Indirect regioselective heteroarylation of indoles through a Friedel-Crafts reaction with (E)-1,4-diaryl-2-buten-1,4-diones

Article abstract of DOI:10.1016/j.tet.2009.09.011

A two-step synthesis of 3-heteroaryl indoles has been developed. The first step of the sequence involves a Friedel-Crafts alkylation of indoles with 1,4-diaryl-2-buten-1,4-diones to give the corresponding indoles bearing a 1,4-dicarbonyl moiety. The reaction is catalyzed by InCl₃ and takes place with good yields. Cyclization of the diones under different Paal-Knorr conditions allows to prepare indoles substituted at the C3 position with 3-furanyl, 3-pyrrolyl- and 3-thienyl moieties.

Full text of DOI:10.1016/j.tet.2009.09.011

Tetrahedron 65 (2009) 9264–9270
Contents lists available at ScienceDirect
Tetrahedron
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Indirect regioselective heteroarylation of indoles through a Friedel–Crafts
reaction with (E)-1,4-diaryl-2-buten-1,4-diones
*
´
´
´
Gonzalo Blay, Isabel Fernandez, Alicia Monleon, Jose R. Pedro , Carlos Vila
`
´
`
Departament de Qu´ımica Organica, Facultat de Quımica, Universitat de Valencia, Dr. Moliner 50, E-46100 Burjassot, Spain
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 1 July 2009
Received in revised form 3 September 2009
Accepted 3 September 2009
Available online 9 September 2009
A two-step synthesis of 3-heteroaryl indoles has been developed. The first step of the sequence involves
a Friedel–Crafts alkylation of indoles with 1,4-diaryl-2-buten-1,4-diones to give the corresponding in-
doles bearing a 1,4-dicarbonyl moiety. The reaction is catalyzed by InCl3 and takes place with good yields.
Cyclization of the diones under different Paal–Knorr conditions allows to prepare indoles substituted at
the C3 position with 3-furanyl, 3-pyrrolyl- and 3-thienyl moieties.
Ó 2009 Elsevier Ltd. All rights reserved.
Keywords:
Biaryls
Indoles
Furans
Pyrroles
Thiophenes
Friedel–Crafts alkylation
Cross-coupling
1. Introduction
coupling partners, reactions involving their heteroaryl analogues are
less straightforward,11 especially when both partners are heterocy-
Biaryls are common moieties present in high value molecules
such as organic dyes, conducting polymers, asymmetric ligands or
pharmaceuticals.1 Therefore, the development of efficient methods
to connect two arene nuclei has been a topic of great relevance in
organic synthesis.2 Three general procedures have been used to carry
out the formation of these carbon–carbon biaryl linkage.3 The most
widely known and used procedure is the cross-coupling reaction of
a nucleophilic unit Ar–Y (Y¼BR2, SnR3, MgX, ZnX corresponding to
the Suzuki–Miyaura,4 Stille,5 Kumada6 and Negishi7 reactions, re-
spectively) with an electrophilic aryl reagent Ar–X (X¼halogen or
sulfonate). In fact, an impressive progress in the development of
efficient catalytic systems to achieve this kind of reactions has been
made in the last years. Besides the already classical procedures
mentioned above, recent advances include the use of aryl carbinols
and nitriles,8 carboxylic acids (or their salts)9 and silanolates10 as
valid replacements for aryl boronic acids and organometallic com-
pounds as nucleophilic components of the cross-coupling reaction.
Despite the success of these reactions, some drawbacks still remain.
For instance, the overall process includes the prefunctionalization of
the substrates as nucleophilic and electrophilic reagents; besides,
although simple aryl halides and aryl boronic acids are successful
cles.12 Thus, although the preparation of indolyl boronic acids and
boronate esters has been carried out by several groups,13 only few
efficient procedures for the Suzuki–Miyaura cross-coupling in-
volving the indole nucleus have been reported.13h,i,14
A second general method involves a direct arylation reaction in
which an aryl boronic acid is replaced by a simple unfunctionalized
arene. Although a variety of electron-rich heterocycles have been
arylated using this methodology,15 the reaction with indoles is
limited to the use of homoaryl halides as electrophilic component;
furthermore the regioselectivity of the arylation depends on the
protecting group of the indole nitrogen atom.
The third general method is the cross-coupling reaction of two
simple unactivated arenes. Fagnou and co-workers3 have recently
discovered the arylation of indoles with excess arenes under Pd(II)
catalysis, and DeBoef and co-workers16 have also described the
arylation of indoles and benzofuranes. However, in both cases the
reaction is limited to coupling with homoarenes and, besides,
the arylation of unprotected (N–H) indoles has not been resolved.
The best results were obtained with N-acetylindoles although the
yields and regioselectivities were moderate.
According to these antecedents and despite the recent advances,
the access to biheteroaryl compounds, especially those bearing two
linked electron-rich heterocycles; i.e., a five-membered heterocycle
linked to the heterocyclic ring of indole, remains very limited.
Therefore the development of synthetic procedures addressed to
* Corresponding author. Tel.: þ34 963544329; fax: þ34 963544328.
E-mail address: jose.r.pedro@uv.es (J.R. Pedro).
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.09.011

G. Blay et al. / Tetrahedron 65 (2009) 9264–9270
9265
this kind of compounds constitutes an interesting challenge to or-
ganic chemists. In this paper we present a novel two-step synthesis
of 3-heteroaryl indoles.
O
O
Ar
R
R
O
InCl3
Ar
Ar
+
Ar
N
H
CH2Cl2
O
N
2. Results and discussion
1
2
H
3
Taking into consideration that 1,4-dicarbonyl compounds are
the most important starting materials for the preparation of furans,
pyrroles and thiophenes (Paal–Knorr synthesis) we envisioned the
procedure for the synthesis of 3-heteroaryl substituted indoles
outlined in Scheme 1. The procedure involves the introduction in
a first step of a 1,4-dicarbonyl moiety on the indole framework via
a Friedel–Crafts alkylation with (E)-1,4-diaryl-2-buten-1,4-diones.
In a second step the 1,4-dicarbonyl moiety would be transformed
into furan, pyrrole or thiophene rings via a Paal–Knorr cyclization
under different conditions.
O
O
O
O
Ar
Ph
R
Ar
Ph
N
H
N
H
3aa (Ar = Ph), 90%
3ba (R = Me), 95%
3ca (R = OMe), 89%
3da (R = Br), 92%
3ab (Ar = p-MeC6H4), 87%
3ac (Ar = 3,4-Me2C6H3), 75%
3ad (Ar = p-FC6H4), 90%
O
O
R
O
O
O
R
O
O
Ph
R
Ph
+
R
N
H
Ph
Ph
O
N
H
1
2
3
Me
N
N
H
Me
H
X
R
R
3ea, 97%
3fa, 96%
4, X = O
5, X = NH,
6, X = N-allyl
7, X = S
O
O
O
Ph
O
Ph
N
H
Ph
Ph
Scheme 1. Two-step synthetic sequence to 3-heteroaryl indoles.
NH
N
Me
8, 74%
The introduction of functionalized alkyl groups at the 3-position
of indole by means of a Friedel–Crafts reaction using various elec-
trophilic reagents constitutes a well established synthetic strategy.17
However, there are no literature precedents on the Friedel–Crafts
reaction of indoles 1 with (E)-1,4-diaryl-2-buten-1,4-diones 2 as
electrophilic partners. Recently, indium trichloride has emerged
as a mild, air stable and water tolerant Lewis acid in various organic
transformations.18 In particular it has been used to activate but-2-
ene-1,4-diones as Michael acceptors against acetoacetates as
nucleophiles.19 Also, the tolerance of the indole framework to in-
dium trichloride has been demonstrated in several catalytic re-
actions.20 Accordingly, we anticipated that indium trichloride could
be a suitable catalyst for the Friedel–Crafts alkylation of indoles.
Thus, after some experimentation, we found that the reaction be-
tween indole (1a) and (E)-1,4-diphenyl-2-buten-1,4-dione (2a)
proceeded smoothly in dichloromethane at room temperature in the
presence of 10 mol % InCl3 with complete substrate conversion after
3 h, providing the expected product 3aa in 90% isolated yield. Under
these conditions, several (E)-1,4-diaryl-2-buten-1,4-diones 2 con-
taining either electron-donating (2b–c) or electron-withdrawing
(2d) substituents on the phenyl ring reacted with indole (1a). In all
cases the corresponding alkylated products 3aa–ad were obtained in
good yields (75–90%). The scope of the reaction with respect to the
indole substrate was also explored. A number of C5, C7, C2 and
N1-substituted indoles 2b–f were reacted with (E)-1,4-diphenyl-2-
buten-1,4-dione (2a). In general, the reaction time (3–4 h) and yield
of products 3ba–fa did not show a significant dependence with the
electronic features of the substituent on the indole substrate. We
also tested the reaction of pyrrole with compound 2a. In this case
10 equiv of pyrrole was used to avoid double alkylation at the 2- and
5-positions of pyrrole. In this way the product of monoalkylation at
the 2-position of pyrrole 8 was obtained in 74% yield after 0.5 h. The
result of the InCl3-catalyzed Friedel–Crafts alkylation is shown in
Scheme 2.
3ga, 85%
(from pyrrole)
Scheme 2. InCl3-catalyzed Friedel–Crafts alkylation of indoles 1 and pyrrole with
(E)-1,4-diaryl-2-buten-1,4-diones 2.
With the 1,4-dicarbonyl-functionalized indoles in our hands we
proceeded tothe construction of thefive-membered heterocyclic ring
via a Paal–Knorr strategy. First we studied the synthesis of furanyl
indoles. Various dicarbonyl compounds 3 were subjected to de-
O
O
O
Ar
Ar
Ar
Ar
TsOH
toluene, 80 o
C
N
H
N
H
3
4
O
O
Ar
Ar
Ph
Ph
Me
N
N
H
H
4aa (Ar = Ph), 82%
4ab (Ar = p-MeC6H4), 92
4ba (R = Me), 92%
%
O
Ph
Ph
N
Me
H
4ea (R = Me), 93%
Scheme 3. Cyclization of dicarbonyl indoles 3 to furanyl indoles 4.

9266
G. Blay et al. / Tetrahedron 65 (2009) 9264–9270
hydration upon treatment with 10 mol % p-toluenesulfonic acid in
toluene at 80 ꢀC.21 Cyclization of the 1,4-diketone moiety provided
the corresponding furan derivatives 4 in good yields, from 82 to 93%
(Scheme 3).
The synthesis of indoles substituted with a pyrrole ring was
examined next. Reaction of compounds 3 with excess of ammo-
nium acetate in a mixture of EtOH–CHCl3 (2:3) as the solvent at
50 ꢀC afforded the trisubstituted pyrroles 5, having an unsub-
stituted nitrogen atom in the pyrrole ring in good yields (67–90%).
Compound 6aa, bearing an N-allyl pyrrole ring, could also be
obtained in 68% yield by using allylamine instead of ammonium
acetate (Scheme 4).
Finally, we achieved the synthesis of indoles bearing a thio-
phene ring 7.22 The 1,4-diketones 3 were reacted with Lawesson’s
reagent in order to obtain the corresponding thiophenes 7. Cycli-
zation to furan took place in some extent as a side reaction. Dif-
ferent solvents and temperatures were studied in order to
minimize the formation of the furan ring. The best results with
compound 3aa were obtained by heating at 90 ꢀC in toluene as
solvent during 30 min, in this way thiophene 7aa was obtained in
79% yield together with furan 4aa (20%). The results for the for-
mation of several thiophenes are shown in Scheme 5.
We also have examined the application of this methodology to
the synthesis of 2-heteroaryl pyrroles. Thus, compound 8 was
transformed into furyl pyrrole 9 (54% yield) and bipyrrole 10 (52%
yield) under the conditions developed for the synthesis of indole
derivatives (Scheme 6).
H
N
O
O
Ar
Ar
Ar
NH4OAc or
AllylNH2
Ar
O
O
O
Ph
Ph
Ph
EtOH-CHCl3
N
N
TsOH
50 o
C
H
Ph
H
3
toluene, 80 o
54%
C
5 or 6
NH
NH
H
H
N
N
Ar
Ar
8
Ph
Ph
9
NH4OAc
MeO
H
N
Ph
Ph
EtOH-CHCl3,
50 o
52%
C
N
N
H
H
NH
10
5aa (Ar = Ph), 78%
5ca, 90%
5ac (Ar = 3,4-Me2C6H3), 67%
Scheme 6. Cyclization of dicarbonyl pyrrole 8 to furyl pyrrole 9 and bipyrrole 10.
H
N
N
Ph
Ph
Ph
Ph
3. Conclusion
In summary, we have developed a new strategy for the synthesis
of biheteroaryl compounds that involves a Friedel–Crafts alkylation
reaction of indoles (or pyrrole) with 2-buten-1,4-diones followed
by a Paal–Knorr reaction of the 1,4-dicarbonyl moiety introduced in
the first reaction. The overall sequence is an alternative to the cross-
coupling between two electron-rich heterocycles, which is limited
and troublesome. This strategy appears as a convenient method for
the synthesis of highly substituted biheteroaryl compounds.
Me
71%
N
N
H
H
5fa
,
6aa, 68%
Scheme 4. Cyclization of dicarbonyl indoles 3 to pyrrolyl indoles 5 and 6.
O
4. Experimental section
4.1. General
O
S
Ar
Ar
Ar
Lawesson
reagent
Ar
toluene, 90 oC
N
N
Commercial reagents were used as purchased. Dichloromethane
and toluene were distilled from CaH2 and stored over 4 Å molecular
sieves. Reactions were monitored by TLC analysis using Merck Silica
Gel 60 F-254 thin layer plates. Flash column chromatography was
performed on Merck silica gel 60, 0.040–0.063 mm. 1H NMR were
run at 300 MHz for 1H and at 75 MHz for 13C NMR, and referenced
to the solvent as internal standard. MS(EI) were run at 70 eV. The
starting 1,4-diketones were prepared by Friedel–Crafts acylation of
aromatic compounds with fumaroyl chloride according to pro-
cedures reported in the literature.23
H
H
3
7
S
S
Ar
Ar
Ph
Ph
Br
N
N
H
H
7aa (Ar = Ph), 79%
7da, 78%
7ad (Ar = p-FC6H4), 80%
4.2. Experimental procedure for the Friedel–Crafts reaction
S
Ph
Ph
Endione 2a (R¼Ph, 118.0 mg, 0.5 mmol) was added to a solution
of InCl3 (11.1 mg, 0.05 mmol) in CH2Cl2 (2 mL) under nitrogen. After
stirring for 10 min, a solution of indole (1a, 42.2 mg, 0.6 mmol) in
CH2Cl2 (2 mL) was added and the mixture was stirred at room
temperature until completion (TLC). Water (5 mL) was then added
and the mixture was extracted with diethyl ether (3ꢁ15 mL). The
organic layer was washed with brine (15 mL) and dried over MgSO4.
Me
N
Me
7ga, 68%
Scheme 5. Cyclization of dicarbonyl indoles 3 to thienyl indoles 7.

G. Blay et al. / Tetrahedron 65 (2009) 9264–9270
9267
After filtration, the solvent was removed under reduced pressure
and the mixture was chromatographed eluting with hexane–EtOAc
mixtures (from 9:1 to 8:2) to give 3aa (158.8 mg, 90%).
(s, 3H); 13C NMR (75 MHz, CDCl3)
d
199.2 (C), 198.8 (C), 136.5 (C),
134.8 (C), 133.2 (CH), 132.7 (CH), 129.4 (C), 128.8 (CH), 128.5 (CH),
128.4 (CH), 128.2 (CH), 126.2 (C), 124.2 (CH), 122.9 (CH), 118.2 (CH),
112.7 (C), 111.1 (CH), 42.8 (CH2), 39.6 (CH), 21.55 (CH3); MS(EI) m/z
(%): 367 (Mþ, 45), 263 (22), 262 (83), 106 (16), 105 (100), 77 (41);
HRMS: 367.1579 (Mþ), C25H21NO2 requires 367.1572.
4.2.1. 2-(1H-Indol-3-yl)-1,4-diphenylbutane-1,4-dione (3aa). Reaction
time: 3 h; (yield 90%); oil; 1H NMR (300 MHz, CDCl3)
d 8.13 (br s,
1H), 8.06 (dd, J¼6.9,1.5 Hz, 2H), 7.98 (dd, J¼7.2,1.2 Hz, 2H), 7.79 (dd,
J¼7.8,1.8 Hz,1H), 7.55 (tt, J¼7.4, 1.5 Hz,1H), 7.49–7.34 (m, 6H), 7.25–
7.15 (m, 2H), 7.01 (d, J¼2.4 Hz,1H), 5.62 (dd, J¼10.2, 3.6 Hz,1H), 4.26
(dd, J¼18.1, 10.2 Hz, 1H), 3.45 (dd, J¼18.2, 3.5 Hz, 1H); 13C NMR
4.2.6. 2-(5-Methoxy-1H-indol-3-yl)-1,4-diphenylbutane-1,4-dione
(3ca). Reaction time: 3 h; (yield 89%); oil; 1H NMR (300 MHz,
CDCl3)
d
8.04–8.07 (m, 3H), 7.99 (dd, J¼7.8, 1.5 Hz, 2H), 7.56 (tt,
(75 MHz, CDCl3)
d
199.1 (C), 198.2 (C), 136.5 (C), 136.4 (C), 133.2
J¼7.8, 1.6 Hz, 1H), 7.42–7.50 (m, 3H), 7.37 (t, J¼7.5 Hz, 2H), 7.24 (d,
J¼8.7, 1H), 7.19 (d, J¼2.4, 1H), 6.99 (d, J¼2.4, 1H), 6.88 (dd, J¼9,
2.4 Hz, 1H), 5.54 (dd, J¼10.2, 3.6 Hz, 1H), 4.25 (dd, J¼18.0, 10.2 Hz,
1H), 3.88 (s, 3H), 3.43 (dd, J¼18.0, 3.45 Hz, 1H); 13C NMR (75 MHz,
(CH), 132.7 (CH), 128.8 (CH), 128.5 (CH), 128.4 (CH), 128.2 (CH),
126.0 (C), 122.8 (CH), 122.5 (CH), 120.0 (CH), 118.7 (CH), 113.2 (C),
111.4 (CH), 42.8 (CH2), 39.6 (CH); MS(EI) m/z (%): 353 (Mþ, 27), 335
(14), 248 (37), 105 (100), 77 (34); HRMS: 353.1414 (Mþ), C24H19NO2
requires 353.1416.
CDCl3)
d 199.1 (C), 198.8 (C), 154.4 (C), 136.6 (C), 136.5 (C),
133.2 (CH), 132.7 (CH), 131.5 (C), 128.7 (CH), 128.5 (CH), 128.4 (CH),
128.2 (CH), 126.4 (C), 123.5 (CH), 112.9 (C), 112.8 (CH), 112.2 (CH),
100.3 (CH), 56.0 (CH3), 42.7 (CH2), 39.7 (CH); MS(EI) m/z (%): 383
(Mþ, 57), 279 (25), 278 (75), 106 (25), 105 (100), 77 (57); HRMS:
383.1526 (Mþ), C25H21NO3 requires 383.1521.
4.2.2. 2-(1H-Indol-3-yl)-1,4-di-p-tolylbutane-1,4-dione (3ab). Reaction
time: 3 h; (yield 87%); oil; 1H NMR (300 MHz, CDCl3)
d 8.14 (s, 1H),
7.97 (d, J¼8.1 Hz, 2H), 7.88 (d, J¼8.4 Hz, 2H), 7.79 (dd, J¼7.7, 1.5 Hz,
1H), 7.34 (dd, J¼7.8, 2.0 Hz, 1H), 7.14–7.24 (m, 6H), 7.00 (d, J¼2.4 Hz,
1H), 5.59 (dd, J¼10.2, 3.6 Hz, 1H), 4.22 (dd, J¼18.0, 10.2 Hz, 1H), 3.40
(dd, J¼18.0, 3.6 Hz, 1H), 2.39 (s, 3H), 2.33 (s, 3H); 13C NMR (75 MHz,
4.2.7. 2-(5-Bromo-1H-indol-3-yl)-1,4-diphenylbutane-1,4-dione
(3da). Reaction time: 3 h; (yield 92%); oil; 1H NMR (300 MHz,
CDCl3)
d
198.8 (C), 198.4 (C), 143.9 (C), 143.4 (C), 136.4 (C), 134.1 (C),
CDCl3)
d
8.22 (s, 1H), 8.04 (dd, J¼7.9, 1.5 Hz, 2H), 7.98 (dd, J¼7.9,
134.0 (C), 129.2 (CH), 129.1 (CH), 128.9 (CH), 128.3 (CH), 126.0 (C),
122.7 (CH), 122.4 (CH), 119.9 (CH), 118.7 (CH), 113.5 (C), 111.4 (CH),
42.7 (CH2), 39.4 (CH), 21.6 (CH3), 21.6 (CH3); MS(EI) m/z (%): 381
(Mþ, 28), 262 (26), 119 (100), 91 (24); HRMS: 381.1765 (Mþ),
C26H23NO2 requires 381.1728.
1.5 Hz, 2H), 7.90 (d, J¼1.8 Hz, 1H), 7.56 (tt, J¼7.4, 1.8 Hz, 1H), 7.42–
7.51 (m, 3H), 7.38 (t, J¼7.4, 2H), 7.29 (dd, J¼8.7, 1.8 Hz, 1H), 7.20 (d,
J¼8.7 Hz, 1H), 7.02 (d, J¼2.4 Hz, 1H), 5.54 (dd, J¼10.2, 3.6 Hz, 1H),
4.22 (dd, J¼10.2, 3.6 Hz, 1H), 3.41 (dd, J¼18.0, 3.6 Hz, 1H); 13C NMR
(75 MHz, CDCl3) d 198.9 (C), 198.5 (C), 136.7 (C), 136.3 (C), 135.0 (C),
133.3 (CH), 132.9 (CH), 128.7 (CH), 128.6 (CH), 128.5 (CH), 128.2
(CH), 127.7 (C), 125.5 (CH), 124.0 (CH), 121.3 (CH), 113.4 (C), 112.9
(CH), 42.8 (CH2), 39.4 (CH); MS(EI) m/z (%): 431 (Mþ, 12), 105 (100),
77 (18); HRMS: 431.0536 (Mþ), C24H18BrNO2 requires 431.0521.
4.2.3. 2-(1H-Indol-3-yl)-1,4-bis(3,4-dimethylphenyl)butane-1,4-di-
one (3ac). Reaction time: 4 h; (yield 75%); oil; 1H NMR (300 MHz,
CDCl3) d 8.12 (s, 1H), 7.86 (s, 1H), 7.79–7.82 (m, 2H), 7.75 (s, 1H), 7.72
(d, J¼7.8 Hz, 1H), 7.34 (dd, J¼6.9, 2.4 Hz, 1H), 7.15–7.24 (m, 3H), 7.10
(d, J¼7.8 Hz, 1H), 7.01 (d, J¼2.4 Hz, 1H), 5.59 (dd, J¼10.2, 3.6 Hz, 1H),
4.21 (dd, J¼18.0, 10.2 Hz, 1H), 3.42 (dd, J¼18.0, 3.6 Hz, 1H), 2.30 (s,
3H), 2.28 (s, 3H), 2.24 (s, 3H), 2.23 (s, 3H); 13C NMR (75 MHz, CDCl3)
4.2.8. 2-(7-Methyl-1H-indol-3-yl)-1,4-diphenylbutane-1,4-dione
(3ea). Reaction time: 3 h; (yield 97%); oil; 1H NMR (300 MHz,
CDCl3)
d
8.09 (s, 1H), 8.06 (dd, J¼7.9, 1.5 Hz, 2H), 7.98 (dd, J¼7.9,
d
199.1 (C), 198.6 (C), 142.6 (C), 142.2 (C), 136.7 (C), 136.6 (C), 136.4
1.5 Hz, 2H), 7.65 (d, J¼7.8 Hz, 1H), 7.55 (tt, J¼6.8, 1.7 Hz, 1H), 7.41–
7.48 (m, 3H), 7.35 (t, J¼7.5 Hz, 2H), 7.13 (t, J¼7.5 Hz, 1H), 7.04 (d,
J¼8.1 Hz, 1H), 7.02 (d, J¼2.4 Hz, 1H), 5.61 (dd, J¼10.2, 3.3 Hz, 1H),
4.26 (dd, J¼18.3, 10.2 Hz, 1H), 3.44 (dd, J¼18.2, 3.5 Hz), 2.45 (s, 3H);
(C), 134.5 (C), 134.4 (C), 129.8 (CH), 129.7 (CH), 129.6 (CH), 129.3
(CH), 126.5 (CH), 126.1 (C), 125.9 (CH), 122.7 (CH), 122.4 (CH), 119.9
(CH), 118.8 (CH), 113.7 (C), 111.4 (CH), 42.8 (CH2), 39.4 (CH), 20.0
(CH3), 19.9 (CH3), 19.8 (CH3), 19.7 (CH3); MS(EI) m/z (%): 409 (Mþ, 7),
133 (100), 105 (17); HRMS: 409.2035 (Mþ), C28H27NO2 requires
409.2042.
13C NMR (75 MHz, CDCl3)
d 199.1 (C), 198.7 (C), 136.5 (c), 136.0 (C),
133.2 (CH), 132.7 (CH), 128.7 (CH), 128.5 (CH), 128.4 (CH), 128.1
(CH), 125.5 (C), 123.0 (CH), 122.5 (CH), 120.7 (C), 120.3 (CH), 116.3
(CH), 113.1 (C), 42.9 (CH2), 39.7 (CH), 16.5 (CH3); MS(EI) m/z (%): 367
(Mþ, 22), 262 (34), 105 (100), 77 (26); HRMS: 367.1577 (Mþ),
C25H21NO2 requires 367.1572.
4.2.4. 1,4-Bis(4-fluorophenyl)-2-(1H-indol-3-yl)butane-1,4-dione
(3ad). Reaction time: 3 h; (yield 90%); oil; 1H NMR (300 MHz,
CDCl3)
d
8.16 (S, 1H), 8.07 (dd, J¼8.7, 5.4 Hz, 2H), 8.00 (dd, J¼8.7,
5.4 Hz, 2H), 7.76 (d, J¼7.2 Hz, 1H), 7.37 (d, J¼7.8 Hz, 1H), 7.24 (td,
J¼7.2, 2.0 Hz, 1H), 7.19 (td, J¼7.4, 1.3 Hz, 1H), 7.10 (t, J¼8.5 Hz, 2H),
6.98–7.06 (m, 3H), 5.54 (dd, J¼10.2, 3.3 Hz, 1H), 4.22 (dd, J¼18.0,
10.2 Hz, 1H), 3.83 (dd, J¼18.0, 3.3 Hz, 1H); 13C NMR (75 MHz, CDCl3)
4.2.9. 2-(2-Methyl-1H-indol-3-yl)-1,4-diphenylbutane-1,4-dione
(3fa). Reaction time: 3 h; (yield 96%); oil; 1H NMR (300 MHz,
CDCl3)
d 7.97–8.01 (m, 4H), 7.88 (s, 1H), 7.68–7.73 (m, 1H), 7.54 (tt,
J¼7.4, 1.5 Hz, 1H), 7.40–7.46 (m, 3H), 7.32 (t, J¼7.4 Hz, 2H), 7.19–7.23
(m, 1H), 7.08–7.13 (m, 2H), 5.53 (dd, J¼9.3, 4.2 Hz, 1H), 4.37 (dd,
J¼9.3, 4.2 Hz, 1H), 3.28 (dd, J¼18.0, 4.2 Hz, 1H), 2.46 (s, 3H); 13C
d
197.5 (C), 197.1 (C), 165.5 (d, J¼253.5 Hz, C), 165.5 (d, J¼252.6 Hz,
C), 136.4 (C), 132.9 (d, J¼3.0 Hz, C), 132.8 (d, J¼3.0 Hz, C), 131.4 (d,
J¼9.2 Hz, CH), 130.8 (d, J¼9.2 Hz, CH), 125.8 (C), 122.72 (CH), 122.68
(CH), 120.2 (CH), 118.5 (CH), 115.7 (d, J¼21.8 Hz, CH), 115.5 (d,
J¼21.8 Hz, CH), 112.9 (C), 111.5 (CH), 42.7 (CH2), 39.6 (CH); MS(EI)
m/z (%): 389 (Mþ, 3), 123 (100), 95 (23); HRMS: 389.1216 (Mþ),
C24H17F2NO2 requires 389.1227.
NMR (75 MHz, CDCl3)
d 198.9 (C), 198.9 (C), 136.8 (C), 136.7 (C),
135.2 (C), 133.1 (CH), 132.5 (CH), 132.0 (C), 128.5 (CH), 128.3 (CH),
128.1 (CH), 127.3 (C), 121.3 (CH), 119.8 (CH), 118.5 (CH), 110.3 (CH),
108.2 (C), 40.6 (CH2), 40.1 (CH), 12.2 (CH3); MS(EI) m/z (%): 367 (Mþ,
40), 263 (19), 262 (95), 105 (100), 77 (18); HRMS: 367.1577 (Mþ),
C25H21NO2 requires 367.1572.
4.2.5. 2-(5-Methyl-1H-indol-3-yl)-1,4-diphenylbutane-1,4-dione
(3ba). Reaction time: 3 h; (yield 95%); oil; 1H NMR (300 MHz,
4.2.10. 2-(1-Methyl-1H-indol-3-yl)-1,4-diphenylbutane-1,4-dione
CDCl3)
d
8.04–8.07 (m, 3H), 7.99 (dd, J¼8.3, 1.4 Hz, 2H), 7.58–7.52
(3ga). Reaction time: 3 h; (yield 85%); oil; 1H NMR (300 MHz,
(m, 2H), 7.44–7.50 (m, 3H), 7.36 (t, J¼7.4 Hz, 2H), 7.25 (d, J¼9.3, 1H),
7.05 (dd, J¼8.4, 1.5, 1H), 6.96 (d, J¼2.4, 1H), 5.58 (dd, J¼10.5, 3.3 Hz,
1H), 4.25 (dd, J¼18.2, 10.4 Hz, 1H), 3.42 (dd, J¼18.0, 3.3 Hz, 1H), 2.49
CDCl3)
d
8.08 (dd, J¼7.8, 1.5 Hz, 2H), 7.99 (dd, J¼7.8, 1.5 Hz, 2H),
7.79 (d, J¼7.8 Hz, 1H), 7.55 (tt, J¼7.4, 2.1 Hz, 1H), 7.41–7.50 (m, 3H),
7.37 (t, J¼7.5 Hz, 2H), 7.23–7.31 (m, 2H), 7.16–7.21 (m, 1H), 6.9 (s,

9268
G. Blay et al. / Tetrahedron 65 (2009) 9264–9270
1H), 5.61 (dd, J¼10.2, 3.6 Hz, 1H), 4.26 (dd, J¼18.3, 10.2 Hz, 1H),
3.70 (s, 3H), 3.44 (dd, J¼18.2, 3.5 Hz, 1H); 13C NMR (75 MHz,
d
8.18 (br s, 1H), 7.81 (dd, J¼7.8, 1.2 Hz, 2H), 7.71 (dd, J¼8.4,
1.5 Hz, 2H), 7.44 (dd, J¼7.7 Hz, 2H), 7.37–7.19 (m, 6H), 7.08–7.01
CDCl3)
d
199.1 (C), 198.7 (C), 137.2 (C), 136.53 (C), 136.49 (C), 133.1
(m, 2H), 6.89 (s, 1H), 2.56 (s, 3H); 13C NMR (75.5 MHz, CDCl3)
(C), 132.7 (CH), 128.8 (CH), 128.5 (CH), 128.4 (CH), 128.1 (CH),
127.4 (CH), 126.4 (C), 112.0 (CH), 119.5 (CH), 118.7 (CH), 111.5 (C),
109.5 (CH), 43.2 (CH2), 39.4 (CH), 32.8 (CH3); MS(EI) m/z (%): 367
(Mþ, 20), 262 (53), 105 (100), 77 (24); HRMS: 367.1575 (Mþ),
C25H21NO2 requires 367.1572.
d 152.2 (C), 148.1 (C), 135.7 (C), 131.5 (C), 130.7 (C), 128.7 (CH),
128.3 (CH), 127.4 (CH), 127.0 (CH), 126.1 (C), 125.5 (CH), 123.8
(CH), 122.9 (CH), 122.5 (CH), 120.4 (C), 120.2 (CH), 118.1 (CH),
117.2 (C), 110.7 (CH), 110.3 (C), 16.6 (CH3); MS (EI) m/z (%): 349
(Mþ, 100), 244 (19); HRMS: 349.1467 (Mþ), C25H19NO requires
349.1467.
4.2.11. 1,4-Diphenyl-2-(1H-pyrrol-2-yl)butane-1,4-dione (8). Reaction
time: 30 min; (yield 74%); mp 128–131 ꢀC (CH2Cl2–hexane); 1H
4.4. Experimental procedure for the cyclization of
compounds 3 to pyrrolyl indoles 5
NMR (300 MHz, CDCl3)
d
8.49 (br s, 1H), 8.07 (dd, J¼8.0, 1.5 Hz, 2H),
7.96 (dd, J¼8.0, 1.5 Hz, 2H), 7.59–7.51 (m, 2H), 7.47–7.42 (m, 4H),
6.71–6.69 (m, 1H), 6.12–6.07 (m, 2H), 5.43 (dd, J¼9.0, 4.5 Hz, 1H),
4.11 (dd, J¼18.2, 9.2 Hz, 1H), 3.49 (dd, J¼18.2, 4.7 Hz, 1H); 13C NMR
A solution of 3aa (88.2 mg, 0.25 mmol) and ammonium acetate
(385 mg, 5.0 mmol) in a mixture of EtOH (4 mL) and CHCl3 (6 mL)
was heated at 50 ꢀC until completion (24 h, TLC). Then, the solvent
was removed under reduced pressure and the concentrated chro-
matographed on silica gel eluting with hexane–diethyl ether (97:3)
to give pyrrolyl indole 5aa (65.2 mg, 78%).
(75 MHz, CDCl3)
d 199.1 (C), 198.3 (C), 136.4 (C), 136.2 (C), 133.4
(CH), 133.2 (CH), 128.8 (CH), 128.6 (CH), 128.1 (CH), 127.4 (C), 118.3
(CH), 108.8 (CH), 107.2 (CH), 43.3 (CH2), 41.3 (CH); MS(EI) m/z (%):
303 (Mþ, 10), 198 (22), 105 (100), 77 (41); HRMS: 303.1283 (Mþ),
C20H17NO2 requires 303.1259.
4.4.1. 3-(2,5-Diphenyl-1H-pyrrol-3-yl)-1H-indole (5aa). Reaction
4.3. Experimental procedure for the cyclization of
compounds 3 to furanyl indoles 4
time: 24 h; (yield 78%); yellow solid, mp 205–208 ꢀC (ether–
hexane); 1H NMR (300 MHz, CDCl3)
d 8.43 (br s, 1H), 8.00 (br s,
1H), 7.52–7.48 (m, 3H), 7.38–7.30 (m, 5H), 7.21–7.08 (m, 6H), 7.03
A solution of 3aa (88.2 mg, 0.25 mmol) and TsOH (4.8 mg,
0.025 mmol) in toluene (10 mL) was heated at 80 ꢀC until completion
(5 h, TLC). Then, thesolventwasremovedunderreducedpressureand
the concentrated chromatographed on silicagel eluting withhexane–
diethyl ether (95:5) to give furanyl indole 4aa (68.7 mg, 82%).
(d, J¼2.4 Hz, 1H), 6.99 (td, J¼7.5, 0.9 Hz, 1H), 6.72 (d, J¼3 Hz, 1H);
13C NMR (75 MHz, CDCl3)
d 136.1 (C), 133.4 (C), 132.4 (C), 132.1 (C),
129.4 (C), 129.0 (CH), 128.6 (CH), 127.0 (CH), 126.7 (CH), 126.4
(CH), 123.8 (CH), 122.2 (CH), 122.0 (CH), 120.5 (CH), 119.6 (CH),
116.4 (C), 112.0 (C), 111.0 (CH), 109.7 (CH); MS(EI) m/z (%): 334
(Mþ, 100), 333 (16); HRMS: 334.1464 (Mþ), C24H18N2 requires
334.1470.
4.3.1. 3-(2,5-Diphenylfuran-3-yl)-1H-indole (4aa). Reaction time:
5 h; (yield 82%); orange oil; 1H NMR (300 MHz, CDCl3)
d 8.25 (br s,
1H), 7.81 (dd, J¼8.0, 1.5 Hz, 2H), 7.70 (dd, J¼8.4, 1.5 Hz, 2H), 7.50–
4.4.2. 3-(2,5-Bis(3,4-dimethylphenyl)-1H-pyrrol-3-yl)-1H-indole
7.41 (m, 4H), 7.32–7.18 (m, 6H), 7.11 (dd, J¼7.5, 0.9 Hz, 1H), 6.90 (s,
(5ac). Reaction time: 54 h; (yield 67%); orange oil; 1H NMR
1H); 13C NMR (75 MHz, CDCl3)
d
152.2 (C), 148.2 (C), 136.1 (C), 131.5
(300 MHz, CDCl3)
d
8.40 (br s, 1H), 8.03 (br s, 1H), 7.63 (d, J¼7.8 Hz,
(C), 130.7 (C), 128.7 (CH), 128.3 (CH), 127.4 (CH), 127.0 (CH), 126.5
(C), 125.5 (CH), 123.8 (CH), 122.8 (CH), 122.4 (CH), 120.4 (CH), 120.0
(CH), 117.0 (C), 111.2 (CH), 110.7 (CH), 109.8 (C); MS(EI) m/z (%): 335
(Mþ, 100), 306 (11), 230 (34); HRMS: 335.1301 (Mþ), C24H17NO
requires 335.1310.
1H), 7.37–7.34 (m, 2H), 7.30 (d, J¼7.8 Hz, 1H), 7.24 (s, 1H), 7.21–7.05
(m, 6H), 6.97 (d, J¼7.8 Hz, 1H), 6.73 (d, J¼2.7 Hz, 1H), 2.31 (s, 3H),
2.27 (s, 3H), 2.21 (s, 3H), 2.18 (s, 3H); 13C NMR (75.5 MHz, CDCl3)
d
137.0 (C), 136.6 (C), 136.1 (C), 134.7 (C) 131.9 (C), 131.1 (C), 130.2
(C), 130.1 (CH), 129.7 (CH), 129.0 (C), 127.7 (CH), 127.1 (C), 125.1
(CH), 124.5 (CH), 122.2 (CH), 121.8 (CH), 121.2 (CH), 120.6 (CH),
119.4 (CH), 115.7 (C), 112.2 (C), 110.9 (CH), 108.9 (CH), 19.9 (CH3),
19.8 (CH3), 19.5 (CH3), 19.5 (CH3); MS (EI) m/z (%): 390 (Mþ, 100),
389 (11), 388 (10); HRMS: 390.2104 (Mþ), C28H26N2 requires
390.2096.
4.3.2. 3-(2,5-Di-p-tolylfuran-3-yl)-1H-indole (4ab). Reaction time:
20 h; (yield 92%); orange oil; 1H NMR (300 MHz, CDCl3)
d 8.28 (br s,
1H), 7.69 (d, J¼8.1 Hz, 2H), 7.58 (d, J¼8.1 Hz, 2H), 7.50 (d, J¼7.8 Hz,
1H), 7.44 (d, J¼8.1 Hz,1H), 7.27–7.22 (m, 4H), 7.13–7.05 (m, 3H), 6.82
(s, 1H), 2.40 (s, 3H), 2.32 (s, 3H); 13C NMR (75.5 MHz, CDCl3)
d 152.1
(C), 148.1 (C), 137.1 (C), 136.7 (C), 136.1 (C), 129.4 (CH), 128.9 (CH),
128.1 (C), 126.6 (C), 125.4 (CH), 124.5 (C), 123.7 (CH), 123.6 (C), 122.8
(CH), 122.3 (CH), 120.4 (CH), 119.9 (CH), 116.2 (C), 111.2 (CH), 109.2
(CH), 21.3 (CH3), 21.3 (CH3); MS (EI) m/z (%): 363 (Mþ, 100), 244
(14); HRMS: 363.1624 (Mþ), C26H21NO requires 363.1623.
4.4.3. 3-(2,5-Diphenyl-1H-pyrrol-3-yl)-5-methoxy-1H-indole (5ca).
Reaction time: 48 h; (yield 90%); orange oil; 1H NMR (300 MHz,
CDCl3)
7.39 (m, 4H), 7.28–7.16 (m, 6H), 6.83–6.81 (m, 2H), 6.75 (d, J¼2.7 Hz,
1H), 3.59 (s, 3H); 13C NMR (75.5 MHz, CDCl3)
153.6 (C), 133.6 (C),
d
8.56 (br s, 1H), 8.08 (br s, 1H), 7.59 (d, J¼7.5 Hz, 2H), 7.45–
d
132.5 (C), 131.2 (C), 129.1 (C), 128.8 (CH), 128.4 (CH), 126.8 (CH),
126.7 (C), 126.2 (CH), 123.8 (CH), 122.9 (CH), 116.5 (C), 116.5 (C),
112.2 (CH), 111.7 (C), 111.6 (CH), 111.6 (CH), 109.4 (CH), 101.9 (CH),
55.5 (CH3); MS (EI) m/z (%): 364 (Mþ, 100); HRMS: 364.1576 (Mþ),
C25H20N2O requires 364.1576.
4.3.3. 3-(2,5-Diphenylfuran-3-yl)-7-methyl-1H-indole (4ba). Reaction
time: 5 h; (yield 92%); brown solid, mp 135–140 ꢀC (CH2Cl2–hex-
ane); 1H NMR (300 MHz, CDCl3)
d
8.15 (br s, 1H), 7.82 (dd, J¼8.0,
1.5 Hz, 2H), 7.71 (dd, J¼8.4,1.2 Hz, 2H), 7.44 (dd, J¼7.7 Hz, 2H), 7.36–
7.17 (m, 8H), 7.10 (dd, J¼8.25, 1.4 Hz, 2H), 6.90 (s, 1H), 2.40 (s, 3H);
13C NMR (75.5 MHz, CDCl3)
d
152.2 (C), 148.2 (C), 134.5 (C), 131.5 (C),
4.4.4. 3-(2,5-Diphenyl-1H-pyrrol-3-yl)-2-methyl-1H-indole (5fa). Re-
1
130.7 (C), 129.4 (CH), 129.0 (CH), 128.7 (CH), 128.2 (CH), 127.3 (CH),
126.9 (CH),125.5 (CH),124.0 (CH),123.8 (CH),122.9 (CH),119.8 (CH),
117.2 (C), 110.8 (CH), 110.7 (CH), 109.2 (C), 21.4 (CH3); MS (EI) m/z
(%): 349 (Mþ, 100), 243 (19); HRMS: 349.1464 (Mþ), C25H19NO re-
quires 349.1467.
action time: 48 h; (yield 71%); violet oil; H NMR (300 MHz, CDCl3)
d
8.56 (br s, 1H), 7.84 (br s, 1H), 7.58 (dd, J¼8.0, 1.5 Hz, 2H), 7.52 (d,
J¼7.8 Hz, 1H), 7.40 (t, J¼7.7 Hz, 2H), 7.36–7.29 (m, 3H), 7.25–7.19 (m,
3H), 7.16–7.10 (m, 2H), 7.05 (td, J¼7.5, 1.1 Hz, 1H), 6.73 (d, J¼3.0 Hz,
1H), 2.07 (s, 3H); 13C NMR (75.5 MHz, CDCl3)
d 135.5 (C), 133.7 (C),
132.4 (C), 132.0 (C), 131.6 (C), 129.9 (C), 128.9 (CH), 128.8 (C), 128.6
(CH), 126.3 (CH), 126.1 (CH), 125.7 (CH), 123.7 (CH), 121.1 (CH), 119.5
(CH), 119.4 (CH), 116.2 (C), 110.4 (CH), 110.0 (CH), 108.5 (C), 12.4 (CH3);
4.3.4. 3-(2,5-Diphenylfuran-3-yl)-7-methyl-1H-indole (4ea). Reaction
time: 7 h; (yield 93%); orange oil; 1H NMR (300 MHz, CDCl3)

G. Blay et al. / Tetrahedron 65 (2009) 9264–9270
9269
MS (EI) m/z (%): 348 (Mþ, 100), 347 (12); HRMS: 348.1625 (Mþ),
C25H20N2 requires 348.1626.
d
8.16 (br s, 1H), 7.68 (d, J¼8.7, 1.5 Hz, 2H), 7.62–7.61 (m, 1H), 7.46
(s, 1H), 7.44–7.23 (m, 10H), 7.03 (d, J¼2.7 Hz, 1H); 13C NMR
(75.5 MHz, CDCl3)
d 142.6 (C), 137.9 (C), 134.6 (C), 134.5 (C), 134.1
4.5. Experimental procedure for the cyclization of
compounds 3 to N-allyl pyrrolyl indoles 6
(C), 131.2 (C), 129.0 (CH), 128.9 (CH), 128.4 (CH), 128.3 (C), 127.6
(CH), 127.4 (CH), 126.5 (CH), 125.7 (CH), 125.2 (CH), 124.3 (CH),
122.8 (CH), 113.4 (C), 112.5 (CH), 112.3 (C); MS (EI) m/z (%): 431
(Mþ2, 100), 429 (Mþ, 96), 350 (16), 349 (50); HRMS: 429.0189
(Mþ), C24H16BrNS requires 429.0187.
Allylamine (0.3 mL, 0.4 mmol) and acetic acid (0.23 mL) were
added to a solution of compound 3aa (70.1 mg, 0.2 mmol) in
a mixture of EtOH (4 mL) and CHCl3 (6 mL). The reaction mixture
was heated at 50 ꢀC until completion (20 h, TLC). The solvent was
removed under reduced pressure and the concentrated chroma-
tographed on silica gel eluting with hexane–diethyl ether (95:5) to
give 6aa (50.9 mg, 68%).
4.6.4. 3-(2,5-Diphenylthiophen-3-yl)-1-methyl-1H-indole (7ga). Reaction
time: 30 min; (yield 68%); orange oil; 1H NMR (300 MHz, CDCl3)
d 7.68
(d, J¼7.7, 1.5 Hz, 2H), 7.50 (d, J¼8.1 Hz, 1H), 7.50 (s, 1H), 7.46–7.39 (m,
5H), 7.33 (t, J¼7.9 Hz, 2H), 7.27–7.21 (m, 3H), 7.07 (td, J¼7.5, 1.2 Hz, 1H),
6.92 (d, J¼2.4 Hz, 1H), 3.76 (3H, s); 13C NMR (75.5 MHz, CDCl3)
d 142.2
4.5.1. 3-(1-Allyl-2,5-diphenyl-1H-pyrrol-3-yl)-1H-indole (6aa). Brown
(C), 137.0 (C), 136.8 (C), 135.0 (C), 134.3 (C), 132.1 (C), 128.9 (CH), 128.8
(CH), 128.4 (CH), 127.8 (CH), 127.5 (CH), 127.11 (CH), 127.08 (CH), 126.9
(C), 125.6 (CH), 121.7 (CH), 120.4 (CH), 119.5 (CH), 111.0 (C), 109.2 (C),
32.8 (CH3); MS (EI) m/z (%): 365 (Mþ, 100), 349 (14); HRMS: 365.1239
(Mþ), C25H19NS requires 365.1238.
oil; 1H NMR (300 MHz, CDCl3)
d
10.86 (br s, 1H), 7.57 (dd, J¼7.8,
1.2 Hz, 2H), 7.50–7.42 (m, 3H), 7.38–7.30 (m, 6H), 7.03 (tt, J¼7.5,
0.9 Hz, 1H), 6.89 (tt, J¼7.4, 0.9 Hz, 1H), 6.79 (d, J¼2.4 Hz, 1H), 6.57
(s, 1H), 5.64 (ddt, J¼17.1, 10.5, 4.5 Hz, 1H), 4.94 (dd, J¼10.8, 1.4 Hz,
1H), 4.59 (dd, J¼17.1, 1.5 Hz, 1H), 4.54–4.52 (2H, m); 13C NMR
(75 MHz, CDCl3)
d
135.9 (C), 135.4 (CH), 134.1 (C), 133.23 (C),
4.6.5. 2-(2,5-Diphenylfuran-3-yl)-1H-pyrrole (9). Reaction time:
133.21 (C), 131.2 (C), 130.9 (CH), 128.5 (CH), 128.4 (CH), 128.2
(CH), 127.4 (CH), 126.8 (CH), 126.3 (C), 122.1 (CH), 120.7 (CH),
119.4 (CH), 118.5 (CH), 116.5 (C), 115.5 (CH2), 111.3 (CH), 110.2 (C),
109.6 (CH), 46.8 (CH2); MS(EI) m/z (%): 374 (Mþ, 100), 334 (18),
333 (60), 332 (26), 230 (20); HRMS: 374.1783 (Mþ), C27H22N2
requires 374.1783.
30 min; (yield 54%); violet oil; 1H NMR (300 MHz, CDCl3)
d 8.23 (br
s, 1H), 7.75 (dd, J¼7.2, 1.5 Hz, 2H), 7.69 (dd, J¼7.2, 1.5 Hz, 2H), 7.44–
7.38 (m, 4H), 7.34–7.28 (m, 2H), 6.83 (s, 1H), 6.80–6.78 (m, 1H),
6.41–6.39 (m, 1H), 6.31 (q, J¼2.9 Hz, 1H); 13C NMR (75.5 MHz,
CDCl3)
d 152.8 (C), 147.0 (C), 131.2 (C), 130.4 (C), 128.7 (CH), 128.7
(CH), 127.8 (CH), 127.6 (CH), 126.1 (CH), 124.2 (C), 123.8 (CH), 117.9
(CH), 116.5 (C), 109.4 (CH), 108.2 (CH), 107.9 (CH); MS (EI) m/z (%):
285 (Mþ, 100), 284 (26), 256 (10), 180 (18); HRMS: 285.1159 (Mþ),
C20H15NO requires 285.1154.
4.6. Experimental procedure for the cyclization of
compounds 3 to thienyl indoles 7
A solution of Lawesson reagent (60 mg, 0.15 mmol) and com-
pound 3aa (44.2 mg, 0.125 mmol) in toluene (2 mL) was heated at
90 ꢀC under nitrogen until completion (30 min, TLC). The solvent
was removed under reduced pressure and the concentrated chro-
matographed on silica gel eluting with hexane–EtOAc (95:5) to give
thienyl indole 7aa (30.7 mg, 79%).
4.6.6. 2,5-Diphenyl-3-(1H-pyrrol-2-yl)-1H-pyrrole
(10). Reaction
8.33
time: 30 min; (yield 52%); blue oil; 1H NMR (300 MHz, CDCl3)
d
(br s, 1H), 7.67 (br s, 1H), 7.50 (dd, J¼8.8, 1.1 Hz, 2H), 7.40–7.18 (m,
9H), 6.60 (d, J¼3.0 Hz, 1H), 6.09 (t, J¼3.0 Hz, 1H), 5.89 (t, J¼3.1 Hz,
1H); 13C NMR (75.5 MHz, CDCl3)
d 138.3 (C), 132.8 (C), 132.3 (C),
132.1 (C), 128.9 (CH), 128.9 (CH), 127.7 (C), 127.2 (CH), 127.2 (CH),
126.5 (CH), 126.4 (CH), 123.8 (CH), 116.1 (C), 106.9 (CH), 105.3 (CH),
104.1 (CH); MS (EI) m/z (%): 284 (Mþ, 89), 283 (45), 282 (15); HRMS:
284.1309 (Mþ), C20H16N2 requires 284.1313.
4.6.1. 3-(2,5-Diphenylthiophen-3-yl)-1H-indole
time: 30 min; (yield 79%); yellow solid, mp 133–137 ꢀC (CH2Cl2–
hexane); 1H NMR (300 MHz, CDCl3)
8.13 (br s, 1H), 7.68 (d,
(7aa). Reaction
d
J¼7.8 Hz, 2H), 7.55 (d, J¼8.1 Hz, 1H), 7.53 (s, 1H), 7.44–7.39 (m, 5H),
Acknowledgements
7.32 (d, J¼7.5 Hz, 1H), 7.28–7.20 (m, 4H), 7.09 (t, J¼7.5 Hz, 1H), 7.04
(d, J¼2.4 Hz, 1H); 13C NMR (75.5 MHz, CDCl3)
d 142.3 (C), 137.5 (C),
´
Financial support from the Ministerio de Ciencia e Innovacion
136.0 (C), 134.9 (C), 134.3 (C), 132.0 (C), 128.9 (CH), 128.8 (CH), 128.4
(CH), 127.5 (CH), 127.2 (CH), 126.9 (CH), 126.5 (C), 125.6 (CH), 123.2
(CH), 122.3 (CH), 120.3 (CH), 120.0 (CH), 112.6 (C), 111.1 (CH); MS(EI)
m/z (%): 351 (Mþ, 100), 350 (29), 349 (26); HRMS: 351.1087 (Mþ),
C24H17NS requires 351.1082.
and FEDER (CTQ 2006-14199/BQU) and from the Generalitat
Valenciana (ACOMP/2009/338) is gratefully acknowledged. C.V. and
A.M. thank the Generalitat Valenciana for grants.
References and notes
4.6.2. 3-(2,5-Bis(4-fluorophenyl)thiophen-3-yl)-1H-indole
Reaction time: 30 min; (yield 80%); orange oil; 1H NMR (300 MHz,
CDCl3)
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