Click chemistry with 2-ethynyl-4,5,6,7-tetrahydroindoles: Towards functionalized tetrahydroindole-triazole ensembles

Article abstract of DOI:10.1055/s-0032-1318149

2-Ethynyl-4,5,6,7-tetrahydroindoles, readily available from 4,5,6,7-tetrahydroindoles and bromoacetylenes on K₂CO₃, when treated with sodium azide in DMSO, afford functionalized tetrahydroindole-triazoles ensembles. The reaction proc

Full text of DOI:10.1055/s-0032-1318149

678▌
PAPER
paper
Click Chemistry with 2-Ethynyl-4,5,6,7-tetrahydroindoles: Towards
Functionalized Tetrahydroindole-Triazole Ensembles
Tetrahydroindole-Triazole Ensembles
Lyubov N. Sobenina,a Denis N. Tomilin,a Igor A. Ushakov,a Albina I. Mikhaleva,a J. Sh. Ma,b G. Yang,b
Boris A. Trofimov*a
a
A. E. Favorsky Irkutsk Institute of Chemistry, Siberian Branch, Russian Academy of Sciences, 1 Favorsky Str., 664033 Irkutsk,
Russian Federation
b
Beijing National Laboratory for Molecular Sciences, CAS Key Laboratory of Photochemistry, Institute of Chemistry,
Chinese Academy of Sciences, Beijing 100190, P. R. of China
Fax +7(3952)419346; E-mail: boris_trofimov@irioch.irk.ru
Received: 02.12.2012; Accepted after revision: 11.01.2013
sents a challenge and remains the subject of a steadily
growing number of investigations.
Abstract: 2-Ethynyl-4,5,6,7-tetrahydroindoles, readily available
from 4,5,6,7-tetrahydroindoles and bromoacetylenes on K2CO3,
when treated with sodium azide in DMSO, afford functionalized
tetrahydroindole-triazoles ensembles. The reaction proceeds under
mild conditions (room temperature) to give triazoles with acyl or
ester moieties in quantitative yields.
Numerous synthetic methods for the preparation of 1,2,3-
triazole derivatives have been developed.18 Among them,
Huisgen 1,3-dipolar cycloaddition between an alkyne and
an azide (‘click chemistry’) is the classical and most ex-
tensively used method.19 However, this method is not so
widespread in the synthesis of triazole ensembles with
pyrrole or indole rings because of the inaccessibility of
starting ethynylpyrroles or ethynylindoles, especially
those bearing electron-withdrawing substituents at the tri-
ple bond.
Key words: click chemistry, cycloaddition, alkynes, sodium azide,
triazoles
The triazole nucleus is one of the most important hetero-
cyclic structures, and is frequently encountered in a num-
ber of natural products and medicines,1 including
antimicrobial,2 anti-inflammatory, analgesic,3 antituber-
cular,4 antiviral,5 anticancer,6 anticonvulsant,7 and
antifungal8 agents. Triazoles have also been incorporated
in a wide variety of therapeutically interesting drugs, in-
cluding H1/H2 histamine receptor blockers, CNS stimu-
lants, antianxiety agents and sedatives.9 Recently, some
new 1,2,3-triazole derivatives have been reported to in-
hibit tumor proliferation, invasion, and metastasis.10 Im-
portantly, they are applied as antimycotics in drugs such
as fluconazole, itraconazole, and voriconazole.11 Tri-
azoles are also used in several industrial fields, such as ag-
rochemicals,12 corrosion inhibitors,13 dyes,14 and optical
brighteners.15
Recently, owing to the discovery of transition-metal- and
solvent-free ethynylation of the pyrrole nucleus with elec-
trophilic haloacetylenes on alumina20 or other active
surfaces,21 2-ethynylpyrroles, 2-ethynyl-4,5,6,7-tetrahy-
droindoles and 3-ethynylindoles having electron-with-
drawing substituents, including acyl and ester moieties at
the triple bond have become readily available. This new
methodology has made 3-(4,5,6,7-tetrahydroindol-2-yl)-
2-propynones 1a–d and 3-(4,5,6,7-tetrahydroindol-2-yl)-
2-propynoates 1e–h particularly accessible on a large-
scale by using 4,5,6,7-tetrahydroindole22 as starting mate-
rial. Consequently, the reaction of these compounds with
sodium azide might be considered as a short-cut to tri-
azole-containing tetrahydroindole moieties.
Further developments in the synthesis of triazoles is clear-
ly of essential importance. Ensembles of triazoles with
other heterocycles, particularly with pyrrole or indole
rings, possess additional potential to act as promising bio-
logically active compounds and components for high-tech
materials. This is supported for instance by the observa-
tions that pyrrolyl- and indolyltriazoles have anticancer6f
and antifungal16 activities and also by the finding that pyr-
rolo-triazolophane ensembles are reported to act as recep-
tors for the pyrophosphate anion.17
These compounds, due to their easy aromatization, might
be suitable intermediates for the synthesis of triazole de-
rivatives with the indole function.
Herein, we disclose an efficient method for the synthesis
of triazole derivatives with tetrahydroindole moieties. The
method comprises the 1,3-dipolar cycloaddition of sodi-
um azide to the C≡C bond of 3-(4,5,6,7-tetrahydroindol-
2-yl)-2-propynones 1a–d and 3-(4,5,6,7-tetrahydroindol-
2-yl)-2-propynoates 1e–h (Scheme 1, Table 1).
Because the ease of azide cyclization is governed by po-
larization of the acetylene, we anticipated that acetylenic
ketones 1a–d and acetylenic esters 1e–h would be reac-
tive enough towards sodium azide in spite of possible ste-
ric effects from the bulky tetrahydroindole substituents.
As expected, these acetylenes easily reacted with sodium
azide in dimethyl sulfoxide (DMSO) at room temperature
However, the development of synthetic strategies for the
preparation of pyrrolyl- or indolyl-triazoles still repre-
SYNTHESIS 2013, 45, 0678–0682
Advanced online publication: 01.02.2013
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DOI: 10.1055/s-0032-1318149; Art ID: SS-2012-Z0842-OP
© Georg Thieme Verlag Stuttgart · New York

PAPER
Tetrahydroindole-Triazole Ensembles
679
O
Ph
Ph
R2
O
O
NaN3
MeI
N
O
N
N
R1
N
R1
N
DMSO, 20–25 °C
6–12 h
N
R
N
N
N
N
N
KOH, DMSO
N
N
R2
R
r.t., 4 h
1a–h
H
Me
H
2a–h
2b,d
4b,d
Ph
Ph
Scheme 1 Synthesis of triazole derivatives 2a–h with tetrahydroin-
dole moieties
O
O
+
Me
+
N
N
N
N
N
N
N
N
Me
R
Me
5b,d
6b
Table 1 Synthesis of Triazole Derivatives 2a–h
R = Me, CH=CH2
R1
R2
Yield of 2a–h (%)
Scheme 3 Alkylation of triazoles 2b and 2d
Pyrrole
1a, 2a
1b, 2b
1c, 2c
1d, 2d
1e, 2e
1f, 2f
H
Ph
95
97
96
94
96
94
97
92
The structural assignment of these regioisomers was
based on 2D 1H-13C HMBC, 1H-15N HMBC, and NOESY
NMR experiments.
Me
Bn
Ph
Ph
In conclusion, we have developed a short-cut to function-
alized tetrahydroindole-triazole ensembles 2a–h from
available 2-ethynyltetrahydroindoles with electron-with-
drawing substituents at the triple bond using ‘click chem-
istry’ (1,3-dipolar addition of azide anion to the triple
bond). The synthesized compounds represent a new fam-
ily of promising precursors for drug design and are potent
building blocks for heterocyclic compounds and anion re-
ceptors; furthermore, the properties of the resulting com-
pounds can be easily fine-tuned by changing their
functionalities.
Vinyl
H
Ph
OEt
OEt
OEt
OEt
Me
Bn
1g, 2g
1h, 2h
Vinyl
(6–12 h) to give the corresponding triazoles 2a–h in es-
sentially quantitative yield. Acetylenic ketones 1a–d are IR spectra were obtained with a Bruker Vertex 70 spectrometer
(400–4000 cm–1, KBr pellets). 1H (400.1 MHz) and 13C NMR
more reactive towards sodium azide than acetylenic esters
1e–h; the reaction time for the former was 6 hours while
12 hours were necessary for the preparation of triazoles
containing the CO2Et group.
(100.6 MHz) spectra were recorded with a Bruker DPX-400 instru-
ment. The concerted application of 1H-1H 2D homonuclear experi-
ments COSY and NOESY and also 1H-13C 2D heteronuclear
experiments HSQC and HMBC were used to differentiate the car-
bon and proton resonances in all cases. TLC was carried out using
TLC Silica gel 60 F254 plates. Elemental analyses were recorded
with an EA FLASH 1112 Series (CHN Analyzer) instrument.
Interestingly, the acetylenic amide 3 appears to be inac-
tive in this cyclization (under analogous conditions), the
starting compounds being recovered almost completely, a
result that is in agreement with previous reports (Scheme
2).19b
1-Phenyl-3-(4,5,6,7-tetrahydroindol-2-yl)-2-propynones 1a–d and
ethyl 3-(4,5,6,7-tetrahydroindol-2-yl)-2-propynoates 1e–h were
prepared from pyrroles and benzoylbromoacetylene and ethyl bro-
mopropynoate, correspondingly, according to previous reports.20,21
O
NMe2
Synthesis of Triazoles 2a–h; General Procedure
NaN3
NaN3 (75 mg, 1.15 mmol) was carefully stirred in DMSO (20 mL)
for 10–15 min, then 2-ethynyl-4,5,6,7-tetrahydriondole 1a–h (1.15
mmol) in DMSO (20 mL) was added and the reaction mixture was
stirred for 6–12 h at r.t. (until TLC showed no traces of starting acet-
ylene). The reaction mixture was diluted with H2O (150 mL) and
neutralized with 10% acetic acid. After 10 min, the formed residue
was filtered off and washed with H2O to give pure product.
O
N
N
N
DMSO, r.t.
6–12 h
N
Me
Me
N
NMe2
H
3
Scheme 2 The reaction of acetylenic amide 3 with NaN3
Triazoles 2b and 2d were alkylated with methyl iodide
under basic conditions using the KOH/DMSO system to
afford a mixture of two possible regioisomers: N-1 (4b
and 4d) and N-2 (5b and 5d) substituted 1,2,3-triazoles in
approximately 1:1 ratio (Scheme 3). In the case of triazole
2b, traces of the third regioisomer, triazole 6b, were de-
tected in the reaction mixture.
Phenyl [5-(4,5,6,7-Tetrahydro-1H-indol-2-yl)-3H-1,2,3-triazol-
4-yl]methanone (2a)
Yield: 0.319 g (95%); light-brown solid; mp 234–236 °C.
IR (KBr): 3457, 3317, 3280, 3060, 2922, 2845, 1631, 1588, 1536,
1462, 1401, 1305, 1251, 1182, 1145, 1057, 982, 953, 896, 793, 748,
698, 523, 467 cm–1.
1H NMR (400 MHz, CDCl3): δ = 11.55 (br s, 1 H, N-H), 8.24–8.23
(m, 2 H, o-PhH), 7.61–7.57 (m, 1 H, p-PhH), 7.52–7.48 (m, 2 H, m-
PhH), 6.56 (d, J = 2.0 Hz, 1 H, H-3), 2.72–2.69 (m, 2 H, CH2-7),
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2013, 45, 678–682

680
L. N. Sobenina et al.
PAPER
2.56–2.54 (m, 2 H, CH2-4), 1.85–1.83 (m, 2 H, CH2-6), 1.78–1.76
(m, 2 H, CH2-5).
13C NMR (100 MHz, DMSO-d6): δ = 187.9, 138.4, 138.1, 137.4,
132.9, 131.0, 130.5, 128.3, 119.3, 116.1, 110.6, 23.4, 23.0, 22.9,
22.7.
1H NMR (400 MHz, CDCl3): δ = 14.07 (br s, 1 H, N-H of triazole),
11.01 (s, 1 H, N-H of pyrrole), 6.62 (d, J = 2.1 Hz, 1 H, H-3), 4.39
(q, J = 7.2 Hz, 2 H, OCH2), 2.65–2.63 (m, 2 H, CH2-7), 2.48–2.46
(m, 2 H, CH2-4), 1.83–1.81 (m, 2 H, CH2-6), 1.72–1.70 (m, 2 H,
CH2-5), 1.33 (t, J = 7.2 Hz, 3 H, CH3).
13C NMR (100 MHz, CDCl3): δ = 163.5, 136.8, 131.4, 130.1, 119.7,
115.5, 109.8, 61.7, 23.6, 23.1, 23.0, 22.7, 14.1.
Anal. Calcd. for C17H16N4O: C, 69.85; H, 5.52; N, 19.17. Found: C,
70.02; H, 5.40; N, 19.02.
Anal. Calcd. for C13H16N4O2: C, 59.99; H, 6.20; N, 21.52. Found:
C, 60.04; H, 6.42; N, 21.29.
Phenyl [5-(1-Methyl-4,5,6,7-tetrahydro-1H-indol-2-yl)-3H-
1,2,3-triazol-4-yl]methanone (2b)
Yield: 0.341 g (97%); yellow solid; mp 108–110 °C.
Ethyl 5-(1-Methyl-4,5,6,7-tetrahydro-1H-indol-2-yl)-3H-1,2,3-
triazole-4-carboxylate (2f)
Yield: 0.296 g (94%); yellow solid; mp 44–46 °C.
IR (KBr): 3457, 3130, 2929, 2846, 1642, 1534, 1450, 1390, 1315,
1276, 1173, 1142, 980, 902, 803, 753, 691 cm–1.
IR (KBr): 3432, 3184, 3159, 2930, 2847, 1725, 1611, 1553, 1445,
1382, 1294, 1236, 1129, 1027, 838, 787, 643 cm–1.
1H NMR (400 MHz, CDCl3): δ = 11.95 (br s, 1 H, N-H), 8.16–8.14
(m, 2 H, o-PhH), 7.59–7.56 (m, 1 H, p-PhH), 7.48–7.45 (m, 2 H, m-
PhH), 6.40 (s, 1 H, H-3), 3.44 (s, 3 H, NMe), 2.56–2.54 (m, 2 H,
CH2-7), 2.51–2.49 (m, 2 H, CH2-4), 1.84–1.82 (m, 2 H, CH2-5),
1.73–1.71 (m, 2 H, CH2-6).
13C NMR (100 MHz, CDCl3): δ = 187.4, 150.4, 141.3, 137.4, 133.1,
132.9, 130.4, 128.3, 118.1, 117.5, 111.5, 31.6, 23.5, 23.1, 23.0,
22.3.
1H NMR (400 MHz, CDCl3): δ = 13.07 (br s, 1 H, N-H), 6.46 (s,
1 H, H-3), 4.38 (q, J = 7.1 Hz, 2 H, OCH2), 3.47 (s, 3 H, NMe),
2.56–2.54 (m, 2 H, CH2-7), 2.51–2.50 (m, 2 H, CH2-4), 1.84–1.82
(m, 2 H, CH2-6), 1.73–1.71 (m, 2 H, CH2-5), 1.35 (t, J = 7.1 Hz,
3 H, CH3).
13C NMR (100 MHz, CDCl3): δ = 161.2, 139.1, 134.2, 132.3, 117.8,
117.7, 111.8, 61.4, 31.6, 23.6, 23.2, 23.1, 22.4, 14.2.
Anal. Calcd. for C18H18N4O: C, 70.57; H, 5.92; N, 18.29. Found: C,
70.25; H, 5.76; N, 18.46.
Anal. Calcd. for C14H18N4O2: C, 61.30; H, 6.61; N, 20.42. Found:
C, 61.68; H, 6.65; N, 20.05.
Phenyl [5-(1-Benzyl-4,5,6,7-tetrahydro-1H-indol-2-yl)-3H-
1,2,3-triazol-4-yl]methanone (2c)
Yield: 0.422 g (96%); yellow solid; mp 58–60 °C.
Ethyl 5-(1-Benzyl-4,5,6,7-tetrahydro-1H-indol-2-yl)-3H-1,2,3-
triazole-4-carboxylate (2g)
Yield: 0.390 g (97%); yellow solid; mp 52–54 °C.
IR (KBr): 3482, 3094, 2927, 2847, 1653, 1599, 1541, 1447, 1399,
1277, 1141, 985, 905, 801, 694 cm–1.
IR (KBr): 3435, 3200, 3137, 2927, 2849, 1725, 1608, 1539, 1448,
1406, 1294, 1185, 1122, 1039, 787, 729, 700, 640 cm–1.
1H NMR (400 MHz, CDCl3): δ = 11.73 (br s, 1 H, N-H), 8.04–8.02
(m, 2 H, o-PhH), 7.57–7.55 (m, 1 H, p-PhH), 7.44–7.42 (m, 2 H, m-
PhH), 7.23–7.19 (m, 3 H, m,p-PhH-CH2), 6.86–6.84 (m, 2 H, o-
PhHCH2), 6.56 (s, 1 H, H-3), 5.20 (s, 2 H, CH2Ph), 2.53–2.51 (m,
2 H, CH2-7), 2.46–2.44 (m, 2 H, CH2-4), 1.79–1.77 (m, 2 H, CH2-
5), 1.73–1.71 (m, 2 H, CH2-6).
1H NMR (400 MHz, CDCl3): δ = 12.39 (br s, 1 H, NH), 7.21–7.14
(m, 3 H, m,p-PhH), 6.84–6.82 (m, 2 H, o-PhH), 6.63 (s, 1 H, H-3),
5.19 (s, 2 H, CH2Ph), 4.36 (q, J = 7.1 Hz, 2 H, OCH2), 2.56–2.54
(m, 2 H, CH2-7), 2.44–2.42 (m, 2 H, CH2-4), 1.78–1.76 (m, 2 H,
CH2-6), 1.73–1.71 (m, 2 H, CH2-5), 1.33 (t, J = 7.1 Hz, 3 H, CH3).
13C NMR (100 MHz, CDCl3): δ = 187.6, 141.5, 138.6, 137.3,
133.03, 133.0, 132.6, 130.4, 128.5, 128.2, 126.9, 125.9, 118.5,
118.2, 112.7, 47.8, 23.4, 23.1, 22.9, 22.2.
13C NMR (100 MHz, CDCl3): δ = 161.1, 141.0, 138.8, 134.9, 132.5,
128.6, 127.0, 126.0, 118.5, 118.2, 112.9, 61.6, 47.9, 23.6, 23.2,
23.1, 22.4, 14.2.
Anal. Calcd. for C24H22N4O: C, 75.37; H, 5.80; N, 14.65. Found: C,
75.75; H, 5.92; N, 14.25.
Anal. Calcd. for C20H22N4O2: C, 68.55; H, 6.33; N, 15.99. Found:
C, 68.21; H, 6.27; N, 15.61.
Phenyl [5-(1-Vinyl-4,5,6,7-tetrahydro-1H-indol-2-yl)-3H-1,2,3-
triazol-4-yl]methanone (2d)
Yield: 0.344 g (94%); yellow solid; mp 132–134 °C.
Ethyl 5-(1-Vinyl-4,5,6,7-tetrahydro-1H-indol-2-yl)-3H-1,2,3-
triazole-4-carboxylate (2h)
Yield: 0.303 g (92%); yellow oil.
IR (KBr): 3481, 3092, 3055, 2930, 2849, 1633, 1599, 1561, 1457,
1424, 1286, 1251, 1168, 1142, 993, 902, 802, 748, 691 cm–1.
IR (KBr): 3432, 3239, 3131, 2931, 2850, 1728, 1642, 1558, 1436,
1382, 1293, 1235, 1193, 1134, 1016, 869, 792 cm–1.
1H NMR (400 MHz, CDCl3): δ = 12.30 (br s, 1 H, N-H), 8.07–8.05
(m, 2 H, o-PhH), 7.56–7.54 (m, 1 H, p-PhH), 7.43–7.41 (m, 2 H, m-
PhH), 6.67 (dd, J = 8.7, 16.0 Hz, 1 H, NCH), 6.51 (s, 1 H, H-3), 4.77
(d, J = 8.7 Hz, 1 H, CH=CH2), 4.75 (d, J = 16.0 Hz, 1 H, CH=CH2),
2.59–2.57 (m, 2 H, CH2-7), 2.50–2.48 (m, 2 H, CH2-4), 1.79–1.77
(m, 2 H, CH2-5), 1.72–1.70 (m, 2 H, CH2-6).
1H NMR (400 MHz, CDCl3): δ = 12.77 (br s, 1 H, NH), 6.78 (dd,
J = 8.9, 16.0 Hz, 1 H, NCH), 6.51 (s, 1 H, H-3), 4.82 (d, J = 8.9 Hz,
1 H, CH=CH2), 4.78 (d, J = 16.0 Hz, 1 H, CH=CH2), 4.36 (q, J =
7.1 Hz, 2 H, OCH2), 2.66–2.64 (m, 2 H, CH2-7), 2.53–2.51 (m, 2 H,
CH2-4), 1.82–1.80 (m, 2 H, CH2-5), 1.74–1.73 (m, 2 H, CH2-6),
1.33 (t, J = 7.1 Hz, 3 H, CH3).
13C NMR (100 MHz, CDCl3): δ = 187.1, 141.3, 138.3, 137.3, 133.1,
132.6, 130.8, 130.4, 128.2, 119.9, 117.2, 114.4, 105.9, 23.7, 23.3,
23.1, 23.0.
13C NMR (100 MHz, CDCl3): δ = 160.8, 138.1, 134.6, 131.7, 130.8,
119.5, 117.0, 114.1, 104.6, 61.3, 23.8, 23.2, 22.9, 22.8, 13.9.
Anal. Calcd. for C15H18N4O2: C, 62.92; H, 6.34; N, 19.57. Found:
C, 62.78; H, 6.52; N, 19.78.
Anal. Calcd. for C19H18N4O: C, 71.68; H, 5.70; N, 17.60. Found: C,
71.48; H, 5.55; N, 17.79.
[1-Methyl-5-(1-methyl-4,5,6,7-tetrahydro-1H-indol-2-yl)-1H-
1,2,3-triazol-4-yl](phenyl)methanone (4b)
Ethyl 5-(4,5,6,7-Tetrahydro-1H-indol-2-yl)-3H-1,2,3-triazole-4-
carboxylate (2e)
Yield: 0.287 g (96%); light-brown solid; mp 182–184 °C.
1H NMR (400 MHz, CDCl3): δ = 8.28–8.26 (m, 2 H, o-PhH), 7.53–
7.52 (m, 1 H, p-PhH), 7.50–7.48 (m, 2 H, m-PhH), 6.06 (s, 1 H, H-
3), 4.00 (s, 3 H, N-Me of triazole), 3.20 (s, 3 H, N-Me of pyrrole),
2.56–2.54 (m, 2 H, CH2-7), 2.50–2.48 (m, 2 H, CH2-4), 1.84–1.82
(m, 2 H, CH2-5), 1.73–1.71 (m, 2 H, CH2-6).
IR (KBr): 3302, 3125, 3082, 2929, 2846, 1690, 1612, 1557, 1479,
1414, 1352, 1304, 1251, 1138, 999, 841, 785, 686 cm–1.
Synthesis 2013, 45, 678–682
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13C NMR (100 MHz, CDCl3): δ = 186.3 (CO), 144.0 (C-4 of tri-
azole), 138.9 (p-Ph), 137.3 (i-Ph), 134.9 (C-5 of triazole), 132.5 (C-
5), 130.5 (o-Ph), 128.1 (m-Ph), 118.2 (C-4), 114.9 (C-2), 110.7 (C-
3), 35.3 (N-Me of triazole), 31.0 (N-Me of pyrrole), 23.5, 23.2, 23.0,
22.2 (CH2-4,5,6,7).
15N NMR (40 MHz, CDCl3): δ = –233.9 (NMe of pyrrole), –141.2
(NMe of triazole), –19.0 (N of triazole).
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[2-Methyl-5-(1-methyl-4,5,6,7-tetrahydro-1H-indol-2-yl)-2H-
1,2,3-triazol-4-yl](phenyl)methanone (5b)
1H NMR (400 MHz, CDCl3): δ = 8.01–7.99 (m, 2 H, o-PhH), 7.53–
7.51 (m, 1 H, p-PhH), 7.50–7.48 (m, 2 H, m-PhH), 6.53 (s, 1 H, H-
3), 4.21 (s, 3 H, N-Me of triazole), 3.50 (s, 3 H, N-Me of pyrrole),
2.62–2.60 (m, 2 H, CH2-7), 2.48–2.46 (m, 2 H, CH2-4), 1.84–1.82
(m, 2 H, CH2-5), 1.73–1.71 (m, 2 H, CH2-6).
13C NMR (100 MHz, CDCl3): δ = 187.1 (CO), 143.5 (C-5 of tri-
azole), 142.1 (C-4 of triazole), 137.7 (i-Ph), 132.8 (p-Ph), 131.7 (C-
5), 130.2 (o-Ph), 128.1 (m-Ph), 119.8 (C-2), 117.5 (C-4), 111.4 (C-
3), 42.2 (N-Me of triazole), 31.7 (N-Me of pyrrole), 23.3, 23.1, 23.0,
22.1 (CH2-4,5,6,7).
15N NMR (40 MHz, CDCl3): δ = –237.0 (NMe of pyrrole), –136.9
(NMe of triazole), –54.6, –44.2 (N of triazole).
[1-Methyl-5-(1-vinyl-4,5,6,7-tetrahydro-1H-indol-2-yl)-1H-
1,2,3-triazol-4-yl](phenyl)methanone (4d)
1H NMR (400 MHz, CDCl3): δ = 8.20–8.18 (m, 2 H, o-PhH), 7.53–
7.51 (m, 1 H, p-PhH), 7.44–7.42 (m, 2 H, m-PhH), 6.52 (dd, J = 9.0,
15.9 Hz, 1 H, NCH), 6.19 (s, 1 H, H-3), 4.59 (d, J = 9.0 Hz, 1 H,
CH=CH2), 4.53 (d, J = 15.9 Hz, 1 H, CH=CH2), 3.98 (s, 3 H, N-
Me), 2.64–2.62 (m, 2 H, CH2-7), 2.51–2.49 (m, 2 H, CH2-4), 1.83–
1.81 (m, 2 H, CH2-5), 1.74–1.72 (m, 2 H, CH2-6).
13C NMR (100 MHz, CDCl3): δ = 186.2 (CO), 144.3 (C-4 of tri-
azole), 137.2 (i-Ph), 135.1 (C-5 of triazole), 132.9 (p-Ph), 132.2 (C-
5), 130.5 (o-Ph), 129.9 (CH=CH2), 128.2 (m-Ph), 119.9 (C-4),
114.2 (C-2), 114.0 (C-3), 104.2 (CH=CH2), 35.3 (NMe), 23.5, 23.1,
23.0, 22.9 (CH2-4,5,6,7).
15N NMR (40 MHz, CDCl3): δ = –213.0 (N of pyrrole), –141.8
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(NMe of triazole), –19.6 (N of triazole).
[2-Methyl-5-(1-vinyl-4,5,6,7-tetrahydro-1H-indol-2-yl)-2H-
1,2,3-triazol-4-yl](phenyl)methanone (5d)
1H NMR (400 MHz, CDCl3): δ = 8.01–7.99 (m, 2 H, o-PhH), 7.53–
7.51 (m, 2 H, m-PhH), 7.44–7.42 (m, 1 H, p-PhH), 6.81 (dd, J = 9.0,
15.9 Hz, 1 H, NCH), 6.45 (s, 1 H, H-3), 4.79 (d, J = 15.9 Hz, 1 H,
CH=CH2), 4.68 (d, J = 9.0 Hz, 1 H, CH=CH2), 4.26 (s, 3 H, N-Me),
2.63–2.61 (m, 2 H, CH2-7), 2.49–2.47 (m, 2 H, CH2-4), 1.83–1.81
(m, 2 H, CH2-5), 1.74–1.72 (m, 2 H, CH2-6).
13C NMR (100 MHz, CDCl3): δ = 186.8 (CO), 143.3 (C-5 of tri-
azole), 142.7 (C-4 of triazole), 137.4 (i-Ph), 132.9 (p-Ph), 131.3
(CH=CH2), 131.2 (C-5), 130.2 (o-Ph), 128.2 (m-Ph), 119.6 (C-2),
119.4 (C-4), 113.4 (C-3), 104.0 (CH=CH2), 42.4 (NMe), 23.4, 23.2,
23.0, 22.9 (CH2-4,5,6,7).
15N NMR (40 MHz, CDCl3): δ = –214.9 (N of pyrrole), –136.3
(NMe of triazole), –52.1, –44.2 (N of triazole).
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Acknowledgment
The authors thank Presidium of RAS (project No. 5.9.1) for the sup-
port of this research. This work was also carried out under financial
support of the leading scientific schools by the President of the Rus-
sian Federation (Grant NSh-1550.2012).
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Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synthesis.SnuIomprifgtooatrinSugpIoi
nnfomartit
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