PtCl2-catalyzed reactions of o-alkynylanilines with ethyl propiolate and dimethyl acetylenedicarboxylate

Article abstract of DOI:10.1016/j.tet.2008.11.095

The PtCl₂-catalyzed reactions between indoles and ethyl propiolate gave rise to mono and double addition products. The composition of the products was largely influenced by the substituents on the indoles as well as the amount of ethyl propiolate used. o-Alkynylanilines reacted with ethyl propiolate and dimethyl acetylenedicarboxylate under the catalysis of PtCl₂ to generate the corresponding 2,3-disubstituted indoles. The reaction proceeded by following a sequential cyclization/intermolecular addition pathway.

Full text of DOI:10.1016/j.tet.2008.11.095

Tetrahedron 65 (2009) 1140–1146
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Tetrahedron
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PtCl2-catalyzed reactions of o-alkynylanilines with ethyl propiolate and
dimethyl acetylenedicarboxylate
*
Xun Li, Jun-Yan Wang, Wei Yu , Long-Min Wu
State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou, Gansu 730000, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 28 May 2008
Received in revised form 10 November 2008
Accepted 26 November 2008
Available online 3 December 2008
The PtCl2-catalyzed reactions between indoles and ethyl propiolate gave rise to mono and double ad-
dition products. The composition of the products was largely influenced by the substituents on the in-
doles as well as the amount of ethyl propiolate used. o-Alkynylanilines reacted with ethyl propiolate and
dimethyl acetylenedicarboxylate under the catalysis of PtCl2 to generate the corresponding 2,3-di-
substituted indoles. The reaction proceeded by following a sequential cyclization/intermolecular addition
pathway.
Keywords:
Indoles
Ó 2008 Elsevier Ltd. All rights reserved.
o-Alkynylanilines
PtCl2
Ethyl propiolate
1. Introduction
employing platinum as catalyst. These studies demonstrate that
a variety of substituted indoles could be accessed though the re-
The indole ring system exists ubiquitously in nature-occurring
products, and many indole-containing compounds exhibit impor-
tant biological and pharmaceutical activities.1 The synthesis of in-
doles has, therefore, been a major area of focus for synthetic organic
chemists over the years.2 Among diverse synthetic strategies to-
ward indoles, the transitional-metal and Lewis acid-catalyzed
functionalization of simple indoles constitutes an atom-economical
and high efficient approach.3 As transitional-metal salts could also
catalyze the cyclization of o-alkynylanilines to indoles,2,4 it is pos-
sible to synthesize muti-substituted indoles through sequential
cyclization/alkylation reactions using substituted o-alkynylanilines
as starting materials. Procedures employing copper, zinc, palla-
dium, platinum, and gold as catalyst have been developed recently
to achieve the goal.5
The addition of electron-rich arenes and heteroarenes to C–C
triple bonds has received much attention recently.6 Gold and
platinum are particularly effective to promote these trans-
formations due to their pronounced alkynophilicity.7 The use of
gold and platinum salts enables these reactions to proceed under
mild conditions with high selectivity.6b,c,8,9 Echavarren et al. re-
cently reported a systematic investigation on the gold-catalyzed
intra and intermolecular addition of indoles to alkynes.10 Cheng
et al.11 investigated the reactions of indoles with alkynyl alcohols
actions of indoles with alkynes.
The gold and platinum-catalyzed reactions of indoles with
electron-poor alkynes such as ethyl propiolate, on the other hand,
are far less explored. One research concerning this issue was con-
ducted by He et al.9b The authors found that the reaction of
N-methyl indole with ethyl propiolate in the presence of AuCl3 led
only to the formation of double addition product (Scheme 1).
N
5% mol AuCl3
CH3CN, r.t
CO2Et
+
CO2Et
N
N
Scheme 1.
Similar results were reported by Fujiwara et al., who employed
Pd(OAc)2 in acetic acid to catalyze the similar transformations.12
Recently, we reexamined the reactions of indoles with ethyl
propiolate using PtCl2 as catalyst. We found that the composition
of the products was largely influenced by the substituents on the
indoles. Furthermore, we extended the reactions to using
o-alkynylanilines as starting materials, which reacted with ethyl
priopiolate and dimethyl acetylenedicarboxylate to give the cor-
responding 2,3-disubstituted indoles. Herein we wish to report
our results.
* Corresponding author. Tel.: þ86 931 8912500; fax: þ86 931 8915557.
E-mail address: yuwei@lzu.edu.cn (W. Yu).
0040-4020/$ – see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.11.095

X. Li et al. / Tetrahedron 65 (2009) 1140–1146
1141
Table 1
PtCl2-catalyzed reactions of indoles with ethyl propiolate (2a)a
Entry
Indole
2a
Reaction time (h)
Products
Yieldb (%)
57 (1a)
H
N
6 (Z-3a)
7 (E-3a)
22 (4a)
1
2
1.2 equiv
3 equiv
40
40
CO2Et
CO2Et
11 (Z-3a)
46 (E-3a)
42 (4a)
N
3a
4a
N
H
H
1a
N
H
N
CO2Et
3
4
1.2 equiv
3 equiv
40
20
53 (4b)
9 (Z-3b)
40 (E-3b)
20 (4b)
CO2Et
N
3b
4b
1b
N
N
28 (3c)
65 (1c)
71 (3c)
CO2Et
5
6
1.2 equiv
3 equiv
63
50
Ph
N
H
Ph
3c
N
1c
H
a
The reactions were carried out in THF at refluxing temperature. PtCl2 (10 mol %) was used as catalyst.
Isolated yields.
b
2. Results and discussion
It is noteworthy that in all the cases summarized in Table 1, the
mono addition products were obtained with the preference for
E-configuration. In the case of 1c, the only isomer that could be
isolated from the reaction mixture was E-3c. This result is in con-
trast to those observed previously for the reactions of electron-rich
arenes with ethyl propiolate, in which Z-selectivity was generally
observed.6a,8,9 We speculated that this E-stereoselectivity might be
caused by the ready isomerization of Z-3 to E-3 under our reaction
conditions. To support this hypothesis, Z-3a was subjected to the
reaction conditions mentioned above to see if the isomerization
could take place. As expected, after 30 h, Z-3a was converted nearly
completely to E-3a. This process must have been very fast in the
case of Z-3c, where the presence of a phenyl group at the 2-position
of the indole ring would cause a strong steric repulsion, and
therefore, only the thermodynamically favored E-3c was obtained.
Similar preference for E-configuration was observed in the
Pd(OAc)2/TFA-catalyzed reactions of mesitylene with 3-butyn-2-
one,6a and the gold-catalyzed hydroarylation of 3-butyne-2-one.8
The cyclization of o-alkynylanilines to indoles can be readily
catalyzed by platinum and gold salts.7d,e Recently, Arcadi et al.
reported that NaAuCl4$2H2O could effect the reactions of o-alky-
The reactions of indoles (1) with ethyl propiolate (2a) were
carried out in the presence of 10 mol % PtCl2. The best results were
obtained when THF was used as solvent at refluxing temperature
(Table 1). Unsubstituted indole (1a) reacted with ethyl propiolate,
forming both the mono addition product 3a and the double addi-
tion product 4a (Table 1, entries 1 and 2). The conversion was low
when only 1.2 equiv of ethyl propiolate was used, with the majority
of 1a recovered. Using 3 equiv of ethyl propiolate raised the yields
of both 4a and 3a. The yields of the products were much lower
when the reactions were performed in other solvents (Table 2). The
reaction did not proceed when AuCl3 was used as catalyst. In the
case of N-methyl indole (1b), only double addition product (4b) was
obtained when 1.2 equiv of ethyl propiolate was used (Table 1, entry
3). This result was consistent with those observed by He et al.9b
When the usage of ethyl propiolate was raised to 3 equiv, the mono
addition products 3b were also obtained beside 4b (Table 1, entry
4). On the other hand, the reaction of 2-phenyl indole (1c) with
ethyl propiolate only gave rise to mono addition product 3c
whatever the amount of ethyl propiolate used (Table 1, entries 5
and 6). These results indicate that the substituents on indoles have
profound effect on the consequence of the reactions between in-
doles and electron-deficient alkynes.
nylanilines with a,b-enones, and the reactions took place by fol-
lowing a sequential cyclization/Michael type addition pathway.5d
On the other hand, Li et al. found that AuCl3/AgOTf-catalyzed re-
actions between o-alkynylanilines and arylacetylenes under neat
conditions led to the formation of N-vinylindoles via a different
mechanism, in which the hydroamination of anilines with aryla-
cetylenes took place prior to the cyclization.5g It was of our interest
to see, which type of products might form if o-alkynylanilines were
allowed to react with ethyl propiolate.
Table 2
The reactions of 1a with ethyl propiolate (2a) in other solventsa
Entry Solvent
2a
Reaction Products and yieldsb (%)
time (h)
1
2
3
4
5
6
ClCH2CH2Clc 1.2 equiv 40
40 (1a), 6 (Z-3a), 5 (E-3a), 36 (4a)
2 (1a), 15 (Z-3a), 23 (E-3a), 45 (4a)
48 (1a), 1 (Z-3a), 3 (E-3a), 22 (4a)
4 (1a), 4 (Z-3a), 14 (E-3a), 40 (4a)
37 (1a), trace (Z-3a), 3 (E-3a) 38 (4a)
6 (Z-3a), 14 (E-3a), 55 (4a)
ClCH2CH2Clc 3 equiv
40
1.2 equiv 40
3 equiv 40
1.2 equiv 40
3 equiv 40
Subsequently, several different substituted o-alkynylanilines (5)
were treated with 3 equiv of ethyl propiolate (2a) in the presence of
10 mol % of PtCl2 in THF at refluxing temperature, and the results
are listed in Table 3. Under the reaction conditions, 2-ethy-
nylbenzenamine (5a) was transformed to indole 1a in good yield
(entry 1), while the intermolecular addition products 3a and 4a
formed in only trace amount. Using 20 mol % of PtCl2 did not im-
prove the yields of 3a and 4a significantly. When 5b was used as the
substrate, the products were complex mixtures (entry 2). On the
CH3CNc
CH3CNc
d
PhCH3
d
PhCH3
a
The reactions were performed on a 0.2 mmol scale with 10 mol % of PtCl2 as
catalyst.
b
The yields were determined by GC and GC–MS.
The reaction was performed at refluxing temperature.
The reaction was performed at 80 ꢀC.
c
d

1142
X. Li et al. / Tetrahedron 65 (2009) 1140–1146
Table 3
Reactions of 2-o-alkynylanilines (5) with electron-deficient alkynes (2)
Entry
1
5
2
Reaction time (h)
40
Productsa
Yieldb (%)
78
2a
N
H
NH2
1a
5a
TMS
2
2a
40
Complex mixtures
NH2
5b
CO2Et
69 (3c)
14 (1c)
Ph
N
3c
Ph
H
3
2a
24
NH2
5c
Ph
N
1c
H
CO2Et
53 (3d)
34 (1d)
Ph
N
H
Ph
3d
4
2a
36
NH2
5d
Ph
N
H
1d
Ph
Cl
Cl
Ph
5
6
2a
2a
36
30
85
75
N
H
NH2
1e
5e
Ph
O2N
O2N
Ph
N
H
NH2
1f
5f
CO2Et
7
2a
14
78
NH2
5g
N
H
3g
CO2Et
56 (3h)
N
H
8
2a
20
NH2
5h
3h
27 (1h)
N
H
1h

X. Li et al. / Tetrahedron 65 (2009) 1140–1146
1143
Table 3 (continued )
Entry
5
2
Reaction time (h)
Productsa
Yieldb (%)
CO2Et
59 (3i)
Cl
Cl
9
2a
40
N
H
NH2
3i
5i
Cl
31 (1i)
N
H
1i
O2N
O2N
10
11
2a
2b
40
40
75
N
H
NH2
1j
5j
MeO2C
CO2Me
Ph
56 (6e)
36 (1e)
Cl
Ph
Cl
N
H
6e
NH2
5e
Cl
Ph
N
H
1e
MeO2C
CO2Me
12
2b
20
85
NH2
N
H
5g
6g
MeO2C
CO2Me
40 (6h)
57 (7h)
N
H
6h
13
2b
36
NH2
5h
N
7h
CO2Me
MeO2C
MeO2C
CO2Me
45 (6i)
Cl
Cl
Cl
14
2b
36
N
H
NH2
6i
5i
49 (1i)
N
H
1i
O2N
O2N
15
2b
40
76
N
NH2
H
1j
5j
a
The products were identified by 1H NMR, 13C NMR, EIMS, and HRMS.
Isolated yields.
b

1144
X. Li et al. / Tetrahedron 65 (2009) 1140–1146
other hand, when 5c and 5d were subject to the condition, 3c and 3d
were generated, respectively, as the major products (entries 3 and
4), along with the cyclization product 1c and 1d. Similarly, 2-hex-1-
nyl benzenamines 5g–5i were transformed to the corresponding
3g–3i by reacting with ethyl propiolate. These results suggest that
the reactions between o-alkynylanilines and ethyl propiolate follow
a cyclization/addition reaction pathway, similar to the reactions of
were obtained, indicating that the electron-withdrawing groups at
the phenyl ring would hinder the addition to ethyl propiolate, but
wouldn’t affect the cyclization to indoles.
To further explore the scope of the protocols, the reactions of 5
with dimethyl acetylenedicarboxylate (2b) were examined. The
results were also summarized in Table 3. As expected, the sub-
strates were transformed to the corresponding 2,3-disubstituted
indoles in moderate to good yields except for 5j. In the case of 5h
(entry 13), beside the normal product 6h, N-substituted product 7h
was also generated.
Attempts were also made to realize the tandem reactions be-
tween o-alkynylanilines and electron-rich alkynes such as phe-
nylacetylene and 1-hexyne. However, only cyclization products
were produced (Scheme 3). The intermolecular addition did not
took place, despite that the reactions of indoles with terminal al-
kynes could be effected by the action of PtCl2.11
o-alkynylanilines with a,b
-enones.5d As indicated in Table 3, the
reactions proceeded with high stereoselectivity, with only the E-
isomers obtained after reaction finished. Based on the previously
reported mechanistic studies dealing with the gold and platinum-
catalyzed hydroarylation of alkynes and alkenes, a reaction mech-
anism as depicted in Scheme 2 was proposed to rationalize the
formation of products 3. The first step should involve the intra-
molecular attack of the amino group on the PtCl2-activated carbon–
carbon triple bond in 5, leading to the formation of intermediate 7.
Compound 7 was converted to 8 by a rapid proton–platinum ex-
change, and the latter then attacked platinum-complexed ethyl
propiolate to give 9. Finally, 9 was protonated to generate 3. It is
generally believed that in the hydroarylation of alkynes under gold
catalysis, the arenes attack the triple bond from the opposite side of
the coordinated gold, leading to the formation of Z-olefins. The
E-selectivity observed under certain circumstances is due to the
isomerization of the initially produced Z-isomer.7h,8 Considering
the similarities on the catalytic behavior between platinum and
gold, we think that the same pattern also works in PtCl2-catalzyed
reactions, and it is probable that the protonation of 9 would first give
rise to sterically demanding Z-3, which then rapidly isomerized to
the thermodynamically more stable E-3. As mentioned above, our
experiments showed that the isomerization from Z-3a to E-3a could
proceed under the reaction conditions, lending support to the
assumption. However, it is also possible that E-3 could be generated
directly from 9. Further theoretical work needs to be done to elu-
cidate this issue.
R
PtCl2
THF, reflux
+
R
R
NH2
N
H
R = phenyl, n-butyl
Scheme 3.
3. Conclusion
In summary, we found that the PtCl2-catalyzed addition of in-
doles to ethyl propiolate led to the formation of both mono addition
and double addition products. The composition of the products was
largely affected by the substituents on the indoles as well as the
amount of ethyl propiolate used. PtCl2 could effectively catalyze the
tandem cyclization/intermolecular addition reactions of o-alkynyl-
anilines with electron-poor alkynes such as ethyl propiolate and
dimethyl acetylenedicarboxylate, and the protocol provides a con-
venient approach for the synthesis of 2,3-disubstituted indoles.
PtCl2
R'
H
H
R
4. Experimental
4.1. General
N
H
7
PtCl2
1H and 13C NMR spectra (300 and 75.5 MHz, respectively) were
recorded on a Varian Mercury Plus-300 spectrometer with TMS as
the internal standard in CDCl3. EIMS spectra were measured on an
HP 5988A spectrometer by direct inlet at 70 eV. The high resolution
mass spectra (HRMS) were measured on a Bruker Daltonics APEX II
47e spectrometer by ESI.
H
PtCl2
R'
R'
R
R
N
NH2
H
8
General procedure for the reactions between 5 and ethyl pro-
piolate (or dimethyl but-2-yne dioate): 0.2 mmol of 5, 0.6 mmol of
ethyl propiolate (or dimethyl but-2-yne dioate), and 5 mg PtCl2
(10 mol %) were added into 1 mL anhydrous THF. The mixture was
stirred at refluxing temperature under argon atmosphere. After the
reaction finished as indicated by TLC analysis, the solvent was re-
moved at reduced temperature. The residual was treated with silica
gel chromatography to give the products.
PtCl2
PtCl2
CO2Et
5
H
R'
R
R'
CO2Et
H
+
N
H
R
PtCl2
CO2Et
N
Z-3
9
H
4.2. Spectroscopic data of the products
E-3
Scheme 2.
For the intermolecular addition to take place, an attachment of
CO2Et
alkyl group or aryl group to the carbon–carbon triple bond would
be necessary, probably by enhancing the nucleophilicity at the
3-position of indoles. The sensitivity to substituents in the addition
step was further demonstrated in the results with 5e, 5f, and 5j
(entries 5, 6, and 10). In these cases, only the cyclization products
N
Z-3a
H
1H NMR (CDCl3, 300 MHz,
7.75 (d, 1H, J¼6.0 Hz), 7.43–7.40 (m, 1H), 7.32–7.23 (m, 3H), 5.83 (d,
d ppm): 8.91 (s, 1H), 8.61 (br s, 1H),

X. Li et al. / Tetrahedron 65 (2009) 1140–1146
1145
1H, J¼12.3 Hz), 4.24 (q, 2H, J¼7.2 Hz),1.35 (t, 3H, J¼7.2 Hz). EIMS m/z
(rel int., %): 291 (Mþ, 17), 218 (44), 143 (48), 84 (100). HRMS (ESI):
calcd for C19H17O2NþH: 292.1332; found: 292.1328.
(rel int., %): 215 (Mþ, 100), 170 (90), 143 (71), 115 (43).13
CO2Et
CO2Et
Ph
3d
E-3a
N
N
H
H
1H NMR (CDCl3, 300 MHz,
d
ppm): 8.47 (br s, 1H), 7.95–7.80 (m,
1H NMR (CDCl3, 300 MHz,
d ppm): 8.35 (br s, 1H), 7.99 (d, 1H,
2H), 7.50 (d, 1H, J¼3.0 Hz), 7.42 (m, 1H), 7.31–7.27 (m, 2H), 6.47 (d,
1H, J¼15.9 Hz), 4.28 (q, 2H, J¼7.2 Hz),1.33 (t, 3H, J¼6.9 Hz). EIMS m/z
(rel int., %): 215 (Mþ, 90), 170 (100), 143 (81), 115 (59).13
J¼16.5 Hz), 7.79 (s, 1H), 7.58–7.46 (m, 5H), 7.32 (d, 1H, J¼8.1 Hz),
7.12 (d, 1H, J¼8.1 Hz), 6.58 (d, 1H, J¼15.9 Hz), 4.26 (q, 2H, J¼7.2 Hz),
2.52 (s, 3H), 1.34 (t, 3H, J¼7.2 Hz); 13C NMR (CDCl3, 75 MHz,
d ppm):
14.4, 21.7, 60.0, 109.5, 111.0, 113.9, 120.7, 124.9, 126.8, 128.9, 129.0,
129.1, 131.2, 131.4, 134.6, 138.8, 142.4, 168.5. EIMS m/z (rel int., %):
305 (Mþ, 45), 260 (17), 232 (100), 217 (58), 115 (21). HRMS (ESI):
calcd for C29H19O2NþH: 306.1489; found: 306.1496.
H
N
CO2Et
4a
CO2Et
N
H
1H NMR (CDCl3, 300 MHz,
d ppm): 7.94 (br s, 2H), 7.59 (d, 2H,
N
H
3g
J¼8.4 Hz), 7.34 (d, 2H, J¼8.4 Hz), 7.16 (t, 2H, J¼7.5 Hz), 7.07–7.01 (m,
4H), 5.12 (d, 1H, J¼7.5 Hz), 4.03 (q, 2H, J¼6.9 Hz), 3.19 (d, 2H, J¼7.
5 Hz), 1.10 (t, 3H, J¼6.9 Hz). EIMS m/z (rel int., %): 332 (Mþ, 3), 245
(15), 215 (34), 170 (39), 115 (41).14
1H NMR (CDCl3, 300 MHz,
d ppm): 8.50 (br s, 1H), 7.96 (d, 1H,
J¼15.9 Hz), 7.88 (m, 1H), 7.32 (m, 1H), 7.23–7.19 (m, 2H), 6.45 (d, 1H,
J¼15.9 Hz), 4.28 (q, 2H, J¼7.2 Hz), 2.87 (t, 2H, J¼7.5 Hz), 1.684–1.635
(m, 2H), 1.43–1.30 (m, 5H), 0.92 (t, 3H, J¼7.2 Hz); 13C NMR (CDCl3,
CO2Et
75 MHz,
d ppm): 13.8, 14.5, 22.4, 26.1, 31.8, 60.0, 109.2, 110.9, 112.0,
120.2, 121.3,122.4, 126.2, 135.7, 137.5, 144.8,168.8. EIMS m/z (rel int.,
%): 271 (Mþ, 38), 196 (20), 183 (44), 168 (45), 154 (100). HRMS (ESI):
calcd for C17H21O2NþH: 272.1645; found: 272.1646.
N
Z-3b
1H NMR (CDCl3, 300 MHz,
d ppm): 8.80 (br s, 1H), 7.74 (d, 1H,
J¼7.5 Hz), 7.34–7.23 (m, 4H), 5.76 (d, 1H, J¼12.3 Hz), 4.22 (q, 2H,
J¼6.9 Hz), 3.86 (s, 3H), 1.34 (t, 3H, J¼6.9 Hz). EIMS m/z (rel int., %):
229 (Mþ, 93), 184 (86), 157 (100), 115 (37).
CO2Et
N
CO2Et
3h
H
1H NMR (CDCl3, 300 MHz,
d ppm): 8.3 (br s, 1H), 7.9 (d, 1H,
E-3b
J¼15.9 Hz), 7.7 (s, 1H), 7.2 (d, 1H, J¼8.1 Hz), 7.02 (d, 1H, J¼7.9 Hz),
6.43 (d, 1H, J¼15.9 Hz), 4.29 (q, 2H, J¼6.9 Hz), 2.87 (t, 2H,
J¼7.8 Hz), 2.48 (s, 3H), 1.66 (m, 2H), 1.43–1.30 (m, 5H), 0.93 (t, 3H,
N
1H NMR (CDCl3, 300 MHz,
d ppm): 7.90 (m, 2H), 7.35–7.28 (m,
J¼6.9 Hz). 13C NMR (CDCl3, 75 MHz,
d ppm): 13.8, 14.5, 21.6, 22.4,
4H), 6.41 (d, 1H, J¼16.5 Hz), 4.27 (q, 2H, J¼6.9 Hz), 3.82 (s, 3H), 1.35
(t, 3H, J¼6.9 Hz). EIMS m/z (rel int., %): 229 (Mþ, 95), 184 (77), 157
(100), 115 (37).15
26.1, 31.9, 60.0, 108.8, 110.5, 111.6, 120.2, 123.8, 126.5, 130.8, 133.9,
137.7, 144.9, 168.8. EIMS m/z (rel int., %): 285 (Mþ, 71), 240 (24), 198
(42), 182 (52), 168 (100). HRMS (ESI): calcd for C18H23O2NþH:
286.1802; found: 286.1798.
N
CO2Et
CO2Et
Cl
N
4b
N
3i
H
1H NMR (CDCl3, 300 MHz,
d
ppm): 7.62 (d, 2H, J¼8.1 Hz), 7.29 (d,
1H NMR (CDCl3, 300 MHz,
d ppm): 8.4 (br s, 1H), 7.89 (d, 1H,
2H, J¼8.1 Hz), 7.21 (t, 2H, J¼7.2 Hz), 7.06 (t, 2H, J¼7.2 Hz), 6.88 (s,
2H), 5.13 (t,1H, J¼7.5 Hz), 4.04 (q, 2H, J¼6.9 Hz), 3.71 (s, 6H), 3.18 (d,
2H, J¼7.5 Hz), 1.12 (t, 3H, J¼7.2 Hz). EIMS m/z (rel int., %): 360 (Mþ,
5), 273 (35), 229 (87), 184 (80), 157 (100).9b
J¼15.9 Hz), 7.84 (s, 1H), 7.25 (d, 1H, J¼9.0 Hz), 7.16 (d, 1H, J¼9.0 Hz),
6.38 (d, 1H, J¼15.9 Hz), 4.29 (q, 2H, J¼7.2 Hz), 2.87 (t, 2H, J¼7.5 Hz),
1.67 (m, 2H), 1.42–1.32 (m, 5H), 0.93 (t, 3H, J¼7.2 Hz); 13C NMR
(CDCl3, 75 MHz, d ppm): 13.8, 14.4, 22.4, 26.1, 31.7, 60.2, 108.9, 111.8,
112.6, 119.8, 122.6, 127.1, 127.3, 134.0, 136.8, 145.8, 168.6. EIMS m/z
(rel int., %): 305 (Mþ, 73), 260 (33), 188 (70), 167 (63), 154 (100).
HRMS (ESI): calcd for C17H20O2NClþH: 306.1255; found: 306.1248.
CO2Et
Ph
3c
H
N
CO2Me
MeO2C
1H NMR (CDCl3, 300 MHz,
d ppm): 8.58 (br s, 1H), 8.03–7.98 (m,
N
H
6g
2H), 7.56–7.41 (m, 6H), 7.32–7.27 (m, 2H), 6.59 (d, 1H, J¼15.9 Hz),
4.24 (q, 2H, J¼7.2 Hz), 1.32 (t, 3H, J¼7.2 Hz); 13C NMR (CDCl3,
75 MHz,
d
ppm): 14.4, 60.1, 109.7, 111.5, 114.0, 120.8, 121.6, 123.3,
1H NMR (CDCl3, 300 MHz,
2H), 7.11–7.04 (m, 3H), 3.77 (s, 3H), 3.57 (s, 3H), 2.54 (t, 2H,
d ppm): 8.21 (br s, 1H), 7.25–7.21 (m,
126.5, 128.3, 128.9, 129.1, 131.2, 136.4, 138.7, 142.4, 168.6. EIMS m/z

1146
X. Li et al. / Tetrahedron 65 (2009) 1140–1146
J¼7.5 Hz), 1.55 (m, 2H), 1.30 (m, 2H), 0.87 (t, 3H, J¼7.5 Hz). 13C NMR
(dd, 1H, J1¼1.8 Hz, J2¼8.7 Hz), 3.58 (s, 3H), 3.48 (s, 3H); 13C NMR
(CDCl3, 75 MHz,
d
ppm): 13.7, 22.3, 26.7, 30.9, 51.7, 52.7, 106.2, 110.6,
(CDCl3, 75 MHz, d ppm): 51.9, 52.7, 106.8, 112.3, 118.5, 122.9, 126.2,
118.5, 119.9, 121.4, 127.8, 128.2, 134.9, 138.4, 139.1, 165.8, 167.8. EIMS
m/z (rel int., %): 315 (Mþ, 100), 256 (38), 241 (33), 154 (92). HRMS
(ESI): calcd for C18H21O4NþH: 316.1543; found: 316.1546.
127.2, 128.4, 128.9, 129.0, 129.4, 131.9, 134.1, 138.1,138.5, 165.7,167.2.
EIMS m/z (rel int., %): 369 (Mþ, 20), 309 (29), 278 (47), 59 (100).
HRMS (ESI): calcd for C20H16O4NClþNa: 392.0660; found:
392.0651.
CO2Me
MeO2C
N
H
Acknowledgements
6h
1H NMR (CDCl3, 300 MHz,
d ppm): 7.99 (br s, 1H), 7.17 (d, 1H,
We thank the National Natural Science Foundation of China (No.
20772053) and Natural Science Foundation of Gansu Province (No.
3ZS061-A25-004) for financial support.
J¼8.4 Hz), 7.10 (s, 1H), 7.00 (s, 1H), 6.94 (d, 1H, J¼8.1 Hz), 3.78 (s,
3H), 3.57 (s, 3H), 2.60 (t, 2H, J¼7.5 Hz), 2.39 (s, 3H),1.60 (m, 2H),1.33
(m, 2H), 0.89 (t, 3H, J¼7.5 Hz). 13C NMR (CDCl3, 75 MHz,
d ppm):
13.8, 21.5, 22.3, 26.7, 30.9, 51.7, 52.8, 105.9, 110.2, 118.3, 122.9, 128.0,
128.1, 129.2, 133.2, 138.5, 139.0, 165.8, 167.9. EIMS m/z (rel int., %):
329 (Mþ, 45), 287 (48), 228 (50), 168 (65). HRMS (ESI): calcd for
C19H23O4NþH: 330.1700; found: 330.1702.
References and notes
1. Sundberg, R. J. Indoles; Academic: London, 1996.
2. For reviews on synthesis of indoles, see: (a) Gribble, G. W. In Comprehensive
Heterocyclic Chemistry II; Katritzky, A. R., Rees, C. W., Scriven, E. F. V., Eds.;
Pergamon: Oxford, UK, 1996; Vol. 2, p 207; (b) Bandini, M.; Melloni, A.; Tom-
masi, S.; Umani-Ronchi, A. Synlett 2005, 1199; (c) Humphrey, G. R.; Kuethe, J. T.
Chem. Rev. 2006, 106, 2875.
3. For recent examples, see: (a) Lane, B. S.; Sames, D. Org. Lett. 2004, 6, 2897; (b)
Reddy, A. V.; Ravinder, T.; Goud, T. V.; Krishnaiah, P.; Raju, T. V.; Venkateswarlu, Y.
Tetrahedron Lett. 2003, 44, 6257; (c) Wang, Y.-Q.; Song, J.; Hong, R.; Li, H.;
Deng, L. J. Am. Chem. Soc. 2006, 128, 8156; (d) Sakai, N.; Annaka, K.; Kona-
kahara, T. Tetrahedron Lett. 2006, 47, 631; (e) Liu, C.; Bender, C. F.; Han, X.;
Widenhoefer, R. A. Chem. Commun. 2007, 3607.
N
7h
MeO2C
CO2Me
1H NMR (CDCl3, 300 MHz,
d ppm): 7.30 (s, 1H), 7.28 (s, 1H), 6.92
(d, 1H, J¼8.4 Hz), 6.84 (d, 1H, J¼8.1 Hz), 6.31 (s, 1H), 3.78 (s, 3H),
3.52 (s, 3H), 2.50 (t, 2H, J¼7.5 Hz), 2.40 (s, 3H), 1.66 (m, 2H), 1.38 (m,
2H), 0.91 (t, 3H, J¼7.5 Hz); 13C NMR (CDCl3, 75 MHz,
d ppm): 13.8,
4. (a) Arcadi, A.; Bianchi, G.; Marinelli, F. Synthesis 2004, 4, 610; (b) Kamijo, S.;
Sasaki, Y.; Yamamoto, Y. Tetrahedron Lett. 2004, 45, 35; (c) Hiroya, K.; Itoh, S.;
Sakamoto, T. J. Org. Chem. 2004, 69, 1126.
21.4, 22.2, 26.5, 30.2, 52.3, 53.3, 101.2, 108.8, 119.9, 122.9, 128.2,
128.9, 129.6, 135.6, 136.7, 141.6, 163.5, 164.3. EIMS m/z (rel int., %):
329 (Mþ, 45), 287 (48), 228 (50), 168 (65). HRMS (ESI): calcd for
C19H23O4NþH: 330.1700; found: 330.1702.
5. (a) Takeda, A.; Kamijo, S.; Yamamoto, Y. J. Am. Chem. Soc. 2000, 122, 5662; (b)
Cacchi, S.; Fabrizi, G.; Parisi, L. M. Synthesis 2004, 1889; (c) Shimada, T.;
Nakamura, I.; Yamamoto, Y. J. Am. Chem. Soc. 2004, 126, 10546; (d) Alfonsi,
M.; Arcadi, A.; Aschi, M.; Bianchi, G.; Marinelli, F. J. Org. Chem. 2005, 70,
2265; (e) Nakamura, M.; Ilies, L.; Otsubo, S.; Nakamura, E. Org. Lett. 2006, 8,
2803; (f) Nakamura, M.; Ilies, L.; Otsubo, S.; Nakamura, E. Angew. Chem., Int.
Ed. 2006, 45, 944; (g) Zhang, Y.; Donahue, J. P.; Li, C.-J. Org. Lett. 2007, 9, 627;
(h) Yin, Y.; Ma, W.; Chai, Z.; Zhao, G. J. Org. Chem. 2007, 72, 5731; (i) Cariou,
K.; Ronan, B.; Mignani, S.; Fensterbank, L.; Malacria, M. Angew. Chem., Int. Ed.
2007, 46, 1881; (j) Li, G.; Huang, X.; Zhang, L. Angew. Chem., Int. Ed. 2008, 47,
346.
6. For reviews, see: (a) Jia, C.; Kitamura, T.; Fujiwara, Y. Acc. Chem. Res. 2001, 34,
633; (b) Nevado, C.; Echavarren, A. M. Synthesis 2005, 157; (c) Bandini, M.;
Emer, E.; Tommasi, S.; Umani-Ronchi, A. Eur. J. Org. Chem. 2006, 3527.
7. For recent reviews on platinum and gold catalysis, see: (a) Ma, S.; Yu, S.; Gu, Z.
Angew. Chem., Int. Ed. 2006, 45, 200; (b) Zhang, L.; Sun, J.; Kozmin, S. A. Adv.
CO2Me
MeO2C
Cl
N
H
6i
1H NMR (CDCl3, 300 MHz,
d ppm): 8.19 (br s, 1H), 7.15 (m, 3H),
7.04 (d, 1H, J¼8.1 Hz), 3.80 (s, 3H), 3.62 (s, 3H), 2.56 (t, 2H, J¼7.5 Hz),
1.59 (m, 2H), 1.31 (m, 2H), 0.88 (t, 3H, J¼7.8 Hz); 13C NMR (CDCl3,
75 MHz,
d ppm): 13.8, 22.3, 26.7, 30.8, 51.9, 53.0, 106.0, 111.6, 118.1,
ˇ
Synth. Catal. 2006, 348, 2271; (c) Jime´nez-Nu´ nez, E.; Echaverren, A. M. Chem.
121.7, 125.7, 128.8, 129.2, 133.3, 137.8, 140.4, 165.5, 167.4. EIMS m/z
(rel int., %): 349 (Mþ, 35), 290 (21), 275 (29), 188 (64), 59 (100).
HRMS (ESI): calcd for C18H20O4NClþH: 350.1154; found 350.1153.
Commun. 2007, 333; (d) Fu¨rstner, A.; Davies, P. W. Angew. Chem., Int. Ed. 2007,
46, 3410; (e) Hashmi, A. S. K. Chem. Rev. 2007, 107, 3180; (f) Gorin, D. J.; Toste, F.
D. Nature 2007, 446, 395; (g) Shen, H. Tetrahedron 2008, 64, 3885; (h) Skouta, R.;
Li, C.-J. Tetrahedron 2008, 64, 4917.
CO2Me
8. Reetz, M.; Sommer, K. Eur. J. Org. Chem. 2003, 3485.
9. (a) Shi, Z.; He, C. J. Org. Chem. 2004, 69, 3669; (b) Li, Z.; Shi, Z.; He, C. J. Orga-
nomet. Chem. 2005, 690, 5049.
MeO2C
Cl
10. Ferrer, C.; Amijs, C. H. M.; Echavarren, A. M. Chem.dEur. J. 2007, 1358.
11. Bhuvaneswari, S.; Jeganmohan, M.; Cheng, C.-H. Chem.dEur. J. 2007, 13, 8285.
12. Lu, W.; Jia, C.; Kitamura, T.; Fujiwara, Y. Org. Lett. 2000, 2, 2927.
13. Kusurkar, R. S.; Patil, U. G. Indian J. Chem., Sect B 1986, 25, 1038.
14. Singh, H.; Singh, K. Tetrahedron 1988, 44, 5897.
Ph
N
H
6e
1H NMR (CDCl3, 300 MHz,
d
ppm): 8.55 (br s, 1H), 7.41–7.32 (m,
5H), 7.24 (d, 1H, J¼1.8 Hz), 7.18 (d, 1H, J¼8.7 Hz), 7.11 (s, 1H), 7.07
15. Sala, G. D.; Izzo, I.; Spinalla, A. Synlett 2006, 1319.