Domino o-alkylation and heteroarylation of iodoarenes: One-pot synthesis of benzocyclohepta[b]indoles

Article abstract of DOI:10.1055/s-0032-1316876

A new strategy for the synthesis of benzocyclohepta[b]indoles via a palladium-catalyzed/norbornene-mediated domino intermolecular alkylation/intramolecular heteroarylation of iodoarenes is devised. This approach provides a straightforward route to polycyclic nitrogen-containing heterocycles with fused seven-membered rings from readily accessible precursors. Georg Thieme Verlag Stuttgart New York.

Full text of DOI:10.1055/s-0032-1316876

1094▌
PAPER
pDapoermino o-Alkylation and Heteroarylation of Iodoarenes: One-Pot Synthesis of
Benzocyclohepta[b]indoles
One-Pot Synthesis of Benzocyclohepta[b]indole
a
s
b
a
Farnaz Jafarpour,* Asieh Otaredi-Kashani, Saeideh Behpajooh
a
School of Chemistry, College of Science, University of Tehran, 14155-6455 Tehran, Iran
Fax +98(21)66495291; E-mail: jafarpur@khayam.ut.ac.ir
b
Building and Housing Research Center, 13145-1696 Tehran, Iran
Received: 16.10.2012; Accepted after revision: 05.03.2013
8
acetylenic esters. However, most of these reactions suffer
from multistep sequences, the need for synthesis of com-
plex starting materials, and low functional-group toler-
Abstract: A new strategy for the synthesis of benzocyclohep-
ta[b]indoles via a palladium-catalyzed/norbornene-mediated domi-
no intermolecular alkylation/intramolecular heteroarylation of
iodoarenes is devised. This approach provides a straightforward ance. Thus, a one step, straightforward and generally
route to polycyclic nitrogen-containing heterocycles with fused applicable reaction protocol for the construction of poly-
seven-membered rings from readily accessible precursors.
cyclic indole skeletons would be highly desirable.
Key words: benzocyclohepta[b]indole, domino reaction, norborn-
ene, one-pot synthesis, palladium
We have recently reported an efficient and straightfor-
ward route to highly functionalized benzo[a]carbazoles
9
based on a domino palladium-catalyzed/norbornene-
10
mediated protocol known as Catellani reaction. The proce-
dure involved the reaction of bromoethylindoles and
iodoarenes, so that sequential o-alkylation of iodo-
arene/heteroaryl C–H functionalization led to formation
of two carbon–carbon bonds from two carbon–hydrogen
Among the heterocycles, indole nucleus is a privileged
structural motif present in a wide range of bioactive mol-
ecules and a common core of over 3000 natural products.
1
Most of indole alkaloids show promising biological activ-
ities and some of them are useful as therapeutic agents.
For instance, selectively substituted cyclohepta[b]indoles
have been reported to act as selective estrogen receptor
11
bonds in one pot. A variety of different substituted iodo-
arenes were tolerated and various six-membered poly-
functionalized indoles were constructed. Inspired by the
results, herein we sought to further extend this methodol-
ogy to construct polycyclic indole-fused scaffolds with
larger ring size. We envisioned that regioselective con-
struction of benzocyclohepta[b]indoles could be achieved
by deprotonative arene alkylation followed by seven-
membered ring formation via direct arylation, which has
been scarcely explored in direct arylation reactions. Cata-
lytic C–H functionalization without the requirement for
the wasteful prefunctionalization of one or both of the
coupling partners, regioselective indole C-2 functional-
ization, and construction of more challenging seven-
membered rings are the advantages of this protocol.
2
modulators. Furthermore, indole alkaloids of type A have
3
been proven to possess agonist activity (Figure 1). In-
dolyl bisphosphonates of type B also have shown anti-
4
bone resorptive and antileishmanial activities (Figure 1).
N
N
PO(OEt)2
PO(OEt)2
n
A
R
B
N
N
N
N
The reaction of methyl 4-iodo-3-nitrobenzoate (2a) and
bromoalkylindole 1a (3.0 equiv) was first examined under
various reaction conditions (Table 1). By screening sever-
Figure 1 Indole alkaloids with pharmaceutical activities
According to the variety of the encountered structures and
their biological and pharmaceutical appliance, many stud-
al palladium/ligand catalytic systems, Pd(OAc) /tri-2-fu-
2
rylphosphine (TFP) proved to be the most effective one
ies have been directed toward their synthesis. The tradi- giving the highest yield (Table 1, entries 1–7). Next some
tional Fisher reaction, which converts aryl hydrazones to other different reaction variables were examined includ-
indoles, suffers from harsh reaction conditions such as el- ing solvent (DME, DMF, DMSO, MeCN, toluene), tem-
5
evated temperatures and requisite acids. Some recent ap-
perature (80, 110, and 130 °C), and time (12, 24, and 48
h), and the best results were obtained in MeCN, heating at
proaches include reaction of o-iodoanilines with enolate
6
ions of 1-benzosuberone, palladium-catalyzed intermo-
110 °C for 24 hours (entries 8–10). The effect of base was
7
lecular direct arylation of indoles with aryl chlorides and
CO afforded the desired product in
also examined and Cs2
3
condensation of tetrahydrocyclohepta[b]indol-6(5H)-one higher yield. Replacing Cs CO with other bases such as
2
3
with an α-cyano ester followed by cycloaddition with K CO , K PO , KOAc, and Ag CO , gave inferior reac-
2
3
3
4
2
3
tivity in this reaction. Furthermore, the efficiency of the
reaction was not increased when higher equivalent of base
was used (entry 11). Higher equivalents of norbornene
also did not increase the yield (data not shown in Table 1).
SYNTHESIS 2013, 45, 1094–1098
Advanced online publication: 20.03.2013
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DOI: 10.1055/s-0032-1316876; Art ID: SS-2012-N0819-OP
Georg Thieme Verlag Stuttgart · New York
©

PAPER
One-Pot Synthesis of Benzocyclohepta[b]indoles
1095
Finally, the original equivalents of bromoalkylindole Table 2 Scope of Annulation Reactions of Indolesa
proved to be the best, since lower equivalent of 1a dimin-
ished the yield considerably (entry 12).
EntryIndole Iodoarene Product
Yield
(
%)
Table 1 Screening of Palladium-Catalyzed Annulation of 1aa
I
[
Pd]/L
NO2
base
Br
norbornene
H
1
1a
CO2Me
53
N
solvent
110 °C, 24 h
N
2
CO Me
H
N
Me O2N
CO2Me
1a
Me
Me O2N
3a
3
a
I
CO2Me
2a
I
NO2
2a
NO2
Entry Catalyst
L
Solvent Base
equiv)
1a
Yield
2
3
4
1a
1a
1b
F
45
35
65
N
b
(
(equiv) (%)
Me O2N
F
I
1
2
3
4
5
6
7
8
9
PdCl2
Ph3P DME
DME
Cs CO (2)
3
3
3
3
3
3
3
3
3
41
12
15
50
15
20
58
23
25
3b
2
3
2b
2c
Pd(dba)2
Ph3P
Cs CO (2)
2 3
NO2
NO2
Pd(acac)2 Ph3P DME
Pd(OAc)2 Ph3P DME
Pd(OAc)2 Cy3P DME
Pd(OAc)2 Bu3P DME
Pd(OAc)2 TFP DME
Pd(OAc)2 TFP DMF
Cs CO (2)
2 3
N
Cs CO (2)
2
3
Me O2N
Cs CO (2)
2
3
3
c
I
Cs CO (2)
2
3
MeO
Cs CO (2)
2
3
NO2
N
Cs CO (2)
2
3
Me O2N
NO2
I
Pd(OAc)2 TFP DMSO Cs CO (2)
2
3
3
d
2
2
d
c
62 (53)c
61
10
Pd(OAc)2 TFP MeCN Cs CO (2)
3
2
3
MeO
11
Pd(OAc)2 TFP MeCN Cs CO (3)
3
2
NO2
2
3
5
6
1b
1b
28
23
12
Pd(OAc)2 TFP MeCN Cs CO (2)
46
N
2
3
Me O2N
a
Reaction conditions: iodoarene 2a (1 equiv), bromoalkylindole 1a (3
equiv), catalyst (10 mol%), ligand (22 mol%), base (2 equiv), nor-
bornene (2 equiv) in solvent (0.1 M) were heated in a sealed tube at
3e
I
1
10 °C for 24 h.
GC yields.
Isolated yield in parenthesis.
NO2
MeO
b
c
N
Me O2N
The optimal conditions of 1a (3.0 equiv) and iodoarene 2a
2
e
3f
in the presence of Pd(OAc) (10 mol%), TFP (22 mol%),
2
Cs CO (2.0 equiv), and norbornene (2.0 equiv) at 110 °C
in MeCN in a sealed tube for 24 hours, gave the polycyclic
I
2
3
MeO
product 3a in 53% isolated yield (Table 2, entry 1).
N
7
1b
1c
63
30
Me
Next the scope of the reaction was investigated. Accord-
ingly various iodoarenes and substituted bromoalkylin-
doles were utilized. A variety of iodoarenes with different
functional groups including methyl, nitro, fluoro, ester,
and arene were tolerated, and polycyclic indole-fused
compounds were obtained in moderate to good yields (Ta-
ble 2). The p-fluoro-substituted iodoarene 2b afforded the
corresponding indole 3b in 45% yield (entry 2). Despite
the moderate yield, this reaction provides a polycyclic-
fused indole bearing a halo group, which is a good partner
for further functionalizations. An o-nitro substituent as the
ortho-blocking group afforded 3c in 35% yield (entry 3).
2f
3g
I
NO2
F
8b
NO2
N
O2N
Me
NO2
3
h
2
d
©
Georg Thieme Verlag Stuttgart · New York
Synthesis 2013, 45, 1094–1098

1096
F. Jafarpour et al.
PAPER
a
Table 2 Scope of Annulation Reactions of Indoles (continued)
R
I
Entry Indole Iodoarene Product
Yield
%)
(
R
R
CsX
CsHCO3
PdL2X
XL2Pd
Cs2CO3
I
0
Pd L2
NO2
F
9b
1c
25
VI
I
N
O2N
N
Me
Me
2
e
3i
N
a
Reaction conditions: iodoarene 2 (1 equiv), bromoalkylindole 1 (3
Me
R
equiv), Pd(OAc) (10 mol%), TFP (22 mol%), Cs CO (2 equiv), and
R
2
2
3
norbornene (2 equiv) in MeCN (0.1 M) were heated in a sealed tube
at 110 °C for 24 h.
b
Ph P (22 mol%) was used.
R
3
XL2Pd
II
PdL2X
When o-fluoro- or o-trifluoromethyl-substituted iodo-
arenes were subjected to the cyclization reaction condi-
tions, no desired seven-membered ring annulated indoles
were isolated and only the acyclic o-alkylated products
were observed. We also explored electron-rich aryl io-
dides such as o-iodoanisole. In accord with the results pre-
viously reported, only electron-deficient iodoarenes were
tolerated under the optimized reaction conditions and just
traces of the desired product was obtained (data not shown
in Table 2).
Cs2CO3
V
N
CsX
CsHCO3
Me
R
L
R
X
Pd
L
Pd
L
The generality of this reaction sequence was also demon-
strated for the seven-membered-ring annulated indoles by
varying the substituents on the bromoalkylindole. Both
electron-donating and electron-withdrawing substituents
were tolerated on the bromoalkylindole when reacted with
aryl iodide. Reaction of methoxy-containing bromoalkyl-
indole 1b and 1-iodo-2,4-dinitrobenzene (2d), provided
L
IV
Br
III
N
Me
N
Me
Scheme 1 Possible mechanistic route to annulated indoles
the desired fused indole ring 3d in 65% yield (Table 2, en- In summary, we have developed a straightforward one-pot
try 4). With other o-nitro-substituted iodoarenes also the approach to highly functionalized seven-membered annu-
desired seven membered scaffolds 3e and 3f were ob- lated indole derivatives that are not easily accessible by
tained albeit in lower yields (entries 5 and 6).
conventional methods applying readily accessible starting
materials. The scope of domino palladium-catalyzed/
norbornene-mediated C–H functionalization reaction has
satisfyingly extended to the construction of biologically
interesting cyclohepta[b]indole scaffolds. Further exploi-
tation of the polycyclic indoles towards the synthesis of
biologically active molecules is in progress.
In view of the importance of the highly fused heterocyclic
compounds, the scope of the reaction was extended for the
construction of naphthocyclohepta[b]indole scaffold. In
this regard the reaction of iodonaphthalene 2f and bro-
moalkylindole 1b was investigated and satisfyingly, poly-
cyclic product 3g was obtained in 63% yield (entry 7).
The bromoalkylindole bearing a fluoro substituent 1c also
gave the desired fused heterocyclic compounds 3h and 3i
All reagents and metal catalysts were commercially available and
used as received. MeCN was distilled under N from CaH and im-
mediately used or stored under 4 Å molecular sieves. Annulation re-
2
2
(entries 8, 9). The advantage of this result is that the fluoro
substituent allows for further functionalization of indoles
via other metal-catalyzed coupling methods.
actions were carried out in an oil bath using Microwave vials (2–5
1
13
mL). H and C NMR spectra were recorded at r.t. on a Bruker AC
1
5
00 MHz spectrometer using CDCl as the solvent. H NMR spectra
3
The possible mechanism for o-alkylation of iodoarene is
1
3
are referenced to TMS (0.00 ppm) and C NMR spectra are refer-
enced from the solvent central peak (77.23 ppm). Chemical shifts
are given in ppm. IR is reported as characteristic bands (cm ) in
1
2
based upon the findings of Catellani and likely proceeds
through a Pd(II)/Pd(IV) catalytic cycle (Scheme 1, III and
–1
IV). Intermediate VI arises from the reductive elimination their maximal intensity.
of the Pd(IV) complex followed by norbornene removal.
Methyl 12-Methyl-1-nitro-5,6,7,12-tetrahydrobenzo[6,7]cyclo-
hepta[1,2-b]indole-3-carboxylate (3a); Typical Procedure
via C–H functionalization of indole at C-2 provides the A vial equipped with a stir bar was charged with aryl iodide 2a (61
Finally, intermolecular cross-coupling of indole and arene
annulated indole.
mg, 0.2 mmol, 1.0 equiv), 3-(3-bromopropyl)-1-methyl-1H-indole
(
1a; 161 mg, 0.6 mmol, 3.0 equiv), Pd(OAc) (4 mg, 10 mol%), TFP
2
Synthesis 2013, 45, 1094–1098
© Georg Thieme Verlag Stuttgart · New York

PAPER
10 mg, 22 mol%), Cs CO (130 mg, 0.4 mmol, 2.0 equiv), and nor-
bornene (38 mg, 0.4 mmol, 2.0 equiv). MeCN (2 mL, 0.1 M) was
then added and the vial was capped. The resulting mixture was heat-
ed in an oil bath at 110 °C for 24 h, cooled, and then filtered through
a short plug of silica gel. Removal of the solvent gave a crude mix-
ture, which was purified by flash column chromatography on silica
gel (hexanes–EtOAc gradient); yield: 37 mg (53%); red oil.
One-Pot Synthesis of Benzocyclohepta[b]indoles
1097
(
Anal. Calcd for C H N O : C, 62.12; H, 4.66; N, 11.44. Found: C,
2
3
19 17
3
5
62.33; H, 4.78, N, 11.61.
9
-Methoxy-12-methyl-1-nitro-5,6,7,12-tetrahydrobenzo[6,7]cy-
clohepta[1,2-b]indole (3e)
Yield: 18 mg (28%); red oil.
–
1
IR (KBr): 1345, 1523, 2854, 2924 cm .
–
1
1
IR (KBr): 1362, 1528, 1723, 2926 cm .
H NMR (500 MHz, CDCl ): δ = 2.29–2.33 (m, 2 H), 2.46–2.50 (m
3
1
2 H), 2.70–2.72 (m, 1 H), 3.03–3.05 (m, 1 H), 3.49 (s, 3 H), 3.93 (s,
H NMR (500 MHz, CDCl ): δ = 2.31–2.33 (m, 2 H), 2.40–2.50 (m,
H), 2.75–2.78 (m, 1 H), 3.09–3.10 (m, 1 H), 3.49 (s, 3 H), 4.00 (s,
H), 7.19 (t, J = 7.3 Hz, 1 H), 7.29–7.35 (m, 2 H), 7.67 (d, J = 7.9
3
3
H), 6.97 (dd, J = 8.8, 2.4 Hz, 1 H), 7.12 (d, J = 2.3 Hz, 1 H), 7.25
2
3
(
d, J = 8.8 Hz, 1 H), 7.47 (t, J = 7.8 Hz, 1 H), 7.65 (d, J = 7.0 Hz, 1
H), 7.99 (d, J = 8.2 Hz, 1 H).
Hz, 1 H), 8.27 (d, J = 1.2 Hz, 1 H), 8.61 (d, J = 1.2 Hz, 1 H).
13C NMR (125 MHz, CDCl
): δ = 19.9, 31.2, 33.2, 34.3, 56.4,
13
3
C NMR (125 MHz, CDCl ): δ = 19.9, 31.3, 33.4, 34.5, 53.1,
3
1
1
00.7, 110.7, 113.2, 115.4, 123.3, 127.1, 128.4, 132.3, 133.8, 134.8,
45.5, 154.6.
1
1
10.1, 117.5, 119.2, 120.1, 123.5, 124.5, 126.8, 130.1, 130.9, 131.2,
35.2, 138.7, 146.0, 165.5.
MS (EI, 70 eV): m/z = 322 [M+].
MS (EI, 70 eV): m/z = 350 [M+].
Anal. Calcd for C H N O : C, 70.79; H, 5.63; N, 8.69. Found: C,
1
9
18
2
3
Anal. Calcd for C H N O : C, 68.56; H, 5.18; N, 8.00. Found: C,
2
0
18
2
4
70.51; H, 5.49; N, 8.52.
68.80; H, 5.29; N, 8.16.
9
-Methoxy-3,12-dimethyl-1-nitro-5,6,7,12-tetrahydroben-
3
-Fluoro-12-methyl-1-nitro-5,6,7,12-tetrahydrobenzo[6,7]cy-
zo[6,7]cyclohepta[1,2-b]indole (3f)
clohepta[1,2-b]indole (3b)
Yield: 15 mg (23%); red oil.
Yield: 28 mg (45%); red oil.
–
1
–1
IR (KBr): 1348, 1525, 2924 cm .
1H NMR (500 MHz, CDCl
): δ = 2.26–2.29 (m, 3 H), 2.43–2.48 (m,
H), 2.52 (s, 3 H), 2.62–2.63 (m, 1 H), 3.48 (s, 3 H), 3.93 (s, 3 H),
.96 (dd, J = 8.8, 2.2 Hz, 1 H), 7.11 (d, J = 2.1 Hz, 1 H), 7.25 (d,
IR (KBr): 1336, 1579, 2924 cm .
1
3
H NMR (500 MHz, CDCl ): δ = 2.27–2.29 (m, 2 H), 2.41–2.46 (m,
3
2
6
2
H), 2.63–2.64 (m, 1 H), 3.07–3.09 (m, 1 H), 3.48 (s, 3 H), 7.18 (t,
J = 7.4 Hz, 1 H), 7.29 (t, J = 7.5 Hz, 1 H), 7.33 (d, J = 8.2 Hz, 1 H),
.38 (dd, J = 8.2, 2.6 Hz, 1 H), 7.66 (d, J = 7.9 Hz, 1 H), 7.74 (dd,
J = 8.1, 2.6 Hz, 1 H).
J = 8.8 Hz, 1 H), 7.47 (s, 1 H), 7.82 (s, 1 H).
7
13
C NMR (125 MHz, CDCl ): δ = 20.0, 23.1, 31.3, 33.2, 34.1, 56.4,
3
1
3
100.7, 110.7, 112.9, 115.0, 123.6, 124.2, 127.1, 132.6, 133.6, 135.6,
C NMR (125 MHz, CDCl ): δ = 19.8, 31.1, 33.5, 34.1, 110.0,
3
1
39.0, 145.2, 148.3, 154.5.
1
1
10.8, 111.1, 115.8, 119.0, 119.9, 121.1, 122.1, 122.9, 123.4, 126.8,
30.8.
MS (EI, 70 eV): m/z = 336 [M+].
MS (EI, 70 eV): m/z = 310 [M+].
Anal. Calcd for C H N O : C, 71.41; H, 5.99; N, 8.33. Found: C,
2
0
20
2
3
71.67; H, 6.11; N, 8.51.
Anal. Calcd for C H FN O : C, 69.67; H, 4.87; N, 9.03. Found: C,
1
8
15
2
2
6
9.91; H, 4.50; N, 9.19.
1
1-Methoxy-14-methyl-7,8,9,14-tetrahydronaph-
tho[2′,1′:6,7]cyclohepta[1,2-b]indole (3g)
1
2-Methyl-1-nitro-5,6,7,12-tetrahydrobenzo[6,7]cyclohep-
Yield: 41 mg (63%); yellow oil.
ta[1,2-b]indole (3c)
1
Yield: 20 mg (35%); red oil.
H NMR (500 MHz, CDCl ): δ = 2.32–2.37 (m, 3 H), 2.67–2.73 (m,
3
–
1
2 H), 2.98–3.00 (m, 1 H), 3.59 (s, 3 H), 3.97 (s, 3 H), 7.01 (dd,
J = 8.8, 2.0 Hz, 1 H), 7.17 (d, J = 2.2 Hz, 1 H), 7.38 (d, J = 8.8 Hz,
1 H), 7.49–7.51 (m, 2 H), 7.54 (d, J = 8.3 Hz, 1 H), 7.85–7.88 (m, 2
H), 7.93–7.95 (m, 1 H).
IR (KBr): 1344, 1523, 2921, 2959 cm .
1
H NMR (500 MHz, CDCl ): δ = 2.27–2.29 (m, 2 H), 2.42–2.46 (m,
H), 2.66–2.69 (m, 1 H), 3.05–3.08 (m, 1 H), 3.49 (s, 3 H), 7.15 (t,
J = 7.3 Hz, 1 H), 7.28 (d, J = 7.1 Hz, 1 H), 7.33 (d, J = 8.1 Hz, 1 H),
.45 (t, J = 7.8 Hz, 1 H), 7.63–7.67 (m, 2 H), 7.98 (d, J = 8.1 Hz, 1
3
2
13
C NMR (75 MHz, CDCl ): δ = 20.2, 32.8, 33.4, 35.2, 56.5, 100.6,
3
7
H).
1
1
10.7, 112.0, 115.7, 125.4, 126.4, 126.8, 127.9, 128.6, 128.7, 128.8,
32.1, 133.1, 134.1, 137.1, 141.2, 154.6.
13
C NMR (125 MHz, CDCl ): δ = 19.9, 31.1, 33.2, 34.4, 110.0,
19.0, 119.7, 122.8, 123.3, 128.4, 134.9.
3
MS (EI, 70 eV): m/z = 327 [M+].
1
MS (EI, 70 eV): m/z = 292 [M+].
Anal. Calcd for C23
H21NO: C, 84.37; H, 6.46; N, 4.28. Found: C,
84.58; H, 6.57; N, 4.41.
Anal. Calcd for C H N O : C, 73.95; H, 5.52; N, 9.58. Found: C,
1
8
16
2
2
7
3.68; H, 5.40; N, 9.73.
9-Fluoro-12-methyl-1,3-dinitro-5,6,7,12-tetrahydroben-
zo[6,7]cyclohepta[1,2-b]indole (3h)
9
-Methoxy-12-methyl-1,3-dinitro-5,6,7,12-tetrahydroben-
Yield: 21 mg (30%); red oil.
zo[6,7]cyclohepta[1,2-b]indole (3d)
1
H NMR (300 MHz, CDCl ): δ = 2.32–2.48 (m, 3 H), 2.56–2.61 (m,
3
Yield: 48 mg (65%); red oil.
1
H), 2.87–2.90 (m, 1 H), 3.07–3.09 (m, 1 H), 3.50 (s, 3 H), 7.11 (td,
–
1
IR (KBr): 1336, 1527, 2958, 3097 cm .
J = 9.1, 2.5 Hz, 1 H), 7.28 (dd, J = 9.2, 4.3 Hz, 1 H), 7.32 (dd,
1
J = 9.2, 2.5 Hz, 1 H), 8.50 (d, J = 2.0 Hz, 1 H), 8.84 (d, J = 2.0 Hz,
H NMR (500 MHz, CDCl ): δ = 2.36–2.44 (m, 3 H), 2.58–2.60 (m,
3
1
H).
1
H), 2.83–2.87 (m, 1 H), 3.08–3.12 (m, 1 H), 3.46 (s, 3 H), 3.87 (s,
H), 7.01 (dd, J = 8.9, 2.3 Hz, 1 H), 7.08 (d, J = 2.1 Hz, 1 H), 7.24
3
13
C NMR (75 MHz, CDCl ): δ = 20.9, 21.2, 29.7, 103.2, 109.9,
3
(s, 1 H), 8.46 (d, J = 2.1 Hz, 1 H), 8.79 (d, J = 2.1 Hz, 1 H).
120.3, 123.3, 124.9, 127.9, 130.0, 131.7, 133.6, 134.8, 139.2, 140.1,
13
148.2, 148.4.
C NMR (125 MHz, CDCl ): δ = 20.1, 31.6, 33.7, 34.4, 56.3,
3
1
00.7, 111.2, 115.1, 118.2, 118.9, 127.0, 128.5, 130.4, 133.3, 134.6,
Anal. Calcd for C H FN O : C, 60.84; H, 3.97; N, 11.83. Found:
C, 61.19; H, 4.09; N, 12.01.
1
8
14
3
4
146.2, 147.4, 147.9, 155.0.
MS (EI, 70 eV): m/z = 367 [M+].
©
Georg Thieme Verlag Stuttgart · New York
Synthesis 2013, 45, 1094–1098

1098
F. Jafarpour et al.
PAPER
9
-Fluoro-3,12-dimethyl-1-nitro-5,6,7,12-tetrahydroben-
(5) For reviews on the Fisher indole synthesis, see:
zo[6,7]cyclohepta[1,2-b]indole (3i)
(a) Robinson, B. The Fisher Indole Synthesis; Wiley: New
York, 1982. (b) Hughes, D. L. Org. Prep. Proced. Int. 1993,
25, 607.
Yield: 16 mg (25%); red oil.
1
H NMR (300 MHz, CDCl ): δ = 2.22–2.27 (m, 2 H), 2.33–2.42 (m,
3
2
3
7
H), 2.51 (s, 3 H), 2.59–2.63 (m, 1 H), 2.95–2.99 (m, 1 H), 3.48 (s,
H), 7.02 (td, J = 9.1, 2.5 Hz, 1 H), 7.24 (dd, J = 8.9, 4.2 Hz, 1 H),
.28 (dd, J = 9.5, 2.7 Hz, 1 H), 7.47 (s, 1 H), 7.82 (s, 1 H).
(6) Barolo, S. M.; Lukach, A. E.; Rossi, R. A. J. Org. Chem.
2003, 68, 280.
(7) Campeau, L.-C.; Parisien, M.; Jean, A.; Fagnou, K. J. Am.
Chem. Soc. 2006, 128, 581.
13
C NMR (75 MHz, CDCl ): δ = 19.6, 22.7, 29.4, 31.8, 33.3, 33.9,
3
(
8) Yamuna, E.; Zeller, M.; Adero, P. O.; Prasad, K. J. R.
ARKIVOC 2012, (vi), 326.
1
1
03.9, 110.6, 112.5, 117.9, 118.6, 126.4, 126.9, 128.3, 130.9, 132.5,
35.2, 146.1, 147.1, 147.6, 158.2.
(9) Jafarpour, F.; Hazrati, H. Adv. Synth. Catal. 2010, 352, 363.
MS (EI, 70 eV): m/z = 324 [M+].
(
10) For reviews on Catellani reaction, see: (a) Chiusoli, G. P.;
Catellani, M.; Costa, M.; Motti, E.; Della Ca’, N.; Maestri,
G. Coord. Chem. Rev. 2010, 254, 456. (b) Martins, A.;
Mariampillai, B.; Lautens, M. Top. Curr. Chem. 2010, 292,
Anal. Calcd for C H FN O : C, 70.36; H, 5.28; N, 8.64. Found: C,
1
9
17
2
2
70.65; H, 5.43; N, 8.79.
1
. (c) Sehnal, P.; Taylor, R. J. K.; Fairlamb, I. J. S. Chem.
Rev. 2010, 110, 824. (d) Muniz, K. Angew. Chem. Int. Ed.
009, 48, 9412. (e) Catellani, M.; Motti, E.; Della Ca’, N.
Acknowledgment
2
We gratefully acknowledge the financial support of the University
of Tehran and Iran National Science Foundation (INSF).
Acc. Chem. Res. 2008, 41, 1512. (f) Lautens, M.; Alberico,
D.; Bressy, C.; Fang, Y.-Q.; Mariampillai, B.; Wilhelm, T.
Pure Appl. Chem. 2006, 78, 351. (g) Dick, A. R.; Sanford,
M. S. Tetrahedron 2006, 62, 2439.
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synthesis. SnuIoipgfmr tooatrin guSIopi
(
11) For palladium-catalyzed/norbornene-mediated
functionalization of heterocycles, see: (a) Chai, D. I.;
Thansandote, P.; Lautens, M. Chem. Eur. J. 2011, 17, 8175.
(b) Della Ca’, N.; Maestri, G.; Catellani, M. Chem. Eur. J.
nnfo itrmart
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Synthesis 2013, 45, 1094–1098
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