Hg(OTf)2-catalyzed direct vinylation of tryptamines and versatile applications for tandem reactions

Article abstract of DOI:10.1039/c2ob25236h

We have developed a unique catalytic protocol for direct gem-vinylation of tryptamine derivatives employing Hg(OTf)₂ as the optimum catalyst. The intermolecular vinylations with a series of aromatic acetylenes proceeded under ambient temperature at the C2 positions of indoles with high functional group tolerance. Based on the mechanistic insights, we further developed the tandem reactions successfully constructing a quaternary center.

Full text of DOI:10.1039/c2ob25236h

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PAPER
Hg(OTf)2-catalyzed direct vinylation of tryptamines and versatile
applications for tandem reactions†
Haruki Mizoguchi, Hideaki Oikawa and Hiroki Oguri*
Received 1st February 2012, Accepted 22nd March 2012
DOI: 10.1039/c2ob25236h
We have developed a unique catalytic protocol for direct gem-vinylation of tryptamine derivatives
employing Hg(OTf)2 as the optimum catalyst. The intermolecular vinylations with a series of aromatic
acetylenes proceeded under ambient temperature at the C2 positions of indoles with high functional group
tolerance. Based on the mechanistic insights, we further developed the tandem reactions successfully
constructing a quaternary center.
direct C2 vinylation of 3-substituted indoles using a cationic
Introduction
gold(I)-catalyst.8 This conversion offers a rare example of the
gem-selective C–H alkenylation at the indole C2 position
(Scheme 1d), while related manipulations at the pyrrole C2
position have been explored a bit more due to the distinct
regio-selectivities between indole and pyrrole systems as a
nucleophile.9 To our knowledge, catalytic and chemo-selective
protocols for the gem-2-vinylation of 3-substituted indole deriva-
tives remain very limited,10 despite the importance on indole
The indole ring system is ubiquitous in natural products and has
been exploited as a privileged motif for the development of phar-
maceuticals and biologically active agents. During the course of
our synthesis on naturally occurring alkaloids and their ana-
logues,1 we sought to develop a catalytic protocol that allows
gem-selective vinylation of tryptamine derivatives with inten-
tions to minimize the number of steps and amount of waste.
Metal-catalyzed cross-couplings are one of the most reliable
means to install alkenyl groups onto aromatic rings with exqui-
site control in regio-selectivity and olefin geometry.2 However, it
requires premodifications of both coupling partners (Scheme 1a).
The direct C–H functionalization of aromatic systems without
the need for premodifications emerged as a direct and atom-
economical alternative to cross-couplings and the Mizoroki–
Heck reaction.3 For example, the Fujiwara–Moritani reaction
offers direct oxidative functionalization of arenes, yielding trans-
substituted product as the major olefin isomer (Scheme 1b). With
regards to catalytic direct vinylation of an indole system, two
types of approaches have been exploited to date.4 The first
approach involves an oxidative addition, which usually takes
place at the electron-rich C3 position of indoles and thereby
yields a C3-vinylated product.5 In most cases, catalytic functio-
nalization of C–H at the C2 position poses a difficult problem
and often requires a directing group at the N1 or C3 positions,
entailing high temperature conditions (Scheme 1c).6 The other
approach employs a metal activator of alkynes, generating
electrophilic metal complexes and subsequent hydroarylation
reactions.7 In 2007, Echavarren and coworkers reported the
Division of Chemistry, Graduate School of Science, Hokkaido
University, N10 W8, Sapporo 060-0810, Japan. E-mail: oguri@
sci.hokudai.ac.jp; Fax: +81-11-706-3448; Tel: +81-11-706-3429
†Electronic supplementary information (ESI) available: 1H and 13C
NMR spectra of new compounds. See DOI: 10.1039/c2ob25236h
Scheme 1 Synthesis of branched olefins.
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alkaloid synthesis.11 Herein, we report a Hg(OTf)2-catalyzed
direct coupling reaction of indoles and aryl acetylenes yielding
2-vinylated tryptamine derivatives under mild conditions.
Several applications for the tandem reactions are also described.
Results and discussion
Employing tryptamine derivative 1 protected with a nosyl group
and phenyl acetylene 2a as the substrates, we screened catalytic
conditions effecting the direct vinylation at the indole C2 pos-
ition (Table 1). We first applied Echavarren’s conditions exploit-
ing a cationic gold(I) complex.8 The coupling of 1 and 2a gave
the desired product 3a having a gem-substituted vinyl group in
38% yield (entry 1). A further reaction of the product 3a gave
the dimeric product 4 in a comparable yield (37%).12 In order to
achieve highly chemoselective intermolecular alkenylations
without affecting the labile products bearing the vinyl group con-
jugated to an indole system, we found that Hg(OTf)2, also
known as Nishizawa reagent,13 was the optimum catalyst for the
sensitive transformation.14 As shown in entry 2, treatment of 1
and 2a (1.5 equiv.) in dichloromethane with Hg(OTf)2 (5 mol%)
at room temperature for 3 h afforded the desired vinylated
product 3a in 82% yield. Reducing the amount of catalyst to
1 mol% (entry 3) resulted in longer reaction time (24 h), giving
a slightly lower yield (74%). Other mercury(II) salts, including
Hg(OCOCF3)2 and Hg(OAc)2, were not capable of performing
the catalytic conversions (entry 4). Single application of
trifluoromethanesulfonic acid as the Brønsted acid mediator
resulted in no conversion (entry 5).
Fig. 1 Intermolecular gem-alkenylation of either tryptamine or trypto-
phan derivative (1, 5) with aromatic acetylene 2.
Table 1 Screening of catalyst for coupling of 1 with 2a.
Entry
Catalyst
Time
Yield: 3a
Scheme 2
1
2
3
4
5
[AuCl(PPh3) + AgSbF6] (7 mol%)
Hg(OTf)2 (5 mol%)
Hg(OTf)2 (1 mol%)
Hg(OCOCF3)2 (10 mol%)
TfOH (10 mol%)
8 h
3 h
24 h
18 h
38%a
82%
74%b
9%
be a successful application for direct vinylation of L-tryptophan
derivative (5 → 6).15 On the whole, the intermolecular vinylation
of tryptamine derivatives with various aromatic terminal alkynes
occurs regioselectively at the indole C2 position under ambient
temperature.16
a 4 (37%): dimer of 3a. b Recovery of 1 (17%).
To gain mechanistic insights, we performed a conversion
employing an internal acetylene 7 (Scheme 2). Hg(OTf)2-cata-
lyzed alkenylation with 7 also proceeded to afford 8 despite
diminished reactivity and lower yield (66%). This implies a
plausible reaction mechanism, shown in Scheme 3, initiated by
the formation of π-complex A, and thereby activating the
aromatic acetylene. Friedel–Crafts type C–C bond formation
(intermediate A → B) would occur regioselectively at the indole
C2 position due to the presence of alkyl substituent at the C3
position. Regeneration of the indole system could form an
We then investigated the scope of intermolecular vinylations,
employing a series of aromatic terminal alkynes (Fig. 1). The
presence of electron withdrawing substituents on the aromatic
ring gave the corresponding products 3b–3d in good yields.
Alkynes 2e and 2f, conjugated with either coumarine or indole
moieties, also afforded the functionalized tryptamine derivatives
3e and 3f. Conversion of the aromatic acetylene 2g, bearing an
electron donating methoxy substituent, also proceeded efficiently
to give 3g in 83% yield. In addition, this protocol was shown to
This journal is © The Royal Society of Chemistry 2012
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Scheme 3 Proposed mechanism.
Scheme 4
Scheme 5
reaction with the internal acetylene 11 bearing a hydroxyl group.
Intermolecular alkenylation and subsequent intramolecular C–O
bond formation produced 12 in 65% yield, allowing direct for-
mation of the tetrahydrofuran ring attached to an indole
system.17
intermediate C. In situ generation of triflic acid would allow sub-
sequent protonation at the terminal olefinic position (intermedi-
ate C → D), giving product 3a and the regenerated catalyst.
To verify the hypothesis, we then conducted the reaction with
deuterated terminal acetylene 2a–D (Scheme 2). In fact, the deu-
terium was incorporated on the vinylated product 3a–D at both
terminal olefinic positions at almost the same ratios (∼25%).
This is consistent with the proposed mechanism involving proto-
nation and subsequent elimination of the mercury catalyst (C →
D → 3a) aside from the lower deuterium incorporation in 3a–D.
The substantial loss of deuterium (almost 50%) might be attribu-
ted to proton exchange between product 3a and the cationic
species E by a catalytic amount of triflic acid (Scheme 3).
Taking the mechanistic insights into account, we then envi-
sioned tandem reactions by making use of the electrophilic
nature of the vinylated product 3a, presumably being in equili-
brium with the cationic species E. As shown in Scheme 4, the
stirred mixture of 1 and 2a in the presence of Hg(OTf)2 was sub-
jected to sequential treatment of N-methylindole 9 at 45 °C. The
expected tandem coupling reactions gave a 66% yield of the bis-
indole compound 10 with successful construction of a quater-
nary carbon center. Likewise, we also attempted the sequential
Throughout our investigations so far, we found the unique
conversion employing aromatic acetylene 2i with a N,N-
dimethylaniline group as a notable exception (Scheme 5). Treat-
ment of 1 and 2i with Hg(OTf)2 (10 mol%) produced not only
the expected 3i (42%), but also significant amounts of 13 (18%)
and 14 (24%). The unexpected products 13 and 14 are composed
of the pyrrolidinoindoline skeleton,18 bearing one or two units of
N,N-dimethyl-4-vinyl-aniline groups. The formation of 14
suggests a mechanistic rationale involving the C3 vinylation
incorporating a quaternary carbon and subsequent cyclization
between the resulting iminium species and sulfone amide, fol-
lowed by a second vinylation at the N1 position. Despite a lower
yield of the C2 vinylated product 3i, the unique reactivity of the
aromatic acetylene 2i, capable of divergent C2/C3 gem-vinyla-
tions, prompted us to perform the conversion with tryptamine
derivatives 15 bearing a methyl substituent at the indole C2 pos-
ition. As expected, the intermolecular coupling of 15 with 2i
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proceeded regioselectively at C3 with complete conversion of
15. In addition to the expected mono-vinylated product 16, bis-
vinylated product 17, containing two N,N-dimethyl-4-vinyl-
aniline groups, was also formed. Since treatment of 16 and 2i
under identical conditions effected vinylation at the N1 position
to form 17, we assume intermolecular sequential alkenylations
through C3 vinylation, followed by an ene-type reaction of 16
with an activated species of 2i giving 17. It is likely that the treat-
ment of 2i and Hg(OTf)2 could generate an allenyl mercury inter-
mediate F expected to exert anomalous reactivity with increased
ionic and electrophilic properties compared to that of 2a.
In summary, we have developed a Hg(OTf)2-catalyzed proto-
col allowing direct and intermolecular alkenylation of trypta-
mines with aromatic acetylenes at room temperature. Derivatives
of tryptamine and tryptophan were efficiently alkenylated at the
C2 position in a highly chemoselective and regiocontrolled
manner. A variety of functionalities and substituents on aryl
group attached to acetylenes were well tolerated except for the
dimethyl amino substituent. Based on the mechanistic insights,
we further realized a three-component coupling as well as a
sequential cyclization demonstrating the versatile applicability of
this protocol in the development of tandem reactions for assem-
bling elaborated indole derivatives.
acetylene 2a (60 μl, 0.542 mmol) in dichloromethane (3.6 ml).
After stirring for 3 h at room temperature, the mixture was added
saturated NaHCO3 (aq.) and extracted with EtOAc. The organic
extracts were washed with saturated NaHCO3 (aq.), water and
brine, dried over Na2SO4, and concentrated. The residue was
purified by silica-gel column chromatography to afford 3a
(136 mg, 0.304 mmol, 82%) as a pale yellow amorphous.
1H-NMR (400 MHz, CDCl3) δ 2.85 (2H, t, J = 7.3 Hz), 3.30
(2H, td, J = 7.3, 5.7 Hz), 5.24 (1H, t, J = 5.7 Hz), 5.51 (1H, s),
5.68 (1H, s), 7.00 (1H, ddd, J = 7.9, 7.0, 0.9 Hz), 7.16 (1H, ddd,
J = 8.2, 7.0, 0.9 Hz), 7.25 (1H, d, J = 7.9 Hz), 7.30–7.34 (5H,
m), 7.37 (1H, d, J = 7.9 Hz), 7.59–7.65 (2H, m), 7.69 (1H, dd,
J = 5.9, 3.6 Hz), 7.96 (1H, br-s), 7.98 (1H, dd, J = 5.9, 3.4 Hz);
13C-NMR (100 MHz, CDCl3) δ 25.00, 43.96, 110.08, 111.08,
117.31, 118.58, 119.92, 122.77, 125.53, 127.74, 128.20, 128.62,
128.70, 131.02, 132.74, 133.43, 133.47, 135.38, 135.44, 139.77,
141.04, 147.67; UPLC analysis: t = 1.49 min (λmax 300 nm);
HR-MS (ESI) calcd for C24H21N3O4SNa [M + Na]+ 470.1150,
found 470.1161. According to this procedure, deuterium labeling
experiment was performed using deuterated 2a–D.
N-(2-(2-(1-(2-Bromophenyl)vinyl)-1H-indol-3-yl)ethyl)-2-
nitrobenzenesulfonamide (3b)
Experimental section
According to the general procedure, tryptamine derivative 1
(70.8 mg, 0.205 mmol) was treated with corresponding aryl
acetylene and Hg(OTf)2 for 4.5 h to afford 3b (90.6 mg,
0.172 mmol, 84%) as a pale yellow amorphous. 1H-NMR
(400 MHz, CDCl3) δ 2.70 (2H, t, J = 7.5 Hz), 3.20 (2H, td, J =
7.5, 5.9 Hz), 5.14 (1H, t, J = 5.9 Hz), 5.42 (1H, s), 5.74 (1H, s),
7.00 (1H, t, J = 7.5 Hz), 7.15 (1H, t, J = 7.5 Hz), 7.22–7.28 (2H,
m), 7.34–7.43 (3H, m), 7.54 (1H, d, J = 7.7 Hz), 7.64 (1H, d, J
= 3.2 Hz), 7.66 (1H, d, J = 3.4 Hz), 7.74 (1H, dd, J = 5.9, 3.2
Hz), 7.88 (1H, br-s), 8.02 (1H, dd, J = 5.9, 3.4 Hz); 13C-NMR
(100 MHz, CDCl3) δ 24.97, 43.86, 110.12, 111.05, 118.60,
118.72, 120.02, 123.10, 123.21, 125.50, 127.91, 128.76, 129.97,
131.11, 131.56, 132.76, 133.33, 133.44, 133.64, 133.98, 135.61,
141.12, 141.19, 147.84; UPLC analysis: t = 1.76 min (λmax
304 nm); HR-MS (ESI) calcd for C24H20N3O4BrSNa [M + Na]+
548.0256, found 548.0264.
NMR spectra were recorded on JEOL JNM-ECX 400 (1H/
400 MHz, 13C/100 MHz) spectrometers. Chemical Shifts are
reported in δ (ppm) using chloroform, acetonitrile and dimethyl
sulfoxide as an internal standard of δ 7.26, 1.94, 2.50 and 77.16,
1
118.26, 39.52 for H and 13C-NMR, respectively. The medium
pressure liquid chromatography (MPLC) purifications were per-
formed on a YAMAZEN YFLC-AI-580. Analytical ultra per-
formance liquid chromatography (UPLC) was carried out on
WATERS ACQUITY™ UPLC® H-Class system with ACQUITY
UPLC® BEH C18 1.7 μm 2.1 × 50 mm column and PDA detec-
tor (210–400 nm). Sample was dissolved in MeCN and UPLC
fractionation conditions consisted of a linear gradient from 50%
H2O/50% MeCN to 5% H2O/95% MeCN in 3 min at a flow rate
of 0.5 mL min−1, held at MeCN 100% for 0.50 min at a flow
rate of 0.5 mL min−1, then a convex gradient back to 80% H2O/
20% MeCN in 0.5 min at a flow rate of 0.5 mL min−1, then held
at 80% H2O/20% MeCN for 0.5 min at a flow rate of 0.5 mL
min−1. Total run time for each injection was 4.5 min. Com-
pounds were detected by 252 nm UV absorption and character-
ized by photo diode array. Analytical high performance liquid
chromatography (HPLC) was carried out on GILSON 321pump
equipped with a GILSON UV/VIS-151 detector, GILSON
FC203B fraction collector and Inertsil® SIL-100A 10 × 250 mm
column. Where necessary, solvents were distilled from appropri-
ate drying agents prior to use. Flash column chromatography
was performed using Kanto Silica Gel 60N.
N-(2-(2-(1-(4-Fluorophenyl)vinyl)-1H-indol-3-yl)ethyl)-2-
nitrobenzenesulfonamide (3c)
According to the general procedure, tryptamine derivative 1
(107 mg, 0.309 mmol) was treated with corresponding aryl
acetylene and Hg(OTf)2 for 2 h to afford 3c (121 mg,
0.259 mmol, 84%) as a pale yellow amorphous. 1H-NMR
(400 MHz, CDCl3) δ 2.84 (2H, t, J = 7.3 Hz), 3.29 (2H, td, J =
7.3, 5.7 Hz), 5.24 (1H, t, J = 5.7 Hz), 5.50 (1H, s), 5.64 (1H, s),
7.00 (1H, m), 7.01 (2H, d, J = 8.8 Hz), 7.16 (1H, ddd, J = 8.2,
7.0, 0.7 Hz), 7.26–7.33 (3H, m), 7.37 (1H, d, J = 8.2 Hz),
7.61–7.66 (2H, m), 7.69 (1H, dd, J = 5.9, 3.6 Hz), 7.95–8.00
(2H, m); 13C-NMR (100 MHz, CDCl3) δ 24.96, 43.91, 110.12,
111.12, 115.60 (d, J = 21.9 Hz), 117.24, 118.59, 119.99, 122.88,
125.55, 128.13, 129.43 (d, J = 7.6 Hz), 130.97, 132.73, 133.35,
133.47, 135.19, 135.48, 135.87 (d, J = 2.9 Hz), 140.02, 147.63,
162.96 (d, J = 248.9 Hz); UPLC analysis: t = 1.72 min (λmax
General procedure for vinylation of tryptamine and tryptophane
derivatives: 2-nitro-N-(2-(2-(1-phenylvinyl)-1H-indol-3-yl)ethyl)-
benzenesulfonamide (3a)
Hg(OTf)2 (9.02 mg, 0.0181 mmol) was added to a solution of
tryptamine derivative 1 (128 mg, 0.371 mmol) and aryl
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301 nm); HR-MS (ESI) calcd for C24H20N3O4FSNa [M + Na]+
488.1056, found 488.1082.
(3H, m), 7.64–7.67 (1H, m), 7.79 (2H, d, J = 8.4 Hz), 7.89 (1H,
br-s), 7.90–7.95 (2H, m); 13C-NMR (100 MHz, CDCl3) δ 21.69,
24.99, 43.92, 109.25, 110.03, 111.12, 113.55, 117.16, 118.53,
119.88, 120.74, 122.71, 124.31, 125.45, 126.93, 127.17, 128.09,
130.12, 130.84, 131.01, 132.69, 133.34, 133.42, 134.76, 135.14,
135.41, 135.60, 140.79, 145.35, 147.56; UPLC analysis: t =
2.23 min (λmax 299 nm); HR-MS (ESI) calcd for
C33H28N4O6S2Na [M + Na]+ 663.1348, found 663.1368.
N-(2-(2-(1-(3,5-Bis(trifluoromethyl)phenyl)vinyl)-1H-indol-3-yl)-
ethyl)-2-nitrobenzenesulfonamide (3d)
According to the general procedure, tryptamine derivative 1
(789 mg, 2.28 mmol) was treated with corresponding aryl acety-
lene and Hg(OTf)2 for 3.5 h to afford 3d (1.14 g, 1.95 mmol,
1
86%) as a pale yellow amorphous. H-NMR (400 MHz, CDCl3)
N-(2-(2-(1-(4-Methoxyphenyl)vinyl)-1H-indol-3-yl)ethyl)-2-
δ 2.82 (2H, t, J = 7.0 Hz), 3.30 (2H, td, J = 7.0, 5.9 Hz), 5.23
(1H, t, J = 5.9 Hz), 5.76 (1H, s), 5.84 (1H, s), 7.04 (1H, ddd, J =
8.2, 7.0, 0.9 Hz), 7.21 (1H, ddd, J = 8.2, 7.0, 0.9 Hz), 7.32 (1H,
dd, J = 8.2, 0.9 Hz), 7.41 (1H, dd, J = 8.2, 0.9 Hz), 7.61–7.67
(2H, m), 7.67–7.71 (1H, m), 7.80 (2H, br-s), 7.87 (1H, br-s),
7.95 (1H, br-s), 7.98–8.02 (1H, m); 13C-NMR (100 MHz,
CDCl3) δ 25.34, 43.81, 111.13, 111.39, 118.97, 120.42, 120.50,
122.36 (q, J = 3.8 Hz), 123.27 (q, J = 273.7 Hz), 123.55,
125.59, 127.71, 128.10, 131.02, 132.29 (q, J = 33.4 Hz),
132.78, 133.50, 133.55, 133.60, 135.91, 138.97, 142.04, 147.78;
UPLC analysis: t = 2.18 min (λmax 285 nm); HR-MS (ESI) calcd
for C26H19N3O4F6SNa [M + Na]+ 606.0898, found 606.0905.
nitrobenzenesulfonamide (3g)
According to the general procedure, tryptamine derivative 1
(108 mg, 0.312 mmol) was treated with corresponding aryl
acetylene and Hg(OTf)2 for 1.7 h to afford 3g (123 mg,
0.258 mmol, 83%) as a pale yellow amorphous. 1H-NMR
(400 MHz, CDCl3) δ 2.85 (2H, t, J = 7.3 Hz), 3.30 (2H, td, J =
7.3, 5.7 Hz), 3.83 (3H, s), 5.22 (1H, br-t, J = 5.7 Hz), 5.40 (1H,
s), 5.59 (1H, s), 6.86 (2H, d, J = 8.6 Hz), 6.99 (1H, ddd, J = 7.9,
7.3, 0.7 Hz), 7.15 (1H, ddd, J = 8.2, 7.3, 0.9 Hz), 7.25 (2H, d, J
= 8.6 Hz), 7.26 (1H, d, J = 7.9 Hz), 7.36 (1H, d, J = 8.2 Hz),
7.63 (2H, dd, J = 5.9, 3.4 Hz), 7.69 (1H, dd, J = 6.1, 3.4 Hz),
7.95 (1H, br-s), 7.99 (1H, dd, J = 5.9, 3.4 Hz); 13C-NMR
(100 MHz, CDCl3) δ 24.98, 43.97, 55.48, 109.94, 111.06,
114.02, 115.74, 118.57, 119.91, 122.71, 125.60, 128.26, 128.96,
131.06, 132.23, 132.72, 133.40, 133.53, 135.42, 135.71, 140.51,
147.71, 160.01; UPLC analysis: t = 1.64 min (λmax 266,
295 nm); HR-MS (ESI) calcd for C25H23N3O5SNa [M + Na]+
500.1256, found 500.1259.
2-Nitro-N-(2-(2-(1-(2-oxo-2H-chromen-3-yl)vinyl)-1H-indol-3-yl)-
ethyl)benzenesulfonamide (3e).
According to the general procedure, tryptamine derivative 1
(71.3 mg, 0.206 mmol) was treated with corresponding aryl
acetylene and Hg(OTf)2 for 11 h to afford 3e (89.7 mg,
0.174 mmol, 84%) as a pale yellow amorphous. 1H-NMR
(400 MHz, DMSO-d6) δ 2.88–2.96 (2H, m), 3.08–3.16 (2H, m),
5.67 (1H, d, J = 0.9 Hz), 5.92 (1H, d, J = 0.9 Hz), 7.00 (1H,
ddd, J = 7.9, 7.0, 0.9 Hz), 7.08 (1H, ddd, J = 8.2, 7.0, 0.9 Hz),
7.26 (1H, d, J = 8.2 Hz), 7.36 (1H, td, J = 7.5, 0.9 Hz), 7.45
(1H, d, J = 8.4 Hz), 7.46 (1H, d, J = 7.9 Hz), 7.64 (1H, ddd,
J = 8.4, 7.3, 1.6 Hz), 7.74 (1H, dd, J = 7.5, 1.6 Hz), 7.78 (1H,
td, J = 7.6, 1.6 Hz), 7.81 (1H, td, J = 7.5, 1.8 Hz), 7.91 (2H, m),
7.94 (1H, s), 8.19 (1H, s), 10.9 (1H, s); 13C-NMR (100 MHz,
DMSO-d6) δ 25.59, 43.26, 109.04, 111.23, 115.92, 118.29,
118.82, 119.24, 120.79, 121.78, 124.43, 124.56, 126.88, 127.97,
128.80, 129.31, 131.98, 132.59, 132.96, 133.87, 133.93, 135.28,
135.56, 141.83, 147.62, 153.21, 159.06; UPLC analysis: t =
1.50 min (λmax 297 nm); HR-MS (ESI) calcd for
C27H21N3O6SNa [M + Na]+ 538.1049, found 538.1043.
(S)-Methyl 2-(2-nitrophenylsulfonamido)-3-(2-(1-phenylvinyl)-
1H-indol-3-yl)propanoate (6)
According to the general procedure, tryptamine derivative 1
(124 mg, 0.307 mmol) was treated with corresponding aryl
acetylene and Hg(OTf)2 for 3.5 h to afford 6 (129 mg,
0.256 mmol, 83%) as a pale yellow amorphous. 1H-NMR
(400 MHz, CDCl3) δ 3.02 (1H, dd, J = 14.5, 8.2 Hz), 3.12 (1H,
dd, J = 14.5, 5.9 Hz), 3.39 (3H, s), 4.39 (1H, td, J = 8.2, 5.9
Hz), 5.57 (1H, s), 5.73 (1H, s), 5.89 (1H, d, J = 8.2 Hz), 7.00
(1H, ddd, J = 7.9, 7.0, 0.9 Hz), 7.14 (1H, ddd, J = 7.9, 7.0, 0.9
Hz), 7.22 (1H, d, J = 7.9 Hz), 7.36 (5H, br-s), 7.40 (1H, d, J =
7.9 Hz), 7.53 (1H, td, J = 7.5, 1.8 Hz), 7.56 (1H, td, J = 7.5, 1.8
Hz), 7.68 (1H, dd, J = 7.5, 1.8 Hz), 7.80 (1H, dd, J = 7.5, 1.8
Hz), 7.99 (1H, br-s); 13C-NMR (100 MHz, CDCl3) δ 28.52,
52.49, 57.20, 107.89, 111.06, 117.69, 118.67, 120.14, 122.84,
125.54, 127.85, 128.27, 128.67, 128.75, 130.27, 132.72, 133.34,
133.87, 135.33, 136.15, 139.52, 141.09, 147.10, 171.38; UPLC
analysis: t = 1.59 min (λmax 301 nm); HR-MS (ESI) calcd for
C26H23N3O6SNa [M + Na]+ 528.1205, found 528.1222.
2-Nitro-N-(2-(2-(1-(1-tosyl-1H-indol-5-yl)vinyl)-1H-indol-3-yl)-
ethyl)benzenesulfonamide (3f)
According to the general procedure, tryptamine derivative 1
(70.5 mg, 0.204 mmol) was treated with corresponding aryl
acetylene and Hg(OTf)2 for 4 h to afford 3f (104 mg,
0.162 mmol, 79%) as a pale yellow amorphous. 1H-NMR
(400 MHz, CDCl3) δ 2.36 (3H, s), 2.84 (2H, t, J = 7.3 Hz), 3.29
(2H, td, J = 7.3, 5.7 Hz), 5.21 (1H, t, J = 5.7 Hz), 5.49 (1H, d,
J = 0.9 Hz), 5.67 (1H, d, J = 0.9 Hz), 6.60 (1H, dd, J = 3.6, 0.7
Hz), 6.99 (1H, ddd, J = 7.9, 7.3, 0.9 Hz), 7.16 (1H, ddd, J = 8.2,
7.3, 0.9 Hz), 7.23–7.27 (3H, m), 7.30 (1H, dd, J = 8.6, 1.8 Hz),
7.36 (1H, d, J = 7.9 Hz), 7.45 (1H, d, J = 1.8 Hz), 7.55–7.62
(Z)-2-Nitro-N-(2-(2-(1-phenylprop-1-en-1-yl)-1H-indol-3-yl)-
ethyl)benzenesulfonamide (8)
According to the general procedure, tryptamine derivative 1
(106 mg, 0.307 mmol) was treated with internal acetylene 7 and
Hg(OTf)2 for 28 h to afford 8 (93.1 mg, 0.202 mmol, 66%
yield, 13 : 1 mixture of cis : trans isomers), as a pale yellow
4240 | Org. Biomol. Chem., 2012, 10, 4236–4242
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1
amorphous. H-NMR (400 MHz, CDCl3) δ 1.80 (3H, d, J = 7.0
td, J = 8.2, 5.2 Hz), 4.23 (1H, q, J = 7.7 Hz), 5.95 (1H, t, J =
5.0 Hz), 6.91 (1H, t, J = 7.7 Hz), 7.09 (1H, t, J = 7.7 Hz), 7.23
(1H, d, J = 7.7 Hz), 7.27 (1H, d, J = 7.7 Hz), 7.48 (2H, d, J =
8.4 Hz), 7.53 (2H, m), 7.58 (1H, m), 7.93 (1H, m), 7.96 (2H, d,
J = 8.4 Hz), 8.33 (1H, br-s); 13C-NMR (100 MHz, CDCl3) δ
24.41, 25.87, 38.53, 43.38, 52.28, 68.45, 85.02, 107.11, 111.16,
118.23, 119.81, 122.14, 125.29, 125.79, 128.63, 129.43, 129.87,
131.12, 132.42, 133.03, 133.30, 134.41, 138.94, 147.49, 149.71,
166.84; UPLC analysis: t = 1.59 min (λmax 283 nm); HR-MS
(ESI) calcd for C28H27N3O7SNa [M + Na]+ 572.1467, found
572.1474.
Hz), 2.82 (2H, t, J = 7.5 Hz), 3.28 (2H, td, J = 7.5, 6.1 Hz), 5.25
(1H, t, J = 6.1 Hz), 6.41 (1H, q, J = 7.0 Hz), 7.06 (1H, ddd, J =
8.2, 7.0, 0.9 Hz), 7.15–7.27 (6H, m), 7.31 (1H, d, J = 8.2 Hz),
7.45 (1H, d, J = 7.9 Hz), 7.60 (1H, td, J = 7.7, 1.4 Hz), 7.66
(1H, td, J = 7.7, 1.4 Hz), 7.74 (1H, dd, J = 7.7, 1.4 Hz), 7.88
(1H, br-s), 7.99 (1H, dd, J = 7.7, 1.6 Hz); 13C-NMR (100 MHz,
CDCl3) δ 16.35, 25.45, 43.78, 110.18, 111.13, 118.44, 119.73,
122.23, 125.48, 126.62, 127.56, 127.84, 128.60, 129.31, 131.16,
132.73, 133.19, 133.45, 133.46, 133.57, 135.96, 140.61, 147.93;
UPLC analysis: t = 1.77 min (λmax 284 nm); HR-MS (ESI) calcd
for C25H23N3O4SNa [M + Na]+ 484.1307 found 484.1316.
N-(2-(2-(1-(4-(Dimethylamino)phenyl)vinyl)-1H-indol-3-yl)-
ethyl)-2-nitrobenzenesulfonamide (3i)
Compound (10)
Hg(OTf)2 (12.5 mg, 0.0251 mmol) was added to a solution of
tryptamine derivative 1 (86.4 mg, 0.250 mmol) and aryl acety-
lene 2i (109 mg, 0.751 mmol) in dichloromethane (3.5 ml).
After stirring at room temperature for 24 h, the mixture was
added saturated NaHCO3 (aq.) and extracted with EtOAc. The
organic extracts were washed with saturated NaHCO3 (aq.),
water and brine, dried over Na2SO4, and concentrated. The
residue was purified by silica-gel column chromatography to
afford 3i (51.0 mg, 0.104 mmol, 42%), 13 (21.8 mg,
0.0444 mmol, 18%) and 14 (38.1 mg, 0.0599 mmol, 24%).
Hg(OTf)2 (5.00 mg, 0.0100 mmol) was added to a solution of
tryptamine derivative 1 (70.6 mg, 0.204 mmol) and phenyl
acetylene (29 μl, 0.260 mmol) in 1,2-dichloroethane (3.0 ml).
After stirring for 5.5 h at room temperature, N-methyl indole 9
(62 μl, 0.496 mmol) was then added to the reaction mixture and
stirred at room temperature for 12 h and at 45 °C for 10.5 h. The
mixture was cooled to room temperature and added saturated
NaHCO3 (aq.) and extracted with EtOAc. The organic extracts
were washed with saturated NaHCO3 (aq.), water and brine,
dried over Na2SO4, and concentrated. The residue was purified
by silica-gel column chromatography to afford 10 (77.9 mg,
0.135 mmol, 66%) as a pale yellow amorphous. 1H-NMR
(400 MHz, CDCl3) δ 2.36 (3H, s), 2.74 (1H, dd, J = 9.7, 0.9
Hz), 2.76 (1H, d, J = 8.6 Hz), 2.92–3.02 (2H, m), 3.72 (3H, s),
5.07 (1H, br-t, J = 5.9 Hz), 6.40 (1H, s), 6.95 (1H, ddd, J = 7.9,
7.0, 0.9 Hz), 7.02 (1H, ddd, J = 7.9, 7.0, 1.1 Hz), 7.10 (1H, ddd,
J = 8.2, 7.0, 1.1 Hz), 7.17 (1H, d, J = 8.2 Hz), 7.19–7.30 (7H,
m), 7.34 (1H, d, J = 8.2 Hz), 7.40 (1H, d, J = 7.9 Hz), 7.60 (1H,
td, J = 7.7, 1.4 Hz), 7.66 (1H, td, J = 7.7, 1.6 Hz), 7.76 (1H, dd,
J = 7.7, 1.4 Hz), 7.94 (1H, dd, J = 7.7, 1.6 Hz), 7.97 (1H, br-s);
13C-NMR (100 MHz, CDCl3) δ 26.06, 29.03, 32.90, 43.41,
44.97, 107.03, 109.75, 111.04, 118.03, 119.34, 119.55, 121.32,
121.48, 121.58, 121.87, 125.46, 126.29, 126.79, 127.76, 128.35,
128.51, 129.33, 131.15, 132.76, 133.39, 133.68, 133.85, 137.96,
141.56, 146.87, 147.86; UPLC analysis: t = 2.21 min (λmax
284 nm); HR-MS (ESI) calcd for C33H30N4O4SNa [M + Na]+
601.1885, found 601.1883.
1
3i: H-NMR (400 MHz, CDCl3) δ 2.89 (2H, t, J = 7.3 Hz),
2.99 (6H, s), 3.33 (2H, td, J = 7.3, 5.9 Hz), 5.24 (1H, t, J = 5.9
Hz), 5.29 (1H, d, J = 1.1 Hz), 5.55 (1H, d, J = 1.1 Hz), 6.66
(2H, d, J = 8.8 Hz), 6.98 (1H, ddd, J = 7.9, 7.0, 0.9 Hz), 7.14
(1H, ddd, J = 8.2, 7.0, 1.1 Hz), 7.19 (2H, d, J = 8.8 Hz), 7.25
(1H, d, J = 8.2 Hz), 7.35 (1H, d, J = 7.9 Hz), 7.59–7.65 (2H,
m), 7.68 (1H, m), 7.94 (1H, s), 8.00 (1H, m); 13C-NMR
(100 MHz, CDCl3) δ 25.00, 40.55, 44.05, 109.71, 111.00,
112.15, 113.95, 118.50, 119.79, 122.48, 125.54, 127.40, 128.31,
128.58, 131.07, 132.70, 133.34, 133.69, 135.34, 136.24, 140.64,
147.72, 150.74; UPLC analysis: t = 1.88 min (λmax 300 nm);
HR-MS (ESI) calcd for C26H27N4O4S [M + H]+ 491.1753,
found 491.1760.
1
13: H-NMR (400 MHz, CDCl3) δ 2.27 (1H, ddd, J = 12.0,
5.4, 1.1 Hz), 2.57 (1H, ddd, J = 12.0, 11.1, 7.5 Hz), 2.92 (6H,
s), 3.21 (1H, ddd, J = 11.1, 10.0, 5.4 Hz), 3.67 (1H, ddd, J =
10.0, 7.5, 1.6 Hz), 4.77 (1H, br-s), 5.04 (1H, d, J = 0.9 Hz), 5.13
(1H, s), 5.58 (1H, d, J = 1.6 Hz), 6.52 (2H, d, J = 8.8 Hz), 6.59
(1H, d, J = 7.7 Hz), 6.80 (2H, d, J = 8.8 Hz), 6.80 (1H, td, J =
7.5, 1.1 Hz), 7.07 (1H, d, J = 7.5 Hz), 7.12 (1H, td, J = 7.7, 1.1
Hz), 7.58 (1H, td, J = 7.7, 1.6 Hz), 7.61 (1H, dd, J = 7.9, 1.6
Hz), 7.67 (1H, td, J = 7.7, 1.4 Hz), 7.86 (1H, dd, J = 7.9, 1.4
Hz); 13C-NMR (100 MHz, CDCl3) δ 37.18, 40.60, 47.95, 63.96,
82.53, 109.62, 111.91, 114.95, 119.66, 124.29, 129.03, 129.24,
130.46, 131.03, 131.78, 133.29, 133.48, 148.35, 149.31, 149.81,
150.70; UPLC analysis: t = 2.13 min (λmax 243 nm); HR-MS
(ESI) calcd for C26H27N4O4S [M + H]+ 491.1753, found
491.1750.
Compound (12)
Hg(OTf)2 (5.00 mg, 0.0100 mmol) was added to a solution of
tryptamine derivative 1 (70.8 mg, 0.205 mmol) and 11 (61.2 mg,
0.300 mmol) in 1,2-dichloroethane (3.0 ml). After stirring at
room temperature for 14 h, the mixture was treated with
additional 11 (50.0 mg, 0.245 mmol) and stirred for 5 h. The
mixture was then added saturated NaHCO3 (aq.) and extracted
with EtOAc. The organic extracts were washed with saturated
NaHCO3 (aq.), water and brine, dried over Na2SO4, and concen-
trated. The residue was purified by silica-gel column chromato-
graphy to afford 12 (73.5 mg, 0.134 mmol, 65%) as a pale
yellow amorphous. 1H-NMR (400 MHz, CDCl3) δ 2.01 (1H, m),
2.15 (1H, m), 2.68 (2H, dd, J = 7.7, 6.6 Hz), 2.89 (2H, td, J =
7.0, 2.9 Hz), 3.15 (1H, m), 3.25 (1H, m), 3.90 (3H, s), 4.14 (1H,
1
14: H-NMR (400 MHz, CD3CN) δ 2.29–2.34 (2H, m), 2.91
(6H, s), 2.93 (6H, s), 3.24 (1H, m), 4.00 (1H, m), 4.73 (1H, s),
5.00 (1H, d, J = 1.1 Hz), 5.07 (1H, s), 5.22 (1H, d, J = 1.1 Hz),
5.81 (1H, s), 6.37 (1H, d, J = 7.7 Hz), 6.42 (2H, d, J = 9.1 Hz),
6.61 (2H, d, J = 9.1 Hz), 6.64 (2H, d, J = 9.1 Hz), 6.66 (2H, d,
J = 9.1 Hz), 6.78 (1H, td, J = 7.5, 0.9 Hz), 7.06 (1H, ddd, J =
This journal is © The Royal Society of Chemistry 2012
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7.9, 7.5, 1.4 Hz), 7.19 (1H, dd, J = 7.5, 0.9 Hz), 7.57 (1H, ddd,
J = 7.9, 6.8, 1.8 Hz), 7.64–7.72 (3H, m); 13C-NMR (100 MHz,
CD3CN) δ 40.20, 40.50, 40.63, 49.22, 64.16, 86.93, 105.83,
108.82, 112.65, 112.83, 114.51, 119.65, 124.95, 125.03, 125.11,
128.20, 129.66, 129.69, 130.62, 131.42, 132.35, 133.01, 133.95,
135.02, 145.66, 148.64, 150.37, 151.16, 151.72, 152.91; UPLC
analysis: t = 3.11 min (λmax 294 nm); HR-MS (ESI) calcd for
C36H38N5O4S [M + H]+ 636.2645, found 636.2639.
Science and Technology Agency (JST). A fellowship to
H. M. from the JSPS is gratefully acknowledged.
Notes and references
1 H. Mizoguchi, H. Oguri, K. Tsuge and H. Oikawa, Org. Lett., 2009, 11,
3016–3019.
2 Metal-Catalyzed Cross-Coupling Reactions, ed. A. De Meijere, and
F. Diederich, Wiley-VCH, 2nd edn, 2004.
3 Selected recent reviews, see: (a) X. Chen, K. M. Engle, D.-H. Wang and
J.-Q. Yu, Angew. Chem., Int. Ed., 2009, 48, 5094–5115; (b) D. A. Colby,
R. G. Bergman and J. A. Ellman, Chem. Rev., 2010, 110, 624–655.
4 Recent reviews, see: (a) S. Cacchi and G. Fabrizi, Chem. Rev., 2005,
105, 2873–2920; (b) G. R. Humphrey and J. T. Kuethe, Chem. Rev.,
2006, 106, 2875–2911; (c) I. V. Seregin and V. Gevorgyan, Chem. Soc.
Rev., 2007, 36, 1173–1193; (d) M. Bandini and A. Eichholzer, Angew.
Chem., Int. Ed., 2009, 48, 9608–9645; (e) L. Joucla and L. Djakovitch,
Adv. Synth. Catal., 2009, 351, 673–714.
Compounds (16 and 17)
A solution of tryptamine derivative 15 (73.0 mg, 0.203 mmol)
and aryl acetylene 2i (35.0 mg, 0.241 mmol) in dichloromethane
(3.0 ml) was added to Hg(OTf)2 (10.0 mg, 0.0201 mmol) and
stirred for 17.5 h at room temperature. Additional aryl acetylene
2i (29.0 mg, 0.200 mmol) was added and stirred again for 5.5 h.
Sat. NaHCO3 aq. was added to the mixture and it was extracted
with EtOAc. The organic extracts were washed with sat
NaHCO3 aq., water and brine, dried over Na2SO4, and concen-
trated. The residue was purified by silica-gel column chromato-
graphy to afford 16 (48.8 mg, 0.0967 mmol, 48%) and 17
(49.4 mg, 0.0761 mmol, 37%).
5 N. P. Grimster, C. Gauntlett, C. R. A. Godfrey and M. J. Gaunt, Angew.
Chem., Int. Ed., 2005, 44, 3125–3129.
6 (a) E. Capito, J. M. Brown and A. Ricci, Chem. Commun., 2005, 1854–
1856; (b) W. Wang and T. Ikemoto, Tetrahedron Lett., 2005, 46, 3875–
3878; (c) Y. Nakao, K. S. Kanyiva, S. Oda and T. Hiyama, J. Am. Chem.
Soc., 2006, 128, 8146–8147; (d) A. Maehara, H. Tsurugi, T. Satoh and
M. Miura, Org. Lett., 2008, 10, 1159–1162; (e) A. García-Rubia,
B. Urones, R. Gómez Arrayás and J. C. Carretero, Chem.–Eur. J., 2010,
16, 9676–9685; (f) D. J. Schipper, M. Hutchinson and K. Fagnou, J. Am.
Chem. Soc., 2010, 132, 6910–6911.
1
16: H-NMR (400 MHz, CDCl3) δ 2.13 (3H, s), 2.14–2.22
(1H, m), 2.40–2.49 (1H, m), 2.49–2.61 (2H, m), 2.82 (6H, s),
5.15 (1H, t, J = 5.7 Hz), 5.36 (1H, s), 5.49 (1H, s), 6.35 (2H, d,
J = 8.8 Hz), 6.46 (2H, d, J = 8.8 Hz), 7.22 (1H, td, J = 6.8, 0.9
Hz), 7.25 (1H, d, J = 1.8 Hz), 7.33 (1H, ddd, J = 7.7, 6.8, 1.8
Hz), 7.44 (1H, d, J = 7.7 Hz), 7.62–7.71 (2H, m), 7.80 (1H, m),
7.85 (1H, m); 13C-NMR (100 MHz, CDCl3) δ 16.77, 35.24,
39.19, 40.38, 65.69, 111.68, 115.65, 120.25, 122.75, 125.47,
126.06, 127.65, 128.42, 128.60, 131.04, 132.89, 133.33, 133.66,
141.53, 147.84, 147.93, 149.97, 155.62, 184.79; UPLC analysis:
t = 1.47 min (λmax 269 nm); HR-MS (ESI) calcd for
C27H28N4O4SNa [M + Na]+ 527.1729, found 527.1732.
7 For selected recent reviews, see: (a) Y. Yamamoto, I. D. Gridnev, N. T. Patil
and T. Jin, Chem. Commun., 2009, 5075–5087; (b) P. de Mendoza and A.
M. Echavarren, Pure Appl. Chem., 2010, 82, 801–820; (c) A. Leyva-Pérez
and A. Corma, Angew. Chem., Int. Ed., 2012, 51, 614–635.
8 (a) C. Ferrer, C. H. M. Amijs and A. M. Echavarren, Chem.–Eur. J.,
2007, 13, 1358–1373; (b) C. Ferrer, A. Escribano-Cuesta and A.
M. Echavarren, Tetrahedron, 2009, 65, 9015–9020.
9 (a) H. Çavdar and N. Saraçoglu, J. Org. Chem., 2006, 71, 7793–7799;
(b) A. Arcadi, M. Alfonsi, G. Bianchi, G. D’Anniballe and F. Marinelli,
Adv. Synth. Catal., 2006, 348, 331–338; (c) T. Tsuchimoto,
T. Wagatsuma, K. Aoki and J. Shimotori, Org. Lett., 2009, 11, 2129–
2132; (d) For indolizines, see: Y. Yang, K. Cheng and Y. Zhang, Org.
Lett., 2009, 11, 5606–5609.
10 R. Gao and C. S. Yi, J. Org. Chem., 2010, 75, 3144–3146.
11 For excellent books, see: (a) The Alkaloids, ed. A. Brossi, M. Suffness,
Academic Press, Inc., San Diego, 1990, vol. 37; (b) T. Hudlicky, J.
W. Reed, The Way of Synthesis: Evolution of Design and Method for
Natural Products, Wiely-VCH, 2007. Selected synthetic studies, see:
B. Danieli, G. Lesma, G. Palmisano, D. Passarella and A. Silvani, Tetra-
hedron, 1994, 50, 6941–6954; (c) N. Huang, T. Jiang, T. Wang,
M. Soukri, R. Ganorkar, B. Deker, J.-M. Léger, J. Madalengoitia and M.
E. Kuehne, Tetrahedron, 2008, 64, 9850–9856; (d) Y. Han-ya,
H. Tokuyama and T. Fukuyama, Angew. Chem., Int. Ed., 2011, 50, 4884–
4887, and references therein.
12 The dimer 4 was obtained as a 5 : 1 mixture of diastereomers. Although 4
was not fully characterized, NMR spectra of 4 were consistent with the
data reported in ref. 8a.
13 (a) H. Yamamoto, I. Sasaki, Y. Hirai, K. Namba, H. Imagawa and
M. Nishizawa, Angew. Chem., Int. Ed., 2009, 48, 1244–1246;
(b) M. Nishizawa, H. Imagawa and H. Yamamoto, Org. Biomol. Chem.,
2010, 8, 511–521, and references therein.
14 Similar conversion using indium catalyst, see: (a) T. Tsuchimoto and
M. Kanbara, Org. Lett., 2011, 13, 912–915; (b) G. Bhaskar, C. Saikumar
and P. T. Perumal, Tetrahedron Lett., 2010, 51, 3141–3145.
15 The stereogenic center in 5 was almost completely retained through the
vinylation, see ESI†.
1
17: H-NMR (400 MHz, CD3CN) δ 2.13 (1H, td, J = 12.0,
5.0 Hz), 2.44 (1H, td, J = 12.0, 5.0 Hz), 2.53 (1H, m), 2.85 (6H,
s), 2.88 (6H, s), 3.07 (1H, m), 3.77 (1H, d, J = 1.4 Hz), 3.89
(1H, d, J = 1.4 Hz), 4.83 (1H, s), 5.00 (1H, d, J = 0.9 Hz), 5.34
(1H, d, J = 0.9 Hz), 5.60 (1H, s), 5.83 (1H, br-t, J = 5.7 Hz),
6.19 (1H, d, J = 7.5 Hz), 6.41 (2H, d, J = 9.1 Hz), 6.44 (2H, d,
J = 9.1 Hz), 6.61 (2H, d, J = 9.1 Hz), 6.72 (2H, br-d, J = 9.1
Hz), 6.80 (1H, td, J = 7.5, 1.1 Hz), 7.01 (1H, td, J = 7.5, 1.1
Hz), 7.08 (1H, dd, J = 7.5, 1.1 Hz), 7.72 (1H, td, J = 7.7, 1.6
Hz), 7.76 (1H, td, J = 7.7, 1.6 Hz), 7.83 (1H, dd, J = 7.7, 1.6
Hz), 7.85 (1H, dd, J = 7.7, 1.6 Hz); 13C-NMR (100 MHz,
CD3CN) δ 40.46, 40.57, 40.91, 41.31, 56.93, 80.17, 108.13,
109.86, 112.00, 112.68, 113.48, 120.15, 123.47, 124.46, 125.97,
127.81, 129.33, 130.85, 131.50, 132.15, 133.58, 133.67, 135.04,
143.93, 148.76, 148.84, 150.54, 151.76, 153.46, 155.92; UPLC
analysis: t = 2.86 min (λmax 279, 301 nm); HR-MS (ESI) calcd
for C37H40N5O4S [M + H]+ 650.2801, found 650.2785.
16 In place of the CH2CH2NHNs substituent at the indole C3 position, sub-
strates bearing CH2CH2NHBoc or CH2CH2-phthalimide group were also
applicable for the gem-vinylation without substantial decrease of the
yields. The intermolecular alkenylation of 1 with aliphatic acetylenes
were not successful.
17 (a) S. Bhuvaneswari, M. Jeganmohan and C.-H. Cheng, Chem.–Eur. J.,
2007, 13, 8285–8293; (b) K. Ravindar, M. S. Reddy and
P. Deslongchamps, Org. Lett., 2011, 13, 3178–3181.
Acknowledgements
This work was supported by a Grant-in-Aid for Scientific
Research (B) 23310156 to H. Oguri from the Japan Society for
the Promotion of Science (JSPS) and in part by the Naito Foun-
dation and the Science and Technology Research Partnership for
Sustainable Development Program (SATREPS) of the Japan
18 D. Crich and A. Banerjee, Acc. Chem. Res., 2007, 40, 151–161.
4242 | Org. Biomol. Chem., 2012, 10, 4236–4242
This journal is © The Royal Society of Chemistry 2012