A novel and direct synthesis of alkylated 2,2Ј-bithiophene
derivatives using a combination of hypervalent iodine(III) reagent
and BF3ؒEt2O
Hirofumi Tohma, Minako Iwata, Tomohiro Maegawa, Yorito Kiyono, Akinobu Maruyama and
Yasuyuki Kita*
Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita,
Osaka, 565-0871, Japan. E-mail: kita@phs.osaka-u.ac.jp; Fax: ϩ81-6-6879-8229;
Tel: ϩ81-6-6879-8225
Received 5th March 2003, Accepted 24th April 2003
First published as an Advance Article on the web 29th April 2003
A novel nonmetallic oxidative coupling of alkylthiophene
derivatives leading to the corresponding 2,2Ј-bithiophene
derivatives using a combination of a hypervalent iodine(III)
reagent, phenyliodine bis(trifluoroacetate) (PIFA), and
BF3ؒEt2O was developed.
We first examined the dimerization of 3-hexylthiophene (1a)
using PIFA-BF3ؒEt2O. At room temperature, only a complex
mixture was obtained. However, surprisingly, 2,2Ј-bithiophenes
(2a and 3a) were mainly obtained at lower temperatures. Fur-
thermore, both the reaction temperature and the molar ratio of
1a and PIFA remarkably affected the yield of the dimer (2a and
3a), bithiophenes were obtained in 72% yield (by GC) when
the reaction was carried out following the typical procedure
described in the Notes and references section† (entries 1–4,
Table 1). On the other hand, no reaction occurred in the
absence of additives, in the presence of heteropolyacid
(H3[PW12O40]), or in (CF3)2CHOH (entries 5–7, Table 1). To
confirm the differences among the oxidants, typical metal-
induced reaction conditions including the variations in both
temperature and equivalents of the reagents were also re-
examined. As a result, in all cases, no dimer was obtained even
when the reaction was carried out at a temperature lower than
those reported for entries 8–12 in Table 1.
This reaction was applicable to various alkylated bithiophene
syntheses. The results are summarized in Table 2. Although the
regioselectivity† [head to head (H-H) isomer 2 and head to
tail (H-T) isomer 3] of bithiophenes was not observed, the
corresponding 2,2Ј-bithiophenes were obtained exclusively in
moderate to good yields without forming 2,3Ј-linked bithio-
phenes and polymers (entries 1 and 3–6, Table 2). Similarly, the
coupling reactions of di- or tri-alkyl thiophenes (1f–h) also
proceeded smoothly to afford end-capped bithiophenes (2f–h)
in moderate yields (entries 7–9, Table 2).
The oligo- and poly-(3-alkylthiophene) derivatives have
recently received considerable attention due to their useful
physical properties such as electrical conductivity and electro-
luminescence.1 2,2Ј-Bithiophene is one of the most important
precursors of oligo- and poly-thiophenes since it can be poly-
merized under mild conditions due to its lower oxidation poten-
tial compared to thiophene itself, and predominantly yields
higher quality α-linked polymer compared to that prepared
from thiophene monomer by inhibiting the formation of
α,β-defects.1b Therefore, there have been a number of reports on
the preparation of 2,2Ј-bithiophenes, but these methodologies
have been limited to transition metal catalyzed coupling
reactions. Namely, reactions such as Ullmann, Suzuki, Stille,
Negishi, Kumada–Tamao, and the related coupling reactions
via halogenation or metallation of thiophene derivatives have
been the most reliable methods.2 On the other hand, oxidative
coupling of thiophenes seems to be a direct and convenient
route to the preparation of bithiophenes, yet, to the best of our
knowledge, there have been no reports on the oxidative dimer-
ization of thiophenes due to the lower oxidation potential of
the bithiophene compared to the corresponding thiophene,
unless the thiophene itself was activated as its anion form by
treatment with strong base.3 That is, the dimer, which is more
easily oxidized than the monomer, always undergoes further
coupling to afford the polythiophene through successive
steps.4 Therefore, typical oxidative coupling methods using
electrochemical oxidation1a or metal oxidants such as Fe(),1
Tl(),4,5a,b Ru(),5c and Mo()5c have not been utilized for
dimerization, but for oligomerization or polymerization of
alkyl thiophene derivatives.
A plausible reaction mechanism is shown in Scheme 1. Cation
radical B is initially formed from 1 with PIFA-BF3ؒEt2O via
CT-complex A under the reaction conditions in a manner
analogous to those of our previously developed PIFA-induced
reactions7,8 or typical heavy metal oxidations5 yielding aro-
Over the last decade, the use of hypervalent iodine()
reagents has gained importance as a safe alternative to heavy
metal reagents for performing a variety of organic transform-
ations.6 In our ongoing studies on hypervalent iodine chemistry,
we have recently developed mild and high yielding oxidative
biaryl coupling reactions of phenol ethers or alkylarenes via
aromatic cation radical intermediates using a combination of
either phenyliodine() bis(trifluoroacetate) (PIFA) and BF3ؒ
Et2O or PIFA and heteropolyacid.7 As a novel and useful exten-
sion of our studies on biaryl synthesis, we report herein the first
facile and direct oxidative coupling reaction of alkyl thio-
phene derivatives leading to the corresponding bithiophenes
using PIFA-BF3ؒEt2O without any activation of thiophene
monomers.
Scheme 1 A plausible reaction mechanism.
T h i s j o u r n a l i s © T h e R o y a l S o c i e t y o f C h e m i s t r y 2 0 0 3
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 1 6 4 7 – 1 6 4 9
1647
Tohma, Hirofumi
