Direct synthesis of 2-arylazulenes by [8+2] cycloaddition of 2: H -cyclohepta [b] furan-2-ones with silyl enol ethers

Article abstract of DOI:10.1039/c9cc09376a

We developed a procedure for the direct synthesis of 2-arylazulenes, which were obtained in moderate to excellent yields, by [8+2] cycloaddition of 2H-cyclohepta[b]furan-2-ones with aryl-substituted silyl enol ethers. The structures of some 2-arylazulenes were clarified by single-crystal X-ray analysis. The 2-phenylazulene derivatives obtained by this study showed noticeable fluorescence in acidic media.

Full text of DOI:10.1039/c9cc09376a

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Direct synthesis of 2‐arylazulenes by [8 + 2] cycloaddition of
2H‐cyclohepta[b]furan‐2‐ones with silyl enol ethers
Received 00th January 20xx,
Accepted 00th January 20xx
Taku Shoji,*a Shuhei Sugiyama,a Yoshiaki Kobayashi,a Akari Yamazaki,a Yukino Ariga,a Ryuzi Katoh,b
Hiroki Wakui,b Masafumi Yasunami (Deceased)*b and Shunji Itoc
DOI: 10.1039/x0xx00000x
www.rsc.org/
We have developed the procedure for the direct synthesis of 2‐ haloazulene precursors, especially 2‐haloazulenes8 and their
arylazulenes, which were obtained in moderate to excellent yields pseudo halides9, is usually not straightforward. Recently,
by [8 + 2] cycloaddition of 2H‐cyclohepta[b]furan‐2‐ones with aryl‐ Murafuji et al. reported the effective synthetic method for 2‐
substituted silyl enol ethers. The structure of some 2‐arylazulenes iodoazulenes from several azulenes via borylation at the 2‐
was clarified by single‐crystal X‐ray analysis. The 2‐phenylazulene position, followed by the treatment with CuI. This two‐step
derivatives obtained by this study showed noticeable fluorescence procedure enables to give 2‐iodoazulenes, but the use of an
in acidic‐media.
expensive iridium‐catalyst is essential to the borylation step at
the 2‐position of the azulene ring.10
Azulene is one of the non‐alternant aromatic compounds
and fascinates many researchers owing to its unusual reactivity
and properties derived from its polarization structure, as well
as its beautiful blue color. Functionalized azulene derivatives
have been mainly employed in medicinal chemistry.1 In recent
years, azulene derivatives have also prospects for the
application to organic electronics, such as n‐type
semiconductors,2 solar cells,3 non‐linear optics,4 and so on.5
For all of the above cases, the development of the method
for the functionalization of the azulene ring by an effective
procedure is extremely important. However, the characteristic
electronic properties of azulene derivatives sometimes
prevent their selective functionalization. The reactivity of
azulene at the odd‐positions, i.e., 1‐, 3‐, 5‐ and 7‐positions, has
been extensively studied because of their high reactivity
toward the aromatic electrophilic substitution reactions.6
Whereas, the introduction of functional groups to the even‐
numbered positions of azulene, that is, 2‐, 4‐, 6‐ and 8‐
positions, is mostly established by the cross‐coupling reaction.7
Indeed, the cross‐coupling reaction has enabled to access
highly functionalized azulenes. However, these approaches are
suffered from a serious disadvantage for the preparation of
In 1979, Yasunami and Takase et al. have reported the
efficient synthesis of azulenes by [8 + 2] cycloaddition (CA)
reaction of 2H‐cyclohepta[b]furan‐2‐ones with enamines, that
currently becomes one of the efficient methods for azulene
synthesis.11 This procedure is very effective for the preparation
of 2‐alkylazulene derivatives, but it is unsuitable for the
synthesis of 2‐arylazulenes from the viewpoint of their product
yields. Furthermore, the synthesis of 2‐arylazulenes by the
reaction with enamines was adapted only for the synthesis of
2‐phenylazulenes. Therefore, the development of the general
synthetic method for 2‐arylazulenes that is not employed by
the cross‐coupling reaction is one of the important tasks left in
azulene chemistry. From these backgrounds, we have
investigated the applicability of the [8 + 2] CA reaction of 2H‐
cyclohepta[b]furan‐2‐ones with various aryl‐substituted silyl
enol ethers, which show a similar reactivity to the enamines, in
an attempt to find a state‐of‐the‐art method in the synthesis
of 2‐arylazulenes.
The silyl enol ether method was adopted for the 2‐
arylazulene synthesis by using 3 equiv. of phenyl‐substituted
silyl enol ethers under the solvent‐free conditions to deliver
the products 2a
1a 1d (Table 1, entries 1−4). The use of 3 equiv. reagents was
−2d in good to excellent yields (75−92%) from
−
essential to the CA reaction since the employment of less
amount of the silyl enol ether reagents led to significant
decomposition of the starting materials with a small amount of
recovery (see the ESI). In most cases, unlike the cross‐coupling
reactions,7 the gram‐scale synthesis of 2‐phenylazulene
derivatives was possible under the reaction condition. The
a. Department of Material Science, Graduate School of Science and Technology,
Shinshu University, Matsumoto 390‐8621, Nagano, Japan. E‐mail:
tshoji@shinshu‐u.ac.jp
b. Department of Chemical Biology and Applied Chemistry, College of Engineering,
Nihon University, Koriyama 963‐8642, Fukushima, Japan.
c. Graduate School of Science and Technology, Hirosaki University, Hirosaki 036‐
8561, Aomori, Japan.
† Footnotes relaꢀng to the ꢀtle and/or authors should appear here.
Electronic Supplementary Information (ESI) available: [details of any
supplementary information available should be included here]. See
DOI: 10.1039/x0xx00000x
yield of 2a−2d hardly depended on the substituent position of
the alkyl group on the seven‐membered ring. 1,2‐
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Table 2. Reaction of 2H‐cyclohepta[b]furan‐2‐oneVsiewwAirtthicle Oarnyliln‐e
substituted silyl enol ethers.
Diphenylazulene 2e was also similarly obtained from 1e in 70%
yield. The reaction of 1f, 1g, and 1h without ester function also
DOI: 10.1039/C9CC09376A
afforded the corresponding products 3a (66%), 3b (63%) and
3c (71%), but the product yields were a bit low compared with
those of the cases of 1a
that the product yields of 1a
1e 1h implies that the electron‐withdrawing group on 2H‐
−
1d (Table 1, entries 6 and 7). This fact
−
1d were higher than those of
−
cyclohepta[b]furan‐2‐ones enhances the reactivity toward the
[8 + 2] CA reaction with the silyl enol ethers. Removal of the
ester function from 2a
treatment with 100% H3PO4 to afford 3a
(75−96%). As described above, 1,3‐positions of the azulene
ring are the most reactive sites toward electrophiles,6 so that
further functionalization of 3a−3d could be established by the
−
2d was also accomplished by the
3d in excellent yields
[8 + 2] CA
decarboxylation
Product,
Product,
−
Entry
Ar
R2
Yield [%]a
Yield [%]a
1
2
3
4
5
H
4a, 85
4b, 88
4c, 43
4d, 56
4e, 74
5a, 98
5b, 94
5c, 96
5d, 99
5e, 95
H
electrophilic substitution.
H
Table 1. Reaction of 2H‐cyclohepta[b]furan‐2‐ones 1a−1h with a
phenyl‐substituted silyl enol ether.a
H
i‐Pr
6
7
i‐Pr
i‐Pr
4f, 13
4g, 29
5f, 93
5g, 14
[8 + 2] CA decarboxylation
Product, Product,
Yield [%]b Yield [%]b
6
, 61
Entry Substrate R1
R2
H
8
9
H
4h, 86
4i, 59
5h, 93
1
2
3
4
5
6
7
8
1a
1b
1c
1d
1e
1f
CO2Me
2a, 92
2b, 85
2c, 84
2d, 75
2e, 70
3a, 66
3b, 63
3c, 71
3a, 95
CO2Me 6‐i‐Pr
CO2Me 7‐i‐Pr
CO2Me 6‐Me
3b, 96
i‐Pr
Decomp.
3c, 89
a Isolated yield.
3d, 75
Table 3. Reaction of 2H‐cyclohepta[b]furan‐2‐ones with heteroaryl‐
substituted silyl enol ethers.
Ph
H
H
−
−
−
−
H
1g
1h
H
6‐i‐Pr
5‐i‐Pr
H
a 3 equiv. of silyl enol ether was employed. b Isolated yield.
[8 + 2] CA
Product,
Yield [%]a
decarboxylation
Product,
As shown in Table 2, we also examined the substituent
effect on the benzene ring of the silyl enol ethers toward the
product yields by using the reaction of 1a and 1b. As a result,
we found that the yield of the products was greatly influenced
by the electronic nature of the substituent on the benzene ring.
For instance, silyl enol ethers having an electron‐donating
group at the para‐position on the benzene ring produced the
target products in higher yields, compared with those of ones
possessing an electron‐withdrawing group (entries 1−5). This
result means that the electron‐withdrawing group at the para‐
position decreases the reactivity of the silyl enol ethers.
The introduction of the substituent at the ortho‐position
led to the decrement for the reactivity of the silyl enol ethers
toward the [8 + 2] CA process (entry 6). The naphthalene‐
substituted silyl enol ethers reacted with 1a and 1b to give the
corresponding 2‐naphthylazulene derivatives 4g and 4h, but
the yields differed greatly by the substitution positions (entries
7 and 8). Ferrocene‐substituted azulene derivative 4i, which
could not be prepared by the palladium‐catalyzed cross‐
coupling reaction,12 was also obtained by this method in good
yield (entry 9).
Entry
Ar
R2
Yield [%]a
1
2
3
4
5
6
7
H
7a, 22
7b, 10
7c, 75
7d, 79
7e, 72
7f, 73
7g, 73
8a, 94
8b, 84
8c, 99
8d, 95
8e, 51b
8f, 56
8g, 35
H
H
i‐Pr
i‐Pr
H
i‐Pr
8
H
H
H
7h, 23
7i, 46
7j, 30
8h, 44
9
8i, 51
10
Decomp.
11
H
7k, 21
8k, 85
a Isolated yield. b Debrominated product 8d was also obtained in 39%
yield.
The reaction of 1a and 1b with the silyl enol ethers having
a heteroaryl group have also investigated to produce 2‐
2 | J. Name., 2012, 00, 1‐3
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heteroarylazulenes 7a
COMMUNICATION
7k with an ester function (Table 3). Figure 1. Although 8i and 8k showed high planaVriietwyAbrtiecltewOenleinne
−
Although the product yield of the reaction of the silyl enol the azulene ring and the substituted hDeOteI:r1o0c.1y0c3le9/,C49eCCa0n9d3764Af
ethers substituted by electron‐deficient heterocycles (such as indicated the twisted structure due to the steric hindrance
pyridines and thiazole) was rather low (entries 1, 2 and 10), between the ester group on the azulene and benzene ring
thiophene‐
heteroarylazulene derivatives 7c
and
furan‐substituted
ones
gave
2‐ connected.
(a)
(b)
−
7g in good yields (entries
3−7). These results also equate nicely that the electron‐
deficient heterocycles decrease the reactivity of the silyl enol
ethers toward 1a and 1b, as was the case of the reaction with
the silyl enol ethers having an electron‐withdrawing
substituent on the benzene ring. Although the pyrrole ring is
an electron‐rich heterocycle, the yields of the reaction of 1a
with the silyl enol ethers to afford the corresponding 2‐
pyrrolylazulene derivatives were rather low (Table 3, entries
(d)
(c)
8−10); the low yields are due to the instability of 7h
the reaction conditions. Indeed, even though 7a 7g and 7k
showed considerable stability under the ambient conditions,
7h 7j gradually decomposed under the same conditions.
The plausible reaction mechanism for the formation of 2‐
arylazulenes is shown in Scheme 1. Namely, the intermediate
is given by [8 + 2] CA reaction of 2H‐cyclohepta[b]furan‐2‐
ones with the silyl enol ethers, as similar to the reaction with
enamines. Since silyl enol ether is less reactive than enamine,
the higher reaction temperature may be required to proceed
−7j under
−
Fig. 1 ORTEP drawing of (a) 4e (CCDC 1883650), (b) 4f (CCDC
1883651), (c) 8i (CCDC 1883652) and (d) 8k (CCDC 1883653).
−
Azulene derivative is one of the compounds exhibiting the
fluorescence from S2 to S0 states against Kasha's rule, but the
emission intensity is generally weak.13 In recent years, some
researchers, including our group, have reported that several
azulene derivatives exhibit relatively strong fluorescence
under acidic conditions due to the formation of a tropylium ion
substructure by the protonation.7b,7c,14 We found that 2‐
A
the cycloaddition reaction. Then, intermediate
transformed into dihydroazulene intermediate
A
B
is
by
decarboxylation. Eventually, 2‐arylazulene is formed via
phenylazulene derivatives 3a–3c and 5a–5h in an acidic
aromatization of
B
accompanied by the desilication.
solution displayed fluorescence, whose emission maxima
depended on the electronic properties of the substituent at
the para‐position of the benzene ring (Table 2 and Fig. 2). On
O
R1
H
R1
R1
O
R2
R2
Ar
R2
Ar
decarboxylation
O
Ar
[8 + 2]
OTMS
OTMS
the whole, 3a
and higher fluorescence quantum yield than those of parent
azulene, except for 5b. Among the 3a 3c, the isopropyl
–3c and 5a–5h showed longer emission maxima
O
cycloaddition
CO2
B
A
OTMS
–
aromatization
TMSOH
R1
derivatives showed a slight short‐wavelength shift of λfl. The
compounds having an electron‐donating substituent at the
para‐position on the benzene ring, such as 5a, 5b, and 5e,
R2
Ar
were proved to show longer wavelength shifts in the emission
along with lowering the quantum yields. Whereas, 5c having
an electron‐withdrawing group exhibited the opposite effect
(Fig. 2 and 3).
Scheme 1. The plausible reaction mechanism for the formation of 2‐
arylazulenes.
The decarboxylation reaction of 4a−4j with 100% H3PO4
gave the corresponding decarboxylated derivatives in high
yields (Table 2, entries 1−6 and 8). While the reacꢀon of 4g
produced cyclization product 6, which should be produced by
intramolecular Friedel‐Crafts type reaction, in 61% yield, along
with the decarboxylated derivative 5h (Table 2, entry 7).
Whereas, treatment of 4j with 100% H3PO4 under the same
conditions led to the decomposition of the compound (Table 2,
Table 2. Absorption maxima (λmax) and fluorescence properties of 3a
3c and 5a–5h in 30% CF3CO2H/CH2Cl2.
–
Storks
shift [nm]
67
Φfl [%]a
τ
[ns]b
Sample
λmax
λfl
Azulene
3a
353
446
446
442
467
499
434
455
480
443
483
492
420
500
493
488
524
571
484
509
558
495
556
569
0.9
29
34
35
13
0.4
50
23
25
37
21
5
1.5
5.4
5.5
5.7
3.5
0.24
4.2
3.0
2.1
5.3
2.5
1.1
54
3b
47
entry 9). The reaction of 2‐heteroarylazulenes 7a
100% H3PO4 was also afforded the decarboxylated derivatives
8a 8k, except for 7j (Table 3, entries 1−11). The yield of the
target products 8f 8i by the reaction of compounds 7f 7i was
−7k with
3c
42
5a
57
−
5b
72
−
−
5c
50
a bit low (Table 3, entries 6−9), and the case of the reaction of
7j resulted in the complete decomposition (Table 3, entry 10).
All compounds were characterized by NMR and HRMS
experiments as summarized in the ESI. Since the suitable single
crystals for X‐ray structure analysis were obtained in 4e, 4f, 8i,
and 8k, their crystal structures were clarified as summarized in
5d
54
5e
78
5f
52
5g
73
5h
77
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a Quantum yield. b Emission lifetime.
2
3
a) Y. Yamaguchi, K. Ogawa, K. Nakayama, Y. Ohba, H. Katagiri,
View Article Online
J. Am. Chem. Soc. 2013, 135, 19095–19098; b) H. Xin, C. Ge, X.
Yang, H. Gao, X. Yang, X. Gao, Chem. ScDiO. 2I:0101.610, 39/C9CC09376A
7, 6701−6705;
c) H. Xin, C. Ge, X. Jiao, X. Yang, K. Rundel, C. R. McNeill, X.
Gao, Angew. Chem. Int. Ed. 2018, 57, 1322−1326; d) H. Xin, J.
Li, C. Ge, X. Yang, T. Xue, X. Gao, Mater. Chem. Front. 2018, 2,
975−985.
a) X.‐H. Zhang, C. Li, W.‐B. Wang, X.‐X. Cheng, X.‐S. Wang, B.‐
W. Zhang, J. Mater. Chem. 2007, 17, 642–649; b) E.
Puodziukynaite, H.‐W. Wang, J. Lawrence, A. J. Wise, T. P.
Russell, M. D. Barnes, T. Emrick, J. Am. Chem. Soc. 2014, 136
,
11043–11049; c) H. Nishimura, N. Ishida, A. Shimazaki, A.
Wakamiya, A. Saeki, L. T. Scott, Y. Murata, J. Am. Chem. Soc.
2015, 137, 15656–15659.
4
5
a) P. G. Lacroix, I. Malfant, G. Iftime, A. C. Razus, K. Nakatani,
J. A. Delaire, Chem. Eur. J. 2000, 6, 2599–2608; b) C. Lambert,
G. Nöll, M. Zabel, F. Hampel, E. Schmälzlin, C. Bräuchle, K.
Meerholz, Chem. Eur. J. 2003, 9, 4232–4239; c) L. Cristian, I.
Sasaki, P. G. Lacroix, B. Donnadieu, I. Asselberghs, K. Clays, A.
Fig. 2 UV/Vis and fluorescence spectra of 3a and 5a
−5d in 30%
C. Razus, Chem. Mater. 2004, 16, 3543–3551.
CF3CO2H/CH2Cl2.
a) J. Xia, B. Capozzi, S. Wei, M. Strange, A. Batra, J. R. Moreno,
R. J. Amir, E. Amir, G. C. Solomon, L. Venkataraman, L. M.
Campos, Nano Lett. 2014, 14, 2941–2945; b) J.‐X. Dong, H.‐L.
Zhang, Chin. Chem. Lett. 2016, 27, 1097–1104; c) T. Shoji, S.
Ito, Chem. Eur. J. 2017, 23, 16696–16709; d) Y. Zhou, G.
Baryshnikov, X. Li, M. Zhu, H. Ågren, L. Zhu, Chem. Mater.
2018, 30, 8008−8016.
5b
6
7
a) K.‐P. Zeller, Azulene, in Methoden der Organischen
Chemie (Houben‐Weyl), 4th ed. (Ed.: H. Kropf), Thieme,
Stuttgart, 1985, Vol. V, Part 2c, pp. 127–418; b) G. Fischer,
Adv. Heterocycl. Chem. 2009, 97, 131–218; c) S. Ito, T. Shoji,
N. Morita, Synlett 2011, 2279–2298.
5a
5c
3a
5d
Fig. 3 Photos of 3a and 5a−5d in 30% CF3CO2H/CH2Cl2 under the
irradiation of UV light (λex = 365 nm).
In summary, we have established the direct synthesis of 2‐
arylazulenes by [8 + 2] CA reaction of 2H‐cyclohepta[b]furan‐2‐
one derivatives with aryl‐substituted silyl enol ethers. Since
the precursors are readily available, the synthetic procedure
possesses significant advantages in comparison with the cross‐
coupling strategy by using aryl‐ and heteroarylmetal reagents
with 2‐haloazulenes and their pseudo halides, which are
known to be difficult to prepare.
This work was supported by JSPS KAKENHI Grant Number
17K05780. We thank Professor Dr. Shigeki Mori and Professor
Dr. Tetsuo Okujima, Ehime University, for helping us to analyse
the X‐ray diffraction results. We also thank Mr. Yuya Endo and
Mr. Tatsuki Nagahata, Hirosaki University, for their technical
assistance.
a) A. L. Crombie, J. L. Kane, Jr., K. M. Shea, R. L. Danheiser, J.
Org. Chem. 2004, 69, 8652–8667; b) E. Amir, R. J. Amir, L. M.
Campos, C. J. Hawker, J. Am. Chem. Soc. 2011, 133, 10046–
10049; c) E. Amir, M. Murai, R. J. Amir, J. S. Cowart Jr., M. L.
Chabinyc, Craig J. Hawker, Chem. Sci. 2014, 5, 4483–4489; d)
T. Shoji, A. Maruyama, T. Araki, S. Ito, T. Okujima, Org.
Biomol. Chem. 2015, 13, 10191–10197; e) T. Shoji, T. Araki, S.
Sugiyama, A. Ohta, R. Sekiguchi, S. Ito, T. Okujima, K. Toyota,
J. Org. Chem. 2017, 82, 1657−1665; f) T. Shoji, S. Ito, Adv.
Heterocycl. Chem. 2018, 126, 1–54.
8
a) T. Nozoe, S. Seto, S. Matsumura, Bull. Chem. Soc. Jpn.
1962, 35, 1990–1998; b) S. Ito, A. Nomura, N. Morita, C.
Kabuto, H. Kobayashi, S. Maejima, K. Fujimori, M. Yasunami,
J. Org. Chem. 2002, 67, 7295–7302.
9
S. Ito, R. Yokoyama, T. Okujima, T. Terazono, T. Kubo, A. Tajiri,
M. Watanabe, N. Morita, Org. Biomol. Chem. 2003, 1, 1947–
1952.
Conflicts of interest
10
M. Narita, T. Murafuji, S. Yamashita, M. Fujinaga, K. Hiyama,
Y. Oka, F. Tani, S. Kamijo, K. Ishiguro, J. Org. Chem. 2018, 83
,
There are no conflicts to declare.
1298−1303.
11 a) P.‐W. Wang, M. Yasunami, K. Takase, Tetrahedron Lett.
1971, 45, 4275−4278; b) M. Yasunami, A. Chen, P.‐W. Yang, K.
Notes and references
Takase, Chem. Lett. 1980, 9, 579–582; c) M. Yasunami, S.
1
a) Y. Tanaka, K. Shigenobu, Cardiovasc. Drug Rev. 2001, 19,
Miyoshi, N. Kanegae, K. Takase, Bull. Chem. Soc. Jpn. 1993,
66, 892–899.
12 T. Shoji, K. Miyashita, T. Araki, M. Tanaka, A. Maruyama, R.
Sekiguchi, S. Ito, T. Okujima, Synthesis 2016, 48, 2438–2448.
297–312; b) W. Pham, R. Weissleder, C.‐H. Tung, Angew.
Chem. Int. Ed. 2002, 41, 3659–3662; c) S. Lçber, H. Hîbner, A.
Buschauer, F. Sanna, A. Argiolas, M. R. Melis, P. Gmeiner,
Bioorg. Med. Chem. Lett. 2012, 22, 7151–7154; d) K. Ikegai,
M. Imamura, T. Suzuki, K. Nakanishi, T. Murakami, E.
Kurosaki, A. Noda, Y. Kobayashi, M. Yokota, T. Koide, K.
Kosakai, Y. Okhura, M. Takeuchi, H. Tomiyama, M. Ohta,
Bioorg. Med. Chem. 2013, 21, 3934–3948; e) J. Peet, A.
Selyutina, A. Bredihhin, Bioorg. Med. Chem. 2016, 24, 1653–
1657; f) T. O. Leino, A. Turku, J. Yli‐Kauhaluoma, J. P.
Kukkonen, H. Xhaard, E. A. A. Wallén, Eur. J. Med. Chem.
2018, 15, 88–100.
13 a) M. Kasha, Discuss. Faraday Soc. 1950,
Chem. Rev. 2012, 112, 4541–4568.
9, 14–19; b) T. Itoh,
14 a) M. Koch, O. Blacque, K. Venkatesan, Org. Lett. 2012, 14
1580–1583; b) T. Shoji, T. Araki, N. Iida, K. Miura, A. Ohta, R.
Sekiguchi, S. Ito, T. Okujima, Org. Chem. Front. 2019, , 195–
,
6
204; c) T. Shoji, K. Miura, A. Ohta, R. Sekiguchi, S. Ito, Y. Endo,
T. Nagahata, S. Mori, T. Okujima, Org. Chem. Front. 2019, 6,
2801–2811.
4 | J. Name., 2012, 00, 1‐3
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DOI: 10.1039/C9CC09376A
We have developed the procedure for the direct synthesis of 2-arylazulenes. The 2-
arylazulenes are formed in moderate to excellent yield by [8 + 2] cycloaddition of 2H-
cyclohepta[b]furan-2-one derivatives with aryl-substituted silyl enol ethers.