One-pot oxidative carbon-carbon bond formation of 3-benzylic and 3-allylic indoles with carbon nucleophiles

Article abstract of DOI:10.1016/j.tet.2008.03.033

Indolenines were generated at -78 °C from 3-benzylic or 3-allylic indoles by dehydrogenation with N-tert-butylbenzenesulfinimidoyl chloride, and a carbon-carbon bond was formed at -78 °C in a one-pot manner by treating these indolenines with various carbon nucleophiles such as active methylene compounds or organocuprates.

Full text of DOI:10.1016/j.tet.2008.03.033

Tetrahedron 64 (2008) 5262–5267
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Tetrahedron
journal homepage: www.elsevier.com/locate/tet
One-pot oxidative carbon–carbon bond formation of 3-benzylic
and 3-allylic indoles with carbon nucleophiles
*
*
Jun-ichi Matsuo , Yumi Tanaki, Hiroyuki Ishibashi
Division of Pharmaceutical Sciences, Graduate School of Natural Science and Technology, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Japan
a r t i c l e i n f o
a b s t r a c t
Indolenines were generated at ꢀ78 ꢁC from 3-benzylic or 3-allylic indoles by dehydrogenation with
N-tert-butylbenzenesulfinimidoyl chloride, and a carbon–carbon bond was formed at ꢀ78 ꢁC in a one-
pot manner by treating these indolenines with various carbon nucleophiles such as active methylene
compounds or organocuprates.
Article history:
Received 20 February 2008
Received in revised form 10 March 2008
Accepted 11 March 2008
Available online 14 March 2008
Ó 2008 Elsevier Ltd. All rights reserved.
1. Introduction
Me2N
Nu
R
R
R
base
Nu-H
3-Alkylindoles are frequently found as a part of biologically
important natural products and pharmaceutical agents, and they
have been synthesized by various methods.1,2 Since the first report
by Snyder in 1944,3a the reaction of carbon nucleophiles with
3-(N,N-dimethylaminomethyl)indole (gramine, 1) or its derivatives
has been an important and conventional method for the synthesis
of various 3-substituted indoles (Eq. 1).4 The C–C bond formation
proceeds via reactive indolenines 2,3b which are usually gen-
erated from 1 in the presence of nucleophile (e.g., ethyl acet-
amidomalonate) under several conditions; employment of base at
high temperature,3a,c employment of base and N-alkylating agent
(e.g., iodomethane and methylsulfate) at room temperature,3d and
employment of tri-n-butylphosphine in refluxing acetonitrile.3e
The similar fragmentation reaction to 2 is considered to proceed
from isolable intermediates such as 3-(1-arylsulfonylalkyl)indole,5
3-(alkoxymethyl)indole,3b 3-(hydroxymethyl)indole,6 3-(ethyl-
thiomethy)indole,7 and3-(1-phenyl-N-methylaminomethyl)indole.8
Indolenines 2 are believed to form in a variety of reactions such as
synthesis of bisindolylalkanes from indoles and aldehydes.9 Also, it is
considered that indolenine moiety may be an intermediate in the
mechanism of the action of the dehydrogenase enzymes.10 Thus,
indolenine intermediate plays important role in the chemical syn-
theses and in biochemical transformations. It was reported that free
indolenines 2 were unstable, but sulfuric acid or hydrogen chloride
salts of these indolenines were prepared as stable compounds by
reaction of indoles with aromatic aldehydes in the presence of the
corresponding acid.11
ð1Þ
N
H
N
N
H
2
3
R = H: gramine (1)
(4)13 to generate a reactive intermediate followed by trapping it
with carbon nucleophiles. This method provides a unique C–C bond
formation at a position where it is difficult to form a new C–C bond
by other methods. For example, one-pot oxidative Mannich re-
actions of N-Cbz amines14a and lactams,14b and oxidative Michael
addition of 1,3-dicarbonyl compounds14c have been carried out
efficiently.15 In the course of our study, we considered the possi-
bility for generating free indolenine intermediate 2 by oxidative
activation of 3-alkylindole 5 with 4 (Scheme 1). Thus, metalated
indole 6 reacts with 4 at the 3-position of indole to afford an
intermediate 7 in which elimination should proceed via a five-
Cl
S
4
t
Ph
N t
Bu
N
Bu
R
R
Ph
base
H
S
N
N
H
R
N
7
6
5
R
R
Nu-H
3
Nu
We have been studying mild oxidative C–H activation12 of
organic molecules with N-tert-butylbenzenesulfinimidoyl chloride
N
2
N
H
8
S
Bu
Ph
N t
H
* Corresponding authors. Tel./fax: þ81 76 234 4439.
E-mail address: jimatsuo@p.kanazawa-u.ac.jp (J. Matsuo).
Scheme 1. Generation of indolenine 2 by oxidation of 5 with 4 and one-pot carbon–
carbon bond formation.
0040-4020/$ – see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.03.033

J.-ichi Matsuo et al. / Tetrahedron 64 (2008) 5262–5267
5263
Table 1
Generation of free indolenine 2a by oxidation of 5a with 4 and successive addition of ethyl cyanoacetatea
CO2Et
Ph
NC
Ph
3) NC
CO2Et
Ph
1) base
2) 4
addition
conditions
N
H
N
H
N
THF, 30 min
oxidation
temperature
5a
3a
2a
Entry
Base
Oxidation temperature
Addition conditions
Yieldb (%)
1
2
3
4
5
6
n-BuLi
n-BuLi
LHMDS
NHMDS
KHMDS
i-Pr2NEt
ꢀ78 ꢁ
C
C
ꢀ78 ꢁC, 30 min
ꢀ100 ꢁC, 30 min
ꢀ78 ꢁC, 30 min
ꢀ78 ꢁC, 30 min
ꢀ78 ꢁC, 30 min
ꢀ78 ꢁC to rt
81
63
81
61
33
Trace
ꢀ100 ꢁ
ꢀ78 ꢁC
ꢀ78 ꢁ
C
ꢀ78 ꢁC
ꢀ78 ꢁC to rt
a
Compound 5a (1.0 equiv), base (1.3 equiv), 4 (1.5 equiv) and ethyl cyanoacetate (1.5 equiv) were employed.
Isolated yield. A mixture of diastereomers (dr (diastereomer ratio)¼50:50) was obtained in each case.
b
membered transition state to form free indolenine 2 at low tem-
(12% yield). Next, several 3-benzylic and 3-allylic indoles were
subjected to this oxidative alkylation. 3-(4-Chlorobenzyl)indole
(5b) and 3-(4-methoxybenzyl)indole (5c) reacted smoothly to af-
ford the corresponding adducts 3k (78%) and 3l (72%), respectively.
3-Cinnamylindole (5d) also reacted with ethyl cyanoacetate
regioselectively to afford 3m in 84% yield, while 3-allylindole (5e)
gave 3n in 36% yield along with its regioisomer 3n0 (11%). On the
other hand, the present oxidative C–C bond formation of 3-meth-
ylindole and 3-ethylindole with ethyl cyanoacetate gave only
a trace amount of products. The unprecedented high reactivity of 2
toward active methylene compounds may be ascribed to facilitate
the attack of carbanion to protonated indolenine 8 under neutral
conditions (see Scheme 1).
perature. Thus-formed reactive intermediate 2 would react with
carbon nucleophile to give indole derivative 3 in a one-pot manner.
One-pot introduction of a carbon–carbon bond onto the alkyl
substituents of 3-alkylindoles (5 to 3) is a challenging route for
derivatizing them, and, to the best of our knowledge, such one-pot
bond formation has not been reported to date.
We would like to report here a new method for generating free
indolenine 2 by dehydrogenation of 3-alkylindoles 5 with 4 at
ꢀ78 ꢁC, and unexpectedly high reactivity of indolenine 2 toward
carbon nucleophiles such as ethyl cyanoacetate. The reaction
profile of organometallic agents toward 2 is also described.
2. Results and discussion
2.2. One-pot C–C bond formation of 3-benzylindole (5a) with
organometallic agents
2.1. One-pot C–C bond formation of 3-benzylic and 3-allylic
indoles with active methylene compounds
Organometallic agents were next examined as a nucleophile in
the present one-pot C–C bond formation of 5a. After screening
some organometallic reagents, alkyllithium (MeLi, 25% yield) and
Grignard reagents (MeMgBr, 32% yield; PhMgBr, 35% yield) were
found to be not suitable for the present carbon–carbon bond for-
mation, while alkylzinc (Me2Zn, 50% yield; Et2Zn, 70% yield) gave
the alkylated products in moderate yields. It was found that higher-
order cyanocuprates gave the desired alkylated and arylated
products in good yields (Table 3). Methyl, n-butyl, tert-butyl, and
phenyl groups were introduced smoothly at the benzylic position
of 5a.
First, suitable reaction conditions for oxidation of 3-benzyl-
indole (5a) with 4 were investigated (Table 1). Lithiation of 5a with
n-BuLi followed by reaction with 4 at ꢀ78 ꢁC proceeded immedi-
ately. In order to trap the indolenine intermediate 2a, ethyl cya-
noacetate was added. Although gramine derivatives were reported
to react with active methylene compounds above at room tem-
perature,3,4 the present C–C bond formation proceeded at surpris-
ingly low temperature (at ꢀ78 ꢁC) to afford adduct 3a in 81% yield
(entry 1). Moreover, the intermediate 2a reacted even at ꢀ100 ꢁC
(entry 2). Elevation of reaction temperature from ꢀ78 ꢁC to room
temperature did not improve the yield of 3a. The use of lithium
hexamethyldisilazide (LHMDS) instead of n-BuLi also gave 3a in
81% yield (entry 3). It was noted that lithium ion was superior to
sodium or potassium ion as a counter cation of metalated indole 6,
since sodium hexamethyldisilazide (NHMDS) and potassium
hexamethyldisilazide (KHMDS) gave 3a in 61 and 33% yields,
respectively (entries 4 and 5). The effect of metal ion might be
explained by regioselectivity (C-3 vs N) in the reaction of 6 and 4.
The use of diisopropylethylamine as a base gave only a trace
amount of the desired product 3a (entry 6).
3. Conclusion
3-Benzylic and 3-allylic indoles were activated by oxidation
with 4 to form free indolenines 2 at ꢀ78 ꢁC, and various carbon
nucleophiles such as active methylene compounds and organo-
cuprates reacted with them at ꢀ78 ꢁC in a one-pot manner. The
present oxidative activation of indoles with 4 will be applicable to
various types of nucleophiles and to stereoselective bond formation
because of high reactivity observed on 2. The present method can
be regarded as a new method for generating free indolenine. Re-
cently, Ir-16 or Pd17-catalyzed direct alkylation of indoles with
benzylic or allylic alcohols to the corresponding 3-alkylindoles has
been reported.18 Various 3-alkylindoles are now readily prepared,
and the present method will be useful for rapid and further de-
rivatization of 3-alkylindoles. Therefore, a diverse chemical library
of 3-substituted indoles can be constructed and it would provide an
opportunity to discover a more potent drug candidate.
We then investigated the substrate generality of 4-mediated
oxidative alkylation of 3-alkylindoles (Table 2). In addition to ethyl
cyanoacetate, ethyl allylcyanoacetate and ethyl benzylcyanoacetate
reacted to afford the corresponding alkylated products in 83% and
78% yields, respectively (entries 1 and 2). Malonic acid esters
(entries 3–6), ketoesters (entry 7), and 1,3-diketones (entries 8 and
9) also reacted to give the products in moderate to good yields,
whereas the reaction with nitromethane proceeded very sluggishly

5264
J.-ichi Matsuo et al. / Tetrahedron 64 (2008) 5262–5267
Table 2 (continued)
Table 2
Yielda
(%)
Oxidative carbon–carbon bond formation of 3-benzylic and 3-allylic indoles with
various carbon nucleophiles bearing active methylene or methine protons
Entry Indole
NuH
Product
O
Nu
O
Ph
Ph
R
R
Ph
O
O
1) n-BuLi
3) Nu-H
-78 °C, 30 min
9
5a
5b
5c
5d
5e
3j
63
78f
72f
2) 4
THF, -78 °C
Ph
Ph
N
H
N
H
N
3b-n
5a-e
H
CO2Et
5a: R = Ph; 5b: R = 4-ClC6H4; 5c: R = 4-MeOC6H4; 5d: R = CH=CHPh;
5e: R = CH=CH2
NC
10
11
12
13
NC
CO2Et
CO2Et
CO2Et
CO2Et
3k
3l
Cl
Entry Indole
NuH
Product
Yielda
(%)
N
H
CO2Et
NC
CO2Et
Ph
NC
NC
NC
CO2Et
NC
NC
NC
1
5a
3b
83b
OMe
N
H
N
H
CO2Et
NC
Ph
CO2Et
Ph
3m 84g
NC
CO2Et
Ph
2
3
4
5a
5a
5a
3c
3d
3e
78c
Ph
N
H
CO2Et
N
H
NC
36h
3n
CO2Et
Ph
EtO2C
CO2Et
CO2Et
N
H
66 (78)d
a
Isolated yield.
dr¼64:36.
N
H
b
c
dr¼67:33.
Determined by 1H NMR analysis using an internal standard.
d
e
f
Me
CO2Et
Ph
EtO2C
dr¼56:44.
CO2Et
dr¼50:50.
g
h
Me
75
dr¼60:40.
CO2Et
dr¼60:40. Regioisomer 3n0 was also obtained in 11% yield.
N
H
CO2Et
Ph
CO2Et
CN
N
H
3n'
EtO2C
CO2Et
CO2Et
5
6
5a
5a
3f
55
71
Ph
Ph
Table 3
Oxidative carbon–carbon bond formation of 5a with various higher-order
N
H
cyanocupratesa
R
CO2Bn
Ph
BnO2C
Ph
Ph
CO2Bn
CO2Bn
1) n-BuLi
3) R2CuCNLi2
-78 °C, 30 min
3g
2) 4
THF, -78 °C
N
H
N
H
N
H
9a-d
5a
O
Entry
R
Product
Yieldb (%)
CO2Et
Ph
1
2
3
4
Me
9a
9b
9c
9d
54
77
54
82
O
7
8
5a
5a
3h
54d,e
n-Bu
t-Bu
Ph
CO2Et
N
H
a
About reaction conditions, see Table 1.
Determined by 1H NMR analysis.
b
O
O
O
O
4. Experimental
4.1. General
3i
56
Ph
N
H
All melting points were determined on a Yanagimoto micro
melting point apparatus and are uncorrected. Infrared (IR) spectra
(continued)

J.-ichi Matsuo et al. / Tetrahedron 64 (2008) 5262–5267
5265
were recorded on a Shimadzu FTIR-8100. 1H NMR spectra were
4.2.2. 2-Allyl-2-cyano-3-(1H-indol-3-yl)-3-phenylpropionic acid
ethyl ester (3b)
recorded on a JEOL JNM EX270 (270 MHz) or a JEOL JNM GSX500
(500 MHz) spectrometer; chemical shifts (d) are reported in parts
per million relative to tetramethylsilane. Splitting patterns are
designated as s, singlet; d, doublet; t, triplet; q, quartet; m, multi-
plet. 13C NMR spectra were recorded on a JEOL JNM GSX500
(500 MHz) spectrometer with complete proton decoupling.
Chemical shifts are reported in parts per million relative to tetra-
methylsilane with the solvent resonance as the internal standard
CDCl3 and DMSO-d6. High resolution mass spectra (HRMS) were
recorded on a JEOL JMS-SX-102A mass spectrometer. Elemental
analyses were carried out on a Yanaco CHN Corder MT-5. Analytical
TLC was performed on Merck precoated TLC plates (silica gel 60
GF254, 0.25 mm). Silica gel column chromatography was carried out
on silica gel 60N (Kanto Kagaku Co., Ltd., spherical, neutral, 63–
210 mm). Preparative thin layer chromatography (PTLC) was carried
out on silica gel Wakogel B-5F. THF was distilled under argon from
sodium/benzophenone ketyl. All oxidative carbon–carbon bond
formations were carried out under argon in dried glassware with
magnetic stirring.
N-tert-Butylbenzenesufinimidoyl chloride (4) was prepared
according to the modified literature procedure19 of employing
1.3 equiv of N,N-dichloro-tert-butylamine, and 1 was stored in a
refrigerator. 3-Alkylindoles (5a,20 5b,20 5d,17 and 5e17) were
prepared by the reported methods. Ethyl allylcyanoacetate and
ethyl benzylcyanoacetate were prepared by alkylation of ethyl
cyanoacetate (t-BuOK and alkylating agent). Other active methy-
lene compounds and methine compounds were purchased and
used after distillation.
Diastereomers were separated by preparative TLC (hexane/
benzene/ethyl acetate¼8:8:1). The less polar diastereomer; white
powder; mp 107.5–108.5 ꢁC. 1H NMR (500 MHz, CDCl3) d 0.99 (t,
J¼7.0 Hz, 3H), 2.67 (dd, J¼6.7, 14 Hz, 1H), 2.79 (dd, J¼7.9, 14 Hz, 1H),
4.01 (q, J¼7.0 Hz, 2H), 4.78 (s, 1H), 5.11–5.15 (m, 2H), 5.72–5.80 (m,
1H), 7.13 (t, J¼7.6 Hz, 1H), 7.20 (t, J¼7.3 Hz, 2H), 7.24–7.28 (m, 2H),
7.36 (d, J¼7.9 Hz, 1H), 7.58 (d, J¼7.3 Hz, 2H), 7.64 (d, J¼7.9 Hz, 1H),
7.71 (d, J¼2.4 Hz, 1H), 8.34 (s, 1H); 13C NMR (125.7 MHz, CDCl3)
d 13.7, 41.7, 48.4, 56.7, 62.5, 111.3, 113.1, 118.1, 119.5, 120.0, 120.1,
122.5, 122.5, 127.5, 127.8, 128.5, 128.6, 130.8, 135.3, 139.5, 168.1; IR
(CHCl3, cmꢀ1) 3021, 2359, 1736, 1211. Anal. Calcd for C23H22N2O2: C,
77.07; H, 6.19; N, 7.82. Found: C, 76.74; H, 6.16; N, 7.68.
The more polar diastereomer; white powder; mp 150.5–151 ꢁC.
1H NMR (500 MHz, CDCl3) d 0.99 (t, J¼7.0 Hz, 3H), 2.40 (dd, J¼6.7,
13.7 Hz, 1H), 2.72 (dd, J¼7.9, 13.7 Hz, 1H), 4.01 (q, J¼7.0 Hz, 2H),
4.78 (s, 1H), 5.16 (d, J¼4.9 Hz, 1H), 5.18 (s, 1H), 5.76–5.82 (m, 1H),
7.00 (t, J¼7.6 Hz, 1H), 7.12 (t, J¼7.0 Hz, 1H), 7.25–7.36 (m, 5H), 7.55
(d, J¼6.7 Hz, 2H), 7.80 (d, J¼2.4 Hz, 1H), 8.24 (s, 1H); 13C NMR
(125.7 MHz, CDCl3) d 13.7, 42.1, 48.6, 55.3, 62.6, 111.0, 114.2, 118.6,
119.0, 119.6, 120.7, 121.9, 122.4, 126.8, 127.9, 128.6, 129.6, 130.6,
135.5, 138.1, 168.2; IR (CHCl3, cmꢀ1) 3478, 2359, 1740, 1227. Anal.
Calcd for C23H22N2O2: C, 77.07; H, 6.19; N, 7.82. Found: C, 76.83; H,
6.18; N, 7.76.
4.2.3. 2-Benzyl-2-cyano-3-(1H-indol-3-yl)-3-phenylpropionic acid
ethyl ester (3c)
Diastereomers were separated by preparative TLC (benzene/
ethyl acetate¼100:1). The less polar diastereomer; white amor-
phous; 1H NMR (500 MHz, CDCl3) d 0.81 (t, J¼7.2 Hz, 3H), 3.19 (d,
J¼13.6 Hz, 1H), 3.36 (d, J¼13.6 Hz, 1H), 3.79–3.89 (m, 2H), 4.94 (s,
1H), 7.14–7.26 (m, 10H), 7.38 (d, J¼8.1 Hz, 1H), 7.61 (d, J¼8.1 Hz, 2H),
7.72 (d, J¼8.1 Hz, 1H), 7.82 (d, J¼2.4 Hz, 1H), 8.38 (s, 1H); 13C NMR
(125.7 MHz, CDCl3) d 13.5, 43.2, 49.0, 58.6, 62.4, 111.4, 113.2,
118.2, 119.5, 120.0, 122.6, 122.7, 127.5, 127.6, 127.9, 128.4, 128.5,
128.7, 129.9, 134.5, 135.4, 139.5, 168.0; IR (CHCl3, cmꢀ1) 3476,
1736; HRMS (EI) calculated for C27H24N2O2: 408.18378. Found:
408.18390.
4.2. Typical procedure for the oxidative C–C bond formation
of 3-alkylindole with active methylene compounds (Table 1,
entry 1)
To a stirred solution of 5a (50 mg, 0.241 mmol) in THF (3 mL)
was added dropwise a solution of n-BuLi (1.65 N in hexane, 0.19 mL,
0.31 mmol) at ꢀ78 ꢁC. After the mixture was stirred for 15 min at
the same temperature, a solution of 4 (77 mg, 0.36 mmol) in THF
(1 mL) was added at ꢀ78 ꢁC. After the mixture was stirred for
30 min at the same temperature, ethyl cyanoacetate (0.04 mL,
0.38 mmol) was added at ꢀ78 ꢁC, and the reaction mixture was
stirred for 30 min at the same temperature. The reaction mixture
was then treated with saturated aqueous NaHCO3, and the resulting
mixture was extracted with ethyl acetate (three times). The com-
bined organic extracts were dried over anhydrous Na2SO4, filtered,
and concentrated in vacuo. The crude product was purified by thin
layer chromatography on silica gel (hexane/ethyl acetate¼5:1) to
afford 3a (62 mg, 0.195 mmol, 81%) as a white solid.
The more polar diastereomer; white amorphous; 1H NMR
(500 MHz, CDCl3) d 0.80 (t, J¼7.1 Hz, 3H), 2.88 (d, J¼13.4 Hz, 1H),
3.28 (d, J¼13.4 Hz, 1H), 3.80–3.89 (m, 2H), 4.94 (s, 1H), 7.02 (t,
J¼7.4 Hz, 1H), 7.13 (t, J¼7.6 Hz, 1H), 7.20–7.40 (m, 10H), 7.65 (d,
J¼7.3 Hz, 2H), 7.77 (d, J¼2.4 Hz, 1H), 8.14 (s, 1H); 13C NMR
(125.7 MHz, CDCl3) d 13.5, 43.7, 49.3, 56.9, 62.5, 111.0, 114.3, 118.7,
119.2, 119.7, 121.9, 122.4, 126.9, 127.7, 127.9, 128.4, 128.7, 129.8,
129.8, 134.2, 135.5, 138.2, 168.1; IR (CHCl3, cmꢀ1) 3478, 2245, 1736,
1242; HRMS (EI) calculated for C27H24N2O2: 408.18378. Found:
408.18410.
4.2.1. 2-Cyano-3-(1H-indol-3-yl)-3-phenylpropionic acid ethyl
ester (3a)8b
4.2.4. Ethyl 2-[1H-indol-3-yl(phenyl)methyl]malonate (3d)8d
White silky fiber; mp 183.5–184.0 ꢁC (hexane/ethyl acetate)
[lit.8d 165–167 ꢁC (from EtOH)]. 1H NMR (500 MHz, CDCl3) d 0.97 (t,
J¼7.1 Hz, 3H), 1.00 (t, J¼7.1 Hz, 3H), 3.95–4.30 (m, 4H), 4.29 (d,
J¼11.8 Hz, 1H), 5.08 (d, J¼11.8 Hz, 1H), 7.02 (t, J¼7.7 Hz, 1H), 7.10–
7.14 (m, 3H), 7.20–7.26 (m, 3H), 7.36 (d, J¼7.6 Hz, 2H), 7.54 (d,
J¼8.1 Hz, 1H), 8.09 (s, 1H); 13C NMR (125.7 MHz, CDCl3) d 13.7, 13.7,
42.6, 58.4, 61.4, 61.4, 111.0, 116.9, 119.3, 119.4, 120.9, 122.2, 126.7,
126.7, 128.2, 128.3, 136.2, 141.4, 167.8, 168.0.
A mixture of diastereomers (63:27); white solid; mp 79.5–
80.5 ꢁC (hexane/ethyl acetate) [lit.8b 91–93 ꢁC (from aqueous
AcOH)]. 1H NMR (500 MHz, CDCl3, major diastereomer) d 1.10 (t,
J¼7.5 Hz, 3H), 4.07–4.20 (m, 2H), 4.32 (d, J¼6.7 Hz, 1H), 5.04 (d,
J¼6.7 Hz, 1H), 7.01–7.08 (m, 1H), 7.23–7.39 (m, 6H), 7.46 (d, J¼
7.3 Hz, 2H), 8.15 (s, 1H); 1H NMR (500 MHz, CDCl3, minor di-
astereomer) d 1.08 (t, J¼7.5 Hz, 3H), 4.07–4.20 (m, 2H), 4.19 (d,
J¼6.7 Hz, 1H), 5.10 (d, J¼6.7 Hz, 1H), 7.01–7.08 (m, 1H), 7.15–7.20
(m, 1H), 7.23–7.39 (m, 6H), 7.50 (d, J¼2.4 Hz, 1H), 8.19 (s, 1H); 13C
NMR (67.8 MHz, CDCl3, major diastereomer) d 13.6, 43.1, 44.2, 62.9,
111.3, 113.1, 116.1, 118.6, 119.6, 122.1, 122.5, 126.5, 127.6, 127.9, 128.6,
136.0, 139.6, 165.2; 13C NMR (67.8 MHz, CDCl3, minor diastereomer)
d 13.7, 43.1, 45.0, 62.8, 111.3, 114.5, 116.3, 118.8, 119.7, 122.2, 122.4,
126.0, 127.8, 128.3, 128.6, 136.2, 138.6, 165.3.
4.2.5. Ethyl 2-[1H-indol-3-yl(phenyl)methyl]-2-methyl-
malonate (3e)
Pale yellow oil; 1H NMR (500 MHz, CDCl3) d 0.93 (t, J¼7.0 Hz,
3H), 1.10 (t, J¼7.0 Hz, 3H), 1.66 (s, 3H), 3.91–3.99 (m, 2H), 4.08 (q,
J¼7.0 Hz, 2H), 5.36 (s, 1H), 6.99 (t, J¼7.6 Hz, 1H), 7.09–7.15 (m, 2H),
7.18–7.21 (m, 2H), 7.27 (d, J¼7.9 Hz, 1H), 7.40 (d, J¼2.4 Hz, 1H), 7.44

5266
J.-ichi Matsuo et al. / Tetrahedron 64 (2008) 5262–5267
(dd, J¼7.0, 1.5 Hz, 3H), 8.11 (s, 1H); 13C NMR (67.8 MHz, CDCl3)
d 13.5, 13.7, 19.1, 46.7, 59.2, 61.3, 61.3, 110.8, 115.2, 119.1, 119.2, 121.9,
122.4, 126.5, 127.7, 127.9, 130.3, 135.3, 140.2, 171.2, 171.5; IR (CHCl3,
cmꢀ1) 3480, 2350, 1728; HRMS (EI) calculated for C23H25NO4:
379.17836. Found 379.17920.
4.2.11. 2-Cyano-3-(1H-indol-3-yl)-3-(4-chlorophenyl)propionic
acid ethyl ester (3k)
A mixture of diastereomers (50:50); colorless oil; 1H NMR
(500 MHz, CDCl3) d 1.09 (t, J¼7.3 Hz, 3H), 1.13 (t, J¼7.3 Hz, 3H),
4.07–4.16 (m, 5H), 4.31 (d, J¼6.1 Hz, 1H), 5.02 (d, J¼6.7 Hz, 1H), 5.08
(d, J¼6.1 Hz, 1H), 7.01–7.10 (m, 2H), 7.17–7.38 (m, 15H), 7.46 (d,
J¼2.4 Hz, 1H), 8.23 (s, 1H), 8.28 (s, 1H); 13C NMR (125.7 MHz, CDCl3)
d 13.7, 13.8, 42.4, 42.5, 44.0, 44.8, 63.0, 111.3, 111.4, 112.8,114.3, 115.9,
116.0,118.6,118.8,119.9,120.0,122.0,122.1,122.7,122.8,125.9,126.4,
128.9, 129.0, 129.4, 129.8, 133.6, 133.8, 136.1, 136.2, 137.1, 138.2,
165.0, 165.0; IR (CHCl3, cmꢀ1) 3476, 1745, 1223; HRMS (EI) calcu-
lated for C20H17N2O2Cl: 352.09786. Found 352.09807.
4.2.6. Ethyl 2-benzyl-2-[1H-indol-3-yl(phenyl)methyl]-
malonate (3f)
Colorless needles; mp 135.5–136.0 ꢁC; 1H NMR (500 MHz,
CDCl3) d 0.85 (t, J¼7.3 Hz, 3H), 1.01 (t, J¼7.3 Hz, 3H), 3.43 (d,
J¼14.0 Hz, 1H), 3.60 (d, J¼14.0 Hz, 1H), 3.84–4.03 (m, 4H), 5.16 (s,
1H), 6.98–7.01 (m, 3H), 7.10–7.19 (m, 7H), 7.31 (d, J¼8.5 Hz,1H), 7.40
(d, J¼7.9 Hz, 3H), 7.72 (d, J¼2.4 Hz, 1H), 8.11 (s, 1H); 13C NMR
(67.8 MHz, CDCl3) d 13.4, 13.6, 42.0, 48.3, 60.8, 60.9, 64.4, 110.8,
115.3,118.8,119.3,121.8, 122.9,126.5,126.6,127.5, 127.8,127.9, 130.2,
130.3, 135.4, 136.8, 140.4, 170.1, 171.1; IR (CHCl3, cmꢀ1) 3480, 1717.
Anal. Calcd for C27H29NO4: C, 76.46; H, 6.42; N, 3.07. Found: C,
76.63; H, 6.51; N, 3.09.
4.2.12. 2-Cyano-3-(1H-indol-3-yl)-3-(4-methoxyphenyl)propionic
acid ethyl ester (3l)
A mixture of diastereomers (50:50); white powder; mp 128–
128.5 ꢁC; 1H NMR (500 MHz, CDCl3) d 1.08 (t, J¼7.0 Hz, 3H), 1.12 (t,
J¼7.0 Hz, 3H), 3.74 (s, 3H), 3.75 (s, 3H), 4.07–4.16 (m, 5H), 4.30 (d,
J¼6.1 Hz, 1H), 4.99 (d, J¼6.1 Hz, 1H), 5.05 (d, J¼6.7 Hz, 1H), 6.80–
6.84 (m, 4H), 7.00 (t, J¼7.3 Hz, 1H), 7.04 (t, J¼7.3 Hz, 1H), 7.15–7.36
(m, 11H), 7.45 (d, J¼2.4 Hz, 1H), 8.21 (br s, 1H), 8.25 (br s, 1H); 13C
NMR (125.7 MHz, CDCl3) d 13.7, 13.8, 42.4, 42.5, 44.5, 45.2, 55.2,
55.2, 62.8, 62.8, 111.2, 111.3, 113.6, 114.0, 114.1, 115.1, 116.2, 116.4,
118.8, 119.0, 119.8, 121.9, 122.0, 122.4, 122.5, 126.1, 126.6, 128.5,
128.6,128.9,129.0,129.1,129.5,130.7,131.8,136.1,136.3,159.0,159.1,
165.3, 165.3; IR (CHCl3, cmꢀ1) 3478, 2253, 1744, 1512, 1252; HRMS
(EI) calculated for C21H20O3N2: 348.14740. Found: 348.14812.
4.2.7. Benzyl 2-[1H-indol-3-yl(phenyl)methyl]malonate (3g)
White powder; mp 135.8–136.2 ꢁC; 1H NMR (500 MHz, CDCl3)
d 4.42 (d, J¼12.0 Hz, 1H), 4.90–4.97 (m, 4H), 5.12 (d, J¼12.0 Hz, 1H),
6.94 (d, J¼7.3 Hz, 2H), 7.02–7.05 (m, 4H), 7.16–7.28 (m, 11H), 7.32 (d,
J¼7.3 Hz, 2H), 7.51 (d, J¼7.9 Hz, 1H), 7.87 (s, 1H); 13C NMR
(125.7 MHz, CDCl3) d 42.9, 58.3, 67.1, 67.1, 111.0, 116.4, 119.2, 119.5,
121.1,122.2,126.5,126.7,127.9,128.0,128.0,128.1,128.1,128.3,128.4,
135.0, 135.1, 136.2, 141.1, 167.6, 167.7; IR (CHCl3, cmꢀ1) 3478, 2386,
1755, 1732. Anal. Calcd for C32H27NO4: C, 78.51; H, 5.56; N, 2.86.
Found: C, 78.45; H, 5.60; N, 2.92.
4.2.13. 2-Cyano-3-(1H-indol-3-yl)-5-phenylpenta-4-enoic acid
ethyl ester (3m)
4.2.8. Ethyl 2-[1H-indol-3-yl(phenyl)methyl]-3-oxobutanoate
A mixture of diastereomers (60:40); colorless oil; 1H NMR
(500 MHz, CDCl3, major diastereomer) d 1.20 (t, J¼7.0 Hz, 3H), 4.05–
4.08 (m, 1H), 4.21 (q, J¼7.0 Hz, 2H), 4.60–4.63 (m, 1H), 6.51–6.70 (m,
2H), 7.11–7.39 (m, 9H), 7.64 (d, J¼7.9 Hz, 1H), 8.23 (br s, 1H); 1H NMR
(500 MHz, CDCl3, minor diastereomer) d 1.06 (t, J¼7.0 Hz, 3H), 4.05–
4.08 (m, 3H), 4.60–4.63 (m, 1H), 6.51–6.70 (m, 2H), 7.11–7.39 (m, 9H),
7.64 (d, J¼7.9 Hz,1H), 8.26 (s,1H); 13C NMR (125.7 MHz, CDCl3, mixture
of diastereomers) d13.7,14.0, 41.2, 41.3, 44.6, 44.7, 62.8, 62.8,111.4,111.6,
112.6, 113.7, 115.8, 116.1, 118.3, 118.8, 119.9, 120.0, 122.2, 122.4, 122.5,
122.7, 125.5, 125.6, 126.2, 126.5, 126.6, 127.5, 127.9, 127.9, 128.6, 132.6,
133.8,136.1,136.2,136.3,136.4,165.2; IR (CHCl3,cmꢀ1) 3478, 2359,1745;
HRMS (EI) calculated for C22H20N2O2: 344.15248. Found 344.15233.
(3h)8c
A
mixture of diastereomers (83:17); white powder; mp
162–162.5 ꢁC (from hexane/benzene¼1:1) [lit.8c 162–163 ꢁC
(EtOH)]. 1H NMR (500 MHz, CDCl3, major diastereomer) d 0.97 (t,
J¼7.3 Hz, 3H), 2.04 (s, 3H), 3.94–4.00 (m, 2H), 4.50 (d, J¼11.6 Hz,
1H), 5.09 (d, J¼11.6 Hz,1H), 7.01–7.35 (m, 9H), 7.54 (d, J¼7.9 Hz,1H),
8.03 (s, 1H); 1H NMR (500 MHz, CDCl3, minor diastereomer) d 0.99
(t, J¼7.3 Hz, 3H), 2.14 (s, 3H), 3.94–4.00 (m, 2H), 4.38
(d, J¼12.3 Hz,1H), 5.06 (d, J¼12.2 Hz,1H), 7.01–7.35 (m, 9H), 7.54 (d,
J¼7.9 Hz, 1H), 8.06 (s, 1H); 13C NMR (125.7 MHz, CDCl3, major
diastereomer) d 13.8, 30.3, 42.6, 61.4, 65.9, 111.0, 117.3, 119.4,
119.5, 120.7, 122.3, 126.8, 128.1, 128.1, 128.4, 128.6, 136.2, 141.3,
168.0.
4.2.14. 2-Cyano-3-(1H-indol-3-yl)penta-4-enoic acid ethyl ester
(3n)
4.2.9. 3-[1H-Indol-3-yl(phenyl)methyl]pentane-2,4-dione (3i)8d
Colorless plates; mp 153.5–154.0 ꢁC (from hexane/ethyl
acetate¼5:2) [lit.8d mp 150–152 ꢁC (from EtOH)]. 1H NMR
(500 MHz, CDCl3) d 1.93 (s, 3H), 2.05 (s, 3H), 4.64 (d, J¼12.2 Hz, 1H),
5.09 (d, J¼12.2 Hz, 1H), 7.04 (t, J¼7.0 Hz, 1H), 7.11–7.16 (m, 3H), 7.23
(t, J¼7.6 Hz, 2H), 7.30 (t, J¼7.9 Hz, 3H), 7.53 (d, J¼7.9 Hz, 1H), 8.09
(br s, 1H); 13C NMR (125.7 MHz, CDCl3) d 27.6, 31.3, 43.2, 75.3, 111.1,
116.6,119.0,119.8, 121.2, 122.6,126.3,126.8,128.1, 128.6,136.2,141.3,
203.5, 204.1; IR (CHCl3, cmꢀ1) 3478, 1721, 1696, 1356.
A mixture of diastereomers (60:40); colorless oil; 1H NMR
(500 MHz, CDCl3, major diastereomer) d 1.24 (t, J¼7.0 Hz, 3H), 3.99
(d, J¼6.1 Hz, 1H), 4.22 (q, J¼7.0 Hz, 2H), 4.44–4.47 (m, 1H), 5.25–
5.37 (m, 2H), 6.13–6.28 (m, 1H), 7.11–7.24 (m, 3H), 7.38 (d, J¼7.9 Hz,
1H), 7.59 (t, J¼8.2 Hz,1H), 8.20 (br s, 1H); 1H NMR (500 MHz, CDCl3,
minor diastereomer) d 1.08 (t, J¼7.0 Hz, 3H), 3.99 (d, J¼6.1 Hz, 1H),
4.07 (q, J¼7.0 Hz, 2H), 4.44–4.47 (m, 1H), 5.25–5.37 (m, 2H), 6.13–
6.28 (m, 1H), 7.11–7.24 (m, 2H), 7.31 (d, J¼2.4 Hz, 1H), 7.36 (d,
J¼7.9 Hz, 1H), 7.59 (t, J¼8.2 Hz, 1H), 8.23 (br s, 1H); 13C NMR
(125.7 MHz, CDCl3, mixture of diastereomers) d 13.7,13.9, 41.6, 44.2,
44.3, 111.4, 111.5, 112.2, 113.4, 115.6, 116.0, 117.5, 118.2, 118.7, 118.8,
119.7, 119.9, 122.2, 122.4, 122.5, 122.6, 125.6, 126.2, 134.3, 136.0,
136.2, 136.3, 165.2, 165.3; IR (CHCl3, cmꢀ1) 3478, 2361, 1743; HRMS
(EI) calculated for C16H16N2O2: 268.12118. Found 268.12117.
4.2.10. 2-[1H-Indol-3-yl(phenyl)methyl]-1,3-diphenylpropane-1,3-
dione (3j)
White powder; mp 171–172 ꢁC; 1H NMR (500 MHz, DMSO)
d 5.34 (d, J¼11.5 Hz, 1H), 6.89–7.02 (m, 4H), 7.07 (t, J¼7.6 Hz, 2H),
7.20 (d, J¼7.8 Hz, 1H), 7.37–7.41 (m, 4H), 7.50–7.57 (m, 5H), 7.61 (s,
1H), 8.03 (d, J¼7.0 Hz, 2H), 8.08 (d, J¼7.0 Hz, 2H), 10.8 (br s, 1H);
13C NMR (125.7 MHz, DMSO) d 43.7, 60.0, 111.1, 116.7, 118.3, 118.5,
121.0, 122.1, 125.9, 126.5, 127.7, 128.5, 128.5, 128.6, 128.6, 128.7,
133.4, 135.8, 136.3, 136.4, 142.6, 193.4, 194.4; IR (CHCl3, cmꢀ1) 3480,
1728; HRMS (EI) calculated for C30H23O2N: 429.17288. Found:
429.17405.
4.3. Typical experimental procedure for oxidative C–C bond
formation of 3-benzylindole 5a with higher-order
cyanocuprates (Table 3, entry 4)
A solution of Ph2Cu(CN)Li2 was prepared as follows; to a stirred
solution of copper(I) cyanide (61.2 mg, 0.68 mmol) in Et2O (4 mL)

J.-ichi Matsuo et al. / Tetrahedron 64 (2008) 5262–5267
5267
was added dropwise a solution of phenyllithium (1.14 N in cyclo-
hexane/ether, 1.06 ml, 1.21 mmol) at ꢀ20 ꢁC for 1 h.
the Ministry of Education, Culture, Sports, Science, and Technology
of Japan.
To a stirred solution of 5a (50 mg, 0.24 mmol) in THF (3 mL) was
added dropwise a solution of n-BuLi (1.61 N in hexane, 0.20 mL,
0.32 mmol) at ꢀ78 ꢁC. After the mixture was stirred at the same
temperature for 15 min, a solution of 4 (83 mg, 0.38 mmol) in THF
(1 mL) was added at ꢀ78 ꢁC. After the mixture was stirred at the
same temperature for 30 min, a solution of Ph2Cu(CN)Li2 was
added at ꢀ78 ꢁC with a cannula, and the reaction mixture
was stirred at the same temperature for 30 min and the product 9d
was obtained in usual manner.
References and notes
1. (a) Sundberg, R. Indoles; Academic: San Diego, 1996; (b) Robinson, B. The Fischer
Indole Synthesis; Wiley-Interscience: New York, NY, 1982; (c) Sundberg, R. The
Chemistry of Indoles; Academic: New York, NY, 1970.
2. For reviews on the synthesis of indoles: (a) Humphrey, R. R.; Kuethe, J. T. Chem.
Rev. 2006, 106, 2875–2911; (b) Gilchrist, T. L. J. Chem. Soc., Perkin Trans. 1 2001,
2491–2515; (c) Gribble, G. W. J. Chem. Soc., Perkin Trans. 1 2000, 1045–1075; (d)
Pindur, U.; Adam, R. J. Heterocycl. Chem. 1988, 25, 1–8.
3. (a) Snyder, H.; Smith, C.; Stewart, J. J. Am. Chem. Soc. 1944, 66, 200–204; (b)
Albright, J. D.; Snyder, H. R. J. Am. Chem. Soc. 1959, 81, 2239–2245; (c) Howe, E.
E.; Zambito, A. J.; Snyder, H. R.; Tishler, M. J. Am. Chem. Soc. 1945, 67, 38–39; (d)
Albertson, N. F.; Archer, S.; Suter, C. M. J. Am. Chem. Soc. 1945, 67, 36–37; (e)
Somei, M.; Karasawa, Y.; Kaneko, C. Heterocycles 1981, 16, 941–949.
4. Review: Semenov, B. B.; Granik, V. G. Pharm. Chem. J. 2004, 38, 287–310.
5. (a) Ballini, R.; Palmieri, A.; Petrini, M.; Torregiani, E. Org. Lett. 2006, 8, 4093–
4096; (b) Palmieri, A.; Petrini, M. J. Org. Chem. 2007, 72, 1863–1866.
6. (a) Runti, C. Gazz. Chim. Ital. 1951, 81, 613–620; (b) Runti, C.; Orlando, G. Ann.
Chim. (Rome) 1953, 43, 308–314.
4.3.1. 3-(1-Phenylethyl)indole (9a)5a
White solid; 1H NMR (500 MHz, CDCl3) d 1.70 (t, J¼7.3 Hz, 3H),
4.37 (q, J¼7.3 Hz, 1H), 6.98–7.37 (m, 10H), 7.96 (s, 1H); 13C NMR
(125.7 MHz, CDCl3) d 22.4, 36.9,111.0,119.2,119.7,121.0,121.9,122.3,
125.9, 127.4, 128.3, 128.7, 136.6, 146.8.
4.3.2. 3-(1-Phenylpentyl)indole (9b)
7. Poppelsdorf, F.; Holt, S. J. J. Chem. Soc. 1954, 4094–4101.
Colorless plates; mp 74.5–75.5 ꢁC; 1H NMR (270 MHz, CDCl3)
d 0.86 (t, J¼7.0 Hz, 3H), 1.27–1.35 (m, 4H), 1.96–2.03 (m, 1H), 2.14–
2.21 (m, 1H), 4.14 (t, J¼7.6 Hz, 1H), 6.97–7.02 (m, 2H), 7.11 (d,
J¼8.1 Hz, 1H), 7.15 (d, J¼7.8 Hz, 1H), 7.23–7.30 (m, 5H), 7.44 (d,
J¼8.1 Hz, 1H), 7.83 (s, 1H); 13C NMR (125.7 MHz, CDCl3) d 14.0, 22.8,
30.3, 35.9, 42.9, 111.0, 119.2, 119.5, 120.7, 120.9, 121.9, 125.8, 127.1,
127.9, 128.2, 136.5, 145.6; IR (CHCl3, cmꢀ1) 3481, 1456; HRMS (EI)
calculated for C21H19N: 263.16740. Found 263.16743.
8. (a) Semenov, B. B.; Novikov, K. A.; Lysenko, K. A.; Kachala, V. V. Tetrahedron Lett.
2006, 47, 3479–3483; (b) Semenov, B. B.; Smushkevich, V. V. Y. I.; Levina, I. I.;
Kurkovskaya, L. N.; Lysenko, K. A.; Kachala, V. V. Chem. Heterocycl. Comp. 2005,
41, 730–738; (c) Semenov, B. B.; Smushkevich, Y. I.; Grintselev-Knyazev, G. V.;
Antipin, M. Y. Russ. Chem. Bull., Int. Ed. 2001, 50, 570–571; (d) Semenov, B. B.;
Smushkevich, Y. I. Russ. Chem. Bull., Int. Ed. 2001, 50, 543–545.
9. Recent examples: (a) Gibbs, T. J. K.; Tomkinson, N. C. O. Org. Biomol. Chem. 2005,
3, 4043–4045; (b) Shirakawa, S.; Kobayashi, S. Org. Lett. 2006, 8, 4939–4942; (c)
Ke, B.; Qin, Y.; He, Q.; Huang, Z.; Wang, F. Tetrahedron Lett. 2005, 46, 1751–1753.
10. (a) Schellenberg, K. A. J. Biol. Chem. 1965, 240, 1165–1169; (b) Schellenberg, K. A.
J. Biol. Chem. 1967, 242, 1815–1820; (c) Schellenberg, K. A.; McLean, G. W. J. Am.
Chem. Soc. 1966, 88, 1077–1079; (d) Schellenberg, K. A.; McLean, G. W.; Lipton,
H. L.; Lietman, P. S. J. Am. Chem. Soc. 1967, 89, 1948–1950; (e) Huffman, R. W.;
Bruice, T. C. J. Am. Chem. Soc. 1967, 89, 6243–6251.
4.3.3. 3-(2,2-Dimethyl-1-phenylpropyl)indole (9c)
White powder; mp 87.5–88.5 ꢁC; 1H NMR (270 MHz, CDCl3)
d 1.04 (s, 9H), 4.15 (s, 1H), 7.02–7.40 (m, 9H), 7.58 (d, J¼7.7 Hz, 1H),
7.98 (s, 1H); 13C NMR (67.8 MHz, CDCl3) d 29.0, 35.2, 53.6, 110.7,
117.8, 119.0, 119.1, 121.0, 121.8, 125.7, 127.5, 128.8, 130.0, 135.1, 143.3;
IR (CHCl3, cmꢀ1) 3481, 1456; HRMS (EI) calculated for C21H19N:
263.16740. Found 263.16682.
11. Burr, G. O.; Gortner, R. A. J. Am. Chem. Soc. 1924, 46, 1224–1246.
12. Recent reports: (a) Catino, A. J.; Nicholas, J. M.; Nettles, B. J.; Doyle, M. P. J. Am.
Chem. Soc. 2006, 128, 5648–5649; (b) Murahashi, S.-I.; Komiya, N.; Terai, H.
Angew. Chem., Int. Ed. 2005, 44, 6931–6933; (c) Li, Z.; Li, C.-J. J. Am. Chem. Soc.
2005, 127, 3672–3673 and references are cited therein.
13. (a) Matsuo, J. J. Synth. Org. Chem. Jpn. 2004, 62, 574–583; (b) Mukaiyama, T.
Angew. Chem., Int. Ed. 2004, 43, 5590–5614.
14. (a) Matsuo, J.; Tanaki, Y.; Ishibashi, H. Org. Lett. 2006, 8, 4371–4374; (b) Matsuo,
J.; Tanaki, Y.; Ishibashi, H. Tetrahedron Lett. 2007, 48, 3233–3236; (c) Matsuo, J.;
Kawai, H.; Ishibashi, H. Tetrahedron Lett. 2007, 48, 3155–3158.
15. For application to other one-pot C–C bond formations, see: (a) Matsuo, J.; Ai-
zawa, Y. Chem. Commun. 2005, 2399–2401; (b) Matsuo, J.; Shibata, T.; Kitagawa,
H.; Mukaiyama, T. ARKIVOC 2001, 58–65; (c) Kerr, W. J.; Pearson, C. M.; Thur-
ston, G. J. Org. Biomol. Chem. 2006, 4, 47–50; (d) Crawford, J. J.; Henderson, K.
W.; Kerr, W. J. Org. Lett. 2006, 8, 5073–5076.
16. Whitney, S.; Grigg, R.; Derrick, A.; Keep, A. Org. Lett. 2007, 9, 3299–3302.
17. Kimura, M.; Futamata, M.; Mukai, R.; Tamaru, Y. J. Am. Chem. Soc. 2005, 127,
4592–4593.
18. (a) Nickel-catalyzed reaction: Pratt, E. T.; Botimer, L. W. J. Am. Chem. Soc. 1957,
79, 5248–5250; (b) Wenkert, E.; Angell, E. C.; Ferreira, V. F.; Michelotti, E. L.;
Piettre, S. R.; Sheu, J.-H.; Swindell, C. S. J. Org. Chem. 1986, 51, 2343–2351.
19. Matsuo, J.; Iida, D.; Tatani, K.; Mukaiyama, T. Bull. Chem. Soc. Jpn. 2002, 75, 223–
234.
4.3.4. 3-Diphenylmethylindole (9d)21
White needles; mp 124.5–124.8 ꢁC (lit.21 121 ꢁC); 1H NMR
(500 MHz, CDCl3) d 5.66 (s, 1H), 6.54 (d, J¼2.2 Hz, 1H), 6.96–6.99
(m, 1H), 7.14–7.28 (m, 12H), 7.33 (d, J¼8.1 Hz, 1H), 7.88 (s, 1H); 13C
NMR (125.7 MHz, CDCl3) d 48.8, 111.0, 119.4, 119.9, 122.1, 124.0,
126.2, 127.0, 128.3, 129.0, 136.7, 143.9.
Acknowledgements
The authors are grateful for the financial support from Takeda
Science Foundation, the Research Foundation for Pharmaceutical
Sciences and the Sasakawa Scientific Research Grant from The Ja-
pan Science Society, and a Grant-in-Aid for Scientific Research from
20. Ernest, F. P.; Laurence, W. B. J. Am. Chem. Soc. 1957, 79, 5248–5250.
21. Yasuda, M.; Somyo, T.; Baba, A. Angew. Chem., Int. Ed. 2006, 45, 793–796.