Copper-Catalyzed Successive C?C bond formations on Indoles or Pyrrole: A Convergent Synthesis of Symmetric and Unsymmetric Hydroxyl Substituted N-H Carbazoles

Article abstract of DOI:10.1002/adsc.201800154

A novel copper-catalyzed successive C?Cbond formations on indoles and pyrrole approach for the direct synthesis of hydroxyl substituted N-H carbazoles is described. The current process represents an atom-economical method for the preparation of both symmetric and unsymmetric densely substituted and hydroxyl containing N-H carbazoles from easily accessible starting materials without the need for expensive metals and harsh reaction conditions. (Figure presented.).

Full text of DOI:10.1002/adsc.201800154

Title: Copper-Catalyzed Successive C-C bond formations on Indoles or
Pyrrole: A Convergent Synthesis of Symmetric and Unsymmetric
Hydroxyl Substituted N-H Carbazoles
Authors: Yu Qiao, Xin-Xing Wu, Yupeng Zhao, Yongqing Sun, Baoguo
Li, and Shufeng Chen
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To be cited as: Adv. Synth. Catal. 10.1002/adsc.201800154
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10.1002/adsc.201800154
Advanced Synthesis & Catalysis
COMMUNICATION
DOI: 10.1002/adsc.201((will be filled in by the editorial staff))
Copper-Catalyzed Successive C-C bond formations on Indoles
or Pyrrole: A Convergent Synthesis of Symmetric and
Unsymmetric Hydroxyl Substituted N-H Carbazoles
Yu Qiaoa, Xin-Xing Wua, Yupeng Zhaoa, Yongqing Suna, Baoguo Lia, Shufeng Chena*
a
Inner Mongolia Key Laboratory of Fine Organic Synthesis, College of Chemistry and Chemical Engineering, Inner
Mongolia University, Hohhot 010021, China
Fax: (+86)-471-499-2982; e-mail: shufengchen@imu.edu.cn
Received: ((will be filled in by the editorial staff))
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201######.((Please
delete if not appropriate))
Abstract. A novel copper-catalyzed successive C-C bond
formations on indoles and pyrrole approach for the direct
synthesis of hydroxyl substituted N-H carbazoles is
described. The current process represents an atom-
economical method for the preparation of both symmetric
and unsymmetric densely substituted and hydroxyl
containing N-H carbazoles from easily accessible starting
materials without the need for expensive metals and harsh
reaction conditions.
Figure 1. Some representative naturally occurring
bioactive hydroxyl substituted N-H carbazoles.
been devoted by the synthetic organic chemistry
community to the development of practical and
convenient methods for the efficient preparation of
functionalized carbazoles during the past several
decades.[4]
Keywords: hydroxyl substituted N-H carbazoles; C-C
bond formation; copper; indoles; pyrrole
Hydroxyl substituted N-H carbazoles are a
common structural motif present in many biologically
active carbazole natural products (Figure 1).
Although there are a large number of methods for the
synthesis of the carbazole scaffold, the reports for
direct preparation of hydroxyl substituted N-H
carbazoles are quite limited.[5] Indole-to-carbazole
transformation represents one of concise methods for
Carbazole and its derivatives are important types of
nitrogen containing heterocyclic compounds that play
a significant role in both chemistry and biology.[1] For
example, numerous molecules, containing the
carbzole
motif,
have
shown
considerable
carbazole
constructions,
offering
convenient
pharmacological activities such as antiviral,
opportunities to obtain the desired functionalized
antimalarial, antiestrogenic
and
antitumor
carbazole derivatives.[6] For instance, Ma and co-
properties.[2] Beside this, cabazoles are also widely
used in various organic photoelectronic materials and
chromophores due to their structural rigidity and
workers have developed
a
AuCl-catalyzed
benzannulation reaction of 1-indoyl-2,3-allenols for
the synthesis of methoxyl substituted carbazoles in
2011 (Scheme 1, eq 1).[7] Subsequently, the same
group has also reported an unexpected gold-catalyzed
reaction for the synthesis of polysubstituted 2-
oxygenated carbazoles from 4-benzoxyl-1-(indol-2-
yl)-2-alkynols (Scheme 1, eq 2).[8] More recently,
Wang and co-workers discovered a Rh(III)-catalyzed
C2 C–H/alkyne annulation reaction of 3-(1H-indol-3-
extensive
π-conjugation.[3]
Consequently,
considerable effort has
H3C
A1: R = (CH2)4CH3
O
OH
HN
H3C
A2: R = (CH2)2CH(CH3)Et
A3: R = (CH2)4CH(CH3)2
A4: R = (CH2)6CH3
OH
CH3
N
H
N
H
R
yl)-3-oxopropanenitriles
to
access
hydroxyl
Antiostatins A1-A4
Siamenol (anti-HIV)
substituted N-H carbazoles for the first time (Scheme
1, eq 3).[9] However, the use of the above-mentioned
poorly available substrates and the operation of
deprotection have restricted applications of these
reactions. Moreover, the direct synthesis of both
symmetric and unsymmetric carbazoles is still
OH
H
N
O
H
HO
OCH3
CH3
O
O
OH
N
N
H
H
CH3
H3C
Carbazomycin B
(5-lipoxygenase inhibitor)
Mukonal (antimalarial)
Clausamine A (antitumor)
relatively
underdeveloped.
Therefore,
the
development of efficient methodologies with atom
1
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10.1002/adsc.201800154
Advanced Synthesis & Catalysis
R
economy starting from easily obtainable substrates to
give both symmetric and unsymmetric carbazoles
bearing an unprotected NH unit as well as a hydroxyl
group is still highly desirable.
O
-
annulation at
R'
C2 position
OH
O
R
N
+
+ R'
-
H
O
+
C
N
+
R'
H
O
+
R
-
N
Michael type
addition
annulation at
C1 position
O
H
A
R
spiroindolization
N
O
H
R'
O
migration
N
HO
R
R' R'
R
R
OH
H
HO
OMe
AuCl
OH
R'
B
(eq 1)
OMe
aromatization
N
OH
N+
H
N
N
H
Bn
R
R
D
R
Bn
R4 R3
symmetric hydroxyl
substituted carbazole
OBz
R3
R4
OBz
OH
N
R1
[IPrAuCl]/AgSbF6
H
R'
5 mol%
R1
R5
OH
(eq 2)
unsymmetric hydroxyl
substituted carbazole
N
N
R5
R2
R2
Scheme 2. Our strategy for the construction of the
symmetric and unsymmetric hydroxyl substituted N-H
carbazoles.
CN
HO
O
CN
R2 (eq 3)
[Cp*RHCl2]2 (5 mol%)
R2
R1
Cu(OAc)2 H2O (2.5 equiv.)
R1
+
Table 1. Optimization of reaction conditions.[a]
N
H
N
H
R3
R3
Ph
O
OH
Ph
cat. (10 mol %)
solvent , temp.
Scheme 1. Synthesis of oxygenated carbazoles.
Ph
+
Ph
N
O
N
H
H
1a
2a
3a
Recently, we became interested in the synthesis and
exploring the reactivity of 1,2-dicarbonyl-3-enes,
especially toward heterocyclic ring formation.[10]
Inspired by these results, we envisage whether that
indole without any substituents at C2 and C3
positions could undergo electrophilic attack twice in
tandem when a suitable dielectrophile is employed.
Obviously, the 1,2-dicarbonyl-3-ene is an ideal
dielectrophile. Our original hypothesis is shown in
Scheme 2. First, the Michael type addition reaction
occurred at one electrophilic site (C4) of the 1,2-
dicarbonyl-3-ene, leading to the alkylated product A
on the C3 position of indole. Subsequently, the C2
position of indole attacks another electrophilic site
(C1 or C2) through an intramolecular manner,
affording the cyclization intermediate B or C. It
should be noted that another possible pathway for the
formation of intermediate B maybe through the
stepwise spiroindolization/migration sequence via
intermediate D.[11] Next, a hydroxyl substituted NH
free carbazole product could be generated
preferentially through the aromatization of
intermediate B. Besides, we anticipated that the
symmetric carbazole product could be formed when a
T
t
Yield
(%)b
Entry Catalyst
Solvent
(oC) (h)
1
Cu(OTf)2 THF
70
70
70
70
70
70
70
70
70
70
70
70
40
80
2.5 69
2.5 48
2
3
4
Zn(OTf)2 THF
AgOTf THF
Sc(OTf)3 THF
2.5 34
4.0 trace
4.0 trace
2.5 30
2.5 15
2.5 79
2.5 63
2.5 31
2.5 trace
2.5 10
2.5 32
2.5 88
5
6
Y(OTf)3
CuCl2
THF
THF
THF
7
CuSO4
8
9
Cu(OTf)2 1,4-dioxane
Cu(OTf)2 PhCH3
10
11
12
13
14
15
Cu(OTf)2 Cl(CH2)2Cl
Cu(OTf)2 CH3CN
Cu(OTf)2 CH3NO2
Cu(OTf)2 1,4-dioxane
Cu(OTf)2 1,4-dioxane
Cu(OTf)2 1,4-dioxane
100 2.5 68
[a] Reaction conditions: 1a (0.45 mmol), 2a (0.3 mmol)
and catalyst (0.03 mmol) in 4.0 mL of solvent at indicated
temperature.
[b] Yield of isolated product after chromatography.
nonsubstituted pyrrole is used instead of indole. If the
hypothesis is successful, it will provide rapid access
to various synthetically valuable symmetric and
unsymmetric hydroxyl substituted N-H carbazoles
from readily available starting materials in an
efficient manner with high atom economy.
To study the feasibility of the hypothesis, we
initially chose the 1,4-diphenylbut-3-ene-1,2-dione
1a and the indole 2a as reactants in the model
reaction (Table 1). To our delight, the carbazole
compound 3a was obtained as the only product in
69% isolated yield when Cu(OTf)2 was used as the
o
catalyst in THF at 70 C for 2.5 hours (entry 1).
Encouraged by this initial result, the effect of
catalysts was subsequently investigated. First, the
2
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10.1002/adsc.201800154
Advanced Synthesis & Catalysis
examination on other metal triflates (entries 2−5)
indicated that Cu(OTf)2 was clearly the better choice
for this carbazole formation reaction. For instance,
only trace of product 3a was detected by TLC when
Sc(OTf)3 or Y(OTf)3 was employed as the catalyst
(entries 4 and 5). Next, two copper catalysts, CuCl2
and CuSO4, were examined under the similar reaction
conditions and a low yield of 3a was obtained,
respectively (entries 6 and 7). Subsequently, the
reaction was verified using Cu(OTf)2 as the catalyst
in the presence of several solvents (entries 8-12); 1,4-
dioxane was found to be the best to obtain the
corresponding carbazole 3a in 79% yield at 70 oC for
2.5 hours (entry 8). Further adjustments showed a
noticeable effect on the reaction temperature, which
with little variation the yields of the isolated products
3a–j. For example, 1,4-disubstituted but-3-ene-1,2-
diones bearing alkyl, methoxyl or halide groups on
the 3 or 4-position of the phenyl rings gave the
corresponding products (3b-i) in good yields. In
addition, substrate with an ortho-substituted aromatic
ring of R1 needed longer reaction time and gave
slightly lower yield of the product 3j, probably due to
the steric hindrance effect. A selection of substrates
displaying R2 substituent of but-3-ene-1,2-diones was
then examined. Under standard reaction conditions,
various substituents on the aromatic ring of R2 were
all compatible with the present method and afforded
the corresponding carbazole products in good yields
(3k-m). However, the substrate containing a nitro
group on the aromatic ring of R2 did not yield any
desired carbazole product (3n). Moreover, only a
complex mixture was obtained with an alkyl
substituted conjugated diketone 1o or 1p under the
standard conditions (3o and 3p). Importantly, an
effective gram-scale synthesis of 3a (2.11 g, 74%)
was carried out to demonstrate the scalability of this
transformation. Finally, the structure of 3i was
unambiguously confirmed by X-ray crystallographic
analysis (Figure 2).[13]
o
gave an 88% yield of the product at 80 C (entries
13–15). Finally, the conditions in entry 14 (Table 1)
were identified as the optimal conditions.
Table 2. Scope of substituted but-3-ene-1,2-dione
derivatives.[a]
R1
O
R2
Cu(OTf)2 (10 mol %)
R1
+
OH
dioxane , 80 o
C
N
O
N
H
3a-p
H
R2
1a-p
2a
C5H11
H3C
C2H5
Ph
OH
OH
N
OH
OH
H
Ph
N
N
H
N
H
H
Ph
Ph
Ph
3a, 2.5 h, 88% (74%)b
3b, 2.5 h, 87%
3c, 2.5 h, 84%
3d, 2.5 h, 83%
Br
Cl
H3CO
F
OH
OH
OH
OH
3i
5c
N
N
N
N
H
Ph
H
Ph
H
Ph
H
Ph
Figure 2. X-Ray structure of 3i and 5c.
3g, 3.0 h, 85%
3e, 2.5 h, 83%
3f, 3.0 h, 84%
3h, 3.0 h, 81%
Ph
Br
Ph
Cl
OH
Next, the reaction scope of the indoles was
examined (Table 3). The results indicated that a broad
spectrum of substituted indoles can be employed in
this transformation and affording the desired
carbazole products 3q-x in moderate to good yields.
Specifically, an iodo substituent on the 5-position is
well tolerated, thus allowing post-reaction
transformation of 3v through a series of cross
coupling chemistry. Moreover, a strong electron-
withdrawing group, such as nitro, was also
compatible with the present catalytic system and
afforded the carbazole 3w in 62% yield, albeit with a
longer reaction time. More interestingly, N-methyl
substituted indole 2i also successfully underwent the
N
H
OH
N
H
OH
OH
N
N
Br
H
Ph
H
Ph
CH3
3i, 3.0 h, 80%
3j, 3.5 h, 72%
3k, 3.0 h, 81%
3l, 2.5 h, 84%
Ph
Ph
Ph
OH
OH
N
H
N
H
OH
OH
N
CH3
H
CH3
N
H
Ph
CH3
3m, 2.5 h, 78%
NO2
3n, 5.0 h, 0%
3p, complex mixture
3o, complex mixture
[a] Reaction conditions: 1a-p (0.45 mmol), 2a (0.3 mmol)
and Cu(OTf)2 (0.03 mmol) in 4.0 mL of dioxane at 80 C
and isolated yields were reported. [b] The reaction was
performed on a gram scale.
o
With the optimized reaction conditions in hand, we
next focused our attention on substrate scope to
determine the generality of this carbazole formation
reaction. As illustrated in Table 2, we initially
focused on the 1,4-disubstituted but-3-ene-1,2-diones,
which were easily prepared according to the reported
Table 3. Scope of substituted indole derivatives.[a]
literature.[10a,12]
Substrates
bearing
various
substituents on the phenylring of R1 proved reactive
3
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10.1002/adsc.201800154
Advanced Synthesis & Catalysis
R2
R2
Ph
OH
O
HO
Cu(OTf)2 (20 mol %)
TsOH (10 mol %)
O
R1
Cu(OTf)2 (10 mol %)
R2
R1
Ph
R1
+
+
Ph
OH
OH
dioxane, 80 o
C
dioxane, 70 oC, 4h
N
R2
N
H
O
N
R2
3q-x
O
N
R1
Ph
Ph
R1
H
1a
1a-j
5a-j
4a
2b-i
Ph
N
Ph
CH3 Ph
Ph Ph
Ph Ph
OH
OH
HO
HO
Ph
Ph
OH
HO
OH
H3CO
F
OH
N
N
H
H
Ph
N
H
N
H
H
Ph
N
3q, 2.5 h, 86%
3r, 2.5 h, 81%
3s, 2.5 h, 82%
Ph
H
Ph
Ph
Ph
Cl
Ph
F
Cl
Cl
F
I
5a, 52%
5b, 43%
5c, 42%
OH
OH
Br
OH
N
N
N
Ph
Ph
H
Ph
H
Ph
OH
H
Ph
HO
Ph
Ph
Ph
Ph
OH
HO
OH
HO
3t, 2.5 h, 80%
3u, 2.5 h, 79%
3v, 2.5 h, 81%
N
Ph
Ph
H
N
Cl
Cl
N
H
H
OH
OH
O2N
Br
Br
N
N
Br
Br
H
Ph
Ph
5d, 41%
5e, 37%
5f, 39%
CH3
3x, 3.0 h, 82%
3w, 4.5 h, 62%
Ph
Ph
OH
HO
[a] Reaction conditions: 1a (0.45 mmol), 2b-i (0.3 mmol)
and Cu(OTf)2 (0.03 mmol) in 4.0 mL of dioxane at 80 C
and isolated yields were reported.
R
R
o
OH
HO
R = 4-CH3C6H4, 5h, 41%
N
R = 4-CH3OC6H4, 5i, 37%
R = 4-ClC6H4, 5j, 40%
H
reaction to afford the carbazole product 3x in high
yield.
N
H
Ph
Ph
Me
Me
5g, 44%
Naturally, as we envisioned in Scheme 1, we
decided to test the more challenging pyrrole substrate
in order to gauge the full capability of this interesting
method.[14, 15] We found that under slightly modified
reaction conditions, the synthetically valuable
symmetric densely substituted and hydroxyl
containing carbazoles were formed in moderate
yields (Table 4). It should be noted that increasing the
loading of the copper catalyst as well as the addition
of TsOH (10 mol%) are necessary for the promotion
of the reaction. Subsequent investigation indicated
that a series of substituents on the phenyl ring of both
R1 and R2 in the substituted but-3-ene-1,2-diones
were all compatible with the present catalytic system
and afforded the desired symmetric carbazoles in
acceptable yields (5a–j). Moreover, the structure of
the product 5c was also confirmed by X-ray
crystallographic analysis (Figure 2).[13]
[a] Reaction conditions: 1 (0.9 mmol), 4a (0.3 mmol),
Cu(OTf)2 (0.06 mmol) and TsOH (0.03 mmol) in 4.0 mL
o
of dioxane at 70 C for 4 hours and isolated yields were
reported.
For the mechanistic studies of this transformation,
two control experiments were carried out carefully
(Scheme 3). First, we successfully isolated the C3-
alkylated intermediate 6 of indole in 92% yield by
O
Ph
Ph
O
O
Cu(OTf)2 (10 mol%)
+
Ph
(Eq 4)
Ph
dioxane, 25 oC, 1h
N
N
H
O
H
1a
2a
6, 92 %
O
Ph
Ph
Ph
Cu(OTf)2 (10 mol%)
dioxane, 80 oC, 1.5h
OH
O
(Eq 5)
Ph
3a, 93%
N
N
H
H
6
Table 4. Synthesis of symmetric carbazoles from
various substituted but-3-ene-1,2-diones with
pyrrole.[a]
Scheme 3. Control experiments.
o
decreasing the reaction temperature to 25 C (Eq 4).
Subsequently, the compound 6 afforded the desired
carbazole product 3a in 93% yield when it was heated
o
under the standard conditions at 80 C (Eq 5). These
results and the X-ray structures of the products are
strongly supported our initial hypothesis of the
possible reaction pathway as shown in Scheme 1. The
driving force for the selective annulation at C1
position of intermediate 6 could be attributed to the
formation of six member ring and aromatization
process.
4
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10.1002/adsc.201800154
Advanced Synthesis & Catalysis
In conclusion, we have developed
a
new
[2] For selected examples of biologically important
carbazoles, see: a) A. Zhang, G. Lin, Bioorg. Med.
Chem. Lett. 2000, 10, 1021. b) C.-C. Chang, I.-C. Kuo,
J.-J. Lin, Y.-C. Lu, C.-T. Chen, H.-T. Back, P.-J. Lou,
T.-C. Chang, Chem. Biodiversity. 2004, 1, 1377. c)
M.-J. Hsu, Y. Chao, Y.-H. Chang, F.-M. Ho, Y.-L.
Huang, L.-J. Huang, T.-Y. Luh, C.-P. Chen, W.-W.
Lin, Biochem. Pharmacol. 2005, 70, 102. d) A. R.
Howard-Jones, C. T. Walsh, J. Am. Chem. Soc. 2006,
128, 12289. e) T. Janosik, N. Wahlström, J. Bergman,
Tetrahedron 2008, 64, 9159. f) L.-X. Liu, X.-Q.
Wang, B. Zhou, L.-J. Yang, Y. Li, H.-B. Zhang, X.-D.
Yang, Sci. Rep. 2015, 5, 1310.
methodology, thus allowing the selective annulation
of a but-3-ene-1,2-dione with an unprotected indole
or pyrrole derivative leading to both symmetric and
unsymmetric hydroxyl containing N-H carbazoles
with the use of Cu(OTf)2 as an efficient catalyst.
Simple and readily available starting materials, broad
substrate scope, inexpensive copper catalyst and high
atom economy make this transformation more
efficient. Moreover, the presence of a free hydroxyl
as well as an amino group on the carbazole products
makes it possible for chemists to transformation
further according to demand. We foresee that this
general and operationally simple approach can
provide direct access to various symmetric and
unsymmetric carbazole compounds and might have a
major impact on the synthesis of structurally complex
[3] For recent reviews, see: a) G. Sathiyan, E. K. T.
Sivakumar, R. Ganesamoorthy, R. Thangamuthu, P.
Sakthivel, Tetrahedron Lett. 2016, 57, 243. b) F.
Dumur, Org. Electron. 2015, 25, 345. c) J.-P.
Lellouche, R. R. Koner, S. Ghosh, Rev. Chem. Eng.
2013, 29, 413. d) N. Koumura, K. Hara, Heterocycles
2013, 87, 275. e) J. Li, A. C. Grimsdale, Chem. Soc.
Rev. 2010, 39, 2399.
molecules,
functionalized
materials,
and
pharmaceuticals.
Experimental Section
[4] For selected reviews, see: a) I. Bauer, H.-J. Knꢀlker,
Top. Curr. Chem. 2011, 309, 203. b) A. W. Schmidt,
K. R. Reddy, H.-J. Knꢀlker, Chem. Rev. 2012, 112,
3193. c) N. Yoshikai, Y. Wei, Asian J. Org. Chem.
2013, 2, 466.
General procedure for the Cu(OTf)2-catalyzed
reaction of but-3-ene-1,2-diones with indoles
To a solution of but-3-ene-1,2-dione (0.45 mmol) and
indole (0.3 mmol) in dioxane (4.0 mL) was added
Cu(OTf)2 (0.03 mmol) under an air atmosphere. The
resulting mixture was heated at 70 °C for the indicated
time. After completion of the reaction, the mixture was
cooled to room temperature. The solvent was removed in a
vacuum, and the resulting residue was purified on a silica
gel column (petroleum ether/EtOAc = 10:1) to provide the
desired products 3.
[5] a) B. Witulski, C. Alayrac, Angew. Chem. 2002, 114,
3415; Angew. Chem. Int. Ed. 2002, 41, 3281. b) M. P.
Krahl, A. Jäger, T. Krause, H.-J. Knölker, Org.
Biomol. Chem. 2006, 4, 3215. c) J. T. Kuethea, K. G.
Childers, Adv. Synth. Catal. 2008, 350, 1577.
[6] For selected examples of carbazoles synthesis from
pre-functionalized indoles, see: a) Y. Qiu, D. Ma, C.
Fu, S. Ma. Org. Biomol. Chem. 2013, 11, 1666. b) S.
K. Bhunia, A. Polley, R. Natarajan, R. Jana, Chem.
Eur. J. 2015, 21, 16786. c) Y. Huang, X. Li, L. Fu, Q.
Guo. Org. Lett. 2016, 18, 6200. d) C. R. Reddy, R. R.
Valleti, U. Dilipkumar, Chem. Eur. J. 2016, 22, 2501.
e) C. Kuo, A. Konala, L. Lin, T. Chiang, C. Huang, T.
Yang, V. Kavala, C. Yao, Chem. Commun. 2016, 52,
7870. f) J. T. R. Liddon, M. J. James, A. K. Clarke, P.
O’Brien, R. J. K. Taylor, W. P. Unsworth, Chem. Eur.
J. 2016, 22, 8777. g) M. J. James, P. O’Brien, R. J. K.
Taylor, W. P. Unsworth, Angew. Chem. 2016, 128,
9823; Angew. Chem. Int. Ed. 2016, 55, 9671. h) B. Li,
B. Zhang, X. Zhang, X. Fan, Chem. Commun. 2017,
53, 1297. i) A. Banerjee, S. Sahu, M. S. Maji, Adv.
Synth. Catal. 2017, 359, 1860.
General procedure for the preparation of
symmetric carbazoles from pyrrole
To a solution of but-3-ene-1,2-dione (0.9 mmol) and
pyrrole (0.3 mmol) in dioxane (4.0 mL) was added
Cu(OTf)2 (0.06 mmol) under an air atmosphere. The
resulting mixture was stirred at room temperature for 1 h,
and then TsOH (0.03 mmol) was added. Next, the mixture
was heated at 70 °C for 4 hours. After completion of the
reaction, the mixture was cooled to room temperature. The
solvent was removed in a vacuum, and the resulting
residue was purified on a silica gel column (petroleum
ether/EtOAc = 10:1) to provide the desired products 5.
Acknowledgements
This project was generously supported by the National Natural
Science Foundation of China (21662025) and the Natural
Science Foundation of Inner Mongolia Autonomous Region of
China (2014JQ02). We thank Ms Wanrong Zhao and Mr
Shengxiao Li in our group for their assistance with some
additional experiments during preparation of the revised
manuscript.
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10.1002/adsc.201800154
Advanced Synthesis & Catalysis
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6
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10.1002/adsc.201800154
Advanced Synthesis & Catalysis
COMMUNICATION
Copper-Catalyzed Successive C-C bond formations
on Indoles or Pyrrole: A Convergent Synthesis of
Symmetric and Unsymmetric Hydroxyl Substituted
N-H Carbazoles
Adv. Synth. Catal. Year, Volume, Page – Page
Yu Qiao, Xin-Xing Wu, Yupeng Zhao, Yongqing
Sun, Baoguo Li, Shufeng Chen*
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