Concise synthesis of well-defined linear and branched oligothiophenes with nickel-catalyzed regiocontrolled cross-coupling of 3-substituted thiophenes by catalytically generated magnesium amide

Article abstract of DOI:10.1002/chem.201203331

The synthesis of linear and branched oligothiophenes of well-defined structures is performed with regioselective deprotonation of 3-substituted thiophenes and nickel-catalyzed cross-coupling of the thus formed metalated species with a bromothiophene. The reaction of 3-hexylthiophene with EtMgCl and 2,2,6,6-tetramethylpiperidine (TMP-H, 10 mol %) induces the metalation selectively at the 5-position by use of the catalytically generated hindered magnesium amide (TMPMgCl) and the subsequent reaction of a 2-halo-3- hexylthiophene (bromide or chloride) in the presence of a nickel catalyst affords a head-to-tail (HT)-type dimer. By repeating the same sequence, the linear oligothiophene up to a 4-mer is synthesized in good yield. The reaction of 3-hexylthiophene with 2,3-dibromothiophene also takes place to afford a branched oligothiophene 3-mer in quantitative yield. The obtained 3-mer is also metalated at the sterically less-hindered position in a regioselective manner furnishing a 7-mer in >99 % yield after a further coupling reaction with 2,3-dibromothiophene. These dendrimers react with several multifunctionalized organic electrophiles, leading to a variety of branched oligothiophenes. Copyright

Full text of DOI:10.1002/chem.201203331

DOI: 10.1002/chem.201203331
Concise Synthesis of Well-Defined Linear and Branched Oligothiophenes
with Nickel-Catalyzed Regiocontrolled Cross-Coupling of 3-Substituted
Thiophenes by Catalytically Generated Magnesium Amide
Shota Tanaka, Daiki Tanaka, Go Tatsuta, Kohei Murakami, Shunsuke Tamba,
Atsushi Sugie, and Atsunori Mori*[a]
Abstract: The synthesis of linear and
branched oligothiophenes of well-de-
fined structures is performed with re-
gioselective deprotonation of 3-substi-
tuted thiophenes and nickel-catalyzed
cross-coupling of the thus formed
metalated species with a bromothio-
phene. The reaction of 3-hexylthio-
phene with EtMgCl and 2,2,6,6-tetra-
methylpiperidine (TMP-H, 10 mol%)
induces the metalation selectively at
the 5-position by use of the catalytical-
ly generated hindered magnesium
amide (TMPMgCl) and the subsequent
reaction of a 2-halo-3-hexylthiophene
(bromide or chloride) in the presence
of a nickel catalyst affords a head-to-
tail (HT)-type dimer. By repeating the
same sequence, the linear oligothio-
phene up to a 4-mer is synthesized in
good yield. The reaction of 3-hexylthio-
phene with 2,3-dibromothiophene also
takes place to afford a branched oligo-
thiophene 3-mer in quantitative yield.
The obtained 3-mer is also metalated
at the sterically less-hindered position
in a regioselective manner furnishing a
7-mer in >99% yield after a further
coupling reaction with 2,3-dibromo-
thiophene. These dendrimers react
with several multifunctionalized organ-
ic electrophiles, leading to a variety of
branched oligothiophenes.
Keywords: cross-coupling
·
den-
drimers · NHC ligands · nickel cata-
lysts · oligothiophenes
Introduction
cross-coupling reactions of organoboron[11] and organotin[12]
reagents and the synthesis requires a two-step sequence in
each extension of the number of generations involving tran-
sition-metal-catalyzed coupling and further transformation
of the thus coupled dendron into the corresponding organo-
metallic reagent.[13] Accordingly, a rather multistep synthetic
pathway has been repeated when oligothiophene dendrimers
of higher order generations are designed. Development of a
more concise preparative method for thiophene dendrimers
is, therefore, intriguing.
Oligothiophenes and polythiophenes have recently attracted
remarkable attention as materials showing conductive, semi-
conductive, nonlinear optical, and liquid–crystalline charac-
teristics, among others. They are employed as thin-film or-
ganic transistors,[1] liquid–crystalline compounds,[2] and dye-
sensitized organic photovoltaic cells.[3] Oligothiophenes com-
posed of a thiophene unit bearing a substituent at the 3-po-
sition form three types of possible regioisomers, head-to-
head (HH), tail-to-tail (TT), and head-to-tail (HT). Among
these, the HT isomer generally shows a superior perform-
ance due to decreased steric congestion and thus extended
p-conjugation.[1d,3b–d,4] Development of a concise preparative
method of HT-type oligothiophenes is, therefore, an impor-
tant issue in organic synthesis.[5,6]
On the other hand, we have been engaged in the coupling
À
reaction at the C H bond of heteroaromatic compounds
with various organic electrophiles.[14,15] The method allows
À
remarkable step efficiency by the direct activation of the C
H bond or in situ formation of metallic species by deproto-
native metalation prior to the coupling compared with exist-
ing cross-coupling with the isolated organometallic com-
pounds, such as boron, silicon, and tin reagents.
Branched oligothiophene dendrimers have also been stud-
ied as represented by the pioneering work of Advincula and
Bꢀuerle as potentially applicable light-harvesting,[7] self-as-
sembly,[8] and optoelectronic materials.[9,10] These oligothio-
phene dendrimers have been synthesized by employing
We have recently reported HT-type oligothiophene[16,17]
and polythiophene[18] syntheses with nickel-catalyzed cross-
À
coupling at the C H bond of thiophene, in which a stoichio-
metric amount of magnesium amide TMPMgCl·LiCl (TMP-
H=2,2,6,6-tetramethylpiperidine), recognized as a Knochel–
Hauser base,[19] served as an efficient deprotonating agent
for in situ formation of the metalated species. A series of
linear oligothiphenes can be synthesized by repeating the
coupling reaction, in which a single one-pot reaction has ex-
tended a thiophene unit in a facile manner in contrast to
multistep conventional cross-coupling pathways. Although
[a] S. Tanaka, D. Tanaka, G. Tatsuta, K. Murakami, S. Tamba,
Dr. A. Sugie, Prof. Dr. A. Mori
Department of Chemical Science and Engineering, Kobe University
1-1 Rokkodai, Nada, Kobe 657-8501 (Japan)
Fax : (+81)78-803-6181
E-mail: amori@kobe-u.ac.jp
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201203331.
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FULL PAPER
Table 1. Regioselectivity in the metalation of 1a with several amines
we have also shown that the combination of a Grignard re-
agent and catalytic secondary amine[20,21] is equally effective,
for the metalation, as the use of a stoichiometric amount of
the Knochel–Hauser base, the reaction conditions of such a
catalytic metalation process have hardly been optimized and
the scope and limitations are not yet clear. Herein, we de-
scribe further studies of such a catalytic system of deproto-
nation for the synthesis and the application to the concise
stepwise synthesis of well-defined linear HT-type oligothio-
phenes.
(10 mol%) and EtMgCl.[a]
Amine
T
[8C]
t
Conv. [%]
[h]
(2a-CHO/3a-CHO)[b]
TMP-H
RT
24
10
24
24
24
1
28 (>99:1)
56 (>99:1)
95 (>99:1)
86 (93:7)
80 (91:9)
26 (96:4)
reflux
reflux
reflux
reflux
reflux
iPr2NH
Cy2NH
[a] The reaction was performed with 1a (0.5 mmol), EtMgCl (0.6 mmol),
and amine (0.05 mmol) in THF (0.6 mL). [b] Conversion and the ratio of
2a-CHO/3a-CHO was estimated by H NMR spectroscopic analysis.
Furthermore, we envisaged that such regioselective depro-
tonation of thiophene and the subsequent coupling reaction
with 2,3-dibromothiophene in the presence of a nickel cata-
lyst could afford a branched thiophene 3-mer and repeating
of a similar reaction extends the generation leading to the
oligothiophene dendron, which would be a much simpler
and step-economic synthesis of oligothiophene dendrimers.
We also disclose that a variety of well-defined branched
1
in inferior conversion. Although the reaction with 10 mol%
of TMP-H at room temperature for 24 h selectively afforded
2a-CHO, the conversion fell to 28%. The reaction with di-
AHCTUNGTREGiNNNU sopropylamine (iPr2NH) resulted in inferior regioselectivity
and reactivity. The use of dicyclohexylamine (Cy2NH) was
also found to induce slightly inferior regioselectivity al-
though the reaction proceeded smoothly. We have recently
shown that metalation of 2-chloro-3-hexylthiophene with
EtMgCl and 10 mol% of Cy2NH proceeded completely
within 1 h;[18a] however, the reaction of 3-hexylthiophene, in
oligoACHTUNGTRENNUNGthiophenes are synthesized by the stepwise regioselec-
tive metalation and the following cross-coupling reaction of
multifunctionalized organic electrophiles.
À
Results and Discussion
which the C H bond at the 5-position is less acidic, for 1 h
underwent the metalation in insufficient conversion (26%).
The transition-metal-catalyzed cross-coupling reaction of
4-bromotoluene in the presence of a palladium catalyst
(PEPPSI-IPr, [1,3-bis(2,6-diisopropylphenyl)immidazol-2-yli-
dene](3-chloropyridyl)palladium(II))[22] was carried out with
the above optimized metalation conditions of 1a at the 5-
position by using EtMgCl and TMP-H (10 mol%) for 24 h
to afford the 5-arylated product exclusively in 81% yield.
The arylation reactions with several 3-substituted thiophenes
When 3-hexylthiophene (1a) was treated with ethyl magne-
sium chloride (EtMgCl) and TMP-H (10 mol%) for 24 h in
THF under reflux, the reaction proceeded to give the metal-
À
othiophene at the C H bond of the 5-position selectively,
which was confirmed by treatment with DMF to afford the
corresponding 2-formyl-4-hexylthiophene (2a-CHO), exclu-
sively (Scheme 1).
À
were then examined to study the selectivity for the C H
bond, as summarized in Table 2. The reaction of 3-fluoroal-
Table 2. Regiochemistry of the reaction with 3-substituted thiophenes.[a]
Scheme 1. Regioselective deprotonation of 3-hexylthiophene with
EtMgCl and TMP-H.
We examined the regioselectivity in the metalation of 1a
with ethylmagnesium chloride (EtMgCl) and a catalytic
amount of several secondary amines to form the corre-
sponding thienylmagnesium compounds. Table 1 summarizes
the results. The progress of the reaction was confirmed by
quenching the mixture with DMF to afford 2-formyl-4-hex-
ylthiophene (2a-CHO) and 2-formyl-3-hexylthiophene (3a-
CHO). The reaction with 10 mol% of TMP-H under reflux
in THF for 24 h completely proceeded to afforded 2a-CHO,
exclusively, whereas shorter reaction periods (10 h) resulted
[a] Unless otherwise noted, the reaction was carried out with 3-substitut-
ed thiophene (0.50 mmol), 4-bromotoluene (0.75 mmol), EtMgCl
(0.60 mmol), TMP-H (0.05 mmol), and PEPPSI-IPr (0.01 mmol) in THF
(2.0 mL). The ratio of 2- and 5-arylated products was estimated by
1H NMR spectroscopic analysis. [b] The ratio of 2- and 5-arylated prod-
ucts was determined by GC analysis. [c] The reaction was performed with
4-bromoanisole (0.75 mmol).
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A. Mori et al.
kylated thiophene 1b and 3-arylated thiophene 1d with 4-
bromotoluene also occurred regioselectively at the 5-posi-
tion. The reaction of 3-methylthiophene (1c) resulted in
slightly inferior regioselectivity (97:3). By contrast, the reac-
tion of 3-methoxythiophene (1e) resulted in predominantly
the 2-arylated product, probably due to the directing effect
of the methoxy group in the reaction with the magnesium
amide. Less selective metalation was found to occur with an
alkynyl-group-substituted thiophene 1 f.
With regioselective metalation at the 5-position of 3-sub-
stituted thiophene, we focused on the application to the for-
mation of a HT-type thiophene–thiophene bond. The reac-
tion of 1a with 2-bromo-3-hexylthiophene (4a) was exam-
ined with several transition-metal catalysts. As shown in
Table 3, the reaction with a nickel catalyst bearing a biden-
Table 3. The reaction of 1a with 2-bromo-3-hexylthiophene (4a) with
transition-metal catalyst.[a]
Scheme 2. HT-type oligothiophene synthesis with regioselective cross-
coupling.
Catalyst
EtMgCl
[equiv]
4a
[equiv]
T
[8C]
t
Yield
[%][c]
G
G
[h]
ing the quaterthiophene in 53% yield. It was observed that
the yield decreased as the number of thiophene units in-
creased. When the deprotonation was performed with a stoi-
chiometric amount of EtMgCl along with TMP-H
(10 mol%) in the reaction of 5a, it was found that only
83% of the dimer underwent the deprotonation, which was
confirmed to lead to the corresponding aldehyde by treat-
ment with DMF. Increasing the amount of EtMgCl to
1.5 equivalents resulted in the formation of a dianion, which
suggested deprotonation also at the more hindered 2-posi-
tion to afford mono- and diformylated products in 69 and
31% yields, respectively. However, it was found that no cou-
pling reaction at the hindered position took place in the re-
action of 5a with 4a, providing 6a in 90% yield with [NiCl2-
G
G
1.0
1.0
1.0
1.0
1.2
1.2
60
60
60
60
60
24
24
20
2
90
77
77
89
>99
E
1.0[b]
1.0
A
E
1.2
U
1.2[b]
20
[a] Unless otherwise noted, the reaction was performed with 1a
(0.50 mmol) in THF (2.0 mL). [b] The reaction was carried out with 1a
(1.0 mmol) in THF (3.0 mL). [c] Yield of the isolated product.
tate diphosphine, [NiCl2ACTHNUTRGNEU(GN dppp)] (dppp=1,3-bis(diphenyl-
phosphino)propane), at 608C for 24 h proceeded to afford
the HT-type dimer 5a in an excellent yield (90%). The reac-
tion of [NiCl
2ACHTUNGTRENNUNG(dppe)] (dppe=1,2-bis(diphenylphosphino)-
ethane) also resulted in a good yield. The use of a combina-
AHCTUNGRTEG(NUNN dppp)] (2.0 mol%) or 92% yield with [NiCl2ACHTUNGTREG(NUNN IPr)ACHTUNGTRENNUNG(PPh3)]
tion of [Ni
N
(2.0 mol%) as the sole product. The yield of the reaction of
6a with 1.8 equivalents of EtMgCl improved to 76% with
[NiClACHTUNRTGENNUG(IPr)ACHUTNGTRNEN(NGU PPh3)] (2.0 mol%). A similar trend was also ob-
served in the reaction with a stoichiometric amount of
TMPMgCl·LiCl to afford a 65% yield of 7a, whereas the
yield was much lower (47%) from the deprotonation with
1.2 equivalents of the corresponding base.[16]
We envisaged a further improvement of the atom efficien-
cy of the HT-type oligothiophene synthesis with 2-chloro-3-
hexylthiophene (8a) instead of bromide 4a. However, the
reaction of 1a with 2-chloro-3-hexylthiophene (8a) in the
achieved with nickel catalyst [NiCl
PPh3 and the NHC ligand N,N’-bis[(2,6-diisopropylphenyl)-
imidazol]-2-ylidene (IPr) to afford 5a in a quantitative yield
G
at 608C for 24 h. The reaction with [NiCl
forded 5a in 89% yield within 2 h.
The synthesis of HT-type oligomers of 3-hexylthiophene
by using a combination of EtMgCl and TMP-H (10 mol%)
was carried out as summarized in Scheme 2. The obtained
HT-bithiophene (5a) was subjected to further reaction with
presence of [NiCl2ACTHNUTRGNE(NUG dppp)] as the catalyst at 608C for 20 h
only afforded 5a in 19% yield. Nevertheless, as shown in
Scheme 3, the reaction with 8a was found to take place suc-
4a in the presence of [NiCl
G
cessfully with [NiCl2ACTHNGUTERNU(NG IPr)ACHTUNGTNER(NUNG PPh3)] (2.0 mol%) the catalyst to
terthiophene 6a in 78% yield. The obtained 6a reacted with
4a to give HT-type tetramer 7a in a similar manner, furnish-
give 5a in excellent yield. It is worth noting that the effect
of the NHCs is markedly different from the one in the reac-
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Synthesis of Well-Defined Linear and Branched Oligothiophenes
FULL PAPER
Scheme 5. Synthetic strategy of thiophene dendrimers.
tion of the thiophene dendron. A step-economic synthesis of
oligothiophene dendrimers compared with conventional
Scheme 3. HT-type oligothiophene synthesis with 2-chloro-3-hexylthio-
phene (8a).
AHCTUNGTRENNUNG
protocols involving the formation of thienyl boron or tin re-
agents, followed by cross-coupling is depicted in
Scheme 5.[13]
The reaction of 3-hexylthiophene (1a) with 2,3-dibromo-
thiophene (10) was first carried out in a similar manner to
the reaction of linear oligothiophenes. As shown in Table 4,
tion with bromothiophene, which has reacted smoothly with
bidentate phosphines as a ligand. The HT-trimer (6a) and
tetramer (7a) were also obtained in good to excellent yields
in a similar manner.
Oxidative homocoupling through the regioselective de-
protonation of 1a was also examined.[25] The reaction of 1a
with a transition-metal salt under an oxygen atmosphere
proceeded to afford tail-to-tail (TT)-type bithiophene (9a).
The reaction with 5.0 mol% of nickel chloride at room tem-
perature for 24 h took place to give 9a exclusively in 64%
yield. The use of copper chloride resulted in 69% yield
(Scheme 4). It is remarkable that the TT-type bithiophene is
Table 4. The reaction of 1a with 10 in the presence of nickel catalyst.[a]
Entry
1a/10
Catalyst
T [8C]
t
Yield [%]
3T
11
1[b]
2
3
4
5
6
7
8
2.5:1
2.5:1
1:1
1:1
1:1
1:1
1:1
1:1
N
(IPr)
N
RT
RT
RT
60
60
60
24 h
>99[c]
78[c]
0
0
0
32
0
14
21
26
10 min
10 min
23 h
24 h
24 h
41[c]
17[c]
33[d]
6[d]
60
60
24 h
24 h
<1[d]
<1[d]
N
Scheme 4. Synthesis of TT-type bithiophene by oxidative homocoupling
of 1a.
[a] Unless otherwise noted, the reaction was carried out with 1a
(0.50 mmol), TMP-H (0.05 mmol), EtMgCl (0.50 mmol), and nickel cata-
lyst (0.01 mmol) in THF (2.0 mL). [b] The reaction was performed with
1a (3.0 mmol). [c] Yield of the isolated product. [d] The yield of 3T and
synthesized in a single step, whereas conventional synthesis
has been performed with two or more steps involving a
much less atom- and step-economic bromination/debromina-
tive homocoupling sequence.
Our interest then turned to the synthesis of dendritic
oligoACHTUNGTRENNUNGthiophenes with the regioselective cross-coupling reac-
1
11 was estimated by H NMR spectroscopic analysis.
the reaction of 1a with EtMgCl and TMP-H (10 mol%)
under reflux in THF for 24 h induced the metalation at the
5-position selectively. The following addition of 2,3-dibro-
tion of 3-substituted thiophenes. We envisaged that the re-
gioselective deprotonation of thiophene and the subsequent
reaction with 2,3-dibromothiophene (10) in the presence of
a nickel catalyst would afford a thiophene dendron 3-mer
and repeating the similar reaction would extend the genera-
mothiophene (10) in the presence of [NiCl2ACTHNGUTRENNU(G IPr)ACHTUNGTRENNUNG(PPh3)]
(2.0 mol%) at room temperature for 24 h afforded thio-
phene dendron 3-mer (3T) in a quantitative yield (Table 4,
entry 1). It is also remarkable that the reaction was found to
be rather fast and proceeded in 78% yield within 10 min,
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A. Mori et al.
whereas monocoupling product 11 was not observed at all in
spite of the fact that the carbon–bromine bond at the 3-posi-
tion is much less reactive than that at the 2-position
(Table 4, entry 2).
We next performed the reaction of an equimolar amount
of 3-hexylthiophene (1a) with 2,3-dibromothiophene (10) in
the presence of [NiCl2ACTHNUTRGNNEG(U IPr)CAHTUNGTNER(NUGN PPh3)] (Table 4, entry 3). Even
when the reaction was carried out with a 1:1 ratio of 1a and
10 and 2.0 mol% of the catalyst, complete consumption of
1a was confirmed at room temperature after 10 min to
afford 3T in 41% yield with recovery of 2,3-dibromothio-
phene (54%) and the monocoupling product 11 was not ob-
served at all. A similar effect was observed with a palladium
catalyst PEPPSI-IPr in the reaction of several multihalogen-
ated organic electrophiles with a variety of organometallic
reagents;[26,27] however, the reaction of thiophene catalyzed
Scheme 6. Reaction of 10 with a thienyl boronic acid ester and thienyl-
ACHUTNGRENsNUG tanACHTUNGTRENaNNGU nnes. dba=dibenzylideneacetone.
by [NiCl2ACHTUNGTRENNUNG(IPr)ACHTUNGTRENNUNG(PPh3)] indicated the improved performance
to undergo the multiple coupling reaction. Indeed, the reac-
tion of 1a and 10 with PEPPSI-IPr (2.0 mol%) as the cata-
lyst at 608C for 23 h resulted in a mixture of 3T and 11 in
17 and 32% yields, respectively (Table 4, entry 4). We also
carried out the reaction with other nickel and palladium cat-
alysts (Table 4, entries 5–8). The reaction with [NiCl2ACTHNUTRGNEU(GN dppe)]
at 608C for 24 h gave 3T in 33% yield, and the monocou-
pling product 11 was not observed at all. The reaction with
a nickel catalyst with a bidentate diphosphine ligand, [NiCl2-
ACHTUNGTRENNUNG
CHTUNGTRENNUNG
proceeded to afford 11 in a poor yield. Although the reac-
tion with a palladium catalyst with a bulky phosphine
ligand, [PdACHTUNGTRENNUNG(PtBu3)2], proceeded, the yield was found to be
much inferior.
The observed multiple coupling seems to be the specific
case in the reaction of a thienyl magnesium reagent with a
nickel NHC catalyst, whereas such a drastic effect has not
been found in the preceding synthesis of thiophene den-
drimers with thienyl boron and tin reagents. Indeed, the re-
lated reaction of 4-hexyl-2-tributylstannylthiophene (1a-
nBu3Sn) with 10 preferentially afforded the monocoupling
product 11 in 83% yield and 3T in a poor yield (7%) when
the reaction was carried out employing an equimolar
amount of the organometallic reagent and dibromothio-
phene 10 (Scheme 6). A similar trend was also observed in
the reaction of thienylboronate pinacol ester (1a-Bpin) to
afford an 80% yield of 11 along with a 5% yield of 3T. Ac-
cordingly, it has been necessary to accomplish complete con-
version with the Suzuki–Miyaura or Migita–Kosugi–Stille
protocols,[28] thus, longer reaction periods and use of excess
of the organometallic reagent have been conducted in the
conventional reactions. In addition, separation of the once-
formed monocoupled byproduct and the desired dendrimer
must be performed. By contrast, the reaction of 1a with the
nickel catalyst does not require such troublesome separation
of the undesired byproducts.
Scheme 7. Thiophene dendrimer synthesis up to the 15-mer.
obtained 3T was also metalated selectively at the sterically
less-hindered position by TMP-H/EtMgCl and the reaction
with 10 at 608C for 20 h led to the thiophene dendron 7-mer
(7T) in a quantitative yield. Treatment of 7T with TMP-H
(10 mol%) and EtMgCl and the reaction with 10 at 608C
for 24 h led to the 15-mer 15T in 46% yield.
The synthesis of the thiophene dendrimer bearing the flu-
À
oroalkyl group,[29,15b]
ACHTNUGTNERN(NUG CH2)3C4F9, was also achieved suc-
cessfully in a similar manner, as shown in Scheme 8. The de-
protonation reaction of 3-fluoroalkylated thiophene 1b with
EtMgCl/TMP-H (10 mol%) also took place at the 5-position
selectively and the subsequent reaction with 10 in the pres-
We next performed further extension of thiophene den-
drimer up to a 15-mer in a similar manner (Scheme 7). The
ence of [NiCl2ACHTNUGRTNENUG(IPr)ACHTUTGNREN(NGUN PPh3)] (2.0 mol%) at 608C for 27 h af-
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Synthesis of Well-Defined Linear and Branched Oligothiophenes
FULL PAPER
Our further concern is the regioselective coupling of thio-
phene dendrimers with several bromothiophenes and aryl
halides. These results are summarized in Scheme 9. The re-
action of 3T with 2,5-dibromothiophene (12) at 608C for
23 h smoothly took place to give 2,5-(3T)2-Th in >99%
yield. The reaction of 7T with 12 also occurred to afford 2,5-
(7T)2-Th in 87% yield. A benzene-ring-centered thiophene
dendrimer was obtained by the reaction of 7T with 1,3,5-tri-
bromobenzene in the presence of palladium catalyst
PEPPSI-IPr to give 1,3,5-(7T)3-Ph in 90% yield. The reac-
tion of 3T in the presence of CuCl2 (5.0 mol%) under an
oxygen atmosphere at 608C for 26 h proceeded to afford ho-
mocoupling product (3T)2 in 64% yield. The homocoupling
reaction of 7T also afforded (7T)2 in 51% yield.
Scheme 8. Synthesis of 3-fluoroalkylated thiophene dendrimers.
forded 3T-RF in a quantitative yield. In addition, 7T-RF was
also obtained by the cross-coupling reaction of 3T-RF with
10 in 80% yield.
Further transformations of the obtained dendrimers 3T
and 7T are plausible when the synthesis is performed with a
regioselective deprotonative coupling reaction with 3-hex-
Scheme 9. Synthesis of thiophene dendrimer derivatives.
Chem. Eur. J. 2013, 19, 1658 – 1665
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A. Mori et al.
ylthiophene (1a), in contrast to the fact that conventional
thiophene dendrimers bearing hexyl groups adjacent to the
sulfur atom would limit the related transformations. As
shown in Scheme 10, the reaction of 3T with NBS
Experimental Section
General procedure for the reaction of 3-hexylthiophene (1a) with
EtMgCl/TMP-H (10 mol%) and 2-bromo-3-hexylthiophene (4a): A solu-
tion of EtMgCl in THF (1.21 mL, 1.2 mmol) and TMP-H (0.017 mL,
0.1 mmol) were added to a Schlenk tube (20 mL) equipped with a mag-
netic stirring bar. 3-Hexylthiophene (1a, 0.180 mL, 1.0 mmol) was added
to the solution and stirring was continued under reflux for 24 h. Then,
THF (1.8 mL), 2-bromo-3-hexylthiophene (4a, 0.239 mL, 1.2 mmol), and
À
(2.2 equiv) at 08C proceeded at the C H bond adjacent to
[NiCl2ACTHNUGTRENN(UG IPr)ACHTUNGTREN(NUGN PPh3)] (15.6 mg, 0.02 mmol) were added successively. The
mixture was allowed to stir at 608C for 20 h. After cooling to room tem-
perature, the mixture was quenched with a saturated aqueous solution of
ammonium chloride (1.0 mL). The solution was poured into a mixture of
diethyl ether/water and two phases were separated. The aqueous layer
was extracted twice with diethyl ether and the combined organic layers
were dried over anhydrous sodium sulfate and concentrated under re-
duced pressure to leave a crude oil, which was purified by column chro-
matography on silica gel by using hexanes as the eluent to afford 5-(3-
hexylthiophen-2-yl)-3-hexylthiophene (5a, light-yellow oil, 335.2 mg,
>99%).
General procedure for the reaction of 3-hexylthiophene (1a) and 2,3-di-
bromothiophene (10) with EtMgCl/TMP-H (10 mol%): EtMgCl (0.99m,
7.5 mL, 7.5 mmol) in THF and TMP-H (0.01 mL, 0.75 mmol) were added
to a Schlenk tube (50 mL) equipped with a magnetic stirring bar. 3-Hex-
ylthiophene (1a, 0.048 mL, 7.5 mmol) was added to the solution and stir-
ring was continued under reflux for 24 h. The reaction mixture was
cooled to 08C (CAUTION! Exotherm by the reaction causes boiling of
the solvent) and then THF (1.5 mL), 2,3-dibromothiophene (10,
0.074 mL, 3.0 mmol), and [NiCl2ACTHNUTRGENNUG(IPr)ACHTUGNTREN(NUNG PPh3)] (7.8 mg, 0.01 mmol) were
added successively. The mixture was allowed to stir at room temperature
for 24 h. The mixture was quenched with a saturated aqueous solution of
ammonium chloride (1.0 mL). The solution was poured into a mixture of
diethyl ether/water and the two phases were separated. The aqueous
layer was extracted with twice diethyl ether and the combined organic
layers were dried over anhydrous sodium sulfate. Concentration of the
solvent under reduced pressure left a crude oil, which was purified by
column chromatography on silica gel by using hexanes as an eluent to
afford 3T (1.25 g, yellow oil, >99%).
Scheme 10. Regioselective bromination of thiophene dendrimers with N-
bromosuccinimide (NBS).
the hexyl group selectively to afford dibrominated product
3T-Br2 in an excellent yield (98%), whereas the similar re-
action with 3.5 equivalents of NBS at 608C led to the tribro-
minated product 3T-Br3 in a quantitative yield. These results
suggest that further transformation of the thus prepared
bromides would be possible. The similar reaction of 7T with
5.0 equivalents of NBS in THF and acetic acid at 08C af-
forded the tetrabrominated 7T-Br4 in 80% yield.
Acknowledgements
The authors thank financial support for Scientific Research (B) by JSPS,
Japan, and the Nagase Science Promotion Foundation. S.T. (the 5th
author) acknowledges the JSPS Research Fellowship for Young Scien-
tists. S.T. (the 1st author) is thankful for a Sasagawa Scientific Research
Fellowship by The Japan Science Society for financial support.
Conclusion
We have shown that regioselective deprotonation of 3-sub-
stituted thiophenes with
a combination of a catalytic
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Received: September 18, 2012
Revised: October 29, 2012
Published online: December 19, 2012
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