A palladium-catalyzed tandem cyclization-cross-coupling reaction using indolylborate as a transfer agent

Article abstract of DOI:10.1016/j.tet.2006.09.065

Investigation of the palladium-catalyzed tandem cyclization-cross-coupling reaction using indolylborate (2) as a transfer agent has been carried out. Furthermore, the cross-coupling reaction performed under carbon monoxide led to the generation of indolyl

Full text of DOI:10.1016/j.tet.2006.09.065

Tetrahedron 62 (2006) 11580–11591
A palladium-catalyzed tandem cyclization-cross-coupling reaction
using indolylborate as a transfer agent
a
a
b
Minoru Ishikura,a, Norinobu Takahashi, Koji Yamada and Reiko Yanada
*
aFaculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido 061-0293, Japan
bFaculty of Pharmaceutical Sciences, Hiroshima International University, 5-1-1 Hirokoshingai, Kure, Hiroshima 737-0112, Japan
Received 28 August 2006; revised 11 September 2006; accepted 19 September 2006
Abstract—Investigation of the palladium-catalyzed tandem cyclization-cross-coupling reaction using indolylborate (2) as a transfer agent
has been carried out. Furthermore, the cross-coupling reaction performed under carbon monoxide led to the generation of indolyl ketones.
Ó 2006 Elsevier Ltd. All rights reserved.
1. Introduction
2. Results and discussion
Metal-catalyzed cross-coupling reactions have now become
a quite significant synthetic tool for the carbon–carbon bond
formation, and have furnished an enormous variety of fasci-
nating transformations.1 Within this research, the search for
palladium-catalyzed tandem Heck-type carbocyclization-
cross-coupling reactions has provided a vast development
that complex entities can be built up in a one-pot protocol,2
in which various organometallic reagents such as zinc, tin,
and magnesium compounds were adapted as transfer agents
to take advantage of their high reactivity. The Suzuki cross-
coupling protocol has now emerged as the method of choice
in various chemical transformations,3 for which phenyl-
boronic acid is ranked among the premier transfer agents,
whereas the use of organoboron compounds in the tandem
process is of limited significance.4 Notably, tetravalent orga-
noboron compounds (ate complexes) have proven to offer
less practical advantages over other agents.5
At first, we have set about our study by reacting 2, generated
from the corresponding indole (1) and triethylborane in
situ,9 with 3 in the presence of a catalytic amount of palla-
dium complex (5 mol %). The following common mechanis-
tic scheme might account for the present reaction (Scheme
1); (1) the palladium-catalyzed Heck-type cyclization of 3,
(2) the transmetalation between complex (A) and 2 possibly
involving transfer of the indole ring and/or the Et group, and
(3) the subsequent reductive elimination. The implementa-
tion of the present protocol requires a potent transfer of
the indole ring of 2 (A/B) to produce 4, while competitive
transfer of the ethyl group of 2 (A/C) should account for
the formation of 5.
On treating 2a with 1 and 2 equiv of 3a in the presence of
Pd(OAc)2, 4a was obtained in 60 and 53% yields, respec-
tively, along with substantial amounts of 5a as a byproduct.
Eventually, the successful reaction of 2a with 3a could be
achieved using an excess amount of 2a (ca. 2 equiv) in the
presence of Pd(OAc)2 in THF at 60 ꢀC, which proceeded to
completion within 30 min, allowing the isolation of 4a in
78% yield along with trace amounts of 5a (Table 1). On the
other hand, marked retardation in the yield of 4a and the ap-
preciable appearance of 5a were observed in the reaction
with PPh3. Under the same conditions, treatment of 2a with
bromide (3b) resulted in a lower yield of 4a together with
substantial amounts of 5a.
In connection with our project to elucidate indolylborate (2)
as a potential synthetic intermediate,6 we have previously
disclosed that 2 is highly effective, though nevertheless an
ate complex, in the palladium-catalyzed cross-coupling pro-
cess.7 By taking advantage of the attractive features of 2 in
the cross-coupling reaction, we have interested in whether
2 might also be valid as a transfer agent in the palladium-
catalyzed tandem cyclization-cross-coupling process, and
herein, we report the detailed results of our investigation.8
The (E)-configuration in 4a was firmly established based on
NOE experiments, in which irradiation of the H20-proton at
d 4.82 gave NOE enhancement of the methyl group at d 2.04
(Chart 1).
Keywords: Indolylborate; Cascade reaction; Cross-coupling reaction;
Carbonylation; Palladium catalyst.
* Corresponding author. Tel./fax: +81 133 23 1245; e-mail: ishikura@
hoku-iryo-u.ac.jp
0040–4020/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2006.09.065

M. Ishikura et al. / Tetrahedron 62 (2006) 11580–11591
11581
Scheme 1.
The reaction of 2a with 3e and 3f was messy, allowing the
isolation of 4c only in a low yield. This is likely due to the
lower stability of complex (A) (R¼H) during the transmeta-
lation step.
A closely related reaction outcome could be observed on the
reaction of 2 with 6 (Table 2). When the reaction was per-
formed in the presence of PPh3, a decrease in the yield of
7 and the appearance of 8 were observed.
Chart 1.
It is possible that the increased steric bulkiness on the Pd in
A (L¼PPh3) or the decrease in the positive charge on the Pd
in A (X¼Br)10 might hamper the coordination–transmetala-
tion step, thus allowing enough time for side reactions and
resulting in the formation of 4a and 5a with the observed
selectivity.
Subjection of iodides (9)11 to the reaction with 2a under the
same conditions also afforded cross-coupling products (10)
in good yields (Scheme 2).
To explore the advantage of this reaction, we next investi-
gated the reaction of 2 with 11 having an olefin moiety under
the same conditions. The initially attempted reaction of 2a
with 11 was messy, and resulted in the isolation of 12 and
13 in low yields (Table 3).
A clear steric effect was observed during the reaction of
N-Boc-indolylborate (2c). The reaction of 2c with 3a
became sluggish, giving 4f in 23% yield along with 5a
(20%) and unreacted 3a (18%) after heating for 2 h. With
3c having a bulky TMS group on the alkyne terminus, the
reaction of 2c failed to isolate cross-coupling products, re-
sulting in substantial amounts of 3c and other unidentified
compounds.
Due to the possible presence of multiple paths acting simul-
taneously in the decomposition of the s-alkyl palladium
complex (D),12 there is no clear account for the formation
of 12. One possibility suggests that the homolytic cleavage

11582
M. Ishikura et al. / Tetrahedron 62 (2006) 11580–11591
Table 1. Tandem cyclization-cross-coupling reaction of 2 with 3a
of the C–Pd bond, a commonly observable side reaction, is
responsible for the generation of 12 (Scheme 3).13 On the
other hand, the nucleophilic attack of 2a with a spontaneous
intramolecular alkyl migration to complex (D) could have
produced 13.14
2
3
PdLn
Time Yield (%)b Yield (%)b
(h)
of 4
of 5
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
3a
3a
3a
3a
3a
3a
3a
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2+2PPh3
Pd2(dba)3CHCl3
Pd2(dba)3CHCl3+4PPh3
PdCl2(CH3CN)2
1
1
0.5
1
0.5
1
0.5
1
1
1
2
1
2
0.5
0.5
0.5
1
1
0.5
1
0.5
1
1
53 (4a)c
60 (4a)d
78 (4a)
37 (4a)
75 (4a)
34 (4a)
75 (4a)
53 (4a)
35 (4a)
50 (4a)
29 (4a)
53 (4a)
35 (4a)
71 (4b)
71 (4b)
72 (4b)
55 (4b)
51 (4b)
34 (4c)
24 (4c)
29 (4c)
12 (4c)
27 (4c)
18 (4c)
70 (4d)
65 (4e)
55 (4d)
43 (4e)
23 (4f)
—
13 (5a)c
10 (5a)d
—
30 (5a)
—
As several factors are generally known to enhance the stabil-
ity of the s-monoalkyl palladium complex, an increase in
sterical hindrance was envisioned to exert an influence on
the stability of s-alkyl palladium intermediate, enabling
the cross-coupling reaction to proceed.
31 (5a)
—
3b Pd(OAc)2
15 (5a)
23 (5a)
20 (5a)
35 (5a)
15 (5a)
25 (5a)
—
—
—
15 (5b)
15 (5b)
—
—
—
—
—
—
—
3b Pd(OAc)2+2PPh3
3b Pd2(dba)3CHCl3
3b Pd2(dba)3CHCl3+4PPh3
3b PdCl2(CH3CN)2
3b PdCl2(CH3CN)2+2PPh3
3c
3c
3c
Then, we next carried out the reaction using 14 under the
same conditions (Table 4). As was expected, treatment of
2a,b with 14 in the presence of Pd(OAc)2 smoothly produced
the cross-coupling product (15) in good yields. However, the
presence of PPh3 markedly altered the reaction outcome by
resulting in a lower yield of 15 along with 16.15 A reason
for this result is that the s-alkyl palladium intermediate, gen-
erated from 14 by the way of carbopalladation, might possi-
bly undergo homolytic cleavage of the C–Pd bond to give 16.
Pd(OAc)2
PdCl2(CH3CN)2
Pd2(dba)3CHCl3
3d Pd(OAc)2
3d PdCl2(CH3CN)2
3e
3e
3e
3e
3f
3f
Pd(OAc)2
Pd(OAc)2+2PPh3
Pd2(dba)3CHCl3
Pd2(dba)3CHCl3+4PPh3
Pd(OAc)2
Pd(OAc)2+2PPh3
Pd(OAc)2
Pd(OAc)2
Otherwise, treatment of 2a with 17 allowed the isolation of
two kinds of cross-coupling products 18a and 19a, in which
a marked propensity for the yield of 18a to exceed that of
19a in the presence of PPh3 was observed (Table 5). To
our surprise, 19b was exclusively obtained in the reaction
of 2b with 17, and no additional products by way of the cas-
cade reaction were isolated. The reaction of 2c was also
sluggish, giving rise to lower yield of 18b together with
the recovery of unreacted 17.
1
1
1
1
1
3
3
2b 3a
2b 3c
2b 3b Pd(OAc)2
2b 3d Pd(OAc)2
2c
2c
10 (5b)
10 (5a)
15 (5b)
20 (5a)
—
3a
3c
Pd(OAc)2
Pd(OAc)2
a
The reaction was carried out using indole (1) (2 equiv), 3 (1 equiv), and
palladium complex (5 mol %) in THF under argon atmosphere at 60 ꢀC.
Yields based on 3.
Indole (1a) (1 equiv) and 3a (2 equiv) and yield based on 1a.
Indole (1a) (1 equiv) and 3a (1 equiv).
b
c
d
The conformational space of 14 is restricted by the presence
of carbonyl sp2 carbon involved in the tether, which enforces
Table 2. Tandem cyclization-cross-coupling reaction of 2 with 6
O
N
Me
I
R
1) tert- or
O
O
6
a: R=Me
n-BuLi
b: R=TMS
+
[ 2 ]
1
N
N
Me
Me
2) BEt3
PdLn (5 mol%)
THF / Ar / reflux
N
Z
7
R
R
8
a: R=Me
b: R=TMS
a: Z=Me R=Me
b: Z=Me R=TMS
c: Z=OMe R=Me
d: Z=OMe R=TMS
e: Z=Boc R=Me
2
6
PdLn
Time (h)
Yield (%)a of 7
Yield (%)a of 8
2a
2a
2a
2a
2a
2a
2a
2b
2b
2c
2c
6a
6a
6a
6a
6a
6b
6b
6a
6b
6a
6b
Pd(OAc)2
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
2
74 (7a)
55 (7a)
71 (7a)
70 (7a)
55 (7a)
73 (7b)
63 (7b)
43 (7c)
45 (7d)
23 (7e)
—
—
Pd(OAc)2+2PPh3
Pd2(dba)3CHCl3
PdCl2(CH3CN)2
PdCl2(CH3CN)2+2PPh3
Pd(OAc)2
PdCl2(CH3CN)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
18 (8a)
—
—
10 (8a)
—
5 (8b)
—
—
15 (8a)b
20 (8b)c
4
a
Yields based on 6.
Recovery of 6a (20%).
Recovery of 6b (30%) with unidentified products.
b
c

M. Ishikura et al. / Tetrahedron 62 (2006) 11580–11591
11583
Scheme 2.
Table 3. Tandem cyclization-cross-coupling reaction of 2 with 11
Me
N
Me
O
O
N
I
Me
11
1) tert-BuLi
[ 2a]
Me
+
1a
PdLn (5 mol%)
THF / Ar / reflux
O
2) BEt3
N
Me
N
Me
12
13
PdLn
Time (h)
Yield (%)a of 12
Yield (%)a of 13
Pd(OAc)2
0.5
0.5
0.5
0.5
26
—
29
24
4
—
5
2
b
b
Pd(OAc)2+2PPh3
Pd2(dba)3CHCl3
PdCl2(CH3CN)2
a
Yields based on 11.
Unidentified products.
b
Heck-type cyclization path. On the other hand, the lack of
conformational restriction in 17 and free rotation around
the C–N bond before the cyclization now made the direct
cross-coupling process more favorable. Stabilization through
the coordination of PPh3 seems to be enough to minimize
the transmetalation, so that the tandem cyclization-cross-
coupling process might proceed.
Upon treatment of 2 with 20 under the same conditions,
cross-coupling products 21 and 22 were similarly obtained,
where the yield of 21 was greater than that of 22 in the ab-
sence of PPh3 (Table 6).
These results demonstrate that indolylborate (2) successfully
serves as a transfer agent in the tandem cyclization-cross-
coupling reaction. As we have previously reported the suc-
cessful use of 2 for indolyl ketone synthesis by the way of
the palladium-catalyzed carbonylative-cross-coupling reac-
tion,16 we then wondered if this protocol could be expanded
to the cascade of cyclization–carbonylation-cross-coupling
process.
When 2a was simply treated with 14 in the presence of
PdCl2(PPh3)2 (5 mol %) in THF at 60 ꢀC under carbon mon-
oxide (10 atm), a 65% yield of ketone (23a) was obtained to-
gether with a small amount of 15a (Table 7). The reaction
using 2c was less effective, producing ketone (23b) in
51% yield accompanied by the recovery of unreacted 14.
Under the same conditions, the reaction of 2a with 17 also
proceeded to afford ketone (24) along with 18a and 19a. Un-
fortunately, on the treatment of 2a with 20, ketone (25) was
obtained but in low a yield allowing the isolation of ketone
(26) along with 22 (Scheme 4).
In summary, we have disclosed that 2, which is a tetravalent
organoboron compound, could offer practical advantages as
a transfer agent in the palladium-catalyzed tandem cycliza-
tion-cross-coupling reaction. Moreover, it was also shown
that 2 is effective for tandem cyclization–carbonylation-
cross-coupling reactions, providing indolyl ketones.
Scheme 3.

11584
M. Ishikura et al. / Tetrahedron 62 (2006) 11580–11591
Table 4. Tandem cyclization-cross-coupling reaction of 2 with 14
Me
N
O
1) tert- or
n-BuLi
2) BEt3
Me
I
Me
N
Me
14
N
[ 2 ]
1
+
O
PdLn (5 mol%)
THF / Ar / reflux
O
N
Z
Me
16
Me
Me
15
a: Z=Me
b: Z=OMe
c: Z=Boc
2
PdLn
Time (h)
Yield (%)a of 15
Yield (%)a of 16
2a
2a
2b
2b
2c
2c
Pd(OAc)2
Pd(OAc)2+2PPh3
Pd(OAc)2
PdCl2(CH3CN)2
Pd(OAc)2
Pd(OAc)2+2PPh3
0.5
0.5
0.5
0.5
6
75 (15a)
53 (15a)
74 (15b)
70 (15b)
12 (15c)
—
—
16
—
—
30
45
6
a
Yields based on 14.
Table 5. Tandem cyclization-cross-coupling reaction of 2 with 17
Ac
N
1) tert- or
Ac
Me
I
Ac
N
N
17
n-BuLi
[ 2 ]
+
1
PdLn (5 mol%)
THF / Ar / reflux
Me
2) BEt3
N
Z
N
Z
Me
18
19
a: Z=Me
b: Z=OMe
a: Z=Me
b: Z=Boc
2
PdLn
Time (h)
Yield (%)a of 18
Yield (%)a of 19
2a
2a
2a
2a
2b
2b
2c
2c
Pd(OAc)2
0.5
0.5
0.5
0.5
0.5
0.5
6
13 (18a)
65 (18a)
12 (18a)
10 (18a)
—
—
31 (18b)
51 (18b)
60 (19a)
10 (19a)
72 (19a)
75 (19a)
80 (19b)
70 (19b)
Pd(OAc)2+2PPh3
Pd2(dba)3CHCl3
PdCl2(CH3CN)2
Pd(OAc)2
Pd(OAc)2+2PPh3
Pd(OAc)2
Pd(OAc)2+2PPh3
b
—
—
c
6
a
Yields based on 17.
Recovery of 17 (20%).
Recovery of 17 (10%).
b
c
Table 6. Tandem cyclization-cross-coupling reaction of 2 with 20
O
Me
N
Me
Me
N
Me
O
O
1) tert- or
n-BuLi
I
20
[ 2 ]
+
1
N
Me
PdLn (5 mol%)
THF / Ar / reflux
2) BEt3
N
Z
N
Z
Me
22
21
a: Z=Me
b: Z=OMe
c: Z=Boc
a: Z=Me
b: Z=OMe
2
PdLn
Pd(OAc)2
Pd(OAc)2+2PPh3
Pd(OAc)2
Pd(OAc)2+2PPh3
Pd(OAc)2
Pd(OAc)2+2PPh3
Time (h)
Yield (%)a of 21
Yield (%)a of 22
2a
2a
2b
2b
2c
2c
1
1
1
1
5
5
26 (21a)
68 (21a)
35 (21b)
63 (21b)
32 (21c)
57 (21c)
54 (22a)
5 (22a)
20 (22b)
5 (22b)
b
—
—
c
a
Yields based on 20.
Recovery of 20 (20%) and unidentified products.
Recovery of 20 (10%) and unidentified products.
b
c

M. Ishikura et al. / Tetrahedron 62 (2006) 11580–11591
11585
J¼7.5 Hz), 7.80 (d, 1H, J¼8.1 Hz). 13C NMR (CDCl3) d:
3.7, 38.9, 73.7, 80.6, 99.9, 127.7, 128.3, 128.4, 128.5,
128.9, 129.4, 130.1, 132.1, 135.3, 140.0, 144.2, 170.3. MS
m/z: 375 (M+). Anal. Calcd for C17H14INO: C, 54.42; H,
3.76; N, 3.73. Found: C, 54.30; H, 3.87; N, 3.68.
Table 7. Tandem cyclization–carbonylation-cross-coupling reaction of 2
with 14
1) tert- or
Me
N
14
n-BuLi
+
15a
1
[ 2 ]
2) BEt3
CO (10 atm)
PdLn (5 mol%)
THF
O
N
Z
Me
O
3.1.2. N-(2-Bromophenyl)-N-but-2-yn-1-ylbenzamide
(3b). Treatment of 3f (2 g, 6.3 mmol) with iodomethane
(0.5 mL, 8 mmol) according to the literature10 produced
3b in 71% yield after separation by MPLC with hexane–
AcOEt (10:1) as an eluent.
23
a: Z=Me
b: Z=Boc
2
PdLn
Yield (%)a of 23
Yield (%)a of 15
2a
2a
2c
2c
Pd(OAc)2
36 (23a)
65 (23a)
22 (23b)
51 (23b)
31 (15a)
5 (15a)
—
1
Viscous oil. IR (CHCl3): 1646 cmꢁ1. H NMR (CDCl3) d:
PdCl2(Ph3P)2
Pd(OAc)2
PdCl2(Ph3P)2
b
1.76 (s, 3H), 4.09 (qd, 1H, J¼2.0, 17.2 Hz), 5.09 (d, 1H,
J¼17.2 Hz), 7.05–7.25 (m, 6H), 7.36 (d, 2H, J¼7.5 Hz),
7.54 (d, 1H, J¼8.1 Hz). 13C NMR (CDCl3) d: 3.69, 38.5,
73.8, 80.5, 123.2, 127.8, 128.1, 128.3, 129.4, 130.1, 132.5,
133.6, 135.3, 141.3, 170.5. HRMS m/z Calcd for
C17H14BrNO: 327.0259 and 329.0238. Found: 327.0264
and 329.0225.
c
—
a
Yields based on 14.
Recovery of 14 (30%).
Recovery of 14 (10%).
b
c
3. Experimental
3.1. General
3.1.3. N-(2-Iodophenyl)-N-[3-(trimethylsilyl)prop-2-yn-
1-yl]benzamide (3c). Treatment of 3e (2 g, 5.5 mmol)
with chlorotrimethylsilane (1 mL, 8 mmol) according to
the literature10 produced 3c in 68% yield after separation
by MPLC with hexane–AcOEt (10:1) as an eluent.
Melting points were recorded on a Yamato MP21 apparatus
and are uncorrected. MS and high-resolution MS spectra
were recorded on a Micromass AutoSpec 3100 mass spec-
trometer. IR spectra were measured on a Hitachi Model
270-30 spectrometer. The NMR experiments were per-
formed with a JEOL JNM-LA300 or JNM-ECA500 spec-
trometer, and chemical shifts are expressed in parts per
million (d) with TMS as an internal reference. Medium pres-
sure liquid chromatography (MPLC) was performed on
silica gel (Silica Gel 60N, Kanto Chemical Co., Ltd.).
Viscous oil. IR (CHCl3): 2340, 1660 cmꢁ1 1H NMR
.
(CDCl3) d: 0.09 (s, 9H), 4.16 (d, 1H, J¼17.2 Hz), 5.20 (d,
1H, J¼17.2 Hz), 6.91–6.94 (m, 1H), 7.10–7.28 (m, 5H),
7.38 (d, 2H, J¼7.5 Hz), 7.78 (d, 1H, J¼8.0 Hz). 13C NMR
(CDCl3) d: 0.1, 39.0, 90.2, 100.2, 127.2, 128.5, 128.7,
129.6, 130.1, 132.5, 135.3, 139.9, 143.9, 170.1. HRMS m/z
Calcd for C19H20INOSi: 433.0358. Found: 433.0348.
3.1.1. N-(2-Iodophenyl)-N-but-2-yn-1-ylbenzamide (3a).
Treatment of 3e (2 g, 5.5 mmol) with iodomethane (0.5 mL,
8 mmol) according to the literature10 produced 3a in 70%
yield after separation by MPLC with hexane–AcOEt (10:1)
as an eluent.
3.1.4. N-(2-Bromophenyl)-N-[3-(trimethylsilyl)prop-2-
yn-1-yl]benzamide (3d). Treatment of 3f (2 g, 6.3 mmol)
with chlorotrimethylsilane (1 mL, 8 mmol) according to
the literature10 produced 3d in 69% yield after separation
by MPLC with hexane–AcOEt (10:1) as an eluent.
Colorless crystals. Mp 73–74 ꢀC (hexane–AcOEt). IR
1
(CHCl3): 1642 cmꢁ1. H NMR (CDCl3) d: 1.76 (s, 3H),
Colorless crystals. Mp 82–83 ꢀC (hexane–AcOEt). IR
4.07 (qd, 1H, J¼2.0, 17.2 Hz), 5.09 (d, 1H, J¼17.2 Hz),
(CHCl3): 2320, 1646 cmꢁ1 1H NMR (CDCl3) d: 0.08
.
6.90–6.93 (m, 1H), 7.12–7.25 (m, 5H), 7.38 (d, 2H,
(s, 9H), 4.19 (d, 1H, J¼17.2 Hz), 5.20 (d, 1H, J¼17.2 Hz),
Scheme 4.

11586
M. Ishikura et al. / Tetrahedron 62 (2006) 11580–11591
7.04–7.25 (m, 6H), 7.34–7.40 (m, 2H), 7.52 (d, 1H,
J¼8.0 Hz). 13C NMR (CDCl3) d: ꢁ0.2, 38.5, 90.1, 100.2,
123.5, 127.7, 127.9, 128.2, 129.5, 130.1, 132.8, 133.5,
135.3, 140.7, 170.3. MS m/z: 385, 387 (M+). Anal. Calcd
for C19H20BrNOSi: C, 59.07; H, 5.22; N, 3.63. Found: C,
58.89; H, 5.28; N, 3.49.
Colorless crystals. Mp 79–80 ꢀC (hexane–AcOEt). IR
1
(CHCl3): 1648, 1622 cmꢁ1. H NMR (CDCl3) d: 1.81 (s,
3H), 3.23 (s, 3H), 4.97 (s, 1H), 5.04 (s, 1H), 7.00 (dt, 1H, J¼
1.2, 8.0 Hz), 7.16 (d, 1H, J¼7.5 Hz), 7.34 (t, 1H, J¼7.5 Hz),
7.86 (dd, 1H, J¼1.2, 8.0 Hz). 13C NMR (CDCl3) d: 20.6,
36.9, 99.1, 119.1, 129.3, 129.4, 129.5, 140.3, 147.0, 171.8.
MS m/z: 301 (M+). Anal. Calcd for C11H12INO: C, 43.87;
H, 4.02; N, 4.65. Found: C, 43.77; H, 4.02; N, 4.56.
3.1.5. N-But-2-yn-1-yl-2-iodo-N-methylbenzamide (6a).
Treatment of 2-iodo-N-methyl-N-prop-2-yn-1-ylbenzamide
(1.8 g, 6.3 mmol) with iodomethane (0.5 mL, 8 mmol) ac-
cording to the literature10 produced 6a in 65% yield after
separation by MPLC with hexane–AcOEt (3:1) as an eluent.
3.1.9. N-(2-Iodophenyl)-N-(2-methylprop-2-en-1-yl)-
acetamide (17). Treatment of N-(2-iodophenyl)acetamide,
readily available from 2-iodoaniline and acetyl chloride,
with methallyl chloride according to a common procedure
using sodium hydride gave 17 in 80% yield.
1
Viscous oil. IR (CHCl3): 1632 cmꢁ1. H NMR (CDCl3) d:
1.79 and 1.83 (two s, 3H), 4.07 (dd, 1H, J¼2.3, 16.7 Hz),
5.09 (d, 1H, J¼16.7 Hz), 6.90–6.93 (m, 1H), 7.15–7.22
(m, 5H), 7.38 (d, 2H, J¼7.5 Hz), 7.80 (d, 1H, J¼7.5 Hz).
13C NMR (CDCl3) d: 3.7, 32.1, 35.5, 35.9, 36.4, 41.1,
72.6, 73.1, 80.3, 81.3, 92.3, 92.6, 127.1, 128.5, 130.3, 139.3,
142.1, 142.3, 170.3. HRMS m/z Calcd for C12H12INO:
312.9964. Found: 312.9953.
Colorless crystals. Mp 68–69 ꢀC (hexane–AcOEt). IR
1
(CHCl3): 1655 cmꢁ1. H NMR (CDCl3) d: 1.79 (s, 3H),
1.80 (s, 3H), 3.32 (d, 1H, J¼14.9 Hz), 4.64 (s, 1H), 4.82 (s,
1H), 4.97 (d, 1H, J¼14.9 Hz), 7.05 (t, 1H, J¼7.5 Hz), 7.16
(dd, 1H, J¼1.5, 7.5 Hz), 7.36 (t, 1H, J¼7.5 Hz), 7.93 (d,
1H, J¼8.0 Hz). 13C NMR (CDCl3) d: 20.7, 22.9, 54.0,
100.2, 114.2, 129.4, 129.8, 130.3, 140.4, 140.5, 144.8,
170.2. MS m/z: 315 (M+). Anal. Calcd for C12H14INO: C,
45.73; H, 4.48; N, 4.44. Found: C, 45.88; H, 4.50; N, 4.31.
3.1.6. 2-Iodo-N-methyl-N-[3-(trimethylsilyl)prop-2-yn-1-
yl]benzamide (6b). Treatment of 2-iodo-N-methyl-N-prop-
2-yn-1-ylbenzamide (1.8 g, 6.3 mmol) with chlorotri-
methylsilane (1 mL, 8 mmol) according to the literature10
produced 6b in 60% yield after separation by MPLC with
hexane–AcOEt (3:1) as an eluent.
3.1.10. 2-Iodo-N-methyl-N-(2-methylprop-2-en-1-yl)benz-
amide (20). Treatment of 2-iodo-N-methylbenzamide,
readily available from 2-iodobenzoyl chloride and methyl-
amine, with methallyl chloride according to a common pro-
cedure using sodium hydride gave 20 in 78% yield.
Colorless crystals. Mp 53–54 ꢀC (hexane–AcOEt). IR
1
(CHCl3): 1634 cmꢁ1. H NMR (CDCl3) d: 0.15 and 0.17
(two s, 9H), 2.88 and 3.18 (two s, 3H), 3.86 (d, 1H, J¼
7.5 Hz), 4.43 (s, 1H), 7.05–7.09 (m, 1H), 7.22 (dd, 1H,
J¼1.5, 8.0 Hz), 7.27 (dd, 1H, J¼1.5, 8.0 Hz), 7.37–7.41
(m, 1H), 7.82 (dd, 1H, J¼2.9, 8.1 Hz). 13C NMR (CDCl3)
d: ꢁ0.1, 32.2, 35.4, 36.9, 41.7, 89.6, 90.5, 92.3, 92.6, 99.2,
99.5, 127.1, 127.3, 128.4, 128.5, 130.3, 130.4, 139.3,
142.1, 170.3. MS m/z: 371 (M+). MS m/z: 371 (M+). Anal.
Calcd for C14H18INOSi: C, 45.29; H, 4.89; N, 3.77. Found:
C, 45.30; H, 4.74; N, 3.76.
1
Viscous oil. IR (CHCl3): 1638 cmꢁ1. H NMR (CDCl3) d:
1.57 and 1.82 (two s, 3H), 2.73 and 3.04 (two s, 3H), 3.58
and 3.68 (two d, 1H, J¼14.9 Hz), 4.12 (s, 1H), 4.85 and
4.90 (two s, 1H), 4.95 (s, 1H), 7.00–7.08 (m, 1H), 7.15–
7.22 (m, 1H), 7.30–7.40 (m, 1H), 7.73–7.83 (m, 1H). 13C
NMR (CDCl3) d: 20.0, 20.5, 32.3, 35.6, 52.4, 56.8, 92.2,
92.9, 113.3, 113.4, 127.1, 127.3, 128.2, 128.4, 130.1,
130.2, 139.1, 139.3, 140.0, 140.2, 142.3, 143.0, 170.7,
171.2. HRMS m/z Calcd for C12H14INO: 315.0120. Found:
315.0133.
3.1.7. (2E)-N-(2-Iodophenyl)-N-methylbut-2-enamide
(11). Treatment of (2E)-N-(2-iodophenyl)but-2-enamide,
readily available from 2-iodoaniline and trans-crotonyl chlo-
ride in 80% yield, with iodomethane according to a common
procedure using sodium hydride gave 11 in 85% yield.
3.2. General procedure for the tandem cross-coupling
reaction of indolylborate (2) with 3, 6, 9,11 11, 14, 17,
and 20
Colorless crystals. Mp 107–108 ꢀC (hexane–AcOEt). IR
To a THF solution of indolylborate (2) generated from indole
(1) (2 mmol) in situ under an argon atmosphere, 3, 6, 9, 11,
14, 17, or 20 (1 mmol) and the palladium complex
(0.05 mmol) were added at room temperature, and then,
the whole was heated at 60 ꢀC for the time indicated in
Table 1. The mixture was ice-cooled, and 10% NaOH
(10 mL) and 30% H2O2 (2 mL) were added. After stirring
for 10 min, the mixture was diluted with AcOEt (100 mL),
washed with brine, and dried over MgSO4. The solvent was
removed, and the residue was separated by MPLC with
hexane–AcOEt.
1
(CHCl3): 1664, 1620 cmꢁ1. H NMR (CDCl3) d: 1.73 (dd,
3H, J¼1.8, 6.9 Hz), 3.21 (s, 3H), 5.48 (dd, 1H, J¼1.8,
15.5 Hz), 6.94 (dq, 1H, J¼6.9, 15.5 Hz), 7.08 (dt, 1H,
J¼1.8, 8.0 Hz), 7.24 (dd, 1H, J¼1.8, 8.0 Hz), 7.41 (dt, 1H,
J¼1.8, 8.0 Hz), 7.93 (dd, 1H, J¼1.8, 8.0 Hz). 13C NMR
(CDCl3) d: 18.1, 36.1, 99.8, 122.2, 129.5, 129.7, 129.9,
140.2, 142.0, 145.9, 165.9. MS m/z: 301 (M+). Anal. Calcd
for C11H12INO: C, 43.87; H, 4.02; N, 4.65. Found: C,
43.83; H, 4.05; N, 4.54.
3.1.8. N,2-Dimethyl-N-(2-methylphenyl)acrylamide (14).
Treatment of N-(2-iodophenyl)-2-methylacrylamide, readily
available from 2-iodoaniline and methacryl chloride in 85%
yield, with iodomethane according to a common procedure
using sodium hydride gave 14 in 90% yield.
3.2.1. 2-[(1E)-1-(1-Benzoyl-1,2-dihydro-3H-indol-3-yl-
idene)ethyl]-1-methyl-1H-indole (4a). Colorless crystals.
Mp 180–181 ꢀC (hexane–AcOEt). IR (CHCl3): 1642 cmꢁ1
.
1H NMR (CDCl3) d: 2.04 (br s, 3H), 3.53 (s, 3H), 4.82

M. Ishikura et al. / Tetrahedron 62 (2006) 11580–11591
11587
(br s, 2H), 6.14 (d, 1H, J¼7.8 Hz), 6.39 (s, 1H), 6.60–6.75 (m,
1H), 6.90–7.15 (m, 1H), 7.16 (t, 1H, J¼7.8 Hz), 7.25 (t,
1H, J¼7.8 Hz), 7.36 (d, 1H, J¼7.8 Hz), 7.48–7.56 (m, 4H),
7.57–7.62 (m, 2H), 7.64 (d, 1H, J¼7.8 Hz). 13C NMR
(CDCl3) d: 23.0, 29.6, 55.1, 99.1, 109.5, 118.4, 119.6,
120.5, 121.3, 122.8, 124.1, 126.7, 128.1, 128.5, 128.6,
129.0, 130.3, 133.4, 136.7, 136.8, 140.3, 168.4. MS m/z:
378 (M+). Anal. Calcd for C26H22N2O: C, 82.51; H, 5.86;
N, 7.40. Found: C, 82.31; H, 5.99; N, 7.25.
3.2.6. tert-Butyl 2-[(1E)-1-(1-Benzoyl-1,2-dihydro-3H-
indol-3-ylidene)ethyl]-1H-indole-1-carboxylate (4f). Color-
less crystals. Mp 177–178 ꢀC (AcOEt–hexane). IR (CHCl3):
1
1724, 1640 cmꢁ1. H NMR (CDCl3) d: 1.49 (s, 9H), 1.98
(br s, 3H), 4.73 (br s, 2H), 6.45 (s, 1H), 6.57 (d, 1H,
J¼8.0 Hz), 6.69 (br s, 1H), 7.26 (t, 1H, J¼7.5 Hz), 7.34 (t,
1H, J¼7.5 Hz), 7.48–7.60 (m, 7H), 8.24 (d, 1H, J¼8.5 Hz).
13C NMR (CDCl3) d: 22.9, 28.1, 50.5, 83.6, 107.9, 115.9,
120.7, 123.0, 123.1, 124.2, 124.3, 127.0, 128.7, 128.9,
129.6, 130.5, 136.4, 137.1, 139.5, 149.8, 168.8. MS m/z:
464 (M+). Anal. Calcd for C30H28N2O3: C, 77.56; H, 6.08;
N, 6.03. Found: C, 77.48; H, 6.20; N, 5.87.
3.2.2. 2-[(Z)-(1-Benzoyl-1,2-dihydro-3H-indol-3-yl-
idene)(trimethylsilyl)methyl]-1-methyl-1H-indole (4b).
Colorless crystals. Mp 190–191 ꢀC (hexane–AcOEt). IR
1
(CHCl3): 1642, 1600 cmꢁ1. H NMR (CDCl3) d: 0.06 (s,
3.2.7. (3E)-1-Benzoyl-3-(1-methylpropylidene)indoline
1
9H), 3.49 (s, 3H), 4.90 (br s, 2H), 5.91 (d, 1H, J¼8.3 Hz),
6.15 (s, 1H), 6.60–6.70 (m, 1H), 7.00–7.18 (m, 1H), 7.14
(t, 1H, J¼7.8 Hz), 7.21 (t, 1H, J¼7.8 Hz), 7.34 (d, 1H,
J¼8.3 Hz), 7.42–7.56 (m, 4H), 7.56–7.61 (m, 3H). 13C
NMR (CDCl3) d: ꢁ1.1, 29.6, 56.4, 97.8, 109.5, 119.4,
120.0, 120.6, 124.4, 126.8, 128.6, 128.7, 129.9, 130.0,
130.6, 136.7, 136.9, 140.0, 147.0, 168.3. MS m/z: 436
(M+). Anal. Calcd for C28H28N2OSi: C, 74.02; H, 6.46; N,
6.42. Found: C, 76.87; H, 6.46; N, 6.49.
(5a). Viscous oil. IR (neat): 1666, 1580 cmꢁ1. H NMR
(CDCl3) d: 1.13 (t, 3H, J¼7.4 Hz), 1.71 (br s, 3H), 2.46 (q,
2H, J¼7.4 Hz), 4.56 (br s, 2H), 7.04 (br s, 1H), 7.43–7.58
(m, 8H). 13C NMR (CDCl3) d: 11.7, 21.3, 27.5, 55.7,
117.3, 123.5, 123.9, 124.1, 125.1, 126.9, 127.4, 128.7,
137.1, 145.5, 168.5. HRMS m/z Calcd for C19H19NO:
277.1467. Found: 277.1470.
3.2.8. (3Z)-1-Benzoyl-3-[1-(trimethylsilyl)propylidene]-
indoline (5b). Viscous oil. IR (CHCl3): 1636, 1598 cmꢁ1
.
3.2.3. 2-[(E)-(1-Benzoyl-1,2-dihydro-3H-indol-3-yl-
idene)methyl]-1-methyl-1H-indole (4c). Colorless crystals.
Mp 171–172 ꢀC (hexane–AcOEt). IR (CHCl3): 1642,
1H NMR (acetone-d6) d: 0.05 (s, 9H), 1.09 (t, 3H,
J¼7.5 Hz), 2.55 (q, 2H, J¼7.5 Hz), 4.67 (s, 2H), 7.08 (t,
1H, J¼8.0 Hz), 7.38 (br s, 1H), 7.45–7.54 (m, 4H), 7.58–
7.64 (m, 2H), 7.68 (d, 1H, J¼7.5 Hz). 13C NMR (acetone-
d6) d: ꢁ1.1, 13.1, 24.2, 57.1, 117.3, 123.9, 125.4, 126.8,
128.5, 128.8, 130.1, 130.6, 135.4, 137.6, 140.2, 146.1,
167.8. HRMS m/z Calcd for C21H25NOSi: 335.1705. Found:
335.1701.
1
1590 cmꢁ1. H NMR (CDCl3) d: 3.65 (s, 3H), 4.86 (br s,
2H), 6.40 (br s, 1H), 6.65 (s, 1H), 6.80–6.90 (m, 1H), 7.14
(dt, 1H, J¼1.2, 7.8 Hz), 7.20–7.25 (m, 1H), 7.23 (dt, 1H,
J¼1.0, 7.8 Hz), 7.33 (d, 1H, J¼7.8 Hz), 7.46–7.56 (m,
5H), 7.57–7.62 (m, 2H), 7.62 (d, 1H, J¼7.8 Hz). 13C NMR
(CDCl3) d: 30.3, 57.2, 101.7, 109.5, 109.7, 119.9, 120.6,
121.8, 123.9, 124.1, 127.1, 128.0, 128.6, 128.9, 130.5,
130.6, 135.4, 136.9, 137.4, 137.7, 137.8, 168.6. MS m/z:
364 (M+). Anal. Calcd for C25H20N2O: C, 82.39; H, 5.53;
N, 7.69. Found: C, 82.45; H, 5.72; N, 7.69.
3.2.9. (4E)-2-Methyl-4-[1-(1-methyl-1H-indol-2-yl)ethyl-
idene]-3,4-dihydroisoquinolin-1(2H)-one (7a). Colorless
crystals. Mp 181–182 ꢀC (hexane–AcOEt). IR (CHCl3):
1638 cmꢁ1. 1H NMR (CDCl3) d: 2.31 (s, 3H), 3.05 (s, 3H),
3.27 (s, 3H), 4.36 (d, 2H, J¼5.2 Hz), 6.38 (d, 1H,
J¼7.5 Hz), 6.51 (s, 1H), 6.95 (dt, 1H, J¼1.2, 7.5 Hz),
7.11–7.14 (m, 2H), 7.17–7.22 (m, 2H), 7.60 (d, 1H,
J¼8.0 Hz), 8.07 (dd, 1H, J¼1.2, 8.0 Hz). 13C NMR
(CDCl3) d: 22.6, 30.0, 35.0, 51.4, 101.6, 109.7, 119.9,
120.4, 121.8, 125.8, 126.3, 127.6, 127.7, 127.8, 128.8,
131.1, 136.4, 137.2, 140.7, 164.1. MS m/z: 316 (M+). Anal.
Calcd for C21H20N2O: C, 79.71; H, 6.37; N, 8.85. Found:
C, 79.51; H, 6.61; N, 8.82.
3.2.4. 2-[(1E)-1-(1-Benzoyl-1,2-dihydro-3H-indol-3-yl-
idene)ethyl]-1-methoxy-1H-indole (4d). Colorless crystals.
Mp 124–125 ꢀC (hexane–AcOEt). IR (CHCl3): 1640 cmꢁ1
.
1H NMR (CDCl3) d: 2.16 (br s, 3H), 3.89 (s, 3H), 4.81
(br s, 2H), 6.30 (s, 1H), 6.73 (br s, 1H), 6.83 (d, 1H,
J¼8.0 Hz), 7.05–7.15 (m, 1H), 7.15 (t, 1H, J¼7.5 Hz), 7.27
(t, 1H, J¼7.5 Hz), 7.46 (d, 1H, J¼8.0 Hz), 7.49–7.55 (m,
4H), 7.57–7.69 (m, 3H). 13C NMR (CDCl3) d: 22.4, 55.4,
65.8, 97.3, 108.6, 117.2, 120.4, 121.1, 122.4, 123.5, 124.0,
127.0, 128.8, 129.2, 129.3, 129.5, 130.6, 132.4, 133.5,
136.4, 136.9, 168.7. MS m/z: 394 (M+). Anal. Calcd for
C26H22N2O2: C, 79.16; H, 5.62; N, 7.10. Found: C, 79.10;
H, 5.78; N, 6.97.
3.2.10. (4Z)-2-Methyl-4-[(1-methyl-1H-indol-2-yl)(tri-
methylsilyl)methylene]-3,4-dihydroisoquinolin-1(2H)-
one (7b). Viscousoil.IR(neat):1646 cmꢁ1. 1HNMR(CDCl3)
d: 0.01 (s, 9H), 3.00 (s, 3H), 3.59 (s, 3H), 3.65 (d, 1H,
J¼13.5 Hz), 3.98 (d, 1H, J¼13.5 Hz), 6.18 (s, 1H), 7.14 (t,
1H, J¼7.5 Hz), 7.22 (t, 1H, J¼7.5 Hz), 7.33 (d, 1H, J¼
8.0 Hz), 7.51–7.53 (m, 2H), 7.59–7.63 (m, 2H), 8.10–8.12
(m, 1H). 13C NMR (CDCl3) d: 0.44, 30.1, 34.9, 54.0, 99.8,
109.4, 119.8, 120.2, 121.0, 126.9, 128.1, 128.5, 129.7, 129.9,
130.7, 136.0, 137.1, 137.2, 140.6, 146.6, 164.5. HRMS m/z
Calcd for C23H26N2OSi: 374.1814. Found: 374.1805.
3.2.5. 2-[(Z)-(1-Benzoyl-1,2-dihydro-3H-indol-3-yl-
idene)(trimethylsilyl)methyl]-1-methoxy-1H-indole (4e).
Viscous oil. IR (neat): 1646, 1600 cmꢁ1
.
1H NMR
(CDCl3) d: 0.06 (s, 9H), 3.90 (s, 3H), 4.84 (br s, 2H), 6.02
(s, 1H), 6.60 (d, 1H, J¼7.5 Hz), 6.67–6.74 (m, 1H), 7.08–
7.18 (m, 1H), 7.13 (t, 1H, J¼7.5 Hz), 7.22 (t, 1H,
J¼7.5 Hz), 7.45 (d, 1H, J¼8.0 Hz), 7.35–7.65 (m, 7H).
13C NMR (CDCl3) d: ꢁ0.12, 56.8, 65.8, 94.7, 108.3,
120.0, 120.7, 121.4, 124.1, 124.3, 124.9, 127.0, 128.8,
130.7, 132.2, 136.8, 137.0, 146.6, 168.4. HRMS m/z Calcd
for C28H28N2O2: 452.1920. Found: 452.1916.
3.2.11. (4E)-4-[1-(1-Methoxy-1H-indol-2-yl)ethylidene]-
2-methyl-3,4-dihydroisoquinolin-1(2H)-one (7c). Color-
less crystals. Mp 170–171 ꢀC (hexane–AcOEt). IR
1
(CHCl3): 1640 cmꢁ1. H NMR (CDCl3) d: 2.32 (s, 3H),

11588
M. Ishikura et al. / Tetrahedron 62 (2006) 11580–11591
3.26 (s, 3H), 3.78 (s, 3H), 4.33 (s, 2H), 6.23 (s, 1H), 6.72 (d,
1H, J¼8.0 Hz), 7.01 (t, 1H, J¼7.5 Hz), 7.10 (t, 1H,
J¼7.5 Hz), 7.19–7.24 (m, 2H), 7.31 (d, 1H, J¼8.0 Hz),
7.51 (d, 1H, J¼8.0 Hz), 8.07 (d, 1H, J¼8.0 Hz). 13C NMR
(CDCl3) d: 21.4, 35.2, 51.5, 65.2, 99.0, 108.6, 120.4,
121.0, 122.6, 123.4, 123.8, 126.4, 127.7, 127.9, 128.8,
128.9, 130.8, 132.7, 136.8, 136.9, 164.5. MS m/z: 332
(M+). Anal. Calcd for C21H20N2O2$1/10H2O: C, 75.47; H,
6.09; N, 8.38. Found: C, 75.51; H, 6.19; N, 8.28.
d: 1.10–1.35 (m, 6H), 2.26 (s, 3H), 3.00 (s, 3H), 3.15–3.45
(m, 2H), 4.10–4.30 (m, 4H), 6.39 (s, 1H), 6.42 (d, 1H,
J¼8.0 Hz), 6.64 (t, 1H, J¼7.5 Hz), 6.97 (dt, 1H, J¼1.0,
7.3 Hz), 7.05–7.16 (m, 4H), 7.57 (d, 1H, J¼7.5 Hz). 13C
NMR (CDCl3) d: 14.0, 22.8, 29.8, 34.7, 35.6, 54.8, 61.5,
100.4, 109.4, 119.4, 120.1, 121.0, 124.5, 125.9, 126.8,
127.7, 128.0, 128.1, 131.7, 134.3, 135.7, 136.9, 142.8,
170.9. HRMS m/z Calcd for C27H29NO4: 431.2097. Found:
431.2112.
3.2.12. (4Z)-4-[(1-Methoxy-1H-indol-2-yl)(trimethyl-
silyl)methylene]-2-methyl-3,4-dihydro-isoquinolin-1(2H)-
3.2.17. Diethyl (4E)-4-[(1-methyl-1H-indol-2-yl)(tri-
methylsilyl)methylene]-3,4-dihydronaphthalene-2,2(1H)-
dicarboxylate (10b). Viscous oil. IR (neat): 1732 cmꢁ1. 1H
NMR (CDCl3) d: 0.18 (s, 9H), 1.18 (t, 3H, J¼7.3 Hz), 1.24
(t, 3H, J¼7.3 Hz), 3.22 (s, 3H), 3.26 (s, 2H), 3.34 (d, 1H,
J¼15.0 Hz), 3.49 (d, 1H, J¼15.0 Hz), 3.91–4.09 (m, 4H),
6.10 (s, 1H), 6.60–6.75 (m, 2H), 6.97 (dt, 1H, J¼2.0,
7.5 Hz), 7.04–7.10 (m, 1H), 7.10 (dt, 1H, J¼1.0, 7.5 Hz),
7.14 (d, 1H, J¼7.5 Hz), 7.51 (d, 1H, J¼7.5 Hz). 13C NMR
(CDCl3) d: 0.49, 14.0, 29.5, 34.0, 37.7, 54.6, 61.6, 99.5,
108.9, 119.1, 119.8, 120.0, 126.4, 127.6, 128.1, 128.4, 131.8,
134.9, 136.0, 136.7, 141.7, 150.0, 170.0, 171.0. HRMS m/z
Calcd for C27H29NO4: 489.2336. Found: 489.2342.
1
one (7d). Viscous oil. IR (CHCl3): 1640 cmꢁ1. H NMR
(CDCl3) d: 0.00 (s, 9H), 3.04 (s, 3H), 3.98 (s, 3H), 3.95–
4.01 (m, 1H), 4.09–4.15 (m, 1H), 6.05 (s, 1H), 7.13 (t, 1H,
J¼7.5 Hz), 7.23 (t, 1H, J¼7.5 Hz), 7.42 (d, 1H,
J¼8.0 Hz), 7.45–7.55 (m, 2H), 7.56 (d, 1H, J¼8.0 Hz),
7.65–7.69 (m, 1H), 8.08–8.14 (m, 1H). 13C NMR (CDCl3)
d: 0.98, 34.6, 54.0, 65.3, 96.9, 108.2, 120.4, 120.5, 121.8,
124.1, 126.7, 128.1, 129.6, 129.9, 130.6, 132.4, 133.5,
137.3, 137.5, 146.5, 164.4. HRMS m/z Calcd for
C23H26N2O2Si: 390.1764. Found: 390.1752.
3.2.13. tert-Butyl 2-[(1E)-1-(2-methyl-1-oxo-2,3-di-
hydroisoquinolin-4(1H)-ylidene)ethyl]-1H-indole-1-car-
boxylate (7e). Colorless crystals. Mp 166–167 ꢀC (hexane–
AcOEt). IR (CHCl3): 1722, 1636 cmꢁ1. 1H NMR (CDCl3) d:
1.59 (s, 9H), 2.16 (s, 3H), 3.24 (s, 3H), 4.27 (d, 2H,
J¼4.0 Hz), 6.13 (s, 1H), 6.79 (d, 1H, J¼8.0 Hz), 7.03 (t,
1H, J¼7.5 Hz), 7.18 (t, 1H, J¼7.5 Hz), 7.20 (t, 1H,
J¼7.5 Hz), 7.29 (t, 1H, J¼7.5 Hz), 7.37 (d, 1H, J¼7.5 Hz),
8.05 (d, 1H, J¼7.5 Hz), 8.18 (d, 1H, J¼8.0 Hz). 13C NMR
(CDCl3) d: 21.6, 28.1, 35.1, 50.9, 84.1, 108.8, 115.5, 120.9,
123.0, 124.3, 125.8, 126.7, 127.5, 127.8, 128.6, 128.9,
129.4, 130.8, 136.5, 136.7, 140.5, 149.8, 164.4. MS m/z:
402 (M+). Anal. Calcd for C25H26N2O3$2/3H2O: C, 72.44;
H, 6.65; N, 6.76. Found: C, 72.65; H, 6.43; N, 6.72.
3.2.18. 3-Ethyl-1-methyl-1,3-dihydro-2H-indol-2-one
(12). Viscous oil. IR (CHCl3): 1696 cmꢁ1 1H NMR
.
(CDCl3) d: 0.88 (t, 3H, J¼7.5 Hz), 1.95–2.08 (m, 2H),
3.19 (s, 3H), 3.40 (t, 1H, J¼5.7 Hz), 6.82 (d, 1H,
J¼7.5 Hz), 7.05 (t, 1H, J¼7.5 Hz), 7.24–7.30 (m, 2H). 13C
NMR (CDCl3) d: 10.2, 23.8, 26.2, 46.7, 107.9, 122.3,
123.9, 127.9, 129.1, 140.2, 178.1. HRMS m/z Calcd for
C11H13NO: 175.0997. Found: 175.0981.
3.2.19. 3-[1-(2-Ethyl-1-methyl-1H-indol-3-yl)ethyl]-1-
methyl-1,3-dihydro-2H-indol-2-one (13). Colorless crys-
tals. Mp 198–199 ꢀC (hexane–AcOEt). IR (CHCl3):
1
1692 cmꢁ1. H NMR (CDCl3) d: 0.82 (t, 3H, J¼7.5 Hz),
1.86 (d, 3H, J¼6.9 Hz), 2.49 (q, 2H, J¼7.5 Hz), 3.16 (s,
3H), 3.17–3.22 (m, 1H), 3.66 (s, 3H), 3.88 (d, 1H, J¼
10.4 Hz), 6.03 (d, 1H, J¼6.9 Hz), 6.65 (t, 1H, J¼7.5 Hz),
6.69 (d, 1H, J¼7.5 Hz), 7.02 (t, 1H, J¼7.5 Hz), 7.12 (t, 1H,
J¼7.5 Hz), 7.16 (t, 1H, J¼7.5 Hz), 7.30 (d, 1H, J¼8.0 Hz),
7.61 (d, 1H, J¼8.0 Hz). 13C NMR (CDCl3) d: 14.1, 17.6,
19.2, 26.1, 29.6, 34.9, 50.0, 107.4, 109.0, 112.9, 118.9,
119.9, 120.6, 121.6, 125.6, 126.2, 127.6, 128.8, 137.1,
139.2, 144.2, 177.6. MS m/z: 332 (M+). Anal. Calcd for
C22H24N2O$1/5H2O: C, 78.63; H, 7.32; N, 8.34. Found: C,
78.64; H, 7.38; N, 8.33.
3.2.14. (4E)-2-Methyl-4-(1-methylpropylidene)-3,4-di-
hydroisoquinolin-1(2H)-one (8a). Colorless crystals. Mp
100–101 ꢀC (hexane–AcOEt). IR (CHCl3): 1632,
1
1600 cmꢁ1. H NMR (CDCl3) d: 1.17 (t, 3H, J¼7.5 Hz),
1.92 (s, 3H), 2.35 (q, 2H, J¼7.5 Hz), 3.17 (s, 3H), 4.09 (s,
2H), 7.26–7.38 (m, 2H), 7.43 (dt, 1H, J¼1.1, 7.5 Hz), 8.07
(dd, 1H, J¼1.5, 7.8 Hz). 13C NMR (CDCl3) d: 13.0, 18.5,
27.7, 34.9, 51.1, 122.7, 126.7, 127.0, 127.9, 129.5, 130.5,
137.3, 137.7, 164.6. MS m/z: 215 (M+). Anal. Calcd for
C14H17NO: C, 78.10; H, 7.96; N, 6.51. Found: C, 78.21; H,
8.08; N, 6.43.
3.2.20. 1,3-Dimethyl-3-[(1-methyl-1H-indol-2-yl)-
methyl]-1,3-dihydro-2H-indol-2-one (15a). Colorlesscrys-
tals. Mp 106–107 ꢀC (hexane–AcOEt). IR (CHCl3):
1708 cmꢁ1. 1H NMR (CDCl3) d: 1.50 (s, 3H), 3.09 (s, 3H),
3.14 (d, 1H, J¼14.6 Hz), 3.22 (d, 1H, J¼14.6 Hz), 3.36 (s,
3H), 6.02 (s, 1H), 6.72 (d, 1H, J¼7.5 Hz), 6.90 (d, 1H,
J¼7.3 Hz), 6.95 (t, 1H, J¼7.3 Hz), 7.02 (t, 1H, J¼7.3 Hz),
7.11 (t, 1H, J¼7.8 Hz), 7.16 (d, 1H, J¼8.0 Hz), 7.21 (t, 1H,
J¼7.8 Hz), 7.44 (d, 1H, J¼7.5 Hz). 13C NMR (CDCl3) d:
22.9, 26.0, 29.6, 33.9, 48.6, 101.7, 108.0, 109.1, 119.1,
119.9, 120.7, 122.2, 123.1, 127.5, 128.0, 132.8, 135.2,
136.9, 143.1, 179.9. MS m/z: 304 (M+). Anal. Calcd for
C20H20N2O: C, 78.92; H, 6.62; N, 9.20. Found: C, 78.89;
H, 6.73; N, 9.08.
3.2.15. (4Z)-2-Methyl-4-[1-(trimethylsilyl)propylidene]-
3,4-dihydroisoquinolin-1(2H)-one (8b). Viscous oil. IR
1
(neat): 1642, 1598 cmꢁ1. H NMR (acetone-d6) d: 0.06 (s,
9H), 0.84 (t, 3H, J¼7.5 Hz), 2.17 (q, 2H, J¼7.5 Hz), 2.86
(s, 3H), 3.90 (s, 2H), 7.11–7.30 (m, 3H), 7.73 (dd, 1H,
J¼1.5, 8.3 Hz). 13C NMR (CDCl3) d: 1.2, 15.9, 25.8, 34.3,
55.6, 127.5, 128.5, 128.6, 131.0, 131.3, 138.3, 138.5,
145.3, 164.5. HRMS m/z Calcd for C16H23NOSi:
273.1549. Found: 273.1547.
3.2.16. Diethyl (4Z)-4-[1-(1-methyl-1H-indol-2-yl)ethyl-
idene]-3,4-dihydronaphthalene-2,2(1H)-dicarboxylate
(10a). Viscous oil. IR (neat): 1732 cmꢁ1. 1H NMR (CDCl3)

M. Ishikura et al. / Tetrahedron 62 (2006) 11580–11591
11589
3.2.21. 3-[(1-Methoxy-1H-indol-2-yl)methyl]-1,3-
dimethyl-1,3-dihydro-2H-indol-2-one (15b). Colorless
crystals. Mp 121–122 ꢀC (hexane–AcOEt). IR (CHCl3):
128.0, 129.3, 130.5, 132.8, 136.2, 137.9, 140.9, 141.9,
170.5. MS m/z: 318 (M+). Anal. Calcd for C21H22N2O: C,
79.21; H, 6.96; N, 8.80. Found: C, 79.48; H, 7.07; N, 8.73.
1702 cmꢁ1 1H NMR (CDCl3) d: 1.55 (s, 3H), 3.17 (s,
.
3H), 3.32 (s, 2H), 3.92 (s, 3H), 5.73 (s, 1H), 6.78 (d, 1H,
J¼7.5 Hz), 6.99–7.06 (m, 2H), 7.11 (d, 1H, J¼7.5 Hz),
7.16 (t, 1H, J¼7.5 Hz), 7.25 (t, 1H, J¼8.0 Hz), 7.33 (d,
1H, J¼8.0 Hz), 7.41 (d, 1H, J¼8.0 Hz). 13C NMR
(CDCl3) d: 23.9, 26.4, 32.5, 48.5, 65.0, 97.4, 108.2, 108.3,
120.0, 120.5, 121.6, 122.5, 123.4, 123.9, 128.2, 131.6,
132.4, 133.2, 143.3, 180.1. MS m/z: 320 (M+). Anal. Calcd
for C20H20N2O2: C, 74.98; H, 6.29; N, 8.74. Found: C,
74.89; H, 6.37; N, 8.65.
3.2.26. N-[2-(1-Methoxy-1H-indol-2-yl)phenyl]-N-(2-
methylprop-2-en-1-yl)acetamide (19b). Colorless crystals.
Mp 168–169 ꢀC (hexane–AcOEt). IR (neat): 1644 cmꢁ1. 1H
NMR (CDCl3) d: 1.67 (s, 3H), 2.01 (s, 3H), 3.05 (d, 1H,
J¼14.9 Hz), 3.70 (s, 3H), 4.56 (s, 1H), 4.72 (s, 1H), 4.81
(d, 1H, J¼14.9 Hz), 6.41 (s, 1H), 7.15 (t, 1H, J¼7.5 Hz),
7.24–7.30 (m, 2H), 7.40–7.49 (m, 3H), 7.60 (d, 1H,
J¼8.0 Hz), 7.80 (dd, 1H, J¼1.7, 7.5 Hz). 13C NMR
(CDCl3) d: 20.7, 22.9, 53.2, 64.5, 100.4, 109.1, 113.3,
120.9, 121.3, 123.2, 124.3, 128.1, 128.2, 129.1, 130.7,
131.9, 132.7, 133.3, 140.8, 141.0, 170.9. MS m/z: 334
(M+). Anal. Calcd for C21H22N2O2$1/10H2O: C, 75.02; H,
6.66; N, 8.33. Found: C, 74.98; H, 6.61; N, 8.36.
3.2.22. tert-Butyl 2-[(1,3-dimethyl-2-oxo-2,3-dihydro-1H-
indol-3-yl)methyl]-1H-indole-1-carboxylate (15c). Vis-
1
cous oil. IR (neat): 1708 cmꢁ1. H NMR (CDCl3) d: 1.44
(s, 3H), 1.55 (s, 9H), 3.16 (s, 3H), 3.62 (d, 1H,
J¼14.9 Hz), 3.82 (d, 1H, J¼14.9 Hz), 6.22 (s, 1H), 6.74
(d, 1H, J¼8.0 Hz), 6.92–6.96 (m, 2H), 7.11–7.21 (m, 3H),
7.38 (d, 1H, J¼7.5 Hz), 7.93 (d, 1H, J¼8.5 Hz). 13C NMR
(CDCl3) d: 23.6, 26.3, 28.2, 35.8, 48.8, 83.9, 108.0, 109.9,
115.8, 120.0, 122.4, 122.6, 123.4, 123.6, 127.9, 128.9,
133.4, 136.5, 136.9, 143.1, 150.6, 180.4. HRMS m/z Calcd
for C24H26N2O3: 390.1943. Found: 390.1951.
3.2.27. 2,4-Dimethyl-4-[(1-methyl-1H-indol-2-yl)-
methyl]-3,4-dihydroisoquinolin-1(2H)-one (21a). Color-
less crystals. Mp 118–119 ꢀC (hexane–AcOEt). IR
1
(CHCl3): 1638 cmꢁ1. H NMR (CDCl3) d: 1.43 (s, 3H),
2.95 (d, 1H, J¼14.5 Hz), 3.01 (s, 3H), 3.23 (s, 3H), 3.24 (d,
1H, J¼14.5 Hz), 3.27 (d, 1H, J¼12.6 Hz), 3.62 (d, 1H,
J¼12.6 Hz), 6.29 (s, 1H), 6.86 (d, 1H, J¼8.0 Hz), 7.07–
7.12 (m, 1H), 7.13–7.17 (m, 2H), 7.29 (dt, 1H, J¼1.8,
8.0 Hz), 7.36 (dt, 1H, J¼1.2, 7.5 Hz), 7.56 (d, 1H,
J¼8.0 Hz), 8.18 (dd, 1H, J¼1.2, 8.0 Hz). 13C NMR
(CDCl3) d: 22.7, 29.1, 35.6, 36.0, 38.3, 59.0, 102.9, 109.4,
119.6, 119.9, 121.1, 124.7, 127.4, 127.6, 128.4, 128.7,
132.0, 135.8, 137.3, 144.4, 164.7. MS m/z: 318 (M+). Anal.
Calcd for C21H22N2O$3/10H2O: C, 77.89; H, 7.03; N, 8.65.
Found: C, 77.99; H, 6.92; N, 8.54.
3.2.23. 2-[(1-Acetyl-3-methyl-2,3-dihydro-1H-indol-
3-yl)methyl]-1-methyl-1H-indole (18a). Colorless crystals.
Mp 151–152 ꢀC (hexane–AcOEt). IR (CHCl3): 1652 cmꢁ1
.
1H NMR (CDCl3) d: 1.51 (s, 3H), 2.23 (s, 3H), 3.01 (d, 1H,
J¼18.0 Hz), 3.06 (d, 1H, J¼18.0 Hz), 3.15 (s, 3H), 3.76 (d,
1H, J¼10.3 Hz), 4.07 (d, 1H, J¼10.3 Hz), 6.31 (s, 1H),
6.73 (d, 1H, J¼7.5 Hz), 6.94 (t, 1H, J¼7.5 Hz), 7.10 (t, 1H,
J¼7.5 Hz), 7.16–7.24 (m, 3H), 7.56 (d, 1H, J¼7.5 Hz),
8.21 (d, 1H, J¼8.0 Hz). 13C NMR (CDCl3) d: 24.3, 25.1,
29.3, 37.8, 44.4, 62.0, 101.9, 109.4, 117.1, 119.7, 120.0,
121.1, 122.8, 123.9, 127.6, 128.5, 136.2, 137.3, 138.0, 142.1,
168.9. MS m/z: 318 (M+). Anal. Calcd for C21H22N2O: C,
79.21; H, 6.96; N, 8.80. Found: C, 79.48; H, 7.07; N, 8.73.
3.2.28. 4-[(1-Methoxy-1H-indol-2-yl)methyl]-2,4-di-
methyl-3,4-dihydroisoquinolin-1(2H)-one (21b). Viscous
1
oil. IR (neat): 1648, 1602 cmꢁ1. H NMR (CDCl3) d: 1.38
(s, 1H), 2.99 (d, 1H, J¼14.5 Hz), 3.15 (d, 1H, J¼14.5 Hz),
3.21 (s, 3H), 3.31 (d, 1H, J¼12.6 Hz), 3.40 (d, 1H,
J¼12.6 Hz), 3.85 (s, 3H), 6.02 (s, 1H), 7.11 (t, 1H,
J¼7.5 Hz), 7.22 (t, 1H, J¼7.5 Hz), 7.28 (d, 1H, J¼7.5 Hz),
7.38 (t, 2H, J¼7.5 Hz), 7.47 (dt, 1H, J¼1.7, 7.5 Hz), 7.54
(d, 1H, J¼8.0 Hz), 8.19 (dd, 1H, J¼1.7, 7.5 Hz). 13C NMR
(CDCl3) d: 22.7, 34.9, 35.4, 38.3, 57.3, 64.6, 99.1, 108.4,
120.4, 120.5, 121.9, 123.9, 124.2, 127.3, 128.3, 128.7,
131.8, 132.0, 132.5, 145.5, 164.7. HRMS m/z Calcd for
C21H22N2O2: 334.1681. Found: 334.1678.
3.2.24. tert-Butyl 2-[(1-acetyl-3-methyl-2,3-dihydro-1H-
indol-3-yl)methyl]-1H-indole-1-carboxylate (18b). Color-
less crystals. Mp 167–168 ꢀC (hexane–AcOEt). IR (CHCl3):
1724, 1648 cmꢁ1. 1H NMR (CDCl3) d: 1.44 (s, 3H), 1.65 (s,
9H), 2.17 (s, 3H), 3.35 (d, 1H, J¼14.9 Hz), 3.67 (d, 1H,
J¼10.3 Hz), 3.75 (d, 1H, J¼14.9 Hz), 4.09 (d, 1H, J¼
10.3 Hz), 6.14 (s, 1H), 7.00–7.08 (m, 2H), 7.16–7.28 (m,
3H), 7.42 (d, 1H, J¼8.0 Hz), 7.99 (d, 1H, J¼8.0 Hz), 8.18
(d, 1H, J¼8.0 Hz). 13C NMR (CDCl3) d: 24.3, 26.8, 28.3,
38.7, 44.7, 61.2, 84.3, 110.4, 115.8, 117.1, 120.1, 122.6,
122.9, 123.8, 128.1, 128.9, 136.4, 137.6, 138.8, 142.1, 150.9,
168.7. MS m/z: 404 (M+). Anal. Calcd for C25H28N2O3: C,
74.23; H, 6.98; N, 6.93. Found: C, 74.23; H, 6.98; N, 6.93.
3.2.29. tert-Butyl 2-[(2,4-dimethyl-1-oxo-1,2,3,4-tetra-
hydroisoquinolin-4-yl)methyl]-1H-indole-1-carboxylate
(21c). Colorless crystals. Mp 141–142 ꢀC (hexane–AcOEt).
IR (CHCl3): 1728, 1646 cmꢁ1. 1H NMR (CDCl3) d: 1.32 (s,
3H), 1.69 (s, 9H), 3.18 (s, 3H), 3.37 (d, 1H, J¼12.6 Hz), 3.38
(d, 1H, J¼14.8 Hz), 3.42 (d, 1H, J¼12.6 Hz), 3.80 (d, 1H,
J¼14.8 Hz), 6.01 (s, 1H), 7.10 (d, 1H, J¼7.4 Hz), 7.18 (t,
1H, J¼7.4 Hz), 7.23 (d, 1H, J¼7.4 Hz), 7.34 (t, 1H,
J¼7.4 Hz), 7.38 (dt, 1H, J¼1.1, 7.4 Hz), 7.42 (d, 1H,
J¼7.4 Hz), 7.97 (d, 1H, J¼8.5 Hz), 8.14 (dd, 1H, J¼1.1,
8.5 Hz). 13C NMR (CDCl3) d: 22.5, 28.4, 35.5, 36.8, 38.7,
58.2, 84.3, 111.3, 115.7, 120.1, 122.8, 123.7, 124.6, 127.0,
128.3, 128.6, 128.8, 131.7, 136.6, 137.5, 145.2, 150.9,
164.8. MS m/z: 404 (M+). Anal. Calcd for C25H28N2O3: C,
74.23; H, 6.98; N, 6.93. Found: C, 74.16; H, 7.07; N, 6.81.
3.2.25. N-[2-(1-Methyl-1H-indol-2-yl)phenyl]-N-(2-
methylprop-2-en-1-yl)acetamide (19a). Colorless crystals.
Mp 120–121 ꢀC (hexane–AcOEt). IR (CHCl3): 1648 cmꢁ1
.
1H NMR (CDCl3) d: 1.61 (s, 3H), 2.00 (s, 3H), 3.07 (d, 1H,
J¼15.0 Hz), 3.61 (s, 3H), 4.54 (s, 1H), 4.64 (d, 1H,
J¼15.0 Hz), 4.71 (s, 1H), 6.44 (s, 1H), 7.15 (t, 1H, J¼
7.5 Hz), 7.24–7.30 (m, 2H), 7.35–7.45 (m, 4H), 7.62 (d,
1H, J¼8.0 Hz). 13C NMR (CDCl3) d: 20.5, 23.0, 31.1,
54.0, 102.7, 109.6, 113.4, 120.2, 121.0, 122.2, 127.9,

11590
M. Ishikura et al. / Tetrahedron 62 (2006) 11580–11591
1
3.2.30. N-Methyl-2-(1-methyl-1H-indol-2-yl)-N-(2-meth-
ylprop-2-en-1-yl)benzamide (22a). Viscous oil. IR (neat):
1638 cmꢁ1. 1H NMR (CDCl3) d: 1.28 and 1.47 (two s, 3H),
2.55 and 2.75 (two s, 3H), 2.88–3.04 (two br s, 1H), 3.63
(s, 3H), 4.44 and 4.56 (two s, 1H), 4.60 and 4.74 (two s,
1H), 4.85–4.98 (m, 1H), 6.51 and 6.55 (two s, 1H), 7.07–
7.15 (m, 1H), 7.20–7.27 (m, 1H), 7.30–7.50 (m, 4H), 7.55–
7.64 (m, 1H). 13C NMR (CDCl3) d: 19.4, 19.7, 28.1, 28.2,
31.2, 32.1, 35.6, 52.3, 56.6, 102.2, 103.0, 109.7, 112.5, 113.0,
119.8, 120.6, 120.8, 121.8, 126.8, 127.3, 127.9, 128.4, 128.5,
128.6, 128.7, 128.9, 129.6, 130.9, 131.3, 137.6, 138.0, 138.3,
138.5, 139.9, 140.0, 170.1, 171.2. HRMS m/z Calcd for
C21H22N2O: 318.1732. Found: 318.1728.
(CHCl3): 1706, 1602 cmꢁ1. H NMR (CDCl3) d: 1.42 (s,
3H), 1.47 (s, 9H), 3.19 (s, 3H), 3.54 (s, 2H), 6.82 (d, 1H,
J¼8.0 Hz), 6.89 (s, 1H), 6.96 (t, 1H, J¼7.5 Hz), 7.18–7.25
(m, 3H), 7.38 (t, 1H, J¼8.0 Hz), 7.55 (d, 1H, J¼8.0 Hz),
7.97 (d, 1H, J¼8.6 Hz). 13C NMR (CDCl3) d: 24.7, 26.4,
27.7, 45.6, 48.0, 84.8, 108.1, 114.7, 114.9, 122.3, 122.4,
122.5, 123.3, 127.2, 127.4, 128.0, 133.2, 137.7, 138.4,
143.9, 149.5, 180.1, 189.4. MS m/z: 418 (M+). Anal. Calcd
for C25H26N2O4$3/10H2O: C, 70.84; H, 6.33; N, 6.61.
Found: C, 70.94; H, 6.20; N, 6.44.
3.3.3. 2-(1-Acetyl-3-methyl-2,3-dihydro-1H-indol-3-yl)-
1-(1-methyl-1H-indol-2-yl)ethanone (24). Colorless crys-
tals. Mp 91–92 ꢀC (hexane–AcOEt). IR (CHCl3):
3.2.31. 2-(1-Methoxy-1H-indol-2-yl)-N-methyl-N-(2-
methylprop-2-en-1-yl)benzamide (22b). Viscous oil. IR
1648 cmꢁ1 1H NMR (CDCl3) d: 1.50 (s, 3H), 2.21 (s,
.
3H), 3.17 (d, 1H, J¼15.8 Hz), 3.46 (d, 1H, J¼15.8 Hz),
3.96 (d, 1H, J¼11.0 Hz), 4.03 (s, 3H), 4.34 (d, 1H,
J¼11.0 Hz), 7.05 (t, 1H, J¼7.5 Hz), 7.15 (t, 1H,
J¼6.9 Hz), 7.18–7.27 (m, 3H), 7.34–7.42 (m, 2H), 7.66 (d,
1H, J¼8.0 Hz), 8.20 (d, 1H, J¼8.0 Hz). 13C NMR
(CDCl3) d: 24.3, 26.4, 32.3, 42.8, 49.2, 61.3, 110.5, 112.1,
117.2, 121.0, 122.2, 123.0, 123.9, 125.7, 126.4, 128.3,
135.2, 139.0, 140.3, 141.7, 168.9, 192.1. MS m/z: 346
(M+). Anal. Calcd for C22H22N2O2: C, 76.28; H, 6.40; N,
8.09. Found: C, 76.30; H, 6.48; N, 7.98.
(neat): 1630 cmꢁ1 1H NMR (CDCl3) d: 1.51 and 1.60
.
(two s, 3H), 2.66 and 2.93 (two s, 3H), 3.18–3.25 (m, 1H),
3.78 (s, 3H), 3.95–4.15 (m, 1H), 4.70 and 4.74 (two s,
1H), 4.82 (s, 1H), 6.51 and 6.52 (two s, 1H), 7.09–7.15
(m, 1H), 7.22–7.29 (m, 1H), 7.38–7.51 (m, 4H), 7.56 and
7.57 (two d, 1H, J¼8.0 Hz), 7.75 (d, 1H, J¼8.3 Hz). 13C
NMR (CDCl3) d: 19.8, 20.0, 32.3, 35.8, 52.5, 56.7, 64.7,
100.3, 100.6, 108.8, 113.1, 120.6, 120.7, 121.2, 121.3,
122.8, 122.9, 124.1, 127.2, 127.3, 127.4, 127.5, 128.3,
128.5, 128.9, 129.0, 130.2, 130.4, 133.4, 134.0, 134.1,
136.4, 137.1, 140.1, 140.3, 170.9, 171.5. HRMS m/z Calcd
for C21H22N2O2: 334.1681. Found: 334.1680.
3.3.4. 2,4-Dimethyl-4-[2-(1-methyl-1H-indol-2-yl)-2-oxo-
ethyl]-3,4-dihydroisoquinolin-1(2H)-one (25). Viscous
oil. IR (CHCl3): 1642 cmꢁ1 1H NMR (CDCl3) d: 1.53
.
3.3. General procedure for the tandem cyclization–
carbonylation-cross-coupling reaction of 2 with
14, 17, and 20
(s, 3H), 3.09 (s, 3H), 3.12 (d, 1H, J¼14.3 Hz), 3.20
(d, 1H, J¼14.3 Hz), 3.52 (d, 1H, J¼12.6 Hz), 3.68 (d,
1H, J¼12.6 Hz), 4.04 (s, 3H), 7.10 (s, 1H), 7.13 (dt,
1H, J¼1.8, 8.0 Hz), 7.31–7.41 (m, 4H), 7.46 (t, 1H,
J¼7.5 Hz), 7.63 (d, 1H, J¼8.0 Hz), 8.12 (d, 1H, J¼
7.5 Hz). 13C NMR (CDCl3) d: 23.1, 32.4, 35.1, 37.7, 47.5,
57.2, 110.4, 112.5, 120.9, 123.1, 123.8, 125.6, 126.3,
127.3, 128.3, 128.7, 132.1, 135.6, 140.4, 145.2, 164.6,
192.0. HRMS m/z Calcd for C22H22N2O2: 346.1681. Found:
346.1673.
To a THF solution of indolylborate (2) generated from indole
(1)(2 mmol)insituunderan argonatmosphere, 3, 6, 9, 11, 14,
17, or 20 (1 mmol) was added, and the apparatus was filled
with carbon monoxide. Palladium complex (0.05 mmol)
was placed in a flask, and then carbon monoxide was intro-
duced up to 10 atm. Thewholewas heated at 60 ꢀC overnight.
The mixture was ice-cooled, and 10% NaOH (10 mL) and
30% H2O2 (2 mL) were added. After stirring for 10 min,
the mixture was diluted with AcOEt (100 mL), washed with
brine, and dried over MgSO4. The solvent was removed,
and the residuewas separated by MPLC with hexane–AcOEt.
3.3.5. N-Methyl-2-[(1-methyl-1H-indol-2-yl)carbonyl]-
N-(2-methylprop-2-en-1-yl)benzamide (26). Viscous oil.
1
IR (neat): 1632 cmꢁ1. H NMR (CDCl3) d: 1.63 and 1.67
(two s, 3H), 2.86 and 2.92 (two s, 3H), 3.76 (s, 1H), 4.03
(s, 1H), 4.10 (s, 3H), 4.87 (s, 1H), 4.90 and 4.94 (two s,
1H), 6.95 (d, 1H, J¼4.6 Hz), 7.10–7.16 (m, 1H), 7.35–
7.58 (m, 5H), 7.60–7.64 (m, 1H), 7.73 (d, 1H, J¼7.5 Hz).
13C NMR (CDCl3) d: 19.9, 20.1, 32.0, 32.6, 36.3, 52.7,
53.5, 57.3, 110.3, 112.5, 112.9, 115.7, 115.8, 120.8, 123.2,
125.9, 126.2, 126.3, 126.7, 127.2, 128.2, 128.3, 129.9,
130.1, 130.8, 135.1, 137.6, 137.9, 138.2, 138.5, 140.5,
140.6, 170.6, 171.3, 188.4, 188.5. HRMS m/z Calcd for
C22H22N2O2: 346.1681. Found: 346.1677.
3.3.1. 1,3-Dimethyl-3-[2-(1-methyl-1H-indol-2-yl)-2-oxo-
ethyl]-1,3-dihydro-2H-indol-2-one (23a). Colorless crys-
tals. Mp 145–146 ꢀC (hexane–AcOEt). IR (CHCl3): 1702,
1
1662, 1612 cmꢁ1. H NMR (CDCl3) d: 1.44 (s, 3H), 3.30
(s, 3H), 3.62 (d, 1H, J¼17.2 Hz), 3.73 (d, 1H, J¼17.2 Hz),
3.81 (s, 3H), 6.87 (d, 1H, J¼8.0 Hz), 6.96 (t, 1H, J¼
7.5 Hz), 7.13 (t, 1H, J¼8.0 Hz), 7.17 (d, 1H, J¼7.5 Hz),
7.24 (t, 1H, J¼7.5 Hz), 7.26–7.31 (m, 2H), 7.37 (t, 1H, J¼
7.5 Hz), 7.67 (d, 1H, J¼8.0 Hz). 13C NMR (CDCl3) d: 25.1,
26.5, 32.0, 45.7, 46.9, 108.2, 110.3, 111.3, 120.8, 122.1,
122.2, 122.9, 125.7, 126.0, 127.9, 133.6, 134.4, 140.0,
143.8, 180.7, 189.9. MS m/z: 332 (M+). Anal. Calcd for
C21H20N2O2: C, 75.88; H, 6.06; N, 8.43. Found: C, 75.80;
H, 6.08; N, 8.29.
Acknowledgements
This was supported in part by ‘Academic Frontier’ Project
for Private University: matching fund subsidy from Ministry
of Education, Culture, Sports, Science, and Technology,
2002–2006, in part by a Grant-in-Aid for High Technology
Research Program from Ministry of Education, Culture,
Sports, Science and Technology of Japan, and in part by
3.3.2. tert-Butyl 2-[(1,3-dimethyl-2-oxo-2,3-dihydro-
1H-indol-3-yl)acetyl]-1H-indole-1-carboxylate (23b).
Colorless crystals. Mp 154–155 ꢀC (hexane–AcOEt). IR

M. Ishikura et al. / Tetrahedron 62 (2006) 11580–11591
11591
Thangavelanthum, R.; Thompton-Pett, M.; Wilson, D.
Tetrahedron 1997, 53, 11803–11826.
6. Ishikura, M. Curr. Org. Chem. 2002, 6, 507–521.
7. Ishikura, M.; Terashima, M. J. Chem. Soc., Chem. Commun.
1989, 135–136.
a Grant-in-Aid for Scientific Research (No. 18590011) from
the Ministry of Education, Culture, Sports, Science and
Technology of Japan.
8. Ishikura, M. J. Chem. Soc., Chem. Commun. 1995, 409–410.
9. Ishikura, M.; Agata, I.; Katagiri, N. J. Heterocycl. Chem. 1999,
36, 873–879.
References and notes
1. (a) Diederich, F.; Stang, P. J. Metal-catalyzed Cross-coupling
Reactions; Wiley-VCH: Weinheim, 1998; (b) Prim, D.;
Campage, J. M.; Joseph, D.; Andrioletti, B. Tetrahedron
2002, 58, 2041–2075; (c) Chinchilla, R.; Najera, C.; Yus, M.
Chem. Rev. 2004, 104, 2667–2722.
2. (a) Grigg, R. J. Heterocycl. Chem. 1994, 31, 631–639; (b)
Grigg, R.; Sridharan, V. Comprehensive Organometallic
Chemistry II; Abel, E. W., Stone, F. G. A., Wilkinson, G.,
Eds.; Pergamon: Oxford, 1995; Vol. 12, pp 299–321.
10. (a) Ozawa, F.; Sugimoto, T.; Yuasa, M.; Yamamoto, T.;
Yamamoto, A. Organometallics 1984, 3, 683–692; (b)
Huang, L.; Ozawa, F.; Yamamoto, A. Organometallics 1990,
9, 2603–2611.
11. Wang, R. T.; Chou, F. L.; Luo, F. T. J. Org. Chem. 1990, 55,
4846–4849.
12. (a) Collman, J. P.; Hegedus, L. S.; Norton, J. R.; Finke, R. G.
Principles and Applications of Organotransition Metal
Chemistry; University Science Books: Mill Valley, CA, 1987;
(b) Cornils, B.; Hermann, W. A. Applied Homogeneous Catal-
ysis with Organometallic Compounds; Wiley: Weinheim, 1999;
(c) Tsuji, J. Transition Metal Reagents and Catalysts: Innova-
tions in Organic Synthesis; Wiley: Chichester, UK, 2000.
13. Canty, A. J. Comprehensive Organometallic Chemistry II;
Abel, E. W., Stone, F. G. A., Wilkinson, G., Eds.; Pergamon:
Oxford, 1995; Vol. 9, pp 225–290.
3. Suzuki, A.; Brown, H. C. Organic Syntheses via Boranes;
Aldrich Chemical: Milwaukee, WI, 2003; Vol. 3.
4. (a) Couty, S.; Liegault, B.; Meyer, C.; Cossy, J. Org. Lett. 2004,
6, 2511–2514; (b) Yanada, R.; Obika, S.; Inokuma, T.; Yanada,
K.; Yamashita, M.; Ohta, S.; Takemoto, Y. J. Org. Chem. 2005,
70, 6972–6975; (c) Cheung, W. S.; Patch, R. J.; Player, M. R.
J. Org. Chem. 2005, 70, 3741–3744.
5. (a) Burns, B.; Grigg, R.; Sridharan, V.; Stevenson, P.; Worakun,
T. Tetrahedron Lett. 1989, 30, 1135–1138; (b) Negishi, E.;
Noda, Y.; Lamaty, F.; Vawter, E. J. Tetrahedron Lett. 1990,
31, 4393–4396; (c) Grigg, R.; Redpath, J.; Sridharan, V.;
Wilson, D. Tetrahedron Lett. 1994, 35, 4429–4432; (d) Grigg,
R.; Sandano, J. M.; Santhakumar, V.; Sridharan, V.;
14. Ishikura, M.; Matsuzaki, Y.; Agata, I.; Katagiri, N. Tetrahedron
1998, 54, 13929–13942.
15. Shaughnessy, K. H.; Hamann, B. C.; Hartwig, J. F. J. Org.
Chem. 1998, 63, 6546–6553.
16. Ishikura, M.; Terashima, M. J. Org. Chem. 1994, 59, 2634–
2637.