Studies on palladium-catalyzed synthesis of dihydrocycloocta-[b]indoles and Their thermal reactivities with maleimide or maleic anhydride

Article abstract of DOI:10.1002/adsc.201400644

A palladium(0)-catalyzed reaction of 2-allyl-3-indolyl boronates/propargylic carbonates was observed to afford dihydrocycloocta[b]indoles highly efficiently via carbon-carbon coupling, [1,5]-hydrogen migration involving dearomatization, and electrocyclization involving rearomatization. Their thermal reactions with the addition of dienophiles involving eletrocyclization and [4+2] cycloaddition have been studied.

Full text of DOI:10.1002/adsc.201400644

UPDATES
DOI: 10.1002/adsc.201400644
Studies on Palladium-Catalyzed Synthesis of Dihydrocycloocta-
[b]indoles and their Thermal Reactivities with Maleimide or
Maleic Anhydride
Can Zhua and Shengming Maa,b,*
a
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of
Sciences, 345 Lingling Lu, Shanghai 200032, Peopleꢀs Republic of China
Fax : (+86)-21-6260-9305; e-mail: masm@sioc.ac.cn
Department of Chemistry, Fudan University, 220 Handan Lu, Shanghai 200433, Peopleꢀs Republic of China
b
Received: July 3, 2014; Published online: November 14, 2014
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201400644.
Abstract: A palladium(0)-catalyzed reaction of 2-
allyl-3-indolyl boronates/propargylic carbonates was
observed to afford dihydrocycloocta[b]indoles
highly efficiently via carbon-carbon coupling, [1,5]-
hydrogen migration involving dearomatization, and
electrocyclization involving rearomatization. Their
thermal reactions with the addition of dienophiles
involving eletrocyclization and [4+2] cycloaddition
have been studied.
struct eight-membered compounds from 1,2,4Z,7-tet-
raenes.[6] The Pd(0)-catalyzed coupling reaction has
been considered as an efficient approach to produce
arylallenes. Recently, an efficient protocol has been
developed in this group for the synthesis of dihydro-
cycloocta[b]indoles from 2-allyl-3-iodoindoles 1 and
propargylic bromides 2 directly, with the intermediacy
of 2-allyl-3-allenylindoles [Eq. (1)].[7]
Keywords: allenes; coupling; cyclization; cycloaddi-
tion; dihydrocycloocta[b]indoles; palladium
The structure of cycloalka[b]indoles, a class of ring-
fused heteroaromatic compounds, has been widely ob-
served in various artificial compounds displaying in-
teresting biological and pharmacological activities, as
well as in natural products, and has, thus, attracted
considerable attention.[1] Typical approaches towards
cycloalka[b]indoles are based on the formation of an
indole unit starting from cyclic substrates, for exam-
ple, Fischer indole synthesis,[2] which suffers from
some drawbacks such as harsh reaction conditions to-
Further substrate scope examination showed that
gether with the use of non-readily-available starting the reaction worked quite well with terminal propar-
materials, and ring-formation reaction of indole-con- gylic bromides, as well as primary propargylic bro-
taining substrates, which is usually favored for the for- mides, giving the corresponding products in moderate
mation of five- or six-membered rings.[3,4] Up to now, to good yields, however, non-terminal tertiary propar-
methodologies for the efficient synthesis of this type gylic bromides (R1, R2, R3 ¼H) led to disappointing
of skeleton, especially those involving the formation results: Conducting the coupling reaction of 2-allyl-3-
of unfavorable fused 8-membered rings are limited iodo-1-tosyl-1H-indole 1a with internal tertiary prop-
and, thus, highly desirable. On the other hand, allenes argylic bromides, such as 2-methyl-4-phenylbut-2-ynyl
have been proven to be efficient building blocks for bromide 2a, under the standard conditions afforded
the construction of potentially useful carbo- and het- a trace amount of the corresponding dihydrocyclooc-
erocycles.[5] Recently, we have reported a tandem ta[b]indole 3o, with a 70% yield of the reduced prod-
[1,5]-hydrogen migration/8p-electrocyclization to con- uct, i.e., indole 4 [Eq. (2), Scheme 1]. Thus, a new ap-
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Scheme 1. The Suzuki–Miyaura cross-coupling approach towards a highly efficient synthesis of dihydrocycloocta[b]indoles.
proach is highly desirable. On the other hand, the easily obtained in 56% and 63% yields, respectively,
highly efficient Suzuki–Miyaura cross-coupling reac- which could be used for further studies [Eq. (4)].
tion has been proven to be an extremely important
[8,9]
ꢀ
tool for the formation of C C bonds.
Thus, we en-
visioned that the Suzuki–Miyaura cross-coupling reac-
tion of propargylic carbonates 6 with 2-allyl-3-indolyl
boronates 5 would generate 3-allenylindoles Int-1 in
principle, which will be followed by cycloisomeriza-
tion to afford diversified dihydrocycloocta[b]indoles 3
[Eq. (3), Scheme 1].
The N-subtituted 2-allyl-3-iodoindole derivatives
1 were synthesized via the palladium-catalyzed Sono-
gashira cross-coupling, N-substitution and electrophil-
ic cyclization. The results are listed in Scheme 2.
With these results in hand, we turned to examine
Transformation of the iodoindoles 1 to 3-indolyl the coupling of N-tosyl 2-allyl-3-indolyl boronate 5a
boronates 5[10] could be achieved via Pd-catalyzed with internal tertiary propargylic carbonate 6a. When
[11]
coupling with B2pin2 or HBpin.[9d,e,12] When the re- the reaction was carried out in dioxane at 858C cata-
action was carried out in dioxane at 808C catalyzed lyzed by 5 mol% Pd(PPh3)4 in the presence of
by 3 mol% Pd(PPh3)4 in the presence of HBpin and 3.0 equiv. of K3PO4 and 3.0 equiv. of H2O, dihydrocy-
Et3N, 2-allyl-3-indolyl boronates 5a and 5b were cloocta[b]indole 3o was obtained in 87% yield in one
step [Eq. (5)]. The structure of 3o was determined by
X-ray single crystal diffraction analysis (Figure 1).[13]
Scheme 2. Synthesis of substituted 2-allyl-3-iodoindoles 1.
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nal position (Table 1, entries 1–5), i.e., R1 =H, n-Bu,
allyl, cinnamyl and CH2OMe, leading to the corre-
sponding bridged-ring products in good to excellent
yields. The reaction worked very well using a tertiary
propargylic carbonate (R2 =R3 =Et), thus, producing
10f in 81% yield (Table 1, entry 6). It is worth men-
tioning that propargylic carbonates with a cyclic unit
[R2 =-(CH2)n-] are also compatible under the standard
protocol, forming spiro compounds in decent yields
(Table 1, entries 7–10). Further studies showed that
the dienophiles have a great influence on the reaction
(Table 1, entries 11 and 12). A fluorine substituent
may be introduced to the indole unit, producing the
corresponding indole derivative 10m in 67% yield
(Table 1, entry 13).
Finally, the reaction could be conducted on a 1 g
scale to afford 10g in 68% yield [Eq. (7)].
Figure 1. ORTEP drawing of 3o.
Based on the successful attempt to construct
a multi-substituted dihydrocycloocta[b]indole skele-
ton, we envisioned its subsequent thermal reaction
with dienophiles: Coupling/cyclization reaction of 5a
with 6b, followed by the removal of K3PO4 via filtra-
tion and cycloaddition with N-ethylmaleimide (11a),
afforded the bridged product 10a in 96% NMR yield,
directly [Eq. (6)].
The octatomic and bridged-ring structure of these
products 10a–m was further confirmed by the X-ray
single crystal diffraction study of (a) 10b and (b) 10i
(Figure 2).[14,15]
Based on our previous observation and theoretical
calculation,[6,7] a mechanism was proposed to explain
the coupling/cyclization–cycloaddition reaction: The
Suzuki–Miyaura coupling reaction of 2-allyl-3-indolyl
boronates 5 and propargylic carbonates 6 produced 3-
allenylindoles Int-1, which would be followed by cy-
cloisomerization to generate dihydrocycloocta[b]in-
doles 3 via palladium(0)-catalyzed carbon-carbon cou-
pling, [1,5]-hydrogen migration, and electrocycliza-
tion, involving a dearomatization and aromatization.
Subsequent thermal reaction occurred upon heating
with the dienophiles: electrocyclization of dihydrocy-
cloocta[b]indoles 3 would form tetracyclic intermedi-
ates Int-5 via the reversible 6p-pericyclic process. The
cyclic diene unit in Int-5 would react with dienophiles
With the standard protocol shown in Eq. (6), the 11 via [4+2]cycloaddition to generate endo-type
scope of the propargylic carbonates is quite general: indole derivatives highly diastereoselectively
Various substituents could be introduced to the termi- (Scheme 3).
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Table 1. Palladium-catalyzed cross-coupling reaction and cyclization of 5 with 6 and the subsequent thermal reaction with di-
enophiles 11.[a]
Entry
5
R
6
11
X
Yield of 10 [%][b]
R1
R2
1
H (5a)
H (5a)
H (5a)
H (5a)
H (5a)
H (5a)
H (5a)
H (5a)
H (5a)
H (5a)
H (5a)
H (5a)
F (5b)
n-Bu
H
allyl
cinnamyl
Me (6b)
Me (6c)
Me (6d)
Me (6e)
Me (6f)
Et (6g)
-(CH2)4- (6h)
-(CH2)5- (6i)
-(CH2)5- (6j)
-(CH2)6- (6k)
Me (6b)
NEt (11a)
NEt (11a)
NEt (11a)
NEt (11a)
NEt (11a)
NEt (11a)
NEt (11a)
NEt (11a)
NEt (11a)
NEt (11a)
NPh (11b)
O (11c)
88 (10a)
64 (10b)
68 (10c)
66 (10d)
90 (10e)
81 (10f)
73 (10g)
77 (10h)
81 (10i)
74 (10j)
68 (10k)
55 (10l)
67 (10m)
2[c]
3
4
5
6
7
8
9
10
CH2OMe
H
H
H
Me
H
H
H
H
11[c,d]
12[c,e]
13
Me (6b)
-(CH2)4- (6h)
NEt (11a)
[a]
The reactions were carried out on a 1.0 mmol scale in 10 mL of dioxane for the first step and 10 mL of toluene for the
second step.
Yield of isolated product.
The reactions were carried out without H2O (3.0 equiv.) for the first step.
The reactions were carried out at 1108C for 16 h for the second step.
The reactions were carried out at 1108C for 30 h for the second step.
[b]
[c]
[d]
[e]
Figure 2. ORTEP drawings of (a) 10b and (b) 10i.
In conclusion, we have developed a Pd(0)-catalyzed bonates takes advantage of the classic Suzuki–
coupling/cyclization reaction of 2-allyl-3-indolyl boro- Miyaura coupling and, thus, shows much better sub-
nates with propargylic carbonates to construct dihy- strate scope with the poly-substituted propargylic
drocycloocta[b]indoles.[16] The novel approach starting compounds. Further cycloaddition of dienophiles
from 2-allyl-3-indolyl boronates and propargylic car- forms bridged products highly diastereoselectively.
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Scheme 3. Proposed mechanism.
erence in CDCl3 and 13C NMR spectra were measured rela-
tive to the signal of CDCl3 (77.0 ppm). 19F NMR spectra
were measured with Cl3CF (0 ppm) as the internal refer-
ence.
This tandem coupling-cyclization and subsequent
thermal reaction is highly efficient, which proceeds
through palladium(0)-catalyzed carbon-carbon cou-
pling, [1,5]-hydrogen migration, electrocyclization,
and cycloaddition, involving overall dearomatization
and aromatization twice. Further studies in this area
are currently under way in our laboratory.
Synthesis of Starting Materials 1
2-(Pent-4-en-1-ynyl)aniline (8a): To a flame-dried three-
necked flask were added PdCl2(PPh3)2 (1.408 g, 2.0 mmol),
CuI (382 mg, 2.0 mmol), 2-iodoaniline 7a (21.982 g, 0.10
Experimental Section
General Experimental Methods
Dioxane used in these experiments was distilled over
sodium wire, acetonitrile used in the experiments was dis-
tilled over CaH2, dichloromethane used in the experiments
was dried over CaH2. All the temperatures are referred to
the oil baths used. K3PO4 was purchased from Alfa.
Pd(PPh3)4 was purchased from Sigma-Aldrich. Pinacol
borane was purchased from TCI. N-Iodosuccinimide was
mol), pent-1-en-4-yne[17] (260 mL, 0.13 mol, 0.50m in THF),
and Et3N (150 mL) sequentially under an Ar atmosphere.
The resulting mixture was stirred at room temperature.
After 9 h, the reaction was complete as monitored by TLC.
1
purchased from Darui Chemistry. All H NMR spectra were
measured with tetramethylsilane (0 ppm) as the internal ref-
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Evaporation and column chromatography on silica gel
K2CO3 (13.476 g, 98 mmol), NIS (NIS=N-iodosuccinimide,
21.721 g, 97 mmol), and MeCN (200 mL) sequentially under
an Ar atmosphere. The resulting mixture was stirred at
ꢀ108C for 30 min. The resulting mixture was allowed to
warm up to room temperature. After 26 h, the reaction was
over as monitored by TLC. After filtration through a short
column (100–200 mesh, 5 cm) of silica gel to remove the
salts (3ꢂ20 mL of CH2Cl2), the combined solvent was
washed with saturated Na2S2O3 (aq., 100 mL), extracted
with CH2Cl2 (3ꢂ100 mL), and dried over anhydrous
Na2SO4. After filtration, evaporation of the solvent and
chromatography on silica gel (eluent: petroleum ether/ethyl
acetate=20/1) afforded the desired product 1a as a solid;
yield: 10.532 g (75%); mp 88–908C (petroleum ether/
(eluent: petroleum ether/ethyl acetate=20/1) afforded the
1
desired product 8a as an oil; yield; 15.130 g (96%). H NMR
(300 MHz, CDCl3): d=7.31–7.23 (m, 1H, Ar-H), 7.13–7.04
(m, 1H, Ar-H), 6.71–6.62 (m, 2H, Ar-H), 5.98–5.83 (m, 1H,
=CH), 5.41 (dd, J=16.8 Hz, 1.2 Hz, 1H, one proton of =
CH2), 5.16 (d, J=10.1 Hz, 1.4 Hz, 1H, one proton of =CH2),
4.15 (brs, 2H, NH2), 3.28–3.18 (m, 2H, CH2); 13C NMR
(CDCl3, 100 MHz): d=147.7, 132.5, 132.1, 129.0, 117.8,
116.2, 114.1, 108.4, 91.8, 79.3, 23.9; MS (EI): m/z=158
(M+ +1, 12.25), 157 (M+, 100); IR (neat): n=3472, 3378,
3187, 3079, 3027, 2981, 2885, 2810, 1640, 1613, 1573, 1492,
1456, 1417, 1402, 1308, 1263, 1245, 1158, 1141, 1031 cmꢀ1
;
HR-MS (EI): m/z=157.0891, calcd. for C11H11N [M+]:
157.0891.
1
CH2Cl2). H NMR (400 MHz, CDCl3): d=8.18–8.08 (m, 1H,
Ar-H), 7.63 (d, J=8.0 Hz, 2H, Ar-H), 7.37–7.20 (m, 3H, Ar-
H), 7.12 (d, J=8.0 Hz, 2H, Ar-H), 6.06–5.92 (m, 1H, =CH),
5.20–5.05 (m, 2H, =CH2), 3.94 (d, J=5.2 Hz, 2H, CH2), 2.25
(s, 3H, CH3); 13C NMR (CDCl3, 100 MHz): d=145.0, 138.6,
136.3, 135.5, 133.6, 131.6, 129.8, 126.4, 125.4, 124.1, 121.5,
117.0, 114.9, 74.3, 33.2, 21.4; MS (EI): m/z=438 (M+ +1,
6.22), 437 (M+, 28.53), 155 (100); IR (KBr): n=1638, 1597,
1552, 1493, 1447, 1403, 1371, 1306, 1252, 1219, 1190, 1172,
N-[2-(Pent-4-en-1-ynyl)phenyl]-4-methylbenzenesulfona-
mide (9a): To a three-necked flask were added 8a (544 mg,
3.5 mmol), pyridine (0.6 mL, d=0.98 gmLꢀ1, 588 mg,
1151, 1119, 1089, 1054, 1023 cmꢀ1
;
anal. calcd. for
C18H16INO2S: C 49.44, H 3.69, N 3.20; found: C 49.46, H
3.58, N 3.05.
2-Allyl-5-fluoro-3-iodo-1-tosyl-1H-indole (1b):
To
a flame-dried three-necked flask were added PdCl2(PPh3)2
(143 mg, 0.20 mmol), CuI (39 mg, 0.20 mmol), 4-fluoro-2-io-
7.4 mmol), CH2Cl2 (20 mL), and TsCl (TsCl=para-toluene-
sulfonyl chloride) (860 mg, 4.5 mmol) sequentially. The re-
sulting mixture was stirred at room temperature. After 5 h,
the reaction was over as monitored by TLC, and quenched
with 20 mL of HCl (aq., 1.0M). After separation of the or-
ganic layer, the water layer was extracted with CH2Cl2 (3ꢂ
50 mL). The combined organic layer was dried over anhy-
drous Na2SO4, filtered, evaporated, and purified via column
chromatography on silica gel (eluent: petroleum ether/ethyl
acetate=10/1) to afford the desired product 9a as a solid;
yield; 883 mg (82%); mp 82–858C (petroleum ether/
CH2Cl2). 1H NMR (300 MHz, CDCl3): d=7.66 (d, J=
7.2 Hz, 2H, Ar-H), 7.57 (d, J=8.7 Hz, 1H, Ar-H), 7.30–7.15
(m, 5H, Ar-H and NH), 6.99 (t, J=7.8 Hz, 1H, Ar-H), 5.93–
5.78 (m, 1H, =CH), 5.31 (d, J=17.4 Hz, 1H, one proton of
=CH2), 5.20 (d, J=9.9 Hz, 1H, one proton of =CH2), 3.22–
3.15 (m, 2H, CH2), 2.35 (s, 3H, CH3); 13C NMR (CDCl3,
100 MHz): d=143.8, 137.4, 135.9, 131.9, 131.5, 129.4, 128.9,
127.1, 124.2, 119.5, 116.6, 114.5, 93.9, 77.3, 23.6, 21.4; MS
(EI): m/z=312 (M+ +1, 22.35), 311 (M+, 100); IR (KBr):
n=3255, 1641, 1598, 1487, 1450, 1393, 1329, 1290, 1256,
1187, 1165, 1092, 1042, 1019 cmꢀ1
;
anal. calcd for
doaniline 7b (2.375 g, 10 mmol), pent-1-en-4-yne (30 mL,
0.50M in THF, 15 mmol), and Et3N (30 mL) sequentially
under an Ar atmosphere. The resulting mixture was stirred
at room temperature. After 20 h, the reaction was over as
monitored by TLC. The mixture was evaporated to afford
the crude product 8b, which was used as the starting materi-
al in the next step without further purification and charac-
terization.
C18H17NO2S: C 69.43, H 5.50, N 4.50J found: C 69.06, H
5.70, N 4.21.
2-Allyl-3-iodo-1-tosyl-1H-indole (1a): To a flame-dried
three-necked flask were added 9a (9.999 g, 32 mmol),
To a one-necked flask were added crude 8b (10 mmol),
pyridine (1.45 mL, d=0.98 gmLꢀ1, 1.421 g, 18 mmol),
CH2Cl2 (30 mL), and TsCl (TsCl=para-toluenesulfonyl
chloride) (2.472 g, 13 mmol) sequentially. The resulting mix-
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ture was stirred at room temperature. After 7 h, the reaction
was over as monitored by TLC, which was quenched with
20 mL of HCl (aq., 1.0M). After separation of the organic
layer, the water layer was extracted with CH2Cl2 (3ꢂ
50 mL). The combined organic layer was dried over anhy-
drous Na2SO4. After filtration, evaporation of the solvent af-
forded the crude product 9b, which was used as the starting
material in the next step without further purification and
characterization.
desired product 5a as a solid; yield: 2.450 g (56%); mp 115–
1178C (petroleum ether/ethyl ether). 1H NMR (400 MHz,
CDCl3): d=8.13–8.06 (m, 1H, Ar-H), 7.97–7.93 (m, 1H, Ar-
H), 7.66 (d, J=8.0 Hz, 2H, Ar-H), 7.27–7.18 (m, 2H, Ar-H),
7.15 (d, J=8.0 Hz, 2H, Ar-H), 6.18–6.02 (m, 1H, =CH), 5.15
(dd, J=17.2 Hz, 1.6 Hz, 1H, one proton of =CH2), 5.01 (dd,
J=10.0 Hz, 1.6 Hz, 1H, one proton of =CH2), 4.14 (d, J=
6.4 Hz, 2H, CH2), 2.30 (s, 3H, Ar-CH3), 1.34 (s, 12H, 4ꢂ
CH3); 13C NMR (CDCl3, 100 MHz): d=149.4, 144.7, 137.0,
136.6, 136.2, 133.2, 129.7, 126.5, 123.9, 123.5, 122.2, 116.0,
114.3, 83.2, 32.0, 24.9, 21.5; MS (EI): m/z=438 (M+ +1,
11.88), 437 (M+, 20.92), 101 (100); IR (KBr): n=3077, 3050,
2979, 2931, 1637, 1600, 1558, 1494, 1474, 1452, 1422, 1400,
1372, 1316, 1289, 1243, 1214, 1191, 1173, 1191, 1173, 1145,
To a flame-dried three-necked flask were added crude 9b
(10 mmol), K2CO3 (4.145 g, 30 mmol), NIS (6.749 g,
30 mmol), and MeCN (80 mL) sequentially under an Ar at-
mosphere. The resulting mixture was stirred at ꢀ108C for
30 min. The resulting mixture was then allowed to warm up
to room temperature and after 14 h the reaction was over as
monitored by TLC. After filtration, the mixture was washed
with an aqueous solution of Na2S2O3 (1%, 50 mL), extracted
with Et2O (3ꢂ50 mL), and dried over anhydrous Na2SO4.
After filtration, evaporation of the solvent and chromatog-
raphy on silica gel (eluent: petroleum ether/ethyl acetate/di-
chloromethane=40/1/1) afforded the desired product 1b as
a solid; yield: 3.800 g (83% for 3 steps); mp 81–838C (petro-
leum ether/ethyl ether). 1H NMR (400 MHz, CDCl3): d=
8.10 (dd, J=9.0 Hz, 4.2 Hz, 1H, Ar-H), 7.63 (d, J=8.0 Hz,
2H, Ar-H), 7.18 (d, J=7.6 Hz, 2H, Ar-H), 7.08–6.97 (m,
2H, Ar-H), 6.03–5.89 (m, 1H, =CH), 5.20–5.04 (m, 2H, =
CH2), 3.92 (d, J=5.6 Hz, 2H, CH2), 2.31 (s, 3H, Ar-CH3);
13C NMR (CDCl3, 100 MHz): d=160.0 (d, J=240.6 Hz),
145.3, 140.5, 135.3, 133.3, 133.1 (d, J=10.2 Hz), 132.6, 129.9,
126.4, 117.2, 116.3 (d, J=8.7 Hz), 113.2 (d, J=24.9 Hz),
107.3 (d, J=24.9 Hz), 73.3 (d, J=3.6 Hz), 33.4, 21.5;
19F NMR (CDCl3, 376 MHz): d=ꢀ118.8; MS (EI): m/z=
456 (M+ +1, 25.50), 455 (M+, 93.57), 172 (100); IR (KBr):
n=3080, 2981, 2923, 1638, 1612, 1596, 1548, 1494, 1468,
1444, 1373, 1338, 1307, 1294, 1258, 1215, 1156, 1121, 1089,
1058 cmꢀ1; anal. calcd. for C18H15FINO2S: C 47.49, H 3.32, N
3.08; found: C 47.49, H 3.33, N 2.98.
1119, 1090, 1060, 1027, 1018 cmꢀ1
;
anal. calcd. for
C24H28BNO4S: C 65.91, H 6.45, N 3.20; found: C 66.17, H
6.65, N 3.16.
2-Allyl-5-fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-
2-yl)-1-tosyl-1H-indole (5b): Following the procedure for
the preparation of 5a, the reaction of Pd(PPh3)4 (209 mg,
0.18 mmol), 1b (2.740 g, 6.0 mmol)/dioxane (12 mL), Et3N
(8.3 mL, d=0.73 gmLꢀ1, 6.059 g, 60 mmol), HBpin (1.156 g,
9.0 mmol)/dioxane (12 mL) afforded the desired product 5b
1
as an oil: yield: 1.720 g (63%). H NMR (400 MHz, CDCl3):
d=8.03 (dd, J=9.4 Hz, 4.6 Hz, 1H, Ar-H), 7.67–7.59 (m,
3H, Ar-H), 7.18 (d, J=8.0 Hz, 2H, Ar-H), 6.96 (td, J=
9.0 Hz, 2.7 Hz, 1H, Ar-H), 6.14–6.02 (m, 1H, =CH), 5.16
(dd, J=17.2 Hz, 1.6 Hz, 1H, one proton of =CH2), 5.02 (dd,
J=10.0 Hz, 1.6 Hz, 1H, one proton of =CH2), 4.12 (d, J=
6.4 Hz, 2H, CH2), 2.32 (s, 3H, Ar-CH3), 1.34 (s, 12H, 4ꢂ
CH3); 13C NMR (CDCl3, 100 MHz): d=159.8 (d, J=
237.6 Hz), 151.1, 144.9, 136.3, 136.0, 134.5 (d, J=10.6 Hz),
133.3 (d, J=1.2 Hz), 129.8, 126.4, 116.3, 115.3 (d, J=9.2 Hz),
111.6 (d, J=24.7 Hz), 107.9 (d, J=23.6 Hz), 83.3, 32.1, 24.9,
21.5; 19F NMR (CDCl3, 376 MHz): d=ꢀ120.5; MS (EI):
m/z=456 (M+ +1, 15.6), 455 (M+, 53.85), 200 (100); IR
(neat): n=3083, 2979, 2932, 1637, 1612, 1589, 1558, 1494,
1466, 1452, 1395, 1372, 1317, 1266, 1254, 1214, 1192, 1173,
1154, 1144, 1121, 1090, 1063 cmꢀ1; HR-MS (EI): m/z=
454.1769, calcd. for C24H2710BFNO4S [M+]: 454.1774; m/z=
455.1735, calcd. for C24H2711BFNO4S [M+]: 455.1738.
Synthesis of 2-Allyl-3-indolyl Boronates 5
2-Allyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-
tosyl-1H-indole (5a): To a flame-dried three-necked flask
were added Pd(PPh3)4 (348 mg, 0.30 mmol), 1a (4.373 g,
10.0 mmol)/dioxane
(20 mL),
Et3N
(13.9 mL,
HBpin (1.921 g,
d=
0.73 g. mLꢀ1,
10.147 g,
100 mmol),
Synthesis of (6Z,10Z)-9,9-Dimethyl-11-phenyl-5-tosyl-
8,9-dihydro-5H-cycloocta[b]indole (3o)
15.0 mmol)/dioxane (20 mL) sequentially under an Ar at-
mosphere. After the mixture was stirred at 808C for 13 h,
the reaction was complete as monitored by TLC. After
evaporation of the solvent, purification via column chroma-
tography on silica gel (eluent: petroleum ether/ethyl ether=
100/1 then petroleum ether/ethyl ether=80/1) afforded the
To a flame-dried Schlenk tube were added 5a (87.4 mg,
0.2 mmol), Pd(PPh3)4 (11.7 mg, 0.010 mmol), K3PO4
(129.5 mg, 0.6 mmol)/dioxane (1 mL), propargylic carbonate
6a (89.0 mg, 0.4 mmol), and H2O (10.8 mL, d=1.0,
0.6 mmol)/dioxane (1 mL) sequentially under an Ar atmos-
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3903

UPDATES
Can Zhu and Shengming Ma
phere. After the mixture was stirred at 858C for 14 h, the re-
action was complete as monitored by TLC. Et2O (20 mL)
was added to the resulting mixture. The mixture was then
filtered to remove the inorganic salts through a short
column of silica gel (2 cm, 100–200 mesh, eluent: 3ꢂ20 mL
of Et2O). After evaporation of the solvent, purification via
column chromatography on silica gel (eluent: petroleum
ether/ethyl ether=30/1 then petroleum ether/dichlorome-
thane=1/1) and then recrystallization from dichloromethane
and petroleum ether (1/40) afforded the desired product 3o
as a solid; yield: 78.5 mg (87%); mp 229–2328C (petroleum
ether/dichloromethane). 1H NMR (400 MHz, CDCl3): d=
8.20 (d, J=8.4 Hz, 1H, Ar-H), 7.70 (d, J=8.4 Hz, 2H, Ar-
H), 7.22–7.09 (m, 7H, Ar-H), 7.05–6.95 (m, 2H, Ar-H), 6.92
(t, J=7.4 Hz, 1H, Ar-H), 6.64 (d, J=8.0 Hz, 1H, CH=),
6.52–6.41 (m, 1H, CH=), 5.99 (s, 1H, CH=), 2.33 (s, 3H, Ar-
CH3), 2.26 (t, J=11.0 Hz, 1H, one proton of CH2), 1.69 (dd,
J=12.2 Hz, 6.2 Hz, 1H, one proton of CH2), 1.24 (s, 3H,
CH3), 0.98 (s, 3H, CH3); 13C NMR (CDCl3, 100 MHz): d=
144.7, 144.6, 143.3, 136.91, 136.88, 135.6, 133.4, 130.3, 129.9,
129.5, 127.9, 127.3, 126.8, 126.7, 124.3, 123.3, 123.1, 121.6,
121.3, 114.3, 39.5, 38.6, 31.8, 31.5, 21.5; MS (EI): m/z=454
(M+ +1, 0.94), 453 (M+, 1.85), 242 (100); IR (KBr): n=2960,
2863, 1597, 1492, 1469, 1452, 1411, 1369, 1306, 1293, 1230,
1208, 1187, 1174, 1150, 1138, 1117, 1089, 1029 cmꢀ1; anal.
calcd. for C29H27NO2S: C 76.79, H 6.00, N 3.09; found: C
76.56, H 6.08, N 2.82.
used for the next step directly without further purification
and charactization.
To a flame-dried Schlenk tube were added the obtained
crude product/toluene (5 mL), N-ethylmaleimide 11a
(249.6 mg, 2.0 mmol)/toluene (5 mL) sequentially under an
Ar atmosphere. After the mixture was stirred at 1108C for
24 h, the reaction was complete as monitored by TLC. After
evaporation, the mixture was purified by column chroma-
tography on silica gel (eluent: petroleum ether/ethyl ace-
tate=7/1 then petroleum ether/ethyl acetate=5/1) to afford
the desired product 10a as a solid; yield: 493.7 mg (88%);
mp
205–2088C
(petroleum
ether/dichloromethane).
1H NMR (300 MHz, CDCl3): d=8.11 (d, J=7.8 Hz, 1H, Ar-
H), 7.89 (d, J=8.4 Hz, 2H, Ar-H), 7.75 (d, J=8.1 Hz, 1H,
Ar-H), 7.32–7.16 (m, 4H, Ar-H), 4.75–4.68 (m, 1H, CH),
3.20–2.80 (m, 6H, 2ꢂCH2 and 2ꢂCH), 2.53–2.40 (m, 1H,
CH), 2.37 (s, 3H, Ar-CH3), 2.22 (d, J=8.7 Hz, 1H, CH),
1.75–1.48 (m, 3H, CH2 and CH), 1.48–1.30 (m, 2H, CH2),
1.12 (s, 3H, CH3), 1.05 (t, J=6.9 Hz, 3H, CH3), 0.57–0.40
(m, 4H, CH3 and CH), 0.15 (t, J=7.1 Hz, 3H, CH3);
13C NMR (CDCl3, 100 MHz): d=176.6, 176.0, 145.0, 136.1,
135.8, 135.7, 129.7, 127.6, 127.2, 123.4, 123.3, 120.1, 120.0,
114.1, 48.7, 45.1, 44.9, 44.8, 36.3, 36.0, 35.9, 32.82, 32.80, 32.6,
30.2, 25.8, 24.2, 23.3, 21.5, 14.1, 11.9; MS (EI): m/z=559
(M+ +1, 1.26), 558 (M+, 3.09), 84 (100); IR (KBr): n=2952,
2927, 2862, 1770, 1698, 1598, 1444, 1403, 1374, 1350, 1227,
1188, 1178, 1155, 1133, 1090, 1027 cmꢀ1; anal. calcd. for
C33H38N2O4S: C 70.94, H 6.86, N 5.01; found: C 70.95, H
7.00, N 4.86.
Synthesis of 10 via Palladium-Catalyzed Cross-
Coupling Reaction and Cyclization of 5 with 6 and
the Subsequent Thermal Reaction with Dienophiles
11
Synthesis of 10c: Following the procedure for the prepa-
ration of 10a, the reaction of 5a (437.9 mg, 1.0 mmol),
Pd(PPh3)4 (57.4 mg, 0.050 mmol), K3PO4 (636.9 mg,
3.0 mmol)/dioxane (5 mL), 6d (366.0 mg, 2.0 mmol), and
H2O (54.0 mL, d=1.0 gmLꢀ1, 54.0 mg, 3.0 mmol)/dioxane
(5 mL) afforded the crude product after filtration.
The reaction of the obtained crude product/toluene
(5 mL), N-ethylmaleimide 11a (251.9 mg, 2.0 mmol)/toluene
(5 mL) afforded the desired product 10c as a solid (eluent:
petroleum ether/ethyl acetate=7/1); yield: 369.7 mg (68%);
Synthesis of 10a (Typical Procedure I): To a flame-dried
Schlenk tube were added 5a (438.8 mg, 1.0 mmol),
Pd(PPh3)4 (57.9 mg, 0.050 mmol), K3PO4 (636.6 mg,
3.0 mmol)/dioxane (5 mL), 6b (396.4 mg, 2.0 mmol), and
H2O (54.0 mL, d=1.0 gmLꢀ1, 54.0 mg, 3.0 mmol)/dioxane
(5 mL) sequentially under an Ar atmosphere. After the mix-
ture was stirred at 858C for 12 h, the reaction was complete
as monitored by TLC. Et2O (15 mL) was added to the re-
sulting mixture. The reaction mixture was then filtered to
remove the inorganic salts through a short column of silica
gel (3 cm, 100–200 mesh, petroleum ether as the eluent
before adding the sample, eluent: 3ꢂ15 mL of Et2O). Evap-
oration of the solvent afforded the crude product, which was
mp
100–1038C
(petroleum
ether/dichloromethane).
1H NMR (400 MHz, CDCl3): d=8.12 (d, J=7.6 Hz, 1H, Ar-
H), 7.89 (d, J=8.4 Hz, 2H, Ar-H), 7.73–7.68 (m, 1H, Ar-H),
7.30–7.20 (m, 4H, Ar-H), 6.11–5.98 (m, 1H, =CH), 5.38 (dd,
J=17.2 Hz, 1.6 Hz, 1H, one proton of =CH2), 5.30 (dd, J=
3904
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Adv. Synth. Catal. 2014, 356, 3897 – 3911

UPDATES
Studies on Palladium-Catalyzed Synthesis of Dihydrocycloocta[b]indoles
ethyl acetate=5/1); yield: 407.4 mg (66%); mp 138–1408C
(petroleum ether/dichloromethane). 1H NMR (400 MHz,
CDCl3): d=8.13 (d, J=7.6 Hz, 1H, Ar-H), 7.90 (d, J=
8.8 Hz, 2H, Ar-H), 7.74 (d, J=6.8 Hz, 1H, Ar-H), 7.42 (d,
J=7.6 Hz, 2H, Ar-H), 7.38–7.20 (m, 7H, Ar-H), 6.73 (d, J=
15.6 Hz, 1H, =CH), 6.49–6.38 (m, 1H, =CH), 4.73 (dd, J=
4.0 Hz, 2.8 Hz, 1H, CH), 4.11 (dd, J=13.2 Hz, 7.6 Hz, 1H,
one proton of CH2), 3.33 (dd, J=13.4 Hz, 7.8 Hz, 1H, one
proton of CH2), 3.12–2.93 (m, 2H, NCH2), 2.93–2.79 (m,
3H, 3ꢂCH), 2.37 (s, 3H, Ar-CH3), 2.22 (d, J=8.8 Hz, 1H,
CH), 1.44 (dd, J=11.6 Hz, 8.4 Hz, 1H, one proton of CH2),
1.15 (s, 3H, CH3), 0.60 (s, 3H, CH3), 0.53 (dd, J=12.0 Hz,
7.6 Hz, 1H, CH), 0.18 (t, J=7.2 Hz, 3H, CH3); 13C NMR
(CDCl3, 100 MHz): d=176.5, 176.2, 145.0, 137.2, 136.1,
135.9, 135.8, 134.7, 129.8, 128.5, 127.4, 127.3, 127.2, 126.1,
125.0, 123.6, 123.5, 119.8, 119.6, 114.2, 48.9, 45.8, 45.1, 44.7,
36.34, 36.30, 35.9, 33.8, 32.9, 32.7, 32.6, 24.4, 21.5, 12.0; MS
(ESI): m/z=641 (M+Na+), 619 (M+H+); IR (KBr): n=
3055, 3026, 2973, 2949, 2926, 2862, 1769, 1697, 1597, 1495,
1442, 1403, 1376, 1368, 1349, 1265, 1228, 1188, 1177, 1152,
1134, 1125, 1091, 1028 cmꢀ1; anal. calcd. for C38H38N2O4S: C
73.76, H 6.19, N 4.53; found: C 73.65, H 6.20, N 4.40.
10.0 Hz, 2.0 Hz, 1H, one proton of =CH2), 4.73 (dd, J=
4.2 Hz, 3.0 Hz, 1H, CH), 3.97 (dd, J=13.0 Hz, 7.8 Hz, 1H,
one proton of CH2), 3.18 (dd, J=13.2 Hz, 7.6 Hz, 1H, one
proton of CH2), 3.10–2.91 (m, 3H, NCH2 and CH), 2.91–
2.81 (m, 2H, 2ꢂCH), 2.37 (s, 3H, Ar-CH3), 2.19 (d, J=
8.8 Hz, 1H, CH), 1.43 (ddd, J=12.4 Hz, 8.4 Hz, 1.4 Hz, 1H,
one proton of CH2), 1.11 (s, 3H, CH3), 0.57–0.45 (m, 4H,
CH3 and one proton of CH2), 0.16 (t, J=7.2 Hz, 3H, CH3);
13C NMR (CDCl3, 100 MHz): d=176.5, 176.1, 145.0, 136.0,
135.82, 135.77, 133.3, 129.7, 127.4, 127.2, 123.5, 123.4, 119.7,
119.5, 114.1, 48.6, 45.1, 44.9, 44.6, 36.3, 35.8, 34.7, 32.8, 32.6,
32.5, 24.2, 21.5, 11.9; MS (EI): m/z=543 (M+ +1, 3.70), 542
(M+, 11.91), 361 (100); IR (KBr): n=2949, 2926, 1769, 1697,
1597, 1442, 1402, 1376, 1367, 1349, 1227, 1188, 1177, 1151,
1134, 1091, 1028 cmꢀ1; anal. calcd. for C32H34N2O4S: C 70.82,
H 6.31, N 5.16; found: C 70.67, H 6.33, N 4.88.
Synthesis of 10e: Following the procedure for the prepa-
ration of 10a, the reaction of 5a (438.0 mg, 1.0 mmol),
Pd(PPh3)4 (58.0 mg, 0.050 mmol), K3PO4 (637.8 mg,
3.0 mmol)/dioxane (5 mL), 6f (372.5 mg, 2.0 mmol), and
H2O (54.0 mL, d=1.0 gmLꢀ1, 54.0 mg, 3.0 mmol)/dioxane
(5 mL) afforded the crude product after filtration.
Synthesis of 10d: Following the procedure for the prepa-
ration of 10a, the reaction of 5a (436.8 mg, 1.0 mmol),
Pd(PPh3)4 (57.9 mg, 0.050 mmol), K3PO4 (636.3 mg,
3.0 mmol)/dioxane (5 mL), 6e (516.8 mg, 2.0 mmol), and
H2O (54.0 mL, d=1.0 gmLꢀ1, 54.0 mg, 3.0 mmol)/dioxane
(5 mL) afforded the crude product after filtration.
The reaction of the obtained crude product/toluene
(5 mL), N-ethylmaleimide 11a (250.9 mg, 2.0 mmol)/toluene
(5 mL) afforded the desired product 10d as a solid (eluent:
petroleum ether/ethyl acetate=7/1 then petroleum ether/
The reaction of the obtained crude product/toluene
(5 mL), N-ethylmaleimide 11a (250.8 mg, 2.0 mmol)/toluene
(5 mL) afforded the desired product 10e as a solid (eluent:
petroleum ether/ethyl acetate=5/1); yield: 490.5 mg (90%);
mp
203–2068C
(petroleum
ether/dichloromethane).
1H NMR (300 MHz, CDCl3): d=8.12 (d, J=7.5 Hz, 1H, Ar-
H), 7.89 (d, J=8.1 Hz, 2H, Ar-H), 7.47 (d, J=7.5 Hz, 1H,
Ar-H), 7.33–7.18 (m, 4H, Ar-H), 4.96 (d, J=9.0 Hz, 1H,
one proton of OCH2), 4.78–4.68 (m, 1H, CH), 4.29 (d, J=
8.7 Hz, 1H, one proton of OCH2), 3.58 (s, 3H, OCH3), 3.15
(d, J=7.8 Hz, 1H, CH), 3.10–2.80 (m, 4H, NCH2 and 2ꢂ
CH), 2.45 (d, J=8.7 Hz, 1H, CH), 2.37 (s, 3H, Ar-CH3),
1.42 (t, J=9.8 Hz, 1H, one proton of CH2), 1.12 (s, 3H,
CH3), 0.56–0.42 (m, 4H, one proton of CH2 and CH3), 0.17
Adv. Synth. Catal. 2014, 356, 3897 – 3911
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UPDATES
Can Zhu and Shengming Ma
(t, J=7.2 Hz, 3H, CH3); 13C NMR (CDCl3, 100 MHz): d=
176.6, 176.2, 145.0, 136.0, 135.9, 135.7, 129.7, 127.2, 126.8,
123.6, 123.5, 119.6, 117.9, 114.2, 70.5, 59.3, 47.2, 46.1, 44.5,
44.2, 36.5, 36.2, 35.8, 33.0, 32.7, 32.6, 24.0, 21.5, 11.9; MS
(ESI): m/z=547 (M+H+), 569 (M+Na+); IR (KBr): n=
3053, 2976, 2949, 2814, 1770, 1698, 1598, 1494, 1476, 1445,
1403, 1377, 1351, 1308, 1294, 1265, 1227, 1188, 1177, 1146,
1135, 1125, 1092, 1059, 1028, 1013 cmꢀ1; anal. calcd. for
C31H34N2O5S: C 68.11, H 6.27, N 5.12; found: C 68.09, H
6.47, N 4.97.
Synthesis of 10f: Following the procedure for the prepa-
ration of 10a, the reaction of 5a (437.8 mg, 1.0 mmol),
Pd(PPh3)4 (58.1 mg, 0.050 mmol), K3PO4 (636.1 mg,
3.0 mmol)/dioxane (5 mL), 6g (341.5 mg, 2.0 mmol), and
H2O (54.0 mL, d=1.0 gmLꢀ1, 54.0 mg, 3.0 mmol)/dioxane
(5 mL) afforded the crude product after filtration.
The reaction of the obtained crude product/toluene
(5 mL), N-ethylmaleimide 11a (252.0 mg, 2.0 mmol)/toluene
(5 mL) afforded the desired product 10g as a solid (eluent:
petroleum ether/ethyl acetate=5/1 then petroleum ether/
ethyl acetate=3/1); yield: 388.1 mg (73%); mp 256–2588C
(petroleum ether/dichloromethane). 1H NMR (400 MHz,
CDCl3): d=8.10–8.04 (m, 1H, Ar-H), 7.89 (d, J=8.4 Hz,
2H, Ar-H), 7.54–7.48 (m, 1H, Ar-H), 7.30–7.23 (m, 4H, Ar-
H), 4.68 (t, J=3.8 Hz, 1H, CH), 4.00 (t, J=3.2 Hz, 1H,
CH), 3.08–2.88 (m, 5H, NCH2 and 3ꢂCH), 2.41 (d, J=
8.4 Hz, 1H, CH), 2.36 (s, 3H, Ar-CH3), 1.65–1.48 (m, 3H,
CH2 and one proton of CH2), 1.48–1.37 (m, 1H, one proton
of CH2), 1.37–1.19 (m, 3H, CH2 and one proton of CH2),
1.17–1.05 (m, 1H, one proton of CH2), 0.54 (dd, J=12.4 Hz,
6.8 Hz, 1H, one proton of CH2), 0.40–0.31 (m, 1H, one
proton of CH2), 0.07 (t, J=7.2 Hz, 3H, CH3); 13C NMR
(CDCl3, 100 MHz): d=177.1, 176.7, 144.9, 136.1, 135.9,
135.8, 129.7, 127.6, 127.1, 123.8, 123.5, 118.8, 118.1, 114.0,
46.7, 45.5, 44.7, 44.3, 42.8, 36.55, 36.50, 33.54, 33.50, 32.7,
32.1, 23.4, 22.6, 21.4, 11.7; MS (EI): m/z=529 (M+ +1, 5.98),
528 (M+, 16.16), 166 (100); IR (KBr): n=3054, 2949, 2869,
1773, 1705, 1597, 1494, 1481, 1448, 1403, 1378, 1292, 1269,
1226, 1177, 1145, 1092, 1022, 1009 cmꢀ1; anal. calcd. for
C31H32N2O4S: C 70.43, H 6.10, N 5.30; found: C 70.27, H
5.98, N 5.23.
Gram-Scale Synthesis of 10g: To a flame-dried Schlenk
tube were added 5a (1.0070 g, 2.3 mmol), Pd(PPh3)4
(132.7 mg, 0.115 mmol), K3PO4 (1.4650 g, 6.9 mmol)/dioxane
(12 mL), 6h (773.9 mg, 4.6 mmol), and H2O (124.2 mL, d=
1.0 gmLꢀ1, 124.2 mg, 6.9 mmol)/dioxane (11 mL) sequential-
ly under an Ar atmosphere. After the mixture was stirred at
858C for 12 h, the reaction was complete as monitored by
TLC. Et2O (30 mL) was added to the resulting mixture. The
reaction mixture was then filtered to remove the inorganic
salts through a short column of silica gel (3 cm, 100–200
mesh, eluent: 3ꢂ15 mL of Et2O). Evaporation of the solvent
afforded the crude product which was used for the next step
directly without further purification and charactization.
To a flame-dried Schlenk tube were added the obtained
crude product/toluene (12 mL), N-ethylmaleimide 11a
(575.7 mg, 4.6 mmol)/toluene (11 mL) sequentially under an
H2O (54.0 mL, d=1.0 gmLꢀ1, 54.0 mg, 3.0 mmol)/dioxane
(5 mL) afforded the crude product after filtration.
The reaction of the obtained crude product/toluene
(5 mL), N-ethylmaleimide 11a (250.8 mg, 2.0 mmol)/toluene
(5 mL) afforded the desired product 10f as a solid (eluent:
petroleum ether/ethyl acetate=5/1); yield: 430.0 mg (81%);
mp
193–1968C
(petroleum
ether/dichloromethane).
1H NMR (300 MHz, CDCl3): d=8.13–8.07 (m, 1H, Ar-H),
7.86 (d, J=8.4 Hz, 2H, Ar-H), 7.55–7.46 (m, 1H, Ar-H),
7.34–7.19 (m, 4H, Ar-H), 4.67 (t, J=3.8 Hz, 1H, CH), 4.06
(t, J=2.7 Hz, 1H, CH), 3.10–2.80 (m, 5H, NCH2 and 3ꢂ
CH), 2.36 (s, 3H, Ar-CH3), 2.17 (d, J=8.1 Hz, 1H, CH),
1.50–1.33 (m, 3H, CH2 and CH), 0.98–0.82 (m, 1H, one
proton of CH2), 0.77–0.58 (m, 4H, CH3 and one proton of
CH2), 0.47–0.26 (m, 4H, CH3 and one proton of CH2), 0.06
(t, J=7.2 Hz, 3H, CH3); 13C NMR (CDCl3, 100 MHz): d=
177.1, 176.7, 145.0, 136.2, 136.05, 135.99, 129.7, 127.6, 127.1,
123.9, 123.6, 119.3, 118.0, 114.2, 46.3, 45.0, 44.7, 41.7, 36.6,
33.8, 33.7, 32.8, 31.7, 31.5, 23.4, 21.5, 11.7, 7.8, 7.5; MS (EI):
m/z=531 (M+ +1, 4.80), 530 (M+, 12.26), 166 (100); IR
(KBr): n=2961, 2935, 2875, 1773, 1699, 1597, 1447, 1401,
1372, 1348, 1225, 1187, 1177, 1135, 1121, 1090, 1022 cmꢀ1
;
anal. calcd. for C31H34N2O4S: C 70.16, H 6.46, N 5.28; found:
C 70.14, H 6.44, N 5.22.
Synthesis of 10g: Following the procedure for the prepa-
ration of 10a, the reaction of 5a (438.8 mg, 1.0 mmol),
Pd(PPh3)4 (57.9 mg, 0.050 mmol), K3PO4 (634.5 mg,
3.0 mmol)/dioxane (5 mL), 6h (336.0 mg, 2.0 mmol), and
3906
asc.wiley-vch.de
ꢁ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2014, 356, 3897 – 3911

UPDATES
Studies on Palladium-Catalyzed Synthesis of Dihydrocycloocta[b]indoles
The reaction of the obtained crude product/toluene
(5 mL), N-ethylmaleimide 11a (250.7 mg, 2.0 mmol)/toluene
(5 mL) afforded the desired product 10h as a solid (eluent:
petroleum ether/ethyl acetate=5/1 then petroleum ether/
ethyl acetate=3/1); yield: 420.5 mg (77%); mp 217–2198C
(petroleum ether/ethyl acetate). 1H NMR (400 MHz,
CDCl3): d=8.12–8.04 (m, 1H, Ar-H), 7.87 (d, J=8.4 Hz,
2H, Ar-H), 7.53–7.46 (m, 1H, Ar-H), 7.32–7.22 (m, 4H, Ar-
H), 4.69 (t, J=3.6 Hz, 1H, CH), 4.09 (t, J=2.8 Hz, 1H,
CH), 3.10–2.85 (m, 5H, NCH2 and 3ꢂCH), 2.36 (s, 3H, Ar-
CH3), 2.18 (d, J=8.4 Hz, 1H, CH), 1.55–1.22 (m, 6H, 3ꢂ
CH2), 1.22–1.08 (m, 2H, CH2), 1.00–0.81 (m, 2H, CH2),
0.67–0.57 (m, 1H, one proton of CH2), 0.39 (dd, J=12.4 Hz,
7.2 Hz, 1H, one proton of CH2), 0.05 (t, J=7.2 Hz, 3H,
CH3); 13C NMR (CDCl3, 100 MHz): d=177.0, 176.6, 144.9,
136.1, 136.0, 135.9, 129.7, 127.5, 127.1, 123.8, 123.6, 119.1,
118.0, 114.1, 47.0, 44.8, 44.7, 40.5, 39.0, 36.6, 34.6, 33.5, 32.7,
32.2, 31.3, 25.8, 23.0, 22.4, 21.4, 11.7; MS (EI): m/z=543
(M+ + 1, 5.93), 542 (M+, 16.39), 166 (100); IR (KBr): n=
3054, 2922, 2850, 1773, 1701, 1597, 1494, 1481, 1448, 1402,
1376, 1266, 1225, 1187, 1177, 1142, 1121, 1090, 1023,
1009 cmꢀ1; anal. calcd. for C32H34N2O4S: C 70.82, H 6.31, N
5.16; found: C 71.02, H 6.59, N 4.86.
Ar atmosphere. After the mixture was stirred at 1108C for
24 h, the reaction was complete as monitored by TLC. After
evaporation, the mixture was purified by column chroma-
tography on silica gel (eluent: petroleum ether/ethyl ace-
tate=5/1) to afford the desired product 10g as a solid; yield:
827.1 mg (68%); mp 256–2588C (petroleum ether/dichloro-
methane). 1H NMR (400 MHz, CDCl3): d=8.12–8.04 (m,
1H, Ar-H), 7.89 (d, J=8.0 Hz, 2H, Ar-H), 7.55–7.47 (m,
1H, Ar-H), 7.32–7.21 (m, 4H, Ar-H), 4.69 (t, J=3.4 Hz, 1H,
CH), 4.01 (t, J=2.4 Hz, 1H, CH), 3.08–2.86 (m, 5H, NCH2
and 3ꢂCH), 2.41 (d, J=7.6 Hz, 1H, CH), 2.36 (s, 3H, Ar-
CH3), 1.65–1.48 (m, 3H, CH2 and one proton of CH2), 1.48–
1.37 (m, 1H, one proton of CH2), 1.37–1.18 (m, 3H, CH2
and one proton of CH2), 1.18–1.04 (m, 1H, one proton of
CH2), 0.53 (dd, J=12.4 Hz, 6.8 Hz, 1H, one proton of CH2),
0.40–0.29 (m, 1H, one proton of CH2), 0.07 (t, J=7.2 Hz,
3H, CH3); 13C NMR (CDCl3, 100 MHz): d=177.1, 176.7,
144.9, 136.0, 135.84, 135.78, 129.7, 127.5, 127.1, 123.7, 123.5,
118.7, 118.1, 114.0, 46.6, 45.5, 44.6, 44.3, 42.7, 36.52, 36.46,
33.50, 33.46, 32.7, 32.0, 23.4, 22.6, 21.4, 11.7.
Synthesis of 10i: Following the procedure for the prepa-
ration of 10a, the reaction of 5a (438.2 mg, 1.0 mmol),
Pd(PPh3)4 (57.6 mg, 0.050 mmol), K3PO4 (634.5 mg,
Synthesis of 10h: Following the procedure for the prepa-
ration of 10a, the reaction of 5a (438.0 mg, 1.0 mmol),
Pd(PPh3)4 (57.0 mg, 0.050 mmol), K3PO4 (635.0 mg,
3.0 mmol)/dioxane (5 mL), 6i (365.1 mg, 2.0 mmol), and
H2O (54.0 mL, d=1.0 gmLꢀ1, 54.0 mg, 3.0 mmol)/dioxane
(5 mL) afforded the crude product after filtration.
3.0 mmol)/dioxane (5 mL), 6j (392.9 mg, 2.0 mmol), and
H2O (54.0 mL, d=1.0 gmLꢀ1, 54.0 mg, 3.0 mmol)/dioxane
(5 mL) afforded the crude product after filtration.
The reaction of the obtained crude product/toluene
(5 mL), N-ethylmaleimide 11a (251.9 mg, 2.0 mmol)/toluene
(5 mL) afforded the desired product 10i as a solid (eluent:
petroleum ether/ethyl acetate=5/1 then petroleum ether/
ethyl acetate=3/1); yield: 452.0 mg (81%); mp 81–848C
(petroleum ether/dichloromethane). 1H NMR (400 MHz,
CDCl3): d=8.13 (d, J=7.6 Hz, 1H, Ar-H), 7.86 (d, J=
8.4 Hz, 2H, Ar-H), 7.67 (d, J=7.2 Hz, 1H, Ar-H), 7.31–7.18
(m, 4H, Ar-H), 4.71 (t, J=3.6 Hz, 1H, CH), 3.10–2.89 (m,
3H, NCH2 and CH), 2.85–2.76 (m, 1H, CH), 2.51 (d, J=
7.2 Hz, 1H, CH), 2.36 (s, 3H, Ar-CH3), 2.11 (s, 3H, CH3),
1.79 (d, J=8.8 Hz, 1H, CH), 1.64 (d, J=12.4 Hz, 1H, one
proton of CH2), 1.54 (dd, J=12.0 Hz, 8.8 Hz, 1H, one
Adv. Synth. Catal. 2014, 356, 3897 – 3911
ꢁ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
3907

UPDATES
Can Zhu and Shengming Ma
proton of CH2), 1.44 (d, J=12.4 Hz, 1H, one proton of
CH2), 1.37 (d, J=12.8 Hz, 1H, one proton of CH2), 1.33–
1.22 (m, 1H, one proton of CH2), 1.22–0.87 (m, 4H, 2ꢂ
CH2), 0.82 (d, J=12.4 Hz, 1H, one proton of CH2), 0.43–
0.27 (m, 2H, CH2), 0.10 (t, J=7.0 Hz, 3H, CH3); 13C NMR
(CDCl3, 100 MHz): d=176.4, 176.2, 144.9, 136.3, 136.1,
135.4, 129.7, 127.5, 127.1, 123.5, 123.4, 120.5, 119.6, 114.2,
55.9, 50.0, 45.1, 41.4, 41.0, 40.7, 36.4, 33.6, 32.9, 32.6, 32.4,
26.0, 22.4, 21.8, 21.5, 20.3, 11.8; MS (EI): m/z=557 (M+ +1,
1.85), 556 (M+, 4.85), 180 (100); IR (KBr): n=2974, 2925,
2852, 1770, 1697, 1597, 1444, 1402, 1377, 1348, 1227, 1188,
1177, 1150, 1135, 1123, 1091, 1063 cmꢀ1; anal. calcd. for
C33H36N2O4S: C 71.19, H 6.52, N 5.03; found: C 71.20, H
6.66, N 4.75.
calcd. for C33H36N2O4S: C 71.19, H 6.52, N 5.03; found: C
71.26, H 6.65, N 4.80.
Synthesis of 10m: Following the procedure for the prepa-
ration of 10a, the reaction of 5b (455.3 mg, 1.0 mmol),
Pd(PPh3)4 (57.5 mg, 0.050 mmol), K3PO4 (636.9 mg,
Synthesis of 10j: Following the procedure for the prepa-
ration of 10a, the reaction of 5a (437.5 mg, 1.0 mmol),
Pd(PPh3)4 (58.2 mg, 0.050 mmol), K3PO4 (636.9 mg,
3.0 mmol)/dioxane (5 mL), 6h (336.9 mg, 2.0 mmol), and
H2O (54.0 mL, d=1.0 gmLꢀ1, 54.0 mg, 3.0 mmol)/dioxane
(5 mL) afforded the crude product after filtration.
The reaction of the obtained crude product/toluene
(5 mL), N-ethylmaleimide 11a (249.7 mg, 2.0 mmol)/toluene
(5 mL) afforded the desired product 10m as a solid (eluent:
petroleum ether/ethyl acetate=5/1 then petroleum ether/
ethyl acetate=3/1); yield: 361.2 mg (66%); mp 179–1818C
(petroleum ether/ethyl acetate). 1H NMR (400 MHz,
CDCl3): d=8.02 (dd, J=9.0 Hz, 4.2 Hz, 1H, Ar-H), 7.86 (d,
J=8.8 Hz, 2H, Ar-H), 7.28 (d, J=8.0 Hz, 2H, Ar-H), 7.16
(dd, J=8.8 Hz, 2.4 Hz, 1H, Ar-H), 7.01 (td, J=9.0 Hz,
2.7 Hz, 1H, Ar-H), 4.66 (dd, J=4.8 Hz, 3.2 Hz, 1H, CH),
3.94 (d, J=3.0 Hz, 1H, CH), 3.10–2.87 (m, 5H, NCH2 and
3ꢂCH), 2.43–2.35 (m, 4H, CH3 and CH), 1.65–1.07 (m, 8H,
4ꢂCH2), 0.49 (dd, J=12.6 Hz, 6.6 Hz, 1H, one proton of
CH2), 0.40–0.32 (m, 1H, one proton of CH2), 0.12 (t, J=
7.2 Hz, 3H, CH3); 13C NMR (CDCl3, 100 MHz): d=177.0,
176.6, 159.7 (d, J=239.8 Hz), 145.2, 137.9, 135.9, 132.1 (d,
J=0.9 Hz), 129.8, 128.6 (d, J=9.9 Hz), 127.2, 118.6 (d, J=
4.0 Hz), 115.0 (d, J=9.7 Hz), 111.7 (d, J=25.7 Hz), 103.9 (d,
J=23.9 Hz), 46.6, 45.5, 44.6, 44.3, 42.8, 36.7, 36.6, 33.58,
33.56, 32.8, 32.1, 23.4, 22.7, 21.5, 11.8; 19F NMR (CDCl3,
376 MHz): d=ꢀ119.6; MS (EI): m/z=547 (M+ +1, 14.67),
546 (M+, 41.20), 339 (100); IR (KBr): n=2951, 2869, 1773,
1701, 1617, 1596, 1494, 1452, 1402, 1377, 1365, 1349, 1291,
1226, 1186, 1174, 1145, 1133, 1091 cmꢀ1; anal. calcd. for
C31H31FN2O4S: C 68.11, H 5.72, N 5.12; found: C 68.04, H
5.86, N 4.90.
3.0 mmol)/dioxane (5 mL), 6k (393.0 mg, 2.0 mmol), and
H2O (54.0 mL, d=1.0 gmLꢀ1, 54.0 mg, 3.0 mmol)/dioxane
(5 mL) afforded the crude product after filtration.
The reaction of the obtained crude product/toluene
(5 mL), N-ethylmaleimide 11a (251.2 mg, 2.0 mmol)/toluene
(5 mL) afforded the desired product 10j as a solid (eluent:
petroleum ether/ethyl acetate=7/1 then petroleum ether/
ethyl acetate=5/1); yield: 410.0 mg (74%); mp 101–1048C
(petroleum ether/ethyl acetate). 1H NMR (400 MHz,
CDCl3): d=8.12–8.06 (m, 1H, Ar-H), 7.86 (d, J=8.4 Hz,
2H, Ar-H), 7.54–7.48 (m, 1H, Ar-H), 7.31–7.22 (m, 4H, Ar-
H), 4.67 (dd, J=4.4 Hz, 3.2 Hz, 1H, CH), 4.08 (t, J=3.2 Hz,
1H, CH), 3.09–2.85 (m, 5H, NCH2 and 3ꢂCH), 2.36 (s, 3H,
Ar-CH3), 2.20 (d, J=8.8 Hz, 1H, CH), 1.73–1.64 (m, 1H,
one proton of CH2), 1.56–1.07 (m, 10H, 5ꢂCH2), 1.04–0.93
(m, 1H, one proton of CH2), 0.80–0.70 (m, 1H, one proton
of CH2), 0.39 (dd, J=12.4 Hz, 7.2 Hz, 1H, one proton of
CH2), 0.07 (t, J=7.2 Hz, 3H, CH3); 13C NMR (CDCl3,
100 MHz): d=177.1, 176.7, 144.9, 136.2, 136.1, 135.9, 129.7,
127.6, 127.1, 123.8, 123.6, 119.0, 118.0, 114.1, 47.6, 44.8, 44.7,
44.1, 41.8, 36.6, 36.5, 34.9, 33.6, 32.8, 31.9, 28.0, 27.6, 22.9,
22.7, 21.5, 11.7; MS (ESI): m/z=579 (M+Na+), 574 (M+
Synthesis of 10b (Typical Procedure II): To a flame-dried
Schlenk tube were added 5a (437.6 mg, 1.0 mmol),
Pd(PPh3)4 (57.8 mg, 0.050 mmol), K3PO4 (635.7 mg,
3.0 mmol)/dioxane (5 mL), and 6c (285.6 mg, 2.0 mmol)/di-
oxane (5 mL) sequentially under an Ar atmosphere. After
the mixture was stirred at 858C for 12 h, the reaction was
complete as monitored by TLC. Et2O (15 mL) was added to
the resulting mixture. The reaction mixture was then filtered
+
NH4 ), 557 (M + H+); IR (KBr): n=3053, 2924, 2852, 1773,
1699, 1597, 1494, 1480, 1447, 1401, 1372, 1348, 1271, 1225,
1187, 1176, 1162, 1135, 1121, 1090, 1021, 1010 cmꢀ1; anal.
3908
asc.wiley-vch.de
ꢁ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2014, 356, 3897 – 3911

UPDATES
Studies on Palladium-Catalyzed Synthesis of Dihydrocycloocta[b]indoles
(d, J=8.4 Hz, 2H, Ar-H), 7.59–7.54 (m, 1H, Ar-H), 7.35–
7.25 (m, 2H, Ar-H), 7.18–7.12 (m, 1H, Ar-H), 7.10–7.03 (m,
2H, Ar-H), 6.95 (d, J=8.4 Hz, 2H, Ar-H), 6.25–6.19 (m,
2H, Ar-H), 4.75 (dd, J=4.6 Hz, 3.0 Hz, 1H, CH), 4.11 (t,
J=3.0 Hz, 1H, CH), 3.15 (dd, J=7.8 Hz, 3.0 Hz, 1H, CH),
3.08 (dd, J=7.8 Hz, 3.4 Hz, 1H, CH), 3.06–2.98 (m, 1H,
CH), 2.26–2.18 (m, 4H, Ar-CH3 and CH), 1.56 (ddd, J=
12.0 Hz, 8.4 Hz, 1.6 Hz, 1H, CH), 1.13 (s, 3H, CH3), 0.68
(dd, J=12.2 Hz, 7.4 Hz, 1H, CH), 0.49 (s, 3H, CH3);
13C NMR (CDCl3, 100 MHz): d=176.2, 176.0, 144.7, 136.2,
135.8, 135.7, 131.3, 129.6, 128.5, 127.9, 127.5, 127.0, 126.0,
124.0, 123.7, 118.7, 118.4, 114.0, 47.9, 45.0, 44.9, 36.8, 36.6,
34.8, 33.6, 32.4, 31.8, 23.0, 21.4; MS (EI): m/z=551 (M+ +1,
5.37), 550 (M+, 13.61), 166 (100); IR (KBr): n=3063, 2951,
2926, 2862, 1777, 1716, 1597, 1498, 1481, 1448, 1414, 1387,
1293, 1267, 1242, 1212, 1175, 1148, 1121, 1090, 1064,
1023 cmꢀ1; anal. calcd. for C33H30N2O4S: C 71.98, H 5.49, N
5.09; found: C 71.68, H 5.69, N 4.81.
to remove the inorganic salts through a short column of
silica gel (3 cm, 100–200 mesh, petroleum ether as the
eluent before adding the sample, eluent: 3ꢂ15 mL of Et2O).
Evaporation of the solvent afforded the crude product,
which was used for the next step directly without further pu-
rification and charactization.
To a flame-dried Schlenk tube were added the obtained
crude product/toluene (5 mL), N-ethylmaleimide 11a
(250.5 mg, 2.0 mmol)/toluene (5 mL) sequentially under an
Ar atmosphere. After the mixture was stirred at 1108C for
24 h, the reaction was complete as monitored by TLC. After
evaporation, the mixture was purified by column chroma-
tography on silica gel (eluent: petroleum ether/ethyl ace-
tate=5/1 then petroleum ether/ethyl acetate=3/1 twice) to
afford the desired product 10b as a solid; yield: 319.5 mg
(64%); mp 195–1978C (petroleum ether/dichloromethane).
1H NMR (400 MHz, CDCl3): d=8.11–8.04 (m, 1H, Ar-H),
7.88 (d, J=8.4 Hz, 2H, Ar-H), 7.56–7.48 (m, 1H, Ar-H),
7.32–7.23 (m, 4H, Ar-H), 4.72–4.67 (m, 1H, Ar-CH), 4.01 (t,
J=3.0 Hz, 1H, CH), 3.08–2.86 (m, 5H, NCH2 and 3ꢂCH),
2.37 (s, 3H, Ar-CH3), 2.18 (d, J=8.4 Hz, 1H, CH), 1.50–1.41
(m, 1H, one proton of CH2), 1.10 (s, 3H, CH3), 0.55–0.42
(m, 4H, CH3 and one proton of CH2), 0.09 (t, J=7.2 Hz,
3H, CH3); 13C NMR (CDCl3, 100 MHz): d=177.0, 176.8,
145.0, 136.2, 136.1, 135.8, 129.8, 127.6, 127.2, 123.9, 123.6,
118.7, 118.2, 114.1, 48.1, 44.79, 44.76, 36.7, 36.5, 34.8, 33.1,
32.8, 32.4, 31.7, 22.9, 21.5, 11.8; MS (EI): m/z=503 (M+ +1,
5.93), 502 (M+, 21.21), 166 (100); IR (KBr): n=3054, 2949,
2926, 2863, 1773, 1699, 1597, 1447, 1401, 1371, 1349, 1294,
1268, 1225, 1187, 1176, 1161, 1144, 1121, 1090, 1026,
1010 cmꢀ1; anal. calcd. for C29H30N2O4S: C 69.30, H 6.02, N
5.57; found: C 68.90, H 6.13, N 5.41.
Synthesis of 10l: Following the procedure for the prepa-
ration of 10b, the reaction of 5a (437.6 mg, 1.0 mmol),
Pd(PPh3)4 (57.8 mg, 0.050 mmol), K3PO4 (636.7 mg,
Synthesis of 10k: Following the procedure for the prepa-
ration of 10b, the reaction of 5a (438.7 mg, 1.0 mmol),
Pd(PPh3)4 (57.8 mg, 0.050 mmol), K3PO4 (633.9 mg,
3.0 mmol)/dioxane (5 mL), and 6c (286.0 mg, 2.0 mmol)/di-
oxane (5 mL) afforded the crude product after filtration.
The reaction of the obtained crude product/toluene
(5 mL), N-phenylmaleimide 11b (345.9 mg, 2.0 mmol)/tolu-
ene (5 mL) afforded the desired product 10k as a solid
(eluent: petroleum ether/ethyl acetate=5/1 then petroleum
ether/ethyl acetate=3/1 twice); yield: 373.4 mg (68%); mp
113–1168C (petroleum ether/ethyl acetate). 1H NMR
(400 MHz, CDCl3): d=8.10 (d, J=7.6 Hz, 1H, Ar-H), 7.77
3.0 mmol)/dioxane (5 mL), and 6c (285.0 mg, 2.0 mmol)/di-
oxane (5 mL) afforded the crude product after filtration.
The reaction of the obtained crude product/toluene
(5 mL), maleic anhydride 11c (196.9 mg, 2.0 mmol)/toluene
Adv. Synth. Catal. 2014, 356, 3897 – 3911
ꢁ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
3909

UPDATES
Can Zhu and Shengming Ma
(5 mL) afforded the desired product 10l as a solid (eluent:
petroleum ether/ethyl acetate=5/1); yield: 262.5 mg (55%);
S. Tommasi, A. Umani-Ronchi, J. Am. Chem. Soc.
2006, 128, 1424.
mp
252–2548C
(petroleum
ether/dichloromethane).
[5] For reviews see: a) R. Zimmer, C. U. Dinesh, E. Nan-
danan, F. A. Khan, Chem. Rev. 2000, 100, 3067; b) J. A.
Marshall, Chem. Rev. 2000, 100, 3163; c) X. Lu, C.
Zhang, Z. Xu, Acc. Chem. Res. 2001, 34, 535; d) R. W.
Bates, V. Satcharoen, Chem. Soc. Rev. 2002, 31, 12;
e) S. Ma, Acc. Chem. Res. 2003, 36, 701; f) L.-L. Wei,
H. Xiong, R. P. Hsung, Acc. Chem. Res. 2003, 36, 773;
g) S. Ma, Chem. Rev. 2005, 105, 2829; h) S. Ma, Acc.
Chem. Res. 2009, 42, 1679; i) B. Alcaide, P. Almendros,
C. Aragoncillo, Chem. Soc. Rev. 2010, 39, 783; j) S. Ma,
in: Handbook of Organopalladium Chemistry for Or-
ganic Synthesis, (Ed.: E. Negishi), Wiley, New York,
2002, pp 1491–1523; k) S. Ma, in: Topics in Organome-
tallic Chemistry, (Ed.: J. Tsuji), Springer-Verlag, Heidel-
berg, 2005, Vol. 15, pp 183–210; l) S. Ma, Aldrichimica
Acta 2007, 40, 91; m) M. Jeganmohan, C.-H. Cheng,
Chem. Commun. 2008, 27, 3101; n) A. S. K. Hashmi,
Angew. Chem. 2000, 112, 3737; Angew. Chem. Int. Ed.
2000, 39, 3590; o) L. K. Sydnes, Chem. Rev. 2003, 103,
1133; p) A. Hoffmann-Rçder, N. Krause, Angew.
Chem. 2002, 114, 3057; Angew. Chem. Int. Ed. 2002, 41,
2933; q) C. Aubert, L. Fensterbank, P. Garcia, M. Mal-
acria, A. Simonneau, Chem. Rev. 2011, 111, 1954; r) N.
Krause, C. Winter, Chem. Rev. 2011, 111, 1994; s) F.
Lꢄpez, J. L. MascareÇas, Chem. Eur. J. 2011, 17, 418;
t) P. Rivera-Fuentes, F. Diederich, Angew. Chem. 2012,
124, 2872; Angew. Chem. Int. Ed. 2012, 51, 2818; u) S.
Yu, S. Ma, Angew. Chem. 2012, 124, 3128; Angew.
Chem. Int. Ed. 2012, 51, 3074.
1H NMR (300 MHz, CDCl3): d=8.07 (d, J=7.5 Hz, 1H, Ar-
H), 7.82 (d, J=7.8 Hz, 2H, Ar-H), 7.54 (d, J=6.9 Hz, 1H,
Ar-H), 7.37–7.22 (m, 4H, Ar-H), 4.76 (t, J=3.3 Hz, 1H,
CH), 4.10–4.02 (m, 1H, CH), 3.32–3.20 (m, 2H, 2ꢂCH),
3.02–2.90 (m, 1H, CH), 2.36 (s, 3H, Ar-CH3), 2.15 (d, J=
7.8 Hz, 1H, CH), 1.53–1.42 (m, 1H, CH), 1.09 (s, 3H, CH3),
0.52–0.39 (m, 4H, Ar-CH3 and CH); 13C NMR (CDCl3,
75 MHz): d=171.3, 145.3, 135.9, 135.8, 135.6, 130.0, 127.2,
127.0, 124.4, 123.8, 118.6, 118.4, 114.2, 47.6, 45.9, 45.1, 36.24,
36.17, 34.7, 33.3, 32.2, 31.5, 23.1, 21.6; MS (EI): m/z=476
(M+ +1, 5.76), 475 (M+, 15.47), 166 (100); IR (KBr): n=
3056, 2953, 2927, 2864, 1861, 1836, 1779, 1597, 1494, 1481,
1447, 1415, 1370, 1269, 1232, 1212, 1188, 1176, 1161, 1149,
1122, 1079, 1025, 1008 cmꢀ1; anal. calcd. for C27H25NO5S: C
68.19, H 5.30, N 2.95; found: C 67.99, H 5.25, N 2.74.
Acknowledgements
Financial support from National Basic Research Program
(2011CB808700) and National Natural Science Foundation
of China (21232006). We thank Mr. Shangze Wu in this
group for reproducing the preparation of 10c, 10i and 10l in
Table 1.
[6] a) S. Ma, Z. Gu, J. Am. Chem. Soc. 2006, 128, 4942;
b) Z. Gu, S. Ma, Chem. Eur. J. 2008, 14, 2453.
References
[7] C. Zhu, X. Zhang, X. Lian, S. Ma, Angew. Chem. 2012,
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[8] For reviews of the Suzuki–Miyaura cross-coupling reac-
tion, see: N. Miyaura, A. Suzuki, Chem. Rev. 1995, 95,
2457.
[9] For selected examples, see: a) T. Moriya, N. Miyaura,
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3910
asc.wiley-vch.de
ꢁ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2014, 356, 3897 – 3911

UPDATES
Studies on Palladium-Catalyzed Synthesis of Dihydrocycloocta[b]indoles
Org. Chem. 2008, 73, 5589; e) H. A. Duong, S. Chua,
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graphic Data Centre via www.ccdc.cam.ac.uk/data_re-
quest/cif.
[15] Crystal data for 10i: C33H36N2O4S, MW =556.70, mono-
clinic, space group P21/c, final R indices [I> 2 s(I)],
R1 =0.0440, wR2 =0.1203, R indices (all data), R1 =
[13] Crystal data for 3o: C29H27NO2S, MW =453.58, mono-
clinic, space group P21/n, final R indices [I> 2 s(I)],
R1 =0.0560, wR2 =0.1369, R indices (all data), R1 =
0.0589,
wR2 =0.1314,
a=16.7448(11) ꢆ,
a=908,
b=
b=
0.0675,
wR2 =0.1467,
a=9.9720(12) ꢆ,
b=
14.5622(10) ꢆ,
c=12.1746(8) ꢆ,
10.8277(13) ꢆ, c=22.550(3) ꢆ, a=908, b=101.280(2)o,
g=908, V=2387.8(5) ꢆ3, T=293(2) K, Z=4, reflec-
tions collected/unique: 13928/4688 (R(int)=0.0677),
number of observations [> 2s(I)] 3742; parameter:
302. CCDC 1002893 contains the supplementary crys-
tallographic data for this paper. These data can be ob-
tained free of charge from The Cambridge Crystallo-
graphic Data Centre via www.ccdc.cam.ac.uk/data_re-
quest/cif.
97.4490(10)8, g=908, V=2943.6(3) ꢆ3, T=293(2) K,
Z=4,
reflections
collected/unique:
17456/5772
(R(int)=0.0269), number of observations [> 2s(I)]
4361; parameter: 364. CCDC 1005442 contains the sup-
plementary crystallographic data for this paper. These
data can be obtained free of charge from The
Cambridge
Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
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[14] Crystal data for 10b: C29H30N2O4S, MW =502.61, tri-
clinic, space group P-1, final R indices [I> 2 s(I)], R1 =
0.0434, wR2 =0.1178, R indices (all data), R1 =0.0525,
wR2 =0.1256, a=8.3668(10) ꢆ, b=9.0470(11) ꢆ, c=
16.803(2) ꢆ,
a=83.024(2)8,
b=88.243(2)o,
g=
84.434(3)8, V=1256.3(3) ꢆ3, T=293(2) K, Z=2, reflec-
tions collected/unique: 7689/4932 (R(int)=0.0273),
number of observations [> 2s(I)] 4085; parameter:
330. CCDC 1005441 contains the supplementary crys-
tallographic data for this paper. These data can be ob-
tained free of charge from The Cambridge Crystallo-
[17] a) G. Zhu, E.-i. Negishi, Chem. Eur. J. 2008, 14, 311;
b) C. Roberts, J. C. Walton, J. Chem. Soc. Perkin Trans.
2 1981, 553.
Adv. Synth. Catal. 2014, 356, 3897 – 3911
ꢁ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
3911