Synthesis of 3-allenylindoles and 3-dienylindoles by Br?nsted acid catalyzed allenylation of 2-arylindoles with tertiary propargylic alcohols

Article abstract of DOI:10.1055/s-0029-1217543

The Br?nsted acid catalyzed direct nucleophilic substitution of tertiary propargylic alcohols with 2-aryl-substituted indoles has been studied. A competitive allenylation process takes place with appropriate substituents on the alkynol moiety. Starting fr

Full text of DOI:10.1055/s-0029-1217543

LETTER
1985
Synthesis of 3-Allenylindoles and 3-Dienylindoles by Brønsted Acid Catalyzed
Allenylation of 2-Arylindoles with Tertiary Propargylic Alcohols
A
llenylation of In
o
doles berto Sanz,*a Mukut Gohain,a Delia Miguel,a Alberto Martínez,a Félix Rodríguezb
a
Departamento de Química, Área de Química Orgánica, Facultad de Ciencias, Universidad de Burgos, Pza. Misael Bañuelos s/n,
09001-Burgos, Spain
Fax +34(947)258831; E-mail: rsd@ubu.es
Instituto Universitario de Química Organometálica ‘Enrique Moles’, Universidad de Oviedo, C/ Julián Clavería 8, 33006-Oviedo, Spain
b
Received 5 March 2009
2-arylindoles as the nucleophilic partner. Thus, in this pa-
per we wish to report a new synthesis of 3-allenyl-2-aryl-
and 2-aryl-3-dienyl-indoles from tertiary propargylic al-
cohols under Brønsted acid catalysis.
Abstract: The Brønsted acid catalyzed direct nucleophilic substitu-
tion of tertiary propargylic alcohols with 2-aryl-substituted indoles
has been studied. A competitive allenylation process takes place
with appropriate substituents on the alkynol moiety. Starting from
2-arylindoles, new 3-allenyl and 3-dienylindole derivatives have
been easily synthesized.
When we investigated the reaction of commercially avail-
able 2-phenylindole 1a with model tertiary propargylic al-
cohol 2a under our reported standard conditions,11 that is,
PTSA catalysis using acetonitrile as solvent at room tem-
perature, the expected C3-propargylated indole 3aa
(R = H) was obtained along with a minor isomeric com-
pound which was identified as the C3-dienyl derivative
4aa (R = H, Scheme 1). Whereas the formation of indole
3aa is explained through a Brønsted acid catalyzed direct
nucleophilic substitution reaction,11 the generation of the
indole 4aa could be understood by a competitive allenyla-
tion reaction leading to the allene derivative 5aa (R = H),
which undergoes further isomerization under the acidic
conditions to the observed dienyl indole 4aa (Scheme 1).
Key words: catalysis, indoles, allenes, dienes, nucleophilic substi-
tution
Indoles are building blocks of many natural products and
have applications as biologically active compounds and in
material science.1 Thus, the selective functionalization of
indoles has attracted considerable attention,2 and several
successful approaches for the synthesis of 3-substituted
indoles have been developed based on the nucleophilic
nature of the indole nucleus.3 However, few methods are
available for the introduction of quaternary carbons at the
C3-position of indoles.4 Moreover, no methods are known
for the direct synthesis of C3-allenyl or C3-dienyl indole
derivatives from nonfunctionalized starting indole com-
pounds.5 Whereas the C3-alkylation of indolyl derivatives
through Friedel–Crafts processes usually requires the use
of strong electrophilic reagents,6 recently, alcohols have
been reported as useful electrophiles under transition-
metal7 as well as Lewis acid catalysis.8 The easy availabil-
ity of alcohols and the fact that water would be the only
byproduct of the substitution reactions make the direct
catalytic nucleophilic substitution of indoles with alco-
hols a powerful reaction. The metal-free version of this
process by using Brønsted acids as catalysts is much more
appealing than the use of transition metals or typical
Lewis acids.9
R
Ph
Ph
Ph
N
H
1a
+
Ph
N
PTSA (5 mol%)
MeCN, r.t.
H
R
3
and / or
Ph
OH
Ph
Ph
Ph
Ph
N
H
R
4
2a R = H
b R = Me
Ph
Ph
•
R
R
H
3:4 yield (%)
Ph
4:1
79
70
N
H
Me 0:1
5
Following our interest in Brønsted acid catalyzed nucleo-
philic substitution reactions,10 we have recently reported
the C3-selective propargylation and benzylation of in-
doles with tertiary alcohols catalyzed by p-toluenesulfon-
ic acid (PTSA).11 Taking into account that in this initial
study we did not evaluate the behaviour of 2-substituted
indoles and due to the high synthetically usefulness of the
resulting C3-alkylated indoles for subsequent transforma-
tions,12 we further studied this type of process by using
Scheme 1 Competitive propargylation/allenylation of 2-phenylin-
dole 1a with tertiary alkynols 2a,b
At this point, we suspected that the steric hindrance of the
substituents at the propargylic position of the starting
alkynol could play a vital role in the regioselectivity of the
alkylation reaction of 2-phenylindole derivatives.13 To
check this possibility we studied the reaction of 1a with
tertiary alkynol 2b bearing a bulkier substituent at the pro-
pargylic position. This reaction led exclusively to the iso-
lation of the C3-dienyl indole 4ab (R = Me) as a single
geometrical isomer (Scheme 1).14
SYNLETT 2009, No. 12, pp 1985–1989
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x
.x
x
.2
0
0
9
Advanced online publication: 03.07.2009
DOI: 10.1055/s-0029-1217543; Art ID: D07009ST
© Georg Thieme Verlag Stuttgart · New York

1986
R. Sanz et al.
LETTER
Table 1 PTSA-Catalyzed Reactions of 2-Phenylindoles 1a–c with Alkynols 2b–e
R3
R3
R4
R1
R1
R2
R1
OH
PTSA (5 mol%)
MeCN, r.t.
R2
+
R4
and/or
R2
Ph
R4
Ph
R3
2b–e
Ph
N
H
1a–c
N
N
H
H
3
4
Entry
Indole
1a
R1
H
Alkynol
2b
R2
R3
R4
Product
4ab
Yield (%)a
1
2
3
4
5
6
Ph
Me
Me
Me
Et
Ph
70
67
69
54c
68
59
1b
Cl
OMe
H
2b
Ph
Ph
4bb
1c
2b
Ph
Ph
4cb
1a
2c
Ph
n-Bu
Ph
3ac + 4acb
3ad
1a
H
2d
c-C3H5
Ph
Me
–
1a
H
2ed
Ph
3ae
a Isolated yield after column chromatography.
b A 4:1 ratio of isomers was determined by 1H NMR analysis of the crude reaction mixture.
c Yield of the isolated major isomer 3ac.
d 1,3-Diphenylpropyn-2-ol.
In order to further understand the factors controlling the of our method, we decided to carry out a set of experi-
outcome of the process, we studied the reaction of differ- ments by using different 2-arylindoles 1a,d–g15 and sev-
ent 2-phenylindole derivatives 1a–c15 with tertiary eral phenyl-substituted tertiary benzylic alkynols 2b,f–j
alkynols 2b–d bearing bulky substituents at the propar- under the standard conditions (Table 2).
gylic position (R3π H, Table 1). First, when alkynol 2b
Table 2 Synthesis of C3-Dienylindole Derivatives 4a
was tested against different indoles 1a–c, without substit-
uents or containing electron-withdrawing or electron-
donating groups at the benzenoid moiety, the correspond-
ing dienylindole derivatives 4 were exclusively obtained
R
Ph
OH
H+
Ar2
+
Ar2
Ar1
Ar1
Ph
N
(Table 1, entries 1–3). The effect of the substituent at the
terminal position of the starting alkynol (R4) was also
studied. Thus, the reaction of propargylic alcohol 2c,
bearing an alkyl group at this position, with indole 1a
mainly afforded the corresponding C3-propargylated de-
rivative 3ac (Table 1, entry 4). In addition, treatment of 2-
phenylindole 1a with a dialkyl-substituted tertiary alkynol
such as 2d, or with a secondary propargylic alcohol like
2e, gave rise exclusively to the corresponding C3-propar-
gylated indoles 3 (Table 1, entries 5 and 6).
H
R
N
H
1
2
4
Entry 1
Ar1
2
Ar2
R
ProductYield
(%)b
1
2
3
4
5
6
7
8
9
1d 4-FC6H4
2b Ph
2b Ph
2b Ph
2b Ph
Me
Me
Me
Me
Et
4db
4eb
4fb
4gb
4af
4ag
4dg
4eg
4ah
4ai
70
60
65
61
66
73
72
60
67
54
58
1e
1f
4-MeOC6H4
2-MeOC6H4
1g 2-Thc
1a Ph
This study allowed us to determine that formation of in-
doles 3 or 4 from 2-phenylindole derivatives seems to de-
pend on the substituents present both at the propargylic
and the terminal position of the triple bond in the starting
alkynol. A delicate balance between the stability of the fi-
nal products, the electrophilicities of the intermediate car-
bocations, the nucleophilicities of the different indoles,3
and steric factors probably account for the observed regi-
oselectivities. In any case, it seems that only tertiary pro-
pargylic alcohols such as 2b, with aryl substituents at both
the propargylic and the terminal positions (R2 and R4), as
well as with a bulky substituent at the other propargylic
position (R3π H), are appropriate starting materials to get
the C3-dienylindole derivatives 4.16 However, it should be
taken into account that these compounds 4 are not easily
available by other strategies. So, in order to test the scope
2f
Ph
1a Ph
2g 4-ClC6H4 Me
2g 4-ClC6H4 Me
2g 4-ClC6H4 Me
2h 4-ClC6H4 Et
1d 4-FC6H4
1e
4-MeOC6H4
1a Ph
10 1a Ph
2i
2-Thc
2-Thc
Me
Et
11 1a Ph
2j
4aj
a Reaction conditions: 1 (0.5 mmol), 2 (0.52 mmol), PTSA (0.025
mmol) in MeCN (2 mL) at r.t.
b Isolated yield after column chromatography.
c 2-Thienyl.
Synlett 2009, No. 12, 1985–1989 © Thieme Stuttgart · New York

LETTER
Allenylation of Indoles
1987
As shown in Table 2 the process seems to be general with same way as 2k leading to new and interesting C3-alle-
respect to the aryl substituent at the C-2 of the indole moi- nylindoles 5 in good yields. In most cases, the correspond-
ety (Ar1) as electron-withdrawing, electron-donating, and ing indole derivative 5 is easily isolated by simple
heteroaromatic groups are well tolerated. Regarding the filtration as it precipitates from the reaction medium. In
substitution of the tertiary alkynol we found that substitut- some cases, variable small amounts of the corresponding
ed aryl or heteroaromatic groups could be present at one dienes 4 remain in solution. In those cases where any of
of the propargylic positions (Ar2) whereas different alkyl the starting compounds are not soluble in the reaction me-
groups could be located at the other propargylic position dia, a larger amount (20 mol%) of PTSA had to be added
(CH2R in Table 2).
in order to complete the reaction.
Further evidence for the proposed mechanism outlined in We have also examined the acid-catalyzed isomerization
Scheme 1 for the formation of C3-dienylindoles 4 was of allene derivatives 5 to the corresponding dienes 4 (see
found when we studied the behaviour of 2-phenylindole Scheme 2) with allenylindoles 5dk and 5ek. In these cases
1a with tertiary alkynol 2k, bearing an isopropyl group at dienylindoles 4dk and 4ek could be isolated in almost
the propargylic position. Under standard Brønsted acid quantitative yield by refluxing an acetonitrile solution of
catalysis a mixture of the expected dienylindole 4ak and the corresponding allenyl derivative 5 in the presence of
the C3-allenylindole 5ak was obtained after silica gel col- PTSA (5 mol%).
umn chromatography. Gratifyingly, by carrying out the
In summary, the C3-selective functionalization of 2-
purification on alumina instead of silica we were able to
arylindoles by reaction with tertiary propargylic alcohols
selectively isolate the allene derivative 5ak in 65% yield
under Brønsted acid catalysis is reported. A new and
straightforward synthesis of interesting 3-allenyl and
(Scheme 2). Moreover, refluxing 5ak in acetonitrile with
a catalytic amount of PTSA (5 mol%) for ca. 5 hours, al-
Table 3 Synthesis of C3-Allenylindole Derivatives 5a
lowed us to obtain the corresponding diene 4ak in almost
quantitative yield after a simple filtration through a pad of
alumina (Scheme 2). These results support the competi-
tive allenylation reaction for tertiary alkynols bearing
bulky substituents at the propargylic position. The isomer-
ization of allenes 5 to dienes 4 seems to be slowed down
when the substituent at the propargylic position is
branched instead of linear.
Ph
Ar2
R
•
OH
H+
+
Ar2
Ar1
Ar1
Ph
R
N
N
H
H
1
2
5
Entry 1 Ar1
2
Ar2
R
Prod. Yield
(%)b
1
2
3
4
5
6
7
8
9
1d 4-FC6H4
2k
Ph
Ph
Ph
Ph
i-Pr
i-Pr
i-Pr
5dk 67
5ek 82c
5gk 70e
Ph
N
Ph
Ph
H
1e 4-MeOC6H4 2k
•
1a
PTSA (5 mol%)
MeCN, r.t.
+
OH
1g 2-Thd
1a Ph
2k
2l
Ph
5ak
65%
c-C3H5 5al 55f
N
H
Ph
H+, MeCN
reflux
Ph
1a Ph
2m 4-MeOC6H4 c-C3H5 5am 75c
Ph c-C3H5 5el
80c
1e 4-MeOC6H4 2m 4-MeOC6H4 c-C3H5 5em 75c
Ph
2k
1e 4-MeOC6H4 2l
Ph
Ph
4ak
95%
N
H
1a Ph
1a Ph
2n
2o
2p
2p
Ph
Ph
Ph
Ph
Ph
Ph
Ph
c-C4H7 5an 69
c-C5H9 5ao 70
c-C6H11 5ap 81
c-C6H11 5dp 82
c-C5H9 5eo 65c
c-C5H9 5go 68
c-C6H11 5gp 75
Scheme 2 Reaction of 2-phenylindole 1a with alkynol 2k and iso-
lation of C3-allenylindole 5ak
10 1a Ph
Due to the potential interest of C3-allenylindoles and to
the fact that to the best of our knowledge a direct route to
these compounds has not been described, we synthesized
a variety of allene derivates 5 by the PTSA-catalyzed
reaction of 2-arylindoles 1 with tertiary alkynols 2k–p
(Table 3). Again, different 2-arylindoles 1d–g were ini-
tially tested with isopropyl-substituted alkynol 2k and the
corresponding allenylindoles 5 were isolated in good
yields (Table 3, entries 1–3). Moreover, other alkynols
2l–p bearing groups at the propargylic position such as
cyclopropyl (Table 3, entries 4–7), cyclobutyl (Table 3,
entry 8), cyclopentyl (Table 3, entries 9, 12, and 13), and
cyclohexyl (Table 3, entries 10, 11, and 14) behave in the
11 1d 4-FC6H4
12 1e 4-MeOC6H4 2o
13 1g 2-Thd
14 1g 2-Thd
2o
2p
a Reaction conditions: 1 (0.5 mmol), 2 (0.52 mmol), PTSA (0.025
mmol) in MeCN (2 mL) at r.t.
b Isolated yield after column chromatography.
c The amount of 20 mol% of PTSA was used.
d 2-Thienyl.
e Ca. 10% of the propargylated derivative 3gk was also formed.
f Ca. 20% of the propargylated derivative 3al was also isolated.
Synlett 2009, No. 12, 1985–1989 © Thieme Stuttgart · New York

1988
R. Sanz et al.
LETTER
(2) For recent reviews, see: (a) Cacchi, S.; Fabrizi, G. Chem.
Rev. 2005, 105, 2873. (b) Humphrey, G. R.; Kuethe, J. T.
Chem. Rev. 2006, 106, 2875.
(3) Lakhdar, S.; Westermaier, M.; Terrier, F.; Goumont, R.;
Boubaker, T.; Ofial, A. R.; Mayr, H. J. Org. Chem. 2006, 71,
9088.
3-dienylindoles has been developed through an environ-
mentally friendly process with water as the only side
product of the reaction.
(4) See, for instance: (a) Palmieri, A.; Petrini, M. J. Org. Chem.
2007, 72, 1863. (b) Bhuvaneswari, S.; Jeganmohan, M.;
Cheng, C.-H. Chem. Eur. J. 2007, 13, 8285. (c) Wang,
S.-Y.; Ji, S.-J. Synlett 2007, 2222. (d) Rozenman, M. M.;
Kanan, M. W.; Liu, D. R. J. Am. Chem. Soc. 2007, 129,
14933. (e) Kong, W.; Cui, J.; Yu, Y.; Chen, G.; Fu, C.; Ma,
S. Org. Lett. 2009, 11, 1213.
(5) 1-(3-Indolyl)-buta-1,3-dienes are usually prepared in several
steps and poor overall yields. See, for instance: (a) Sheu,
J.-H.; Chen, Y.-K.; Chung, H.-F.; Lin, S.-F.; Sung, P.-J.
J. Chem. Soc., Perkin Trans. 1 1998, 1959. (b) Wada, A.;
Babu, G.; Shimomoto, S.; Ito, M. Synlett 2001, 1759.
(6) For a review, see: Bandini, M.; Melloni, A.; Tommasi, S.;
Umani-Ronchi, A. Synlett 2005, 1199.
(7) (a) Ru: Nishibayashi, Y.; Yoshikawa, M.; Inada, Y.; Hidai,
M.; Uemura, S. J. Am. Chem. Soc. 2002, 124, 11846.
(b) Re: Kennedy-Smith, J. J.; Young, L. A.; Toste, F. D. Org.
Lett. 2004, 6, 1325. (c) Ru: Zaitsev, A. B.; Gruber, S.;
Pregosin, P. S. Chem. Commun. 2007, 4692. (d) Ir:
Whithney, S.; Grigg, R.; Derrick, A.; Keep, A. Org. Lett.
2007, 9, 3299.
(8) (a) InCl3: Yasuda, M.; Somyo, T.; Baba, A. Angew. Chem.
Int. Ed. 2006, 45, 793. (b) Sc(OTf)3: Yadav, J. S.;
Subba Reddy, B. V.; Raghavendra Rao, K. V.;
General Procedure for the Synthesis of 3-Dienylindole Deriva-
tives 4
Synthesis of 3-[(1Z,3E)-1,3-Diphenylpenta-1,3-dienyl]-2-phe-
nyl-1H-indole (4ab)
To a mixture of alkynol 2b (123 mg, 0.52 mmol) and 2-phenylin-
dole (1a; 97 mg, 0.5 mmol) in analytical grade MeCN (2 mL) PTSA
(4.8 mg, 0.025 mmol) was added. The reaction was stirred at r.t. for
0.5 h (the completion of the reaction was monitored by GC-MS and
TLC). The solvent was removed under reduced pressure, and the
residue was purified by silica gel column chromatography (eluent:
hexane–Et2O, 7:1) to afford 4ab (144 mg, 70%) as a white solid; mp
136–138 °C. 1H NMR (300 MHz, CDCl3): d = 1.53 (d, J = 7.1 Hz,
3 H), 5.41 (qd, J = 7.1, 1.0 Hz, 1 H), 6.64–6.72 (m, 3 H), 6.76–6.82
(m, 2 H), 6.88–6.94 (m, 1 H), 6.99 (d, J = 7.4 Hz, 1 H), 7.03–7.10
(m, 2 H), 7.11 (s, 1 H), 7.22–7.31 (m, 2 H), 7.31–7.37 (m, 4 H),
7.41–7.46 (m, 2 H), 7.60–7.66 (m, 2 H), 7.76 (s, 1 H) ppm. 13C
NMR (75.4 MHz, CDCl3): d = 15.1 (CH3), 110.3 (CH), 113.0 (C),
119.5 (CH), 120.8 (CH), 122.0 (CH), 125.3 (CH), 126.1 (2 ¥ CH),
126.6 (2 ¥ CH), 127.0 (2 ¥ CH), 127.3 (CH), 127.4 (2 ¥ CH),
127.5 (CH), 127.6 (CH), 128.0 (CH), 128.3 (2 ¥ CH), 128.5 (2
¥ CH), 128.9 (C), 132.8 (C), 135.8 (C), 136.4 (C), 137.1 (C), 139.7
(C), 141.7 (C), 142.5 (C) ppm. LRMS (EI): m/z = 411 (25) [M+],
382 (100), 304 (38). HRMS (EI): m/z calcd for C31H25N: 411.1987;
found: 411.1995.
Narayana Kumar, G. G. K. S. Tetrahedron Lett. 2007, 48,
5573. (c) FeCl3: Jana, U.; Maiti, S.; Biswas, S. Tetrahedron
Lett. 2007, 48, 7160. (d) I2: Srihari, P.; Bhunia, D. C.;
Sreedhar, P.; Mandal, S. S.; Shyam Sunder Reddy, J.;
Yadav, J. S. Tetrahedron Lett. 2007, 48, 8120.
General Procedure for the Synthesis of 3-Allenylindole Deriva-
tives 5
Synthesis of 3-(1,3-Diphenyl-4-methylpenta-1,2-dienyl)-2-(4-
methoxy)-phenyl-1H-indole (5ek)
(9) (a) Shirakawa, S.; Kobayashi, S. Org. Lett. 2007, 9, 311.
(b) Motokura, K.; Nakagiri, N.; Mizugaki, T.; Ebitani, K.;
Kaneda, K. J. Org. Chem. 2007, 72, 6006. (c) Le Bras, J.;
Muzart, J. Tetrahedron 2007, 63, 7942.
To a mixture of alkynol 2k (130 mg, 0.52 mmol) and 2-(4-methox-
yphenyl)indole (1e; 112 mg, 0.5 mmol) in analytical grade MeCN
(2 mL) PTSA (19 mg, 0.1 mmol) was added. The reaction was
stirred at r.t. for 1 h (the completion of the reaction was monitored
by GC-MS and TLC) whereas a solid precipitated, which was fil-
trated to afford 5ek (187 mg, 82%) as a whitish solid; mp 141–143
°C. 1H NMR (300 MHz, CDCl3): d = 0.97 (d, J = 6.5 Hz, 3 H), 1.19
(d, J = 6.5 Hz, 3 H), 2.78–2.92 (m, 1 H), 3.74 (s, 3 H), 6.64 (d,
J = 8.6 Hz, 2 H), 7.03 (t, J = 7.5 Hz, 1 H), 7.08–7.28 (m, 9 H), 7.32–
7.49 (m, 6 H), 8.15 (br s, 1 H) ppm. 13C NMR (75.4 MHz, CDCl3):
d = 22.3 (CH3), 22.5 (CH3), 29.6 (CH), 55.4 (CH3), 105.0 (C), 108.3
(C), 110.8 (CH), 114.2 (2 ¥ CH), 115.4 (C), 120.17 (CH), 120.22
(CH), 122.2 (CH), 125.2 (C), 126.6 (2 ¥ CH), 126.7 (CH), 126.8
(CH), 127.2 (2 ¥ CH), 128.3 (2 ¥ CH), 128.6 (2 ¥ CH), 129.1 (2
¥ CH), 129.9 (C), 135.5 (C), 135.9 (C), 136.6 (C), 137.4 (C), 159.3
(C), 206.4 (C) ppm. LRMS (EI): m/z = 455 (30) [M+], 412 (100),
378 (56), 291 (59), 223 (64), 115 (51), 91 (82), 77 (56). HRMS (EI):
m/z calcd for C33H29N: 455.2249; found: 455.2262.
(10) (a) Sanz, R.; Martínez, A.; Álvarez-Gutiérrez, J. M.;
Rodríguez, F. Eur. J. Org. Chem. 2006, 1383. (b) Sanz, R.;
Martínez, A.; Miguel, D.; Álvarez-Gutiérrez, J. M.;
Rodríguez, F. Adv. Synth. Catal. 2006, 348, 1841. (c) Sanz,
R.; Miguel, D.; Martínez, A.; Álvarez-Gutiérrez, J. M.;
Rodríguez, F. Org. Lett. 2007, 9, 727. (d) Sanz, R.; Miguel,
D.; Martínez, A.; Álvarez-Gutiérrez, J. M.; Rodríguez, F.
Org. Lett. 2007, 9, 2027. (e) Sanz, R.; Martínez, A.;
Álvarez-Gutiérrez, J. M.; Rodríguez, F. Synthesis 2007,
3252. (f) Sanz, R.; Martínez, A.; Guilarte, V.; Álvarez-
Gutiérrez, J. M.; Rodríguez, F. Eur. J. Org. Chem. 2007,
4642.
(11) Sanz, R.; Miguel, D.; Álvarez-Gutiérrez, J. M.; Rodríguez,
F. Synlett 2008, 975.
(12) Sanz, R.; Miguel, D.; Rodríguez, F. Angew. Chem. Int. Ed.
2008, 47, 7354.
(13) We have observed that the presence of an alkyl substituent at
the C-2 of the indole nucleus does not give rise to significant
competitive allenylation processes.
(14) The 1Z,3E-isomer was mainly formed. Variable amounts of
the 1Z,3Z-isomer were detected in the crude product. After
column chromatography we usually isolated the major
isomer slightly contaminated with the minor one, probably
due to further isomerization under the purification
conditions. The stereochemistry was assessed by NOESY
experiments on 4cb, and the rest of the compounds were
assigned by inference. Moreover, the structure of 4af was
confirmed by single-crystal X-ray diffraction analysis
Acknowledgment
We gratefully thank Junta de Castilla y León (BU012A06) and Mi-
nisterio de Educación y Ciencia (MEC) and FEDER (CTQ2007-
61436/BQU) for financial support. D.M. and A.M. thank MEC for
a FPU predoctoral fellowship. M.G. thanks MEC for a ‘Young For-
eign Researchers’ contract (SB2006-0215).
References and Notes
(1) Sundberg, R. J. Indoles; Academic Press: San Diego, 1996.
Synlett 2009, No. 12, 1985–1989 © Thieme Stuttgart · New York

LETTER
(CCDC 729740 contains the supplementary crystallographic
Allenylation of Indoles
1989
modified Madelung synthesis, see: Houlihan, W. J.; Parrino,
V. A.; Uike, Y. J. Org. Chem. 1981, 46, 4511.
(16) We have checked that the presence of alkyl or aryl groups at
the nitrogen atom of the starting 2-phenylindole derivative
mainly gives rise to propargylated products regardless the
substituents of the alkynol.
data for this compound. These data can be obtained free of
charge from The Cambridge Crystallographic Data Centre
via www.ccdc.cam.ac.uk/ data_request/cif).
(15) (a) Indoles 1b,d–g were prepared by standard Fisher indole
synthesis, see: Fusco, R.; Sannicolo, F. J. Org. Chem. 1981,
46, 83. (b) On the other hand, indole 1c was obtained by a
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