Syntheses of 2-(pentafluorophenyl)thiophene derivatives via the palladium-catalyzed Suzuki reaction

Article abstract of DOI:10.1055/s-2005-865335

Various bis(pentafluorophenyl)-substituted thiophene and selenophene derivatives are effectively synthesized by the palladium-catalyzed Suzuki reaction using pentafluorophenyl boronic acid. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2005-865335

PAPER
1589
Syntheses of 2-(Pentafluorophenyl)thiophene Derivatives via the Palladium-
Catalyzed Suzuki Reaction
S
ynthese
s
of 2-(Pe
a
ntafluoroph
z
enyl)thioph
u
ene Derivati
o
ves Takimiya,* Naoto Niihara, Tetsuo Otsubo
Department of Applied Chemistry, Graduate School of Engineering, Hiroshima University, Higashi-Hiroshima 739-8527, Japan
Fax +81(82)4245494; E-mail: ktakimi@hiroshima-u.ac.jp
Received 1 November 2004; revised 17 February 2005
This paper is dedicated to Professor Jan Becher on the occasion of his retirement.
Suzuki reaction between 3 and 2-iodopyridine in the pres-
Abstract: Various bis(pentafluorophenyl)-substituted thiophene
ence of Ag2O.8 This has impelled us to explore the synthe-
sis of 2-(pentafluorophenyl)thiophene derivatives by a
and selenophene derivatives are effectively synthesized by the pal-
ladium-catalyzed Suzuki reaction using pentafluorophenyl boronic
similar reaction. Although our initial trials using the Cam-
mers-Goodwin protocol were not successful, we have fi-
nally found satisfactory reaction conditions, which are
applicable to the synthesis of various pentafluorophenyl-
substituted thiophene and selenophene derivatives.
acid.
Keywords: boron, palladium, catalyst, cross-coupling, fluorine
A pentafluorophenyl group is an attractive functional in
the growing field of material chemistry. Introduction of
the group, with a strong electron-withdrawing nature,1
into various p-electron systems was recently reported,
proving that it is very effective in the perturbation of the
electronic structure and/or crystal structure of the manip-
ulated p-electron systems.2 For example, Facchetti et al.
reported that the introduction of the groups at the termi-
nals of a-quaterthiophene brought about an inversion
from p- to n-carrier type in field-effect transistor opera-
tion.2a Another example is the pentafluorophenyl-substi-
tuted dithienylethene derivative reported by Irie et al.,
which, thanks to the mutual strong interaction of the
groups, underwent highly effective photocyclization and
photocycloreversion in the crystal (and co-crystal)
forms.2b
F
F
S
F
F
F
1
F
F
F
F
F
F
B(OH)2
F
X
F
F
F
2a X = I
2b X = Br
3
2c X = SO2Cl
2d X = NHNH2
In these investigations, 2-(pentafluorophenyl)thiophene
(1) and its derivatives are key compounds, which were
previously synthesized by the palladium-catalyzed Suzuki
reaction between pentafluoroiodobenzene (2a) and
thiophene boric acid derivative2b or by the Stille reaction
between pentafluorobromobenzene (2b) and 2-tributyl-
stannylthiophene.2a Although other coupling approaches
to 1 were reported using pentafluorobenzenesulfonyl
chloride (2c)3 or pentafluorophenylhydrazine (2d),4 these
methods are not likely to be applicable to the synthesis of
its derivatives, because of the low yields, low selectivity,
or requirement of excess reagents.
Figure 1
Table 1 summarizes results of the reaction of 3 with 2-
bromothiophene under various reaction conditions includ-
ing those generally employed for the Suzuki reaction
(Table 1, entry 1) and those reported for the synthesis of
2-pentafluorophenylpyridine8 (Table 1, entry 2). The re-
action without Ag2O as an additive gave no detectable 1
in the reaction mixture (Table 1, entry 1). Although a trace
amount of 1 was detected upon changing the base to
t-BuOK with Ag2O as an additive (Table 1, entry 2), the
main product in this reaction was 2-(4-tert-butyloxy-
2,3,5,6-tetrafluorophenyl)thiophene (4, 26% isolated
yield). Compound 4 is probably produced by a nucleo-
philic substitution reaction of the tert-butoxide anion at
the para position of the thiophene ring. To avoid the use
of nucleophilic t-BuOK as a base, sodium hydroxide
(Table 1, entry 3) or potassium phosphate (Table 1, entry
4) were examined. With sodium hydroxide, 1 was ob-
tained (8% yield), but the reaction gave an intractable
complex mixture. The reaction with potassium phosphate
also gave a complex mixture with a slightly increased
Considering the ready accessibility of a-halothiophenes
by electrophilic substitutions of thiophenes, commercially
available pentafluorophenylboronic acid (3)5 is the coun-
terpart of choice for the Suzuki coupling;6 however, the
reagent has been known to be rather inferior in the Suzuki
reaction.7 Very recently, Cammers-Goodwin et al. report-
ed the synthesis of 2-(pentafluorophenyl)pyridine by the
SYNTHESIS 2005, No. 10, pp 1589–1592
x
x.
x
x
.
2
0
0
5
Advanced online publication: 25.04.2005
DOI: 10.1055/s-2005-865335; Art ID: F16104SS
© Georg Thieme Verlag Stuttgart · New York

1590
K. Takimiya et al.
PAPER
Table 1 The Suzuki Reactions of Pentafluorophenyl Boronic Acid
(3) with 2-Bromothiophene
Table 2 Suzuki Coupling Reactions of Pentafluorophenyl Boronic
Acid (3) with Various Dibromothiophene and Dibromoselenophene
Derivatives
F
F
F
F
F
F
F
F
F
+
(HO)2B
F
S
Br
S
Br Ar Br
+
F
Ar
F
3
F
F
F
F
5
3
F
F
F
F
1
6
Solvent Catalyst
Base/
Temp Time Result
Additive (°C)
(h)
20
4
Entry
1
BrArBr
5
Product Yield
6
(%)
1
2
DME
Pd(PPh3)4
K2CO3
85
85
0%
6a
72
DME–
t-BuOH
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
t-BuOK
1 (trace)
4a (26%)
Ag2O
Br
Br
Br
S
S
2
3
6b
6c
6d
66
42
84
3
4
5
DME
DME
DMF
NaOH
Ag2O
85
85
85
20
4
1 (8%)
Br
Br
K3PO4
Ag2O
1 (20%)
1 (68%)
2
K3PO4
Ag2O
4
Br
S
3
a 2-(4-tert-Butoxy-2,3,5,6-tetrafluorophenyl)thiophene.
4
R
F
S
S
S
Br
Br
Br
F
S
S
S
OtBu
F
R
R
R = n-C6H13
F
5
6e
78
4
R
S
Br
yield of 1 (20%). In contrast, a change of the solvent from
DME to DMF dramatically increased the yield of 1 to
68% isolated yield (Table 1, entry 5).
S
S
R = n-C8H17
S
6
7
6f
60
57
Using the optimized reaction condition (Table 1, entry 5),
we attempted the synthesis of various bis(pentafluorophe-
nyl)-substituted thiophene and selenophene derivatives
(6) from the corresponding dibromo precursors (5). As
shown in Table 2, this method is quite effective to synthe-
size a wide range of compounds, including oligothio-
phenes with various chain lengths (Table 2, entry 2–5),
thiophene-fused system such as thieno[3,2:b]thiophene
(entry 6,7), and several selenophene homologues.
Br
Br
S
S
6g
Br
Br
S
S
8
9
6h
6i
78
69
Br
Br
Br
Br
Se
Se
In conclusion, we have established an effective method
for the synthesis of pentafluorophenyl-substituted
thiophene and selenophene derivatives using commercial-
ly available pentafluorophenyl boronic acid (3) and bro-
mo-thiophenes and -selenophenes. Since the bromide
precursors are easily accessible, the present method is po-
tentially useful for the synthesis of various pentafluo-
rophenyl substituted compounds for electronic or
photochemical functional materials. Research in this area
is currently underway.
2
erating at 372 MHz. Chemical shifts were reported as d values
(ppm) relative to internal standards, TMS for 1H and 13C NMR and
CFCl3 for 19F NMR. EI-MS spectra were obtained on a Shimadzu
QP-5050A spectrometer using an electron impact ionization proce-
dure (70 eV). MALDI-TOF MS spectra were obtained on a Shimad-
zu KOMPACT-MALDI PROBE spectrometer using a dithranol
matrix. The molecular ion peaks of the selenium-containing com-
pounds showed a typical selenium isotopic pattern, and all the sele-
nium-containing mass peaks are reported for 80Se. Elemental
analyses were performed by Mr. Hideaki Iwatani, Microanalytical
Laboratory in Department of Applied Chemistry, Faculty of Engi-
neering, Hiroshima University.
All reactions were carried out under a nitrogen atmosphere with an-
hydrous solvents. Column chromatography was carried out with
1
Daisogel IR-60 (63–210 mm). Melting points are uncorrected. H
and 13C NMR spectra were recorded on a JEOL Lambda 400 spec-
trometer operating at 400 MHz and 100 MHz, respectively. 19F
NMR spectra were recorded on a JEOL AL-400S spectrometer op-
Synthesis 2005, No. 10, 1589–1592 © Thieme Stuttgart · New York

PAPER
Syntheses of 2-(Pentafluorophenyl)thiophene Derivatives
1591
2-(Pentafluorophenyl)thiophene (1); Typical Procedure
A mixture of 2-bromothiophene (163 mg, 1.0 mmol), pentafluo-
rophenyl boronic acid (212 mg, 1.0 mmol), tetrakis(triphenylphos-
phine)palladium (81.5 mg, 0.08 mmol), Ag2O (460 mg, 2.0 mmol),
and K3PO4·n-hydrate (1.7 g) in DMF (7 mL) was stirred at 85 °C for
4 h. The mixture was poured into water (30 mL) and extracted with
CH2Cl2 (3 × 30 mL). The combined extract was washed with water
(3 × 50 mL), dried (MgSO4), and concentrated in vacuo. Column
chromatography on silica gel eluted with CH2Cl2 to remove highly
polar impurities followed by recrystallization from CH2Cl2–hexane
(1:1) gave faint colorless fine crystals of 2-(pentafluorophe-
nyl)thiophene (1, 170 mg, 68%); mp 42–43 °C.
3,3¢¢¢-Dihexyl-5,5¢¢¢-bis(pentafluorophenyl)-2,2¢:5¢,2¢¢:5¢¢,2¢¢¢-
quaterthiophene (6d)
Yield: 84%; orange needles (CHCl3–hexane, ca. 1:2); mp 127–
130 °C.
1H NMR (CDCl3): d = 0.90 (t, J = 7.1 Hz, 6 H), 1.30–1.46 (m, 12
H), 1.69 (quint, J = 7.8 Hz, 4 H), 2.83 (t, J = 7.8 Hz, 4 H), 7.12 (d,
J = 4.0 Hz, 2 H), 7.19 (d, J = 4.0 Hz, 2 H), 7.38 (s, 2 H).
13C NMR (CDCl3): d = 14.09, 22.60, 29.16, 29.30, 30.50, 31.62,
124.14, 127.10, 127.13, 133.11, 133.25, 134.08, 137.27, 139.79,
and a series of multiplets in the aromatic region (ArCF).
19F NMR (CDCl3): d = –162.55 (m, 4 F), –156.50 (t, J = 20.2 Hz, 2
F), –140.31 (dd, J = 6.4, 22.3 Hz, 4 F).
MS (MALDI-TOF): m/z = 830 [M+].
1H NMR (CDCl3): d = 7.19 (m, 1 H), 7.53 (m, 1 H), 7.56 (dd, J =
5.2, 1.0 Hz, 1 H).
13C NMR (CDCl3): d = 126.27, 127.27, 128.22, 130.11, and a series
of multiplets in the aromatic region (ArCF).
Anal. Calcd for C40H32F10S4: C, 57.82; H, 3.88. Found: C, 58.07; H,
3.79.
19F NMR (CDCl3): d = –162.70 (m, 2 F), –156.49 (t, J = 21.0 Hz, 1
F), –140.50 (dd, J = 7.2 Hz, 21.6 Hz, 2 F).
MS (EI): m/z = 250 [M+].
3,3¢¢¢-Dioctyl-5,5¢¢¢-bis(pentafluorophenyl)-2,2¢:5¢2 ¢¢:5¢¢,2¢¢¢-qua-
terthiophene (6e)
Yield: 78%; orange fine crystals (CHCl3–hexane, ca. 1:2); mp 137–
Anal. Calcd for C10H3F5S: C, 48.01; H, 1.21. Found: C, 47.79; H,
1.10.
138 °C.
1H NMR (CDCl3): d = 0.87 (t, J = 7.0 Hz, 6 H), 1.21–1.46 (m, 20
H), 1.66–1.74 (t, J = 7.7 Hz, 4 H), 2.83 (m, 4 H), 7.12 (d, J = 4.0
Hz, 2 H), 7.19 (d, J = 4.0 Hz, 2 H), 7.38 (s, 2 H).
13C NMR (CDCl3): d = 14.16, 22.77, 29.33 (× 2), 29.46, 29.56,
30.55, 31.92, 124.17, 127.09, 127.14, 133.14, 133.36, 134.13,
137.33, 139.75, and a series of multiplets in the aromatic region
(ArCF).
19F NMR (CDCl3): d = –162.55 (m, 4 F), –156.50 (t, J = 20.7 Hz, 2
F), –140.30 (dd, J = 6.4, 21.8 Hz, 4 F).
MS (MALDI-TOF): m/z = 886 [M+].
2,5-Bis(pentafluorophenyl)thiophene (6a)
Yield: 72%; pale yellow fine needles (CHCl3–hexane, 1:1);
mp 112–113 °C.
1H NMR (CDCl3): d = 7.60 (br s, 2 H).
13C NMR (CDCl3): d = 129.19, 130.19, and a series of multiplets in
the aromatic region (ArCF).
19F NMR (CDCl3): d = –161.98 (m, 4 F), –154.88 (t, J = 21.8 Hz, 2
F), –139.75 (dd, J = 6.2, 20.6 Hz, 4 F).
MS (EI): m/z = 416 [M+].
Anal. Calcd for C44H40F10S4: C, 59.58; H, 4.55. Found: C, 59.65; H,
4.45.
Anal. Calcd for C16H2F10S: C, 46.17; H, 0.48. Found: C, 46.03; H,
0.42.
2,5-Bis(pentafluorophenyl)thieno[3,2-b]thiophene (6f)
Yield: 60%; pale yellow needles (CHCl3–hexane, ca. 2:1); mp 233–
235 °C.
1H NMR (CDCl3): d = 7.70 (s, 2 H).
19F NMR (CDCl3): d = –161.94 (m, 4 F), –154.78 (t, J = 21.4 Hz, 2
F), –139.88 (dd, J = 5.8, 20.9 Hz, 4 F).
5,5¢-Bis(pentafluorophenyl)-2,2¢-bithiophene (6b)
Yield: 66%; yellow fine needles (CHCl3–hexane, 1:1); mp 182–
184 °C.
1H NMR (CDCl3): d = 7.32 (d, J = 3.2 Hz, 2 H), 7.50 (d, J = 3.2 Hz,
2 H).
13C NMR (CDCl3): d = 124.52, 126.07, 131.11, 138.85, and a series
of multiplets in the aromatic region (ArCF).
19F NMR (CDCl3): d = –162.26 (m, 4 F), –155.85 (t, J = 21.8 Hz, 2
F) –140.08 (dd, J = 6.2, 20.4 Hz, 4 F).
MS (EI): m/z = 472 [M+].
Anal. Calcd for C18H2F10S2: C, 45.77; H, 0.43. Found: C, 45.60; H,
0.47.
MS (EI): m/z = 498 [M+].
2,6-Bis(pentafluorophenyl)dithieno[3,2-b:2¢,3¢-d]thiophene (6g)
Yield: 57%; yellow fine crystals(CHCl3); mp 244–246 °C.
Anal. Calcd for C20H4F10S2: C, 48.20; H, 0.81. Found: C, 48.13; H,
0.76.
1H NMR (CDCl3): d = 7.75 (s, 2 H).
19F NMR (CDCl3): d = –161.78 (m, 4 F), –154.99 (t, J = 21.0 Hz, 2
5,5¢¢-Bis(pentafluorophenyl)-2,2¢:5¢,2¢¢-terthiophene (6c)
F), –139.88 (dd, J = 5.9, 20.6 Hz, 4 F).
Yield: 42%; bright orange fine needles (CHCl3); mp 90–191 °C.
MS (EI): m/z = 528 [M+].
1H NMR (CDCl3): d = 7.15 (s, 2 H), 7.21 (d, J = 4.0 Hz, 2 H), 7.46
(d, J = 4.0 Hz, 2 H).
19F NMR (CDCl3): d = –162.35 (m, 4 F), –156.12 (t, J = 20.8 Hz, 2
F), –140.18 (dd, J = 6.2, 20.9 Hz, 4 F).
Anal. Calcd for C20H2F10S3: C, 45.46; H, 0.38. Found: C, 45.49; H,
0.40.
2,5-Bis(pentafluorophenyl)selenophene (6h)
Yield: 78%; pale yellow fine needles (CHCl3–hexane, 1:1);
mp 134–136 °C.
1H NMR (CDCl3): d = 7.86 (br s, 2 H).
MS (EI): m/z = 580 [M+].
Anal. Calcd for C24H6F10S3: C, 49.66; H, 1.04. Found: C, 49.59; H,
1.07.
13C NMR (CDCl3): d = 132.55, 133.89, and a series of multiplets in
the aromatic region (ArCF).
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K. Takimiya et al.
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19F NMR (CDCl3): d = –162.08 (m, 4 F), –155.19 (t, J = 21.8 Hz, 2
F), –139.83 (dd, J = 6.1, 21.0 Hz, 4 F).
MS (EI): m/z = 464 [M+].
References
(1) Korenaga, T.; Kadowaki, K.; Ema, T.; Sakai, T. J. Org.
Chem. 2004, 69, 7340.
(2) (a) Facchetti, A.; Yoon, M.-H.; Stern, C. L.; Katz, H. E.;
Marks, T. J. Angew. Chem. Int. Ed. 2003, 42, 3900.
(b) Morimoto, M.; Kobatake, S.; Irie, M. Cryst. Growth Des.
2003, 3, 847. (c) Che, C.-M.; Hou, Y.-J.; Chan, M. C. W.;
Guo, J.; Liu, Y.; Wang, Y. J. Mater. Chem. 2003, 13, 1362.
(d) Ponzini, F.; Zagha, R.; Hardcastle, K.; Siegel, J. S.
Angew. Chem. Int. Ed. 2000, 39, 2323. (e) Sakamoto, Y.;
Suzuki, T.; Miura, A.; Fujikawa, H.; Tokito, S.; Taga, Y. J.
Am. Chem. Soc. 2000, 122, 1832. (f) Heidenhain, S. B.;
Sakamoto, Y.; Suzuki, T.; Miura, A.; Tokito, S.; Taga, Y. J.
Am. Chem. Soc. 2000, 122, 10240.
Anal. Calcd for C16H2F10Se: C, 41.49; H, 0.44. Found: C, 41.38; H,
0.32.
5,5¢-Bis(pentafluorophenyl)-2,2¢-biselenophene (6i)
Yield: 69%; yellow needles (CHCl3–hexane, 1:1); mp 202–203 °C.
1H NMR (CDCl3): d = 7.33 (m, 2 H), 7.70 (d, J = 4.0 Hz, 2 H).
13C NMR (CDCl3): d = 126.99, 127.24, 130.13, 133.37, and a series
of multiplets in the aromatic region (ArCF).
19F NMR (CDCl3): d = –162.34 (m, 4 F), –156.04 (t, J = 21.4 Hz, 2
F), –140.26 (dd, J = 5.8, 21.2 Hz, 4 F).
MS (EI): m/z = 594 [M+].
(3) Kamigata, N.; Yoshikawa, M.; Shimizu, T. J. Fluorine
Chem. 1998, 87, 91.
Anal. Calcd for C20H4F10Se2: C, 40.57; H, 0.68. Found: C, 40.64; H,
0.65%.
(4) Demir, A. S.; Reis, ; Emrullahoglu, E. Tetrahedron 2002, 58,
8055.
(5) Pentafluorophenylboronic acid can be purchased from
Aldrich. The reagent is also readily prepared, see: Frohn,
H.-J.; Adonin, N. Y.; Bardin, V. V.; Starichenko, V. F. Z.
Anorg. Alleg. Chem. 2002, 628, 2827.
(6) Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457.
(7) Havelková, M.; Hocek, M.; Česnek, M.; Dvořák, D.
Synthesis 1999, 1145.
Acknowledgment
This work was partially supported by an Industrial Technology Re-
search Grant Program in 2004 from New Energy and Industrial
Technology Development Organization (NEDO) of Japan. One of
the authors (KT) is indebted to the Satake Foundation for Research
and Education for financial support. The authors are grateful to
Prof. Y. Yamamoto and Prof. A. Kawachi (Hiroshima University)
for the measurement of 19F NMR spectra.
(8) Chen, J.; Cammers-Goodwin, A. Tetrahedron Lett. 2003,
44, 1503.
Synthesis 2005, No. 10, 1589–1592 © Thieme Stuttgart · New York