A facile synthesis of indolo[3,2,1-jk]carbazoles via palladium-catalyzed intramolecular cyclization

Article abstract of DOI:10.1016/j.tetlet.2012.07.093

A new efficient synthesis of indolo[3,2,1-jk]carbazoles by the palladium-catalyzed cyclization of N-(2-bromoaryl)carbazoles is described. The reaction involves intramolecular C-C bond formation, coupled with the cleavage of a C-X bond and a C-H bond on carbazole ring. Substitutions on N-aryl core with either electron-donating or electron-withdrawing groups are introduced, and different reaction factors for cyclization are evaluated.

Full text of DOI:10.1016/j.tetlet.2012.07.093

Tetrahedron Letters 53 (2012) 5248–5252
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A facile synthesis of indolo[3,2,1-jk]carbazoles via palladium-catalyzed
intramolecular cyclization
Jun Lv a, Qiancai Liu a, , Jie Tang a, Franc Perdih b, Kristof Kranjc b
⇑
a Department of Chemistry, East China Normal University, Shanghai 200241, China
b Faculty of Chemistry and Chemical Engineering, University of Ljubljana, SI-1000, Slovenia
a r t i c l e i n f o
a b s t r a c t
Article history:
A new efficient synthesis of indolo[3,2,1-jk]carbazoles by the palladium-catalyzed cyclization of N-(2-
bromoaryl)carbazoles is described. The reaction involves intramolecular C–C bond formation, coupled
with the cleavage of a C–X bond and a C–H bond on carbazole ring. Substitutions on N-aryl core with
either electron-donating or electron-withdrawing groups are introduced, and different reaction factors
for cyclization are evaluated.
Received 14 February 2012
Revised 10 July 2012
Accepted 17 July 2012
Available online 27 July 2012
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
Indolo[3,2,1-jk]carbazoles
Intramolecular cyclization
Palladium
Catalysis
Organic
p
-conjugated oligomers and polymers with heteroat-
via C–H cleavage of C-1 of carbazole; (3) copper-catalyzed C–N
bond formation route: heterocycles such as dibenzo[2,3:5,6]pyrro-
lizino[1,7-bc]-indolo[1,2,3-lm]carbazole (Scheme 1c) have been re-
ported through C–C/C–N formation by bis-diazonium perchlorate,
(4) copper-catalyzed cyclization of 5,11-bis(2-chlorophenyl)-indo-
lo[3,2-b]carbazole. However, the synthesis of these compounds is
hampered by the harsh reaction conditions (high temperature
and high vacuum), which could cause those sensitive intermediates
decomposed, or it is limited to intermediate availability. Therefore,
it is worthwhile to explore novel synthetic approach to this kind of
compounds due to their potentials in material chemistry.
The development of facile and efficient synthetic methodologies
always plays a key role in organic synthesis. The direct arylation of
arenes via C–H bond activation and halogen exchange catalyzed or
mediated by transition metal catalysts has received significant
attention. Palladium-catalyzed formation of carbon–carbon bonds
via intramolecular C–X/C–H cross-coupling has emerged as an effi-
cient and straightforward solution for the synthesis of a variety of
heterocycles and carbocycles. Palladium-catalyzed C–H intermo-
lecular and/or intramolecular arylation offers one of the most effi-
cient and reliable methods for the construction of cyclic
compounds.6 Recently we have reported the synthesis of inde-
no[1,2,3-jk]fluorenes, a type of strained molecules by palladium-
catalyzed intramolecular arylation through C–H activation.7 It
was previously reported that the C–H at C-1 position of carbazole
ring could be activated and 6-member ring could be formed
through intramolecular arylation.8
oms are useful compounds as organic functional materials which
are widely applied in organic light-emitting diodes (OLEDs), organic
field-effect transistors (OFETs), nonlinear optical devices (NLO), and
organic solar cells. Heteroatom(s) are often contained or incorpo-
rated in these
p-conjugated systems, and they generally play an
important role in the properties of the materials.1 Compounds with
carbazole core such as indolo-carbazoles have been synthesized by
well-defined routes. Indolo[3,2,1-jk]carbazoles (Scheme 1a), a spe-
cial kind of indolo-carbazole positional isomers with an indolo- and
a carbazole ring fused in a strained model, can be considered as aza-
analogue of indeno[1,2,3-jk]fluorene (fluoradene, Scheme 1b). They
also show quite interesting properties under electro-oxidation con-
ditions.2–4 Indolo[3,2,1-jk]carbazoles generally possess high ther-
mostability, good fluorescence quantum yield in solution as well
as strong electron donor ability, which led them promising compo-
nents as charge transporting materials, conducting thin-film mate-
rials, and efficient electron donating component for fluorescent
chromophores.5
However, there are only few reports about indolo[3,2,1-jk]carb-
azoles so far (Scheme 1). Several procedures for the construction of
indolo[3,2,1-jk]carbazoles were reported: (1) a two-step approach
by high-temperature flash vacuum pyrolysis (FVP) of 2-nitroaryl-
carbazoles through aryl radical pathway;2–5 (2) a three-step route
starting from the Ullmann coupling of carbazole and 1-fluoro-2-
nitrobenzene, followed by the reduction and Sandmeyer process
Considering the harsh condition or low efficiency of previous
methods mentioned above, we undertook a target to establish a
⇑
Corresponding author. Tel.: +86 21 5434 0097; fax: +86 21 5434 0119.
E-mail address: qcliu@chem.ecnu.edu.cn (Q. Liu).
0040-4039/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2012.07.093

J. Lv et al. / Tetrahedron Letters 53 (2012) 5248–5252
5249
X
2
1
3
4
11
9
N
N
5
N
Y
X
7b
7a
7
8a
10
6
8
(a)
(b)
(c)
Scheme 1.
R
R
R
R
X
R
R
Br
N
cat. Pd
cat. Cu
or NaH
N
+
Br
N
H
R'
R'
R'
(3)
(2)
(1)
(4)
R' = H (a), X = I
R = H (a)
R' = Me (b), X = I
R' = tBu(c), X = I
R' = OMe (d), X = I
R' = COOEt (e), X = F
R' = NO2(f), X = F
R = tBu (b)
NH2
R'
Br
N
+
MeO
OMe
Br
O
R'
R' = tBu (c).COOEt (e), NO2(f)
Scheme 2. Synthetic route for indolo[3,2,1-jk]carbazoles.
Table 1
Optimization of palladium-catalyzed cyclization of 4aa from 3aa
Entrya
Catalyst
Base
Solvent
Timeb (h)
Yieldc (%)
Pd(OAc)2, BnEt3NCl
base, solvent, heat
N
N
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
K2CO3
NaHCO3
KHCO3
NEt3
Na2CO3
K2CO3
NaHCO3
KHCO3
NEt3
DMF
DME
6
14
14
6
13
13
6
6
6
6
4
4
6
6
6
6
6
67
32
17
60
19
30
69
42
44
52
80
83
47
49
53
66
Trace
Br
1,4-Dioxane
NMP
PhMe
p-Xylene
DMF
DMF
DMF
DMF
DMA
DMA
DMA
DMA
DMA
DMA
DMA
3aa
4aa
Scheme 3. Optimization of ring-closure reaction from 3aa to 4aa.
concise and efficient synthetic route for indolo[3,2,1-jk] carbazoles,
which can be considered as aza-analogue of fluoradene. Based on
experiences on palladium-catalyzed intramolecular arylation
through C–H activation and aryl ortho-bromide elimination de-
scribed above, we designed an alternative route for the synthesis
of these strained molecules (Scheme 2). For this purpose, suitable
carbazole precursors such as carbazole (1a) and 3,6-di-tert-butylc-
arbazole (1b) were chosen, compound 1b could be obtained by
alkylation of carbazole (69%).9 Considering the functional group
compatibility, a series of 2-bromoaryl- carbazole substrates were
prepared by three major approaches: (1) most of them were ob-
tained by copper-catalyzed Ullmann coupling of 1a or 1b with dif-
ferent compounds 2; (2) 3ac, 3ae, and 3af were obtained more
efficiently by the reaction of 2-bromo-4-substituted-aniline with
2,5-dimethoxytetrafuran in refluxing glacial acetic acid; (3) 3bf
was obtained only by the reaction of 2bf and 1b with NaH as the
base (Scheme 2).10
d
Pd(OAc)2
Pd(OAc)2
K2CO3
K2CO3
e
a
All reactions were carried out at refluxing, Pd(OAc)2 (15 mol %), 3aa
(0.62 mmol), base (5 equiv), BnEt3NCl (100 mol %), PPh3 (35 mol %), and solvent
(50 mL).
b
Reaction time for consumption of 3aa by thin layer chromatography (TLC).
Isolated yield.
Pd(OAc)2 (10 mol %).
Pd(OAc)2 (5 mol %).
c
d
e
The intramolecular arylation coupling reaction was initially
screened with substrate 3aa by using a protocol by us7 and others8

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J. Lv et al. / Tetrahedron Letters 53 (2012) 5248–5252
Table 2
Indolo[3,2,1-jk]carbazoles
Entry
Precursor
Indolo[3,2,1-jk]carbazole
Time (h)
Yielda (%)
N
N
Br
Br
1
6
83
3aa
N
4aa
N
2
3
6
6
80
70
Me
Me
4ab
3ab
N
N
Br
Br
tBu
tBu
3ac
4ac
N
N
4
5
6
6
12
12
66
43
29
OMe
3ad
OMe
4ad
N
N
Br
COOEt
4ae
COOEt
3ae
N
N
Br
NO2
NO2
4af
3af
N
N
7
6
83
Br
Br
3ba
4ba
N
N
8
6
80
Me
Me
3bb
4bb
N
N
Br
9
6
71
3bc
4bc

J. Lv et al. / Tetrahedron Letters 53 (2012) 5248–5252
5251
Table 2 (continued)
Entry
Precursor
Indolo[3,2,1-jk]carbazole
Time (h)
Yielda (%)
N
N
b
Br
10
6
—
OMe
OMe
4bd
3bd
N
N
Br
11
12
43
COOEt
3be
COOEt
4be
N
N
Br
12
12
28
NO2
NO2
4bf
3bf
a
Isolated yield.
b
Dehalogenated by–products formed. See Supplementary data for detail.
in the presence of Pd(OAc)2 as catalyst, Na2CO3 as base, and
BnEt3NCl as additive in refluxed N,N-dimethylformamide (DMF)
under nitrogen atmosphere, the reaction proceeded smoothly,
the starting materials were totally converted within 6 h, and the
target compound 4aa was obtained with an isolated yield of 67%
(Scheme 3, Table 1, entry 1).
Therefore, we performed a list of experiments with focus on
precursor 3aa where sequential changes were made to solvents,
base, and catalyst loadings for the optimization of the reaction con-
ditions. We examined several solvents such as DMF, N,N-dimethyl-
acetamide (DMA), dimethoxyethane (DME), 1,4-dioxane, N-
methylpyrrolidene (NMP), toluene, and p-xylene and found the
cyclization could be proceeded both in polar and non-polar sol-
vents, among the solvents considered, DMA afforded the best re-
sults (83%, Table 1, entry 12).
Pd(OAc)2
L=PPh3
N
Br
[Pd(0)Ln]
N
(3)
HBr
(4)
N
PdBr
PdBr
N
(A)
The effect of base was also studied both in DMF and DMA,
K2CO3 was found to be superior to other four bases (Na2CO3, NaH-
CO3, KHCO3, Et3N) examined both in DMF and DMA (Table 1, en-
tries 7 and 11). Then we secured the solvent and base for further
evaluation. As for catalyst loading, we found that the isolated
yields of 4aa are almost the same when Pd(OAc)2 was taken 15–
30 mol %. However, when the catalyst loading was decreased to
5 mol % there is only trace of the desired product (as shown by
TLC, Table 1, entry 17), which could not be isolated. While the cat-
alyst loading was changed to 10 mol %, the yield was increased to
66% (Table 1, entry 16). Therefore conditions involving 15 mol %
of Pd(OAc)2, 35 mol % of PPh3, 1 equiv of BnEt3NCl, 5 equiv of
K2CO3 in refluxing DMA were selected to the generality of this
method for further synthesis of other indolo[3,2,1-jk]carbazoles.
With optimized conditions in hand, we set out to examine the
general scope of the reaction (Table 2). The 12 substrates 3aa–
3bf with different substituents were examined, we found the cycli-
zation could be proceeded within 6 h for most of them, the target
molecules could be isolated in fair to good yields when the substit-
uents are H, Me, tBu, and OMe, while those substrates with elec-
tron withdrawing groups at para-position of phenyl ring could
(B)
Scheme 4. Plausible mechanism for Palladium-catalyzed cyclization.
also be finished in longer time (ca. 12 h) with dropped isolated
yields (28–43%, Table 2 entries 5–6, 11–12).
The proposed mechanism for palladium-catalyzed cyclization
toward indolo[3,2,1-jk]-carbazoles is shown in Scheme 4 (with
the formation of 4aa as e.g.). Presumably, initially oxidative addi-
tion of 3 with palladium might form aryl-palladium intermediate
(A), followed by addition to the double bond of carbazole ring to
give intermediate (B), the b-hydrogen elimination is triggered by
attack of bases to aromatic protons to form compound 4.6–8
In summary, we have described a novel approach to indo-
lo[3,2,1-jk]carbazoles with various functional groups by palla-
dium-catalyzed transformation, where N-(2-bromoaryl)carbazoles
are cyclized to give the target molecules via C–X/C–H cross-cou-
pling. Palladium facilitates the formation of an aromatic palladium
bromide by oxidation addition, while the base provides the
driving force for carbon–carbon bond formation of the expected

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Acknowledgments
The authors thank the Shanghai Natural Science Foundation of
China (Contract No. 09ZR1409400) and Shanghai Committee of Sci-
ence and Technology of China (Grant No. 10520710100), and Chi-
na-Slovenia bilateral governmental exchange program (Pd/Fe-
catalyzed C–H bond activation, Grant number 9–15) for financial
support. We also thank the large instruments open foundation of
East China Normal University for supporting analysis.
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.tetlet.2012.07.
093.
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