Efficient synthesis of carbazoles via PtCl2-catalyzed RT cyclization of 1-(indol-2-yl)-2,3-allenols: Scope and mechanism

Article abstract of DOI:10.1039/c1ob06474f

A detailed study on the scope of the efficient PtCl₂-catalyzed synthesis of carbazoles from 1-(indol-2-yl)-2,3-allenols is described. Through isotopic labeling experiments, it is confirmed that the reaction proceeds through a unique metal carbene intermediate, which undergoes subsequent highly selective 1,2-hydrogen migration to afford carbazoles. The reaction shows wide scope and allows the introduction of a variety of different substituents at different positions on the carbazole due to the substituent-loading capability of both indole and the allene moiety.

Full text of DOI:10.1039/c1ob06474f

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PAPER
Efficient synthesis of carbazoles via PtCl2-catalyzed RT cyclization of
1-(indol-2-yl)-2,3-allenols: scope and mechanism†
Wangqing Kong, Chunling Fu and Shengming Ma*
Received 29th August 2011, Accepted 11th October 2011
DOI: 10.1039/c1ob06474f
A detailed study on the scope of the efficient PtCl2-catalyzed synthesis of carbazoles from 1-(indol-2-yl)-
2,3-allenols is described. Through isotopic labeling experiments, it is confirmed that the reaction proceeds
through a unique metal carbene intermediate, which undergoes subsequent highly selective 1,2-hydrogen
migration to afford carbazoles. The reaction shows wide scope and allows the introduction of a variety of
different substituents at different positions on the carbazole due to the substituent-loading capability of
both indole and the allene moiety.
Introduction
Tricyclic carbazole derivatives are well-known alkaloids present
in plants, and many of these compounds show biological activi-
ties such as anti-oxidative, anti-tumor, anti-bacterial, anti-
microbial, psychotropic, anti-histaminic, anti-inflammatory, and
antibiotic.1 In addition, carbazole derivatives are also widely
used as organic materials with special thermal,2 electrical,3
optical,3,4 electroluminescent,5 hole-transporting, and light-emit-
ting properties.6 The important potential applications of these
carbazole derivatives have made them attractive targets for
organic synthesis.7 Scheme 1 schematically presents some of the
well-established protocols: (a) classical methods are the Fischer–
Borsche synthesis from phenylhydrazone and the Graebe–
Ullmann synthesis involving 2-(N-phenylamino)anilines;
however, the yields and regioselectivity are low;8 (b) reductive
cyclization of o-nitrobiphenyl derivatives9 requires high tempera-
ture (>140 °C) and it is almost non-regioselective; (c) the tricar-
bonyliron cyclohexadienylium salts may react with the
Scheme 1 Main strategies for the synthesis of carbazoles.
arylamines via electrophilic aromatic substitution followed by
oxidative cyclization to afford carbazoles,7a,7f,7g which has
construction of carbazoles; however, the starting materials such
already been applied in the total synthesis of various naturally
occurring carbazole alkaloids. However, utilization of stoichio-
metric amounts of tricarbonyliron and oxidant such as MnO2
as o-haloanilines, arynes10a,10b and boronic acids11,12 with pre-
existing and extensive substitution are difficult to prepare, thus,
these methods lacks atom economy/efficiency as well as regio-
make this type of reaction much less attractive; (d) Pd-catalyzed
selectivity in some cases; (e) inter- or intramolecular alkyne
pyrrole formation via N,N-diarylamines (d1),10 2-aminobiphenyl
cyclotrimerizations,13 nevertheless, require not-readily-available
starting materials such as diynamides and the regioselectivity is
(d2),11 1,1′-biphenyl-2,2′-diyl ditriflate or 2,2′-dihalobiphenyl
(with primary amines) (d3),12 have also been reported for the
rather poor (1 : 1 to 6 : 1).
For biological screening, the diversity in carbazole synthesis,
especially the regioselectivity of the installation of substituents
onto each of the nine positions of the carbazole skeleton, is very
challenging and important. Thus, the development of a mild,
efficient and regio-controlled diversified method for the prep-
aration of carbazole alkaloids, which is suitable for the introduc-
tion of specific substituent(s) to any position of the carbazole
Laboratory of Molecular Recognition and Synthesis, Department of
Chemistry, Zhejiang University, Hangzhou 310027 Zhejiang, People’s
Republic of China. E-mail: masm@sioc.ac.cn; Fax: (+86) 21-62609305
†Electronic supplementary information (ESI) available: The spectro-
scopic data (1H and 13C) for all the new compounds. See DOI: 10.1039/
c1ob06474f
2164 | Org. Biomol. Chem., 2012, 10, 2164–2173
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Table 1 PtCl2-catalyzed cyclization reaction of 4-non-substituted 1-
(indol-2-yl)-2,3-allenols
Table 2 PtCl2-catalyzed cyclization reaction of 4-mono-substituted 1-
(indol-2-yl)-2,3-allenols
1
3
Time
(h)
Yield of 2
Entry R1
R2
R3
(%)a
Entry R1 R2 R3
R4
Time (h) Yield of 4 (%)a
1
2
3
4
5
6
7
8
Et
Et
Et
Et
Et
Et
Et
Et
Et
Et
Et
Et
Et
H
H (1a)
H (1b)
H (1c)
H (1d)
H (1e)
H (1f)
H (1g)
H (1h)
H (1i)
H (1j)
H (1k)
4
3
3
4
16
15
36
24
23
12
24
13
18
70 (2a)
74 (2b)
74 (2c)
70 (2d)
69 (2e)
76 (2f)
67 (2g)
83 (2h)
64 (2i)
84 (2j)
81 (2k)
77 (2l)
77 (2m)
1
2
3
4
5
6
7
8
H
H
H
H
H
H
H
H
H
H
Me
H
H
H
H
H
H
H
H
H
H
H
H
n-C5H11 H (3a)
2
2
20
5
14
2
83 (4a)
86 (4b)
38 (4c)
50 (4d)
92 (4e)
75 (4f)
75 (4g)
85 (4h)
81 (4i)
75 (4j)
81 (4k)
78 (4l)
n-C4H9
allyl
Ph
p-MeC6H4
p-MeOC6H4
COOMe
CONMe2
CH2OH
CH2OEt
CH2OAc
Me
i-C3H7
Bn
H (3b)
H (3c)
H (3d)
H (3e)
Ph
n-C6H13 5-Me (3f)
n-C6H13 5-OMe (3g)
3
Me
4-Me (3h)
20
12
16
2
9
9
n-C6H13 4-Me (3i)
n-C6H13 5-Br (3j)
n-C6H13 H (3k)
10
11
12
13
10
11
12
CH2OCOOMe H (1l)
n-C4H9
Me n-C6H13 H (3l)
21
4-Me
(1m)
a Isolated yield.
14
15
16
17
18
19
20
21
Et
Et
Et
Et
Me
Me
Ph
Ph
5-Me (1n) 17
4-Me (1o) 20
7-Me (1p) 21
H (1q)
H (1r)
H (1s)
H (1t)
H (1u)
70 (2n)
81 (2o)
68 (2p)
60 (2q)
81 (2r)
71 (2s)
78 (2t)
72 (2u)
CH2OH
CH2OH
OBn
n-C4H9
Ph
14, and 19–21), or a benzyloxyl group (entry 17); the reaction of
1c is especially noteworthy since this reaction shows an interest-
ing exclusive cyclization of the allene instead of the alkene func-
tionality (entry 3);17 in addition, this reaction tolerates many
functional groups, such as COOMe, CONMe2 and CH2OH
(entries 7–9, 15 and 16); in entries 10–12, it should also be
noted that the secondary hydroxyl group was exclusively elimi-
nated to form the carbazole ring even when R2 is CH2OEt,
CH2OAc or CH2OCOOMe. Moreover, as expected, different
substituents may be loaded onto the indole ring to give the corre-
sponding carbazole derivatives smoothly (entries 13–16).
11
4
4
19
16
Ph
PMP Ph
a Isolated yield.
skeleton, is still of high current interest. On the other hand, Pt-
catalyzed reactions have recently been demonstrated to be power-
ful tools in synthetic organic chemistry14 owing to their extra-
ordinary potential for functional group tolerance.15 Moreover,
these processes are conveniently performed under mild reaction
conditions and no significant redox chemistry is involved.
Recently, in a communication, we have described a novel
approach to the carbazole skeleton through a Pt-catalyzed cycli-
zation of 1-(indol-2-yl)-2,3-allenols.16 Due to the ready avail-
ability of the starting allenols with their strong substituent-
loading capability, this method meets the requirement of diver-
sity, selectivity, and is atom economical by just releasing one
molecule of water. In this paper, we wish to disclose our recent
comprehensive studies on the scope and mechanism.
Cyclization reaction of 4-mono-substituted 1-(indol-2-yl)-2,3-
allenols
The scope of the reaction with regard to the 4-mono-substituted
1-(indol-2-yl)-2,3-allenols was also examined. The yields are
better when R3 is a normal alkyl group (entries 1, 2 and 6–12,
Table 2) or an aryl group (entry 5, Table 2) than those with an
isopropyl (entry 3, Table 2) or benzyl group, probably due to the
steric effect (entry 4, Table 2). Different substituents may be pre-
introduced to the indole ring (entries 6–10, Table 2). The tertiary
alcohol 3k can also smoothly afford the corresponding carbazole
4k in 81% yield (entry 11, Table 2). Meanwhile, the substi-
tutions can also be introduced to the 2-position of 2,3-allenols
(entry 12, Table 2).
Results and discussion
Cyclization reaction of 4-non-substituted 1-(indol-2-yl)-2,3-
allenols
Mechanistic study
In the preliminary study, we investigated the generality of the
cyclization of various 4-non-substituted 1-(indol-2-yl)-2,3-alle-
nols. Some of the typical results are listed in Table 1: the protect-
ing groups of nitrogen on the indole moiety may be an alkyl
(entries 1–19) or an aryl group (entries 20 and 21); R2 may be H
(entry 1), an alkyl (entries 2, 13, and 18), an aryl (entries 4–6,
In order to unveil the mechanism, we then prepared the deuter-
ium-labeled α-allenol 1-(1-ethyl-5-methyl-1H-indol-2-yl)deca-4-
deutero-2,3-dien-1-ol 3f-D (98% D): firstly, oxidation of non-1-
yn-3-ol afforded the corresponding alkynone,18 which was sub-
sequently reduced with LiAlD4.19 The tetrahydropyranyloxy-
This journal is © The Royal Society of Chemistry 2012
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protected propargylic alcohol reacted with n-BuLi to generate
the corresponding 1-alkynyl lithium, which was treated with the
carbonyl group of indole-2-carbaldehyde, followed by reduction
with LiAlH4 to afford 3f-D (Scheme 2).20
being carried out in our laboratory and will be reported in due
course.
Experimental section
General information
1H and 13C nuclear magnetic resonance spectra were recorded
with an instrument operated at 300 MHz for 1H NMR and
75 MHz for 13C NMR. CDCl3 was used as solvent in all NMR
experiments. Chemical shifts (δ) are given in parts per million
(ppm). Infrared spectra were recorded on a FT-IR spectrometer.
Mass spectra were obtained in EI mode. HRMS was carried out
in EI mode. Thin layer chromatography was performed on pre-
coated glass-back plates and visualized with UV light at 254 nm.
Flash column chromatography was performed on silica gel.
Toluene and THF were refluxed in the presence of sodium using
diphenyl ketone as indicator and distilled right before use. PtCl2
was purchased from Alfa.
Scheme 2 Preparation of 3f-D.
The reaction of 3f-D in toluene under the catalysis of PtCl2
(5 mol%) at rt proceeded smoothly affording 4f-D in 86% yield
with 94% D-incorporation at the 3-position of the newly formed
phenyl ring. This result led us to propose the mechanism shown
in Scheme 3: the reaction of PtCl2 with 3f-D would form inter-
mediate M2 via the coordination of the allene moiety with the
platinum atom followed by nucleophilic attack of indolyl C3 to
the metal-activated electrophilic CvC double bond. Subsequent
protonation of the hydroxyl group followed by elimination of
H2O affords cyclic vinylic platinum carbene intermediate M3.
Subsequent 1,2-D shift of carbene intermediate M3 would afford
the final product 4f-D. The mechanism must be different from
that which we previously observed in the Au-catalyzed reaction
of 1-arylalka-2,3-dienyl acetates.21
For the analytical data of 1a–1d, 1g–1i, 1n–1p, 1r–1t, 3a–3b,
3d, 3f–3g, 3k, 2a–2d, 2g–2i, 2n–2p, 2r–2t, 4a–4b, 4d, 4f–4g,
and 4k, see the supporting information of ref. 16.
1. Synthesis of 3-deutero-1-nonyn-3-ol23
To a 10 mL dried three-necked flask were added Fe(NO3)3·9H2O
(202.5 mg, 0.5 mmol), TEMPO (156.1 mg, 1.0 mmol), NaCl
(19.2 mg, 0.5 mmol), non-1-yn-3-ol (1.4002 g, 10 mmol) and
DCE (10 mL) under an atmosphere of oxygen. The resulting
mixture was stirred at room temperature with oxygen from a
balloon until the reaction was complete as monitored by TLC
(petroleum ether/ethyl acetate = 10/1). The resulting mixture was
diluted with diethyl ether (30 mL), dried over anhydrous
Na2SO4, and filtered through a short column of silica gel to
remove the inorganic salts. After evaporation, the residue was
purified by column chromatography on silica gel (petroleum
ether/diethyl ether = 40/1) to afford 1-nonyn-3-one (1.2420 g,
90%).18 liquid, 1H NMR (300 MHz, CDCl3) δ 3.21 (s, 1H), 2.57
(t, J = 7.8 Hz, 2H), 1.70–1.58 (m, 2H), 1.40–1.19 (m, 6H), 0.87
(t, J = 6.6 Hz, 3H); 13C NMR (75 MHz, CDCl3) δ 187.6, 81.4,
78.3, 45.4, 31.4, 28.5, 23.7, 22.4, 14.0.
To a suspension of LiAlD4 (0.941 g, 23 mmol) in 40 mL of
ether was added dropwise a solution of 1-nonyn-3-one (3.501 g,
25 mmol) in 20 mL of ether under N2 at −78 °C over 30 min.
The resulting mixture was stirred at −78 °C for another 1 h and
quenched with water. The resulting mixture was extracted with
ether. The combined extracts were dried over MgSO4, filtered,
evaporated, and purified by chromatography on silica gel to
Scheme 3 Isotopic distribution experiment and mechanism.
Conclusion
1
afford 3-deutero-1-nonyn-3-ol (2.997 g, 84%): liquid, H NMR
In conclusion, we have reported a new modular synthesis of car-
bazoles via the Pt-catalyzed cyclization of 1-(indol-2-yl)-2,3-
allenols that involves 1,2-H migration of a metal carbene inter-
mediate, and demonstrated that this methodology allows for the
synthesis of carbazoles with a variety of substituents at almost
any position on the rings. Through this study, we have demon-
strated that this new methodology for the synthesis of the poten-
tially useful carbazole substructure may find wide applications in
organic synthesis and in particular in projects oriented towards
drug discovery and new organic materials based on carbazoles.
Further studies on the synthetic applications of this reaction are
(300 MHz, CDCl3) δ 2.45 (s, 1H), 1.92 (s, 1H), 1.80–1.60 (m,
2H), 1.48–1.38 (m, 2H), 1.39–1.20 (m, 6H), 0.88 (t, J = 6.6 Hz,
3H);13C NMR (75 MHz, CDCl3) δ 85.0, 72.8, 37.5, 31.7, 28.9,
24.9, 22.5, 14.0.
2. Synthesis of 4-non-substituted 1-(indol-2-yl)-2,3-allenols
1e–1f, 1j–1m and 1u16
(1) 1-(1-Ethyl-1H-indol-2-yl)-2-(p-tolyl)buta-2,3-dien-1-ol
(1e). Typical procedure: to a mixture of 1-ethyl-1H-indole-2-
2166 | Org. Biomol. Chem., 2012, 10, 2164–2173
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carbaldehyde (0.8712 g, 5 mmol) and indium powder (1.1421 g,
10 mmol) in a saturated aqueous solution of NH4Cl (20 mL) and
THF (4 mL) was added 1-bromo-3-(4-methylphenyl)prop-2-yne
(1.5812 g, 7.5 mmol) with vigorously stirring at 0 °C. After
10 h, the reaction was complete as monitored by TLC, the
mixture was quenched with 20 mL of H2O, extracted with
diethyl ether (20 mL×3), and dried over anhydrous Na2SO4.
After filtration and evaporation, the residue was purified by
column chromatography on silica gel (petroleum ether/ethyl
acetate = 10/l) to afford 1e (1.3094 g, 86%): oil; 1H NMR
(300 MHz, CDCl3) δ 7.79 (d, J = 7.8 Hz, 1H, ArH), 7.60–7.53
(m, 1H, ArH), 7.52–7.42 (m, 3H, ArH), 7.41–7.27 (m, 3H,
ArH), 6.70 (s, 1H, ArH), 6.04–5.90 (m, 1H, CH), 5.58 (dd, J =
12.2 and 2.6 Hz, 1H, one proton from CH2v), 5.50 (dd, J =
12.0 and 2.4 Hz, 1H, one proton from CH2v), 4.62–4.27 (m,
2H, NCH2), 3.11 (d, J = 7.8 Hz, 1H, OH), 2.53 (s, 3H, ArCH3),
1.62 (t, J = 7.1 Hz, 3H, CH3); 13C NMR (75 MHz, CDCl3) δ
207.0, 139.3, 137.0, 136.9, 129.2, 127.2, 126.3, 121.8, 121.0,
119.3, 109.3, 109.0, 101.6, 82.6, 65.1, 38.3, 21.0, 15.4; IR
(neat) ν (cm−1) 3405, 3050, 2976, 2921, 2859, 1941, 1611,
1540, 1511, 1460, 1380, 1347, 1316, 1263, 1221, 1188, 1164,
1139, 1125, 1079, 1042; MS (70 ev, EI) m/z (%) 304 (M++1,
22.67), 303 (M+, 100); HRMS Calcd for C21H21NO (M+):
303.1623, Found: 303.1624.
11.2 and 1.8 Hz, 1H, one proton from CH2OC), 3.97 (dt, J =
11.1 and 2.0 Hz, 1H, one proton from CH2OC), 3.57–3.39 (m,
2H, OCH2), 3.29–3.19 (m, 1H, OH), 1.34 (t, J = 7.2 Hz, 3H,
CH3), 1.19 (t, J = 6.9 Hz, 3H, CH3); 13C NMR (75 MHz,
CDCl3) δ 205.8, 139.0, 136.9, 127.4, 121.4, 120.7, 119.3, 109.2,
102.7, 100.5, 78.5, 69.5, 66.9, 65.9, 38.3, 15.03, 15.00; IR
(neat) ν (cm−1) 3416, 3055, 2975, 2931, 2871, 1958, 1610,
1540, 1480, 1460, 1412, 1373, 1347, 1316, 1271, 1222, 1164,
1138, 1124, 1092, 1036, 1014; MS (70 ev, EI) m/z (%) 272
(M++1, 14.64), 271 (M+, 75.93), 182 (100); HRMS Calcd for
C17H21NO2 (M+): 271.1572, Found: 271.1571.
(4) 2-((1-Ethyl-1H-indol-2-yl)(hydroxy)methyl)buta-2,3-dienyl
acetate (1k). The reaction of 1-ethyl-1H-indole-2-carbaldehyde
(0.6954 g, 4 mmol), indium powder (1.1412 g, 10 mmol), and
4-bromobut-2-ynyl acetate (1.5612 g, 7.5 mmol) in THF (4 mL)
and saturated aqueous NH4Cl solution (20 mL) at 0 °C for 20 h
afforded 1k (0.6988 g, 61%) (petroleum ether/ethyl acetate = 10/
1
l∼5/1): oil; H NMR (300 MHz, CDCl3) δ 7.62–7.51 (m, 1H,
ArH), 7.31 (d, J = 8.1 Hz, 1H, ArH), 7.26–7.14 (m, 1H, ArH),
7.13–7.02 (m, 1H, ArH), 6.25 (d, J = 1.2 Hz, 1H, ArH),
5.50–5.41 (m, 1H, CH), 5.15–5.01 (m, 2H, CH2v), 4.68 (d, J =
12.0 Hz, 1H, one proton from CH2OAc), 4.54 (d, J = 12.0 Hz,
1H, one proton from CH2OAc), 4.22 (q, J = 7.2 Hz, 2H, NCH2),
3.01–2.68 (m, 1H, OH), 1.92 (s, 3H, COCH3), 1.36 (t, J = 7.2
Hz, 3H, CH3); 13C NMR (75 MHz, CDCl3) δ 206.2, 170.8,
138.2, 137.1, 127.2, 121.8, 120.9, 119.5, 109.3, 102.5, 100.9,
80.4, 66.0, 62.2, 38.5, 20.8, 15.1; IR (neat) ν (cm−1) 3425,
3039, 2980, 2925, 1960, 1739, 1606, 1543, 1461, 1378, 1347,
1316, 1233, 1165, 1027; MS (70 ev, EI) m/z (%) 286 (M++1,
19.08), 285 (M+, 93.58), 182 (100); HRMS Calcd for
C17H19NO3 (M+): 285.1365, Found: 285.1366.
The following compounds 1f, 1j–1m and 1u were prepared
according to this procedure.
(2) 1-(1-Ethyl-1H-indol-2-yl)-2-(4-methoxyphenyl)-buta-2,3-
dien-1-ol (1f). The reaction of 1-ethyl-1H-indole-2-carbaldehyde
(0.8701 g, 5 mmol), indium powder (1.1412 g, 10 mmol), and
3-bromo-1-(4-methoxylphenyl)propyne (1.6910 g, 7.5 mmol) in
THF (4 mL) and saturated aqueous NH4Cl solution (20 mL) at
0 °C for 11 h afforded 1f (1.1015 g, 69%) (petroleum ether/ethyl
(5) 2-((1-Ethyl-1H-indol-2-yl)(hydroxy)methyl)buta-2,3-dienyl
methyl carbonate (1l). The reaction of 1-ethyl-1H-indole-2-
carbaldehyde (0.6752 g, 4 mmol), indium powder (1.2105 g,
10 mmol), and 4-bromobut-2-ynyl methyl carbonate (1.2452 g,
6.0 mmol) in THF (4 mL) and saturated aqueous NH4Cl solution
(20 mL) at 0 °C for 11 h afforded 1l (0.7103 g, 61%) (petroleum
ether/ethyl acetate = 10/1∼5/1): oil; 1H NMR (300 MHz,
CDCl3) δ 7.58 (dt, J = 7.6 and 1.0 Hz, 1H, ArH), 7.32 (dd, J =
8.1 and 0.9 Hz, 1H, ArH), 7.25–7.16 (m, 1H, ArH), 7.13–7.04
(m, 1H, ArH), 6.47 (s, 1H, ArH), 5.56–5.45 (m, 1H, CH),
5.19–5.04 (m, 2H, CH2v), 4.78 (dt, J = 12.0 and 1.8 Hz, 1H,
one proton from CH2OCOO), 4.59 (dt, J = 12.3 and 2.3 Hz, 1H,
one proton from CH2OCOO), 4.35–4.18 (m, 2H, NCH2), 3.69
(s, 3H, COOCH3), 2.53 (d, J = 6.3 Hz, 1H, OH), 1.37 (t, J = 7.1
Hz, 3H, CH3); 13C NMR (75 MHz, CDCl3) δ 206.3, 155.5,
138.1, 137.1, 127.2, 121.9, 120.9, 119.5, 109.4, 102.2, 100.9,
80.5, 65.7, 65.6, 54.9, 38.4, 15.1; IR (neat) ν (cm−1) 3487,
3056, 2957, 2883, 1960, 1748, 1611, 1540, 1461, 1375, 1347,
1264, 1165, 1139, 1126, 1106, 1080, 1037, 1014; MS (70 ev,
EI) m/z (%) 302 (M++1, 8.92), 301 (M+, 46.48), 182 (100);
HRMS Calcd for C17H19NO4 (M+): 301.1314, Found: 301.1312.
1
acetate = 10/l ∼ 5/1): oil; H NMR (300 MHz, CDCl3) δ 7.52
(dt, J = 7.9 and 0.9 Hz, 1H, ArH), 7.37–7.31 (m, 1H, ArH),
7.28–7.16 (m, 3H, ArH), 7.09–7.03 (m, 1H, ArH), 6.83–6.75
(m, 2H, ArH), 6.43 (s, 1H, ArH), 5.76 (s, 1H, CH), 5.42 (dd, J =
11.9 and 2.9 Hz, 1H, one proton from CH2v), 5.34 (dd, J =
12.0 and 2.7 Hz, 1H, one proton from CH2v), 4.48–4.21 (m,
2H, NCH2), 3.74 (s, 3H, OCH3), 2.35 (bs, 1H, OH), 1.44 (t, J =
7.2 Hz, 3H, CH3); 13C NMR (75 MHz, CDCl3) δ 206.9, 158.7,
139.3, 137.0, 127.7, 127.2, 126.1, 121.8, 121.0, 119.4, 114.0,
109.3, 108.7, 101.7, 82.7, 65.3, 55.2, 38.4, 15.4; IR (neat) ν
(cm−1) 3424, 3057, 2973, 2943, 2841, 1941, 1607, 1573, 1510,
1460, 1414, 1347, 1315, 1249, 1180, 1035; MS (70 ev, EI) m/z
(%) 320 (M++1, 22.32), 319 (M+, 100); HRMS Calcd for
C21H21NO2 (M+): 319.1572, Found: 319.1570.
(3) 2-(Ethoxymethyl)-1-(1-ethyl-1H-indol-2-yl)buta-2,3-dien-
1-ol (1j). The reaction of 1-ethyl-1H-indole-2-carbaldehyde
(0.8701 g, 5 mmol), indium powder (1.2104 g, 10 mmol), and
1-bromo-4-ethoxybut-2-yne (1.3402 g, 7.5 mmol) in THF
(4 mL) and saturated aqueous NH4Cl solution (20 mL) at 0 °C
for 17 h afforded 1j (1.1099 g, 81%) (petroleum ether/ethyl
acetate = 10/1∼5/1): oil; 1H NMR (300 MHz, CDCl3) δ
7.63–7.54 (m, 1H, ArH), 7.30 (dd, J = 8.4 and 0.6 Hz, 1H,
ArH), 7.24–7.14 (m, 1H, ArH), 7.13–7.05 (m, 1H, ArH), 6.47
(s, 1H, ArH), 5.57–5.48 (m, 1H, CH), 4.99 (q, J = 2.1 Hz, 2H,
CH2v), 4.20 (dq, J = 7.2 and 1.5 Hz, 2H, NCH2), 4.08 (dt, J =
(6) 1-(1-Ethyl-4-methyl-1H-indol-2-yl)-2-butylbuta-2,3-dien-
1-ol (1m). The reaction of 1-ethyl-4-methyl-1H-indole-2-carb-
aldehyde (0.9359 g, 5 mmol), indium powder (1.1512 g,
10 mmol), and 1-bromohept-2-yne (1.3219 g, 7.5 mmol) in THF
(4 mL) and saturated aqueous NH4Cl solution (20 mL) at 0 °C for
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12 h afforded 1m (1.1462 g, 81%) (petroleum ether/ethyl acetate
= 20/1): oil; H NMR (300 MHz, CDCl3) δ 7.20–7.05 (m, 2H,
Hz, 3H, CH3); 13C NMR (75 MHz, CDCl3) δ 197.3, 138.2,
136.92, 136.90, 133.2, 128.4, 127.9, 127.8, 127.4, 121.7, 121.0,
119.3, 109.3, 101.0, 93.6, 71.0, 67.0, 38.5, 15.2; IR (neat) ν
(cm−1) 3416, 3033, 2979, 2929, 2865, 1959, 1612, 1537, 1459,
1380, 1347, 1316, 1218, 1164, 1014; MS (70 ev, EI) m/z (%)
320 (M++1, 3.24), 319 (M+, 14.10), 172 (100); HRMS Calcd for
C21H21NO2 (M+): 319.1572, Found: 319.1574.
1
ArH), 6.88 (d, J = 6.6 Hz, 1H, ArH), 6.44 (s, 1H, ArH), 5.26 (t, J
= 2.4 Hz, 1H, CH), 5.10–4.91 (m, 2H, CH2v), 4.23 (d, J = 7.2
Hz, 2H, NCH2), 2.53 (s, 3H, ArCH3), 2.29 (d, J = 5.7 Hz, 1H,
OH), 2.07–1.79 (m, 2H, CH2), 1.51–1.21 (m, 7H, 2×CH2+CH3),
0.86 (t, J = 7.2 Hz, 3H, CH3); 13C NMR (75 MHz, CDCl3) δ
204.1, 138.2, 136.8, 130.3, 127.1, 121.9, 119.6, 107.0, 99.5,
80.4, 67.6, 38.5, 29.7, 28.3, 22.3, 18.6, 15.1, 13.9; IR (neat) ν
(cm−1) 3416, 3050, 2957, 2930, 2871, 1956, 1606, 1587, 1541,
1495, 1456, 1429, 1378, 1350, 1296, 1235, 1159, 1128, 1080,
1031; MS (70 ev, EI) m/z (%) 283 (M+, 38.24), 266 (100);
HRMS Calcd for C19H25NO (M+): 283.1936, Found: 283.1935.
4. Synthesis of 4-mono-substituted 1-(indol-2-yl)-2,3-allenols
3c, 3f-D, and 3h–3j
(1) 1-(1-Ethyl-1H-indol-2-yl)-5-methylhexa-2,3-dien-1-ol (3c).
Typical procedure: to a solution of 8c (1.1012 g, 6 mmol) and
THF (25 mL) was added dropwise n-BuLi (2.5 mL, 2.5 M in
hexane, 6 mmol) at −78 °C with stirring under a nitrogen atmos-
phere within 10 min. After being stirred for 1 h at −78 °C, a sol-
ution of 1-ethyl-1H-indole-2-carbaldehyde (1.0354 g, 6 mmol)
in anhydrous THF (5 mL) was added dropwise at this tempera-
ture within 15 min. Then the mixture was allowed to warm up to
room temperature, quenched with a saturated aqueous solution of
NH4Cl (20 mL), and extracted with diethyl ether (25 mL×3).
The ether layer was dried over anhydrous Na2SO4, filtrated, and
concentrated in vacuo. The product 9c was then used without
further purification.
(7) 1-(1-(4-Methoxybenzyl)-1H-indol-2-yl)-2-phenyl-buta-2,3-
dien-1-ol (1u). The reaction of 1-(4-methoxybenzyl)-1H-indole-
2-carbaldehyde (0.9912 g, 4 mmol), indium powder (1.0125 g,
8 mmol), and 3-bromo-1-phenylpropyne (1.1925 g, 6 mmol) in
THF (4 mL) and saturated aqueous NH4Cl solution (20 mL) at
0 °C for 10 h afforded 1u (1.3000 g, 91%) (petroleum ether/
ethyl acetate = 5/1∼3/1): oil;1H NMR (300 MHz, CDCl3) δ
7.57–7.50 (m, 1H, ArH), 7.33–7.24 (m, 1H, ArH), 7.21–7.02
(m, 7H, ArH), 7.01–6.91 (m, 2H, ArH), 6.83–6.74 (m, 2H,
ArH), 6.50 (s, 1H, ArH), 5.69 (dt, J = 8.3 and 2.6 Hz, 1H, CH),
5.49 (d, J = 2.4 Hz, 2H, NCH2), 5.40 (dd, J = 12.2 and 2.9 Hz,
1H, one proton from CH2v), 5.32 (dd, J = 12.0 and 2.7 Hz, 1H,
one proton from CH2v), 3.75 (s, 3H, OCH3), 2.29 (d, J = 8.4
Hz, 1H, OH); 13C NMR (75 MHz, CDCl3) δ 207.2, 158.9,
139.9, 138.2, 133.7, 130.0, 128.3, 127.5, 127.1, 127.0, 126.4,
122.3, 121.0, 119.7, 114.1, 109.6, 109.1, 102.4, 82.8, 64.8, 55.3,
46.4; IR (neat) ν (cm−1) 3422, 3055, 2937, 2841, 1941, 1612,
1582, 1512, 1495, 1461, 1420, 1348, 1315, 1246, 1176, 1034;
MS (70 ev, EI) m/z (%) 382 (M++1, 8.05), 381 (M+, 25.66), 121
(100); HRMS Calcd for C26H23NO2 (M+): 381.1729, Found:
381.1731.
To an ice-cold suspension of LiAlH4 (0.2357 g, 6 mmol) in
dry Et2O (25 mL) under N2 was added dropwise a solution of 9c
prepared in the previous step in Et2O (5 mL) within 10 min.
Then the mixture was allowed to warm up to room temperature.
After being stirred for 1 h, the resulting mixture was quenched
with water. The aqueous layer was extracted with diethyl ether
(15 mL × 3) and dried over anhydrous Na2SO4. Filtration, evap-
oration, and column chromatography on silica gel (petroleum
ether/ethyl acetate = 10/1) gave 3c (0.6167 g, combined yield
from 8c to 3c is 40%): solid; m.p. 71.2–72.5 °C (ethyl acetate/
3. Synthesis of 1-(1-ethyl-1H-indol-2-yl)-2-(benzyloxy)buta-2,3-
dien-1-ol (1q)22
Typical procedure: to a solution of benzyloxylpropa-1,2-diene
(1.6012 g, 11 mmol) in THF (30 mL) was added dropwise n-
BuLi (4 mL, 2.5 M in hexane, 10 mmol) at −40 °C with stirring
under a nitrogen atmosphere within 10 min. After being stirred
for 50 min at −40 °C, a solution of 1-ethyl-1H-indole-2-carbal-
dehyde (1.7412 g, 10 mmol) in THF (10 mL) was added drop-
wise at this temperature within 20 min. Then the mixture was
allowed to warm up to room temperature, quenched with a satu-
rated aqueous solution of NH4Cl (20 mL), and extracted with
diethyl ether (25 mL×3). The combined organic layer was
washed with water and dried over anhydrous K2CO3. After fil-
tration and evaporation, the residue was purified by column
chromatography on alkali-Al2O3 (petroleum ether/ethyl acetate =
1
n-hexane); H NMR (300 MHz, CDCl3) δ 7.61 (dd, J = 8.0 and
0.8 Hz, 1H, ArH), 7.35 (dd, J = 8.3 and 0.8 Hz, 1H, ArH),
7.28–7.18 (m, 1H, ArH), 7.15–7.05 (m, 1H, ArH), [(6.51, s),
(6.50, s), 1H, ArH], 5.78–5.66 (m, 1H, CH), 5.58–5.48 (m, 1H,
CHv), 5.47–5.37 (m, 1H, CHv), 4.47–4.20 (m, 2H, NCH2),
2.50–2.30 (m, 1H, CH(Me)2), [2.09 (d, J = 6.6 Hz), 2.06 (d, J =
6.6 Hz), 1H, OH], 1.43 (t, J = 7.2 Hz, 3H, CH2), [1.09 (d, J =
1
5/l∼3/1) to give 1q (1.8125 g, 57%): oil; H NMR (300 MHz,
CDCl3) δ 7.58 (d, J = 8.7 Hz, 1H, ArH), 7.38–7.26 (m, 6H,
ArH), 7.24–7.16 (m, 1H, ArH), 7.13–7.04 (m, 1H, ArH), 6.52
(s, 1H, ArH), 5.61 (d, J = 2.4 Hz, 2H, CH2v), 5.48 (d, J = 7.2
Hz, 1H, CH), 4.76 (d, J = 12.0 Hz, 1H, one proton from OCH2),
4.71 (d, J = 12.0 Hz, 1H, one proton from OCH2), 4.36–4.14
(m, 2H, NCH2), 2.46 (d, J = 7.5 Hz, 1H, OH), 1.36 (t, J = 7.2
6.6 Hz), 1.04 (d, J = 6.6 Hz), 6H, 2×CH3]; IR (KBr) ν (cm−1
)
3374, 3047, 2961, 2930, 2866, 1962, 1610, 1540, 1460, 1420,
1379, 1347, 1315, 1220, 1165, 1127, 1078, 1041; MS (70 ev,
EI) m/z (%) 256 (M++1, 4.37), 255 (M+, 22.59), 237 (M+-OH,
76.37), 222 (100); Elemental analysis calcd (%) for C17H21NO:
C, 79.96; H, 8.29; N, 5.49; Found: C, 80.11, H, 8.17; N, 5.27.
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Compounds 3f-D and 3h–3j were prepared according to this
procedure.
(2) 1-(1-Ethyl-5-methyl-1H-indol-2-yl)-4-deuterodeca-2,3-dien-
1-ol (3f-D). The reaction of 8f-D,23 prepared from 3-deutero-1-
nonyn-3-ol described in the Experimental Part 1 of this manu-
script (0.7225 g, 3.2 mmol)/THF (15 mL), n-BuLi (1.3 mL,
2.5 M in hexane, 3.3 mmol), and 1-ethyl-5-methyl-1H-
indole-2-carbaldehyde (0.5910 g, 3.2 mmol)/THF (5 mL)
afforded 9f-D. The product 9f-D was then used without further
purification.
The reaction of 9f-D and LiAlH4 (0.1247 g, 3.3 mmol) in
Et2O (25 mL) afforded 3f-D (0.4881 g, combined yield from 8f-
D to 3f-D is 50%, 98% D) (petroleum ether/ethyl acetate = 10/
(4) 1-(1-Ethyl-4-methyl-1H-indol-2-yl)deca-2,3-dien-1-ol (3i).
The reaction of 8f (0.9124 g, 4 mmol)/THF (25 mL), n-BuLi
(1.7 mL, 2.5 M in hexane, 4 mmol), and 1-ethyl-4-methyl-
1H-indole-2-carbaldehyde (0.7412 g, 4 mmol)/THF (5 mL)
afforded 9i. The product 9i was then used without further
purification.
1
1): liquid; H NMR (300 MHz, CDCl3) δ 7.41–7.34 (m, 1H,
ArH), 7.22 (d, J = 8.4 Hz, 1H, ArH), 7.03 (dd, J = 8.4 Hz and
1.5 Hz, 1H, ArH), [(6.40, s)(6.39, s), 1H, ArH], 5.65–5.55 (m,
1H, CH), 5.45–5.35 (m, 1H, CHv), 4.40–4.15 (m, 2H, NCH2),
2.43 (s, 3H, ArCH3), 2.15–1.98 (m, 3H, CH2+OH), 1.50–1.20
(m, 11H, 4×CH2+CH3), 0.95–0.80 (m, 3H, CH3); IR (neat) ν
(cm−1); 3385, 2955, 2927, 2856, 1955, 1573, 1542, 1483, 1456,
1415, 1378, 1347, 1299, 1270, 1224, 1181, 1159, 1126, 1113,
1079; MS (70 ev, EI) m/z (%) 313 (M++1, 19.69), 312 (M+,
96.31), 212 (M+-C7H14D, 100); Elemental analysis calcd for
C21H28NOD: C, 80.72; H, 9.68; N, 4.48; Found: C, 80.59, H,
9.60; N, 4.36.
The reaction of 9i and LiAlH4 (0.1565 g, 4 mmol) in Et2O
(30 mL) afforded 3i (0.3860 g, combined yield from 8f to 3i is
31%) (petroleum ether/ethyl acetate
=
10/1): solid;
m.p. 65.3–66.9 °C (ethyl acetate/n-hexane); 1H NMR
(300 MHz, CDCl3) δ 7.24–7.04 (m, 2H, ArH), 6.91 (d, J = 6.6
Hz, 1H, ArH), [(6.524, s)(6.515, s), 1H, ArH], 5.71–5.59 (m,
1H, CH), 5.54–5.37 (m, 2H, CHv), 4.43–4.19 (m, 2H, NCH2),
2.55 (s, 3H, ArCH3), 2.20–2.01 (m, 3H, NCH2+OH), 1.55–1.20
(m, 11H, 4×CH2+CH3), 0.97–0.84 (m, 3H, CH3); IR (KBr) ν
(cm−1) 3312, 2954, 2926, 2854, 1964, 1588, 1534, 1495, 1455,
1432, 1368, 1350, 1287, 1233, 1158, 1147; MS (70 ev, EI) m/z
(%) 311 (M+, 4.60), 293 (M+-H2O, 100); Elemental analysis
calcd for C21H29NO: C, 80.98; H, 9.38; N, 4.50; Found: C,
80.98, H, 9.50; N, 4.47.
(5) 1-(5-Bromo-1-ethyl-1H-indol-2-yl)deca-2,3-dien-1-ol (3j).
The reaction of 8f (0.4601 g, 2 mmol)/THF (10 mL), n-BuLi
(0.8 mL, 2.5 M in hexane, 2 mmol) and 1-ethyl-5-bromo-
1H-indole-2-carbaldehyde (0.5035 g, 2 mmol)/THF (5 mL)
afforded 9j. The product 9j was then used without further purifi-
cation.
(3) 1-(1-Ethyl-4-methyl-1H-indol-2-yl)penta-2,3-dien-1-ol
(3h). The reaction of 8a (0.8315 g, 5 mmol)/THF (35 mL), n-
BuLi (2 mL, 2.5 M in hexane, 5 mmol) and 1-ethyl-4-methyl-
1H-indole-2-carbaldehyde (0.9412 g, 5 mmol)/THF (5 mL)
afforded 9h. The product 9h was then used without further
purification.
The reaction of 9h and LiAlH4 (0.2001 g, 5 mmol) in Et2O
(30 mL) afforded 3h (0.4047 g, combined yield from 8a to 3h is
34%) (petroleum ether/ethyl acetate
= 10/1∼5/1): solid;
1
m.p. 125–126 °C (ethyl acetate/n-hexane); H NMR (300 MHz,
CDCl3) δ 7.23–7.07 (m, 2H, ArH), 6.89 (d, J = 7.2 Hz, 1H,
ArH), [(6.52, s), (6.48, s), 1H, ArH], 5.70≥5.57 (m, 1H, CH),
5.56–5.34 (m, 2H, CHv), 4.43–4.19 (m, 2H, NCH2), 2.54 (s,
3H, ArCH3), 2.12–2.02 (m, 1H, OH), 1.84–1.68 (m, 3H,
The reaction of 9j and LiAlH4 (0.0891 g, 2 mmol) in Et2O
(20 mL) afforded 3j (0.2297 g, combined yield from 8f to 3j is
31%) (petroleum ether/ethyl acetate = 10/1–5/1): liquid; 1H
NMR (300 MHz, CDCl3) δ 7.70 (t, J = 1.5 Hz, 1H, ArH), 7.29
(dd, J = 8.7 and 1.8 Hz, 1H, ArH), 7.18 (d, J = 9.0 Hz, 1H,
ArH), [(6.42, s)(6.41, s), 1H, ArH], 5.65–5.53 (m, 1H, CH),
5.52–5.42 (m, 1H, CHv), 5.41–5.31 (m, 1H, CHv), 4.38–4.08
(m, 2H, NCH2), 2.37 (bs, 1H, OH), 2.19–2.00 (m, 2H, CH2),
1.55–1.19 (m, 11H, 4×CH2+CH3), 1.00–0.83 (m, 3H, CH3); IR
CH3Cv), 1.41 (t, J = 7.4 Hz, 3H, CH3); IR (KBr) ν (cm−1
)
3312, 2979, 2936, 2898, 1967, 1604, 1584, 1537, 1495, 1467,
1448, 1430, 1368, 1349, 1277, 1238, 1159, 1150, 1081; MS
(70 ev, EI) m/z (%) 242 (M++1, 17.43), 241 (M+, 100); Elemen-
tal analysis calcd for C16H19NO: C, 79.63; H, 7.94; N, 5.80;
Found: C, 79.62, H, 7.98; N, 5.64.
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(neat) ν (cm−1) 3355, 2955, 2927, 2855, 1964, 1609, 1567,
1540, 1462, 1447, 1410, 1379, 1349, 1326, 1265, 1216, 1160,
1146, 1128, 1113, 1079; MS (70 ev, EI) m/z (%) 377 (M+(81Br),
37.58), 375 (M+(79Br), 38.74), 145 (100); Elemental analysis
calcd for C20H26NBrO: C, 65.13; H, 7.16; N, 3.62; C, 65.33; H,
7.46; N, 3.30.
6. Synthesis of 1-(1-ethyl-1H-indol-2-yl)-2-methyldeca-2,3-
dien-1-ol (3l)24
To a solution of 3-chloronon-1-yne (1.1902 g, 7.5 mmol) in
Et2O (25 mL) was added dropwise n-BuLi (3 mL, 2.5 M in
hexane, 7.5 mmol) at −78 °C with stirring under a nitrogen
atmosphere within 10 min. After being stirred for 40 min at
−78 °C,
a solution of 1-ethyl-1H-indole-2-carbaldehyde
(1.2995 g, 7.5 mmol) in anhydrous Et2O (5 mL) was added
dropwise at this temperature within 5 min. Then the mixture was
allowed to warm up to −40 °C within 1.2 h. CuCN (34.0 mg,
0.38 mmol) was then added at −60 °C, followed by the addition
of a solution of CH3MgBr in Et2O (7.5 mL, 3 M in Et2O,
22.5 mmol) dropwise at −60 °C with stirring under a nitrogen
atmosphere within 15 min. After the addition was over, the reac-
tion mixture was stirred for 21 h at −30 °C as monitored by
TLC, quenched with saturated ammonium chloride solution
(30 mL), extracted with ether (3 × 30 mL), washed with water,
and dried over anhydrous Na2SO4. Filtration, evaporation and
column chromatography on silica gel (petroleum ether/ethyl
5. Synthesis of 1-(1-ethyl-1H-indol-2-yl)-4-phenylbuta-2,3-
dien-1-ol (3e)
To a solution of 8e (1.4657 g, 10 mmol) and THF (25 mL) was
slowly added dropwise n-butyl lithium (4.0 mL, 2.5 M in
hexane, 10 mmol) at −78 °C with stirring under a nitrogen
atmosphere within 10 min. After being stirred for 40 min at
−78 °C,
a solution of 1-ethyl-1H-indole-2-carbaldehyde
(1.7314 g, 10 mmol) in anhydrous THF (5 mL) was added drop-
wise at this temperature within 10 min. Then the mixture was
allowed to warm up to room temperature, quenched with the
addition a saturated aqueous solution of NH4Cl (20 mL), and
extracted with diethyl ether (25 mL×3). The ether layer was
dried over anhydrous Na2SO4, filtrated, concentrated in vacuo,
and column chromatography on silica gel (petroleum ether/ethyl
acetate = 10/1) afforded 9e, which was then used in the next
step.
1
acetate = 20/1) afforded 3l (0.4652 g, 20%): liquid; H NMR
(300 MHz, CDCl3) δ 7.57 (d, J = 7.8 Hz, 1H, ArH), 7.31 (d, J =
8.1 Hz, 1H, ArH), 7.25–7.14 (m, 1H, ArH), 7.13–7.01 (m, 1H,
ArH), 6.44 (s, 1H, ArH), 5.46–5.37 (m, 1H, CHv), 5.26–5.18
(m, 1H, CH), 4.26 (q, J = 7.2 Hz, 2H, NCH2), 2.24 (d, J = 5.7
Hz, 1H, OH), 2.06 (q, J = 6.9 Hz, 2H, CH2), 1.68 (d, J = 2.7
Hz, 3H, CH3C =), 1.46–1.20 (m, 11H, 4×CH2+CH3), 0.91–0.82
(m, 3H, CH3); IR (neat) ν (cm−1) 3401, 2959, 2926, 2855, 1971,
1656, 1614, 1563, 1537, 1459, 1372, 1346, 1315, 1227, 1168,
1123, 10100; MS (70 ev, EI) m/z (%) 311 (M+, 9.76), 293 (M+-
H2O, 69.25), 208 (100); Elemental analysis calcd for
C21H29NO: C, 80.98; H, 9.38; N, 4.50; Found: C, 80.74, H,
9.49; N, 4.38.
To a solution of CuBr (0.7251 g, 5 mmol) and 9e in Et2O
(50 mL) was added dropwise a solution of EtMgBr in Et2O
(50 mL, 1 M in Et2O, 50 mmol) at −30 °C with stirring under a
nitrogen atmosphere within 40 min. After the addition, the reac-
tion mixture was stirred for 12 h as monitored by TLC at this
temperature, quenched with saturated ammonium chloride sol-
ution (30 mL), extracted with ether (3 × 30 mL), washed with
water, and dried over anhydrous Na2SO4. Filtration, evaporation
and column chromatography on silica gel (petroleum ether/ethyl
acetate = 20/1–10/1) afforded 3e (0.3225 g, 11%): solid;
7. Synthesis of carbazoles16
1
m.p. 122–123 °C (ethyl acetate/n-hexane); H NMR (300 MHz,
CDCl3) δ 7.62 (d, J = 7.8 Hz, 1H, ArH), 7.43–7.18 (m, 7H,
ArH), 7.11 (t, J = 7.4 Hz, 1H, ArH), 6.58 (s, 1H, ArH), 6.48
(dd, J = 6.5 and 2.3 Hz, 1H, CHv), 6.12 (t, J = 6.2 Hz, 1H,
CHv), 5.63–5.50 (m, 1H, CH), 4.48–4.18 (m, 2H, NCH2), 2.14
(d, J = 6.6 Hz, 1H, OH), 1.41 (t, J = 7.2 Hz, 3H, CH3); IR
(KBr) ν (cm−1) 3321, 3045, 2985, 1953, 1489, 1460, 1347,
1314, 1221, 1161, 1101, 1026; MS (70 ev, EI) m/z (%) 290
(M++1, 8.67), 289 (M+, 40.09), 198 (100); Elemental analysis
calcd for C20H19NO: C, 83.01; H, 6.62; N, 4.84; Found: C,
83.18, H, 6.72; N, 4.65.
(1) 9-Ethyl-2-p-tolyl-9H-carbazole (2e). Typical procedure:
to a dry Schlenk tube were added sequentially PtCl2 (4.1 mg,
0.015 mmol), 1e (92.5 mg, 0.31 mmol), and toluene (1.5 mL)
under N2. After continuous stirring for 16 h at rt, the reaction
was complete as monitored by TLC. Evaporation and column
chromatography on silica gel (petroleum ether/ethyl acetate =
100/l) afforded 2e (60.2 mg, 69%): solid; m.p. 146–147 °C
(ethyl acetate/n-hexane); 1H NMR (300 MHz, CDCl3) δ
8.15–8.04 (m, 2H, ArH), 7.62 (d, J = 8.4 Hz, 2H, ArH), 7.55 (s,
1H, ArH), 7.49–7.40 (m, 2H, ArH), 7.37 (d, J = 7.8 Hz, 1H,
ArH), 7.33–7.14 (m, 3H, ArH), 4.35 (q, J = 7.2 Hz, 2H, NCH2),
2.40 (s, 3H, ArCH3), 1.41 (t, J = 7.4 Hz, 3H, CH3); 13C NMR
(75 MHz, CDCl3) δ 140.45, 140.38, 139.4, 139.1, 136.8, 129.5,
127.4, 125.5, 122.8, 122.0, 120.6, 120.4, 118.9, 118.4, 108.4,
106.7, 37.5, 21.1, 13.8; IR (KBr) ν (cm−1) 3057, 3023, 2975,
2919, 1627, 1600, 1564, 1519, 1491, 1470, 1457, 1442, 1383,
1348, 1327, 1251, 1231, 1124, 1086, 1053; MS (70 ev, EI) m/z
(%) 286 (M++1, 19.16), 285 (M+, 83.40), 270 (100); Elemental
analysis calcd for C21H19N: C, 88.38; H, 6.71; N, 4.91; Found:
C, 88.06, H, 6.57; N, 5.14.
The following compounds were prepared according to this
procedure.
2170 | Org. Biomol. Chem., 2012, 10, 2164–2173
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(2) 9-Ethyl-2-(4-methoxyphenyl)-9H-carbazole
(2f). The
1574, 1481, 1443, 1379, 1327, 1266, 1188, 1157, 1134, 1087,
1001; MS (70 ev, EI) m/z (%) 284 (M++1, 19.16), 283 (M+,
100); HRMS Calcd for C17H17NO3 (M+): 283.1208, Found:
283.1209.
reaction of PtCl2 (14.0 mg, 0.05 mmol) and 1f (320.0 mg,
1.0 mmol) in toluene (5.0 mL) at rt for 15 h afforded 2f
(230.1 mg, 76%) (petroleum ether/ethyl acetate = 40/l), solid;
1
m.p. 132–133 °C (ethyl acetate/n-hexane); H NMR (300 MHz,
(6) 9-Ethyl-2-butyl-5-methyl-9H-carbazole (2m). The reac-
tion of PtCl2 (8.0 mg, 0.03 mmol) and 1m (172.5 mg,
0.6 mmol) in toluene (3 mL) at rt for 18 h afforded 2m
(124.9 mg, 77%) (petroleum ether/ethyl acetate = 80/l): liquid;
1H NMR (300 MHz, CDCl3) δ 8.22 (d, J = 8.1 Hz, 1H, ArH),
7.51–7.40 (m, 1H, ArH), 7.39–7.30 (m, 2H, ArH), 7.21 (d, J =
7.8 Hz, 1H, ArH), 7.11 (d, J = 6.9 Hz, 1H, ArH), 4.43 (q, J =
7.2 Hz, 2H, NCH2), 2.99 (s, 3H, ArCH3), 2.96 (t, J = 7.8 Hz,
2H, ArCH2), 1.95–1.75 (m, 2H, CH2), 1.65–1.45 (m, 5H,
CH2+CH3), 1.10 (t, J = 7.2 Hz, 3H, CH3); 13C NMR (75 MHz,
CDCl3) δ 140.3, 140.2, 140.0, 133.0, 124.8, 122.3, 121.5, 120.2,
119.6, 107.7, 105.8, 37.3, 36.4, 34.3, 22.5, 20.8, 14.0, 13.7; IR
(neat) ν (cm−1) 3048, 2955, 2929, 2856, 1623, 1597, 1585,
1500, 1488, 1447, 1378, 1322, 1273, 1252, 1221, 1188, 1165,
1152, 1138, 1106, 1080, 1013; MS (70 ev, EI) m/z (%) 266
(M++1, 21.33), 265 (M+, 100); HRMS Calcd for C19H23N (M+):
265.1830, Found: 265.1830.
CDCl3) δ 8.15–8.04 (m, 2H, ArH), 7.70–7.60 (m, 2H, ArH),
7.52 (d, J = 0.9 Hz, 1H, ArH), 7.50–7.35 (m, 3H, ArH),
7.27–7.18 (m, 1H, ArH), 7.06–6.96 (m, 2H, ArH), 4.37 (q, J =
7.2 Hz, 2H, NCH2), 3.85 (s, 3H, ArOCH3), 1.43 (t, J = 7.2 Hz,
3H, CH3); 13C NMR (75 MHz, CDCl3) δ 159.0, 140.5, 140.3,
138.8, 134.8, 128.5, 125.4, 122.8, 121.7, 120.6, 120.3, 118.8,
118.2, 114.2, 108.4, 106.5, 55.3, 37.4, 13.8; IR (KBr) ν (cm−1
)
3051, 2974, 2943, 2835, 1618, 1601, 1558, 1519, 1491, 1458,
1328, 1247, 1180; MS (70 ev, EI) m/z (%) 302 (M++1, 22.89),
301 (M+, 100), 286 (M+-CH3, 81.17); Elemental analysis calcd
for C21H19NO: C, 83.69; H, 6.35; N, 4.65; Found: C, 83.82, H,
6.56; N, 4.54.
(3) 2-(Ethoxymethyl)-9-ethyl-9H-carbazole (2j). The reac-
tion of PtCl2 (4.1 mg, 0.015 mmol) and 1j (82.0 mg, 0.3 mmol)
in toluene (1.5 mL) at rt for 12 h afforded 2j (64.5 mg, 84%)
(petroleum ether/ethyl acetate
=
20/l): liquid; 1H NMR
(300 MHz, CDCl3) δ 8.12–7.98 (m, 2H, ArH), 7.48–7.31 (m,
3H, ArH), 7.25–7.14 (m, 2H, ArH), 4.69 (s, 2H, CH2OEt), 4.31
(q, J = 7.3 Hz, 2H, NCH2), 3.59 (q, J = 7.0 Hz, 2H, OCH2),
(7) 2-(Benzyloxy)-9-ethyl-9H-carbazole (2q). The reaction of
PtCl2 (3.0 mg, 0.01 mmol) and 1q (64.5 mg, 0.2 mmol) in
toluene (1 mL) at rt for 11 h afforded 2q (36.5 mg, 60%) (pet-
1.38 (t, J = 7.2 Hz, 3H, CH3), 1.28 (t, J = 7.1 Hz, 3H, CH3); 13
C
1
roleum ether/ethyl acetate = 20/l): liquid; H NMR (300 MHz,
NMR (75 MHz, CDCl3) δ 140.12, 140.08, 136.3, 125.4, 122.7,
122.3, 120.3, 120.2, 118.7, 108.4, 107.5, 73.4, 65.6, 37.4, 15.3,
13.7; IR (neat) ν (cm−1) 3054, 3022, 2974, 2931, 2867, 1630,
1602, 1573, 1497, 1480, 1443, 1379, 1327, 1302, 1235, 1178,
1157, 1102, 1020, 1001; MS (70 ev, EI) m/z (%) 254 (M++1,
15.28), 253 (M+, 77.23), 208 (100); HRMS Calcd for
C17H19NO (M+): 253.1467, Found: 253.1467.
CDCl3) δ 8.03–7.91 (m, 2H, ArH), 7.49 (d, J = 7.2 Hz, 2H,
ArH), 7.44–7.25 (m, 5H, ArH), 7.23–7.14 (m, 1H, ArH),
6.97–6.88 (m, 2H, ArH), 5.16 (s, 2H, OCH2Ar), 4.25 (q, J = 7.2
Hz, 2H, NCH2), 1.36 (t, J = 7.2 Hz, 3H, CH3); 13C NMR
(75 MHz, CDCl3) δ 158.1, 141.1, 140.0, 137.1, 128.5, 127.9,
127.6, 124.3, 123.0, 121.1, 119.5, 118.8, 117.0, 108.1, 107.6,
94.2, 70.5, 37.4, 13.6; IR (neat) ν (cm−1) 2979, 2937, 2871,
1636, 1601, 1579, 1501, 1460, 1371, 1327, 1189, 1118, 1029;
MS (70 ev, EI) m/z (%) 302 (M++1, 12.17), 301 (M+, 53.18),
210 (100); HRMS Calcd for C21H19NO (M+): 301.1467, Found:
301.1472.
(4) 2-Acetoxymethyl-9-ethyl-9H-carbazole (2k). The reac-
tion of PtCl2 (4.1 mg, 0.015 mmol) and 1k (85.1 mg, 0.3 mmol)
in toluene (1.5 mL) at rt for 24 h afforded 2k (64.7 mg, 81%)
(petroleum ether/ethyl acetate
=
10/l): liquid; 1H NMR
(300 MHz, CDCl3) δ 8.14 (t, J = 5.1 Hz, 2H, ArH), 7.60–7.40
(m, 3H, ArH), 7.36–7.24 (m, 2H, ArH), 5.37 (s, 2H, CH2OAc),
4.38 (q, J = 7.3 Hz, 2H, NCH2), 2.20 (s, 3H, COCH3), 1.47 (t, J
= 7.2 Hz, 3H, CH3); 13C NMR (75 MHz, CDCl3) δ 170.9,
140.2, 139.8, 133.2, 125.7, 122.8, 122.5, 120.4, 119.3, 118.8,
108.5, 108.4, 67.1, 37.4, 21.0, 13.7; IR (neat) ν (cm−1) 3053,
2976, 2883, 1738, 1631, 1602, 1574, 1499, 1445, 1379, 1327,
1235, 1157, 1133, 1122, 1087, 1024; MS (70 ev, EI) m/z (%)
268 (M++1, 19.59), 267 (M+, 100); HRMS Calcd for
C17H17NO2 (M+): 267.1259, Found: 267.1262.
(8) 9-(4-Methoxybenzyl)-2-phenyl-9H-carbazole (2u). The
reaction of PtCl2 (40.1 mg, 0.15 mmol) and 1u (912.4 mg,
2.39 mmol) in toluene (8 mL) at rt for 16 h afforded 2u
(623.3 mg, 72%) (petroleum ether/ethyl acetate = 40/l): solid;
1
m.p. 123–124 °C (ethyl acetate/n-hexane); H NMR (300 MHz,
CDCl3) δ 8.14 (t, J = 8.9 Hz, 2H, ArH), 7.66 (d, J = 7.2 Hz, 2H,
ArH), 7.56 (s, 1H, ArH), 7.53–7.29 (m, 6H, ArH), 7.28–7.18
(m, 1H, ArH), 7.10 (d, J = 8.7 Hz, 2H, ArH), 6.78 (d, J = 9.0
Hz, 2H, ArH), 5.48 (s, 2H, NCH2), 3.72 (s, 3H, OCH3); 13C
NMR (75 MHz, CDCl3) δ 158.9, 142.1, 141.2, 141.1, 139.3,
129.1, 128.7, 127.6, 127.5, 127.0, 125.8, 122.8, 122.2, 120.6,
120.4, 119.3, 118.9, 114.1, 109.0, 107.4, 55.2, 46.0; IR (KBr) ν
(cm−1) 1609, 1599, 1561, 1511, 1487, 1458, 1435, 1326, 1247,
1175; MS (70 ev, EI) m/z (%) 364 (M++1, 10.47), 363 (M+,
37.22), 121 (100); Elemental analysis calcd for C26H21NO: C,
85.92; H, 5.82; N, 3.85; Found: C, 86.16, H, 5.91; N, 3.78.
(5) 2-(Methoxycarbonyloxy)methyl-9-ethyl-9H-carba-zole
(2l). The reaction of PtCl2 (6.1 mg, 0.023 mmol) and 1k
(151.1 mg, 0.5 mmol) in toluene (2.5 mL) at rt for 13 h afforded
2k (109.0 mg, 77%) (petroleum ether/ethyl acetate = 20/l):
1
liquid; H NMR (300 MHz, CDCl3) δ 8.10–8.00 (m, 2H, ArH),
7.50–7.32 (m, 3H, ArH), 7.26–7.15 (m, 2H, ArH), 5.34 (s, 2H,
CH2OCOOMe), 4.29 (q, J = 7.2 Hz, 2H, NCH2), 3.78 (s, 3H,
COOCH3), 1.37 (t, J = 7.2 Hz, 3H, CH3); 13C NMR (75 MHz,
CDCl3) δ 155.7, 140.3, 139.8, 132.5, 125.8, 123.0, 122.5,
120.45, 120.40, 119.2, 118.8, 108.5, 108.4, 70.5, 54.7, 37.4,
13.7; IR (neat) ν (cm−1) 2975, 2949, 2895, 1747, 1631, 1603,
(9) 9-Ethyl-4-isopropyl-9H-carbazole (4c). The reaction of
PtCl2 (4.1 mg, 0.015 mmol) and 3c (78.0 mg, 0.31 mmol) in
toluene (1.5 mL) at rt for 20 h afforded 4c (27.2 mg, 38%) (pet-
1
roleum ether/ethyl acetate = 100/l): liquid; H NMR (300 MHz,
This journal is © The Royal Society of Chemistry 2012
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(13) 9-Ethyl-4-hexyl-5-methyl-9H-carbazole (4i). The reac-
tion of PtCl2 (2.8 mg, 0.01 mmol) and 3i (62.1 mg, 0.20 mmol)
in toluene (1.0 mL) at rt for 12 h afforded 4i (47.5 mg, 81%)
CDCl3) δ 8.22 (d, J = 7.8 Hz, 1H, ArH), 7.51–7.38 (m, 3H,
ArH), 7.33–7.25 (m, 1H, ArH), 7.24–7.20 (m, 1H, ArH), 7.16
(d, J = 7.5 Hz, 1H, ArH), 4.37 (q, J = 7.1 Hz, 1H, NCH2), 3.97
(heptet, J = 0.9 Hz, 1H, CH(Me)2), 1.49 (d, J = 6.9 Hz, 6H,
CH3), 1.42 (t, J = 7.3 Hz, 3H, CH3); 13C NMR (75 MHz,
CDCl3) δ 144.7, 140.1, 139.9, 125.7, 124.8, 123.1, 122.6, 120.2,
118.7, 114.7, 108.2, 106.0, 37.4, 30.3, 22.6, 13.7; IR (neat) ν
(cm−1) 3063, 2964, 2877, 1615, 1594, 1576, 1498, 1471, 1460,
1433, 1381, 1329, 1250, 1154, 1088; MS (70 ev, EI) m/z (%)
238 (M++1, 13.09), 237 (M+, 67.34), 222 (100); HRMS Calcd
for C17H19N (M+): 237.1517, Found: 237.1517.
(petroleum ether/ethyl acetate
=
80/l): liquid; 1H NMR
(300 MHz, CDCl3) δ 7.44–7.34 (m, 2H, ArH), 7.33–7.26 (m,
2H, ArH), 7.11–7.02 (m, 2H, ArH), 4.38 (q, J = 7.1 Hz, 2H,
NCH2), 3.37 (t, J = 8.0 Hz, 2H, ArCH2), 3.00 (s, 3H, ArCH3),
1.83–1.68 (m, 2H, CH2), 1.51–1.38 (m, 5H, CH2+CH3),
1.37–1.25 (m, 4H, 2×CH2), 0.90 (t, J = 7.1 Hz, 3H, CH3); 13C
NMR (75 MHz, CDCl3) δ 140.7, 140.6, 138.1, 132.6, 125.2,
125.1, 122.4, 121.2, 106.1, 106.0, 37.3, 37.2, 32.5, 31.8, 29.1,
25.4, 22.6, 14.1, 13.3; IR (neat) ν (cm−1) 2961, 2926, 2856,
1593, 1569, 1496, 1474, 1449, 1389, 1317, 1152; MS (70 ev,
EI) m/z (%) 294 (M++1, 23.25), 293 (M+, 100); HRMS Calcd
for C21H27N (M+): 293.2144, Found: 293.2143.
(10) 9-Ethyl-4-phenyl-9H-carbazole (4e). The reaction of
PtCl2 (4.2 mg, 0.015 mmol) and 3e (84.1 mg, 0.29 mmol) in
toluene (1.5 mL) at rt for 14 h afforded 4e (72.2 mg, 92%) (pet-
1
roleum ether/ethyl acetate = 20/l): liquid; H NMR (300 MHz,
CDCl3) δ 7.75–7.67 (m, 2H, ArH), 7.65–7.52 (m, 5H, ArH),
7.51–7.43 (m, 3H, ArH), 7.17 (dd, J = 7.2 and 1.2 Hz, 1H,
ArH), 7.10–6.98 (m, 1H, ArH), 4.45 (q, J = 7.3 Hz, 2H, NCH2),
1.51 (t, J = 7.4 Hz, 3H, CH3); 13C NMR (75 MHz, CDCl3) δ
141.4, 140.2, 140.0, 137.8, 129.2, 128.3, 127.4, 125.4, 125.3,
122.5, 120.5, 120.3, 118.4, 108.2, 107.3, 37.5, 13.7; IR (neat) ν
(cm−1) 3052, 3028, 2975, 2932, 2896, 1618, 1591, 1572, 1504,
1469, 1458, 1449, 1383, 1324, 1293, 1262, 1223, 1180, 1152,
1117, 1083, 1027; MS (70 ev, EI) m/z (%) 272 (M++1, 15.90),
271 (M+, 69.49), 256 (100); HRMS Calcd for C20H17N (M+):
271.1361, Found: 271.1361.
(14) 3-Bromo-9-ethyl-5-hexyl-9H-carbazole (4j). The reac-
tion of PtCl2 (2.9 mg, 0.011 mmol) and 3j (75.0 mg,
0.20 mmol) in toluene (1.0 mL) at rt for 16 h afforded 4j
(53.6 mg, 75%) (petroleum ether/ethyl acetate = 40/l): liquid; 1H
NMR (300 MHz, CDCl3) δ 8.21 (d, J = 1.2 Hz, 1H, ArH), 7.51
(dd, J = 8.6 and 2.0 Hz, 1H, ArH), 7.39 (t, J = 7.8 Hz, 1H,
ArH), 7.29–7.20 (m, 2H, ArH), 7.02 (d, J = 7.2 Hz, 1H, ArH),
4.28 (q, J = 7.2 Hz, 2H, NCH2), 3.15 (t, J = 7.8 Hz, 2H,
ArCH2), 1.90–1.72 (m, 2H, CH2), 1.60–1.25 (m, 9H,
3×CH2+CH3), 0.91 (t, J = 6.8 Hz, 3H, CH3); 13C NMR
(75 MHz, CDCl3) δ 140.6, 138.9, 138.5, 127.6, 126.2, 125.3,
124.6, 119.9, 111.5, 109.6, 106.3, 37.6, 34.3, 31.8, 29.5, 22.7,
14.2, 13.7; IR (neat) ν (cm−1) 2961, 2929, 2856, 1615, 1592,
1573, 1499, 1470, 1455, 1417, 1380, 1330, 1304, 1270, 1247,
1150, 1115, 1066, 1008; MS (70 ev, EI) m/z (%) 359 (M+(81Br),
100), 357 (M+(79Br), 94.91); HRMS Calcd for C20H24N79Br
(M+): 357.1092, Found: 357.1091.
(11) 3-Deutero-9-ethyl-4-hexyl-6-methyl-9H-carbazole
(4f-
D). The reaction of PtCl2 (4.2 mg, 0.015 mmol) and 3f-D
(93.2 mg, 0.3 mmol) in toluene (2 mL) at rt for 2 h afforded 4f-
D (75.2 mg, 86%, 94% D) (petroleum ether/ethyl acetate = 100/
l): liquid; 1H NMR (300 MHz, CDCl3) δ 7.92 (s, 1H, ArH),
7.42–7.19 (m, 4H, ArH), 6.99 (d, J = 6.9 Hz, 0.06H, ArH), 4.35
(q, J = 7.1 Hz, 2H, NCH2), 3.21 (t, J = 8.0 Hz, 2H, ArCH2),
2.56 (s, 3H, ArCH3), 1.93–1.76 (m, 2H, CH2), 1.62–1.47 (m,
2H, CH2), 1.46–1.28 (m, 7H, 2×CH2+CH3), 0.91 (t, J = 6.9 Hz,
3H, CH3); 13C NMR (75 MHz, CDCl3) δ 140.4, 138.4, 138.1,
127.8, 126.1, 125.1, 123.0, 122.8, 120.5, 118.9 (t, JD-C = 23.0
Hz), 107.8, 105.9, 37.3, 34.4, 31.8, 29.63, 29.55, 22.7, 21.6,
14.2, 13.7; IR (neat) ν (cm−1) 2955, 2928, 2858, 1594, 1576,
1489, 1467, 1379, 1348, 1326, 1306, 1266, 1229, 1151, 1131,
1114, 1080; MS (70 ev, EI) m/z (%) 295 (M++1, 22.85), 294
(M+, 100); HRMS Calcd for C21H26DN (M+): 294.2206, Found:
294.2201.
(15) 9-Ethyl-4-hexyl-2-methyl-9H-carbazole (4l). The reac-
tion of PtCl2 (3.1 mg, 0.012 mmol) and 3l (61.0 mg,
0.20 mmol) in toluene (1.0 mL) at rt for 21 h afforded 4l
(44.7 mg, 78%) (petroleum ether/ethyl acetate = 80/l): liquid; 1H
NMR (300 MHz, CDCl3) δ 8.07 (d, J = 8.1 Hz, 1H, ArH),
7.47–7.36 (m, 2H, ArH), 7.25–7.18 (m, 1H, ArH), 7.07 (s, 1H,
ArH), 6.85 (s, 1H, ArH), 4.33 (q, J = 7.2 Hz, 2H, NCH2), 3.16
(t, J = 7.8 Hz, 2H, ArCH2), 2.54 (s, 3H, ArCH3), 1.89–1.76 (m,
2H, CH2), 1.58–1.30 (m, 9H, 3×CH2+CH3), 0.90 (t, J = 7.2 Hz,
3H, CH3); 13C NMR (75 MHz, CDCl3) δ 140.7, 139.9, 138.2,
135.5, 124.3, 122.9, 122.2, 121.1, 118.6, 118.4, 108.1, 106.3,
37.3, 34.5, 31.8, 29.8, 29.6, 22.7, 22.1, 14.1, 13.7; IR (neat) ν
(cm−1) 2961, 2927, 2853, 1618, 1600, 1573, 1471, 1460, 1374,
1347, 1328, 1251, 1191, 1158, 1113, 1026; MS (70 ev, EI) m/z
(%) 294 (M++1, 22.55), 223 (M+, 94.79), 223 (100); HRMS
Calcd for C21H27N (M+): 293.2144, Found: 293.2150.
(12) 9-Ethyl-4,5-dimethyl-9H-carbazole (4h). The reaction
of PtCl2 (4.1 mg, 0.015 mmol) and 3h (73.0 mg, 0.30 mmol) in
toluene (1.5 mL) at rt for 20 h afforded 4h (57.7 mg, 85%) (pet-
1
roleum ether/ethyl acetate = 80/l): liquid; H NMR (300 MHz,
CDCl3) δ 7.50–7.39 (m, 2H, ArH), 7.35 (d, J = 7.5 H, 2H,
ArH), 7.10 (dd, J = 7.2 Hz and 0.3 Hz, 2H, ArH), 4.41 (q, J =
7.2 Hz, 2H, NCH2), 3.13 (s, 6H, ArCH3), 1.47 (t, J = 7.2 Hz,
3H, CH3); 13C NMR (75 MHz, CDCl3) δ 140.4, 132.3, 125.2,
122.4, 122.3, 106.2, 37.2, 26.2, 13.3; IR (neat) ν (cm−1) 3063,
3041, 2965, 2930, 1616, 1592, 1574, 1498, 1484, 1450, 1442,
1388, 1371, 1345, 1318, 1252, 1213, 1152, 1074, 1049, 1036;
MS (70 ev, EI) m/z (%) 224 (M++1, 10.84), 223 (M+, 60.31),
208 (M+-CH3, 100); HRMS Calcd for C16H17N (M+): 223.1361,
Found: 223.1363.
Acknowledgements
Financial support from the Major State Basic Research and
Development Program (2009CB825300) and the National
Natural Science Foundation of China (20732005) is greatly
appreciated. Shengming Ma is a Qiu Shi Adjunct Professor at
Zhejiang University. We thank Jinxian Liu in our group for
reproducing the results in entry 11 in Table 1, entry 3 in Table 2.
2172 | Org. Biomol. Chem., 2012, 10, 2164–2173
This journal is © The Royal Society of Chemistry 2012

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N. Zheng and S. L. Buchwald, J. Org. Chem., 2008, 73, 7603;
(c) D. S. J. Jean, Jr., S. F. Poon and J. L. Schwarzbach, Org. Lett., 2007,
9, 4893.
Notes and references
1 (a) R. S. Kapil, The Alkaloids, R. H. F. Manske, Ed.; Academic Press,
New York, 1971; Vol 13, p 273; (b) H. P. Husson, The Alkaloids,
A. Brossi, Ed.; Academic Press, New York, 1985; Vol 26, p 1;
(c) D. P. Chakraborty, The AlkaloidsA. Bossi, Ed.; Academic Press,
New York, 1993; Vol. 44, p 257; (d) H. J. Knölker, Advances in Nitrogen
Heterocycles, C. J. Moody, Ed.; JAI, Greenwich, 1995; Vol. 1, p 173;
(e) C. Ito, M. Itoigawa, A. Sato, C. M. Hasan, M. A. Rashid, H. Tokuda,
T. Mukainaka, H. Nishino and H. Furukawa, J. Nat. Prod., 2004, 67,
1488; (f) P. Bhattacharyya, D. P. Chakraborty, Progress in the Chemistry
of Organic Natural Products, W. Herz, H. Grisebach, G. W. Kirby, ed.;
Springer, Wien, 1987; Vol 52, p 159.
2 M. Häussler, J. Liu, R. Zheng, J. W. Y. Lam, A. Qin and B. Z. Tang,
Macromolecules, 2007, 40, 1914.
3 F. Sanda, T. Nakai, N. Kobayashi and T. Masuda, Macromolecules, 2004,
37, 2703.
4 (a) J. L. Díaz, A. Dobarro, B. Villacampa and D. Velasco, Chem. Mater.,
2001, 13, 2528; (b) R. M. Adhikari, R. Mondal, B. K. Shah and
D. C. Neckers, J. Org. Chem., 2007, 72, 4727.
5 (a) K. R. Justin Thomas, J. T. Lin, Y.-T. Tao and C.-W. Ko, J. Am. Chem.
Soc., 2001, 123, 9404; (b) J. Huang, Y. Niu, W. Yang, Y. Mo, M. Yuan
and Y. Cao, Macromolecules, 2002, 35, 6080.
6 (a) V. Van Dijken, J. J. A. M. Bastiaansen, N. M. M. Kiggen,
B. M. W. Langeveld, C. Rothe, A. Monkman, I. Bach, P. Stössel and
K. Brunner, J. Am. Chem. Soc., 2004, 126, 7718; (b) W.-Y. Wong, L. Liu,
D. Cui, L. M. Leung, C.-F. Kwong, T.-H. Lee and H.-F. Ng, Macromol-
ecules, 2005, 38, 4970; (c) R. M. Adhikari and D. C. Neckers, J. Org.
Chem., 2009, 74, 3341.
7 (a) H.-J. Knölker and K. R. Reddy, Chem. Rev., 2002, 102, 4303;
(b) N. Campbell and B. M. Barclay, Chem. Rev., 1947, 40, 359;
(c) J. Bergman and B. Pelcman, Pure Appl. Chem., 1990, 62, 1967;
(d) C. J. Moody, Synlett, 1994, 681; (e) B. C. G. Söderberg, Curr. Org.
Chem., 2000, 4, 727; (f) H.-J. Knölker, Chem. Soc. Rev., 1999, 28, 151;
(g) H.-J. Knölker, Top. Curr. Chem., 2005, 244, 115 For some most
recent reports, see: (h) K. Hirano, Y. Inaba, N. Takahashi, M. Shimano,
S. Oishi, N. Fujii and H. Ohno, J. Org. Chem., 2011, 76, 1212;
(i) M. Tiano and P. Belmont, J. Org. Chem., 2008, 73, 4101;
( j) M. Yamashita, H. Horiguchi, K. Hirano, T. Satoh and M. Miura,
J. Org. Chem., 2009, 74, 7481; (k) M. Yamashita, K. Hirano, T. Satoh
and M. Miura, Org. Lett., 2009, 11, 2337; (l) C.-C. Chen, L.-Y. Chin,
S.-C. Yang and M.-J. Wu, Org. Lett., 2010, 12, 5652.
8 (a) F. M. Miller and W. N. Schinske, J. Org. Chem., 1978, 3, 3384;
(b) T. L. Gilchrist, Heterocyclic ChemistryPitman, London, 1985;
(c) E. Campaigne and R. D. Lake, J. Org. Chem., 1959, 24, 478;
(d) E. Campaigne, L. Ergener, J. V. Hallum and R. D. Lake, J. Org.
Chem., 1959, 24, 487.
9 (a) M. Pizzotti, S. Cenini, S. Quici and S. Tollari, J. Chem. Soc., Perkin
Trans. 2, 1994, 913; (b) J. H. Smitrovich and I. W. Davies, Org. Lett.,
2004, 6, 533; (c) J. T. Kuethea and K. G. Childers, Adv. Synth. Catal.,
2008, 350, 1577; (d) A. W. Freeman, M. Urvoy and M. E. Criswell,
J. Org. Chem., 2005, 70, 5014.
12 (a) K. Nozaki, K. Takahashi, K. Nakano, T. Hiyama, H.-Z. Tang,
M. Fujiki, S. Yamaguchi and K. Tamao, Angew. Chem., Int. Ed., 2003,
42, 2051; (b) T. Kitawaki, Y. Hayashi, A. Ueno and N. Chida, Tetrahe-
dron, 2006, 62, 6792; (c) A. Kuwahara, K. Nakano and K. Nozaki,
J. Org. Chem., 2005, 70, 413.
13 (a) B. Witulski and C. Alayrac, Angew. Chem., Int. Ed., 2002, 41, 3281;
(b) M. F. Martínez-Esperόn, D. Rodríguez, L. Castedo and C. Saá, Org.
Lett., 2005, 7, 2213.
14 For selected reports on platinum-catalyzed reactions see: (a) S. J. Pastine,
S. M. Youn and D. Sames, Org. Lett., 2003, 5, 1055; (b) C. Liu, X. Han,
X. Wang and R. A. Widenhoefer, J. Am. Chem. Soc., 2004, 126, 3700;
(c) I. Nakamura, G. B. Bajracharya, H. Wu, K. Oishi, Y. Mizushima,
I. Gridnev and Y. Yamamoto, J. Am. Chem. Soc., 2004, 126, 15423;
(d) A. Fürstner and P. W. Davies, J. Am. Chem. Soc., 2005, 127, 15024;
(e) B. P. Taduri, Y.-F. Ran, C.-W. Huang and R.-S. Liu, Org. Lett., 2006,
8, 883; (f) S. F. Kirsch, J. T. Binder, C. Liébert and H. Menz, Angew.
Chem., Int. Ed., 2006, 45, 5878; (g) A. Fürstner and C. Aïssa, J. Am.
Chem. Soc., 2006, 128, 6306; (h) C. R. Smith, E. M. Bunnelle,
A. J. Rhodes and R. Sarpong, Org. Lett., 2007, 9, 1169;
(i) S. Bhuvaneswari, M. Jeganmohan and C.-H. Cheng, Chem.–Eur. J.,
2007, 13, 8285; ( j) K. Cariou, B. Ronan, S. Mignani, L. Fensterbank and
M. Malacria, Angew. Chem., Int. Ed., 2007, 46, 1881; (k) B. Trillo,
F. López, M. Gulías, L. Castedo and J. Mascareñas, Angew. Chem., Int.
Ed., 2008, 47, 951; (l) S. Yang, Z. Li, X. Jian and C. He, Angew. Chem.,
Int. Ed., 2009, 48, 3999; (m) W. Kong, J. Cui, G. Chen, C. Fu and S. Ma,
Org. Lett., 2009, 11, 1213; (n) N. T. Patil, R. D. Kavthe, V. S. Raut and
V. V. N. Reddy, J. Org. Chem., 2009, 74, 6315; (o) R. Chaudhuri,
A. Das, H. Y. Liao and R. S. Liu, Chem. Commun., 2010, 46, 4601;
(p) C. H. Oh, H. J. Yi, J. H. Lee and D. H. Lim, Chem. Commun., 2010,
46, 3007; (q) N. T. Patil, R. D. Kavthe, V. S. Raut, V. S. Shinde and
B. Sridhar, J. Org. Chem., 2010, 75, 1277.
15 For selected Pt-catalyzed applications in total synthesis, see:
(a) A. Fürstner, H. Szillat, B. Gabor and R. Mynott, J. Am. Chem. Soc.,
1998, 120, 8305; (b) B. M. Trost and G. A. Doherty, J. Am. Chem. Soc.,
2000, 122, 3801; (c) Y. Harrak, C. Blaszykowski, M. Bernard, K. Cariou,
E. Mainetti, V. Mouriès, A.-L. Fensterbank and M. Malacria, J. Am.
Chem. Soc., 2004, 126, 8656; (d) A. S. K. Hashmi and M. Rudolph,
Chem. Soc. Rev., 2008, 37, 1766.
16 W. Kong, C. Fu and S. Ma, Chem. Commun., 2009, 4572.
17 (a) C. Liu and R. A. Widenhoefer, Org. Lett., 2007, 9, 1935; (b) X. Han
and R. A. Widenhoefer, Org. Lett., 2006, 8, 3801; (c) C. Liu,
C. F. Bender, X. Han and R. A. Widenhoefer, Chem. Commun., 2007,
3607; (d) C. Liu and R. A. Widenhoefer, J. Am. Chem. Soc., 2004, 126,
10250; (e) Z. Zhang, C. Liu, R. E. Kinder, X. Han, H. Qian and
R. A. Widenhoefer, J. Am. Chem. Soc., 2006, 128, 9066.
18 S. Ma, J. Liu, S. Li, B. Chen, J. Cheng, J. Kuang, Y. Liu, B. Wan, Y. Wang,
J. Ye, Q. Yu, W. Yuan and S. Yu, Adv. Synth. Catal., 2011, 353, 1005.
19 J. A. Marshall and X.-J. Wang, J. Org. Chem., 1991, 56, 4913.
20 (a) B. M, Trost, C. Jonasson and M. Wuchrer, J. Am. Chem. Soc., 2001,
123, 2736; (b) B. M. Trost and C. Jonasson, Angew. Chem., Int. Ed.,
2003, 42, 2063; (c) J. S. Cowie, P. D. Landor and S. R. Landor, J. Chem.
Soc., Perkin Trans. 1, 1973, 720.
21 (a) C. Park and P. H. Lee, Org. Lett., 2008, 10, 3359; (b) J. Mo and
P. H. Lee, Org. Lett., 2010, 12, 2570; (c) W. Kong, C. Fu and S. Ma,
Eur. J. Org. Chem., 2010, 6545.
10 (a) Z. Liu and R. C. Larock, Org. Lett., 2004, 6, 3739; (b) Z. Liu and R.
C. Larock, Tetrahedron, 2007, 63, 347; (c) R. B. Bedford and
C. S. J. Cazin, Chem. Commun., 2002, 2310; (d) R. B. Bedford and
M. Betham, J. Org. Chem., 2006, 71, 9403; (e) R. Forke, M. P. Krahl,
K. Krause, G. Schlechtingen and H.-J. Knölker, Synlett, 2007, 2, 268;
(f) B. Åkermark, L. Eberson, E. Jonsson and E. Petterssont, J. Org.
Chem., 1975, 40, 1365; (g) H. Hagelin, J. D. Oslob and B. Åkermark,
Chem.–Eur. J., 1999, 5, 2413; (h) M. P. Krahl, A. Jäger, K. Krause and
H.-J. Knölker, Org. Biomol. Chem., 2006, 4, 3215.
22 Brandsma, H. D. Verkuijsse. Synthesis of Acetylenes, Allenes and Cumu-
lenes, Amsterdam, Elsevier, 1981.
23 W. Kong, J. Cui, Y. Yu, G. Chen, C. Fu and S. Ma, Org. Lett., 2009, 11,
1213.
11 (a) W. C. P. Tsang, N. Zheng and S. L. Buchwald, J. Am. Chem. Soc.,
2005, 127, 14560; (b) W. C. P. Tsang, R. H. Munday, G. Brasche,
24 J. Li, W. Kong, C. Fu and S. Ma, J. Org. Chem., 2009, 74, 5104.
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