Iron(III) chloride promoted desulfitative C-C coupling reaction of α-oxo ketene dithioacetals and indoles: Highly selective synthesis of β,β-bisindolyl and β-indolyl α,β-unsaturated carbonyl compounds

Article abstract of DOI:10.1055/s-0032-1317691

The iron(III) chloride promoted desulfitative C-C coupling of α-oxo ketene dithioacetals with indoles was developed for the synthesis of indole derivatives. In the presence of iron(III) chloride, α-oxo ketene dithioacetals reacted efficiently and highly s

Full text of DOI:10.1055/s-0032-1317691

PAPER
▌3743
paper
Iron(III) Chloride Promoted Desulfitative C–C Coupling Reaction of α-Oxo
Ketene Dithioacetals and Indoles: Highly Selective Synthesis of β,β-Bisindolyl
and β-Indolyl α,β-Unsaturated Carbonyl Compounds
β,β-Bisindolyl and β-Indolyl α,β-Unsaturated Carbonyl Compounds
Haifeng Yu,*a Tiechun Li,a Peiqiu Liaob
a
School of Chemistry and Life Science, Anshan Normal University, Anshan, Liaoning 114007, P. R. of China
Fax +86(412)2960065; E-mail: yuhf@mail.asnc.edu.cn
b
Department of Chemistry, Northeast Normal University, Changchun, Jilin 130024, P. R. of China
Received: 05.09.2012; Accepted after revision: 05.11.2012
as a result of its abundance, low cost, lack of toxicity, sta-
Abstract: The iron(III) chloride promoted desulfitative C–C cou-
bility, and ease of handling.12–15 Although many iron(III)
pling of α-oxo ketene dithioacetals with indoles was developed for
chloride catalyzed or promoted reactions have been
the synthesis of indole derivatives. In the presence of iron(III) chlo-
ride, α-oxo ketene dithioacetals reacted efficiently and highly selec-
documented, there are few reports on iron-catalyzed or
tively with C2-unsubstituted or C2-substituted indoles to afford -promoted desulfitative C–C coupling reactions.16 Here,
excellent yields of β,β-bisindolyl or β-indolyl α,β-unsaturated car-
bonyl compounds, respectively.
we report an iron(III) chloride promoted desulfitative C–C
coupling reaction between α-oxo ketene dithioacetals and
Key words: heterocycles, coupling, indoles, desulfurizations, ca-
talysis
C2-unsubstituted or C2-substituted indoles. Unlike our
previous work,11 this work concentrates on the effect of
groups at the C2 position of the indoles on the coupling re-
action. These effects permit the selective preparation of
The catalytic desulfitative coupling reaction is emerging β,β-bisindolyl or β-indolyl α,β-unsaturated carbonyl com-
as one of the most important tools available for the forma- pounds.
tion of C–C bonds.1–3 Palladium- or copper-catalyzed de-
sulfitative coupling reactions of thio esters with organic
α-Oxo ketene dithioacetals 1, as versatile intermedi-
ates,17–20 were conveniently prepared by the reported pro-
boronic acids have been well developed for the synthesis
tocols in high yields.17,21 We initially examined the
of ketones (Scheme 1, A).1–3 Yu4 and Wang5 and their co-
reaction of 4,4-bis(ethylsulfanyl)but-3-en-2-one (1a; 0.25
mmol) with 1H-indole (2a; 0.25 mmol) in the presence of
workers successfully performed Liebeskind–Srogl cou-
pling and copper-catalyzed desulfitative C–C coupling re-
iron(III) chloride (0.25 mmol) in dichloromethane (2 mL)
actions of α-oxo ketene dithioacetals with organic boronic
at room temperature for 24 hours. The reaction gave the
bisindole product 4,4-di-1H-indol-3-ylbut-3-en-2-one
(3a) exclusively in 12% yield, with 80% recovery of the
starting material 1a (Table 1, entry 1). This result showed
that the reaction in the presence of iron(III) chloride gives
the bisindolyl product 3a in preference to the monoindolyl
product 4a. Next, we examined the reaction in detail un-
der various conditions to identify the optimal conditions;
these results are summarized in Table 1. At room temper-
ature, the yield of the bisindolyl product 3a was slightly
improved by increasing the amount of iron(III) chloride
(entries 2–4), suggesting that the efficiency of the reaction
acids to give polysubstituted olefins (Scheme 1, A). How-
ever, all the published investigations have focused exclu-
sively on palladium- or copper-catalyzed desulfitative
C–C coupling reactions of thioorganic acids with boronic
acids. There is therefore considerable interest in develop-
ing novel desulfitative C–C coupling reactions. The func-
tionalization of indoles had attracted the interest of many
synthetic chemists,6–8 because indole scaffolds are fre-
quently found in natural bioactive products and in impor-
tant pharmaceuticals.9,10 We recently began to study the
desulfitative C–C coupling reactions of α-oxo ketene di-
thioacetals with indoles, and we found that the trifluoro-
is not markedly improved by increasing the amount of
acetic acid-mediated coupling reaction gave potentially
iron(III) chloride at room temperature. The reaction did,
useful indole derivatives.11 Our results suggested that the
however, proceed more efficiently at elevated tempera-
tures (entries 5–9), and 3a was obtained in 95% yield
when the reaction was carried out at 80 °C for two hours
(entry 9). On changing the molar ratio of 1a, 2a, and
acidity of the reaction medium has a marked effect on the
coupling reaction, in that β-indolyl α,β-unsaturated car-
bonyl compounds were obtained as the major products
when concentrated acid was used, whereas β,β-bisindolyl
iron(III) chloride from 1:2:2 to 1:2:1, the yield of 3a fell
α,β-unsaturated carbonyl compounds were exclusively
to 46% and 1a was recovered in 41% yield (entry 10).
obtained in dilute solutions of the acid (Scheme 1, B).11
When iron(III) triflate was used as the catalyst, neither the
Iron(III) chloride has emerged as an alternative and prom- bisindole 3a nor the monoindole 4a was detected, and 1a
ising catalyst for a wide range of organic transformations was almost completely recovered (entries 11 and 12). The
reaction proceeded less efficiently in chloroform, carbon
tetrachloride, or 1,2-dichloroethane (entries 13-15), and
no reaction occurred in tetrahydrofuran (entry 16). Ac-
SYNTHESIS 2012, 44, 3743–3756
Advanced online publication: 16.11.2012
DOI: 10.1055/s-0032-1317691; Art ID: SS-2012-H0702-OP
© Georg Thieme Verlag Stuttgart · New York
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X
cordingly, the optimal reaction conditions are
a

3744
H. Yu et al.
PAPER
A: catalytic desulfitative C-C coupling of thioesters or α-oxo ketene dithioacetals with boronic acids
O
O
R1
R1
SR
SR
R1
R1
R3
Pd or Cu
R3B(OH)2
+
R1
R3(R4)
R3
R3B(OH)2
SR
or R4B(OH)2
O
SR
O
R3
O
Pd or Cu
R2
R2
R2
B: catalytic desulfitative C-C coupling of α-oxo ketene dithioacetals with indoles (our work)
R1
R1
R4
R4
R2
R2
TFA
R5 = Me, aryl, 2-thienyl
FeCl3
O
(20 equiv)
O
R4
R4
EtS
EtS
R5
R1
N
N
R3
N
R2
R5
R1
N
R3
R3
R3
O
R1
this work
previous work
R4
R4
R4
R4
R2
R2
EtS
SEt
TFA
(4 equiv)
O
O
R
5 = H
FeCl3
N
R3
N
R3
N
R3
N
R3
Scheme 1 Catalytic desulfitative C–C coupling reactions
Table 1 Screening of Conditions for Iron(III) Chloride Catalyzed Coupling of 4,4-Bis(ethylsulfanyl)but-3-en-2-one (1a) with 1H-Indole (2a)
O
conditions
NH
O
+
N
H
EtS
1a
SEt
N
N
SEt
(Z/E)-4a
O
H
H
3a
2a
Entrya
Solvent
1a/2a/FeCl3 (mol)
Temp (°C)
Time (h)
Yield (%) of 3ab
1
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CHCl3
1:1:1
1:2:2
1:2:4
1:2:6
1:2:2
1:2:2
1:2:2
1:2:2
1:2:2
1:2:1
1:2:2
1:2:2
1:2:2
1:2:2
1:2:2
1:2:2
r.t.
r.t.
r.t.
r.t.
40
24
24
24
24
10
6
12 (80)c
20 (68)c
22(69)c
25(63)c
43(44)c
61
2
3
4
5
6
50
7
60
5
78
8
70
3
91
9
80
2
95
46 (41)c
10
11d
12d
13
14
15
16
80
10
10
10
10
10
3
r.t.
40
e (95)c
–
e (92)c
–
80
27(59)c
10 (81)c
68
CCl4
80
Cl(CH2)2Cl
THF
reflux
80
10
No reaction
a Reaction conditions: 1a (0.25 mmol), solvent (2 mL), sealed tube.
b Isolated yield.
c Percentage recovery of 1a.
d Reaction performed in the presence of Fe(OTf)3.
e Neither 3a nor 4a was detected.
Synthesis 2012, 44, 3743–3756
© Georg Thieme Verlag Stuttgart · New York

PAPER
β,β-Bisindolyl and β-Indolyl α,β-Unsaturated Carbonyl Compounds
3745
1a/2a/iron(III) chloride ratio of 1:2:2, dichloromethane as the same reaction with indoles 2a or 2d to give high yields
the solvent, and a temperature of 80 °C.
of the corresponding bisindole products 3f–p (entries 6–
16). Surprisingly, treatment of 3-[bis(ethylsulfanyl)meth-
ylene]pentane-2,4-dione (1h) or ethyl 2-acetyl-3,3-
bis(ethylsulfanyl)acrylate (1i) with indole 2d gave the
corresponding deacetylation products 3d (71%) and 3p
(65%), respectively (entries 17 and 18). 2-Acetyl-3,3-
bis(ethylsulfanyl)-N-phenylacrylamide (1j) and indole 2d
showed no reaction under the selected reaction conditions
(entry 19). In the case of the α-alkenoyl ketene dithioace-
tal 1k, the trisindolyl derivative 3q was isolated in 59%
yield in the presence of three equivalents of indole 2d (en-
try 20).
Next, we used the optimized reaction conditions for the
reactions of α-oxo ketene dithioacetals 1a–k with indoles
2a–e to define the scope of the reaction. The results are
summarized in Table 2. Dithioacetal 1a reacted efficiently
with both N-unsubstituted indoles 2a–c and N-substituted
indoles 2d–e to give the corresponding 4,4-bis(indol-3-
yl)but-3-en-2-ones 3a–e in excellent yields (Table 2, en-
tries 1–5). Various α-oxo ketene dithioacetals, such as 1-
aryl-3,3-bis(ethylsulfanyl)prop-2-en-1-ones 1b–e, diethyl
[bis(ethylsulfanyl)methylene]malonate (1f), and ethyl
3,3-bis(ethylsulfanyl)acrylate (1g) efficiently underwent
Table 2 Iron(III) Chloride Promoted Desulfitative C–C Coupling of Dithioacetals 1 with C2-Unsubstituted Indoles 2a
R1
R4
R4
R1
R2
O
R4
R2
FeCl3, 80 °C
CH2Cl2
O
+
N
R3
EtS
SEt
N
R3
N
R3
1
2
3
Entry
Dithioacetal
Indole
Product
Yield (%)b
O
O
1
95
N
H
EtS
SEt
HN
NH
2a
1a
3a
MeO
OMe
MeO
O
N
2
3
4
5
1a
1a
1a
1a
93
96
95
92
H
HN
NH
2b
3b
Br
Br
Br
O
N
H
HN
NH
2c
3c
3d
3e
O
NMe
MeN
NMe
2d
O
NBn
BnN
NBn
2e
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2012, 44, 3743–3756

3746
H. Yu et al.
PAPER
Table 2 Iron(III) Chloride Promoted Desulfitative C–C Coupling of Dithioacetals 1 with C2-Unsubstituted Indoles 2a (continued)
R1
R4
R4
R1
R2
O
R4
R2
FeCl3, 80 °C
CH2Cl2
O
+
N
R3
EtS
SEt
N
R3
N
R3
1
2
3
Entry
Dithioacetal
Indole
Product
Yield (%)b
O
6
2a
93
O
EtS
SEt
HN
NH
1b
3f
O
7
1b
2d
97
MeN
NMe
3g
OMe
O
8
2a
94
O
EtS
SEt
MeN
NMe
1c
3h
OMe
9
1c
2d
96
O
MeN
NMe
3i
Br
Br
10
2a
95
O
O
EtS
SEt
HN
NH
1d
3j
Synthesis 2012, 44, 3743–3756
© Georg Thieme Verlag Stuttgart · New York

PAPER
β,β-Bisindolyl and β-Indolyl α,β-Unsaturated Carbonyl Compounds
3747
Table 2 Iron(III) Chloride Promoted Desulfitative C–C Coupling of Dithioacetals 1 with C2-Unsubstituted Indoles 2a (continued)
R1
R4
R4
R1
R2
O
R4
R2
FeCl3, 80 °C
CH2Cl2
O
+
N
R3
EtS
SEt
N
R3
N
R3
1
2
3
Entry
Dithioacetal
Indole
Product
Yield (%)b
Br
11
1d
2d
94
O
MeN
NMe
3k
S
S
O
O
12
2d
92
EtS
SEt
MeN
NMe
1e
3l
OEt OEt
OEt OEt
OEt
OEt OEt
O
O
O
O
13c
14c
15
2a
2d
2a
2d
82
84
91
92
EtS
SEt
HN
NH
1f
3m
O
O
1f
MeN
NMe
3n
OEt
O
O
EtS
SEt
HN
NH
1g
3o
OEt
O
16
1g
MeN
NMe
3p
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2012, 44, 3743–3756

3748
H. Yu et al.
PAPER
Table 2 Iron(III) Chloride Promoted Desulfitative C–C Coupling of Dithioacetals 1 with C2-Unsubstituted Indoles 2a (continued)
R1
R4
R4
R1
R2
O
R4
R2
FeCl3, 80 °C
CH2Cl2
O
+
N
R3
EtS
SEt
N
R3
N
R3
1
2
3
Entry
17c
Dithioacetal
Indole
Product
Yield (%)b
O
O
2d
3d
71
EtS
SEt
O
1h
O
OEt
18c
2d
2d
3p
65
EtS
SEt
1i
O
O
N
H
19
no reaction
EtS
SEt
1j
O
NMe
20
2d
59
EtS
SEt
O
NMe MeN
1k
3q
a Reaction conditions: 1 (0.25 mmol), 2 (0.5 mmol), FeCl3 (0.5 mmol), CH2Cl2 (2 mL), 80 °C, sealed tube, 2–4 h.
b Isolated yield.
c 6 h.
Furthermore, we also demonstrated the synthesis of the Next, we examined the reaction of dithioacetals 1 with
heterobisindoles through the reaction of (3Z)-4-(ethyl- C2-substituted indoles 2f–h in the presence of iron(III)
sulfanyl)-4-(1-methyl-1H-indol-3-yl)but-3-en-2-one (4b) chloride in dichloromethane. Initially, we examined the
with indole 2a or 2e (Scheme 2). When 4b was treated reaction of dithioacetal 1a with indole 2f under these con-
with 2a or 2e in the presence of one equivalent of iron(III) ditions. When the reaction was performed for three hours,
chloride, the hetrobisindoles 3r and 3s were isolated in the desired product, 4,4-bis(2-methyl-1H-indol-3-yl)but-
yields of 90 and 92%, respectively. The Z/E ratio of these 3-en-2-one (3t) was obtained in only 10% yield, whereas
products was approximately 1:1.
(3E/3Z)-4-(ethylsulfanyl)-4-(2-methyl-1H-indol-3-yl)but-
3-en-2-one (4c) was obtained as the major product in 73%
yield with a Z/E ratio as high as 5:2. This result shows that
the steric bulk of the C2 substituent of 2f hinders disubsti-
tution of 1a to form 3t. On prolonging the reaction to 24
hours, however, we obtained 3t as the major product in
56% yield. Subsequently, we changed the molar ratio of
1a, 2f, and iron(III) chloride from 1:2:2 to 1:3:3, and we
obtained 3t in 72% yield after 12 hours. In a similar fash-
ion, 4c was obtained in 80% yield from a reaction per-
formed with a 1:1:1 molar ratio of 1a, 2f, and iron(III)
chloride for seven hours. The optimal reaction conditions
O
O
2a or 2e (1 equiv)
FeCl3 (1 equiv)
EtS
CH2Cl2, 80 °C, 3 h
N
MeN
NMe
R
4b
3r: R = H, 90%
3s: R = Bn, 92%
Scheme 2
Synthesis 2012, 44, 3743–3756
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PAPER
β,β-Bisindolyl and β-Indolyl α,β-Unsaturated Carbonyl Compounds
3749
are therefore as follows: conditions A: 1a/2f/iron(III) more-acidic conditions A, affording ethyl 3,3-bis(2-meth-
chloride = 1:3:3, temperature = 80 °C, solvent = CH2Cl2 yl-1H-indol-3-yl)acrylate (3y) in 43% yield (entry 6).
for the synthesis of 3t; conditions B: 1a/2f//iron(III) chlo- Reactions of 1a with 2-phenyl-1H-indole (2g) under con-
ride = 1:1:1, temperature = 80 °C, solvent = CH2Cl2 for ditions A or B gave good yields of the monoindole 4i (en-
synthesis of 4c.
try 7) exclusively, whereas the corresponding reactions of
1a with 1-ethyl-2-phenyl-1H-indole (2h) gave good
yields of monindole 4j exclusively (entry 8). This is the
result of the phenyl group at the C2 of the indolyl moiety
in 4i and 4j blocking further substitution to produce the
bisindole products. From our previous work,11 products 4
with a Z-configuration, in which the indolyl and acetyl
groups are positioned anti to one another, were always ob-
tained as the major products.
Having determined the optimal conditions, we examined
the reactions of α-oxo ketene dithioacetals 1a–f with the
C2-substituted indoles 2f–h to define the scope of the re-
action. As shown in Table 3, 1a–f and 2-methyl-1H-in-
dole (2f) reacted efficiently to give the corresponding β,β-
bisindolyl α,β-unsaturated carbonyl compounds 3t–y in
43–90% yield and the β-indolyl α,β-unsaturated carbonyl
compounds 4c–h in 67–85% yield (entries 1–6). Deester-
ification occurred when 1f was treated with 2f under the
Table 3 Iron(III) Chloride Promoted Desulfitative Carbon–Carbon Coupling of Dithioacetals 1 with C2-Substituted Indoles 2
R1
R1
R1
R4
R4
R4
R2
R2
R4
R2
O
O
R5
O
A
B
+
N
R3
EtS
EtS
SEt
2f–h
N
1
N
R3
N
R3
R5
R5
R5
2f R3 = H, R5 = Me
2g R3 = H, R5 = Ph
2h R3 = Et, R5 = Ph
R3
3t–y
4
Entry
Dithioacetal
Indole
Conditionsa
Product
Yield (%)b
NH
1
1a
2f
A
3t
72
O
NH
B
A
B
4c
3u
4d
80 (5:2)c
NH
O
SEt
NH
2
1b
2f
80
O
NH
82 (4:1)c
NH
O
SEt
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2012, 44, 3743–3756

3750
H. Yu et al.
PAPER
Table 3 Iron(III) Chloride Promoted Desulfitative Carbon–Carbon Coupling of Dithioacetals 1 with C2-Substituted Indoles 2 (continued)
R1
R1
R1
R4
R4
R4
R2
R2
R4
R2
O
O
R5
O
A
B
+
N
R3
EtS
EtS
SEt
N
2f–h
1
N
R3
N
R3
R5
R5
R5
2f R3 = H, R5 = Me
2g R3 = H, R5 = Ph
2h R3 = Et, R5 = Ph
R3
3t–y
4
Entry
Dithioacetal
Indole
Conditionsa
Product
Yield (%)b
MeO
NH
3
1c
2f
A
3v
88
O
NH
H3CO
B
A
B
4e
3w
4f
82 (3:1)c
NH
O
SEt
Br
NH
4
1d
2f
83
O
NH
Br
85 (3:1)c
NH
O
SEt
S
NH
5
1e
2f
A
3x
90
O
NH
B
4g
3y
83 (5:1)c
NH
S
O
SEt
NH
EtO
6
1f
2f
Ad
43
O
NH
Synthesis 2012, 44, 3743–3756
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β,β-Bisindolyl and β-Indolyl α,β-Unsaturated Carbonyl Compounds
3751
Table 3 Iron(III) Chloride Promoted Desulfitative Carbon–Carbon Coupling of Dithioacetals 1 with C2-Substituted Indoles 2 (continued)
R1
R1
R1
R4
R4
R4
R2
R2
R4
R2
O
O
R5
O
A
B
+
N
R3
EtS
EtS
SEt
N
2f–h
1
N
R3
N
R3
R5
R5
R5
2f R3 = H, R5 = Me
2g R3 = H, R5 = Ph
2h R3 = Et, R5 = Ph
R3
3t–y
4
Entry
Dithioacetal
Indole
Conditionsa
Product
Yield (%)b
EtO
O
B
4h
67
NH
EtO
O
SEt
A
B
75(6:1)c
73 (6:1)c
7
8
1a
1a
2g
2h
4i
4j
NH
Ph
O
O
SEt
A
B
81 (6:1)c
83 (6:1)c
NEt
Ph
SEt
a Reaction conditions: A: 1 (0.25 mmol), 2 (0.75 mmol), FeCl3 (0.75 mmol), CH2Cl2 (2 mL), 80 °C, sealed tube, 12 h. B: 1 (0.25 mmol), 2 (0.25
mmol), FeCl3 (0.25 mmol), CH2Cl2 (2 mL), 80 °C, sealed tube, 7 h.
b Isolated yield.
c Molar ratio of (Z)- and (E)-isomers of 4, determined by 1H NMR.
d Reaction performed at 100 °C for 24 h.
On the basis of our previous work11 and the current exper- (EtSFeCl2) from intermediate II. In the presence of
imental results, we propose a possible mechanism for the iron(III) chloride, III (R = H) or 4a (R = Me) is attacked
reaction, which is shown in Scheme 3. It is clear that by a second molecule of the indole to afford products 3a
iron(III) chloride promoted Michael addition of dithio- or 3t after elimination of a second molecule of EtSFeCl2.
acetal 1a with the indole occurs initially with formation of However, because of the steric restriction imposed by the
adduct I, which is transformed into intermediate II by methyl group in the C2 position of indole 4a, substitution
elimination of hydrogen chloride. The β-indolyl mono- to form the bisindole 3t occurs slowly. As a result, either
substituted product III (R = H) or 4a (R = Me) is then 4a or 3t can be obtained selectively as the major product
formed by elimination of (ethylsulfanyl)iron dichloride by changing the reaction conditions.
FeCl3
EtS
EtS
R
O
O
N
H
O
enolization
– HCl
FeCl2
S
SEt
FeCl3
Et
EtS
SEt
1a
HN
HN
I
II
R
R
– EtSFeCl2
O
R
O
N
FeCl3
H
SEt
– EtSFeCl2
HN
NH
HN
III R = H; 4a R = Me
R
R
R
3a R = H
3t R = Me
Scheme 3 Proposed mechanism for the coupling reaction
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2012, 44, 3743–3756

3752
H. Yu et al.
PAPER
3,3-Di-1H-indol-3-yl-1-phenylprop-2-en-1-one (3f)
In summary, iron(III) chloride promoted desulfitative C–
C coupling of α-oxoketene dithioacetals with C2-unsub-
stituted or C2-substituted indoles permits the synthesis of
β,β-bisindolyl and β-indolyl α,β-unsaturated carbonyl
compounds selectively in good yields as a result of the ste-
ric effect imposed by the group at the C2 position of in-
doles. The procedure is characterized by simplicity, high
yields, and high selectivity.
Yellow solid; yield: 84.20 mg (93%); mp 236–238 °C.
1H NMR (600 MHz, DMSO-d6): δ = 11.67 (d, J = 1.74 Hz, 1 H,
NH), 11.39 (d, J = 1.74 Hz, 1 H, NH), 7.87 (d, J = 8.0 Hz, 2 H, ArH),
7.59 (d, J = 8.0 Hz, 1 H, ArH), 7.50–7.45 (m, 4 H, ArH and 2-H of
indolyl), 7.40 (t, 3 H, ArH), 7.23 (s, 1 H, HC=C), 7.19 (t, 1 H, ArH),
7.08–7.05 (m, 2 H, ArH), 7.02 (d, J = 7.9 Hz, 1 H, ArH), 6.83 (t, 1
H, ArH).
13C{1H} NMR (150 MHz, DMSO-d6): δ = 189.7, 144.5, 140.0,
137.3, 136.3, 131.4, 130.2, 129.0, 128.2 (2 C), 127.7 (2 C), 126.5,
125.7, 122.0, 121.2, 120.4, 120.2, 119.9, 119.2, 118.2, 116.0, 115.1,
112.4, 111.7.
All the reagents were purchased from commercial sources and used
as received unless otherwise indicated. The products were purified
by column chromatography on silica gel (300–400 mesh). All reac-
tions were monitored by TLC on polyester sheets precoated with
silica gel 60 (F254). 1H and 13C NMR spectra were recorded at r.t.
on a Bruker 600-MHz and 150-MHz spectrometers, respectively,
with Me4Si as the internal standard. All shifts are given in ppm.
Elemental analyses were performed with a Vario EL analyzer. All
melting points are uncorrected. Petroleum ether (PE) used was the
fraction boiling in the 60–90 °C range.
Calcd for C25H18N2O: C, 82.85; H, 5.01; N, 7.73. Found: C, 82.72;
H, 5.11; N, 7.80.
3,3-Bis(1-methyl-1H-indol-3-yl)-1-phenylprop-2-en-1-one (3g)
Yellow solid; yield: 94.62 mg (97%); mp 162–164 °C.
1H NMR(DMSO-d6, 600 MHz): δ = 7.83 (d, J = 7.3 Hz, 2 H, ArH),
7.65 (d, J = 7.8 Hz, 1 H, ArH), 7.54 (s, 2 H, 2-H of indolyl), 7.47 (d,
J = 8.0 Hz, 2 H, ArH), 7.43 (d, J = 8.0 Hz, 1 H, ArH), 7.39 (t, 2 H,
ArH), 7.27 (t, 1 H, ArH), 7.22 (s, 1 H, HC=C), 7.14–7.11 (m, 2 H,
ArH), 7.03 (d, J = 7.7 Hz, 1 H, ArH), 6.90 (t, 1 H, ArH), 3.81 (s, 3
H, NCH3), 3.79 (s, 3 H, NCH3).
13C{1H} NMR (150 MHz, DMSO-d6): δ = 190.0, 144.3, 140.5,
138.3, 137.3, 134.9, 133.6, 131.9, 128.7 (2 C), 128.1 (2 C), 127.4,
126.5, 122.7, 121.8, 121.2, 120.8, 120.6, 119.9, 117.7, 116.3, 114.6,
111.2, 110.4, 33.3, 33.1.
4,4-Di-1H-indol-3-ylbut-3-en-2-one (3a): Typical Procedure
FeCl3 (81.25 mg, 0.5 mmol) was added to a stirred soln of 1a (47.5
mg, 0.25 mmol) and indole 2a (58.5 mg, 0.5 mmol) in CH2Cl2 (2
mL). The tube was sealed and the mixture was heated at 80 °C for
2 h until 1a was completely consumed (TLC). H2O (20 mL) was
added and the mixture was extracted with CH2Cl2 (3 × 15 mL). The
organic phases were combined, dried (MgSO4), and concentrated
under reduced pressure. The residue was purified by flash column
chromatography [silica gel, PE–Et2O (2:1)] to give a yellow solid:
yield: 71.25 mg (95%).
Calcd for C27H22N2O: C, 83.05; H, 5.68; N, 7.17. Found: C, 82.94;
H, 5.59; N, 7.27.
1-(4-Bromophenyl)-3,3-di-1H-indol-3-ylprop-2-en-1-one (3j)
4,4-Bis(2-methyl-1H-indol-3-yl)but-3-en-2-one (3t); Typical
Procedure
Yellow solid; yield: 104.52 mg (95%); mp 203–205 °C.
1H NMR (600 MHz, DMSO-d6): δ = 11.69 (d, J = 1.74 Hz, 1 H,
NH), 11.41 (d, J = 1.74 Hz, 1 H, NH), 7.81 (d, J = 8.5 Hz, 2 H, ArH),
7.60 (d, J = 8.0 Hz, 1 H, ArH), 7.50–7.48 (m, 2 H, ArH and 2-H of
indolyl), 7.43 (d, J = 2.6 Hz, 1 H, 2-H of indolyl), 7.40–7.37 (m, 3
H, ArH), 7.18 (t, 1 H, ArH), 7.15 (s, 1 H, HC=C), 7.08–7.06 (m, 2
H, ArH), 7.01 (d, J = 8.0 Hz, 1 H, ArH), 6.87 (t, 1 H, Ar).
13C{1H} NMR (150 MHz, DMSO-d6): δ = 189.4, 145.6, 139.1,
137.9, 136.8, 136.5, 130.9, 130.1 (2 C), 129.7, 128.6 (2 C), 127.0,
126.2, 122.6, 121.7, 120.9, 120.6, 120.5, 119.7, 118.5, 116.2, 115.5,
112.9, 112.2.
FeCl3 (121.5 mg, 0.75 mmol) was added to a stirred soln of 1a (47.5
mg, 0.25 mmol) and indole 2f (98.25 mg, 0.75 mmol) in CH2Cl2 (2
mL). The tube was sealed and the mixture was heated at 80 °C for
12 h until 1a was completely consumed (TLC). H2O (20 mL) was
added and the mixture was extracted with CH2Cl2 (3 × 15 mL). The
organic phases were combined, dried (MgSO4), and concentrated
under reduced pressure. The residue was purified by flash column
chromatography [silica gel, PE–Et2O (2:1)] to give a yellow solid:
yield: 59.07 mg (72%); mp 207–209 °C.
1H NMR (600 MHz, DMSO-d6): δ = 11.35 (s, 1 H, NH), 11.33 (s, 1
H, NH), 7.33–7.29 (q, 2 H, ArH), 7.11 (d, J = 7.9 Hz, 1 H, ArH),
7.03–6.99 (q, 2 H, ArH), 6.89–6.87 (q, 2 H, ArH), 6.82 (t, 1 H,
ArH), 6.35 (s, 1 H, HC=C), 2.14 (s, 3 H, CH3), 2.02 (s, 3 H, CH3),
1.84 (s, 3 H, CH3).
13C{1H} NMR (150 MHz, DMSO-d6): δ = 198.5, 143.5, 137.8,
136.5, 135.9, 135.8, 128.5, 127.9, 126.0, 121.4, 121.3, 120.3, 119.9,
119.2, 118.8, 113.8, 112.8, 111.5, 111.4, 29.5, 13.2, 12.7.
Calcd for C25H17BrN2O: C, 68.04; H, 3.88; N, 6.35. Found: C,
68.17; H, 3.83; N, 6.25.
1-(4-Bromophenyl)-3,3-bis(1-methyl-1H-indol-3-yl)prop-2-en-
1-one (3k)
Yellow solid; yield: 110.00 mg (94%); mp 220–222 °C.
1H NMR (600 MHz, DMSO-d6): δ = 7.80 (dd, J = 8.5, 1.7 Hz, 2 H,
ArH), 7.66 (d, J = 8.0 Hz, 1 H, ArH), 7.56 (s, 1 H, 2-H of indolyl),
7.55 (d, J = 8.3 Hz, 1 H, ArH), 7.47 (s, 1 H, 2-H of indolyl), 7.43 (d,
J = 8.3 Hz, 1 H, ArH), 7.40 (dd, J = 8.5, 1.8 Hz, 2 H, ArH), 7.26 (t,
1 H, ArH), 7.15 (s, 1 H, HC=C), 7.13 (t, 2 H, ArH), 7.01 (d, J = 8.0
Hz, 1 H, ArH), 6.83 (t, 1 H, ArH), 3.81 (s, 3 H, NCH3), 3.79 (s, 3 H,
NCH3).
13C{1H} NMR (150 MHz, DMSO-d6): δ = 188.6, 144.5, 138.8,
137.9, 136.8, 136.0, 134.6, 133.4, 129.5 (2 C), 128.1 (2 C), 126.9,
126.0, 122.3, 121.4, 120.8, 120.2, 120.1, 119.6, 117.0, 115.5, 114.1,
110.7, 110.0, 32.8, 32.6.
Calcd for C22H20N2O: C, 80.46; H, 6.14; N, 8.53. Found: C, 80.32;
H, 6.25; N, 8.47.
(3E/Z)-4-(Ethylsulfanyl)-4-(1H-indol-3-yl)but-3-en-2-one (4c);
Typical Procedure
FeCl3 (40.63 mg, 0.25 mmol) was added to stirred soln of 1a (47.5
mg, 0.25 mmol) and indole 2f (32.75 mg, 0.25 mmol) in CH2Cl2 (2
mL). The tube was sealed and the mixture was heated at 80 °C for
7 h until 1a was completely consumed (TLC). H2O (20 mL) was
added and the mixture was extracted with CH2Cl2 (3 × 15 mL). The
organic phases were combined, dried (MgSO4), and concentrated
under reduced pressure. The residue was purified by flash column
chromatography [silica gel, PE–Et2O (3:1)] to give a yellow solid:
yield: 51.8 mg (80%).
Calcd for C27H21BrN2O: C, 69.09; H, 4.51; N, 5.97. Found: C,
69.25; H, 4.60; N, 5.88.
3,3-Bis(1-methyl-1H-indol-3-yl)-1-(2-thienyl)prop-2-en-1-one
(3l)
The spectra of the known compounds 3a–e,h,i,o,p,r,s, and 4j
agreed well with those reported in the literature.11
Yellow solid; yield: 91.10 mg (92%); mp 190–192 °C.
Synthesis 2012, 44, 3743–3756
© Georg Thieme Verlag Stuttgart · New York

PAPER
β,β-Bisindolyl and β-Indolyl α,β-Unsaturated Carbonyl Compounds
3753
1H NMR (600 MHz, DMSO-d6): δ = 7.89 (d, J = 3.2 Hz, 1 H, H of
thienyl), 7.86 (d, J = 4.9 Hz, 1 H, H of thienyl), 7.65 (d, J = 8.0 Hz,
1 H, ArH), 7.58 (s, 1 H, 2-H of indolyl), 7.56 (s, 1 H, 2-H of in-
dolyl), 7.55 (d, J = 7.3 Hz, 1 H, ArH), 7.50 (d, J = 8.2 Hz, 1 H, ArH),
7.29 (s, 1 H, HC=C), 7.27 (t, 1 H, ArH), 7.21 (t, 1 H, 4-H of thienyl),
7.18–7.14 (q, 2 H, ArH), 7.04 (d, J = 8.0 Hz, 1 H, ArH), 6.94 (t, 1
H, ArH), 3.87 (s, 3 H, NCH3), 3.82 (s, 3 H, NCH3).
13C{1H} NMR (150 MHz, DMSO-d6): δ = 181.1, 148.6, 144.7,
138.4, 137.3, 135.2, 134.0, 133.3, 130.9, 129.0, 127.6, 126.7, 122.8,
121.9, 121.4, 121.1, 120.7, 120.1, 118.0, 114.8, 114.4, 111.3, 110.6,
33.4, 33.3.
121.6, 121.0, 120.6, 120.5, 119.7, 119.2, 114.5, 113.7, 111.6, 111.1,
13.4, 13.2.
Calcd for C27H22N2O: C, 83.05; H, 5.68; N, 7.17. Found: C, 83.23;
H, 5.60; N, 7.23.
1-(4-Methoxyphenyl)-3,3-bis(2-methyl-1H-indol-3-yl)prop-2-
en-1-one (3v)
Yellow solid; yield: 92.44 mg (88%); mp 134–136 °C.
1H NMR (600 MHz, DMSO-d6): δ = 11.36 (s, 1 H, NH), 11.09 (s, 1
H, NH), 7.81 (d, J = 8.6 Hz, 2 H, ArH), 7.31 (d, J = 8.0 Hz, 1 H,
ArH), 7.21 (d, J = 8.0 Hz, 1 H, ArH), 7.15 (d, J = 7.4 Hz, 1 H, ArH),
7.02 (t, 1 H, ArH), 6.95 (s, 1 H, HC=C), 6.91 (t, 1 H, ArH), 6.87–
6.84 (m, 3 H, ArH), 6.79 (d, J = 7.9 Hz, 1 H, ArH), 6.73 (t, 1 H,
ArH), 3.75 (s, 3 H, OCH3), 2.09 (s, 3 H, CH3), 2.06 (s, 3 H, CH3).
Calcd for C25H20N2OS: C, 75.73; H, 5.08; N, 7.07. Found: C, 75.59;
H, 5.17; N, 7.00.
13C{1H} NMR (150 MHz, DMSO-d6): δ = 189.4, 162.3, 143.8,
137.4, 136.4, 135.7, 135.6, 132.8, 130.2 (2 C), 128.2, 127.9, 121.2,
120.6, 120.5, 120.0, 119.2, 118.9 (2 C), 114.4, 113.7 (2 C), 113.3,
111.3, 110.8, 55.7, 13.0, 12.9.
Diethyl (Di-1H-indol-3-ylmethylene)malonate (3m)
Yellow solid; yield: 82.44 mg (82%); mp 216–218 °C.
1H NMR (600 MHz, DMSO-d6): δ = 11.6 (s, 2 H, NH), 7.43 (d, J =
8.0 Hz, 2 H, ArH), 7.33 (d, J = 2.6 Hz, 2 H, 2-H of indolyl), 7.10 (t,
2 H, ArH), 7.04 (d, J = 8.0 Hz, 2 H, ArH), 6.93 (t, 2 H, ArH), 3.89
(q, 4 H, 2 × OCH2), 0.84 (t, 6 H, 2 × OCH2CH3).
13C{1H} NMR (150 MHz, DMSO-d6): δ = 167.6, 145.2, 137.0,
129.9, 127.0, 122.2, 120.2, 119.7, 117.8, 116.6, 112.5, 60.4, 14.0.
Calcd for C28H24N2O2: C, 79.98; H, 5.75; N, 6.66. Found: C, 80.11;
H, 5.63; N, 6.72.
1-(4-Bromophenyl)-3,3-bis(2-methyl-1H-indol-3-yl)prop-2-en-
1-one (3w)
Yellow solid; yield: 97.13 mg (83%); mp 200–202 °C.
Calcd for C24H22N2O4: C, 71.63; H, 5.51; N, 6.96. Found: C, 71.52;
H, 5.57; N, 7.07.
1H NMR (600 MHz, DMSO-d6): δ = 11.45 (s, 1 H, NH), 11.14 (s, 1
H, NH), 7.64 (d, J = 8.3 Hz, 2 H, ArH), 7.42 (d, J = 8.3 Hz, 2 H,
ArH), 7.33 (d, J = 8.0 Hz, 1 H, ArH), 7.19 (d, J = 8.0 Hz, 2 H, ArH),
7.04 (t, 1 H, ArH), 6.91 (t, 1 H, ArH), 6.89 (t, 1 H, ArH), 6.86 (s, 1
H, HC=C), 6.80 (d, J = 7.8 Hz, 1 H, ArH), 6.76 (t, 1 H, ArH), 2.10
(s, 3 H, CH3), 2.06 (s, 3 H, CH3).
13C{1H} NMR (150 MHz, DMSO-d6): δ = 190.5, 145.5, 139.2,
138.2, 136.9, 135.7, 135.6, 131.1(2 C), 129.8 (2 C), 128.1, 127.8,
125.2, 121.4, 120.9, 120.2, 120.0, 119.5, 119.0, 118.9, 114.0, 113.5,
111.3, 110.8, 13.1, 12.8.
Diethyl [Bis(1-methyl-1H-indol-3-yl)methylene]malonate (3n)
Yellow solid; yield: 90.34 mg (84%); mp 162–164 °C.
1H NMR (400 MHz, DMSO-d6): δ = 7.50 (d, J = 8.2 Hz, 2 H, ArH),
7.39 (s, 2 H, 2-H of indolyl), 7.20 (t, 2 H, ArH), 7.13 (d, J = 7.9 Hz,
2 H, ArH), 7.01 (t, 2 H, ArH), 3.90–3.80 (q, 4 H, 2 × OCH2), 3.81
(s, 6 H, 2 × NCH3), 0.84 (t, 6 H, 2 × NCH3).
13C{1H} NMR (100 MHz, DMSO-d6): δ = 167.7, 144.5, 137.6,
134.3, 127.4, 122.4, 120.6, 120.0, 116.0, 111.0, 60.5, 33.3, 14.0.
Calcd for C26H26N2O4: C, 72.54; H, 6.09; N, 6.51. Found: C, 72.44;
H, 6.12; N, 6.55.
Calcd for C27H21BrN2O: C, 69.09; H, 4.51; N, 5.97. Found: C,
68.93; H, 4.63; N, 6.06.
1,1,5-Tris(1-methyl-1H-indol-3-yl)-5-(4-tolyl)pent-1-en-3-one
(3q)
Yellow solid; yield: 82.79 mg (59%); mp 119–121 °C.
3,3-Bis(2-methyl-1H-indol-3-yl)-1-(2-thienyl)prop-2-en-1-one
(3x)
Yellow solid; yield: 89.13 mg (43%); mp 263–265 °C.
1H NMR (600 MHz, DMSO-d6): δ = 7.50 (d, J = 8.2 Hz, 2 H, ArH),
7.41 (d, J = 7.9 Hz, 1 H, ArH), 7.40 (s, 1 H, 2-H of indolyl), 7.35 (d,
J = 8.2 Hz, 1 H, ArH), 7.30 (s, 1 H, 2-H of indolyl), 7.27–7.23 (q, 2
H, ArH), 7.18 (t, 1 H, ArH), 7.10–7.06 (m, 4 H, ArH and 2-H of in-
dolyl), 7.03 (t, 3 H, ArH), 6.94 (d, J = 7.9 Hz, 1 H, ArH), 6.91–6.88
(q, 2 H, ArH), 6.56 (s, 1 H, HC=C), 4.60 (t, 1 H, CH), 3.82 (s, 3 H,
NCH3), 3.77 (s, 3 H, NCH3), 3.71 (s, 3 H, NCH3), 3.09–3.05 (m, 2
H, CH2), 2.23 (s, 3 H, CH3).
13C{1H} NMR (150 MHz, DMSO-d6) δ = 198.2, 142.6, 142.0,
138.3, 137.3 (2 C), 135.2, 134.7, 132.8, 129.2 (2 C), 128.0 (2 C),
127.7, 127.2, 126.8, 126.3, 122.7, 122.0, 121.6, 121.1, 120.8, 120.7
(2 C), 120.1, 119.5, 118.7, 118.0, 117.4, 114.4, 111.1, 110.6, 110.1,
49.4, 39.1, 33.3, 33.2, 33.0, 21.2.
1H NMR (600 MHz, DMSO-d6): δ = 11.45 (s, 1 H, NH), 11.28 (s, 1
H, NH), 7.85 (d, J = 3.5 Hz, 1 H, H of thienyl), 7.82 (d, J = 4.9 Hz,
1 H, H of thienyl), 7.33 (d, J = 8.0 Hz, 1 H, ArH), 7.29 (d, J = 8.0
Hz, 1 H, ArH), 7.16 (t, 2 H, ArH), 7.11 (s, 1 H, HC=C), 7.03 (t, 1
H, ArH), 6.96 (t, 1 H, ArH), 6.89 (t, 1 H, ArH), 6.79–6.75 (m, 2 H,
ArH and H of thienyl), 2.14 (s, 3 H, CH3), 2.12 (s, 3 H, CH3).
13C{1H} NMR (150 MHz, DMSO-d6): δ = 181.3, 148.6, 145.4,
138.4, 137.7, 135.9, 135.8, 133.3, 130.8, 128.9, 128.4, 128.1, 121.5,
120.9, 120.4, 119.6, 119.3, 119.1, 118.4, 114.8, 113.0, 111.5, 111.1,
13.3, 13.2.
Calcd for C25H20N2OS: C, 75.73; H, 5.08; N, 7.07. Found: C, 75.90;
H, 4.99; N, 7.14.
Calcd for C39H35N3O: C, 83.39; H, 6.28; N, 7.48. Found: C, 83.22;
H, 6.22; N, 7.35.
Ethyl 3,3-Bis(2-methyl-1H-indol-3-yl)acrylate (3y)
Yellow solid; yield: 38.50 mg (43%); mp 100–102 °C.
1H NMR (600 MHz, DMSO-d6): δ = 11.31 (s, 1 H, NH), 11.18 (s, 1
H, NH), 7.29–7.27 (m, 2 H, ArH), 7.09 (d, 1 H, J = 7.7 Hz, ArH),
7.00 (t, 1 H, ArH), 6.95 (t, 1 H, ArH), 6.87 (t, 1 H, ArH), 6.80–6.75
(m, 2 H, ArH), 6.05 (s, 1 H, HC=C), 3.99–3.96 (m, 2 H, OCH2CH3),
2.13 (s, 3 H, CH3), 2.03 (s, 3 H, CH3), 1.07 (t, 3 H, OCH2CH3).
13C{1H} NMR (150 MHz, DMSO-d6): δ = 166.4, 145.6, 137.2,
136.0, 135.7, 135.6, 128.4, 127.8, 121.3, 120.7, 120.1, 119.3, 118.9,
118.8, 114.0, 113.9, 112.1, 111.4, 111.0, 59.2, 14.8, 13.0, 12.9.
3,3-Bis(2-methyl-1H-indol-3-yl)-1-phenylprop-2-en-1-one (3u)
Yellow solid; yield: 78.03 mg (80%); mp 139–141 °C.
1H NMR (600 MHz, DMSO-d6): δ = 11.41 (s, 1 H, NH), 11.10 (s, 1
H, NH), 7.78 (d, J = 7.4 Hz, 2 H, ArH), 7.40 (t, 1 H, ArH), 7.33–
7.28 (m, 3 H, ArH), 7.19 (t, 2 H, ArH), 7.03 (t, 1 H, ArH), 6.94 (s,
1 H, HC=C), 6.92 (t, 1 H, ArH), 6.88 (t, 1 H, ArH), 6.80 (d, J = 7.7
Hz, 1 H, ArH), 6.74 (t, 1 H, ArH), 2.10 (s, 3 H, CH3), 2.07 (s, 3 H,
CH3).
13C{1H} NMR (150 MHz, DMSO-d6): δ = 191.3, 145.2, 140.5,
138.2, 137.0, 136.0, 135.9, 131.9, 128.6 (2 C), 128.5, 128.2 (2 C),
Calcd for C23H22N2O2: C, 77.07; H, 6.19; N, 7.82. Found: C, 77.24;
H, 6.09; N, 7.73.
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2012, 44, 3743–3756

3754
H. Yu et al.
PAPER
(3Z/E)-4-(Ethylsulfanyl)-4-(2-methyl-1H-indol-3-yl)but-3-en-2-
one (4c)
(d, J = 7.7 Hz, 1 H, ArH), 7.37 (d, J = 7.9 Hz, 1 H, ArH), 7.14 (s, 1
H, HC=C), 7.11 (t, 1 H, ArH), 7.08 (t, 1 H, ArH), 2.51 (s, 3 H, CH3),
2.44–2.40 (q, 2 H, SCH2), 0.94 (t, 3 H, SCH2CH3); δ [(E)-4f] =
11.26 (s, 1 H, NH), 7.64 (d, J = 7.7 Hz, 2 H, ArH), 7.48 (d, J = 7.8
Hz, 2 H, ArH), 7.45 (d, J = 7.9 Hz, 1 H, ArH), 7.22 (d, J = 7.9 Hz,
1 H, ArH), 7.02 (t, 1 H, ArH), 6.97 (t, 1 H, ArH), 6.83 (s, 1 H,
HC=C), 2.98–2.96 (q, 2 H, SCH2), 2.25 (s, 3 H, CH3), 1.31 (t, 3 H,
SCH2CH3).
13C{1H} NMR (150 MHz, DMSO-d6): δ [(Z)-4f] = 186.6, 159.0,
138.1, 135.6, 135.1, 132.3 (2 C), 130.3 (2 C), 127.4, 126.7, 121.8,
120.6, 119.5, 118.4, 111.7, 111.2, 26.7, 15.0, 12.6; δ [(E)-4f] =
186.6, 159.0, 136.7, 135.6, 135.1, 131.5 (2 C), 130.2 (2 C), 127.4,
126.0, 121.4, 120.0, 119.1, 117.6, 111.7, 111.2, 26.7, 14.0, 13.0.
Yellow solid; yield: 51.82 mg (80%); mp 123–125 °C; Z/E = 5:2.
1H NMR (600 MHz, DMSO-d6): δ [(Z)-4c] = 11.37 (s, 1 H, NH),
7.45 (d, J = 7.8 Hz, 1 H, ArH), 7.33 (d, J = 7.6 Hz, 1 H, ArH), 7.09
(t, 1 H, ArH), 7.03 (t, 1 H, ArH), 6.36 (s, 1 H, HC=C), 2.43 (s, 3 H,
CH3), 2.34–2.20 (m, 2 H, SCH2), 2.19 (s, 3 H, COCH3), 0.88 (t, 3
H, SCH2CH3); δ [(E)-4c] = 11.43 (s, 1 H, NH), 7.42 (d, J = 7.9 Hz,
1 H, ArH), 7.33 (d, J = 7.6 Hz, 1 H, ArH), 7.09 (t, 1 H, ArH), 7.04
(t, 1 H, ArH), 6.26 (s, 1 H, HC=C), 2.82–2.78 (m, 2 H, SCH2), 2.32
(s, 3 H, CH3), 1.71 (s, 3 H, COCH3), 1.24 (t, 3 H, SCH2CH3).
13C{1H} NMR (150 MHz, DMSO-d6): δ [(Z)-4c] = 195.7, 153.9,
135.5, 134.6, 127.5, 123.9, 121.7, 120.4, 118.4, 111.6, 110.5, 31.0,
26.3, 15.2, 12.4; δ [(E)-4c] = 195.4, 151.9, 136.1, 135.8, 127.5,
123.5, 121.7, 120.2, 118.7, 111.5, 108.8, 29.4, 26.5, 14.0, 12.6.
Calcd for C20H18BrNOS: C, 60.00; H, 4.53; N, 3.50. Found: C,
59.85; H, 4.42; N, 3.60.
Calcd for C15H17NOS: C, 69.46; H, 6.61; N, 5.40. Found: C, 69.30;
H, 6.54; N, 5.49.
(2Z/E)-3-(Ethylsulfanyl)-3-(2-methyl-1H-indol-3-yl)-1-(2-thie-
nyl)prop-2-en-1-one (4g)
Yellow solid; yield: 67.87 mg (83%); mp 139–141 °C; Z/E = 5:1.
(2Z/E)-3-(Ethylsulfanyl)-3-(2-methyl-1H-indol-3-yl)-1-phenyl-
prop-2-en-1-one (4d)
Yellow solid; yield: 65.83 mg (82%); mp 134–136 °C; Z/E = 4:1.
1H NMR (600 MHz, CDCl3): δ [(Z)-4g] = 8.51 (s, 1 H, NH), 7.66–
7.63 (m, 2 H, ArH and H of thienyl), 7.56 (d, J = 4.8 Hz, 1 H, H of
thienyl), 7.36 (d, J = 7.9 Hz, 1 H, ArH), 7.20–7.14 (m, 2 H, ArH),
7.09 (t, 1 H, H of thienyl), 6.96 (s, 1 H, HC=C), 2.52 (s, 3 H, CH3),
2.49–2.45 (q, 2 H, SCH2), 1.03 (t, 3 H, SCH2CH3); δ [(E)-4g] = 8.39
(s, 1 H, NH), 7.68 (d, J = 3.4 Hz, 1 H, H of thienyl), 7.66–7.64 (m,
1 H, ArH) 7.50 (d, J = 5.0 Hz, 1 H, H of thienyl), 7.20–7.14 (m, 1
H, ArH), 7.07 (t, 2 H, ArH), 7.05 (t, 1 H, H of thienyl), 7.01 (s, 1 H,
HC=C), 2.82–2.79 (q, 2 H, SCH2), 2.33 (s, 3 H, CH3), 1.31 (t, 3 H,
SCH2CH3).
13C{1H} NMR (150 MHz, CDCl3): δ [(Z)-4g] = 181.3, 158.3, 146.7,
135.1, 133.1, 132.5, 130.2, 128.1, 127.6, 122.1, 120.8, 119.6, 118.9,
112.3, 110.8, 26.9, 14.4, 12.3; δ [(E)-4g] = 181.3, 158.3, 147.1,
135.1, 133.1, 132.4, 130.5, 127.9, 121.6, 120.3, 120.0, 119.5, 116.6,
112.3, 110.7, 26.9, 13.9, 13.0.
1H NMR (600 MHz, DMSO-d6): δ [(Z)-4d] = 11.5 (s, 1 H, NH),
7.98 (d, J = 7.4 Hz, 2 H, ArH), 7.60 (t, 1 H, ArH), 7.54–7.52 (m, 3
H, Ar H), 7.35 (d, J = 7.9 Hz, 1 H, ArH), 7.16 (s, 1 H, HC=C), 7.11
(t, 1 H, ArH), 7.07 (t, 1 H, ArH), 2.52 (s, 3 H, CH3), 2.41 (q, 2 H,
SCH2), 0.94 (t, 3 H, SCH2CH3); δ [(E)-4d] = 11.23 (s, 1 H, NH),
7.76 (d, J = 7.3 Hz, 2 H, ArH), 7.48–7.44 (m, 2 H, ArH), 7.31 (t, 2
H, ArH), 7.20 (d, J = 7.9 Hz, 1 H, ArH), 7.02 (t, 1 H, ArH), 6.97 (d,
J = 7.5 Hz, 1 H, ArH), 6.90 (s, 1 H, HC=C), 2.97–2.96 (m, 2 H,
SCH2), 2.26 (s, 3 H, CH3), 1.31 (t, 3 H, SCH2CH3).
13C{1H} NMR (DMSO-d6, 150 MHz, DMSO-d6): δ [(Z)-4d] =
187.8, 157.9, 139.2, 135.6, 135.0, 132.7, 129.3 (2 C), 128.3 (2 C),
127.5, 121.8, 120.5, 120.0, 118.4, 111.7, 111.2, 26.6, 15.1, 12.6; δ
[(E)-4d] = 187.8, 157.9, 139.1, 135.6, 135.0, 132.7, 128.7 (2 C),
128.2 (2 C), 127.5, 121.3, 119.9, 119.2, 117.8, 111.7, 111.2, 26.7,
14.0, 13.0.
Calcd for C18H17NOS2: C, 66.02; H, 5.23; N, 4.28. Found: C, 66.14;
H, 5.12; N, 4.35.
Calcd for C20H19NOS: C, 74.73; H, 5.96; N, 4.36. Found: C, 74.86;
H, 5.88; N, 4.41.
Diethyl [(Ethylsulfanyl)(2-methyl-1H-indol-3-yl)methyl-
ene]malonate (4h)
White solid; yield: 60.49 mg (67%); mp 89–91 °C.
(2Z/E)-3-(Ethylsulfanyl)-1-(4-methoxyphenyl)-3-(2-methyl-1H-
indol-3-yl)prop-2-en-1-one (4e)
Yellow solid; yield: 71.98 mg (82%); mp 136–138 °C; Z/E = 3:1.
1H NMR (600 MHz, DMSO-d6): δ = 11.4 (s, 1 H, NH), 7.34 (d, J =
7.8 Hz, 1 H, ArH), 7.29 (d, J = 8.0 Hz, 1 H, ArH), 7.07 (d, J = 7.8
Hz, 1 H, ArH), 7.06–6.99 (q, 1 H, ArH), 4.22–4.18 (q, 2 H, OCH2),
3.74–3.68 (m, 2 H, OCH2), 2.27 (s, 3 H, CH3), 2.22–2.20 (q, 2 H,
SCH2), 1.23 (t, 3 H, OCH2CH3), 0.90 (t, 3 H, OCH2CH3), 0.60 (t, 3
H, SCH2CH3).
13C{1H} NMR (150 MHz, DMSO-d6): δ = 164.9, 164.4, 156.3,
135.7, 135.2, 127.5, 122.6, 121.7, 120.3, 118.3, 111.5, 107.3, 61.0,
60.6, 26.4, 14.9, 14.6, 13.7, 12.5.
1H NMR (600 MHz, DMSO-d6): δ [(Z)-4e] = 11.41 (s, 1 H, NH),
7.95 (d, J = 8.0 Hz, 2 H, ArH), 7.49 (d, J = 7.7 Hz, 1 H, ArH), 7.34
(d, J = 7.9 Hz, 1 H, ArH), 7.11 (s, 1 H, HC=C), 7.08 (t, 1 H, ArH),
7.05–7.01 (m, 2 H, ArH), 6.87 (t, 1 H, ArH), 3.82 (s, 3 H, OCH3),
2.45 (s, 3 H, CH3), 2.37–2.34 (q, 2 H, SCH2), 0.90 (t, 3 H,
SCH2CH3); δ [(E)-4e] = 11.19 (s, 1 H, NH), 7.77 (d, J = 8.0 Hz, 2
H, ArH), 7.44 (d, J = 7.8 Hz, 1 H, ArH), 7.21 (d, J = 7.9 Hz, 1 H,
ArH), 7.05–7.01 (m, 3 H, ArH and HC=C), 7.01 (t, 1 H, ArH), 6.94
(t, 1 H, ArH), 3.75 (s, 3 H, OCH3), 2.90 (q, 2 H, SCH2), 2.22 (s, 3
H, CH3), 1.27 (t, 3 H, SCH2CH3).
Calcd for C19H23NO4S: C, 63.13; H, 6.41; N, 3.88. Found: C, 62.98;
H, 6.52; N, 3.94.
13C{1H} NMR (150 MHz, DMSO-d6): δ [(Z)-4e] = 198.6, 163.0,
156.4, 135.6, 134.8, 132.0, 130.5 (2 C), 127.6, 121.7, 120.5, 120.2,
118.4, 114.5(2 C), 111.7, 111.3, 56.0, 26.5, 15.1, 12.6; δ [(E)-4e] =
186.6, 163.0, 156.4, 135.6, 134.8, 132.1, 130.6 (2 C), 127.6, 121.7,
120.5, 120.2, 118.4, 114.0 (2 C), 111.7, 111.3, 56.0, 26.5, 14.1,
13.0.
(3Z/E)-4-(ethylsulfanyl)-4-(2-phenyl-1H-indol-3-yl)but-3-en-2-
one (4i)
Yellow solid; yield: 58.60 mg (73%); mp 162–164 °C; Z/E = 6:1.
1H NMR (600 MHz, DMSO-d6): δ [(Z)-4i] = 11.81 (s, 1 H, NH),
7.76 (d, J = 7.4 Hz, 2 H, ArH), 7.51 (t, 2 H, ArH), 7.47 (d, J = 8.0
Hz, 2 H, ArH), 7.39 (t, 1 H, ArH), 7.21 (t, 1 H, ArH), 7.11 (m, 1 H,
ArH), 6.43 (s, 1 H, HC=C), 2.22–2.19 (q, 2 H, SCH2), 2.13 (s, 3 H,
COCH3), 0.84 (t, 3 H, SCH2CH3); δ [(E)-4i] = 11.84 (s, 1 H, NH),
7.76 (d, J = 7.4 Hz, 2 H, ArH), 7.51 (t, 2 H, ArH), 7.47 (d, J = 8.0
Hz, 2 H, ArH), 7.39 (t, 1 H, ArH), 7.21 (t, 1 H, ArH), 7.11 (m, 1 H,
ArH), 6.30 (s, 1 H, HC=C), 2.88–2.85 (m, 2 H, SCH2), 1.64 (s, 3 H,
COCH3), 1.24 (t, 3 H, SCH2CH3).
Calcd for C21H21NO2S: C, 71.76; H, 6.02; N, 3.99. Found: C, 71.89;
H, 5.95; N, 4.08.
(2Z/E)-1-(4-Bromophenyl)-3-(ethylsulfanyl)-3-(2-methyl-1H-
indol-3-yl)prop-2-en-1-one (4f)
Yellow solid; yield: 84.79 mg (85%); mp 174–176 °C; Z/E = 3:1.
1H NMR (600 MHz, DMSO-d6): δ [(Z)-4f] = 11.49 (s, 1 H, NH),
7.92 (d, J = 7.8 Hz, 2 H, ArH), 7.72 (d, J = 7.8 Hz, 2 H, ArH), 7.50
13C{1H} NMR (150 MHz, DMSO-d6): δ [(Z)-4i] = 195.9, 155.5,
136.3, 134.8, 131.9, 129.4 (2 C), 128.6, 128.4, 127.7 (2 C), 123.6,
Synthesis 2012, 44, 3743–3756
© Georg Thieme Verlag Stuttgart · New York

PAPER
β,β-Bisindolyl and β-Indolyl α,β-Unsaturated Carbonyl Compounds
3755
123.1, 120.9, 118.9, 112.2, 110.4, 30.9, 26.0, 14.5; δ [(E)-4i] =
195.9, 155.5, 136.3, 134.8, 131.9, 129.4 (2 C), 128.6, 128.4, 127.7(2
C), 123.6, 123.1, 120.9, 118.9, 112.2, 110.4, 30.9, 26.0, 13.4.
Z. J. Chem. Rev. 2011, 111, 1293. (c) Bolm, C.; Legros, J.;
Le Paih, J.; Zani, L. Chem. Rev. 2004, 104, 6217.
(13) Hashiguchi, M.; Obata, N.; Maruyama, M.; Yeo, K. S.;
Ueno, T. K.; Ikebe, T.; Takahashi, I.; Matsuo, Y. Org. Lett.
2012, 14, 3276.
(14) (a) Wang, Y. M.; Bi, X. H.; Li, D. H.; Liao, P. Q.; Wang, Y.
D.; Yang, J.; Zhang, Q.; Liu, Q. Chem. Commun.
Calcd for C20H19NOS: C, 74.73; H, 5.96; N, 4.36. Found: C, 74.63;
H, 6.01; N, 4.42.
(Cambridge) 2011, 47, 809. (b) Wang, Y. M.; Bi, X. H.; Li,
W. Q.; Li, D. H.; Zhang, Q.; Liu, Q.; Ondon, B. S. Org. Lett.
2011, 13, 1722. (c) Huang, D. S.; Wang, H. N.; Xue, F. Z.;
Shi, Y. A. J. Org. Chem. 2011, 76, 7269. (d) Fu, W. J.;
Kiggans, J.; Overbury, S. H.; Schwartz, V.; Liang, C. D.
Chem. Commun. (Cambridge) 2011, 47, 5265. (e) Tang, L.
N.; Pang, Y. L.; Yan, Q.; Shi, L. Q.; Huang, J. H.; Du, Y. F.;
Zhao, K. J. Org. Chem. 2011, 76, 2744.
Acknowledgment
We are grateful to the National Nature Science Foundation of China
(20902010) and the Science Foundation of Anshan City
(2011MS44) for support of this research. Many thanks are due to
Professor Xihe Bi for his critical reading of the manuscript.
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synthesis.SnuIomprifgtooatrinSugpIoi
(15) (a) Xu, T. Y.; Yang, Q.; Li, D. P.; Dong, J. H.; Yu, Z. K.; Li,
Y. X. Chem.–Eur. J. 2010, 16, 9264. (b) Guérinot, A.; Serra-
Muns, A.; Gnamm, C.; Bensoussan, C.; Reymond, S.;
Cossy, J. Org. Lett. 2010, 12, 1808. (c) Van Humbeck, J. F.;
Simonovich, S. P.; Knowles, R. R.; MacMillan, D. W. C.
J. Am. Chem. Soc. 2010, 132, 10012. (d) Yang, L.; Lei, C.-
H.; Wang, D. X.; Huang, Z. T.; Wang, M. X. Org. Lett. 2010,
12, 3918. (e) Gay, R. M.; Manarin, F.; Schneider, C. C.;
Barancelli, D. A.; Costa, M. D.; Zeni, G. J. Org. Chem.
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nnfomartit
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Synthesis 2012, 44, 3743–3756
© Georg Thieme Verlag Stuttgart · New York