Bismuth-catalyzed synthesis of anthracenes via cycloisomerization of o-alkynyldiarylmethane

Article abstract of DOI:10.1016/j.tetlet.2015.10.111

In this study, anthracenes were efficiently synthesized from o-alkynyldiarylmethane using a novel method that exploits the synergistic effect between Bi(OTf)₃ as the catalyst, and trifluoroacetic acid (TFA). Through this reaction, we achieved the rapid and efficient synthesis of anthracenes bearing various functional groups under mild conditions.

Full text of DOI:10.1016/j.tetlet.2015.10.111

Tetrahedron Letters xxx (2015) xxx–xxx
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Bismuth-catalyzed synthesis of anthracenes via cycloisomerization
of o-alkynyldiarylmethane
a,b,
Jungmin Park a, Hyuck Choi a, Deug-Chan Lee b,c, , Kooyeon Lee
⇑
⇑
a Department of Bio-Health Technology, Kangwon National University, Chuncheon 200-701, Republic of Korea
b Department of Medical Biotechnology, Kangwon National University, Chuncheon 200-701, Republic of Korea
c Institute of Bioscience and Biotechnology, Kangwon National University, Chuncheon 200-701, Republic of Korea
a r t i c l e i n f o
a b s t r a c t
Article history:
In this study, anthracenes were efficiently synthesized from o-alkynyldiarylmethane using a novel
method that exploits the synergistic effect between Bi(OTf)3 as the catalyst, and trifluoroacetic acid
(TFA). Through this reaction, we achieved the rapid and efficient synthesis of anthracenes bearing various
functional groups under mild conditions.
Received 14 March 2015
Revised 26 October 2015
Accepted 30 October 2015
Available online xxxx
Ó 2015 Published by Elsevier Ltd.
Keywords:
Anthracene
Hydroarylation
Bismuth
Brønsted acid
Catalysis
Polycyclic aromatic hydrocarbons (PAHs) are important com-
pounds that have been attracting increasing attention in the mate-
rial sciences for their wide range of applications, such as in
photoelectronic devices.1 Anthracene derivatives have also been
extensively studied as promising therapeutic agents,2 optical
devices,3 and polymers.4 Anthracene compounds are commonly
The reaction conditions were optimized using 1-benzyl-2-
ethynylbenzene (1a) as a model substrate (Table 1). The catalytic
activities of various metal triflates (5 mol %) were investigated by
starting material 1a at 60 °C using 1,2-dichloroethane as the sol-
vent. The reaction of 1a did not proceed significantly with Sc
(OTf)3 (Table 1, entry 1). The use of indium, copper, and iron cata-
lysts resulted in the generation of the desired product (2a) with
yields of 21%, 45%, and 46%, respectively. These low yields were
verified by 1H NMR (Table 1, entries 2–4), and the hydration pro-
duct 1-(2-benzylphenyl)ethanone (3a) was confirmed to be gener-
ated as a byproduct. When Bi(OTf)3 was used as the catalyst,
9-methylanthracene (2a) was obtained as the desired product in
65% yield, with 10% yield of the ketone byproduct (3a), after 4 h
(Table 1, entry 5). To improve the yields of the anthracenes, and
minimize byproducts, an attempt was made to enhance the reac-
tivity by adding Brønsted acids. The concurrent use of 1 equiv of
methanesulfonic acid (MsOH) or camphorsulfonic acid (CSA) was
found to reduce the reactivity, and the use of trifluoromethanesul-
fonic acid (TfOH) resulted in a complex reaction mixture (Table 1,
entries 6–8). However, the concurrent use of trifluoroacetic acid
(TFA) increased the yield of 2a to 84% (isolated yield: 79%) after
30 min (Table 1, entry 9).
synthesized via
a Bradsher-type reaction using 2-acyldiaryl-
methane in the presence of a Lewis acid.5 However, this reaction
has disadvantages, including vigorous reaction conditions, low
reaction yields, and a limited range of compatible functional
groups. An effective method for the Au-catalyzed synthesis of
anthracene derivatives via cycloisomerization of o-alkynyldiaryl-
methane has recently been reported.6 The disadvantage of this
method is the use of an expensive gold catalyst and acid. Recently,
a wide range of hydroarylations using Brønsted acid, Au-catalyst,
etc. has been reported.7 We also reported that Fe or Bi can be used
as an effective catalyst for alkyne activation.8 In particular, Bi has
been widely used over the past several years in low-cost, low-
toxicity, and ecofriendly catalysts for organic synthesis.9 This Letter
presents a novel method for efficiently synthesizing anthracene
derivatives via Bi-catalyzed alkyne activation (Scheme 1).
Reducing the amount of TFA to 0.5 equiv led to a decrease in the
yield, and the use of TFA without the catalyst Bi(OTf)3 was shown
to be inefficient (Table 1, entries 10 and 11).
⇑
Corresponding author. Tel.: +82 33 250 6488; fax: +82 33 250 6480 (D.-C.L.);
tel.: +82 33 250 6477; fax: +82 33 250 6470 (K.L.).
E-mail addresses: dclee@kangwon.ac.kr (D.-C. Lee), lky@kangwon.ac.kr (K. Lee).
http://dx.doi.org/10.1016/j.tetlet.2015.10.111
0040-4039/Ó 2015 Published by Elsevier Ltd.
Please cite this article in press as: Park, J.; et al. Tetrahedron Lett. (2015), http://dx.doi.org/10.1016/j.tetlet.2015.10.111

2
J. Park et al. / Tetrahedron Letters xxx (2015) xxx–xxx
Table 2 (continued)
Bi(OTf)3 (5 mol%)
TFA (1.0 equiv)
R2
R2
Entry Subtract
Product
Yieldb
(%)
R1
R1
DCE, 60 o
C
Me
Scheme 1. Bi-catalysis of anthracene.
1f
2f
6
7
70
86
Me
Me
Me
OMe
OMe
Table 1
Optimization of the reaction conditionsa
1g
2g
Ph
Me
Me
ꢀ
catalyst
+
DCE, 60 oC
1h
Me
O
2h
8
61
48
54
46
OMe
F
OMe
F
1a
2a
3a
Entry
Catalyst (5 mol %)
Acid (equiv)
Time (h)
Yieldb (%) [2a:3a]
1i
2c
2j
9
1
2
3
4
5
6
7
8
Sc(OTf)3
In(OTf)3
Cu(OTf)2
Fe(OTf)3
Bi(OTf)3
Bi(OTf)3
Bi(OTf)3
Bi(OTf)3
Bi(OTf)3
Bi(OTf)3
20
20
20
10
4
<1:0
21:3
45:8
Me
Me
1j
46:10
10
11
65 (59)c:10
48:32
F
F
MsOH (1.0)
CSA (1.0)
TfOH (1.0)
TFA (1.0)
TFA (0.5)
TFA (1.0)
4
10
0.5
0.5
0.5
2
35:39
0:0
Cl
Cl
1k
2k
9
10
11
84 (79)c:0
59 (52)c:0
23:0
Me
Me
Me
1l
The Bold values indicate the best reaction condition.
2l
12
13
60
64
a
Cl
Cl
The reaction conditions: 1-benzyl-2-ethylbenzene (1a, 0.3 mol), DCE (2 mL),
under a nitrogen atmosphere.
Yields are based on 2a and determined by crude 1H NMR using dibromo-
b
methane as the internal standard.
1m
2m
c
Isolated yield.
a
Reaction conditions: o-alkynyldiarylmethane (1, 0.3 mmol), Bi(OTf)3 (5 mol %),
TFA (1.0 equiv), solvent (2 mL), under a nitrogen atmosphere.
b
Isolated yield.
Table 2
Bismuth-catalyzed cycloisomerization of o-alkynyldiarylmethane to obtain
anthracenesa
Table 3
Bi(OTf)3 (5 mol%)
Bi-catalysis of anthracene
R2
R2
TFA (1.0 equiv)
Catalyst (5 mol%)
Ph
R1
R1
DCE, 60 oC, 0.5 h
Me
2
Additive (1.0 equiv)
1
Me
DCE, 60 oC
Me
2a
O
Entry Subtract
Product
Yieldb
3a
(%)
Entry
Catalyst
Additive
TFA
Time (h)
Yield (%) 3a:2a
1a
2a
1
79
1
2
3
4
5
Bi(OTf)3
Bi(OTf)3
BiCl3
14
14
24
24
14
84:13
0:97
98:<2
90:<2
91:<2
Me
BiCl3
TFA
TFA
1b
2b
2
67
52
Me
Me
F
Me
a The reaction conditions: 1-(2-benzylphenyl)ethanone (3a, 0.3 mmol), DCE (2 mL),
under a nitrogen atmosphere.
F
b Yields are based on 2a and determined by crude 1H NMR using dibromomethane
as the internal standard.
1c
2c
3
Me
Me
c Isolated yield.
Me
1d
Ph
Me
2d
4
5
70
58
Lewis activation
Me
Me
O
Brφnsted activation
Me
Me
Bi(OTf)3
H
O
1e
2e
O
CF3
Scheme 2. The synergistic effect between Bi(OTf)3 and TFA.
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J. Park et al. / Tetrahedron Letters xxx (2015) xxx–xxx
3
H
Me
[Bi]
Bi(OTf)3
2a
TFA
+
Ph
Me
1a
Bi(OTf)3 / TFA
O
3a
Scheme 3. Proposed mechanism.
After determining the optimal reaction conditions, the reactiv-
ity of various substrates was investigated (Table 2). In the absence
of substituents on the benzene ring, product 2a was obtained in
79% yield (Table 2, entry 1). Anthracene 2b was obtained in 67%
yield from the reaction of 1-benzyl-2-ethynyl-4-methylbenzene
(1b), and when fluorine was introduced at the 5-position of the
benzene substituent, product 3b was obtained in 52% yield (Table 2,
entry 3). By introducing methyl and methoxy functional groups on
the phenyl substituent, the corresponding substituted 9-methylan-
thracenes were obtained in high yields (58–86%) (Table 2, entries
4–8). However, when highly electronegative halides were intro-
duced, slightly lower yields were obtained (46–60%) (Table 2,
entries 9–12). Additionally, when 2-(2-ethynylbenzyl)naphthalene
(1m) was used as the substrate, a substituted tetracene (2m) was
obtained in 64% yield (Table 2, entry 13). However, the reaction
did not proceed for internal alkynes in which methyl or phenyl
substituents were introduced at the terminal alkyne position.
The mechanism of this reaction and the role played by Bi(OTf)3
and Brønsted acids were investigated by reacting the hydration
product 1-(2-benzylphenyl)ethanone (3a) under various catalytic
conditions (Table 3). When Bi(OTf)3 alone was used, the desired
product was obtained in 13% yield after 14 h, with 84% of the sub-
strate left unreacted (Table 3, entry 1). However, when Bi(OTf)3
and TFA were used concurrently, product 3a was obtained in 97%
yield (Table 3, entry 2). In order to determine the effect of the cat-
alyst ligand on this reaction, a comparison was performed with the
use of BiCl3 alone and concurrent use of BiCl3 and TFA, neither of
which resulted in efficient production of 3a (Table 3, entries 3
and 4). Poor reactivity was also observed when TFA alone was used
(Table 3, entry 5).
the reaction. The advantages of this reaction include the use of
an ecofriendly bismuth catalyst, mild reaction conditions, rapid
reaction times, and good yields.
Acknowledgments
This work was supported by the Human Resource Training
Program for Regional Innovation and Creativity through the
Ministry of Education and National Research Foundation of Korea
(No. 2015H1C1A1035955).
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.tetlet.2015.10.
111.
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From the results of this experimental study, the role played by
TFA in this reaction is attributed to the synergetic effect of double
activation of the carbonyl group in the substrate by the Lewis and
Brønsted acids, rather than an increase in catalytic reactivity
(Scheme 2). In order to determine the effect of Brønsted acids,
the reaction was performed in the presence of the proton scav-
enger 2,6-di-tert-butylpyridine. The reaction did not proceed under
these conditions.
The proposed mechanism for this reaction is shown in Scheme 3.
Bi(OTf)3 mediates the p-activation of the C–C triple bond, thus gen-
erating a vinylbismuth intermediate via intramolecular hydroary-
lation, and finally yields anthracene 2a via isomerization.
Additionally, the hydration compound (3a) obtained as a bypro-
duct is proposed to form anthracene 2a as a cyclodehydration
product following double activation by Bi(OTf)3 and TFA.
In this study, we developed a novel method for synthesizing
anthracene derivatives as intramolecular hydroarylation products
via Bi(OTf)3-catalyzed alkyne activation. The yield of this reaction
could be enhanced by the addition of TFA, which facilitated
cyclodehydration of the hydration byproducts generated during
Please cite this article in press as: Park, J.; et al. Tetrahedron Lett. (2015), http://dx.doi.org/10.1016/j.tetlet.2015.10.111