Synthesis and functionalization of 3,3′-bis(spirodienone)-bridged 2,2′-bithiophene: A new building block for redox-active molecular switching materials

Article abstract of DOI:10.1021/ol8015379

(Chemical Equation Presented) Bithiophene derivatives bridged with a bis(spirodienone) unit were synthesized and characterized. Lithiation of the thiophene rings of an unsubstituted derivative proceeded without decomposition of the bis(spirodienone) skeleton. Palladium-catalyzed cross-coupling reactions (Suzuki-Miyaura, Sonogashira) with bromides afforded a variety of π-extended derivatives. Bond breaking and formation under redox conditions were observed by cyclic voltammetry.

Full text of DOI:10.1021/ol8015379

ORGANIC
LETTERS
2008
Vol. 10, No. 17
3837-3840
Synthesis and Functionalization of
3,3′-Bis(spirodienone)-Bridged
2,2′-Bithiophene: A New Building Block
for Redox-Active Molecular Switching
Materials
Hiroyuki Kurata,* Sang Kim, Takahisa Fujimoto, Kouzou Matsumoto,
Takeshi Kawase,† and Takashi Kubo
Department of Chemistry, Graduate School of Science, Osaka UniVersity,
Toyonaka, Osaka 560-0043, Japan
kurata@chem.sci.osaka-u.ac.jp
Received July 8, 2008
ABSTRACT
Bithiophene derivatives bridged with a bis(spirodienone) unit were synthesized and characterized. Lithiation of the thiophene rings of an
unsubstituted derivative proceeded without decomposition of the bis(spirodienone) skeleton. Palladium-catalyzed cross-coupling reactions
(Suzuki-Miyaura, Sonogashira) with bromides afforded a variety of π-extended derivatives. Bond breaking and formation under redox conditions
were observed by cyclic voltammetry.
Due to the ease of functionalization of thiophene rings,
conjugated molecules containing thiophenes are useful build-
ing blocks for electrically and optically interesting materials.1
Some of these molecules show changes in structure and
properties in response to external stimuli; these have received
much attention as candidates for components of molecular
switches.2 For example, many compounds with a dithie-
nylethene skeleton, which is a commonly used photochromic
unit, have been investigated with a view to their application
in photochromic switching materials.3 Furthermore, some
oligothiophene derivatives with switching functions have
been investigated.4 In this context, the synthesis of thiophene-
† Present address: Department of Materials Science and Chemistry,
Graduate School of Engineering, University of Hyogo, Himeji, Hyogo 671-
2201, Japan.
(1) (a) Ba¨uerle, P. In Handbook of Oligo- and Polythiophenes; Fichou,
D., Ed.; Wiley-VCH: Weinheim, 1999; pp 89-182. (b) Takimiya, K.; Kato,
K.; Aso, Y.; Ogura, F.; Otsubo, T. Bull. Chem. Soc. Jpn. 2002, 75, 1795.
(c) Okamoto, T.; Kudoh, K.; Wakamiya, A.; Yamaguchi, S. Chem. Eur. J.
2006, 13, 548. (d) Payne, M. M.; Odom, S. A.; Parkin, S. R.; Anthony,
J. E. Org. Lett. 2004, 6, 3325. (e) Pan, H.; Li, Y.; Wu, Y.; Liu, P.; Ong,
B. S.; Zhu, S.; Xu, G. Chem. Mater. 2006, 18, 3237. (f) Nicolas, Y.;
Blanchard, P.; Levillain, E.; Magali Allain, M.; Nicolas Mercier, N.; Roncali,
J. Org. Lett. 2004, 6, 273. (g) Andrzej Rajca, A.; Rajca, S.; Pink, M.;
Miyasaka, M. Synlett 2007, 1799, and references therein. (h) Liu, W.-J.;
Zhou, Y.; Ma, Y.; Cao, Y.; Wang, J.; Pei, J. Org. Lett. 2007, 9, 4187.
(2) (a) Molecular Switches; Feringa, B. L., Ed.; Wiley-VCH: Weinheim,
2001. (b) Balzani, V.; Venturi, M.; Credi, A. Molecular DeVices and
Machines; Wiley-VCH: Weinheim, 2003. (c) Feringa, B. L. J. Org. Chem.
2007, 72, 6635.
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Chem. Lett. 2006, 35, 1204.
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2074. references therein. (b) Nishida, J.; Miyagawa, T.; Yamashita, Y. Org.
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10.1021/ol8015379 CCC: $40.75
Published on Web 08/07/2008
2008 American Chemical Society

containing molecules that respond to external stimuli opens
the way to the development of new molecular switching
materials.
Scheme 1. Synthesis of Bis(spirodienone) 2a
As a part of a study of nonplanar extended quinones,5 we
recently observed the unexpected formation of 3,3′-bis(spiro-
dienone)-bridged 2,2′-bibenzo[b]thiophene derivative 1 (Fig-
ure 1).6 Compound 1 showed photo- and redox-active
di-tert-butyl-4-hydroxyphenylboronic acid 3 directly from
4-bromo-2,6-di-tert-butylphenol,11 and we prepared bisphe-
nol 4a in 92% yield by Suzuki-Miyaura coupling of 3,3′-
dibromo-2,2′-bithiophene12 with 2.5 equiv of 3. Oxidation
of 4a with DDQ in tetrahydrofuran at room temperature for
2 h afforded bis(spirodienone) 2a in 94% yield.
Compound 2a was obtained as colorless crystals with air
and thermal stability. Recrystallization of 2a from dichlo-
romethane/hexane afforded good single crystals that allowed
characterization of the structure of 2a by X-ray crystal-
lography.13 ORTEP drawings of 2a are shown in Figure 2.
Figure 1. Bis(spirodienone)-bridged bithiophenes 1 and 2.
switching properties through a ring-opening/ring-closing
process. Inspired by this phenomenon, we designed bis-
(spirodienone)-bridged 2,2′-bithiophene derivative 2a, which
was logically derived from 1 by removal of the annelated
benzene rings, as a potential building block for functionalized
π-extended systems with switching properties. Reactive
R-positions on the thiophene rings of 2a were expected to
act as “footholds” for π-extension. In addition, compound
2a has a fixed s-cis conformation. Breaking and formation
of the bis(spirodienone) bridge would allow control of the
conformation of the bithiophene unit,7 which affects the
properties of the molecule.8 As a first step toward such
switchable materials, we here report the synthesis, structure,
and functionalization of 2a to give several derivatives (2c-j)
and describe their redox properties.
The synthesis of 2a was carried out as shown in Scheme
1. In previous work, 3-(3,5-di-tert-butyl-4-hydroxyphenyl)th-
iophene and its O-substituted derivatives have been prepared
by Kumada-Tamao coupling of 3-bromothiophene and 3,5-
di-tert-butyl-4-trimethylsiloxyphenylmagnesium bromide9
and by Suzuki-Miyaura coupling of 3-thiopheneboronic acid
and O-substituted 3,5-di-tert-butyl-4-bromobenzene deriva-
tives.10 We recently discovered an efficient synthesis of 3,5-
Figure 2. ORTEP drawings of 2a: (a) front view and (b) side view.
Hydrogen atoms are omitted for clarity.
The planes of the cyclohexadienone units lie perpendicular
to the thiophene plane and face each other. The dihedral angle
formed by C2-C9-C15-C6 is 48.0(2)°. Therefore, the
central six-membered ring possesses a twisted-chair confor-
mation. The two thiophene rings are twisted with an
S1-C1-C5-S2 dihedral angle of 12.0(4)°. The bond length
(5) (a) Kurata, H.; Tanaka, T.; Oda, M. Chem. Lett. 1999, 749. (b)
Kurata, H.; Takehara, Y.; Kawase, T.; Oda, M. Chem. Lett. 2003, 32, 538.
(c) Kurata, H.; Takehara, Y.; Matsumoto, K.; Kawase, T.; Oda, M. Chem.
Lett. 2005, 34, 1660. (d) Kurata, H.; Takakuwa, H.; Imai, N.; Matsumoto,
K.; Kawase, T.; Oda, M. Bull. Chem. Soc. Jpn. 2007, 80, 1402.
(6) Kurata, H.; Kim, S.; Matsumoto, K.; Kawase, T.; Oda, M. Chem.
Lett. 2007, 36, 386.
(10) (a) Xie, C.; Lahti, P. M. J. Poly. Sci. A 1999, 37, 779. (b) Miyasaka,
M.; Yamazaki, T.; Tsuchida, E.; Nishide, H. Macromolecules 2000, 33,
8511. (c) Xie, C.; Lahti, P. M.; George, C. Org. Lett. 2000, 2, 3417. (d)
Caironi, M.; Natali, D.; Sampietro, M.; Bertarelli, C.; Bianco, A.; Dun-
dulachi, A.; Canesi, E.; Zerbi, G. Appl. Phys. Lett. 2006, 89, 246519.
(11) Kurata, H.; Takehara, Y; Kim, S.; Sakai, K.; Matsumoto, K.;
Kawase, T.; Oda, M Synlett 2007, 2053.
(7) Helical conformations of 3,3′-diaryl-2,2′-bithiophenes have been
reported. Almutairi, A.; Tham, F. S.; Marsella, M. J Tetrahedron 2004, 60,
7187.
(12) (a) Gronowitz, S. Acta Chem. Scand. 1961, 15, 1393. (b) Dahlmann,
U.; Neidlein, R. HelV. Chim. Acta 1996, 79, 755.
(8) (a) Chadwick, J. E.; Kohler, B. E. J. Phys. Chem. 1994, 98, 3631.
(b) Belleteˆte, M.; Leclerc, M.; Durocher, G. J. Phys. Chem. 1994, 98, 9450.
(c) Wong, K-T.; Hung, T. H.; Kao, S. C.; Chou, C. H.; Su, Y. O. Chem.
Commun. 2001, 1268. (d) Marsella, M. J.; Rahbarnia, S.; Wilmot, N. Org.
Biomol. Chem. 2007, 5, 391. (e) Bouzzine, S. M.; Makayssi, A.; Hamidi,
A. M.; Bouachrine, M. THEOCHEM 2008, 851, 254.
(13) Crystallographic data: C36H44O2S2, M ) 572.86, triclinic, space
group P1 (No. 2), a ) 10.1637(1) Å, b ) 11.4120(4) Å, c ) 17.2254(2)
Å, R ) 67.23(1)°, ꢀ ) 71.58(1)°, γ ) 65.98(1)°, V ) 1652.63(6) Å3, Z )
2, Dcalc ) 1.151 g cm-3, F(000) ) 616.00, µ ) 1.90 cm-1 (Mo KR; λ )
0.71070 Å), 16627 reflections measured, 16460 unique, reflection/parameter
ratio ) 20.60, R ) 0.064 for I > 2σ(I), wR ) 0.206 for all data, GOF )
0.83.
(9) Yamamoto, T.; Hayashi, H. J. Poly. Sci. A 1997, 35, 463.
3838
Org. Lett., Vol. 10, No. 17, 2008

of the two spiro carbons (C9-C15) is 1.609(5) Å, which is
slightly shorter than the equivalent in 1 (1.625(5) Å) but
longer than a normal sp3-sp3 carbon bond (1.54 Å).14
It was considered that if the R-positions of the thiophene
rings in 2a could be lithiated without decomposition of the
bis(spirodienone) skeleton, the lithiated intermediate might
act as a useful synthon for reaction with electrophiles.
Treatment of 2.5 equiv of lithium diisopropylamide with 2a
at -70 °C for 1 h afforded dilithiated derivative 2b, which
was transformed to dialdehyde 2c by quenching with DMF
(Scheme 2). In the reaction of 2b with dimethyl disulfide,
base, afforded a mixture of the ring-opened product 4f (59%
yield) and the desired coupling product 2f (35% yield). The
formation of 4f indicated that reduction occurred under the
reaction conditions used. Although the mechanism of reduc-
tion was unclear, compound 4f was obtained selectively in
96% yield by the use of an excess amount of 4-methylphe-
nylboronic acid (5-6 equiv). DDQ-oxidation of 4f gave 2f
in 96% yield. Similar reactions allowed the preparation of
2g, 2h, and 2i from 4-methoxyphenylboronic acid, 4-fluo-
rophenylboronic acid, and sodium 2-thienylboronate,15 re-
spectively. We were able to introduce aryl groups in good
yield by Suzuki-Miyaura coupling followed by oxidation.
Furthermore, Sonogashira coupling of 2e with trimethylsi-
lylacetylene afforded the desired coupling product 2j in 93%
yield.
Scheme 2. Lithiation and Fuctionalization of 2a
The redox properties of 2a and 2c-j were examined by
cyclic voltammetry.16 The redox potentials are summarized
in Table 1, and the cyclic voltammograms of 2a, 2c, 2d,
and 2g are shown in Figure 3.
Table 1. Redox Potentialsa of Bis(spirodienone) Derivatives
2a-j
however, ring-opened isomer 4d was obtained. Compound
4d was then oxidized by DDQ to afford 2d. The formation
of 4d is probably based on reduction of 2d by electron
transfer from methyl thiolate species generated in situ.
Treatment of 2a with n-BuLi or t-BuLi gave complex
mixtures.
The bromination of 2a and successive transition-metal-
catalyzed cross-coupling reactions are summarized in Scheme
3. Treatment of 2.2 equiv of N-bromosuccinimide with 2a
ox
ox
red
red
compound
E
p2
(V)
E
p1
(V)
E
pc
(V)
E
pa
(V)
2a
2c
2d
2e
2f
2g
2h
2i
+1.22
ndd
+1.00
ndd
-2.35
-1.49
-2.21
-2.21
-2.29
-2.30
-2.24
-2.15
-2.05
-0.88
-0.75
-0.85
-0.82
-0.86
-0.90
-0.86
-0.85
-0.82
+0.71b
+1.34
+1.01
+0.73b
+1.10
+1.03
+1.14
+0.45b
+1.02
+0.62
+0.44b
+0.74
+0.64
+0.96
2j
a Versus Fc/Fc+, in 0.1 M nBu4NClO4/CH2Cl2, scan rate 100 mV s-1
,
at 25 °C. b Half-wave potentials. c The second reduction wave was observed
Scheme 3. Suzuki-Miyaura and Sonogashhira Couplings of 2e
at +2.18 V as a reversible wave. d No peak was observed from 0 to +1.5
V.
All of the compounds except 2c showed an irreversible
reduction wave around -2.0 V, and reoxidation waves were
observed around -1.0 V. The large difference in the
reduction/reoxidation potentials (known as hysteresis) indi-
cates that electron transfer and subsequent ring opening
occurred to afford dianion 6, as shown in Scheme 4. Such
hysteresis is a typical feature of dynamic redox systems.17
The substituent effect on the thiophene rings was observed
in 2c and 2d. Due to the electron-withdrawing properties of
the formyl group, the reduction potential of 2c is remarkably
positive than those of the other compounds, and a second
in DMF/CH2Cl2 at room temperature afforded 2e in 99%
yield. We examined the Suzuki-Miyaura coupling reactions
of 2e with arylboronic acids. Treatment of 2e with 2.5 equiv
of 4-methylphenylboronic acid under conventional condi-
tions, using Pd(PPh3)4 as a catalyst and aqueous K2CO3 as a
(15) (a) Kirchbaum, T.; Azumi, R.; Mena-Osteritz, E.; Ba¨uerle, T P.
New J. Chem. 1999, 241. (b) Pei, J.; Ni, J.; Zhou, X.-H.; Cao, X.-Y.; Lai,
Y.-H. J. Org. Chem. 2002, 67, 4924.
(16) Measurements were carried out in CH2Cl2 solution at room
temperature using a glassy carbon electronode with nBu4NClO4 (0.1 M) as
the supporting electrolyte. Scan rate was 100 mV/s.
(14) Recently, a trispiro-conjoined cyclopropane derivative having a
similar bis(spirodienone) structure has been reported and the bond length
of the two spiro-carbons was 1.595(8) Å. Kiyohara, S.; Ishizuka, K.;
Wakabayashi, H.; Miyamae, H.; Kanazumi, M.; Kato, T.; Kobayashi, K
Tetrahedron Lett. 2007, 48, 6877.
(17) (a) Suzuki, T.; Ohta, E.; Kawai, H.; Fujiwara, K.; Fukushima, T
Synlett 2007, 851, and references therein. (b) Ohta, A.; Ueki, C.; Uchiyama,
Y.; Fujimori, K. Heterocycles 2006, 69, 365. (c) Bryce, M. R.; Coffin, M. A.;
Hursthouse, M. B.; Karaulov, A. I.; Mu¨llen, K.; Scheich, H. Tetrahedron
Lett. 1991, 32, 6029.
Org. Lett., Vol. 10, No. 17, 2008
3839

To show formation of ring-opened dianion species,
UV-vis spectral changes upon reduction with Na(Hg) in
degassed THF were determined for 2a and 2i (Figure 4).
Figure 4. UV-vis spectral changes of (a) 2a and (b) 2i upon
reduction with Na(Hg) in degassed THF.
The color of the solutions were clearly changed from
colorless to yellow for 2a and pale yellow to orange for 2i.
The spectral change of 2i was appreciable as a result of its
extended π-conjugation, whereas that of 2a was small. The
finally obseved spectra were confirmed as dianions 6a and
6i by agreement with the independently measured spectra
of 6a and 6i generated from 4a and 4i by deprotonation with
sodium hydride, respectively (Supporting Information).
In conclusion, we have described the synthesis and redox
properties of bis(spirodienone)-bridged bithiophene deriva-
tives 2. Lithiation/fuctionalization of 2a and transition-metal-
catalyzed cross-coupling of 2e are expected to open the way
to the development of new extended π-systems. Conforma-
tional change between the s-cis and s-trans forms of
bithiophene under redox conditions will be a key feature of
control of the structures and properties of the compounds.
Photoresponsive properties of 2a and 2c-j, and further
investigation of the development of novel switching materials
are currently in progress.
Figure 3. Cyclic voltammograms of (a) 2a, (b) 2c, (c) 2d, and (d)
2g.
reduction wave was observed (Figure 3b). This potential may
be assigned as the formation of tetraanion. Meanwhile, the
methylthio derivative 2d afforded two sets of reversible
oxidation waves at relatively low potentials, while the reduc-
tion peak potential was similar to that of 2a (Figure 3c).
The high reversibility of the oxidation waves indicates that
the cation radical and dication species are stabilized by two
methylthio groups.18 In contrast, the electronic effect of the
aryl groups was small; the reduction peaks varied slightly
depending on their electron donating/withdrawing properties.
Compound 2g showed reversible oxidation waves similar to
those of 2d (Figure 3d), which corresponds to the redox
behavior of 5,5′-bis(4-methoxyphenyl)-2,2′-bithiophene.19
Acknowledgment. This work was supported by a Grant-
in-Aid for Scientific Research (No. 16550036) from the Japan
Society for the Promotion of Science.
Scheme 4
.
Bond Breaking/Formation Processes of 2 under
Redox Conditions
Supporting Information Available: Experimental pro-
cedures, spectroscopic data of compounds, and crystal-
lographic data of 2a in CIF format. This material is available
free of charge via the Internet at http://pubs.acs.org.
OL8015379
(18) (a) Suzuki, T.; Shiohara, H.; Monobe, M.; Sakimura, T.; Tanaka,
S.; Yamashita, Y.; Miyashi, T. Angew. Chem., Int. Ed. Engl. 1992, 31, 455.
(b) Henderson, J. C.; Kiya, Y.; Hutchison, G. R.; Abrun˜a, H. D. J. Phys.
Chem. C 2008, 112, 3989.
(19) Hock, J.; Thompson, A. M; W, C.; McCleverty, J. A.; Ward, M. D.
J. Chem. Soc., Dalton Trans. 1996, 4257.
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Org. Lett., Vol. 10, No. 17, 2008