Triflic acid promoted synthesis of polycyclic aromatic compounds

Article abstract of DOI:10.1016/j.tetlet.2009.02.042

The triflic acid (CF₃SO₃H) promoted cyclizations of 2-styrylbiaryls are found to be useful for the synthesis of polycyclic aromatic compounds, including functionalized derivatives of polycyclic aromatic compounds and heterocyclic sys

Full text of DOI:10.1016/j.tetlet.2009.02.042

Tetrahedron Letters 50 (2009) 1924–1927
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Triflic acid promoted synthesis of polycyclic aromatic compounds
*
Ang Li, Daniel J. DeSchepper, Douglas A. Klumpp
Department of Chemistry and Biochemistry, Northern Illinois University, DeKalb, IL 60115, United States
a r t i c l e i n f o
a b s t r a c t
Article history:
The triflic acid (CF3SO3H) promoted cyclizations of 2-styrylbiaryls are found to be useful for the synthesis
of polycyclic aromatic compounds, including functionalized derivatives of polycyclic aromatic com-
pounds and heterocyclic systems. The reaction involves cationic cyclization followed by an elimination
of benzene from the intermediate product.
Received 13 January 2009
Revised 4 February 2009
Accepted 5 February 2009
Available online 10 February 2009
Ó 2009 Elsevier Ltd. All rights reserved.
Keywords:
Superacid
Arenes
Heterocycles
Cyclization
Polycyclic aromatic hydrocarbons and related compounds have
been of great interest due to their relationships to chemical carci-
nogenesis.1 Besides their biological activities, these substances
have likewise been considered important components in material
In our initial investigation of this reaction, 2-styrylbiphenyl (2)
was prepared and reacted with superacidic CF3SO3H.6 This sub-
strate (along with other olefins used in this study) was synthesized
using Suzuki and Wittig coupling reactions (Eq. 2).4 When com-
pound 2 is reacted in superacid, the product mixture is complex,
but some phenanthrene (3, ca. 5–10% yield) is detected by GCMS
(Eq. 3). Other major products from the reaction include 9,10-dihy-
dro-9-phenylphenanthrene (4) and 9-benzyl-9H-fluorene (5). With
the formation of product 5, it is clear that both possible carbocat-
ionic intermediates (7a,b) are generated in the acid. The phenan-
threne (3) is formed by ipso-protonation of the phenyl group of
compound 4 and elimination of benzene. Other minor products
(ca. 5% yield) include biphenyl and dibenz[a,c]anthracene (6).
Although it is not exactly clear how these products are formed,
the presence of compound 6 suggests some type of dimerization
and cleavage reaction steps. Compound 2 was also reacted in the
gas-phase by flash vacuum pyrolysis (200 °C, 10ꢀ2 Torr) over the
solid acid Nafion-H. Overall a similar product mixture was ob-
served; however, the dibenz[a,c]anthracene (6) was not formed.
Since intermolecular reactions are less likely in the gas-phase, this
supports the idea that an intermolecular reaction gives compound
6 in the condensed phase.
science applications. Due to their extended p-systems, they can ex-
hibit novel optical properties.2 Consequently, there is the contin-
ued need for new synthetic routes leading to these types of
compounds and their functionalized derivatives.3 We recently de-
scribed a new superacid-promoted route to aza-polycyclic aro-
matic compounds (Eq. 1).4,5 This chemistry involves the
formation of superelectrophilic intermediates (i.e., 1), followed
by cyclization and elimination of benzene to give the condensed
aromatic compounds (i.e., 2). Because the precursor substrate pos-
sesses an N-heterocyclic ring that is fully protonated in acid, the
cyclizations occur via the dicationic, superelectrophilic intermedi-
ates such as 1. These results raised an interesting question: is it
possible to achieve similar condensation reactions through mono-
cationic reactions (without N-heterocyclic rings) to prepare poly-
cyclic aromatic hydrocarbons? In the following Letter, we
address this question and describe a new superacid-promoted syn-
thetic route to polycyclic aromatic hydrocarbons, substituted
derivatives, and heterocyclic systems.
Ph
Ph
- C6H6
85%
CF3SO3H
25 ºC
N
Ph
N
H
Ph
N
ð1Þ
PhB(OH)2
Pd(OAc)2
PhCH=PPh3
Br
1
2
CHO
CHO
2
Ph
ð2Þ
* Corresponding author. Tel.: +1 815 753 1959; fax: +1 815 753 4802.
E-mail address: dklumpp@niu.edu (D.A. Klumpp).
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.02.042

A. Li et al. / Tetrahedron Letters 50 (2009) 1924–1927
Ph
1925
Table 1
Ph
Ph
Cyclizations of styryl-substituted precursors 8–14 to the condensed products 15–22
in CF3SO3H
Entry Starting material
Product(s)
Yieldd
(%)
Ph
7a
7b
3
4
CF3SO3H
25°C
2
Ph
1
52a
71a
Ph
15
8
Ph
5
6
OCH3
OCH3
ð3Þ
The formation of some phenanthrene (3) from 2-styrylbiphenyl
2
3
Ph
Ph
16
9
(2) was a promising initial result, so a number of styryl-substituted
arenes were prepared and reacted with CF3SO3H (Table 1). Sub-
strate 8 gives naphtho[1,2-a]pyrene (15) as the major product in
fair yield. This system (8) differs from 2-styrylbiphenyl (2) most
notably by the increased nucleophilic character of the pyrenyl
group versus the phenyl group (in 2). Similarly, reactions of the
aryl ether derivatives 9 and 10 provide good yields of the conden-
sation products (entries 2 and 3). In the case of substrate 9, the
reaction with CF3SO3H gives 2-methoxyphenanthrene (16), while
compound 10 produces two regioisomers (17 and 18) from reac-
tion at the 5- and 8-positions of the benzodioxane ring. Nitro-func-
tionalized substrates give the polycyclic aromatic compounds in
good yields, with the preparation of 2-nitrophenanthrene (19)
and 2-nitrochrysene (20). Cyclization of 12 occurs regioselectively
at the 1-position of the naphthyl ring. Although the yields were
low, heterocyclic systems (21 and 22) were prepared from cycliza-
tion of a benzothiophene derivative (13) and the dibenzofuran
derivative (14). Most of the condensation reactions were done by
reacting a CHCl3 solution the substrate with CF3SO3H at 25 °C.
However, in some cases, the reaction conditions needed to be tai-
lored for particular substrates. For example, compound 12 gave
complex product mixtures when the reaction was done at temper-
atures warmer than 0 °C.
O
O
O
O
O
O
34a
41%
10
17
18
O2N
O2N
O2N
O2N
4
5
6
7
81a
78b
42c
12a
Ph
19
11
Ph
20
12
S
S
Ph
13
21
Ph
O
O
22
14
In order to obtain better yields for the conversions, we reasoned
that the 2-phenyl-1-propenyl system should lead to regioselective
protonation and more efficient cyclizations. Several 2-phenyl-1-
propenyl derivatives were prepared and reacted with superacid
(Eqs. 4,5,6). When compounds 23 and 24 were reacted with
CF3SO3H, the polycyclic aromatic hydrocarbons (26 and 28) are
formed in reasonably good yields. The conversion of compound
23 to 9-methylphenanthrene (26) is a marked improvement over
the analogous reaction of 2-styrylbiphenyl (2) to give phenan-
threne (3, Eq. 2). This improvement may be understood by consid-
ering the regioselectivity of protonation. Compounds 23 and 24 are
a
b
c
Reaction done at 25 °C.
Reaction done at 0 °C.
Reaction done at 65 °C.
d
Isolated yields of pure products. Products were characterized by 1H and 13C
NMR and by high resolution and low resolution mass spectra.
protonated exclusively at the 1-carbon position of the olefinic
groups, leading to the stable 3° carbocations (i.e., 27). This leads
to efficient conversions to the phenanthrenes. In the case of com-
pound 24, however, the product mixture also contains a small
amount of 9-methyl-2-phenylphenanthrene (29; visible by NMR),
CF3SO3H
25 ºC
ð4Þ
80%
CH3
Ph
Ph
23
26
27
CH3
CH3
Ph
Ph
CF3SO3H
25 ºC
Ph
ð5Þ
Ph
CH3
H3C
75%
Trace
24
28
29
CH3
Ph
CH3
CF3SO3H
25 ºC
ð6Þ
CH3
O
O
88%
25
30

1926
A. Li et al. / Tetrahedron Letters 50 (2009) 1924–1927
-H+
H+
Ph
Ph
29
28
ð7Þ
ð8Þ
H
CH3
H3C
H
32
31
1) Mg, THF
2)
CF3SO3H
O
33
CH2Br
*
HO
*
CH3
*
*
Ph
CH3
Ph
CH
CH
*
3
*
3
*
*
13C labels:
*
34a
34b
which can be removed from the 10-methyl-2-phenylphenanthrene
(28) by recrystallization. In a similar respect, reaction of compound
25 gives a high yield of the cyclization product 30; however, it is
formed as an inseparable pair of structural isomers (ca. 1:1 ratio).
Presumably, these isomeric products are formed by migration of
the methyl group in product 30 as a result of protonation in super-
acid. The same isomerization evidently occurs with compound 28
(Eq. 6).8 To verify that methyl migration can occur in these sys-
tems, a doubly 13C labeled derivative was also prepared and the
precursor alcohol was reacted in CF3SO3H (Eq. 8). 2-Bro-
momethylbiphenyl gave the Grignard reagent, which reacted with
doubly labeled acetophenone to provide alcohol 33. Upon reaction
with CF3SO3H, the expected 9-methylphenanthrene (34a,b) was
produced quantitatively. NMR analysis showed that the product
9-methylphenanthrene had undergone extensive 13C scrambling,
presumably through methyl migration. The acid-catalyzed migra-
tion of methyl-substituents on arenes is a well-known process,
for example, in the industrial-scale isomerization of xylene iso-
mers.7 In the present case, the isomerization may, however, lead
to undesirable product isomers of the polycyclic aromatic
compounds.
Although it was shown that compound 2 may produce phenan-
threne by flash vacuum pyrolysis at 200 °C over Nafion-H catalyst,
CF3SO3H is the only acid catalyst found to produce the polycyclic
aromatic compounds at modest temperatures in the condensed
phase. A series of solid acids, electrophilic metals, and other cata-
lysts were tested for their activities in the cyclization of compound
9 (Fig. 1). Several of the catalytic systems induced cyclization,
although none gave benzene elimination. Some of the electrophilic
metal catalysts, such as PtCl2, isomerized the olefin group in 9, but
did not give the cyclized products (35 and 36).
The cyclization of styryl-substituted biaryl systems is a new
general synthetic route to polycyclic aromatic systems. This super-
acid-promoted conversion in most cases is thought to involve
monocationic cationic intermediates. For example, in the conver-
sion of compound 9 to 2-methoxyphenanthrene (16), protonation
of the styryl group begins a series of reaction steps involving three
carbocationic species (37–39, Eq. 9). Benzene elimination requires
ipso-protonation of intermediate 35. Thus, very strong acids (or
high temperatures) are required to complete the condensation
reaction. Mechanistically, the overall conversion is similar to the
methoxy-vinyl cyclization strategy developed by the Harvey group,
although in the later case mild acids could be employed.8 In the
case of the nitro-substituted compounds (11 and 12), the reaction
may involve superelectrophilic, diprotonated species. Nitro-substi-
tuted arenes are known to be protonated in CF3SO3H at the nitro
group and they can participate in superelectrophilic reactions.9
This suggests either the dication 40 or the protosolvated species
41 as the initial intermediate. Both 40 and 41 are expected to pos-
sess enhanced electrophilic reactivities compared to related mon-
ocationic species (i.e., 7b). Moreover, protonation of the nitro
group should tend to disfavor the undesired intermediate 42 due
to electrostatic repulsive effects.10
ACID
OCH3
OCH3
9
Ph
35
Ph
36
16
OCH3
Reaction Products and Catalyst Systems
Starting Materials Only
Catalyst Systems:
1. PtCl2, 50 ºC, 24 hr
2. AuCl3, 50 ºC, 24 hr
3. AuCl, 50 ºC, 24 hr
4. CF3CO2H, 25 ºC, 24 hr
5. Sulfated zirconia
Products 35 and 36 Formed
Catalyst Systems:
1. PtCl2/AgOTf, 50 ºC, 24 hr
2. AuCl3/AgOTf, 50 ºC, 24 hr
3. Phosphotungstic acid, 50 ºC, 24 hr
4. Montmorillonite KSF, 50 ºC, 24 hr
5. Nafion SCA-13, 50 ºC, 24 hr
Product 16 Formed
Catalyst System:
1. CF3SO3H, 25 ºC, 24 hr
Figure 1. Reactions of olefin 9 with various acids.

A. Li et al. / Tetrahedron Letters 50 (2009) 1924–1927
1927
OCH3
-H+
H+
OCH3
9
Ph
Ph
35
37
H+
ð9Þ
OCH3
OCH3
16
-H+
-C6H6
H
39
38
δ
CF3SO3
H
δ
HO2N
O2N
HO2N
Ph
Ph
40
41
42 Ph
6. (a) Olah, G. A.; Prakash, G. K. S.; Sommer, J. Superacids; Wiley: New York, 1985;
(b) Trifluoromethanesulfonic acid. e-EROS.
7. (a) Olah, G. A.; Molnar, A. Hydrocarbon Chemistry; Wiley: New York, 2003; See
also: (b) Xu, D.; Duan, Y.; Blair, I. A.; Penning, T. M.; Harvey, R. G. Org. Lett. 2008,
10, 1059.
8. (a) Harvey, R. G.; Dai, Q.; Ran, C.; Penning, T. M. J. Org. Chem. 2004, 69, 2024; (b)
Xu, D.; Penning, T. M.; Blair, I. A.; Harvey, R. G. J. Org. Chem. 2009, 74, 597.
9. (a) Ohwada, T.; Ohta, T.; Shudo, K. J. Am. Chem. Soc. 1986, 108, 3029; (b) Ohta,
T.; Shudo, K.; Okamoto, T. Tetrahedron Lett. 1984, 25, 325; (c) Ohwada, T.; Itai,
A.; Ohta, T.; Shudo, K. J. Am. Chem. Soc. 1987, 109, 7036; (d) Ohwada, T.; Okabe,
K.; Ohta, T.; Shudo, K. Tetrahedron 1990, 46, 7539.
In summary, we have found that reactions of olefinic substrates
with superacid can give polycyclic aromatic products.11 Substi-
tuted derivatives may also be prepared. An addition–elimination
mechanism is proposed for this condensation reaction, including
a superacid-promoted benzene elimination. Most of the conver-
sions are thought to involve monocationic species; however, the
nitro-substituted systems may react via dicationic superelectro-
philes (with protonated nitro groups). The condensations were
found to be most successful when the olefin group tends to be
regioselectively protonated. Good conversions were also observed
with activated (nucleophilic) aryl groups, such pyrenyl and 4-
methoxyphenyl groups.
10. Klumpp, D. A. Chem. Eur. J. 2008, 14, 2004.
11. General procedure for cyclization of the olefins to the polycyclic aromatic
compounds: The olefin (1 mmol) is dissolved in 1 mL of CHCl3 and the
solution is cooled to 0 °C. Triflic acid (3 mL, 30 mmol) is slowly added to the
solution. Depending on the substrate, the mixture is stirred from 2 to 18 h at
reaction temperatures from 0 °C to 65 °C. The solution is then poured over ca.
15 g of ice and it is made slightly basic by dropwise addition of 10 M NaOH. The
mixture is then extracted twice with CHCl3 and the organic phase is washed
with water, followed by two brine washes. The chloroform solution is then
dried over Na2SO4, filtered, and concentrated to yield crude product. Products
are then purified by column chromatography (silica gel, hexanes–ether).
Benzo[b]phenanthro[3,4-d]furan (22): White solid, mp: 135–140 °C. 1H NMR
(CDCl3, 500 MHz) d, ppm: 7.45–7.49 (m, 1H), 7.56–7.59 (m, 1H), 7.72–7.75 (m,
1H), 7.85–7.93 (m, 5H), 8.00–8.02 (d, J = 7.8 Hz, 1H), 8.09–8.10 (d, J = 7.6 Hz,
1H), 8.15–8.17 (d, J = 8.1 Hz, 1H), 9.84–9.86 (d, J = 8.4 Hz, 1H). 13C NMR (CDCl3,
125 MHz) d, ppm: 111.9, 117.9, 118.8, 120.4, 122.1, 123.1, 124.0, 124.3,
126.7, 127.1, 127.2, 127.9, 128.3, 138.7, 132.5, 153.5, 156.1. High resolution
Acknowledgments
Grateful acknowledgment is made to the Donors of the Ameri-
can Chemical Society Petroleum Research Fund for support of this
research (PRF# 44697-AC1) and the National Science Foundation
(CHE-0749907) for support of this work.
References and notes
MS (EI), C20H12
O calcd: 268.08882, found: 268.09060. 10-Methyl-2-
phenylphenanthrene (28): White solid, mp: 105–107 °C. 1H NMR (CDCl3,
500 MHz) d, ppm: 2.80 (s, 3H), 7.45–7.47 (t, J = 7.4 Hz, 1H), 7.55–7.58 (t,
J = 7.7 Hz, 1H), 7.68–7.74 (m, 3H), 7.82–7.82 (d, J = 8.1 Hz, 2H), 7.88–7.90 (dd,
J1 = 8.6 Hz, J2 = 1.5 Hz, 1H), 8.07 (d, J = 1.5 Hz, 1H), 8.11–8.13 (m, 1H), 8.73–8.75
(d, J = 8.6 Hz, 1H), 8.76–8.78 (m, 1H). 13C NMR (CDCl3, 125 MHz) d, ppm: 20.1,
123.1, 124.8, 125.1, 125.9, 126.4, 126.6, 127.0, 127.4, 127.6,129.0, 130.3, 132.2,
132.4, 133.0, 139.2, 141.0. High resolution MS (EI), C21H16 calcd: 268.12520,
found: 268.12415.
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