1170
Published on the web June 12, 2013
Indium-catalyzed Annulation of Indoles with Ethyl (2-Ethynylaryl)methyl Carbonates:
Synthesis and Photoluminescent Properties of Aryl- and Heteroaryl[b]carbazoles
Yuta Nagase, Takuhiro Miyamura, Kensuke Inoue, and Teruhisa Tsuchimoto*
Department of Applied Chemistry, School of Science and Technology, Meiji University,
1-1-1 Higashimita, Tama-ku, Kawasaki, Kanagawa 214-8571
(Received April 26, 2013; CL-130402; E-mail: tsuchimo@isc.meiji.ac.jp)
Table 1. Indium-catalyzed annulation of N-methylindole with
2-ethynylbenzyl ether derivatives 2a
Two successive carbon-carbon bond-forming annulation
of indoles with ethyl (2-ethynylaryl)methyl carbonates and their
heteroaryl analogs under indium catalysis provided aryl- and
heteroaryl[b]carbazoles, photoluminescent properties of which
were then evaluated and compared with those of the corre-
sponding [a]- and [c]-types, thereby showing that the order of
light-emitting efficiency is [a]- < [b]- < [c]-type.
11
In(ONf)3
RO
(20 mol%)
+
+
N
6
Bu2O, 85 °C
N
N
2 : 1
1a
2
3a
4a
Time
/h
Yield
Entry
R in 2
Me (2a)
3a:4ab
/%b
1
2
3
4
5
6
7
8
9
10
11
12
13c
14d
24
3
7
11
29
18
11
<1
19
58
79
54
16
69
17
53
80
9:91
87:13
76:24
64:36
®
Aryl- and heteroaryl-annulated carbazoles (AHACs) have
attracted much attention due to their biological and pharmaco-
logical activities1 as well as unique optoelectronic properties.2
AHACs are classified into [a]-, [b]-, and [c]-types based on the
position at which the (hetero)aryl ring is fused to the carbazole
core. Of these three types, we first established a new synthetic
strategy for the [a]-type that is constructed by annulation of
2-(hetero)arylindoles with propargyl ethers under indium catal-
ysis.3 Replacing 2-(hetero)arylindoles with their 3-analogs also
allowed us to address the [c]-type.4 The strategy features a two
carbon-carbon bond-forming cascade in one batch, where an
indium salt activates both the C¸C and C-O bonds of propargyl
ethers. We envisioned that its application to the [b]-type, which
remains unaddressed, would further enhance the generality and
reliability of the strategy. Although numerous synthetic ap-
proaches to AHACs have been reported due to their interests in a
variety of aspects,1,2 no powerful strategy with a broad substrate
scope capable of offering all the three types has appeared in
literature.5-8 We present herein a new avenue for synthesizing
the [b]-type as a final target of this research project.9 Structural
characteristics governing light-emitting efficiency of the three
types are also discussed.
Initially, we examined the effect of the leaving group OR of
2 in the reaction of N-methylindole (1a) (Table 1). Thus, with
In(ONf)3 (20 mol %, Nf: SO2C4F9) in Bu2O as a useful system
found in our preceding studies,3,4 treating 1a and 2-ethynylben-
zyl methyl ether (2a) at 85 °C for 24 h gave a mixture of 5,6- and
5,11-dimethyl-5H-benzo[b]carbazoles (3a and 4a), albeit in a
low yield (Entry 1). Using 2b-2f with the silyloxy or acyloxy
group gave no marked improvement in the yield, but 2g with
OCO2Me as a carbonate functionality showed much better
performance (Entries 2-7). After the continuous survey of other
carbonate derivatives 2h-2k, ethyl analog 2h proved to be the
most promising, giving 3a preferentially in 79% yield (Entries
8-11).10 2-Ethynylbenzyl alcohol (2l) as a commercial source
was ineffective (Entry 12). The studies on the ratio of 1a and 2h
showed that the use of 2 molar equivalents of 1a relative to 2h is
suitable (Entries 8, 13, and 14). Due to different nucleophilicity
of the C2 and C3 of indoles, achievement of SEAr-based carbon-
carbon bond-forming annulation of indoles that react with two
different functionalities seems not to be an easy task, and in fact,
SiMe3 (2b)
SiMe2t-Bu (2c)
COMe (2d)
COt-Bu (2e)
COCF3 (2f)
CO2Me (2g)
CO2Et (2h)
CO2i-Pr (2i)
CO2t-Bu (2j)
CO2Ph (2k)
H (2l)
24
24
24
24
24
24
24
24
7
67:33
84:16
86:14
83:17
74:26
87:13
73:27
84:16
85:15
CO2Et (2h)
CO2Et (2h)
24
24
aReagents: 1a (0.20 mmol), 2 (0.10 mmol), In(ONf)3 (20
¯mol), and Bu2O (0.10 mL). bDetermined by 1H NMR.
d
c1a:2h = 1.5:1. 1a:2h = 2.5:1.
only a handful of related works have emerged in literature, to our
knowledge.11 The present reaction would thus be an important
new entry for such indole-based annulation.
Having the suitable reaction conditions in hand, we next
explored the scope of the indium-catalyzed annulation (Table 2).
Besides 1a, MeO- and Br-substituted N-methylindoles reacted
with 2h to give the corresponding annulation products as a
mixture of two isomers (Entries 1-3). N-Benzyl- and N-(4-
methoxyphenyl)indoles as well as the N-unsubstituted indole
also worked as nucleophiles (Entries 4-6). The use of indole
acceptor 2m bearing a methyl group at the benzylic position
provided 6,11-dimethyl derivatives 3g and 3h as sole products
(Entries 7 and 8). The annulation reaction of 2m was found to be
much faster than that of 2h (Entries 1 vs. 7, and 3 vs. 8). On the
other hand, using an electrophile having an internal alkynyl
group resulted in no desired annulation.12
The strategy can be extended to synthesize heteroaryl
derivatives. Thus, the reaction of thienyl electrophile 2o led to
the predominant formation of isomer 3i, as was observed in
the case of aryl[b]carbazoles (eq 1). The pentacyclic system
including benzothienyl and benzofuranyl rings could also be
prepared as target structures (eqs 2 and 3). In the use of 2p, [3,2-
b]-type 3j was obtained as a single isomer.
Chem. Lett. 2013, 42, 1170-1172
© 2013 The Chemical Society of Japan
Nagase, Yuta
