Synthesis of bis(indolyl)alkanes by a site-selective gold-catalyzed addition of indoles to butynol derivatives

Article abstract of DOI:10.1016/j.jorganchem.2008.09.059

A new site-selective hydroarylation reaction of alkynes catalyzed by gold complexes and directed by an internal hydroxyl group has been developed. Thus, the treatment of 3-butyn-1-ol derivatives with indoles and a catalytic amount of an in situ formed cat

Full text of DOI:10.1016/j.jorganchem.2008.09.059

Journal of Organometallic Chemistry 694 (2009) 546–550
Contents lists available at ScienceDirect
Journal of Organometallic Chemistry
journal homepage: www.elsevier.com/locate/jorganchem
Synthesis of bis(indolyl)alkanes by a site-selective gold-catalyzed addition
of indoles to butynol derivatives
*
José Barluenga , Amadeo Fernández, Félix Rodríguez, Francisco J. Fañanás
Instituto de Química Organometálica ‘‘Enrique Moles”, Universidad de Oviedo, Julián Clavería 8, 33006 Oviedo, Spain
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 10 July 2008
Received in revised form 26 August 2008
Accepted 30 September 2008
Available online 7 October 2008
A new site-selective hydroarylation reaction of alkynes catalyzed by gold complexes and directed by an
internal hydroxyl group has been developed. Thus, the treatment of 3-butyn-1-ol derivatives with indoles
and a catalytic amount of an in situ formed cationic gold complex leads to the formation of bis(indo-
lyl)alkane derivatives. Particularly interesting is the reaction with terminal alkynes as the double addi-
tion of the indol occurs at the terminal carbon of the triple bond. The reaction conditions are very
mild and the final bis(indolyl)alkanes are obtained in high yields.
Keywords:
Alkynes
Ó 2008 Elsevier B.V. All rights reserved.
C–C-coupling
Gold
Homogeneous catalysis
Indoles
1. Introduction
bisindolyl derivatives are also available from alkynols derived from
3-butyn-1-ol. In contrast to those results found by Echavarren for
A large variety of biologically active natural products contain the
indole system as a central element of their structure [1]. More spe-
cifically, numerous bis(indolyl)alkanes have been isolated from sev-
eral terrestrial and marine natural source and the range of biological
activities possessed by individual members of this series includes
coronary dilatory properties, genotoxicity and antibacterial activity
[2]. However, the discovery of important anti-carcinogenic proper-
ties of some bis(indolyl)alkanes have brought to the forefront the
importance of these compounds [3]. Thus, a significant effort from
the synthetic community has been directed in recent years to the
production of this kind of molecules. Almost all procedures de-
scribed in the literature to access these compounds are based on
the condensation reaction of indoles with aldehydes or ketones in
the presence of protic or Lewis acids [4]. However, Echavarren
et al. have recently published an interesting gold-catalyzed synthe-
sis of bisindolyl derivatives by reaction of alkynes and indoles
(Scheme 1) [5]. This process supposes a formal double addition of
the indole to the alkyne. It is important to remark that this double
addition of the indole always occurs at the internal carbon of the tri-
ple bond. Interestingly, when 4-pentyn-1-ol or 5-hexyn-1-ol are
used as the alkyne counterpart, the corresponding tetrahydrofurane
or tetrahydropyrane derivatives are obtained (Scheme 1) [6].
During our ongoing investigations on the development of new
platinum and gold-catalyzed processes [7], we have found that
terminal alkynes, the double addition of the indole occurs at the
terminal carbon of the triple bond [8]. Details on this hydroxy-di-
rected gold catalyzed double hydroarylation reaction of terminal
and internal alkynes are given in this communication [9].
2. Results and discussion
We initiated our investigations with the reaction of terminal
butynol derivative 1a and N-methylindol 2 in the presence of a cat-
ionic gold(I) complex, in situ generated by reaction of 5 mol% of
(Ph3P)AuCl and 5 mol% of AgSbF6, in dichloromethane as solvent
at room temperature (Table 1, entry 1). This reaction led to the for-
mation of the bis(indolyl)alkane derivative 3a in 77 yield. Surpris-
ingly, compound 3a was obtained as a single regioisomer and
formation of the expected bis(indolyl)alkane where the addition
of the indoles occurred at the internal carbon of the triple bond
was not obtained [5]. This result is also in contrast to the results
observed by Cheng et al. by using similar starting materials but
platinum catalysts as they isolated tetrahydrofurane derivatives
[6]. In view of this differential behaviour we further study the
scope of the reaction by using a range of 3-butyn-1-ol derivatives
1a–f (Table 1). In all cases we obtained the corresponding bis(indo-
lyl)alkane 3 in high yield and as single regioisomers.
All these examples represent a clear example of site-selective
carbon–carbon bond formation across terminal alkynes. However,
much more challenging is the site-selectivity with internal alkynes
and in particular in those cases where both substituents of the
* Corresponding author. Tel./fax: +34 985 103450.
E-mail address: barluenga@uniovi.es (J. Barluenga).
0022-328X/$ - see front matter Ó 2008 Elsevier B.V. All rights reserved.
doi:10.1016/j.jorganchem.2008.09.059

J. Barluenga et al. / Journal of Organometallic Chemistry 694 (2009) 546–550
547
R2
R2
R
Me
(Ph3P)AuCl + AgSbF6
AgCl
H
O
R
OH
1
+
3
+
N
R1
N
R1
N
[Au]
O
2
R2
5 mol %
A
+
N
[Au]+
H
toluene, RT
O
[Au]
5
R2
N
[Au]+
O
Me
4
R = (CH2)nOH
R1
tBu
11
6
n-2
[Au]+
n = 3, 4
tBu
+
+ SbF6
O
−
N
P Au NCMe
R1
[Au]
O
+
N
+
H
O
7
[Au]
N
A
10
O
Scheme 1. Gold(I)-catalyzed reaction of indoles and alkynes (see Refs. [5,6]).
N
2
[Au]
8
9
[Au]+ = [(Ph3P)Au]+ SbF6
−
Table 1
Gold(I)-catalyzed reaction of 3-butyn-1-ol derivatives 1a-f and indol 2.
Scheme 2. Mechanism of formation of bis(indolyl)alkane derivatives 3. For clarity
the substituents of the alkynol derivative are not considered.
R1
R2
R1 R2
5 mol % (Ph3P)AuCl
HO
+
OH
1a-f
N
OH
5 mol % AgSbF6
CH2Cl2, RT
Me
O
2 (1 equiv)
Me
Me
1g
5 mol %
PtCl2
2
N
Me
N
Me
+
5 mol % (Ph3P)AuCl
3a-f
3g
N Me
5 mol % AgSbF6
CH2Cl2, RT
THF, RT
80 %
Entry
Alkynol
R1
R2
Product
Yield (%)a
N
Me
1
2
3
4
5
6
1a
1b
1c
1d
1e
1f
Me
iPr
Ph
H
H
H
Ph
Me
3a
3b
3c
3d
3e
3f
77
84
78
87
70
85
2
92 %
9a
H2C@CH(CH2)2
Ph
–(CH2)5–
Scheme 3. Isolation of intermediate 9a and further reaction with indole 2 to give
3g.
The first step of the catalytic cycle is the coordination of the
metallic complex to the triple bond of the starting alkynol 1 to
form intermediate 4. Intramolecular addition of the hydroxyl
group to the terminal carbon of the triple bond generates 5. Pro-
todemetallation of the latter affords the enol ether 6 and releases
the catalytic species. After an initial coordination of the catalyst
to the double bond of the enol ether 6, the oxonium intermediate
7 is formed. Further nucleophilic attack of the indol 2 affords the
intermediate 8 that evolves through aromatization and protode-
metallation to give the tetrahydrofurane derivative 9. Coordination
of the gold complex to the oxygen of the tetrahydrofurane favours
the opening of the tetrahydrofurane ring to form the intermediate
10. A second nucleophilic attack of the indol 2 affords the interme-
diate 11 that after aromatization and protodemetallation steps
gives rise to the final product 3 releasing the catalytic species.
The role of enol tetrahydrofurane 9 as an intermediate of the
reaction is supported by the following experiment. 3-Pentyn-1-ol
(1g) was treated with one equivalent of indol 2 in the presence
of 5 mol% of PtCl2 in THF under the conditions reported by Cheng
et al. [6], to obtain the expected tetrahydrofurane derivative 9a
in 80% yield (Scheme 3). Compound 9a was isolated and character-
ized and then reacted with 2 under our gold-catalyzed conditions
previously described to give the bis(indolyl)alkane derivative 3g
in 92% yield.
a
Yield of isolated product 3 based on starting alkynol 1.
Table 2
Gold(I)-catalyzed reaction of internal alkynol derivatives 1g–i and indol 2.
OH
R1 R2
OH
R1
R2
R3
5 mol % (Ph3P)AuCl
+
N
5 mol % AgSbF6
CH2Cl2, RT
Me
1g-i
N
Me
N
R3
2
3g-i
Me
Yield (%)a
Entry
Alkynol
R1
R2
R3
Product
1
2
3
1g
1h
1i
H
Me
Me
H
H
H
Me
Bu
(CH2)2Ph
3g
3h
3i
92
87
80
a
Yield of isolated product 3 based on starting alkynol 1.
triple bond are very similar. In order to check the regioselection
across the internal alkyne in the above synthesis of bis(indo-
lyl)alkane derivatives we performed a set of experiments with
homopropargylic alcohols 1g–i (Table 2). As shown, these reactions
led to the corresponding products 3g–i in high yield and most
important as single regioisomers. In all cases, the new carbon–car-
bon bonds are formed at the site distal to the free hydroxyl group
independently of the substitution on the alkyne.
A catalytic mechanism that explains the formation of products 3
is shown in Scheme 2. In first place, we suppose the formation of a
reactive cationic gold complex from (Ph3P)AuCl by reaction with
AgSbF6.
3. Conclusions
Overall, a new site-selective hydroarylation reaction of alkynes
catalyzed by gold complexes and directed by an internal hydroxyl
group has been developed and applied to the synthesis of bis(indo-
lyl)alkanes. Remarkably, when terminal alkynes are used the dou-
ble addition of the indol occurs at the terminal carbon of the triple
bond. When internal alkynes are used, the double addition occurs
at the carbon distal to free hydroxyl group. The reaction conditions

548
J. Barluenga et al. / Journal of Organometallic Chemistry 694 (2009) 546–550
are very mild, high yields are achieved and so, the methodology
here described could be applied to the synthesis of biologically
interesting bis(indolyl)alkanes. Moreover, we speculate that this
site-selective strategy could be further exploited in other carbon–
carbon bond-forming reactions.
4.3.2. 6,6-Bis(1-methyl-1H-indol-3-yl)-2-methyl-hexan-3-ol (3b)
12´
7´
N
OH
3
5
7
11´
10´
1
4. Experimental
2
8´
4
6
8
9´
4.1. General consideration
1´
9
N
1H NMR spectra were recorded on a Bruker AV-600 (600 MHz),
Bruker AMX-400 (400 MHz) or Bruker DPX-300 (300 MHz). Chem-
ical shifts are reported in ppm from tetramethylsilane with the
residual solvent resonance as the internal standard (CHCl3: d
7.26, THF d 3.58, 1.73, acetone d 2.05). Data are reported as follows:
chemical shift, multiplicity (s: singlet, d: doublet, dt: double triplet,
ddd: double doublet of doublets, ddt: double doublet of triplets, t:
triplet, td: triplet of doublets, m: multiplet), coupling constants (J
in Hz), integration and assignment. 13C NMR spectra were recorded
on a Bruker AV-600 (150 MHz), Bruker AMX-400 (100 MHz) or
Bruker DPX-300 (75 MHz) with complete proton decoupling.
Chemical shifts are reported in ppm from tetramethylsilane with
the solvent resonance as internal standard (CDCl3: d 76.95, THF-
d8 d 67.4, 25.3, acetone-d6 d 206.0, 29.8). High-resolution mass
spectrometry was carried out on a Finnigan-Mat 95 spectrometer.
All reactions were conducted in dried glassware under an inert
atmosphere of argon. Solvent (dichloromethane) was dried over
sodium hydride and was used freshly distilled.
10
11
12
Colorless oil. Rf 0.06 (hexane:ethyl acetate, 5:1). 1H NMR
0
(300 MHz, CDCl3) d = 7.65 and 7.64 (2ꢀd, J = 8.0 Hz, 2H; H11;11 ),
0
0
7.30(d, J = 8.0 Hz, 2H; H8;8 ), 7.22 (t, J = 7.6 Hz, 2H; H10;10 ), 7.07 (t,
0
0
J = 7.6 Hz, 2H; H9;9 ), 6.91 and 6.87 (2ꢀs, 2H; H7;7 ), 4.51 (t,
0
J = 7.5 Hz, 1H; H6), 3.74 and 3.73 (2ꢀs, 6H; H12;12 ), 3.45 (dt,
J = 7.8, 5.0 Hz, 1H; H3), 2.50–2.18 (m, 2H), 1.74–1.43 (m, 3H),
0.89 and 0.88 (2ꢀd, J = 6.8 Hz, 6H; H1;1 ). 13C NMR (75 MHz, CDCl3)
0
d
= 137.2, 127.4, 127.3, 126.1, 126.1, 121.2, 119.6, 119.5, 119.0,
118.6, 118.3, 109.0, 33.8, 33.2, 33.1, 32.5, 32.5, 19.0, 16.8. HRMS
calcd. for C25H30N2O 378.2358, found 374.2359.
4.3.3. 4,4-Bis(1-methyl-1H-indol-3-yl)-1-phenylbutan-1-ol (3c)
7´
N
5´
OH
1
4.2. General procedure for the synthesis of bis(indolyl)alkanes 3
3
6´
To a colorless solution of (Ph3P)AuCl (25 mg, 0.05 mmol) in
dichloromethane (2 mL) at room temperature the corresponding
butyn-1-ol 1 (1 mmol), and the indole 2 (289 mg, 2.2 mmol) were
added. The mixture was cooled to 0 °C and AgSbF6 (17 mg,
0.05 mmol) was added. The resulting slurry was warmed to room
temperature and stirred until complete conversion (monitored by
TLC). After removing of the solvent, the crude was purified by flash
column chromatography on silica gel using hexane:ethyl acetate
2:1 as eluent to yield pure compounds 3.
4
2
5
N
6
7
Colorless oil. Rf 0.08 (hexane:ethyl acetate, 5:1). 1H NMR
0
(300 MHz, CDCl3) d = 7.64 and 7.61 (2ꢀd, J = 7.8 Hz, 2H; H6;6 ),
7.45–7.20 (m, 9H), 7.13–7.05 (m, 2H), 6.84 and 6.81 (2ꢀs, 2H;
4.3. Spectral data for bis(indolyl)alkanes 3
0
H5;5 ), 4.76 (t, J = 6.7 Hz, 1H; H4), 4.54 (t, J = 7.4 Hz, 1H; H1), 3.74
0
(s, 6H; H7;7 ), 2.48–2.33 (m, 1H), 2.31–2.16 (m, 1H), 2.08–1.85 (m,
4.3.1. 5,5-Bis(1-methyl-1H-indol-3-yl)pentan-2-ol (3a)
2H). 13C NMR (100 MHz, CDCl3) d = 144.5, 137.1, 128.2, 127.3,
126.1, 125.9, 121.1, 119.5, 118.5, 118.3, 108.9, 74.5, 37.4, 33.6,
32.5, 31.9. HRMS calcd. for C28H28N2O 408.2202, found 408.2202.
8´
7´
N
OH
2
4.3.4. 1,1-Bis(1-methyl-1H-indol-3-yl)-4-phenyloct-7-en-4-ol (3d)
6´
4
7
3
5
1
11´
10´
1
N
OH
N
6
2
9´
8
5
8
6
4
3
7
Ph
10
N
Colorless oil. Rf 0.05 (hexane:ethyl acetate, 5:1). 1H NMR
11
9
0
(300 MHz, CDCl3) d = 7.62 and 7.61 (2ꢀd, J = 7.8 Hz, 2H; H6;6 ),
0
7.29–7.02 (m, 6H), 6.86 and 6.84 (2ꢀs, 2H; H7;7 ), 4.47 (t,
Colorless oil. Rf 0.02 (hexane:ethyl acetate, 5:1). 1H NMR
0
J = 7.4 Hz, 1H; H5), 3.72–3.60 (m, 1H; H2), 3.67 (s, 6H; H8;8 ),
0
(300 MHz, CDCl3) d = 7.55 and 7.44 (2ꢀd, J = 8.0 Hz, 2H; H9;9 ),
2.37–2.16 (m, 2H; H4), 1.62–1.49 (m, 2H; H3), 1.14 (d, J = 6.1 Hz,
3H; H1). 13C NMR (75 MHz, CDCl3) d = 137.1, 126.1, 121.1, 119.5,
118.3, 109.0, 68.1, 37.9, 33.75, 32.4, 32.2, 23.3. HRMS calcd. for
C23H24N2 (MꢁH2O)+ 328.1934, found 328.1929.
7.28–7.13 (m, 7H), 7.07–6.95 (m, 3H), 6.66 and 6.63 (2ꢀs, 2H;
0
H10;10 ), 5.73 (ddt, J = 16.9, 10.7, 6.0 Hz, 1H; H7), 4.90 (d,
J = 10.7 Hz, 1H; H8cis), 4.88 (d, J = 16.9 Hz, 1H; H8trans), 4.39 (t,

J. Barluenga et al. / Journal of Organometallic Chemistry 694 (2009) 546–550
549
Colorless oil. Rf 0.01 (hexane:ethyl acetate, 5:1). 1H NMR
(400 MHz, THF-d8) d = 7.36 (d, J = 7.9 Hz, 2H; H7), 7.27 (d,
J = 7.9 Hz, 2H; H10), 7.09 (s, 2H; H6), 6.97 (t, J = 7.9 Hz, 2H; H8),
6.77 (t, J = 7.9 Hz, 2H; H9), 3.78 (s, 6H; H11), 3.47 (td, J = 6.4,
5.3 Hz, 2H; H1), 3.36 (t, J = 5.3 Hz, 1H; OH), 2.52–2.40 (m, 2H;
H3), 1.88 (s, 3H; H5), 1.49–1.36 (m, 2H; H2). 13C NMR (100 MHz,
THF-d8) d = 139.05, 128.15, 126.98, 123.76, 122.06, 121.47,
118.66, 109.75, 63.63, 39.11, 38.29, 32.68, 29.70, 28.19. HRMS
calcd. for C23H26N2O 346.2045, found 346.2043.
0
J = 7.0 Hz, 1H; H1), 3.64 and 3.62 (2ꢀs, 6H; H11;11 ), 2.04–1.90 (m,
4H), 1.89–1.70 (m, 4H). 13C NMR (75 MHz, CDCl3) d = 145.70,
138.78, 137.07, 127.93, 127.29, 127.22, 126.20, 126.09, 125.35,
121.15, 119.53, 119.44, 118.76, 118.34, 118.29, 114.31, 108.98,
108.93, 77.12, 41.95, 41.61, 33.84, 32.45, 29.79, 27.90. HRMS calcd.
for C32H34N2O 462.2666, found 462.2665.
4.3.5. 5,5-Bis(1-methyl-1H-indol-3-yl)-2-phenylpentan-2-ol (3e)
8
4.3.8. 5,5-Bis(1-methyl-1H-indol-3-yl)nonan-2-ol (3h)
7
N
6
15
13
OH
4
12
N
5
2
9
3
1
11
1
2
10
6
6´
N
7´
3
5
7
8
4
HO
8´
14
N
Colorless oil. Rf 0.18 (hexane:ethyl acetate, 5:1). 1H NMR
0
(400 MHz, CDCl3) d = 7.43 and 7.37 (2ꢀd, J = 7.9 Hz, 2H; H7;7 ),
White solid. M.p.: 177.3–178.1 °C. Rf 0.25 (hexane:ethyl acetate,
2:1). 1H NMR (300 MHz, CDCl3) d = 7.31 and 7.28 (2ꢀs, 2H; H9),
7.27–7.22 (m, 4H; H10,13), 6.97 (dd, J = 7.1, 0.9 Hz, 2H; H12), 6.66
(dd, J = 0.9, 7.1, 2H; H11), 3.80 and 3.79 (2ꢀs, 6H; NMe), 3.69–
3.58 (m, 1H; H2), 3.38 (d, J = 4.6 Hz, 1H; H14), 2.56 (ddd, J = 12.7,
4.6, 4.4 Hz, 1H; H4a), 2.40–2.29 (m, 3H; H4b,5), 1.39–1.11 (m, 6H;
H3,6,7), 1.07 (d, J = 6.1 Hz, 3H; H1), 0.83 (t, J = 7.3 Hz, 3H; H8). 13C
NMR (75 MHz, CDCl3) d = 138.75, 127.97, 127.54, 122.48, 122.44,
121.79, 121.44, 118.44, 109.86, 68.48, 41.83, 36.97, 34.74, 33.41,
32.81, 26.82, 24.13, 24.05, 14.54. HRMS calcd. for C27H34N2O
402.2680, found 402.2671.
7.30–7.03 (m, 9H), 6.96–6.97 (m, 2H), 6.57 and 6.55 (2ꢀs, 2H;
0
0
H6;6 ), 4.28 (t, J = 7.1, 1H; H5), 3.57 and 3.56 (2ꢀs, 6H; H8;8 ),
1.93–1.84 (m, 4H; H3,4), 1.41 (s, 3H; H1). 13C NMR (100 MHz, CDCl3)
d
= 147.6, 137.1, 127.9, 127.3, 127.2, 126.3, 126.1, 124.8, 121.2,
119.5, 119.4, 118.7, 118.4, 118.3, 108.9, 74.8, 42.6, 33.9, 32.5,
30.4, 30.3. HRMS calcd. for C29H30N2O 422.2353, found 422.2353.
4.3.6. 1-[3,3-Bis(1-methyl-1H-indol-3-yl)propyl]cyclohexanol (3f)
10
6
N
4.3.9. 5,5-Bis(1-methyl-1H-indol-3-yl)-7-phenylheptan-2-ol (3i)
5
7
3
8
OH
1
4
9
N
10
2
OH
17
N
9
6
4
2
8
5
7
3
1
12
Colorless oil. Rf 0.17 (hexane:ethyl acetate, 5:1). 1H NMR
(300 MHz, CDCl3) d = 7.54 (d, J = 7.9 Hz, 2H; H6), 7.18 (d,
J = 7.9 Hz, 2H; H9), 7.11 (t, J = 7.9 Hz, 2H; H7), 6.97 (t, J = 7.9 Hz,
2H; H8), 6.78 (s, 2H; H5), 4.35 (t, J = 7.6 Hz, 1H; H4), 3.61 (s, 6H;
H10), 2.21 (td, J = 7.8, 7.6 Hz, 2H; H3), 1.54–1.31 (m, 10H), 0.84–
0.77(m 2H). 13C NMR (75 MHz, CDCl3) d = 137.1, 127.4, 126.1,
121.2, 119.5, 118.9, 118.3, 108.9, 71.4, 41.1, 37.3, 34.2, 32.5, 29.5,
25.7, 22.1. HRMS calcd. for C27H32N2O 400.2515, found 400.2517.
11
13
N
14
16
15
White solid. M.p.: 167.8–168.2 °C. Rf 0.20 (hexane:ethyl acetate,
2:1). 1H NMR (300 MHz, acetone-d6) d = 7.34 (s, 2H; H11), 7.28 (d,
J = 8.0 Hz, 2H; H15), 7.24 (d, J = 8.0 Hz, 2H; H12), 7.20 (d,
J = 7.4 Hz, 2H; H9), 7.11 (t, J = 7.4 Hz, 1H; H10), 7.02 (d, J = 7.4 Hz,
2H; H8), 6.98 (t, J = 8.0 Hz, 2H; H14), 6.67 (t, J = 8.0 Hz, 2H; H13),
3.74 (s, 6H; H16), 3.66 (sextet, J = 6.1 Hz, 1H; H2), 3.37 (d,
J = 4.8 Hz, 1H; H17), 2.68–2.58 (m, 3 H; H4a,6), 2.47–2.34 (m, 3H;
H4b,7), 1.42–1.31 (m, 1H; H3a), 1.30–1.20 (m, 1H; H3b), 1.07 (d,
J = 6.1 Hz, 3H; H1). 13C NMR (75 MHz, acetone-d6) d = 144.6,
139.0, 129.5, 129.3, 128.1, 127.9, 126.5, 122.3, 122.2, 122.0,
121.8, 118.9, 110.2, 68.7, 42.3, 40.2, 35.0, 33.5, 33.1, 31.7, 24.5,
14.6. HRMS calcd. for C31H34N2O 450.2672, found 450.2671.
4.3.7. 4,4-Bis(1-methyl-1H-indol-3-yl)pentan-1-ol (3g)
11
10
9
N
6
8
HO
1
7
5
Acknowledgments
2
4
3
We gratefully acknowledge financial support from the DGICYT
(CTQ2004-08077-C02-01/BQU and CTQ2007-61048/BQU) and
MEC (‘‘Ramón y Cajal” contract to F.R.).
N

550
J. Barluenga et al. / Journal of Organometallic Chemistry 694 (2009) 546–550
(f) A. Khalafi-Nezhad, A. Parhami, A. Zare, A.R.M. Zare, A. Hasaninejad, F. Panahi,
References
Synthesis (2008) 617.
[5] C. Ferrer, C.H.M. Amijs, A.M. Echavarren, Chem. Eur. J. 13 (2007) 1358.
[6] S. Bhuvaneswari, M. Jeganmohan, C.-H. Cheng, Chem. Eur. J. 13 (2007) 8285.
[7] (a) J. Barluenga, A. Fernández, A. Satrústegui, A. Diéguez, F. Rodríguez, F.J.
Fañanás, Chem. Eur. J. 14 (2008) 4153;
(b) J. Barluenga, A. Diéguez, A. Fernández, F. Rodríguez, F.J. Fañanás, Angew.
Chem., Int. Ed. 45 (2006) 2091.
[8] The gold-catalyzed double addition of furan derivatives to unactivated terminal
alkynes also occurs at the internal carbon of the triple bond. See: A.S.K. Hashmi,
M.C. Blanco, Eur. J. Org. Chem. (2006) 4340.
[1] (a) R.J. Sundberg, The Chemistry of Indoles, Academic Press, New York, 1996;
(b) . For some recent reviews, see:S. Patil, J.K. Buolamwini, Curr. Org. Synth. 3
(2006) 477;
(c) S. O’Connor, J.J. Maresh, Nat. Prod. Rep. 23 (2006) 532;
(d) M. Somei, F. Yamada, Nat. Prod. Rep. 22 (2005) 73.
[2] M. Chakrabarty, R. Basak, Y. Harigaya, Heterocycles 55 (2001) 2431.
[3] (a) A. McDougal, M.S. Gupta, K. Ramamoorthy, G. Sun, S.F. Safe, Cancer Lett. 151
(2000) 169;
(b) C. Hong, G.L. Firestone, L.F. Bjeldanes, Biochem. Pharmacol. 63 (2002) 1085;
(c) S.H. Benabadji, R. Wen, J. Zheng, X. Dong, S. Yuan, Acta Pharmacol. Sin. 25
(2004) 666.
[9] (a) For some recent reviews on gold catalysis see: H.C. Shen, Tetrahedron 64
(2008) 3885;
(b) D.J. Gorin, D. Toste, Nature 446 (2007) 395;
[4] (a) For some representative recent examples see: Z.-H. Zhang, L. Yin, Y.-M.
Wang, Synthesis (2005) 1949;
(c) A. Fürstner, P.W. Davies, Angew. Chem., Int. Ed. 46 (2007) 3410;
(d) E. Jiménez-Núñez, A.M. Echavarren, Chem. Commun. (2007) 333;
(e) A.S.K. Hashmi, Chem. Rev. 107 (2007) 3180;;
(f) L. Zhang, J. Sun, S.A. Kozmin, Adv. Synth. Catal. 348 (2006) 2271;
(g) A.S.K. Hashmi, G.J. Hutchings, Angew. Chem., Int. Ed. 45 (2006) 7896;;
(h) R.A. Widenhoefer, X. Han, Eur. J. Chem. (2006) 4555;
(i) A. Hoffmann-Röder, N. Krause, Org. Biomol. Chem. 3 (2005) 387;
(j) A.S.K. Hashmi, Gold Bull. 37 (2004) 51.
(b) R. Murugan, M. Karthikeyan, P.T. Perumal, B.S.R. Reddy, Tetrahedron 61
(2005) 12275;
(c) M. Chakrabarty, A. Mukherji, S. Karmakar, S. Arima, Y. Harigaya,
Heterocycles 68 (2006) 331;
(d) M.L. Deb, P.J. Bhuyan, Tetrahedron Lett. 47 (2006) 1441;
(e) B.-S. Liao, J.-T. Chen, S.-T. Liu, Synthesis (2007) 3125;