Br?nsted acid-catalyzed tandem cycloaromatization of naphthalene-based bisacetals: Selective synthesis of ortho-fused six-hexagon benzenoids

Article abstract of DOI:10.1246/cl.161122

Naphthalenes bearing two acetal moieties connected by a methylene-2,1-phenylene group underwent regioselective tandem cycloaromatization using a catalytic amount of trifluoro-methanesulfonic acid in 1,1,1,3,3,3-hexafluoropropan-2-ol. Five substrates were

Full text of DOI:10.1246/cl.161122

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Brønsted Acid-catalyzed Tandem Cycloaromatization of Naphthalene-based Bisacetals:
Selective Synthesis of ortho-Fused Six-hexagon Benzenoids
Ikko Takahashi, Masaki Hayashi, Takeshi Fujita, and Junji Ichikawa*
Advance Publication on the web December 29, 2016
doi:10.1246/cl.161122
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2016 The Chemical Society of Japan
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1
Brønsted Acid-catalyzed Tandem Cycloaromatization of Naphthalene-based Bisacetals:
Selective Synthesis of ortho-Fused Six-hexagon Benzenoids
Ikko Takahashi, Masaki Hayashi, Takeshi Fujita, and Junji Ichikawa*
Division of Chemistry, Faculty of Pure and Applied Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8571
(
E-mail: junji@chem.tsukuba.ac.jp)
Naphthalenes bearing two acetal moieties connected by a
which was obtained via double O-sulfonylation of
naphthalene-2,7-diol (5a). Bis(vinyl ether) 1a was prepared
via the Suzuki–Miyaura cross-coupling of 4a with (2-
formylphenyl)boronic acid, followed by a Wittig reaction
methylene-2,1-phenylene group underwent regioselective
tandem cycloaromatization using a catalytic amount of
trifluoromethanesulfonic
acid
in
1,1,1,3,3,3-
hexafluoropropan-2-ol. Five substrates were successfully
employed in this protocol to afford ortho-fused six-hexagon
benzenoids with high selectivities and in excellent yields.
with
(methoxymethyl)triphenylphosphonium
chloride.
However, although hydrolysis of 1a afforded the
corresponding dial, it was unstable for use in the subsequent
cycloaromatization. In contrast, bisacetal 2a was directly
prepared via the Suzuki–Miyaura cross-coupling of 4a with 2-
[(1,3-dioxolan-2-yl)methyl]phenylboronic acid pinacolate.
Other bisacetal precursors 2b–e were also prepared similarly
(see Supporting Information).
Polycyclic aromatic hydrocarbons (PAHs) have
polyform structures comprising benzene rings, and are
considered to be promising candidates for functional materials
1
such as electronic devices and liquid crystals. As the number
of benzene rings in PAHs increases, the number of structural
isomers exponentially increases. Although PAHs of
substantial sizes have numerous isomers, research has
typically focused on isomers of specific families such as
1) Suzuki–Miyaura
coupling
HO
OH
O
H CO
1
b–d,2
1d,e,3
1f,4
3
acenes,
phenacenes,
and helicenes, and not on other
(
HO) B
5
2
ortho-fused isomers despite their great potential.
We recently developed
5a
a
Brønsted acid-catalyzed
2) Wittig
cycloaromatization of carbonyl compounds, resulting in the
synthesis of phenanthrene and anthracene derivatives. As the
6
Ph3P
OCH3
TfO
OTf
Cl–
OCH3
1a
method served as
a powerful tool for benzene-ring
O
O
construction, we embarked on the synthesis of PAHs in a
variety of shapes via double cycloaromatization of substrates
bearing two reactive sites. This protocol would enable rapid
access to higher-order PAHs by simultaneous construction of
multiple fused benzene rings.
4
a
Suzuki–Miyaura
coupling
7
O
O
O
We selected naphthalenes
1
and
2
bearing two
B(pin)
O
2
a
phenylacetaldehyde-related moieties as cyclization precursors.
Their tandem cycloaromatization afforded ortho-fused
benzenoids, with the structure depending on the substitution
pattern on the naphthalene ring. As a result, five predicted
isomers of the ortho-fused benzenoids bearing six benzene
rings were selectively synthesized in excellent yields from
readily available cyclization precursors.
Scheme 2. Preparation of bis(vinyl ether) 1a and bisacetal 2a.
We sought suitable conditions for tandem
cycloaromatization of bis(vinyl ether) 1a and bisacetal 2a
as model substrates (Table 1). First, the reaction of 1a was
7
k,8
9
investigated
using
a
catalytic
amount
of
R
trifluoromethansulfonic acid (TfOH) and 1,1,1,3,3,3-
hexafluoropropan-2-ol (HFIP) as a solvent. On treatment
1
0
cat. TfOH
with 15 mol% of TfOH, bis(vinyl ether) 1a at 0.05 M in HFIP
HFIP
underwent
tandem
cycloaromatization
to
afford
R
etc.
ortho-fused six-hexagon
benzenoids 3
1
1
dibenzo[c,m]tetraphene (3a) and naphtho[1,2-c]chrysene
(3a') in 79% total yield and in a 75:25 ratio (Entry 1).
O
OCH
12
R =
3 (1),
(2)
O
Neither more concentrated nor more dilute conditions
improved the total yield of 3a and 3a' (Entries 2 and 3). In
contrast, when bisacetal 2a at 0.1 or 0.3 M in HFIP was
treated with 15 mol% of TfOH, the product yield and ratio
significantly improved to afford 3a exclusively in almost
quantitative yields (Entries 4 and 5). As a result, the
efficiency and selectivity remained excellent even when the
amount of TfOH was reduced to 10 mol% (Entry 7). The
selective formation of 3a is attributed to the following factors:
Scheme 1. Synthesis of ortho-fused six-hexagon benzenoids
via TfOH-catalyzed tandem cycloaromatization.
The cyclization precursors 1a and 2a bearing two
phenylacetaldehyde-related moieties on the 2- and 7-positions
of the naphthalene ring were readily available starting from
naphthalene-2,7-diyl bis(trifluoromethanesulfonate) (4a),

2
(
i) the first cycloaromatization would proceed at the α-
O
O
position of the naphthalene core in accordance with the
regioselectivity observed in normal electrophilic aromatic
substitution reactions and (ii) the second cycloaromatization
might proceed avoiding steric hindrance, which explains the
better selectivity of bisacetal 2a.
1
7
2
O
3
a 97%
O
Table 1.
Screening of conditions for tandem
2
a
cycloaromatization of 1a and 2a
O
O
O
R
1
4
7
2
2
TfOH (X mol%)
HFIP (Y M)
3
a
R
+
0
°C, 15 min
OCH3
O
O
1
2
a: R =
a: R =
2
b
3b 84%
O
O
3
a'
O
a
b
Entry 1a or 2a X (mol%) Y (M)
Total yield (%)
3a/3a'
75:25
75:25
70:30
1
c
1
2
3
4
5
6
7
8
a
1a
1a
1a
2a
2a
2a
2a
2a
15
15
15
15
15
15
10
3
0.05
0.03
0.1
79
3
c
c
5
80
O
71
O
0.1
quant.
quant.
86
> 99:< 1
> 99:< 1
93:7
2c
3c 99%
0.3
O
1.0
O
1
0.3
quant. (97)
77
> 99:< 1
> 99:< 1
0.3
4
6
1
Yield was determined by H NMR spectroscopy using CH
internal standard. Isolated yield was shown in parentheses. Isomer ratio
was determined by H NMR spectroscopy. EE/EZ/ZZ = 37:55:8.
2
Br
2
as an
b
1
c
O
O
3d 95% (98:2)b
2
d
Not only bisacetal 2a but also bisacetals 2b–e
participated in the tandem cycloaromatization under the
abovementioned optimal conditions (Table 2). Naphthalenes
O
O
O
1
b and 1c, bearing two phenylacetaldehyde acetal moieties on
the 1,4- and 1,5-positions, respectively, successfully
underwent tandem cycloaromatization to afford
O
5
1
7
1
3
14
benzo[s]picene (3b) and dibenzo[c,l]chrysene (3c) as the
only products in 84% and 99% yields, respectively (Entries 4
and 5). Although the reactions of 1b and 1c required
cycloaromatization on the less reactive β-positions of the
naphthalene core in the first cyclization, benzenoids 3b and 3c
were obtained in high to excellent yields. Tandem
cycloaromatization of 1,6- and 1,7-disubstituted naphthalenes
3
e 87% (93:7)b
2
e
a
b
Isolated yield. T1otal yield of isomers. Product ratio (3d/3d' or 3e/3e')
was determined by H NMR spectroscopy.
1
1
2
d and 2e also proceeded to afford benzo[a]picene (3d) and
15
naphtho[2,1-c]chrysene (3e), respectively, as major products
Entries 4 and 5). In each case, one of two possible products
(
was selectively formed, presumably because regioselective
cycloaromatization proceeded preferably on the α-position of
the naphthalene core.
3
d'
3e'
a
Table 2. Synthesis of ortho-fused six-hexagon benzenoids 3
In summary, we achieved a systematic synthesis of a
series of rarely offered ortho-fused six-hexagon benzenoids
Entry
2
3
via
TfOH-catalyzed
tandem
cycloaromatization
of
naphthalene-based bisacetals. The use of benzenoids larger

3
than naphthalene as platforms will enable the synthesis of
more extensive ortho-fused benzenoids.
Jeszka, P. Uznański, S. Kania, J. Kuliński, P. Bałczewski, Chem.—
Eur. J. 2012, 18, 4866.
1
0
For reviews on fluorinated alcohols, see: a) J.-P. Bégué, D. Bonnet-
Delpon, B. Crousse, Synlett 2004, 18. b) I. A. Shuklov, N. V.
Dubrovina, A. Börner, Synthesis 2007, 2925. c) T. Dohi, N.
Yamaoka, Y. Kita, Tetrahedron 2010, 66, 5775. d) S. Khaksar, J.
Fluorine Chem. 2015, 172, 51. See also ref. 6 and references cited
therein.
This work was financially supported by JSPS
KAKENHI Grant Number JP16H04105 (J.I.). We
acknowledge generous gifts of (CF
TfOH from Central Glass Co., Ltd.
3 2
) CHOH (HFIP) and
1
1
1
2
No synthetic method is known in the literatures.
Although dibenzo[a,l]tetracene (3a'') is considered to be another
possible product, its formation is not detected at all under
conditions we screened.
Supporting Information is also available electronically
the CSJ-Journal Web site,
on
http://www.csj.jp/journals/chem-lett/index.html.
References and Notes
1
a) R. G. Harvey, Polycyclic Aromatic Hydrocarbons, Wiley-VCH,
New York, 1997. b) J. E. Anthony, Chem. Rev. 2006, 106, 5028. c)
J. E. Anthony, Angew. Chem., Int. Ed. 2008, 47, 452. d) Y.
Yamashita, Sci. Technol. Adv. Mater. 2009, 10, 024313. e) Y.
Kubozono, X. He, S. Hamao, K. Teranishi, H. Goto, R. Eguchi, T.
Kambe, S. Gohda, Y. Nishihara, Eur. J. Inorg. Chem. 2014, 3806.
f) M. Rickhaus, M. Mayor, M. Juríček, Chem. Soc. Rev. 2016, 45,
3
a''
13
a) X.-Q. Tang, R. G. Harvey, J. Org. Chem. 1995, 60, 3568. b) R.
G. Harvey, J.-T. Zhang, E. Luna, J. Pataki, J. Org. Chem. 1998, 63,
6405. c) D. Vasu, H. Yorimitsu, A. Osuka, Angew. Chem., Int. Ed.
2015, 54, 7162.
J. Brison, C. de Bakker, N. Defay, F. Geerts-Evrard, M.-J.
Marchant, R. H. Martin, Bull. Soc. Chim. Belg. 1983, 92, 901.
Compound 3e was synthesized as a minor product. See ref. 14.
14
15
1
542.
2
3
For reviews on acene synthesis, see: a) R. A. Pascal, Jr., Chem. Rev.
2
1
006, 106, 4809. b) H. F. Bettinger, C. Tönshoff, Chem. Rec. 2015,
5, 364.
For selected reports on phenacene synthesis, see: a) F. B. Mallory,
K. E. Butler, A. C. Evans, E. J. Brondyke, C. W. Mallory, C. Yang,
A. Ellenstein, J. Am. Chem. Soc. 1997, 119, 2119. b) A.-E. Gies, M.
Pfeffer, J. Org. Chem. 1999, 64, 3650. c) V. Mamane, P. Hannen,
A. Fürstner, Chem.—Eur. J. 2004, 10, 4556. d) S. Some, B. Dutta,
J. K. Ray, Tetrahedron Lett. 2006, 47, 1221. e) H. Okamoto, M.
Yamaji, S. Gohda, Y. Kubozono, N. Komura, K. Sato, H. Sugino,
K. Satake, Org. Lett. 2011, 13, 2758.
4
5
For reviews on helicene synthesis, see: a) A. Urbano, Angew.
Chem., Int. Ed. 2003, 42, 3986. b) Y. Shen, C.-F. Chen, Chem. Rev.
2
012, 112, 1463. c) M. Gingras, Chem. Soc. Rev. 2013, 42, 968.
For review on comprehensive synthesis of PAHs via
a
a
photochemical oxidative cyclization, see: F. B. Mallory, C. W.
Mallory, Org. React. 1984, 30, 1.
6
7
T. Fujita, I. Takahashi, M. Hayashi, J. Wang, K. Fuchibe, J.
Ichikawa, Eur. J. Org. Chem. doi: 10.1002/ejoc.201601406.
For selected reports on PAH synthesis via tandem cyclization, see:
a) M. B. Goldfinger, K. B. Crawford, T. M. Swager, J. Am. Chem.
Soc. 1997, 119, 4578. b) M. C. Bonifacio, C. R. Robertson, J.-Y.
Jung, B. T. King, J. Org. Chem. 2005, 70, 8522. c) H.-C. Shen, J.-
M. Tang, H.-K. Chang, C.-W. Yang, R.-S. Liu, J. Org. Chem. 2005,
7
0, 10113. d) K. Kamikawa, I. Takemoto, S. Takemoto, H.
Matsuzaka, J. Org. Chem. 2007, 72, 7406. e) T.-A. Chen, T.-J. Lee,
M.-Y. Lin, S. M. A. Sohel, E. W.-G. Diau, S.-F. Lush, R.-S. Liu,
Chem.—Eur. J. 2010, 16, 1826. f) T. Matsuda, T. Moriya, T. Goya,
M. Murakami, Chem. Lett. 2011, 40, 40. g) K. Kitazawa, T. Kochi,
M. Nitani, Y. Ie, Y. Aso, F. Kakiuchi, Chem. Lett. 2011, 40, 300.
h) T. Nakae, R. Ohnishi, Y. Kitahata, T. Soukawa, H. Sato, S. Mori,
T. Okujima, H. Uno, H. Sakaguchi, Tetrahedron Lett. 2012, 53,
1
2
617. i) R. Umeda, S. Miyake, Y. Nishiyama, Chem. Lett. 2012, 41,
15. j) M. Little, H. Lan, J. Raftery, J. J. Morrison, J. J. W.
McDouall, S. G. Yeates, P. Quayle, Eur. J. Org. Chem. 2013, 6038.
k) M. Murai, H. Maekawa, S. Hamao, Y. Kubozono, D. Roy, K.
Takai, Org. Lett. 2015, 17, 708. l) K. Ozaki, K. Kawasumi, M.
Shibata, H. Ito, K. Itami, Nat. Commun. 2015, 6, 6251. m) K. Mori,
T. Murase, M. Fujita, Angew. Chem., Int. Ed. 2015, 54, 6847.
For cycloaromatization of vinyl ethers, see: a) R. G. Harvey, K.
Lim, Q. Dai, J. Org. Chem. 2004, 69, 1372. b) R. G. Harvey, Q.
Dai, C. Ran, T. M. Penning, J. Org. Chem. 2004, 69, 2024. c) K.
Namba, H. Yamamoto, I. Sasaki, K. Mori, H. Imagawa, M.
Nishizawa, Org. Lett. 2008, 10, 1767. d) M. Murai, N. Hosokawa,
D. Roy, K. Takai, Org. Lett. 2014, 16, 4134. e) D. Roy, H.
Maekawa, M. Murai, K. Takai, Chem. Asian J. 2015, 10, 2518.
Cycloaromatization of acetals was reported only for acene
synthesis. See: a) P. Bałczewski, M. Koprowski, A. Bodzioch, B.
Marciniak, E. Różycka-Sokołowska, J. Org. Chem. 2006, 71, 2899.
b) A. Bodzioch, B. Marciniak, E. Różycka-Sokołowska, J. K.
8
9