Chemo- and regioselective ethynylation of 4,5,6,7-tetrahydroindoles with ethyl 3-halo-2-propynoates

Article abstract of DOI:10.1016/j.tetlet.2008.04.046

4,5,6,7-Tetrahydroindoles undergo a rapid, facile (rt, 60 min) ethynylation with ethyl 3-halo-2-propynoates upon grinding with solid K₂CO₃ (without solvent) at C-2 of the tetrahydroindole ring to afford ethyl 3-(4,5,6,7-tetrahydroindol-2-yl)-2-propynoates in 62-90% yield.

Full text of DOI:10.1016/j.tetlet.2008.04.046

Available online at www.sciencedirect.com
Tetrahedron Letters 49 (2008) 3946–3949
Chemo- and regioselective ethynylation of
4,5,6,7-tetrahydroindoles with ethyl 3-halo-2-propynoates
Boris A. Trofimov *, Lyubov’ N. Sobenina, Zinaida V. Stepanova,
Ol’ga V. Petrova, Igor’ A. Ushakov, Al’bina I. Mikhaleva
A. E. Favorsky Irkutsk Institute of Chemistry, Siberian Branch of the Russian Academy of Sciences, 1 Favorsky St., Irkutsk 664033, Russian Federation
Received 7 December 2007; revised 27 March 2008; accepted 8 April 2008
Available online 11 April 2008
Abstract
4,5,6,7-Tetrahydroindoles undergo a rapid, facile (rt, 60 min) ethynylation with ethyl 3-halo-2-propynoates upon grinding with solid
K2CO3 (without solvent) at C-2 of the tetrahydroindole ring to afford ethyl 3-(4,5,6,7-tetrahydroindol-2-yl)-2-propynoates in 62–90%
yield.
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords: 4,5,6,7-Tetrahydroindoles; Indoles; Active surface; K2CO3; Cross-coupling
4,5,6,7-Tetrahydroindoles, due to their easy aromatiza-
tion, are good intermediates to synthesize indoles.1 Conse-
quently, 2-functionalized 4,5,6,7-tetrahydroindoles are
convenient starting materials for the preparation of 2-func-
tionalized indoles. A number of their representatives are
pharmacologically important substances and precursors
for a wide variety of alkaloids such as vindoline,2 vindoro-
sine,2 ellipticine.3 Also, 2-functionalized indoles attract
attention owing to their usefulness in the total synthesis
of polyfunctional complex molecules possessing the indole
scaffold.4 Of special importance are 2-substituted indoles
with acetylenic moieties because they are currently
employed in the design of numerous indole derivatives5
due to the rich chemistry of the acetylenic function.
Although methods for the preparation of 3-substituted
indoles are well developed, syntheses of 2-substituted
indole derivatives still remain less elaborated. Therefore a
new simple access to 2-functionalized indoles, particularly
2-ethynylindoles, might further contribute to the chemistry
and pharmacology of indole compounds.
Amongst the known syntheses of indoles bearing acetyl-
enic substituents at C-2 are cross-couplings of 2-haloin-
doles with terminal acetylenes in the presence of
palladium, copper and a base in different solvents, per-
formed as a rule, under an inert atmosphere.6 However,
2-haloindoles are quite unstable, and decompose at room
temperature.7 The cross-coupling of methyl bro-
mopropynoate with 1-SEM-2-tributylstannylindole in the
presence of Pd(PPh3)46a gives the corresponding 2-ethynyl-
indole in 45% yield. Recently, syntheses of 2-ethynylin-
doles involving simultaneous building of the indole ring
have been documented.8 One of the promising approaches
to indoles with an acetylenic group at C-2 could involve
aromatization of 3-(4,5,6,7-tetrahydroindol-2-yl)-2-propy-
noates. Therefore, a search for a versatile general synthesis
of 3-(4,5,6,7-tetrahydroindol-2-yl)-2-propynoates is a cru-
cial step in solving the above problem.
Previously, the synthesis of ethyl 3-(4,5,6,7-tetrahydro-
indol-2-yl)-2-propynoate by the ethynylation of available9
4,5,6,7-tetrahydroindole 1a with ethyl 3-bromo-(2a) and
ethyl 3-iodo-2-propynoates 2b on active Al2O3 surface
has been described.10 However, this reaction with bro-
mopropynoate was not chemoselective: along with ethyl
3-(4,5,6,7-tetrahydroindol-2-yl)-2-propynoate 3a (46%) a
*
Corresponding author. Tel.: +7 3952 461411/511431; fax: +7 3952
419346.
E-mail address: boris_trofimov@irioch.irk.ru (B. A. Trofimov).
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.04.046

B. A. Trofimov et al. / Tetrahedron Letters 49 (2008) 3946–3949
3947
Table 1
side product, ethyl 3,3-di(4,5,6,7-tetrahydro-1H-indol-2-
yl)acrylate 4a, was also formed in 24% yield (Scheme 1).
The same reaction of 4,5,6,7-tetrahydroindole with
iodopropynoate proceeded to deliver only adduct 4a
(79%).
In this Letter, we report an efficient chemo- and regiose-
lective ethynylation of the known11 4,5,6,7-tetrahydroin-
doles 1a–h with ethyl 3-halo-2-propynoates 2a,b on solid
K2CO3 as a novel active surface to afford the correspond-
ing 3-(4,5,6,7-tetrahydroindol-2-yl)-2-propynoates 3a–h in
62–90% yields (Table 1).12
Ethynylation of substituted 4,5,6,7-tetrahydroindoles 1a–h with ethyl 3-
bromo-2-propynoate 2a on solid K2CO3 (rt, reactants ratio = 1:1)
K2CO3
rt
O
Br
+
OEt
N
R
N
R
1a-h
O
2a
EtO
3a-h
Entry
4,5,6,7-
Reaction
time (h)
Mass excess of
K2CO3 versus
reactants
Product 3
(yield, %)
Tetrahydroindole 1
The reaction proceeded smoothly at room temperature
over about 60 min on grinding the reactants with solid
K2CO3. The reaction was equally efficient in air and under
argon. The reaction course (conversion of reactants 1 and 2
and the formation of ethynylation product 3) was moni-
1
1
1
2
5
3a (50)
3a (55)
3a (90)
3b (82)
3c (80)
3d (90)
3e (64)
N
H
1a
1
2
tored by H NMR spectroscopy of CDCl3 extracts from
N
H
the reaction mixture.Products 3a–h were isolated and puri-
fied chromatographically by placing the solid reaction mix-
ture on the top of an Al2O3-packed column and eluting
with n-hexane and diethyl ether. The yields of pyrroles
3a–h were reproducible (within 5%), also with K2CO3
samples from different suppliers.
1a
3
1
10
10
10
10
10
N
H
1a
In contrast to the similar reaction on Al2O3,10 in the case
of ethyl 3-bromo-2-propynoate 2a we failed to detect any
side products (1H NMR), whereas with ethyl 3-iodo-2-
propynoate 2b, 4,5,6,7-tetrahydroindole 1a gave minor
amounts of 3,3-di(4,5,6,7-tetrahydro-1H-indol-2-yl)acryl-
ate 4a (2–4%). Besides, the latter reaction appeared to be
noticeably slower (41% conversion of pyrrole 1a over
60 min).
The reaction is chemo- and regioselective. The expected
addition products of the type 2-(1-bromo-2-carbethoxy-
ethenyl)-4,5,6,7-tetrahydroindole10 were not detectable in
the reaction mixtures. Also, no traces of corresponding 3-
isomers were observed despite the fact that it is common
knowledge that bulky and branched substituents at posi-
tion 1 of the pyrrole nucleus can direct electrophilic attack
to position 3.13 In this reaction, even bulky substituents
such as CH(Me)OiPr and CH(Me)OBu did not affect the
regioselectivity, though the reaction time was considerably
increased (12 h instead of 60 min) and portion-wise addi-
tion of acetylene 2a to the reaction mixture was required.
Obviously, the slow reaction rate in this case results from
steric hindrance. Generally, this ethynylation reaction tol-
4a
12
1
N
1b
5
N
Me
1c
6
1
N
Ph
1d
7a
12
N
N
Me
Me
OiPr
OBu
1e
1f
8a
12
10
3f (62)
9
1
1
10
10
3g (71)
3h (81)
N
N
SEt
1g
1h
10
Al2O3
O
+
Hal
SPr
rt, 0.5 h
OEt
N
H
1a
N
H
3a
O
2a,b
a
Ratio 1:2 = 1:1.5.
EtO
N
erates various N-substituents on the indole (H, Alk, aral-
kyl, vinyl, acetal and sulfide).
Interestingly, the reaction does not occur in solution
(diethyl ether, CHCl3) either with and without K2CO3.
When neat reactants 1a and ethyl 3-bromo-2-propynoate
+
H
O
N
H
OEt
Hal = Br, I
4a
Scheme 1.

3948
B. A. Trofimov et al. / Tetrahedron Letters 49 (2008) 3946–3949
under solvent-free conditions in air. This novel approach
promises a general and easy access to 2-functionalized
indoles. Further systematic investigations of the reaction
employing other active surfaces (salts and metal oxides)
are underway in this lab.
Br
N
1a + 2a
H
N
H
rt, 0.5 h
O
OEt
5
Acknowledgement
Scheme 2.
This work was supported by the Russian Foundation
for Basic Research (Grant No. 05-03-32289).
2a were ground together for 30 min only adduct 5 was
formed (Scheme 2).10
The key effect of the K2CO3 active surface on the ethy-
nylation reaction was also supported by the influence of
reactants/K2CO3 ratio on the product yield. At the 1:10
ratio the yield of 3a was close to quantitative, while at
higher concentrations of reactants (1:2, 1:5) the yields
decreased to 50–55%. Meanwhile, the addition of K2CO3
(2.5 mol excess) to Al2O3 did not change the usual
References and notes
1. Lim, S.; Jabin, I.; Revial, G. Tetrahedron Lett. 1999, 40, 4177–4180.
2. Kuehne, M. E.; Podhorez, D. E.; Mulamba, T.; Bornmann, W. G. J.
Org. Chem. 1987, 52, 347–353.
3. Modi, S. P.; Zayed, A.-H.; Archer, S. J. Org. Chem. 1989, 54, 3084–
3087.
4. (a) Ishikura, M.; Matsuzaki, Y.; Agata, I.; Katagiri, N. Tetrahedron
1998, 54, 13929–13942; (b) Laronze, M.; Sapi, J. Tetrahedron Lett.
2002, 43, 7925–7928; (c) Cavdar, H.; Saracoglu, N. J. Org. Chem.
2006, 71, 7793–7799; (d) Miyamoto, H.; Okawa, Y.; Nakazaki, A.;
Kobayashi, S. Tetrahedron Lett. 2007, 48, 1805–1808.
5. (a) Passarella, D.; Giardini, A.; Martinelli, M.; Silvani, A. J. Chem.
Soc., Perkin Trans. 1 2001, 127–129; (b) Hibino, S.; Choshi, T. Nat.
Prod. Rep. 2002, 19, 148–180; (c) So¨denberg, B. C. G. Coord. Chem.
Rev. 2003, 241, 147–247.
6. (a) Passarella, D.; Lesma, G.; Deleo, M.; Martinelli, M.; Silvani, A. J.
Chem. Soc., Perkin Trans. 1 1999, 2669–2670; (b) Tokuyama, H.;
Kaburagi, Y.; Chen, X.; Fukuyama, T. Synthesis 2000, 429–434; (c)
Sumi, Sh.; Matsumoto, K.; Tokuyama, H.; Fukuyama, T. Tetra-
hedron 2003, 59, 8571–8587.
7. (a) Powers, J. C. J. Org. Chem. 1966, 31, 2627–2631; (b) Brennan, M.
R.; Erickson, K. L.; Szmalc, F. S.; Tansey, M. J.; Thornton, J. M.
Heterocycles 1986, 24, 2879–2885; (c) Bergman, J.; Venemalm, L. J.
Org. Chem. 1992, 57, 2495–2947.
8. (a) Furstner, A.; Ernst, A.; Krause, H.; Ptock, A. Tetrahedron 1996,
52, 7329–7344; (b) Kamijo, Sh.; Sasaki, Yu.; Yamamoto, Y.
Tetrahedron Lett. 2004, 45, 35–38; (c) Nagamochi, M.; Fang, Y.-Q.;
Lautens, M. Org. Lett. 2007, 9, 2955–2958.
9. (a) Trofimov, B. A.; Mikhaleva, A. I. N-Vinylpyrroles; Nauka:
Novosibirsk, 1984; p 262; (b) Trofimov, B. A. In Advances in
Heterocyclic Chemistry; Academic Press: New York, 1990; Vol. 51; p
177.
(for Al2O3) product ratio
significantly—3a:4a with
Al2O3 = 2:3, and with Al2O3 + K2CO3 = 3:2.10 It is
noteworthy that as yet, K2CO3 has not been mentioned
amongst numerous known active surfaces for effecting
chemical reactions.14
Formally, the ethynylation can be rationalized both as
electrophilic substitution on the pyrrole ring and nucleo-
philic addition of the electron-rich pyrrole ring to the
electron deficient triple bond. In both the cases, the
one-electron transfer step is plausible. Indeed, in the ESR
spectrum of the reaction mixture a singlet (g = 2.0023,
DH = 1.8 mT) was observed, thus confirming a one-elec-
tron transfer step.
To check the possibility of aromatization of the ethyl 3-
(4,5,6,7-tetrahydroindol-2-yl)-2-propynoates, propynoate
3c was refluxed in o-xylene with Pd/C (10% of Pd) for
12 h to give 2-indolepropanoate 8 and 2-indolylacrylate 9
(4:1 ratio) resulting from the hydrogen redistribution
between the cyclohexane ring and the triple bond (Scheme
3).15 This confirms that the ethyl 3-(4,5,6,7-tetrahydroin-
dol-2-yl)-2-propynoates 3 synthesized are convertible to
2-functionalized indoles.
10. Trofimov, B. A.; Sobenina, L. N.; Demenev, A. P.; Stepanova, Z. V.;
Petrova, O. V.; Ushakov, I. A.; Mikhaleva, A. I. Tetrahedron Lett.
2007, 48, 4661–4664.
In conclusion, the facile chemo- and regioselective ethyn-
ylation of 4,5,6,7-tetrahydoindoles with 3-halopropyno-
ates upon grinding with solid K2CO3 to furnish ethyl
3-(4,5,6,7-tetrahydroindol-2-yl)-2-propynoates has been
developed. The reaction proceeds at room temperature
11. (a) Heaney, H.; Ley, S. V. J. Chem. Soc., Perkin Trans. 1 1973, 499–
500; (b) Korostova, S. E.; Mikhaleva, A. I.; Trofimov, B. A.;
Sobenina, L. N.; Vasil’ev, A. N. Zh. Organ. Khim. [Russ. J. Org.
Chem.] 1982, 18, 525–528; (c) Trofimov, B. A.; Korostova, S. E.;
Sobenina, L. N.; Trzhitsinskaya, B. V.; Mikhaleva, A. I.; Sigalov, M.
V. Zh. Organ. Khim. [Russ. J. Org. Chem.] 1980, 16, 1964–1968; (d)
Mikhaleva, A. I.; Korostova, S. E.; Vasil’ev, A. N.; Balabanova, L.
N.; Sokol’nikova, N. P.; Trofimov, B. A. Khim. Geterotsikl. Soedin.
1977, 1636–1639.
12. General procedures for the ethynylation of 4,5,6,7-tetrahydroindoles.
(A). Ethyl 3-bromo-2-propynoate 2a (1 mmol) was added in small
portions (4 portions) with grinding for 10 min (ambient temperature)
to 4,5,6,7-tetrahydroindole 1a,c,d,g,h (1 mmol) and K2CO3 (2–10-fold
amount vs total weight of reactants) in a porcelain mortar. The
mixture self-heated up to 30 °C and became bright-yellow in colour.
Gradually, the colour changed to brown. The reaction mixture was
kept additionally for 50 min under grinding (2–3 min) at regular
intervals of 10 min. The reaction mixture was purified through an
Pd/C
O
+
N
N
Me
o-xylene
O
OEt
Me
EtO
+
3c
8
O
N
Me
OEt
9
Scheme 3.

B. A. Trofimov et al. / Tetrahedron Letters 49 (2008) 3946–3949
3949
Al2O3 column eluting with n-hexane (n-hexane and then diethyl ether
for propynoate 3a) to afford pure ethyl 3-(4,5,6,7-tetrahydro-1H-
indol-2-yl)-2-propynoates 3a,c,d,g,h. Pyrroles 3a and 3d were also
isolated by filtration of the reaction mixture after dilution with water.
(B) Ethyl 3-bromo-2-propynoate 2a (1 mmol) was added in small
portions with grinding for 15 min (ambient temperature) to 4,5,6,7-
tetrahydroindole 1b,e,f (1 mmol) and K2CO3 in a porcelain mortar.
The reaction mixture was kept additionally for 6 h under grinding (2–
3 min) at regular intervals of 30 min, and ethyl 3-bromo-2-propynoate
(0.5 mmol) in small portions was added with grinding for 15 min to
the mixture. The reaction mixture was kept additionally for 5.5 h
without grinding and then purified by column chromatography over
Al2O3 eluting with n-hexane to afford pure ethyl 3-(4,5,6,7-tetrahydro-
1H-indol-2-yl)-2-propynoates 3b,e,f.
The analytical and spectral data of ethyl 3-(4,5,6,7-tetrahydro-1H-
indol-2-yl)-2-propynoate 3a and ethyl 3-(1-vinyl-4,5,6,7-tetrahydro-
1H-indol-2-yl)-2-propynoate 3b have been reported previously.10
Ethyl 3-(1-methyl-4,5,6,7-tetrahydro-1H-indol-2-yl)-2-propynoate (3c):
White crystals (80%), mp 68–69 °C. IR (KBr) m 1694 (C@O), 2184
(C„C); 1H NMR (400.13 MHz, CDCl3) d 1.32 (t, J = 7.1 Hz, 3H,
Me), 1.70 (m, 2H, CH2-5), 1.82 (m, 2H, CH2-6), 2.45 (m, 2H, CH2-4),
2.51 (m, 2H, CH2-7), 3.52 (s, 3H, NMe), 4.25 (q, J = 7.1 Hz, 2H,
OCH2), 6.48 (s, 1H, H-3); 13C NMR (100.6 MHz, CDCl3) d 14.2
(Me), 22.4, 22.7, 22.8, 23.2 (CH2-4,5,6,7), 31.0 (NMe), 61.5 (OCH2),
81.8 (C„), 87.9 („C), 110.3 (C-2), 118.3 (C-3), 119.0 (C-4), 134.7 (C-
5), 154.7 (C@O). Anal. Calcd for C14H17NO2: C, 72.70; H, 7.41; N,
6.06. Found: C, 72.83; H, 7.22; N, 5.86.
Ethyl 3-(1-benzyl-4,5,6,7-tetrahydro-1H-indol-2-yl)-2-propynoate (3d):
White crystals (90%), mp 69–70 °C. IR (KBr) m 1697 (C@O), 2180
(C„C); 1H NMR (400.13 MHz, CDCl3) d 1.29 (t, J = 7.1 Hz, 3H,
Me), 1.67 (m, 2H, CH2-5), 1.74 (m, 2H, CH2-6), 2.39 (m, 2H, CH2-4),
2.47 (m, 2H, CH2-7), 4.21 (q, J = 7.1 Hz, 2H, OCH2), 5.11 (s, 2H,
CH2Ph), 6.55 (s, 1H, H-3), 7.06 (m, 2H, Ho), 7.23 (m, 1H, Hp), 7.29
(m, 2H, Hm); 13C NMR (100.6 MHz, CDCl3) d 14.2 (Me), 22.7, 22.8,
22.9, 23.2 (CH2-4,5,6,7), 48.3 (CH2), 61.5 (OCH2), 81.8 (C„), 87.9
(„C), 110.6 (C-2), 118.9 (C-3), 119.7 (C-4), 126.9 (Co), 127.5 (Cp),
128.7 (Cm), 134.7 (C-5), 137.5 (Ci), 154.7 (C@O). Anal. Calcd. for
C20H21NO2: C, 78.15; H, 6.89; N, 4.56. Found: C, 77.81; H, 7.01; N,
4.88.
Ethyl 3-[1-(1-isopropoxyethyl)-4,5,6,7-tetrahydro-1H-indol-2-yl]-2-
propynoate (3e): Yellowish oil (64%). IR (KBr) m 1693 (C@O), 2175
(C„C); 1H NMR (400.13 MHz, CDCl3) d 0.98 (d, J = 6.1 Hz, 3H,
MeCH), 1.18 (d, J = 5.9 Hz, 3H, MeCH), 1.32 (t, J = 7.1 Hz, 3H,
CH2Me), 1.60 (d, J = 6.1 Hz, 3H, MeCHN), 1.69–1.84 (m, 4H, CH2-
5,6), 2.47 (m, 2H, CH2-4), 2.66 (m, 1H, CH2-7), 2.87 (m, 1H, CH2-7),
3.43 (m, 1H, OCH), 4.26 (q, J = 7.1 Hz, 2H, OCH2), 5.74 (q,
J = 6.1 Hz, 1H, NCH), 6.47 (s, 1H, H-3); 13C NMR (100.6 MHz,
CDCl3) d 14.2 (CH2Me), 21.1, 22.3 (Me2CH), 22.7, 23.0, 23.1, 23.2
(CH2-4,5,6,7), 24.0 (MeCHN), 61.5 (OCH2), 68.6 (OCH), 80.8
(NCH), 81.4 (C„), 88.2 („C), 110.1 (C-2), 119.3 (C-3), 120.5 (C-
4), 134.2 (C-5), 154.7 (C@O). Anal. Calcd for C18H25NO3: C, 71.26;
H, 8.31; N, 4.62. Found: C, 71.57; H, 8.12; N, 4.23.
(q, J = 6.2 Hz, 1H, NCH), 6.46 (s, 1H, H-3); 13C NMR (100.6 MHz,
CDCl3) d 13.9, 14.3 (Me), 19.4 (CH2), 22.0, 23.1, 23.2, 23.3 (CH2-
4,5,6,7), 24.0 (MeCH), 31.5 (CH2), 61.6 (CO2CH2), 67.9 (OCH2), 81.4
(C„), 83.7 (NCH), 88.3 („C), 110.4 (C-2), 119.5 (C-3), 120.5 (C-4),
134.0 (C-5), 154.7 (C@O). Anal. Calcd. for C19H27NO3: C, 71.89; H,
8.57; N, 4.41. Found: C, 71.78; H, 8.42; N, 4.60.
Ethyl 3-1-[2-(ethylsulfanyl)ethyl]-4,5,6,7-tetrahydro-1H-indol-2-yl-2-
propynoate (3g): Colourless oil (71%). IR (KBr) m 1699 (C@O), 2186
(C„C); 1H NMR (400.13 MHz, CDCl3) d 1.26 (t, J = 7.4 Hz, 3H,
Me), 1.32 (t, J = 7.2 Hz, 3H, Me), 1.70 (m, 2H, CH2-5), 1.82 (m, 2H,
CH2-6), 2.46 (m, 2H, CH2-4), 2.56 (m, 4H, SCH2, CH2-7), 2.78 (m,
2H, CH2S), 4.06 (m, 2H, NCH2), 4.25 (q, J = 7.2 Hz, 2H, OCH2),
6.50 (s, 1H, H-3); 13C NMR (100.6 MHz, CDCl3) d 14.0, 14.6 (Me),
22.3, 22.6, 23.0 (CH2-4,5,6,7), 25.8 (SCH2), 31.6 (CH2S), 44.6
(NCH2), 61.2 (OCH2), 81.2 (C„), 87.8 („C), 109.4 (C-2), 118.8
(C-3), 119.0 (C-4), 133.9 (C-5), 154.3 (C@O). Anal. Calcd. for
C17H23NO2S: C, 66.85; H, 7.59; N, 4.58; S, 10.50. Found: C, 66.78; H,
7.89; N, 4.39, S 10.38.
Ethyl 3-1-[2-(propylsulfanyl)ethyl]-4,5,6,7-tetrahydro-1H-indol-2-yl-
2-propynoate ( 3h ): Colourless oil (81%). IR (KBr) m 1698 (C@O),
2185 (C„C); 1H NMR (400.13 MHz, CDCl3) d 0.96 (t, J = 7.2 Hz,
3H, Me), 1.32 (t, J = 6.9 Hz, 3H, Me), 1.61 (m, 2H, CH2), 1.70 (m,
2H, CH2-5), 1.81 (m, 2H, CH2-6), 2.48 (m, 4H, CH2-4,7), 2.57 (m, 2H,
SCH2), 2.76 (m, 2H, CH2S), 4.06 (m, 2H, NCH2), 4.25 (q, J = 6.9 Hz,
2H, OCH2), 6.48 (s, 1H, H-3); 13C NMR (100.6 MHz, CDCl3) d 13.4,
14.3 (Me), 22.6, 22.9, 23.0, 23.3 (CH2-4,5,6,7, CH2), 32.2 (SCH2), 34.3
(CH2S), 44.9 (NCH2), 61.5 (OCH2), 81.6 (C„), 88.0 („C), 109.6 (C-
2), 119.1 (C-4), 119.3 (C-3), 134.3 (C-5), 154.6 (C@O). Anal. Calcd.
for C18H25NO2S: C, 67.68; H, 7.89; N, 4.38; S, 10.04. Found: C,
67.81; H, 8.24; N, 4.39; S 9.86.
13. (a) Belen’kii, L. I. Heterocycles 1994, 37, 2029–2049; (b) Belen’kii, L.
I.; Kim, T. G.; Suslov, I. A.; Chuvylkin, N. D. Russ. Chem. Bull. 2005,
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15. Ethyl 3-(1-methyl-1H-indol-2-yl)propanoate (8) and ethyl 3-(1-methyl-
1H-indol-2-yl)acrylate (9): Propynoate 3c (100 mg, 0.42
mmol) was refluxed in o-xylene (4 mL) in the presence of 10% of
Pd/C (10%) for 12 h. After removing the solvent, the residue (easily
sublimated crystals, mp 50–51 °C, 88 mg) was analyzed by 1H NMR
(8:9, 4:1). Fractionation of this mixture by column chromatography
(Al2O3, n-hexane–diethyl ether, 1:1) gave indole 9 (15 mg, purity 90%)
only. Indole 8 was not isolated. Compound 8: 1H NMR (400.13 MHz,
CDCl3) d 1.16 (t, J = 7.1 Hz, 3H, Me), 2.75 (t, J = 7.3 Hz, 2H,
CH2CO), 3.06 (t, J = 7.3 Hz, 2H, CH2), 3.64 (s, 3H, Me), 4.16 (q,
J = 7.1 Hz, 2H, OCH2), 6.24 (s, 1H, H-3), 6.96 (m, 1H, H-5), 7.07 (m,
1H, H-6), 7.31 (m, 1H, H-7), 7.43 (m, 1H, H-4); 13C NMR
(100.6 MHz, CDCl3) d 14.5 (Me), 22.6 (CH2), 29.6 (NMe), 33.5
(CH2CO), 60.8 (OCH2), 99.2 (C-3), 109.7 (C-7), 119.8 (C-5), 120.4 (C-
4), 121.4 (C-6), 128.9 (C-3a), 138.5 (C-7a), 140.6 (C-2), 172.8 (C@O).
9: 1H NMR (400.13 MHz, CDCl3) d 1.24 (t, J = 7.1 Hz, 3H, Me), 3.76
(s, 3H, NMe), 4.28 (q, J = 7.1 Hz, 2H, OCH2), 6.48 (d, J = 15.7 Hz,
1H, Ha), 7.05 (m, 1H, H-5), 7.07 (m, 1H, H-3), 7.21 (m, 1H, H-6), 7.43
(m, 1H, H-7), 7.56 (m, 1H, H-4), 7.80 (d, J = 15.7 Hz, 1H, Hb).
Ethyl 3-[1-(1-butoxyethyl)-4,5,6,7-tetrahydro-1H-indol-2-yl]-2-propy-
noate (3f): Yellowish oil (62%). IR (KBr) m 1705 (C@O), 2190 (C„C);
1H NMR (400.13 MHz, CDCl3) d 0.86 (t, J = 6.9 Hz, 3H, Me of Bu),
1.33 (t, J = 6.9, 3H, CO2CH2Me), 1.49 (m, 2H, CH2), 1.62 (d,
J = 6.2 Hz, 3H, MeCH), 1.81 (m, 6H, CH2-5,6, CH2), 2.46 (m, 2H,
CH2-4), 2.65 (m, 1H, CH2-7), 2.80 (m, 1H, CH2-7), 3.14 (m, 1H,
OCH2), 3.32 (m, 1H, OCH2), 4.25 (q, J = 6.9 Hz, 2H, CO2CH2), 5.61