A facile synthesis of β-(4-azuleno[1,2-b]thienyl) α,β-unsaturated ketones

Article abstract of DOI:10.1039/a704583b

The facile and novel synthesis of β-(4-azuleno[1,2-b]thienyl) α,β-unsaturated ketones 1 from 2-tropylio-3-(2-furyl)thiophenes 7 is reported; a mechanism involving a novel ring cyclization by intramolecular attack of the tropylium ion at the 2-position of

Full text of DOI:10.1039/a704583b

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A facile synthesis of b-(4-azuleno[1,2-b]thienyl) a,b-unsaturated ketones
Naoki Kusuhara,a Yuka Sugano,a Hideki Takagi,a Hideyoshi Miyakeb and Kimiaki Yamamura*a
a Department of Chemistry, Faculty of Science, Kobe University, Nada, Kobe 657, Japan
b Department of Biofunctional Chemistry, Faculty of Agriculture, Kobe University, Nada, Kobe 657, Japan
The facile and novel synthesis of b-(4-azuleno[1,2-b]thienyl)
+
+
a,b-unsaturated ketones 1 from 2-tropylio-3-(2-furyl)thio-
phenes 7 is reported; a mechanism involving a novel ring
cyclization by intramolecular attack of the tropylium ion at
S
S
the 2-position of the furan ring is postulated.
R
O
O
R
7
8
The azulenoid heterocyclic aromatic compounds which consist
of the azulene ring condensed with heterocyclic aromatic nuclei
are of interest not only for their physical and chemical
properties, but also their pharmaceutical and physiological
H
H
+
activity. Several azulene derivatives condensed with hetero-
R
R
O
aromatics such as thiophene, furan, pyrrole and pyridine rings
are known.1 Most of them were prepared by the heteroaro-
matization of the azulene derivatives, and were restricted to the
parent compounds and alkyl-, aryl- or alkoxycarbonyl-substi-
tuted derivatives. Herein we disclose a novel and facile
synthesis of azuleno[1,2-b]thiophenes having an a,b-unsatu-
O
+
S
S
9
COR
Br
S
R
Br
1
O
2a R = Me
b R = Ph
c R = H
S
Scheme 2
ii
rated ketone group from the corresponding 2-tropylio-3-(2-fur-
yl)thiophenes 7.
i
Br
The synthetic sequence leading to 1 from the readily
available 2-substituted furans 2 is depicted in Scheme 1.†
2-Cycloheptatrienyl-3-(2-furyl)thiophenes 5 were prepared by
the palladium(ii)-catalysed Stille reaction2 of 2-trimethyl-
stannylfurans 3 with 2-cycloheptatrienyl-3-bromothiophene 4.
Thermal sigmatropic rearrangement of 5 to 6 and subsequent
hydride abstraction using triphenylmethyl tetrafluoroborate
gave 2-tropylio-3-(2-furyl)thiophenes 7 in 65–85% yields.‡ It
might be expected that the intramolecular electrophilic substitu-
tion reaction of the tropylium moiety with the furan ring would
afford the tetracyclic carbocations 8, which are isoelectronic
with triphenylene.3 However, when a CH2Cl2 solution of 7a§
was refluxed for 7 h, neutral red–black prisms were obtained
instead of the expected carbocations 8a. The structure of these
prisms was confirmed to be 4-(4-azuleno[1,2-b]thienyl)but-
3-ene-2-one 1a via its spectral data,5 together with elemental
analysis. In the same manner, the chalcone-type compound 1b
and triphenylmethyl derivative 1c were obtained as green–black
needles (43%) and black needles (36%), respectively, from the
corresponding tropylio derivatives 7b and 7c.
R
SnMe3
O
S
3a R = Me
b R = Ph
c R = H
4
iii
iv
S
R
S
O
R
(+isomers)
O
5a R = Me
b R = Ph
c R = H
6a R = Me
b R = Ph
c R = H
v
COR
+
vi
A possible mechanism for the formation of b-(4-azuleno-
[1,2-b]thienyl) a,b-unsaturated ketones 1 from the correspond-
ing 2-tropylio-3-(2-furyl)thiophenes 7 is illustrated in Scheme
2. The intramolecular electrophilic attack of the tropylium ion
on the 2-poisition of the furan ring gives the spiro-type
intermediate 9, which can be converted to 1 by a ring-opening
reaction. Although it is well-known that the 2-position of the
furan ring is much more reactive towards electrophiles than the
3-position and that furans are readily ring-opened under acidic
conditions,4 this is to the best of our knowledge the first
S
R
S
O
1a R = Me
b R = Ph
7a R = Me
b R = Ph
c R = Ph3C
c R = Ph3C
Scheme 1 Reagents and conditions: i, BuLi, Me3SnCl, THF, 278 °C; ii,
BuLi, C7H7+, THF, 278 °C to room temp; iii, PdCl2(Ph3P)2, THF, reflux;
iv, xylene, reflux; v, Ph3C+BF42, CH2Cl2, room temp; vi, CH2Cl2 or
CH2ClCH2Cl
Chem. Commun., 1997
1951

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(quaternary), 143.6 (quaternary), 137.3, 135.7 (quaternary), 134.8, 134.0,
133.7, 133.1 (quaternary), 131.9, 126.4, 125.4, 123.3, 119.8, 116.4
(quaternary), 27.8 (CH3). Calc. for C16H12SO: C, 76.16; H, 4.79. Found: C,
76.30; H, 4.63%.
tropylium ion-mediated furan ring-opening reaction to yield
a,b-unsaturated carbonyl derivatives of azuleno[1,2-b]thio-
phene compounds. Since 2-substituted furans 2 are readily
available and the procedure is simple and easy, it is considered
that this is a valuable general synthetic route to various
b-(4-azuleno[1,2-b]thienyl) a,b-unsaturated ketones.
1 K. Matsui and T. Nozoe, Chem. Ind., 1960, 1302; T. Nozoe, S. Seto and
S. Matsumura, Chem. Ind., 1961, 1715; T. Nozoe and K. Kikuchi, Bull.
Chem. Soc. Jpn., 1963, 36, 633; S. Hayashi, S. Kurokawa, M. Okano and
T. Matsuura, Tetrahedron Lett., 1967, 3443; L. L. Replogle, K.
Katsumoto and H. L. Ammon, J. Am. Chem. Soc., 1968, 90, 1086;
T. Nozoe, K. Takase, T. Nakazawa, S. Sugita and M. Saito, Bull. Chem.
Soc. Jpn., 1974, 47, 1750; K. Kohara, H. Tachibana, Y. Masuyama and
Y. Otani, Bull. Chem. Soc. Jpn., 1979, 52, 1549; K. Yamane, K. Fujimori
and T. Takeuchi, Bull. Chem. Soc. Jpn., 1981, 54, 2537; T. Morita,
T. Nakadate and K. Takase, Heterocycles, 1981, 15, 835; K. Fujimori,
T. Fujita, K. Yamane, M. Yasunami and K. Takase, Chem. Lett., 1983,
1721.
The authors thank Miss Masuko Nishinaka for elemental
analyses. The present work was supported in part by Grant-in-
Aid for Scientific Research (C) (No. 08640685) from the
Ministry of Education, Science, Sports and Culture, Japan.
Footnotes and References
* E-mail: kyama@kobe-u.ac.jp
† All new compounds were fully characterized by mass and 1H NMR
spectroscopy and elemental analysis.
‡ With 6c, triphenylmethyl tetrafluoroborate acts as both a hydride
abstraction reagent and an electrophile, and triphenylmethyl-substituted
tropylium ion derivative 7c was obtained.
2 J. K. Stille, Angew. Chem., Int. Ed. Engl., 1986, 25, 508; T. R. Bailey,
Tetrahedron Lett., 1986, 27, 4407; A. Dondoni, A. R. Mastellari,
A. Medict, E. Negrini and P. Pedrini, Synthesis, 1986, 757; V. N. Kalinin,
Synthesis, 1992, 413; T. N. Mitchell, Synthesis, 1992, 803.
3 K. Yamamura, H. Miyake, S.Nakatsuji and I. Murata, Chem. Lett., 1992,
1213.
§ Selected data for 7a: (dH CD2Cl2, 250 MHz) 2.22 (3 H, s, CH3), 6.20 (1
H, d, furan-H), 6.75 (1 H, d, furan-H), 7.43 (1 H, d, thiophene-H), 7.95 (1
H, d, thiophene-H), 8.68–8.83 (4 H, m, tropylium-H), 8.93–9.00 (2 H, m,
tropylium-H). For 1a: dH (CD3Cl, 250 MHz) 2.46 (3 H, s, CH3), 6.90 (1 H,
d, olefinic-H), 7.26 (2 H, dd, seven-membered ring-H), 7.62 (1 H, dd, seven-
membered ring-H), 7.73 (1 H, d, thiophene-H), 7.89 (1 H, d, thiophene-H),
8.28 (1 H, d, olefinic H), 8.29 (1 H, d, seven-membered ring-H), 8.49 (1 H,
d, seven-membered ring-H), dC (CD3Cl, 75 MHz) 198.2 (CNO), 150.1
4 M. V. Sargent and T. M. Cresp, Comprehensive Organic Chemistry,
Pergamon, Oxford, 1979, vol. 4, p. 693.
Received in Cambridge, UK, 30th June 1997; 7/004583B
1952
Chem. Commun., 1997