Iron-facilitated iodine-mediated electrophilic annulation of N,N-dimethyl-2-alkynylanilines with disulfides or diselenides

Article abstract of DOI:10.1002/adsc.201100349

An efficient synthesis of N-methyl-3-chalcogeno-indoles has been developed via iodine-mediated electrophilic annulation reactions of 2-alkynylaniline derivatives with disulfides or diselenides. In the presence of iodine and iron, a variety of 2-alkynylani

Full text of DOI:10.1002/adsc.201100349

FULL PAPERS
DOI: 10.1002/adsc.201100349
Iron-Facilitated Iodine-Mediated Electrophilic Annulation of
N,N-Dimethyl-2-alkynylanilines with Disulfides or Diselenides
Hui-Ai Du,a Ri-Yuan Tang,a,b Chen-Liang Deng,a Yan Liu,a Jin-Heng Li,b,*
and Xing-Guo Zhanga,*
a
College of Chemistry and Materials Engineering, Wenzhou University, Wenzhou 325035, Peopleꢀs Republic of China
Fax : (+86)-577-8668-9372; phone: (+86)-577-8668-9615; e-mail: zxg@wzu.edu.cn
State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan
b
University, Changsha 410082, Peopleꢀs Republic of China
Fax : (+86)-731-8887-2531; phone: (+86)-731-8887-2576; e-mail: jhli@hunnu.edu.cn
Received: May 4, 2011; Revised: July 7, 2011; Published online: October 10, 2011
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/adcs.201100349.
Abstract: An efficient synthesis of N-methyl-3-chal- leading to the corresponding 3-sulfenylindoles and 3-
cogeno-indoles has been developed via iodine-medi- selenenylindoles in moderate to excellent yields. It is
ated electrophilic annulation reactions of 2-alkynyl- noteworthy that iron can promote the reaction.
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
Introduction
gen sources is interesting. Recently, we were interest-
ed to find that chalcogenyl iodides could be derived
The indole moiety is presented in a wide range of bio- in situ from the reaction of disulfides or diselenides
logically active compounds and natural products, as with I2, which has been applied for the preparation of
well as is useful building block in organic synthesis.[1] 3-chalcogenobenzo[b]furans [Eq. (2)].[9] With a con-
Among the indole derivatives, 3-sulfenylindoles are tinuing interest in the synthesis of chalcogen-contain-
particularly attractive due to their potential use in ing heterocycles,[9,10] we decided to investigate the fea-
therapeutic areas such as cancer,[2] HIV,[3] obesi- sibility of the preparation of 3-chalcogen-substituted
ty[4]and heart disease.[5] Until now, a variety of effi- indoles using the generation of chalcogenyl iodides in
cient methods has been developed for the synthesis of situ and an annulation strategy. Here, we report a
3-sulfenylindoles.[6,7] However, most have focused on simple and efficient synthesis of 3-chalcogenoindoles
the direct sulfenylations of indoles with different sul- by electrophilic annulation of N,N-dimethyl-2-alkyn-
fenylating agents,[6] which is restricted with the func-
ACHTUNGTRENyNUGN lanilines with chalcogenyl iodides derived from disul-
tional groups compatibility and the use of foul smell- fides or diselenides with I2 [Eq. (3)]. It is noteworthy
ing/harmful sulfenylating agents, associated with un- that iron can facilitate the annulation.
necessary economic wastes and environmental pollu-
tion. Recently, Larock and co-workers reported a
novel synthetic approach to 3-chalcogen-substituted Results and Discussion
indoles by (n-Bu)4NI-induced electrophilic cyclization
of N,N-dialkyl-2-alkynylanilines with arylsulfenyl We began our study by examining the reaction be-
chloride or phenylselenenyl chloride in moderate to tween N,N-dimethyl-2-(phenylethynyl)aniline (1a)
excellent yields [Scheme 1, Eq. (1)].[8] However, this and 1,2-diphenyldisulfane (2a) to screen the optimal
method was limited to the use of arylchalcogenyl reaction conditions, and the results are summarized in
chloride. Thus, the development of a general and Table 1. As expected, the reaction of N,N-dimethyl-2-
simple route for synthesizing 3-chalcogen-substituted (phenylethynyl)aniline (1a) with 1,2-diphenyldisulfane
indoles using readily available aryl- and alkyl-chalco- (2a) was carried out smoothly under the reported re-
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Scheme 1. Routes to chalcogen-containing heterocycles.
Table 1. Screening for optimal reaction conditions.[a]
action conditions (PdCl2 combined with I2),[9] provid-
ing the desired product 3 in 84% yield (entry 1). It
was interesting to find that an identical yield was
achieved in the presence of I2 alone (entry 2). These
promoted us to investigate other reaction conditions
to obtain the best results (entries 3–20). After a series
of trials, we found that the presence of iron salts af-
fected the reaction to some extent (entries 3–7): while
both Fe power and FeF3 could enhance the yield of 3
to 95% and 92%, respectively, the other iron salts,
FeCl3, FeCl2 and FeBr3, affected the reaction slightly.
Notably, I2 played a key role in the reaction: without
I2 the reaction could not take place even in the pres-
ence of Fe (entry 8). We were interested to discover
that the reaction gave the desired product 3 in quanti-
tative yield when 5 mol% Fe combined with 1.1 equiv.
I2 was added (entry 10). Among the effects of both
the reaction temperature and solvent examined, it
turned out that the reaction in MeCN at 808C provid-
ed the best results (entries 11–15). In light of the
above results, several N-substituents as the leaving
group were evaluated in the presence of Fe and I2
(entries 16–19). It was found that substrates 1b and
Entry
R
[Fe]
(mol%)
Solvent
T
Yield
N
[oC] [%][b]
1[c]
2
3
4
5
Me (1a)
Me (1a)
Me (1a) Fe (20)
–
–
MeCN
MeCN
MeCN
MeCN
100 84
100 83
100 95
100 92
100 85
100 86
100 86
Me (1a) FeF3 (20)
Me (1a) FeCl3 (20) MeCN
Me (1a) FeCl2 (20) MeCN
Me (1a) FeBr3 (20) MeCN
6
7
8[d]
9
Me (1a) Fe (20)
Me (1a) Fe (10)
Me (1a) Fe (5)
Me (1a) Fe (5)
Me (1a) Fe (5)
Me (1a) Fe (5)
Me (1a) Fe (5)
Me (1a) Fe (5)
MeCN
MeCN
MeCN
MeCN
MeCN
100
0
100 96
100 98
10
11
12
13
14
15
16
17
18
19
20[e]
80
25
98
trace
50
À
À
1c, with an N H group or an N Bn group instead of
CH2ClCH2Cl 80
À
the N Me group, were not suitable substrates for the
annulation reaction (entries 16 and 17). Although N
toluene
DMSO
MeCN
MeCN
MeCN
MeCN
MeCN
80
80
80
80
80
80
80
82
78
trace
mixture
63
À
À
Ac and N Bz groups were suitable leaving groups,
both were less active than the N Me group in terms
H (1b)
Fe (5)
À
Bn (1c) Fe (5)
Ac (1d) Fe (5)
Bz (1e) Fe (5)
Me (1a) Fe (5)
of yields (entries 18 and 19). For example, N-methyl-
N-[2-(phenylethynyl)phenyl]acetamide (1d) was treat-
ed with 1,2-diphenyldisulfane (2a), I2, and Fe to
afford the desired product 3 in moderate yield
(entry 18). To our delight, the optimal reaction condi-
tions were compatible with a 1 mmol scale of sub-
strate 1a (entry 20).
46
96
[a]
Reaction conditions:
1
(0.2 mmol), 2a (0.1 mmol),
1.1 equiv. of I2, and [Fe] in solvent (2 mL) under an N2
atmosphere for 3 h.
Isolated yield.
In the presence of PdCl2 (10 mol%).
In the absence of I2 for 14 h.
1 (1 mmol) and 2a (0.5 mmol) for 10 h.
[b]
[c]
[d]
[e]
With the optimal reaction conditions in hand, we
explored the scope of both N,N-dimethyl-2-alkynyl-
ACHTUNGTRENaNGNU nilines and disulfides for the annulation reaction
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Iron-Facilitated Iodine-Mediated Electrophilic Annulation of N,N-Dimethyl-2-alkynylanilines
Table 2. Electrophilic annulation reactions of 2-alkynylanilines (1) with disulfides (2) in the presence of I2 and Fe.[a]
Entry
Amine 1
Disulfide 2
Yield [%][b]
(Product)
AHCTUNGTRENNUNG
1
81 (4)
2
92 (5)
3
98 (6)
4
92 (7)
5
99 (8)
6
80 (9)
7
83 (10)
81 (11)
95 (12)
92 (13)
97 (14)
99 (15)
67 (16)
8
9
10
11
12
13
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Hui-Ai Du et al.
Yield [%][b]
FULL PAPERS
Table 2. (Continued)
Entry
Amine 1
Disulfide 2
AHCTUNGTRENN(GUN Product)
14
15
16
95 (17)
87 (18)
67 (19)
17
92 (20)
18
19
83 (21)
53 (22)
20
61 (23)
90 (24)
21
[a]
Reaction conditions: 1 (0.2 mmol), 2 (0.1 mmol), I2 (1.1 equiv.), Fe (5 mol%), and MeCN (2 mL) under N2 at 808C for
3 h.
Isolated yield.
[b]
(Table 2). The results disclosed the broader generality 80% yields, respectively (entries 2 and 6). To our de-
of the reaction under the optimal reaction conditions, light, heteroaryl disulfide 2i was also a suitable sub-
and various N,N-dimethyl-2-alkynylanilines 1 under- strate under the optimal conditions: the desired prod-
went the reaction with disulfides 2 in moderate to uct 11 was obtained in 81% yield (entry 8). It was
good yields. Initially, a number of disulfides 2b–2l was found that the optimal conditions were compatible
investigated in the presence of I2 and Fe (entries 1– with aliphatic disulfides (entries 9–11). 1,2-Dicyclo-
11). The results demonstrated that diaryl disulfides, hexyldisulfane (2l), for instance, underwent the reac-
bearing either electron-rich or electron-deficient tion smoothly to afford the target product 14 in 97%
groups on the aryl ring, were successful for reacting yield (entry 11). Subsequently, a variety of N,N-di-
with aniline 1a, providing the corresponding products methyl-2-alkynylanilines 1b–1k was examined in the
4–10 in good to excellent yields (entries 1–7). For ex- presence of I2 and Fe (entries 12–21). Gratifyingly, a
ample, disulfides 2c and 2g, bearing a 4-methoxy series of functional groups, including p-MeC6H4, o-
group or 4-nitro group, reacted with substrate 1a, Fe, MeC6H4, p-MeOC6H4, o-MeOC6H4, p-NO2C6H4, m-
and I2 to give the corresponding products in 92% and CF3C6H4, n-hexyl and tert-butyl, at the terminal
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Iron-Facilitated Iodine-Mediated Electrophilic Annulation of N,N-Dimethyl-2-alkynylanilines
Table 3. Electrophilic annulation reactions of 2-alkynylanilines (1) with diselenides (2) in the presence of I2 and Fe.[a]
Entry
Amine 1
Diselenide 2
Yield [%][b]
(Product)
AHCTUNGTRENNUNG
1
2
3
92 (25)
84 (26)
93 (27)
4
5
6
90 (28)
80 (29)
32 (30)
7
82 (31)
[a]
Reaction conditions: 1 (0.2 mmol), 2 (0.1 mmol), I2 (1.1 equiv.), Fe (5 mol%), and MeCN (2 mL) under N2 at 808C for
3 h.
Isolated yield.
[b]
alkyne was well tolerated under the optimal condi- were also consistent with the optimal conditions.
tions, and the steric hindrance disfavored the reaction Treatment of Me-substituted substrate 1j with disul-
in terms of yields. While substrate 1b, bearing a p- fide 2a, I2 and Fe afforded the cyclization product 23
methylphenyl group at the terminal alkyne, was react- in 61% yield (entry 20). Using F-substituted substrate
ed with disulfide 2a, Fe, and I2 to afford the corre- 1k, a good yield was obtained under the same condi-
sponding product 15 in 99% yield (entry 12), substrate tions (entry 21). However, some substrates, including
1c with a bulky o-methylphenyl group lowered the 2-ethynyl-N,N-dimethylaniline (1l), N,N-dimethyl-2-
yield to 67% (entry 13). N,N-Dimethyl-2-(oct-1-yn- [(trimethylsilyl)ethynyl]aniline
yl)aniline (1h) furnished the desired product 21 in (dimethylamino)phenyl]prop-2-yn-1-ol (1n), were not
83% yield (entry 18); however, another bulky aliphat- suitable substrates for the reaction.
(1m)
and
3-[2-
N
ACHTUNGTRENNUNG
ic alkyne 1i gave the corresponding product 22 in
Subsequently, the reactions between 2-alkynylani-
only 53% yield (entry 19). Notably, substituents, such lines and diselenides were explored under the optimal
as Me or F, on the aryl ring of the aniline moiety conditions (Table 3). In the presence of Fe and I2, ani-
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Scheme 2. Control experiments.
line 1a was treated with diaryl diselenides 2m or 2n
Consequently, possible mechanisms are proposed as
to smoothly give the corresponding products 25 and outlined in Scheme 3 on the basis of the reported
26 in 92% and 84% yields, respectively (entries 1 and mechanisms[8,9] and the present results. The reaction
2). Gratifyingly, an excellent yield was still achieved could be conducted in the presence of I2 alone
from the reaction of substrate 1a with aliphatic disele- (entry 1 in Table 1, and did not proceed through an
nide 2o (entry 3). Encouraged by these results, several iodocyclization process (Scheme 2). These results
anilines 1d–1f and 1k were examined in the presence imply that the reaction of disulfide 2 with I2 may take
of 1,2-diphenyl diselenide (2m), I2 and Fe (entries 4– place to yield the active RSI in situ.[11] Initially, com-
7). The results showed that substrates 1d and 1e with plexation of Fe or Fe(II) with both an alkyne and a
electron-rich aryl groups at the terminal alkyne dis- nitrogen afforded intermediate A, followed by the
ꢀ
played higher activity leading to the desired products electrophilic addition of RSI to the C C triple bond
28 and 29 in good yields. However, aniline 1f with an in intermediate A which gives intermediate B. Inter-
electron-deficient group gave a low yield (32% yield, mediate B undergoes the annulation reaction leading
entry 6). To our delight, F-substituted substrate 1k to intermediate D. A methyl group is removed from
successfully underwent the annulation reaction with intermediate D with the aid of an IÀ nucleophile to
1,2-diphenyldiselenide (2m), I2 and Fe, furnishing the furnish the product. We deduce that the Fe catalyst
target product 31 in good yield (entry 7).
may activate the substrates by complexation with the
To elucidate the mechanism, some control experi- carbon-carbon triple bond (intermediate A). Al-
ments were carried out (Scheme 2). The reaction be- though we did not observe the addition products [Eq.
tween disulfide 2a and I2 was carried out, and PhSI (2) and Eg. (3) in Scheme 2], we cannot rule out the
was observed by GC-MS analysis [Eq. (1)]. It is note- second pathway: the electrophilic addition of I2 to the
ꢀ
worthy that no addition products 33 or 35 were ob- C C triple bond in intermediate A gives intermediate
tained using N,N-dimethyl-2-(phenylethynyl)aniline C, followed by addition of PhSI and cyclization with
(1a) or 1,2-diphenylethyne (34) substrates in the pres- nitrogen resulting in intermediate D.
ence of disulfide 2a, Fe and I2 [Eq. (2) and Eq. (3)].
Although a mixture of products were observed by
GC-MS analysis, (iodomethyl)benzene (36) was not Conclusions
detected [Eq. (4)]. However, the reaction could not
take place under the standard conditions, suggesting In summary, we have developed a new, practical Fe-
that the reaction does not proceed through an iodo- promoted electrophilic annulation method for the
cyclization process.
synthesis of 3-chalcogenoindoles. In the presence of I2
and Fe, a variety of 2-alkynylanilines selectively un-
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Iron-Facilitated Iodine-Mediated Electrophilic Annulation of N,N-Dimethyl-2-alkynylanilines
Scheme 3. Possible mechanism.
700 cmÀ1; LR-MS (EI, 70 eV): m/z (%)=315 (M+, 100), 316
(25), 300 (13), 283 (12), 223 (25).
derwent the electrophilic annulation with numerous
disulfides or diselenides leading to the corresponding
3-sulfenylindoles and 3-selenenylindoles in moderate
to excellent yields. The key to the reaction is the gen-
eration of RYI (Y=S, Se) in situ from the reaction of
RYYR with I2.
1-Methyl-2-phenyl-3-(p-tolylthio)-1H-indole (4):[8a] Yellow
solid, mp 106.1–106.88C (uncorrected) (lit. 106–1088C).
1H NMR (500 MHz, CDCl3): d=7.64 (d, J=7.5 Hz, 1H),
7.45–7.39 (m, 6H), 7.30 (t, J=7.5 Hz, 1H), 7.18 (t, J=
7.5 Hz, 1H), 6.94 (s, 4H), 3.71 (s, 3H), 2.22 (s, 3H);
13C NMR (125 MHz, CDCl3): d=145.7, 137.6, 136.3, 134.1,
130.6, 130.5, 129.8, 129.4, 128.6, 128.2, 125.8, 122.7, 120.8,
119.8, 109.8, 100.1, 31.7, 20.8; IR (KBr): n=1465, 1265, 801,
741, 700 cmÀ1; LR-MS (EI, 70 eV): m/z (%)=329 (M+, 100),
330 (25), 314 (15), 297 (15), 223 (18).
Experimental Section
3-(4-Methoxyphenylthio)-1-methyl-2-phenyl-1H-indole
(5):[12] Pale yellow solid, mp 122.2–124.08C (uncorrected).
1H NMR (500 MHz, CDCl3): d=7.67 (d, J=8.0 Hz, 1H),
7.44–7.37 (m, 6H), 7.29 (t, J=7.5 Hz, 1H), 7.19–7.18 (m,
1H), 7.00 (d, J=8.5 Hz, 2H), 6.68 (d, J=9.0 Hz, 2H), 3.68
(s, 3H), 3.67 (s, 3H); 13C NMR (125 MHz, CDCl3): d=
157.4, 145.4, 137.5, 130.6 (2C), 130.4, 129.7, 128.6, 128.2,
127.9, 122.6, 120.8, 119.7, 114.4; 109.7, 101.2, 55.2, 31.6; IR
(KBr): n=1490, 1265, 1238, 741, 700 cmÀ1; LR-MS (EI,
70 eV): m/z (%)=345 (M+, 100), 346 (26), 330 (31), 313
(11), 223 (14).
3-(4-Chlorophenylthio)-1-methyl-2-phenyl-1H-indole (6):
Yellow solid, mp 119.1–120.28C (uncorrected). 1H NMR
(500 MHz, CDCl3): d=7.61 (d, J=8.0 Hz, 1H), 7.46–7.43
(m, 4H), 7.39–7.37 (m, 2H), 7.35–7.32 (m, 1H), 7.21 (t, J=
7.5 Hz, 1H), 7.09 (d, J=9.0 Hz, 2H), 6.95 (d, J=9.0 Hz,
2H), 3.74 (s, 3H); 13C NMR (125 MHz, CDCl3): d=146.0,
138.6, 137.6, 130.9, 130.5, 130.3, 130.1, 128.9, 128.7, 128.3,
126.8, 122.9, 121.1, 119.6, 109.9, 99.2, 31.7; IR (KBr): n=
1473, 1265, 800, 740, 700 cmÀ1; LR-MS (EI, 70 eV): m/z
(%)=351 (M+, 37)/349 (M+, 100), 351 (37), 350 (24), 317
(12), 223 (25); HR-MS (EI): m/z=349.0689, calcd. for
C21H16ClNS (M+): 349.0686.
Typical Experimental Procedure for the Electrophilic
Tandem Cyclization
To a Schlenk tube were added 2-alkynylaniline derivative 1
(0.2 mmol), disulfide or diselenide
2
(0.1 mmol), I2
(1.1 equiv.), Fe (5 mol%) and MeCN (2 mL). Then the tube
was recharged with nitrogen and stirred at 808C until com-
plete consumption of starting material as monitored by TLC
or GC-MS analysis. After the reaction was finished, the re-
action mixture was filtered through glass filter and washed
with ethyl acetate. The solution was washed with saturated
aqueous Na2S2O3 and extracted with diethyl ether. The com-
bined organic layers were dried with anhydrous Na2SO4 and
concentrated under vacuum. The resulting residue was puri-
fied by column chromatography on silica gel (hexane/ethyl
acetate) to afford the desired product.
1-Methyl-2-phenyl-3-(phenylthio)-1H-indole (3):[8a] Yellow
solid, mp 94.4–95.88C (uncorrected) (lit. 98–1008C).
1H NMR (300 MHz, CDCl3): d=7.73 (d, J=7.8 Hz, 1H),
7.50–7.48 (m, 6H), 7.39–7.36 (m, 1H), 7.29–7.26 (m, 1H),
7.20–7.17 (m, 2H), 7.13–7.08 (m, 3H), 3.78 (s, 1H);
13C NMR (75 MHz, CDCl3): d=145.8, 140.0, 137.6, 130.6,
130.5, 129.7, 128.7, 128.6, 128.2, 125.5, 124.4, 122.8, 120.9,
119.8, 109.8, 99.6, 31.7; IR (KBr): n=1476, 1265, 800, 739,
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3-(4-Fluorophenylthio)-1-methyl-2-phenyl-1H-indole (7):
Yellow solid, mp 111.8–112.38C (uncorrected). 1H NMR
(300 MHz, CDCl3): d=7.63 (d, J=7.8 Hz, 1H), 7.45–7.31
(m, 7H), 7.22–7.17 (m, 1H), 7.01–6.97 (m, 2H), 6.84–6.79
(m, 2H), 3.70 (s, 3H); 13C NMR (75 MHz, CDCl3): d=160.6
(d, JC,F =242.0 Hz, 1C), 145.7, 137.5, 134.8 , 130.5, 130.3,
129.5, 128.8, 128.2, 127.4 (d, JC,F =7.6 Hz, 1C), 122.8, 121.0,
119.5, 115.6 (d, JC,F =21.9 Hz, 1C), 109.9, 100.0, 31.6; IR
(KBr): n=1487, 1266, 800, 742, 702 cmÀ1; LR-MS (EI,
70 eV) m/z (%)=333 (M+, 100), 334 (24), 318 (14), 301
(14), 223 (20); HR-MS (EI): m/z=333.0987, calcd. for
C21H16FNS (M+): 333.0982.
3-(3-Fluorophenylthio)-1-methyl-2-phenyl-1H-indole (8):
Yellow solid, mp 68.8–69.68C (uncorrected). 1H NMR
(300 MHz, CDCl3): d=7.62 (d, J=8.1 Hz, 1H), 7.44–7.32
(m, 7H), 7.23–7.17 (m, 1H), 7.11–7.03 (m, 1H), 6.83 (d, J=
8.1, 1H), 6.71–6.66 (m, 2H), 3.72 (s, 3H); 13C NMR
(75 MHz, CDCl3): d=163.1 (d, JC,F =147.8 Hz, 1C), 146.1,
142.8 (d, JC,F =3.8 Hz, 1C), 137.6, 130.5, 130.2, 129.8 (d,
d=144.0, 137.2, 131.1, 130.8, 129.5, 128.5, 128.3, 122.4, 120.4,
119.4, 109.7, 104.9, 31.3, 20.1; IR (KBr): n=1464, 1265, 800,
741, 700 cmÀ1; LR-MS (EI, 70 eV): m/z (%)=253 (M+, 100),
254 (19), 238 (77), 223 (25), 222 (19); HR-MS (EI): m/z=
253.0917, calcd. for C16H15NS (M+): 253.0920.
3-(Ethylthio)-1-methyl-2-phenyl-1H-indole (13): Yellow
oil. 1H NMR (300 MHz, CDCl3): d=7.75 (d, J=4.5 Hz,
1H), 7.44–7.35 (m, 5H), 7.29 (d, J=4.8 Hz, 1H), 7.23–7.20
(m, 1H), 7.17–7.14 (m, 1H), 3.56 (s, 3H), 2.52–2.47 (m, 2H),
0.95 (t, J=4.5 Hz, 3H); 13C NMR (75 MHz, CDCl3): d=
144.9, 137.2, 131.2, 130.9, 130.3, 128.4, 128.1, 122.4, 120.4,
119.6, 109.6, 103.0, 31.4, 30.5, 15.0; IR (KBr): n=1465, 1266,
800, 742, 701 cmÀ1; LR-MS (EI, 70 eV): m/z=(%): 267 (M+,
94), 239 (21), 238 (100), 223 (80), 222 (22); HR-MS (EI):
m/z=267.1075, calcd. for C17H17NS (M+): 267.1076.
3-(Cyclohexylthio)-1-methyl-2-phenyl-1H-indole
(14):
Yellow solid, mp 105.6–106.38C (uncorrected). 1H NMR
(300 MHz, CDCl3): d=7.90 (d, J=8.1 Hz, 1H), 7.56–7.49
(m, 5H), 7.41–7.35 (m, 1H), 7.32–7.29 (m, 2H), 3.69 (s, 3H),
2.81–2.78 (m, 1H), 1.82–1.79 (m, 2H), 1.67–1.52 (m, 2H),
1.51–1.45 (m, 1H), 1.32–1.17 (m, 1H), 1.14–1.12 (m, 4H);
13C NMR (75 MHz, CDCl3): d=145.3, 137.1, 131.3, 131.1,
130.8, 128.3, 128.0, 122.3, 120.3, 119.9, 109.5, 102.4, 48.0,
33.4, 31.4, 25.9, 25.7; IR (KBr): n=1464, 1265, 800, 740,
699 cmÀ1; LR-MS (EI, 70 eV): m/z (%)=321 (M+, 44), 240
(21), 239 (100), 238 (21), 223 (26); HR-MS (EI): m/z=
321.1548, calcd. for C21H23NS (M+): 321.1546.
J
J
C,F =5.3 Hz, 1C), 129.4, 128.8, 128.3, 122.9, 121.1, 120.9 (d,
C,F =1.5 Hz, 1C), 119.5, 112.1 (d, JC,F =14.3 Hz, 1C), 111.3
(d, JC,F =12.8 Hz, 1C), 109.9, 98.5, 31.7; IR (KBr): n=1467,
1265, 879, 742, 704 cmÀ1; LR-MS (EI, 70 eV): m/z (%)=333
(M+, 100), 334 (26), 301 (11), 238 (11), 223 (24); HR-MS
(EI): m/z=333.0987, calcd. for C21H17FNS (M+): 333.0982.
1-Methyl-3-(4-nitrophenylthio)-2-phenyl-1H-indole (9):[8a]
Yellow solid, mp 161.6–162.38C (uncorrected) (lit. 162–
1648C). 1H NMR (500 MHz, CDCl3): d=7.97 (d, J=8.5,
2H), 7.56 (d, J=8.0 Hz, 1H), 7.49–7.45 (m, 4H), 7.38–7.35
(m, 3H), 7.24–7.21 (m, 1H), 7.09 (d, J=9.0 Hz, 2H), 3.77 (s,
3H); 13C NMR (125 MHz, CDCl3): d=150.4, 146.4, 144.8,
137.7, 130.3, 129.9, 129.1, 129.0, 128.4, 124.8, 123.8, 123.3,
121.4, 119.2, 110.2, 97.0, 31.8; IR (KBr): n=1507, 1331,
1266, 740, 701 cmÀ1; LR-MS (EI, 70 eV): m/z (%)=360
(M+, 100), 361 (25), 281 (11), 238 (10), 223 (23).
3-(4-Chloro-2-nitrophenylthio)-1-methyl-2-phenyl-1H-
indole (10): Yellow solid, mp 206.8–207.88C (uncorrected).
1H NMR (300 MHz, CDCl3): d=8.24 (s, 1H), 7.53–7.36 (m,
8H), 7.27–7.20 (m, 2H), 7.00–6.94 (m, 1H), 3.79 (s, 3H);
13C NMR (75 MHz, CDCl3): d=146.9, 144.8, 139.6, 137.8,
133.4, 130.3, 129.9, 129.7, 129.2, 128.9 (2C), 128.5, 125.6,
123.3, 121.5, 119.3, 110.2, 97.9, 31.8; IR (KBr): n=1335,
1266, 766, 743, 699 cmÀ1; LR-MS (EI, 70 eV): m/z (%)=396
(M+, 3)/394 (M+, 7), 329 (4), 223 (20), 222 (100), 207 (5);
HR-MS (EI): m/z=394.0538, calcd. for C21H15ClN2O2S
(M+): 394.0537.
1-Methyl-3-(phenylthio)-2-p-tolyl-1H-indole (15): Yellow
1
solid, mp 112,6–113.88C (uncorrected). H NMR (300 MHz,
CDCl3): d=7.61 (d, J=7.8 Hz, 1H), 7.40 (d, J=8.4 Hz, 1H),
7.32–7.27 (m, 2H), 7.23–7.19 (m, 3H), 7.17–7.08 (m, 3H),
7.04–6.97 (m, 3H), 3.70 (s, 3H), 2.37 (s, 3H); 13C NMR
(75 MHz, CDCl3): d=146.1, 140.1, 138.8, 137.6, 130.5, 129.8,
129.1, 128.6, 127.5, 125.4, 124.3, 122.7, 120.9, 119.7, 109.8,
99.2, 31.8, 21.5; IR (KBr): n=1476, 1266, 825, 741, 704 cmÀ1
;
LR-MS (EI, 70 eV): m/z (%)=329 (M+, 100), 330 (25), 314
(11), 297 (12), 237 (21); HR-MS (EI): m/z=329.1238, calcd.
for C22H19NS (M+): 329.1233.
1-Methyl-3-(phenylthio)-2-o-tolyl-1H-indole (16): Yellow
1
solid, mp 99.4–100.88C (uncorrected). H NMR (300 MHz,
CDCl3): d=7.64 (d, J=8.7 Hz, 1H), 7.43 (d, J=8.1 Hz, 1H),
7.38–7.31 (m, 3H), 7.29–7.18 (m, 3H), 7.13–7.08 (m, 2H),
7.03–6.97 (m, 3H), 3.55 (s, 3H), 2.09 (s, 3H); 13C NMR
(75 MHz, CDCl3): d=145.6, 139.5, 138.3, 137.3, 131.1, 130.4,
130.0, 129.5, 129.3, 128.5, 125.7, 125.6, 124.3, 122.4, 120.7,
119.7, 109.7, 99.8, 30.9, 19.8; IR (KBr): n=1463, 1265, 739,
703, 690 cmÀ1; LR-MS (EI, 70 eV): m/z (%)=329 (M+, 100),
330 (25), 314 (25), 237 (27), 236 (12); HR-MS (EI): m/z=
329.1238, calcd. for C22H19NS (M+): 329.1233.
2-(4-Methoxyphenyl)-1-methyl-3-(phenylthio)-1H-indole
(17):[8a] Yellow solid, mp 136.4–137.38C (uncorrected) (lit.
136–1388C). 1H NMR (300 MHz, CDCl3): d=7.62 (d, J=
7.8 Hz, 1H), 7.41 (d, J=8.1 Hz, 1H), 7.34–7.28 ( m, 3H),
7.22–7.10 (m, 3H), 7.05–7.01 (m, 3H), 6.96 (d, J=8.4 Hz,
2H), 3.82 (s, 3H), 3.72 (s, 3H); 13C NMR (75 MHz, CDCl3):
d=159.9, 145.9, 140.1, 137.5, 131.8, 129.8, 128.6, 125.4, 124.3,
122.6 (2C), 120.8, 119.6, 113.8, 109.7, 99.1, 55.2, 31.6; IR
(KBr): n=1265, 1249, 740, 703, 691 cmÀ1; LR-MS (EI,
70 eV): m/z (%)=345 (M+, 100), 346 (25), 330 (12), 268 (9),
237 (15).
1-Methyl-2-phenyl-3-(pyridin-2-ylthio)-1H-indole
(11):
Pale solid, mp 140.6–141.38C (uncorrected). 1H NMR
(300 MHz, CDCl3): d=8.36–8.34 (m, 1H), 7.64 (d, J=
7.8 Hz, 1H), 7.45–7.41 (m, 6H), 7.35–7.29 (m, 2H), 7.23–
7.20 (m, 1H), 6.89–6.85 (m, 1H), 6.72 (d, J=8.1 Hz, 1H),
3.73 (s, 3H); 13C NMR (125 MHz, CDCl3): d=163.1, 149.2,
146.0, 137.7, 136.3, 130.2, 129.4, 128.9, 128.7, 128.1, 122.9,
121.0, 119.6, 119.4, 118.9, 109.9, 98.4, 31.7; IR (KBr): n=
1446, 1415, 1265, 741, 701 cmÀ1; LR-MS (EI, 70 eV): m/z
(%)=317 (M+ +1, 24), 316 (M+, 100), 315 (41), 283 (50),
223 (64); HR-MS (EI): m/z=316.1033, calcd. for C20H16N2S
(M+): 316.1034.
1-Methyl-3-(methylthio)-2-phenyl-1H-indole (12): Yellow
oil. 1H NMR (300 MHz, CDCl3): d=7.90 (d, J=7.8 Hz,
1H), 7.57–7.51 (m, 5H), 7.42–7.37 (m, 1H), 7.34–7.31 (m,
2H), 3.69 (s, 3H), 2.26 (s, 3H); 13C NMR (75 MHz, CDCl3):
2-(2-Methoxyphenyl)-1-methyl-3-(phenylthio)-1H-indole
(18):[8a] Pale yellow oil. 1H NMR (300 MHz, CDCl3): d=
2746
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Iron-Facilitated Iodine-Mediated Electrophilic Annulation of N,N-Dimethyl-2-alkynylanilines
7.68 (d, J=7.8 Hz, 1H), 7.48–7.46 (m, 2H), 7.37–7.30 (m,
2H), 7.27–7.18 (m, 1H), 7.17–7.00 (m, 7H), 3.73 (s, 3H),
3.66 (s, 3H); 13C NMR (75 MHz, CDCl3): d=157.8, 143.5,
140.0, 137.3, 132.9, 130.8, 129.6, 128.4, 125.6, 124.1, 122.3,
125.3, 124.4, 124.3, 119.3, 109.6, 98.6, 31.8, 21.5; IR (KBr):
n=1265, 793, 774, 740, 701 cmÀ1; LR-MS (EI, 70 eV): m/z
(%)=329 (M+, 100), 330 (25), 297 (14), 237 (25), 236 (15);
HR-MS (EI): m/z=329.1238, calcd. for C22H19NS (M+):
329.1233.
120.4ACHTUNGTRENNUNG(2C), 119.6, 119.5, 110.9, 109.6, 99.6, 55.3, 31.2; IR
(KBr): n=1464, 1265, 1248, 739, 703 cmÀ1; LR-MS (EI,
70 eV): m/z (%)=345 (M+, 100), 346 (25), 236 (21), 234
(14), 221 (14).
5-Fluoro-1-methyl-2-phenyl-3-(phenylselanyl)-1H-indole
(24): Yellow solid, mp 112.0–113.28C (uncorrected).
1H NMR (300 MHz, CDCl3): d=7.50–7.45 (m, 5H), 7.37–
7.36 (m, 2H), 7.20–7.17 (m, 2H), 7.11–7.07 (m, 4H), 3.77 (s,
1-Methyl-2-(4-nitrophenyl)-3-(phenylthio)-1H-indole (19):
Yellow solid, mp 166.3–167.58C (uncorrected). 1H NMR
(300 MHz, CDCl3): d=8.28 (d, J=8.4 Hz, 2H), 7.67 (d, J=
8.0 Hz, 1H), 7.59 (d, J=8.4 Hz, 2H), 7.46 (d, J=8.1 Hz,
1H), 7.38 (d, J=7.2 Hz, 1H), 7.25–7.22 (m, 1H), 7.17–7.12
(m, 2H), 7.06–7.00 (m, 3H), 3.77 (s, 3H); 13C NMR
(75 MHz, CDCl3): d=147.6, 142.8, 139.1, 138.0, 136.9, 131.5,
129.6, 128.8, 125.4, 124.8, 123.8, 123.5, 121.4, 120.1, 110.1,
3H); 13C NMR (75 MHz, CDCl3): d=158.7 (d, JC,F
=
141.0 Hz, 1C), 147.4, 139.5, 134.0, 130.5 (d, JC,F =5.3 Hz,
1C), 130.1, 128.9, 128.7, 128.3, 125.4, 124.5, 111.1 (d, JC,F
15.0 Hz, 1C), 110.7 (d, JC,F =6.0 Hz, 1C), 104.7 (d, JC,F
=
=
14.3 Hz, 1C), 99.6, 99.5, 31.9; IR (KBr): n=1474, 1266, 776,
741, 701 cmÀ1; LR-MS (EI, 70 eV): m/z (%)=333 (M+, 100),
334 (26), 241 (26), 98 (17), 43 (19); HR-MS (EI): m/z=
333.0987, calcd. for C21H16FNS (M+): 333.0982.
101.6, 32.0; IR (KBr): n=1465, 1339, 1266, 742, 704 cmÀ1
;
LR-MS (EI, 70 eV): m/z (%)=360 (M+, 100), 361 (24), 330
(11), 237 (10), 222 (11); HR-MS (EI): m/z=360.0930, calcd.
for C21H16N2O2S (M+): 360.0927.
1-Methyl-2-phenyl-3-(phenylselanyl)-1H-indole
(25):[8a]
Yellow oil. 1H NMR (300 MHz, CDCl3): d=7.68 (d, J=
7.8 Hz, 1H), 7.44–7.34 (m, 9H), 7.24–7.09 (m, 4H), 3.74 (s,
3H); 13C NMR (75 MHz, CDCl3): d=145.9, 137.7, 134.6,
131.2, 130.8, 130.6, 128.8, 128.6, 128.4, 128.1, 125.2, 122.7,
120.8, 120.7, 109.7, 96.4, 31.7; IR (KBr): n=1474, 1464, 733,
699, 690 cmÀ1; LR-MS (EI, 70 eV): m/z (%)=363 (M+, 28),
329 (35), 283 (100), 279 (22), 204 (24).
1-Methyl-3-(phenylthio)-2-[3-(trifluoromethyl)phenyl]-
1
1H-indole (20): Yellow oil. H NMR (300 MHz, CDCl3): d=
7.69–7.65 (m, 3H), 7.60–7.52 (m, 2H), 7.44 (d, J=8.1 Hz,
1H), 7.37–7.32 (m, 1H), 7.24–7.19 (m, 1H), 7.16–7.11 (m,
2H), 7.04–7.02 (m, 3H), 3.73 (s, 3H); 13C NMR (75 MHz,
CDCl3): d=143.8, 139.5, 137.7, 133.9, 131.3, 130. 7 (q, JC,F
32.3 Hz), 129.7, 128.8, 128.7, 127.4 (q, JC,F =3.8 Hz), 125.8,
125.4 (q, C,F =3.8 Hz), 124.7, 122.8, 122.3 (q, JC,F
258.8 Hz), 120.0, 110.0, 101.0, 31.7; IR (KBr): n=1323, 1266,
1124, 740, 702 cmÀ1; LR-MS (EI, 70 eV): m/z (%)=384
(M+ +1, 24), 383 (M+, 100), 368 (13), 351 (11), 291 (16);
HR-MS (EI): m/z=383.0955, calcd. for C22H16F3NS (M+):
383.0950.
2-Hexyl-1-methyl-3-(phenylthio)-1H-indole (21): Yellow
oil. 1H NMR (300 MHz, CDCl3): d=7.60 (d, J=7.8 Hz,
1H), 7.38 (d, J=8.1 Hz, 1H), 7.30–7.25 (m, 1H), 7.20–7.14
(m, 3H), 7.07 (d, J=7.6 Hz, 3H), 3.81 (s, 3H), 2.97 (t, J=
7.8 Hz, 2H), 1.63–1.53 (m, 2H), 1.30 (m, 6H), 0.88 (t, J=
7.2 Hz, 3H); 13C NMR (75 MHz, CDCl3): d=147.0, 139.9,
137.2, 129.7, 128.5, 125.3, 124.3, 121.7, 120.4, 119.0, 109.1,
97.7, 31.5, 30.3, 29.9, 29.0, 24.9, 22.5, 14.0; IR (KBr): n=
1466, 1439, 1265, 739, 704 cmÀ1; LR-MS (EI, 70 eV): m/z
(%)=323 (M+, 67), 252 (32), 220 (25), 214 (32), 144 (100);
HR-MS (EI): m/z=323.1704, calcd. for C21H25NS (M+):
323.1702.
=
1-Methyl-2-phenyl-3-(p-tolylselanyl)-1H-indole
(26):
Yellow solid, mp 110.2–110.68C (uncorrected). 1H NMR
(300 MHz, CDCl3): d=7.67 (d, J=7.8 Hz, 1H), 7.45–7.37
(m, 6H), 7.31–7.26 (m, 1H), 7.24–7.19 (m, 1H), 7.06 (d, J=
8.1 Hz, 2H), 6.92 (d, J=7.8 Hz, 2H), 3.72 (s, 3H), 2.22 (s,
3H); 13C NMR (75 MHz, CDCl3): d=145.7, 137.7, 135.0,
131.3, 130.8, 130.7, 130.6, 129.7, 128.6, 128.1, 127.7, 122.6,
120.8, 120.7, 109.7, 96.8, 31.8, 20.9; IR (KBr): n=1465, 1266,
800, 741, 702 cmÀ1; LR-MS (EI, 70 eV): m/z (%)=377 (M+,
21), 375 (12), 298 (24), 297 (100), 141 (10); HR-MS (EI):
m/z=377.0678, calcd. for C22H19NSe (M+): 377.0677.
J
=
1-Methyl-3-(methylselanyl)-2-phenyl-1H-indole
(27):
Yellow oil. 1H NMR (300 MHz, CDCl3): d=7.86 (d, J=
8.1 Hz, 1H), 7.56–7.50 (m, 5H), 7.42–7.31 (m, 3H), 3.71 (s,
3H), 2.09 (s, 3H); 13C NMR (75 MHz, CDCl3): d=144.2,
137.4, 131.6, 130.9, 130.3, 128.5, 128.1, 122.4, 120.4, 120.3,
109.6, 98.3, 31.5, 9.1; IR (KBr): n=1465, 1266, 896, 741,
703 cmÀ1; LR-MS (EI, 70 eV): m/z (%)=301 (M+, 100), 299
(48), 286 (77), 271 (53), 206 (63); HR-MS (EI): m/z=
301.0367, calcd. for C16H15NSe (M+): 301.0364.
2-tert-Butyl-1-methyl-3-(phenylthio)-1H-indole
(22):
2-(4-Methoxyphenyl)-1-methyl-3-(phenylselanyl)-1H-
White solid, mp 153.5–154.38C (uncorrected). 1H NMR
(300 MHz, CDCl3): d=7.61 (d, J=7.8 Hz, 1H), 7.33 (d, J=
8.1 Hz, 1H), 7.27–7.22 (m, 1H), 7.16–7.02 (m, 3H), 7.00–
6.95 (m, 3H), 7.05–6.95 (m, 3H), 3.99 (s, 3H), 1.64 (s, 9H);
13C NMR (75 MHz, CDCl3): d=151.0, 141.0, 138.1, 130.8,
128.6, 124.8, 123.9, 122.4, 120.5, 119.5, 108.8, 97.5, 35.1, 34.1,
31.4; IR (KBr): n=1467, 1266, 740, 703, 690 cmÀ1; LR-MS
(EI, 70 eV): m/z (%)=295 (M+, 93), 280 (46), 171 (100), 170
(21), 149 (34); HR-MS (EI): m/z=295.1392, calcd. for
C19H21NS (M+): 295.1389.
indole (28): Yellow solid, mp 123.8–124.48C (uncorrected).
1H NMR (300 MHz, CDCl3): d=7.67 (d, J=7.8 Hz, 1H),
7.43 (d, J=8.1 Hz, 1H), 7.35–7.31 (m, 3H), 7.26–7.07 (m,
6H), 6.98 (d, J=8.4 Hz, 2H), 3.86 (s, 3H), 3.74 (s, 3H);
13C NMR (75 MHz, CDCl3): d=159.8, 145.9, 137.7, 134.7,
132.0, 130.7, 128.8, 128.3, 125.2, 123.4, 122.5, 120.8, 120.5,
113.6, 109.7, 96.1, 55.3, 31.7; IR (KBr): n=1326, 1266, 896,
742, 704 cmÀ1; LR-MS (EI, 70 eV): m/z (%)=393 (M+, 20),
391 (11), 314 (26), 313 (100), 270 (7); HRMS (EI): m/z=
393.0628, calcd. for C22H19NOSe (M+): 393.0626.
1,5-Dimethyl-2-phenyl-3-(phenylthio)-1H-indole
(23):
2-(2-Methoxyphenyl)-1-methyl-3-(phenylselanyl)-1H-
White solid, mp 110.0–110.48C (uncorrected). 1H NMR
(300 MHz, CDCl3): d=7.43–7.39 (m, 6H), 7.31 (d, J=
8.1 Hz, 1H), 7.21–7.11 (m, 3H), 7.05–6.99 (m, 3H), 3.70 (s,
3H), 2.43 (s, 3H); 13C NMR (75 MHz, CDCl3): d=152.1,
146.0, 140.3, 136.0, 130.9, 130.6, 130.5, 130.0, 128.7, 128.2,
indole (29): Yellow oil; 1H NMR (300 MHz, CDCl3): d=
7.70 (d, J=7.8 Hz, 1H), 7.45 (d, J=7.8 Hz, 2H), 7.34–7.19
(m, 5H), 7.13–7.00 (m, 5H), 3.73 (s, 3H), 3.67 (s, 3H);
13C NMR (125 MHz, CDCl3): d=157.9, 143.4, 137.5, 134.7,
133.1, 130.7, 130.5, 128.6 (2C), 128.4, 125.0, 122.2, 120.5,
Adv. Synth. Catal. 2011, 353, 2739 – 2748
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Hui-Ai Du et al.
FULL PAPERS
120.4, 120.3, 110.8, 109.5, 96.5, 55.3, 31.2; IR (KBr): n=
1265, 1247, 739, 704, 690 cmÀ1; LR-MS (EI, 70 eV): m/z
(%)=393 (M+, 33), 314 (24), 313 (100), 234 (21), 220 (19);
HR-MS (EI): m/z=393.0628, calcd. for C22H19NOSe (M+):
393.0626.
1-Methyl-2-(4-nitrophenyl)-3-(phenylselanyl)-1H-indole
(30): Yellow solid, mp 137.7–138.78C (uncorrected).
1H NMR (300 MHz, CDCl3): d=8.29 (d, J=9.0 Hz, 2H),
7.70 (d, J=7.8 Hz, 1H), 7.56 (d, J=8.7 Hz, 2H), 7.45 (d, J=
8.1 Hz, 1H), 7.46–7.36 (m, 1H), 7.26–7.21 (m, 1H), 7.13–
7.09 (m, 5H), 3.77 (s, 3H); 13C NMR (75 MHz, CDCl3): d=
147.7, 142.9, 138.2, 137.8, 133.9, 131.7, 130.6, 129.1, 128.4,
125.7, 123.7, 123.3, 121.4, 121.1, 109.9, 98.4, 32.0; IR (KBr):
n=1465, 1339, 1266, 741, 704 cmÀ1; LR-MS (EI, 70 eV): m/z
(%)=408 (M+, 29), 329 (25), 328 (100), 282 (31), 267 (24);
HR-MS (EI): m/z=408.0374, calcd. for C21H16N2O2Se (M+):
408.0372.
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5-Fluoro-1-methyl-2-phenyl-3-(phenylselanyl)-1H-indole
(31): Yellow oil; H NMR (300 MHz, CDCl3): d=7.46–7.44
1
(m, 3H), 7.39–7.32 (m, 4H), 7.12–7.09 (m, 6H), 3.77 (s,
3H); 13C NMR (75 MHz, CDCl3): d=158.8 (d, JC,F
=
141.0 Hz, 1C), 147.4, 134.3, 134.2, 131.4, 131.0, 130.7, 128.9
(2C), 128.6, 128.5, 128.2, 125.5, 111.0 (d, JC,F =16.5 Hz, 1C),
110.5 (d, JC,F =6.0 Hz, 1C), 105.7 (d, JC,F =14.3 Hz, 1C),
32.0; IR (KBr): n=1474, 1022, 794, 775, 698 cmÀ1; LR-MS
(EI, 70 eV): m/z (%)=381 (M+, 26), 379 (13), 301 (100), 302
(23), 285 (12); HR-MS (EI): m/z=381.0429, calcd. for
C21H16FNSe (M+): 381.0427.
Acknowledgements
We thank the Natural Science Foundation of China (Nos.
20872112 and 21002070), and Zhejiang Provincial Natural
Science Foundation of China (Nos. Y4100307 and Y4080169)
for financial support.
[7] For selected papers on the synthesis of 3-sulfenylin-
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2748
asc.wiley-vch.de
ꢁ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2011, 353, 2739 – 2748