C, 57.03; H, 4.16; N, 4.75.

K. Kobayashi et al. / Tetrahedron 69 (2013) 7936e7942
7939
3.2.3. N-[2-(Sulfonylmethyl)phenyl]formamides 3c and 3d. These
compounds were prepared by treating 2a and 2c with two equi-
molar amounts of NaIO4 in aqueous MeOH at room temperature.8
129.62, 131.57, 132.28 (2C), 142.26. Anal. Calcd for C14H11NOS2: C,
61.51; H, 4.06; N, 5.12. Found: C, 61.36; H, 4.11; N, 5.02.
3.2.5.2. 1-[(4-Chlorophenyl)sulfinylmethyl]]-2-isothiocyanatoben
zene (5b). A yellow solid; mp 64e66 ꢀC (hexane/CH2Cl2); IR (KBr)
3.2.3.1. N-[2-(Phenylsulfonylmethyl)phenyl]formamide
white solid; mp 119e121 ꢀC (hexane/Et2O); IR (KBr) 3333, 1673,
1304 cmꢁ1 1H NMR (500 MHz, CDCl3)
4.38 and 4.40 (2s, com-
bined 2H), 6.67e7.85 (m, 9H), 8.41e8.69 (m, 2H). Anal. Calcd for
C14H13NO3S: C, 61.07; H, 4.76; N, 5.09. Found: C, 60.92; H, 4.52;
N, 5.01.
(3c). A
2188, 2097, 1051 cmꢁ1 1H NMR (500 MHz, CDCl3)
; d 4.11 (d,
;
d
J¼12.6 Hz, 1H), 4.13 (d, J¼12.6 Hz, 1H), 7.19 (d, J¼7.4 Hz, 1H), 7.23 (t,
J¼7.4 Hz, 1H), 7.26 (d, J¼7.4 Hz, 1H), 7.33 (td, J¼7.4, 1.7 Hz, 1H), 7.36
(d, J¼8.6 Hz, 2H), 7.44 (d, J¼8.6 Hz, 2H); 13C NMR (125 MHz, CDCl3)
d
59.16, 125.03, 125.64, 127.11, 127.23, 129.31, 129.83, 131.23, 132.35,
134.07, 137.86, 140.79. Anal. Calcd for C14H10ClNOS2: C, 54.63; H,
3.27; N, 4.55. Found: C, 54.56; H, 3.32; N, 4.41.
3.2.3.2. N-[2-(Ethylsulfonylmethyl)phenyl]formamide
reddish-white solid; mp 91e93 ꢀC (hexane/Et2O); IR (KBr) 3341,
1692, 1299 cmꢁ1 1H NMR (400 MHz, CDCl3)
1.42 and 1.44 (2t,
J¼7.8 Hz each, combined 3H), 3.02 and 3.06 (2q, J¼7.8 Hz each,
combined 2H), 4.315 and 4.324 (2s, combined 2H), 7.23e7.46 (m,
4H), 7.86e8.71 (m, 2H). Anal. Calcd for C10H13NO3S: C, 52.85; H,
5.77; N, 6.16. Found: C, 52.62; H, 5.82; N, 6.02.
(3d). A
;
d
3.2.5.3. 1-Isothiocyanato-2-(phenylsulfonylmethyl)benzene
(5c). An orange solid; mp 119e120 ꢀC (hexane/CH2Cl2); IR (KBr)
2189, 2116, 1319 cmꢁ1; 1H NMR (500 MHz, CDCl3)
d 4.43 (s, 2H), 7.13
(dd, J¼8.0, 1.1 Hz, 1H), 7.28 (ddd, J¼8.0, 7.4, 1.1 Hz, 1H), 7.33 (ddd,
J¼8.0, 7.4, 1.1 Hz, 1H), 7.45 (dd, J¼8.0, 1.1 Hz, 1H), 7.50 (t, J¼8.0 Hz,
2H), 7.64 (t, J¼8.0 Hz,1H), 7.68 (d, J¼8.0 Hz, 2H); 13C NMR (125 MHz,
3.2.4. 1-Isocyano-2-(sulfinyl(or sulfonyl)methyl)benzene 4. These
compounds were prepared by treating 3 with POCl3/Et3N in THF
at 0 ꢀC.9
CDCl3) d 58.49, 124.00, 127.33, 127.44, 128.56, 129.05, 130.28 (2C),
132.54, 134.27, 134.78, 138.83. Anal. Calcd for C14H11NO2S2: C, 58.11;
H, 3.83; N, 4.84. Found: C, 58.00; H, 3.84; N, 4.72.
3.2.4.1. 1-Isocyano-2-(phenylsulfinylmethyl)benzene (4a). A beige
3.2.5.4. 1-(Ethylsulfonylmethyl)-2-isothiocyanatobenzene (5d). A
pale-yellow solid; mp 108e110 ꢀC (hexane/CH2Cl2); IR (KBr) 2192,
solid; mp 94e96 ꢀC (hexane); IR (KBr) 2124, 1032 cmꢁ1 1H NMR
;
(500 MHz, CDCl3)
7.32e7.41 (m, 4H), 7.47e7.52 (m, 5H). Anal. Calcd for C14H11NOS: C,
d
4.14 (d, J¼12.8 Hz, 1H), 4.24 (d, J¼12.8 Hz, 1H),
2134, 1312 cmꢁ1; 1H NMR (400 MHz, CDCl3)
d
1.44 (t, J¼7.3 Hz, 3H),
2.98 (q, J¼7.3 Hz, 2H), 4.35 (s, 2H), 7.30e7.43 (m, 3H), 7.53 (dd,
J¼7.8, 1.5 Hz, 1H). Anal. Calcd for C10H11NO2S2: C, 49.77; H, 4.59; N,
5.80. Found: C, 49.81; H, 4.38; N, 5.59.
69.68; H, 4.59; N, 5.80. Found: C, 69.50; H, 4.68; N, 5.51.
3.2.4.2. 1-[(4-Chlorophenyl)sulfinylmethyl]]-2-isocyanobenzene
(4b). A yellow solid; mp 93e94 ꢀC (hexane); IR (KBr) 2121,
3.3. Typical procedure for the preparation of 2-alkylsulfanyl-
3-sulfinyl(or sulfonyl)-1H-indoles 7
1052 cmꢁ1; 1H NMR (400 MHz, CDCl3)
d
4.14 (d, J¼13.2 Hz,1H), 4.23
(d, J¼13.2 Hz, 1H), 7.34e7.46 (m, 8H); 13C NMR (125 MHz, CDCl3)
d
59.13, 125.71, 126.09, 126.94, 129.38, 129.47, 129.57, 132.01, 135.16,
3.3.1. 2-Methylsulfanyl-3-phenylsulfinyl-1H-indole (7a). To a stirred
solution of 5a (0.15 mg, 0.55 mmol) in THF/DMSO (3 mL, 2:1 v/v) at
0 ꢀC was added NaH (60% in mineral oil; 48 mg, 1.2 mmol) in several
portions. After 5 min, MeI (78 mg, 0.55 mmol) was added and stir-
ring was continued for an additional 10 min at the same tempera-
ture before saturated aqueous NH4Cl (10 mL) was added. The
mixture was extracted with AcOEt (3ꢂ10 mL) and the combined
extracts were washed with water (4ꢂ10 mL) and brine (10 mL),
dried (Na2SO4), and concentrated by evaporation. The residue was
purified by column chromatography on silica gel (AcOEt/hexane 1:1)
to give 7a (0.12 g, 78%); a white solid; mp 101e102 ꢀC (decomp.)
137.89, 141.66, 156.61. Anal. Calcd for C14H10ClNOS: C, 60.98; H,
3.66; N, 5.08. Found: C, 60.88; H, 3.85; N, 5.08.
3.2.4.3. 1-Isocyano-2-(phenylsulfonylmethyl)benzene
pale-orange solid; mp 135e137 ꢀC (hexane); IR (KBr) 2124,
1310 cmꢁ1 1H NMR (500 MHz, CDCl3)
4.51 (s, 2H), 7.27 (d,
(4c). A
;
d
J¼7.8 Hz, 1H), 7.39 (ddd, J¼7.8, 7.3, 1.4 Hz, 1H), 7.45 (ddd, J¼7.8, 7.3,
1.4 Hz, 1H), 7.51 (dd, J¼7.8, 7.3 Hz, 2H), 7.57 (dd, J¼7.8, 1.4 Hz, 1H),
7.66 (tt, J¼7.3, 1.4 Hz, 1H), 7.70 (dd, J¼7.8, 1.4 Hz, 2H). Anal. Calcd for
C14H11NO2S: C, 65.35; H, 4.31; N, 5.44. Found: C, 65.24; H, 4.39;
N, 5.29.
;
(hexane/CH2Cl2); IR (KBr) 3152, 983 cmꢁ1 1H NMR (500 MHz,
CDCl3)
d
2.41 (s, 3H), 6.92 (dd, J¼8.0, 7.4 Hz,1H), 7.08 (ddd, J¼8.0, 7.4,
3.2.4.4. 1-(Ethylsulfonylmethyl)-2-isocyanobenzene
reddish-white solid; mp 77e78 ꢀC (hexane/CH2Cl2); IR (KBr)
2124, 1316 cmꢁ1 1H NMR (400 MHz, CDCl3)
1.44 (t, J¼7.3 Hz,
(4d). A
1.1 Hz, 1H), 7.22 (d, J¼8.0 Hz, 1H), 7.29 (d, J¼8.0 Hz, 1H), 7.41 (t,
J¼7.4 Hz, 1H), 7.47 (dd, J¼8.0, 7.4 Hz, 2H), 7.71 (d, J¼8.0 Hz, 2H), 9.94
;
d
(br s, 1H); 13C NMR (100 MHz, CDCl3)
d 17.56, 111.73, 116.51, 118.32,
3H), 3.00 (q, J¼7.3 Hz, 2H), 4.43 (s, 2H), 7.44e7.51 (m, 3H), 7.65 (d,
120.83, 122.77, 123.96, 124.18, 129.04, 129.87, 137.26, 137.93, 144.73;
MS m/z 287 (Mþ, 14), 239 (100). Anal. Calcd for C15H13NOS2: C,
62.69; H, 4.56; N, 4.87. Found: C, 62.58; H, 4.59; N, 5.50.
J¼8.2 Hz, 1H); 13C NMR (125 MHz, CDCl3)
d 6.27, 54.46, 56.83,
126.47, 127.42, 130.04, 132.08, 132.41, 133.19, 164.42. Anal. Calcd
for C10H11NO2S: C, 57.39; H, 5.30; N, 6.69. Found: C, 57.10; H, 5.29;
N, 6.68.
3.3.2. 2-Ethylsulfanyl-3-phenylsulfinyl-1H-indole (7b). A white
solid; mp 90e93 ꢀC (decomp.) (hexane/CH2Cl2); IR (KBr) 3139,
3.2.5. 1-Isothiocyanato-2-(sulfinyl(orsulfinyl)methyl)benzene 5. These
compounds were prepared by treating 4 with S8 in the presence of
a catalytic amount of Se in THF containing excess Et3N at room
temperature.5
1007 cmꢁ1
;
1H NMR (400 MHz, DMSO-d6)
d
1.27 (t, J¼7.3 Hz, 3H),
3.11e3.16 (m, 2H), 6.90 (dd, J¼7.8, 7.3 Hz, 1H), 7.08e7.14 (m, 2H),
7.38 (d, J¼8.3 Hz, 1H), 7.44 (t, J¼7.3 Hz, 1H), 7.52 (dd, J¼7.8, 7.3 Hz,
2H), 7.59 (d, J¼7.8 Hz, 2H), 11.08 (br, 1H); 13C NMR (100 MHz,
DMSO-d6)
d 14.99, 29.34, 111.87, 118.51, 119.06, 120.82, 123.09,
3.2.5.1. 1-Isothiocyanato-2-(phenylsulfinylmethyl)benzene
(5a). A pale-orange solid; mp 100e102 ꢀC (hexane/CH2Cl2); IR (KBr)
123.82, 124.22, 129.06, 129.89, 135.51, 137.33, 144.77; MS m/z 301
(Mþ, 33), 253 (100). Anal. Calcd for C16H15NOS2: C, 63.75; H, 5.02; N,
4.65. Found: C, 63.68; H, 5.08; N, 4.60.
2189, 2133, 1040 cmꢁ1 1H NMR (400 MHz, CDCl3)
; d 4.11 (d,
J¼13.2 Hz,1H), 4.15 (d, J¼13.2 Hz,1H), 7.17 (d, J¼8.3 Hz,1H), 7.21e7.26
(m, 2H), 7.31 (ddd, J¼8.3, 7.3, 2.9 Hz,1H), 7.44e7.50 (m, 5H); 13C NMR
3.3.3. 2-(Phenylmethyl)sulfanyl-3-phenylsulfinyl-1H-indole (7c). A
white solid; mp 94e96 ꢀC (decomp.) (hexane/CH2Cl2); IR (KBr)
(125 MHz, CDCl3)
d 59.25, 124.17, 125.59, 126.98, 127.17, 128.97 (2C),

7940
K. Kobayashi et al. / Tetrahedron 69 (2013) 7936e7942
3141, 1008 cmꢁ1; 1H NMR (400 MHz, DMSO-d6)
d
4.36 (d, J¼12.7 Hz,
1036 cmꢁ1; 1H NMR (400 MHz, CDCl3)
d
1.37 (t, J¼7.3 Hz, 3H), 1.41
1H), 4.45 (d, 12.7 Hz, 1H), 6.85 (dd, J¼7.8, 7.3 Hz, 1H), 6.99 (d,
(t, J¼7.3 Hz, 3H), 2.97e3.06 (m, 2H), 4.40e4.50 (m, 2H), 6.98 (t,
J¼7.8 Hz, 1H), 7.21 (td, J¼7.8, 1.0 Hz, 1H), 7.32 (d, J¼7.8 Hz, 1H), 7.34
(d, J¼7.8 Hz, 1H), 7.40 (t, J¼7.3 Hz, 1H), 7.45 (dd, J¼7.8, 7.3 Hz, 2H),
J¼8.3 Hz, 1H), 7.11 (t, J¼7.3 Hz, 1H), 7.15e7.18 (m, 2H), 7.27 (s, 5H),
7.38e7.41 (m, 4H),11.09 (br,1H); 13C NMR (100 MHz, CDCl3)
d 39.05,
111.94, 118.66, 119.65, 120.87, 123.33, 123.66, 124.17, 127.50, 128.67,
128.83, 128.94, 129.78, 134.92, 137.40, 137.54, 144.53; MS m/z 363
(Mþ, 58), 315 (100). Anal. Calcd for C21H17NOS2: C, 69.39; H, 4.71; N,
3.85. Found: C, 69.24; H, 4.85; N, 3.64.
7.70 (d, J¼7.8 Hz, 2H); 13C NMR (100 MHz, CDCl3)
d 14.93, 15.28,
32.76, 38.99, 110.41, 120.17, 121.60, 122.27, 123.82, 123.99, 124.86,
128.80, 129.74, 135.96, 137.23, 144.53; MS m/z 329 (Mþ, 67), 281
(100). Anal. Calcd for C18H19NOS2: C, 65.62; H, 5.81; N, 4.25. Found:
C, 65.52; H, 5.79; N, 4.23.
3.3.4. 3-[(4-Chlorophenyl)sulfinyl]-2-methylsulfanyl-1H-indole
(7d). A yellow solid; mp 124e125 ꢀC (hexane/CH2Cl2); IR (KBr)
3.4.3. 1-Phenylmethyl-2-(phenylmethyl)sulfanyl-3-phenylsulfinyl-
1H-indole (8c). A pale-yellow oil; Rf 0.40 (AcOEt/hexane 1:2); IR
3141, 1007 cmꢁ1; 1H NMR (500 MHz, CDCl3)
d 2.41 (s, 3H), 6.95 (dd,
J¼8.0, 7.4 Hz, 1H), 7.10 (dd, J¼8.0, 7.4 Hz, 1H), 7.22 (d, J¼8.0 Hz, 1H),
(neat) 1444, 1036 cmꢁ1 1H NMR (400 MHz, CDCl3)
; d 3.99 (s, 2H),
7.28 (dd, J¼8.0 Hz, 1H), 7.44 (d, J¼8.6 Hz, 2H), 7.63 (d, J¼8.6 Hz, 2H),
5.24 (d, J¼16.6 Hz, 1H), 5.33 (d, J¼16.6 Hz, 1H), 6.96e7.00 (m, 3H),
9.91 (br s, 1H); 13C NMR (100 MHz, CDCl3)
d 18.82, 109.71, 111.59,
7.10e7.16 (m, 4H), 7.21e7.33 (m, 7H), 7.41e7.48 (m, 3H), 7.63 (dd,
119.05, 121.79, 123.68, 124.29, 126.28, 129.17, 136.18, 137.09, 138.22,
142.30. HRMS calcd for C15H13ClNOS2: MþH, 322.0127. Found: m/z
322.0128. Anal. Calcd for C15H12ClNOS2: C, 55.98; H, 3.76; N, 4.35.
Found: C, 55.74; H, 3.87; N, 4.10.
J¼8.3, 2.0 Hz, 2H); 13C NMR (100 MHz, CDCl3)
d 43.10, 47.15, 111.08,
120.22, 121.90, 123.55, 123.95, 124.29, 124.87 (2C), 126.26, 127.69,
127.79, 128.70,128.85, 129.01, 129.85, 135.96,136.42, 136.68,138.03,
144.31; MS m/z 453 (Mþ, 58), 405 (100). Anal. Calcd for
C28H23NOS2: C, 74.14; H, 5.11; N, 3.09. Found: C, 73.91; H, 5.15;
N, 3.07.
3.3.5. 2-Methylsulfanyl-3-phenylsulfonyl-1H-indole (7e). An orange
solid; mp 172e173 ꢀC (hexane/CH2Cl2); IR (KBr) 3318, 1143 cmꢁ1
;
1H NMR (500 MHz, CDCl3)
d
2.56 (s, 3H), 7.17 (t, J¼7.4 Hz, 1H), 7.22
3.4.4. 3-[(4-Chlorophenyl)sulfinyl]-1-methyl-2-methylsulfanyl-1H-
indole (8d). A pale-yellow solid; mp 111e112 ꢀC (hexane/CH2Cl2);
(t, J¼7.4 Hz, 1H), 7.33 (d, J¼7.4 Hz, 1H), 7.44 (t, J¼7.4 Hz, 2H), 7.49 (t,
J¼7.4 Hz,1H), 8.05 (d, J¼7.4 Hz,1H), 8.07 (d, J¼7.4 Hz, 2H), 8.99 (br s,
IR (KBr) 1453, 1037 cmꢁ1 1H NMR (500 MHz, CDCl3)
; d 2.52 (s,
1H); 13C NMR (100 MHz, CDCl3)
d
16.29, 110.98, 113.48, 119.04,
3H), 3.92 (s, 3H), 7.05 (dd, J¼8.0, 6.9 Hz, 1H), 7.26 (dd, J¼8.0,
6.9 Hz, 1H), 7.34 (d, J¼8.0 Hz, 1H), 7.39 (d, J¼8.0 Hz, 1H), 7.42
(d, J¼8.6 Hz, 2H), 7.64 (d, J¼8.6 Hz, 2H); 13C NMR (125 MHz,
122.59, 123.29, 125.92, 126.34, 128.90, 132.66, 135.58, 139.39,
143.35. HRMS calcd for C15H14NO2S2: MþH, 304.0466. Found: m/z
304.0459. Anal. Calcd for C15H13NO2S2: C, 59.38; H, 4.32; N, 4.62.
Found: C, 59.22; H, 4.57; N, 4.40.
CDCl3)
d 20.91, 30.41, 110.40, 119.90, 121.00, 122.00, 123.54, 124.17,
126.22, 129.08, 136.05, 137.88, 138.27, 143.39. HRMS calcd for
C16H15ClNOS2: MþH, 336.0283. Found: m/z 336.0282. Anal. Calcd
for C16H14ClNOS2: C, 57.22; H, 4.20; N, 4.17. Found: C, 57.09; H,
4.28; N, 4.17.
3.3.6. 2-Ethylsulfanyl-3-ethylsulfonyl-1H-indole (7f). A pale-yellow
solid; mp 106e107 ꢀC (hexane/CH2Cl2); IR (KBr) 3272, 1125 cmꢁ1
;
1H NMR (500 MHz, CDCl3)
d
1.25 (t, J¼7.4 Hz, 3H), 1.31 (t, J¼7.4 Hz,
3H), 3.08 (q, J¼7.4 Hz, 2H), 3.30 (q, J¼7.4 Hz, 2H), 7.20e7.24 (m, 2H),
3.4.5. 3-[(4-Chlorophenyl)sulfinyl]-1-(prop-2-enyl)-2-(prop-2-enyl)
sulfanyl-1H-indole (8e). A pale-yellow solid; mp 71e72 ꢀC (hexane/
CH2Cl2); IR (KBr) 1637, 1446, 1039 cmꢁ1; 1H NMR (500 MHz, CDCl3)
7.44 (dd, J¼9.2, 2.3 Hz, 1H), 7.99 (dd, J¼9.2, 2.8 Hz, 1H), 9.45 (br s,
1H); 13C NMR (125 MHz, CDCl3)
d 7.44, 14.51, 28.96, 51.00, 111.24,
112.20, 119.26,122.45,123.56,126.47,135.62,137.48. HRMS calcd for
C12H16NO2S2: MþH, 270.0622. Found: m/z 270.0617. Anal. Calcd for
C12H15NO2S2: C, 53.50; H, 5.61; N, 5.20. Found: C, 53.33; H, 5.80; N,
5.17.
d
3.53e3.61 (m, 2H), 4.94e5.11 (m, 5H), 5.23 (d, J¼10.3 Hz, 1H),
5.83e6.01 (m, 2H), 7.04 (dd, J¼8.0, 7.4 Hz, 1H), 7.22 (dd, J¼8.0,
7.4 Hz, 1H), 7.30 (d, J¼8.0 Hz, 1H), 7.38 (d, J¼8.0 Hz, 1H), 7.43 (d,
J¼8.6 Hz, 2H), 7.65 (d, J¼8.6 Hz, 2H); 13C NMR (125 MHz, CDCl3)
d
41.06, 46.36, 111.11, 117.37, 119.40, 120.02, 121.99, 122.92, 123.60,
3.4. Typical procedure for the preparation of 1-alkyl-2-alkyl
sulfanyl-3-sulfinyl(or sulfonyl)-1H-indoles 8
124.26, 126.29 (2C), 129.08, 132.47, 135.18, 135.99, 137.89, 143.22.
HRMS calcd for C20H19ClNOS2: MþH, 388.0596. Found: m/z
388.0597. Anal. Calcd for C20H18ClNOS2: C, 61.92; H, 4.68; N, 3.61.
Found: C, 61.82; H, 4.66; N, 3.50.
3.4.1. 1-Methyl-2-methylsulfanyl-3-phenylsulfinyl-1H-indole
(8a). To a stirred solution of 5a (0.15 mg, 0.55 mmol) in THF/DMSO
(3 mL, 2:1 v/v) at 0 ꢀC was added NaH (60% in mineral oil; 48 mg,
1.2 mmol) in several portions. After 5 min, MeI (0.20 g, 1.4 mmol)
was added and the temperature was raised to room temperature.
Stirring was continued for 1 h before saturated aqueous NH4Cl
(10 mL) was added. The mixture was worked up in a manner similar
to that described for 7a. The residual solid was purified by re-
crystallization to give 8a (0.14 g, 86%). A pale-yellow solid; mp
3.4.6. 1-Methyl-2-methylsulfanyl-3-phenylsulfonyl-1H-indole
(8f). An orange solid; mp 179e180 ꢀC (hexane/CH2Cl2); IR (KBr)
1447, 1149 cmꢁ1 1H NMR (400 MHz, CDCl3)
; d 2.36 (s, 3H), 3.87 (s,
3H), 7.30e7.36 (m, 3H), 7.42 (t, J¼7.4 Hz, 2H), 7.48 (tt, J¼7.4, 1.1 Hz,
1H), 8.10 (dd, J¼7.4, 1.1 Hz, 2H), 8.36 (dd, J¼8.6, 1.7 Hz, 1H); 13C NMR
(125 MHz, CDCl3)
d 20.56, 30.33, 110.29, 119.24, 120.77, 122.79,
124.27, 125.14, 126.82, 128.69, 132.44, 136.84, 136.97, 143.78. HRMS
calcd for C16H16NO2S2: MþH, 318.0622. Found: m/z 318.0635. Anal.
Calcd for C16H15NO2S2: C, 60.54; H, 4.76; N, 4.41. Found: C, 60.26; H,
4.80; N, 4.39.
116e118 ꢀC (decomp.) (hexane/CH2Cl2); IR (KBr) 1450, 1032 cmꢁ1
1H NMR (500 MHz, CDCl3)
;
d
2.51 (s, 3H), 3.91 (s, 3H), 7.02 (t, J¼8.0,
7.4 Hz, 1H), 7.24 (ddd, J¼8.0, 7.4, 1.1 Hz, 1H), 7.32 (d, J¼8.0 Hz, 1H),
7.38e7.42 (m, 2H), 7.45 (dd, J¼8.0, 7.4 Hz, 2H), 7.72 (d, J¼8.0 Hz,
2H); 13C NMR (100 MHz, CDCl3)
d
20.86, 30.34, 110.26, 120.07,
3.4.7. 3-Ethylsulfonyl-1-methyl-2-methylsulfanyl-1H-indole (8g). A
white solid; mp 82e83 ꢀC (hexane/CH2Cl2); IR (KBr) 1451,
121.50, 121.78, 123.69, 123.99, 124.77, 128.81, 129.79, 137.73, 138.32,
144.63. HRMS calcd for C16H16NOS2: MþH, 302.0673. Found: m/z
302.0665. Anal. Calcd for C16H15NOS2: C, 63.75; H, 5.02; N, 4.65.
Found: C, 63.74; H, 5.09; N, 4.49.
1144 cmꢁ1; 1H NMR (400 MHz, CDCl3)
d
1.29 (t, J¼7.3 Hz, 3H), 2.52
(s, 3H), 3.35 (q, J¼7.3 Hz, 2H), 3.97 (s, 3H), 7.29 (dd, J¼8.3, 7.3,
1.0 Hz, 1H), 7.35e7.40 (m, 2H), 8.20 (dd, J¼8.3, 1.0 Hz, 1H); 13C NMR
(100 MHz, CDCl3)
d 7.46, 21.14, 30.42, 51.21, 110.27, 116.51, 120.78,
3.4.2. 1-Ethyl-2-ethylsulfanyl-3-phenylsulfinyl-1H-indole
(8b). A
122.73, 124.32, 125.84, 136.79, 136.81. HRMS calcd for
C12H16NO2S2: MþH, 270.0622. Found: m/z 270.0619. Anal. Calcd
pale-yellow solid; mp 97e98 ꢀC (hexane/CH2Cl2); IR (KBr) 1436,

K. Kobayashi et al. / Tetrahedron 69 (2013) 7936e7942
7941
for C12H15NO2S2: C, 53.50; H, 5.61; N, 5.20. Found: C, 53.45; H,
5.77; N, 5.13.
d
3.53 (dd, J¼13.2, 6.9 Hz, 1H), 3.59 (dd, J¼13.2, 7.4 Hz, 1H), 3.90 (s,
3H), 5.03 (dd, J¼16.6, 1.1 Hz, 1H), 5.06 (d, J¼9.7 Hz, 1H), 5.88e5.97
(m, 1H), 7.05 (dd, J¼8.0, 7.4 Hz, 1H), 7.26 (ddd, J¼8.0, 7.4, 1.1 Hz, 1H),
7.33 (d, J¼8.0 Hz, 1H), 7.36 (d, J¼8.0 Hz, 1H), 7.42 (d, J¼8.6 Hz,
3.5. Typical procedure for the preparation of 1-alkyl-2-alkyl
sulfanyl-3-sulfinyl-1H-indoles 9
2H), 7.65 (d, J¼8.6 Hz, 2H); 13C NMR (125 MHz, CDCl3)
d 30.70, 41.01,
110.45, 119.25, 119.91, 121.95, 122.38, 123.46, 124.17, 126.30,
129.04, 132.49, 135.60, 135.95, 138.40, 143.27. HRMS calcd for
C18H17ClNOS2: MþH, 362.0440. Found: m/z 362.0441. Anal. Calcd
for C18H16ClNOS2: C, 59.74; H, 4.46; N, 3.87. Found: C, 59.61; H, 4.52;
N, 3.80.
3.5.1. 2-Methylsulfanyl-1-phenylmethyl-3-phenylsulfinyl-1H-indole
(9a). Compound 5a (0.18 g, 0.66 mmol) was treated with NaH (60%
in mineral oil; 58 mg, 1.5 mmol) as described for the preparation of
8a. After 5 min, MeI (93 mg, 0.66 mmol) was added and the tem-
perature was raised to room temperature. Then, BnBr (0.11 g,
0.66 mmol) was added and stirring was continued for 1 h before the
same workup as described for the preparation of 8a. The crude
product was purified by column chromatography on silica gel
(AcOEt/hexane 1:1) to give 9a (0.14 g, 57%). A whitꢁe1solid; mp
3.6. General procedure for the preparation of tricyclic indole
derivatives 10
3.6.1. 10-(Phenylsulfinyl)-3,4-dihydro-2H-[1,3]thiazino[3,2-a]indole
(10a). Compound 5a (0.18 g, 0.64 mmol) was treated with NaH
(60% in mineral oil; 52 mg, 1.3 mmol) as described for the prep-
aration of 8a. After 5 min, Br(CH2)3Br (0.13 g, 0.64 mmol) was
added and the temperature was raised to room temperature.
Stirring was continued for 10 min before the same workup as
described for the preparation of 8a. The residual crude product
was purified by recrystallization from hexane/CH2Cl2 to give 10a
(0.17 g, 83%). A pale-yellow solid; mp 118e120 ꢀC; IR (KBr) 1434,
122e123 ꢀC (hexane/CH2Cl2); IR (KBr) 1445, 1035 cm
;
1H NMR
(500 MHz, CDCl3)
d
2.36 (s, 3H), 5.58 (d, J¼16.6 Hz, 1H), 5.67 (d,
J¼16.6 Hz, 1H), 7.01 (t, J¼7.4 Hz, 1H), 7.06 (d, J¼7.4 Hz, 2H), 7.16 (dd,
J¼8.0, 7.4 Hz, 1H), 7.22 (d, J¼8.0 Hz, 1H), 7.27e7.31 (m, 3H),
7.40e7.44 (m, 2H), 7.48 (t, J¼7.4 Hz, 2H), 7.74 (d, J¼7.4 Hz, 2H); 13C
NMR (100 MHz, CDCl3)
d 21.35, 47.42, 111.01, 120.17, 121.91, 122.32,
123.94, 124.26, 124.75, 126.17, 127.67, 128.87 (2C), 129.87, 136.61,
137.81,137.99,144.50. HRMS calcd for C22H20NOS2: MþH, 378.0986.
Found: m/z 378.0981. Anal. Calcd for C22H19NOS2: C, 69.99; H, 5.07;
N, 3.71. Found: C, 69.97; H, 5.28; N, 3.70.
1031 cmꢁ1; 1H NMR (500 MHz, CDCl3)
d 2.42e2.48 (m, 2H), 3.13 (t,
J¼5.7 Hz, 2H), 4.06e4.11 (m, 1H), 4.15e4.20 (m, 1H), 6.99 (ddd,
J¼8.0, 7.4, 1.1 Hz, 1H), 7.10 (ddd, J¼8.0, 7.4, 1.1 Hz, 1H), 7.18 (d,
J¼8.0 Hz, 1H), 7.28 (d, J¼8.0 Hz, 1H), 7.39 (tt, J¼7.4, 1.1 Hz, 1H), 7.44
(dd, J¼8.0, 7.4 Hz, 2H), 7.70 (dd, J¼8.0, 1.1 Hz, 2H); 13C NMR
3.5.2. 1-Methyl-2-(phenylmethyl)sulfanyl-3-phenylsulfinyl-1H-in-
dole (9b). A pale-yellow solid; mp 114e115 ꢀC (hexane/CH2Cl2); IR
(KBr) 1454, 1033 cmꢁ1
;
1H NMR (500 MHz, CDCl3)
d
3.41 (s, 3H),
(100 MHz, CDCl3) d 23.42, 24.97, 41.98, 108.36, 111.16, 118.41,
4.06 (d, J¼12.6 Hz, 1H), 4.16 (d, J¼12.6 Hz, 1H), 6.99 (ddd, J¼8.0,
7.4, 1.1 Hz, 1H), 7.12 (dd, J¼8.0, 1.1 Hz, 2H), 7.18e7.24 (m, 5H), 7.29
(dd, J¼8.0, 1.1 Hz, 1H), 7.38e7.45 (m, 3H), 7.64 (dd, J¼8.0, 1.1 Hz,
121.81, 121.89, 124.30, 124.83, 128.73, 129.67, 136.63, 138.26,
144.26. HRMS calcd for C17H16NOS2: MþH, 314.0673. Found: m/z
314.0673. Anal. Calcd for C17H15NOS2: C, 65.14; H, 4.82; N, 4.47.
Found: C, 65.13; H, 5.02; N, 4.42.
2H); 13C NMR (125 MHz, CDCl3)
d 30.00, 43.05, 110.34, 120.02,
121.73, 122.68, 123.69, 123.96, 123.83, 124.83, 127.68, 128.66,
128.77, 129.79, 135.71, 136.88, 138.20, 144.39. HRMS calcd for
C22H20NOS2: MþH, 378.0986. Found: m/z 377.0975. Anal. Calcd for
C22H19NOS2: C, 69.99; H, 5.07; N, 3.71. Found: C, 69.91; H, 5.03;
N, 3.43.
3.6.2. 10-[(4-Chlorophenyl)sulfinyl]-3,4-dihydro-2H-[1,3]thiazino
[3,2-a]indole (10b). A yellow solid; mp 134e135 ꢀC (hexane/
CH2Cl2); IR (KBr) 1433, 1032 cmꢁ1 1H NMR (500 MHz, CDCl3)
;
d
2.45e2.48 (m, 2H), 3.14 (t, J¼5.7 Hz, 2H), 4.08e4.13 (m, 1H),
4.17e4.22 (m, 1H), 7.03 (dd, J¼8.0, 7.4 Hz, 1H), 7.13 (dd, J¼8.0, 7.4 Hz,
1H), 7.20 (d, J¼8.0 Hz, 1H), 7.27 (d, J¼8.0 Hz, 1H), 7.42 (d, J¼8.6 Hz,
3.5.3. [2-(Methylsulfanyl)-3-(phenylsulfinyl)-1H-indol-1-yl](phenyl)
methanone (9c). A yellow viscous oil; Rf 0.80 (THF/hexane 1:1); IR
2H), 7.63 (d, J¼8.6 Hz, 2H); 13C NMR (125 MHz, CDCl3)
d 23.38,
(neat) 1703, 1439, 1042 cmꢁ1; 1H NMR (500 MHz, CDCl3)
d
2.56 (s,
24.97, 42.00, 108.49, 110.60, 118.24, 122.00, 122.10, 124.15, 126.30,
128.99, 135.85, 136.92, 138.26, 142.85. HRMS calcd for
C17H15ClNOS2: MþH, 348.0283. Found: m/z 348.0280. Anal. Calcd
for C17H14ClNOS2: C, 58.69; H, 4.06; N, 4.03. Found: C, 58.70; H,
4.12; N, 3.93.
3H), 7.07e7.15 (m, 3H), 7.45 (t, J¼7.4 Hz, 1H), 7.51 (dd, J¼7.8, 7.4 Hz,
4H), 7.65 (dd, J¼7.4, 1.7 Hz, 1H), 7.68 (t, J¼7.4 Hz, 1H), 7.73 (d,
J¼7.8 Hz, 2H), 7.79 (d, J¼7.8 Hz, 2H); 13C NMR (100 MHz, CDCl3)
d
21.78, 113.59, 120.37, 123.46, 124.25, 124.64, 125.04, 128.30,
129.00, 129.14, 130.36, 130.42, 133.86, 134.31, 136.88, 137.97, 143.91,
158.91; MS m/z 391 (Mþ, 19), 270 (47), 105 (100). Anal. Calcd
for C22H17NO2S2: C, 67.49; H, 4.38; N, 3.58. Found: C, 67.20; H, 4.46;
N, 3.38.
3.6.3. 9-[(4-Chlorophenyl)sulfinyl]-2,3-dihydrothiazolo[3,2-a]indole
(10c). A white solid; mp 133e134 ꢀC (hexane/CH2Cl2); IR (KBr)
1452, 1036 cmꢁ1 1H NMR (500 MHz, CDCl3)
; d 3.79e3.87 (m, 2H),
4.26e4.29 (m, 2H), 7.05 (t, J¼7.4 Hz, 1H), 7.11e7.16 (m, 2H), 7.35 (d,
3.5.4. 3-[(4-Chlorophenyl)sulfinyl]-2-methylsulfanyl-1-(phenyl-
methyl)-1H-indole (9d). A pale-purple solid; mp 118e120 ꢀC (hex-
J¼7.4 Hz, 1H), 7.43 (d, J¼8.6 Hz, 2H), 7.64 (d, J¼8.6 Hz, 2H): 13C NMR
(125 MHz, CDCl3)
d 35.87, 45.51, 107.68, 109.68, 118.48, 121.66,
ane/CH2Cl2); IR (KBr) IR 1446, 1039 cmꢁ1
;
1H NMR (500 MHz,
122.30, 126.31, 129.12, 129.56, 134.61, 136.20, 142.66, 145.93. HRMS
calcd for C16H13ClNOS2: MþH, 334.0127. Found: m/z 334.0126. Anal.
Calcd for C16H12ClNOS2: C, 57.56; H, 3.62; N, 4.20. Found: C, 57.47;
H, 3.35; N, 3.96.
CDCl3)
d
2.35 (s, 3H), 5.58 (d, J¼16.6 Hz, 1H), 5.67 (d, J¼16.6 Hz, 1H),
7.03e7.06 (m, 3H), 7.17e7.31 (m, 6H), 7.44 (d, J¼8.0 Hz, 2H), 7.67 (d,
J¼8.0 Hz, 2H); 13C NMR (125 MHz, CDCl3)
d 21.39, 47.48, 111.16,
120.00, 121.78, 122.13, 123.78, 124.45, 126.17, 126.20, 127.75, 128.93,
129.17, 136.09, 136.48, 137.94, 138.03, 143.12. HRMS calcd for
C22H19ClNOS2: MþH, 412.0596. Found: m/z 412.0598. Anal. Calcd
for C22H18ClNOS2: C, 64.14; H, 4.40; N, 3.40. Found: C, 63.87; H,
4.61; N, 3.31.
3.6.4. 10-(Phenylsulfonyl)-3,4-dihydro-2H-[1,3]thiazino[3,2-a]indole
(10d). A white solid; mp 218e219 ꢀC (hexane/CH2Cl2); IR (KBr)
1426, 1151 cmꢁ1 1H NMR (500 MHz, CDCl3)
; d 2.40e2.45 (m, 2H),
3.08 (t, J¼5.7 Hz, 2H), 4.13 (t, J¼5.7 Hz, 2H), 7.18e7.25 (m, 3H), 7.43
(dd, J¼8.0, 7.4 Hz, 2H), 7.48 (t, J¼7.4 Hz, 1H), 8.02 (d, J¼8.0 Hz, 1H),
3.5.5. 3-[(4-Chlorophenyl)sulfinyl]-1-methyl-2-[(prop-2-enyl)sul-
fanyl]-1H-indole (9e). A yellow solid; mp 113e115 ꢀC (hexane/
CH2Cl2); IR (KBr) 1634, 1451, 1037 cmꢁ1; 1H NMR (500 MHz, CDCl3)
8.06 (d, J¼8.0 Hz, 2H); 13C NMR (125 MHz, CDCl3)
d 22.66, 24.63,
42.14, 108.34, 109.33, 118.23, 122.07, 122.64, 124.87, 126.12, 128.78,
132.34, 137.40, 137.54, 143.73. HRMS calcd for C17H16NO2S2: MþH,

7942
K. Kobayashi et al. / Tetrahedron 69 (2013) 7936e7942
330.0632. Found: m/z 330.0619. Anal. Calcd for C17H15NO2S2: C,
References and notes
61.98; H, 4.59; N, 4.25. Found: C, 61.95; H, 4.73; N, 4.20.
1. Greenhouse, R. J.; Muchowski, J. M. U.S. Patent 4,654,360, 1987; Chem. Abstr.
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2. (a) Tanaka, J.; Higa, T.; Bernardinelli, G.; Jefford, C. W. Tetrahedron Lett. 1988, 29,
6091e6094; (b) Tanaka, J.; Higa, T.; Bernardinelli, G.; Jefford, C. W. Tetrahedron
1989, 45, 7301e7310.
3.6.5. 10-(Ethylsulfonyl)-3,4-dihydro-2H-[1,3]thiazino[3,2-a]indole
(10e). A white solid; mp 144e146 ꢀC (hexane/CH2Cl2); IR (KBr)
1432, 1144 cmꢁ1; 1H NMR (500 MHz, CDCl3)
d
1.30 (t, J¼7.4 Hz, 3H),
3. Gilow, H. M.; Brown, C. S.; Copeland, J. N.; Kelly, K. E. J. Heterocycl. Chem. 1991, 28,
1025e1034.
2.43e2.47 (m, 2H), 3.09 (t, J¼5.7 Hz, 2H), 3.18 (q, J¼7.4 Hz, 2H), 4.18
(dd, J¼6.3, 5.7 Hz, 2H), 7.18e7.24 (m, 3H), 7.89 (dd, J¼6.3, 1.7 Hz,
4. For a recent excellent review on the synthesis of 1H-indoles: (a) Humphrey, G.
R.; Kuethe, J. T. Chem. Rev. 2006, 106, 2875e2911; For recent reports: (b) Wei, Y.;
Deb, I.; Yoshikai, N. J. Am. Chem. Soc. 2012, 134, 9098e9101; (c) Gore, S.; Bas-
1H); 13C NMR (125 MHz, CDCl3)
d 7.53, 22.80, 24.63, 42.21, 50.74,
106.44, 108.34, 118.25, 122.05, 122.58, 125.56, 137.29, 137.82. HRMS
calcd for C13H16NO2S2: MþH, 282.0622. Found: m/z 282.0619. Anal.
Calcd for C13H15NO2S2: C, 55.49; H, 5.37; N, 4.98. Found: C, 55.49; H,
5.54; N, 4.97.
€
karan, S.; Konig, B. Org. Lett. 2012, 14, 4568e4571; (d) Gao, D.; Back, T. G. Chem.
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This work was supported in part by a Grant-in-Aid for Scientific
Research (C) 22550035 from Japan Society for the Promotion of
Science. We would like to acknowledge Mrs. Miyuki Tanmatsu of
our University for recording mass spectra and performing com-
bustion analyses.