Selective mono- to perarylations of tetrabromothiophene by a cyclobutene-1,2-diylbisimidazolium preligand

Article abstract of DOI:10.1021/jo201317t

(Cyclobut-1-ene-1,2-diyl)bis(1-methylimidazolium)tetrafluoroborate is applied as preligand in palladium-catalyzed cross-coupling reactions starting from tetrabromothiophene for the synthesis of mono-, bi-, tri-, and tetraaryl-substituted thiophenes bearin

Full text of DOI:10.1021/jo201317t

FEATURED ARTICLE
pubs.acs.org/joc
Selective Mono- to Perarylations of Tetrabromothiophene
by a Cyclobutene-1,2-diylbisimidazolium Preligand
Alireza Rahimi,† Jan C. Namyslo,† Martin H. H. Drafz,† Julian Halm,† Eike H€ubner,† Martin Nieger,‡
Nicola Rautzenberg,† and Andreas Schmidt*,†
†Institute of Organic Chemistry, Clausthal University of Technology, Leibnizstrasse 6, D-38678 Clausthal-Zellerfeld, Germany
‡Laboratory of Inorganic Chemistry, Department of Chemistry, University of Helsinki, P.O. Box 55 (A.I. Virtasen aukio 1),
FIN-00014 Helsinki, Finland
S Supporting Information
b
ABSTRACT: (Cyclobut-1-ene-1,2-diyl)bis(1-methylimidazo-
lium)tetrafluoroborate is applied as preligand in palladium-
catalyzed cross-coupling reactions starting from tetrabromothio-
phene for the synthesis of mono-, bi-, tri-, and tetraaryl-substituted
thiophenes bearing up to four different aryl rings. A synthetic kit
for preparations of nine different substitution patterns of arylated
thiophenes is presented by application of only one single catalyst
system. In agreement with DFT calculations, which predict energetically low rotational barriers in triaryl-3-bromothiophenes and
tetraarylthiophenes, no NOE effects between adjacent aryl rings are detectable. The regioselectivity of their syntheses has therefore been
elucidated by reduction of triaryl-3-bromothiophene to 2,3,5-triarylthiophene followed by HMBC, HSQC, and NOESY NMR
measurements. Additionally, results of an X-ray single structure analysis are presented.
’ INTRODUCTION
catalyst system consisting of Pd(OAc)2 and dicyclohexyl(20,30-
dimethoxy[1,10-biphenyl]-2-yl)-phosphine24 by a one-pot pro-
cedure or a sequence of two cross-couplings via the monoary-
lated thiophenes.23 The bromine atoms in the positions 3,4 of
thiophene were then subsequently replaced by aryl rings to a
symmetric aryl-substituted thiophene. Moreover, a programmed
synthesis of tetraarylthiophenes through sequential CꢀH activa-
tion was developed recently (Scheme 1).25 Thus, ligand-controlled
regiodivergent arylation of 3-methoxy-2-phenylthiophene was
followed by a Pd/bipy/Ag2CO3-catalyzed arylation to afford
thiophenes possessing two different aryl rings in positions 2, 4,
and 5. Tetraarylthiophenes were finally obtained by converting
the methoxy group into a triflate which underwent cross-cou-
pling with arylboronic acids. In summary, this procedure subse-
quently employs four different catalyst systems for the synthesis
of tetraaryl-substituted thiophenes.
An alternative approach to tetraaryl-substituted thiophenes
possessing four identical aryl rings starts from 3-thiophenecar-
boxylic acid, which was reacted with various aryl bromides in the
presence of Pd(OAc)2, PCy3, cesium carbonate, and molecular
sieves in xylene or mesitylene. This approach requires tempera-
tures between 150 and 170 °C, whereupon CꢀH bond cleavage
and decarboxylation occurred26 (Scheme 2).
Due to their optoelectronic and biological activities, arylated
thiophenes are of great interest in materials chemistry as well as
medicinal chemistry. They have been described as photolumi-
nescent compounds,1 semiconductors,2 liquid crystals,3 light-
emitting materials,4 partial structures of light-emitting oligomers,5
organic field-effect transistors,6 and materials displaying aggrega-
tion-induced emission.7 During the last years, arylated thiophene
derivatives have also been reported as potassium channel
blocking,8 antitumor,9 antiparasitic,10 as well as antileishmanial11
agents and as inhibitors of the NorA multidrug transporter of
Staphylococcus aureus12 and 17β-hydroxysteroid dehydrogenase
type 1.13 Moreover, they were identified as agonists of the
sphingosine-1-phosphate 1 receptor14 and as compounds for
β-amyloid plaque imaging.15 As a consequence, much effort is
currently being devoted to the development of reliable and high-
yielding preparative procedures for this interesting class of
compounds. Undoubtedly, the palladium-catalyzed cross-cou-
pling reaction16 proved to be one of the most powerful methods
for the preparation of arylated thiophenes.17 Thus, Stille,18
Negishi,19 and SuzukiꢀMiyaura20 reactions as well as direct aryla-
tions via CꢀH bond activation21 and combinatorial syntheses22
leading to this class of compounds have been described. Tetra-
arylthiophenes possessing four identical aryl substituents with
modest functional group tolerance have been prepared by
SuzukiꢀMiyaura reactions starting from tetrabromothiophene
employing tetrakis(triphenylphosphate)palladium(0) as catalyst
and potassium phosphate23a or potassium carbonate7 as bases,
respectively. The syntheses of symmetric as well as nonsymmetric
2,5-diaryl-3,4-dibromothiophenes have been accomplished by a
In addition, Suzuki couplings of 3,4-diaryl-2,5-dibromothio-
phenes, prepared by bromination of 3,4-diaryl-2,5-dihydrothio-
phene, to tetraaryl-substituted thiophenes having two different
aryl groups in the 2,5- and 3,4-positions were reported.27
Received: July 1, 2011
Published: August 15, 2011
r
2011 American Chemical Society
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Scheme 1. Sequential CH Activation for the Synthesis of
Tetraaryl-Substituted Thiophenes Employing Subsequently
Four Different Catalyst Systems
Scheme 4. SuzukiꢀMiyaura Reactions for the Synthesis
of Sterically Extremely Hindered Biphenyls Employing
Preligand 3
Scheme 5. Acetylene Synthesis Employing Preligand 3
Scheme 2. Synthesis of Tetraaryl-Substituted Thiophenes
Possessing Four Identical Aryl Groups
Scheme 3. Synthesis of the Preligand
Figure 1. Substitution patterns of mono-, di-, tri-, and tetraaryl thio-
phenes described in this work.
In the course of our studies directed toward the chemistry of
heterocyclic mesomeric betaines28 as well as heteroaromatic
salts29 and their conversion into N-heterocyclic carbenes,30 we
prepared (cyclobut-1-ene-1,2-diyl)bis(1-methylimidazolium)chlor-
ide from perchloropropene 1, which we treated with Al/Hg to
give 1,2-dichloro-3,4-bis(dichloromethylene)cyclobut-1-ene 2.
Reaction of cyclobutene 2 with 1-methylimidazole (NMI) re-
sulted in the formation of (cyclobut-1-ene-1,2-diyl)bis(1-methy-
limidazolium)chloride. This was subjected to anion exchange
with sodium tetrafluoroborate, and 3 was finally obtained in 73%
yield from 2 (Scheme 3).31 On deprotonation, the N-hetero-
cyclic carbene of this compound is formed. Depending on the
base strength, a monocarbene or biscarbene is obtained.
We found that the catalytic system consisting of this
new ligand, palladium(II) acetate, and sodium tert-butanolate
in toluene is highly efficient for room temperature SuzukiꢀMiyaura
cross-coupling reactions.32 At elevated temperatures, syntheses of
sterically extremely hindered biaryls were possible for the first time
(Scheme 4).31
We also showed that CoreyꢀFuchs reactions starting from
aldehydes gave geminal dibromides which underwent tandem
SuzukiꢀMiyaura/dehydrobromination reactions to alkynes in
the presence of the new preligand 3 in high yields (Scheme 5).33
We report here that preligand 3 is highly efficient for simple
syntheses of arylated thiophenes possessing up to four different
aryl substituents without the necessity to change the catalyst
system. Figure 1 shows combinations of aryl rings (symbolized)
attached to a thiophene which have been prepared in this work,
that is, monoaryl (I), symmetric and nonsymmetric diaryl (II, III),
triaryl (IV, V), and tetraaryl-substituted thiophenes (VIꢀIX).
’ RESULTS AND DISCUSSION
We first optimized the reaction conditions for monoarylations
and diarylations of tetrabromothiophene with different aromatic
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Scheme 6. Syntheses of Monoarylated and 2,5-Diarylated
Thiophenes
Scheme 7. Syntheses of Thiophenes Possessing Two
Different Aryl Groups in Positions 2,5
Scheme 8. Syntheses of Triarylthiophenes of
General Type IV
and heteroaromatic boronic acids to obtain thiophenes of the
general types I and II (cf. Figure 1). As a model system, we
studied the reaction of phenylboronic acid and tetrabromothio-
phene. Details are presented in the Supporting Information. Best
results for the synthesis of the monoarylated thiophenes 4aꢀh
were obtained when 4.0 mol % of Pd(OAc)2 and 4.0 mol % of the
preligand 3 in toluene were used. Thus, 4a was obtained in 72%
yield (Scheme 6), whereas usage of 6 mol % of Pd(PPh3)4 gave
61% yield.23a The synthesis of 3,4,5-tribromo-2,20-bithiophene
4c and 2,3,4-tribromo-5-(4-methoxyphenyl)thiophene 4e gave
best results when reactions were conducted in a mixture of
toluene and dioxane. Under analogous reaction conditions,
pyridine-3-boronic acid resulted in a mixture of yet unidentified
decomposition products. Addition of 2.2 equiv of aryl boronic
acid yielded the 2,5-diarylthiophenes 5aꢀh under analogous
reaction conditions, except for 5c which required 6 mol % of
catalyst. Conducting the reaction of tetrabromothiophene with
5.0 mol % of Pd(OAc)2 and preligand 3 improved the yield of 5b
to 92%. This compound is literature-known. It was prepared
before in 77% yield with 6 mol % of Pd(PPh3)4 at 90 °C within 12
h.23 We also tested alternative procedures for the synthesis of
these thiophenes, which are presented in the Supporting In-
formation. In our hands, PdCl2(PPh3)2 converted phenylboronic
acid almost quantitatively into biphenyl without attacking the
tetrabromothiophene. Pd(PPh3)4 as catalyst (6 mol %) gave a
42:55 ratio of mono- and bisphenylated 3,4-dibromothiophene,
and only 55% of 5a was isolated. The usage of Xphos (10 mol %)
gave small yields in our experiments. Thus, our catalyst system com-
petes with a catalyst system consisting of Pd(OAc)2 (5 mol %)
gave slightly better yields of 5a (88%)23a and 5c (71%)23a but
smaller yields of 4a (61%).23a Thiophene 5e was obtained in
considerably better yield and in shorter time (82%/12 h vs 43%/
24 h)23b than reported earlier using 6 mol % of Pd(PPh3)4 and
almost identical yields applying Pd(OAc)2 (5 mol %) and SPhos
(10 mol %).23a
We then applied these reaction conditions to prepare hitherto
unknown 2,5-diarylated thiophenes 6 possessing two different
aryl or heteroaryl substituents corresponding to the general type
ꢀ
and Buchwalds biarylmonophoshine ligand (10 mol %), which
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Scheme 9. Syntheses of a Triarylthiophene of General Type V
Figure 3. Most stable conformation of 8 according to DFT calculations.
Scheme 10. Reduction of 8 to 9
Figure 2. Two possible regioisomers of 8. Arrows indicate the calcu-
lated rotational barriers. No NOE effects between the ortho protons have
been detected.
III shown in Figure 1. Again, a solvent mixture of toluene and
dioxane gave the best yields, except for the synthesis of 6a which
was performed in pure toluene (Scheme 7). Thus, the thiophen-
2-yl-furane 6b and the 2,20-bithiophenes 6c,d were prepared in
reasonable yields.
The syntheses of new triarylated thiophenes having identical
aryl rings in positions 2,5 (general type IV, Figure 1) was then
accomplished starting from the thiophenes 5a,b in the presence
of 5 mol % of Pd(OAc)2 and preligand 3 at 80 °C (Scheme 8). As
expected, the use of toluene and dioxane proved to be advanta-
geous with respect to yield and purity.
Choosing the nonsymmetrically substituted thiophene 6a as
starting material for the coupling with 4-methoxyphenyl boronic
acid resulted in the formation of the hitherto unknown 3-bromo-
4-(4-methoxyphenyl)-2-(o-tolyl)-5-(p-tolyl)thiophene 8 with
three different aryl rings (Scheme 9). This compound is a
representative of the general type V.
Elucidation of the regiochemistry of the SuzukiꢀMiyaura
reaction to 8 proved to be challenging, as no NOE effects were
determined between adjacent aryl rings, regardless of solvent
(C6D6, CDCl3, CD2Cl2) and temperature (ꢀ35 to 50 °C). This
is in accordance to DFT calculations, which predict low energetic
barriers for rotation of the aryl rings of the two possible
regioisomers 8 and 80. In their most stable conformations, they
are nonplanar and show long distances between the ortho-
hydrogen atoms (Figure 2).
The distances of the ortho-hydrogen atoms of the p-methoxy-
phenyl and p-tolyl ring of 8 have been calculated to adopt values
between 320 and 431 pm on rotation around the arylthiophene
bonds. In the most stable conformation (Figure 3), the p-tolyl
ring, p-methoxyphenyl ring, and the o-tolyl ring in 8 adopt
torsion angles of 38.8, 59.1, and 76.5°, respectively, in relation
to the thiophene ring. The distance between the ortho-hydrogen
atoms is then 338 pm. The energetic barrier for rotation of the
o-tolyl ring was calculated to be as small as 39 kJ/mol, so that
there is no steric repulsion caused by the van der Waals radius of
Figure 4. Selected peak assignments according to HMBC and HSQC
correlations (CD2Cl2) as well as NOESY effects in C6D6 and measured
2JCH and 3JCH couplings in thiophene 9.
the bromine substituent. Analogous results were obtained for
the regioisomer of 80 (31.1 kJ/mol).
Due to the lack of information available from the NMR spectra
to prove the regiochemistry of the SuzukiꢀMiyaura coupling, we
reduced the bromine atom of 8 by palladium-catalyzed hydro-
debromination and obtained 9 in 81% yield (Scheme 10).
The hydrogen atom of 9 is clearly detectable at δ = 7.12
ppm in CD2Cl2 and 7.15 ppm in C6D6. The 13C NMR data
displayed all expected 21 carbon signals. Analysis of the HH
COSY and HSQC spectra of 9 enabled us to assign all protons to
their bonding carbons, and HMBC experiments confirmed the
structural fragments by long-range CꢀH couplings. In accor-
dance with structure 9, 3-H displays HMBC correlations to the
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Scheme 11. Synthesis of a Tetraaryl-Substituted Thiophenes of General Type VI
Scheme 12. Synthesis of a Tetraaryl-Substituted Thiophene
of General Type VII
Scheme 13. Synthesis of a Thiophene of General Type VIII
Scheme 14. Selective Arylations to a Tetraarylated
Thiophene of Type IX
2
3
expected carbon atoms by JCꢀH and JCꢀH couplings, respec-
tively, as shown in Figure 4. Furthermore, the HMBC correlation
of 6-H of the o-tolyl ring with the thiophene ring was detectable.
Finally, applying deuterobenzene, a mixing time of 0.75 s, and a
pulse repetition delay of 5 s, we were able to detect NOE effects
between the ortho proton of the p-methoxyphenyl ring as well as
of the 2-methyl group and each with 3-H of the thiophene,
respectively. With these results in hand, we can unambiguously
conclude that regioisomer 8 was formed.
Finally, encouraged by the promising results of this investiga-
tion, we subjected selected examples of di- and trisubstituted
thiophenes to additional SuzukiꢀMiyaura couplings to obtain
tetra-substituted thiophenes of the general types VIꢀIX shown
in Figure 1. We used 8 mol % of the catalyst system at 90 °C,
which resulted in the formation of tetraarylthiophenes in good to
very good yields (Schemes 11ꢀ14). Thiophenes 5a and 5b
reacted with p-methoxyphenylboronic acid and 8 mol % of the
catalyst system at 80 °C to the symmetric tetraarylthiophenes
10a and 10b in 75 and 77% yield (Scheme 11). These molecules
belong to general type VI and have been described before, so that
we were able to compare our method to literature-known
procedures. Thiophene 10a gives a considerably better yield
under milder conditions and lower catalyst loadings than
reported.26 Thiophene 10b was synthesized in a similar yield
when 10 mol % of Pd(PPh3)4 at 100 °C for 24 h were used for the
cross-coupling.23
Treatment of 6a with p-methoxyphenylboronic acid and our
catalyst system gave 11 possessing two different types of aryl
groups in the R positions and identical groups in positions
3,4, that is, a new structure according to general type VII
(Scheme 12).
Fortunately, we were able to obtain suitable single crystals
of 11 by slow evaporation in n-hexane, which we subjected to
an X-ray crystallographic examination. The molecular drawing
displays the tetra-fold substitution. The compound crystallized
monoclinic. The p-tolyl ring adopts a torsion angle of ꢀ37.5(2)°,
whereas its neighboring 4-methoxyphenyl ring has a torsion
angle of ꢀ70.2(2)°. The o-tolyl ring is twisted by ꢀ71.4(2)°
from the planar thiophene ring, and its neighboring 4-methox-
yphenyl ring adopts a dihedral angle of ꢀ55.9(2)°. A molecular
drawing is shown in the Supporting Information.
Starting from 7a the thiophene 12 was formed in 57% yield
(Scheme 13). This new arylated thiophene represents the
substitution pattern VIII.
Finally, in a smooth reaction, 8 gave 13 in 51% yield, which has
four different aryl groups (Scheme 14).
Similar to the bromo derivative 8 described above, the
thiophene 13 bearing four different aryl rings displayed no
NOE effects between neighboring aryl substituents. This is in
accordance with calculations which hint at a most stable con-
formation with twisted p-tolyl-, 4-methoxy-, phenyl-, and o-tolyl
rings (41.3, 54.7, 53.7, and 62.2°, respectively). The distances
between hydrogen atoms of the neighboring o-tolyl and the
phenyl ring were calculated to be between 222 and 791 pm
depending on the torsion angles. In the most stable conforma-
tion, the distance is 282 pm. The rotational barrier of the o-tolyl
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General Procedure for SuzukiꢀMiyaura Coupling Reac-
tions of Tetrabromothiophene with Aryl Boronic Acids: A
10 mL flame-dried flask was charged with tetrabromothiophene (0.5
mmol), boronic acid (0.55 mmol for one substitution and 1.1 mmol for
two substitutions), mixture of palladium source and preligand 3 (4 mol %),
and potassium phosphate (1.5 mmol), and then evacuated and
backfilled with nitrogen three times. Five milliliters of solvent was added,
and the mixture was stirred at the temperatures given below for the
indicated periods of time. Then, 5 mL of water was added, and the
product was extracted with dichloromethane, dried over MgSO4 and
concentrated in vacuo. Purification was accomplished by flash column
chromatography.
2,3,4-Tribromo-5-phenylthiophene (4a): A mixture of tetra-
bromothiophene (0.5 mmol, 199.8 mg), phenylboronic acid (0.55
mmol, 67.1 mg), K3PO4 (1.5 mmol, 318.4 mg), and 4 mol % of
[Pd(OAc)2 + ligand] (0.02 mmol, 16.6 mg) in toluene (5 mL) was
stirred at 75 °C for 8 h. Column chromatography (petroleum ether)
provided 142.8 mg (72%) of the title compound as colorless solid: mp
Figure 5. Most stable conformation of 13 according to DFT
calculations.
1
80ꢀ82 °C; H NMR (400 MHz, CDCl3) δ = 7.57ꢀ7.55 (m, 2H),
7.46ꢀ7.41 (m, 3H) ppm; 13C NMR (100 MHz, CDCl3) δ = 139.9,
132.2, 129.1, 128.8, 128.7, 125.4, 118.4, 110.4 ppm; IR (KBr) 3072,
3022, 1480, 1443, 1285, 1266, 1073, 998, 741, 689 cmꢀ1; HRMS (70
eV) calcd for C10H5Br3S 393.76621, found 393.76609.
ring was determined to be only 32 kJ/mol, which means the
absence of steric hindrance (Figure 5).
’ CONCLUSIONS
2,3,4-Tribromo-5-p-tolylthiophene (4b): To a mixture of
tetrabromothiophene (0.5 mmol, 199.8 mg), 4-methylphenylboronic
acid (0.55 mmol, 74.8 mg), K3PO4 (1.5 mmol, 318.4 mg), and 4 mol %
of [Pd(OAc)2 + ligand] (0.02 mmol, 16.6 mg) was added 5 mL of
toluene and stirred at 70 °C for 8 h. Column chromatography
(petroleum ether) gave 166.4 mg (81%) of title compound as colorless
solid: mp 88ꢀ90 °C; 1H NMR (400 MHz, CDCl3) δ 7.45 (d, J = 7.9 Hz,
2H), 7.24 (d, J = 7.9 Hz, 2H), 2.4 (s, 3H) ppm; 13C NMR (100 MHz,
CDCl3) δ 140.1, 139.3, 129.4, 128.7, 125.3, 118.3, 110.0, 109.6, 21.3
ppm; IR (KBr) 3068, 3022, 2917, 1636, 1489, 1437, 1286, 1272, 859,
797, 746 cmꢀ1; HRMS (70 eV) calcd for C11H7Br3S 407.78186, found
407.78205.
3,4,5-Tribromo-2,20-bithiophene (4c): A mixture of polybro-
mothiophene (0.5 mmol, 199.8 mg), 2-thiopheneboronic acid (0.55
mmol, 70.4 mg), K3PO4 (1.5 mmol, 318.4 mg), and 4 mol % of
[Pd(OAc)2 + ligand] (0.02 mmol, 16.6 mg) in 3 mL of toluene plus
2 mL of dioxane was stirred at 80 °C for 12 h. Column chromatography
(petroleum ether) provided 82.6 mg (41%) of the title compound as
light yellow solid: mp 83ꢀ84 °C; 1H NMR (400 MHz, CDCl3) δ 7.4
(dd, J = 5.1, 1.1 Hz, 1H), 7.38 (dd, J = 3.8, 1.1 Hz, 1H), 7.09 (dd, J = 5.1,
3.8 Hz, 1H) ppm; 13C NMR (100 MHz, CDCl3) δ 133.9, 133.5, 127.4,
127.3, 127.1, 118.7, 110.4, 109.4 ppm; IR (KBr) 3096, 2918, 1544, 1484,
1412, 1282, 1077, 840, 700 cmꢀ1; m/z (70 ev) 403.1 [M+]. Anal. Calcd
for C8H3 Br3S2: C, 23.85; H, 0.75. Found: C, 23.77; H, 0.75.
We showed that a catalytic system of preligand 3, palladium-
(II) acetate, and potassium phosphate can be employed for the
sequential synthesis of arylated thiophenes bearing up to four
different aryl rings. Representatives of nine different substitution
patterns have been prepared.
’ EXPERIMENTAL SECTION
General Considerations. Tetrabromothiophene and all boronic
acids were purchased and used without further purification. The solvents
toluene and dioxane were dried over sodium according to standard
procedures. Acetonitrile was dried over CaH2. The ligand was synthe-
sized as described earlier.31 For weighing small amounts of catalyst
(palladium source + ligand) easily and precisely, Pd(OAc)2 (1 mmol,
224.5 mg) and preligand 3 (1.1 mmol, 604.9 mg) were weighed and
mixed in a mortar (ratio = 1:1.1). The resulting fine powder was kept in a
capped vial in a desiccator. Flash chromatography was performed with
silica gel 60 (0.040ꢀ0.063 mm). 1H NMR spectra were recorded at 400
or 600 MHz and 13C NMR spectra at 100 or 150 MHz, with the solvent
peak or tetramethylsilane used as the internal reference. Multiplicities
are described by using the following abbreviations: s = singlet, d =
doublet, t = triplet, q = quartet, sept = septet, and m = multiplet. FT-IR
spectra were obtained in the range of 400 to 4000 cmꢀ1. Solids were
measured as pellets (2.5%) in KBr, and oils were measured as films in
NaCl plates. Melting points are uncorrected and were determined in an
apparatus according to Dr. Tottoli (B€uchi). Accurate masses are listed
employing the 79Br isotope. All yields are isolated yields. All density
functional theory (DFT) calculations were carried out by using the
Jaguar 7.7.107 software running on Linux 2.6.18-238.el5 SMP (x86_64)
on two AMD Phenom II X6 1090T processor workstations (Beowulf
cluster) parallelized with OpenMPI 1.3.4. MM2 optimized structures
were used as starting geometries. Complete geometry optimizations
were carried out on the implemented LACVP* (HayꢀWadt effective
core potential (ECP) basis on heavy atoms, N31G6* for all other atoms)
basis set and with the B3LYP density functional. All calculated structures
were proven to be true minima by the absence of imaginary frequencies.
Plots were obtained using Maestro 9.1.207, the graphical interface of
Jaguar. Rotational barriers have been calculated fully relaxed, fixating one
torsion angle around the rotated bond, and optimizing all remaining
degrees of freedom. Torsion angles were modified in steps of 10°.
2,3,4-Tribromo-5-(naphthalen-1-yl)thiophene (4d): To a
mixture of tetrabromothiophene (0.5 mmol, 199.8 mg), 1-naphthalen-
boronic acid (0.55 mmol, 94.6 mg), K3PO4 (1.5 mmol, 318.4 mg), and 4
mol % of [Pd(OAc)2 + ligand] (0.02 mmol, 16.6 mg) was added 5 mL of
toluene. The reaction mixture was then heated and stirred at 70 °C for 10
h. Column chromatography (petroleum ether) gave 185.5 mg (83%) of
4d as colorless solid: mp 101ꢀ102 °C; 1H NMR (400 MHz, CDCl3) δ
7.96ꢀ7.9 (m, 2H), 7.73ꢀ7.71 (m, 1H), 7.55ꢀ7.46 (m, 4H) ppm; 13C
NMR (100 MHz, CDCl3) δ 138.3, 133.6, 131.6, 130.3, 129.6, 129.4,
128.5, 127.0, 126.5, 125.6, 125.0, 117.6, 113.7, 110.9 ppm; IR (KBr)
3045, 2922, 1592, 1504, 1436, 1338, 1280, 1231, 865, 816, 796 cmꢀ1
HRMS (70 eV) calcd for C14H7Br3S 443.78186, found 443.78212.
;
2,3,4-Tribromo-5-(4-methoxyphenyl)thiophene (4e): Into
a 10 mL oven-dried flask were placed tetrabromothiophene (0.5 mmol,
199.8 mg), 4-methoxybenzeneboronic acid (0.55 mmol, 83.65 mg),
K3PO4 (1.5 mmol, 318.4 mg), 4 mol % of [Pd(OAc)2 + ligand] (0.02
mmol, 16.6 mg), 3 mL of toluene plus 2 mL of dioxane. The reaction
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mixture was then heated and stirred at 80 °C for 10 h. Column
chromatography (petroleum ether/ethyl acetate 50:1) provided
162.2 mg (76%) of 4e as colorless solid: mp 119ꢀ120 °C (mp23
124ꢀ125 °C); 1H NMR (400 MHz, CDCl3) δ 7.48 (d, J = 8.8 Hz, 2H),
6.96 (d, J = 8.8, 2H), 3.85 (s, 3H) ppm; spectroscopic data are identical
to those reported; HRMS (70 eV) calcd for C11H7Br3OS 423.77677,
found 423.77681.
2,3,4-Tribromo-5-(4-(trifluoromethoxy)phenyl)thiophene
(4f): A mixture of tetrabromothiophene (0.5 mmol, 199.8 mg), 4-tri-
fluoromethoxyphenylboronic acid (0.55 mmol, 74.8 mg), K3PO4 (1.5
mmol, 318.4 mg), and 4 mol % of [Pd(OAc)2 + ligand] (0.02 mmol, 16.6
mg) in toluene (5 mL) was stirred at 80 °C for 8 h. After extraction and
column chromatography, a colorless solid was obtained in 67% yield
(161.2 mg): mp 48ꢀ49 °C; 1H NMR (400 MHz, CDCl3) δ 7.59 (d, J =
8.8 Hz, 2H), 7.29 (d, J = 8.8 Hz, 2H) ppm; 13C NMR (100 MHz,
CDCl3) δ 149.7 (d, J = 1.6 Hz), 138.3, 130.8, 130.5, 121.1, 120.3 (q, J =
256 Hz), 118.8, 111.1, 110.7 ppm; IR (KBr) 2963, 2924, 1609, 1530,
1467, 1299, 1208, 1156, 835, 805 cmꢀ1; HRMS (70 eV) calcd for
C11H4Br3F3OS 477.74851, found 477.74823.
2,3,4-Tribromo-5-(m-tolyl)thiophene (4g): A mixture of poly-
bromothiophene (0.5 mmol, 199.8 mg), 3-methylphenylboronic acid
(0.55 mmol, 70.4 mg), K3PO4 (1.5 mmol, 318.4 mg), and 4 mol % of
[Pd(OAc)2 + ligand] (0.02 mmol, 16.6 mg) in 5 mL of toluene was
stirred at 80 °C for 8 h. Column chromatography (petroleum ether)
resulted 162.3 mg (79%) of the title compound as light yellow solid: mp
72ꢀ74 °C; 1H NMR (400 MHz, CDCl3) δ 7.38ꢀ7.28 (m, 3H),
7.24ꢀ7.21 (m, 1H), 2.41 (s, 3H) ppm; 13C NMR (100 MHz, CDCl3)
δ 140.2, 138.6, 132.2, 130.0, 129.6, 128.7, 126.1, 118.5, 110.3, 110.0, 21.5
ppm; IR (KBr) 3031, 2920, 2853, 1603, 1582, 1471, 1271, 1091, 862,
781, 749 cmꢀ1; m/z (70 ev) 411.8 [M+]. Anal. Calcd for C11H7Br3S: C,
32.15; H, 1.72. Found: C, 32.23; H, 1.73.
2,3,4-Tribromo-5-(2,6-dimethylphenyl)thiophene (4h):
To a mixture of tetrabromothiophene (0.5 mmol, 199.8 mg), 2,6-
dimethylphenylboronic acid (0.55 mmol, 82.5 mg), K3PO4 (1.5 mmol,
318.4 mg), and 4 mol % of [Pd(OAc)2 + ligand] (0.02 mmol, 16.6 mg)
was added 5 mL of toluene. The reaction mixture was then heated and
stirred at 80 °C for 10 h. Column chromatography (petroleum ether)
gave 144.5 mg (68%) of 4h as colorless oil: 1H NMR (400 MHz, CDCl3)
δ 7.25 (t, J = 7.5 Hz, 1H), 7.13 (d, J = 7.5 Hz, 2H), 2.14 (s, 3H) ppm; 13C
NMR (100 MHz, CDCl3) δ 138.8, 138.5, 131.1, 129.6, 127.6, 117.2,
112.8, 110.7, 20.3 ppm; IR (NaCl) 3064, 3023, 2921, 2855, 1595, 1465,
1275, 892, 818, 771 cmꢀ1; m/z (70 ev) 425.9 [M+]. Anal. Calcd for
C12H9Br3S: C, 33.91; H, 2.13. Found: C, 33.84; H, 2.14.
3,4-Dibromo-2,5-di(thien-2-yl)thiophene (5c): A mixture of
polybromothiophene (0.5 mmol, 199.8 mg), 2-thiopheneboronic acid
(1.1 mmol, 140.8 mg), K3PO4 (2.5 mmol, 530.6 mg), and 6 mol % of
[Pd(OAc)2 + ligand] (0.03 mmol, 24.9 mg) in 3 mL of toluene plus
2 mL of dioxane was stirred at 80 °C for 16 h. Column chromatography
(petroleum ether/ethyl acetate/100:1) provided 99.5 mg (49%) of a the
title compound as light yellow solid: mp 97ꢀ98 °C, mp23 89ꢀ91 °C; 1H
NMR (400 MHz, CDCl3) δ 7.46 (dd, J = 3.8, 1.1 Hz, 2H), 7.41 (dd, J =
3.8, 1.1 Hz, 2H), 7.11 (dd, J = 5.2, 3.8 Hz, 2H) ppm; 13C NMR (100
MHz, CDCl3) δ 134.0, 131.0, 127.3, 127.1, 126.8, 112.3 ppm; IR (KBr)
3095, 3064, 1483, 1417, 1231, 1219, 1059, 843, 685 cmꢀ1; HRMS
(70 eV) calcd for C12H6Br2S3 403.79984, found 403.80005.
3,4-Dibromo-2,5-di(naphthalen-1-yl)thiophene (5d): To a
mixture of tetrabromothiophene (0.5 mmol, 199.8 mg), 1-naphthalen-
boronic acid (1.2 mmol, 189.2 mg), K3PO4 (2.5 mmol, 530.6 mg), and 4
mol % of [Pd(OAc)2 + ligand] (0.02 mmol, 16.6 mg) was added 5 mL of
toluene. The reaction mixture was then heated and stirred at 75 °C for 14
h. Column chromatography (petroleum ether) gave 192.7 mg (78%) of
5d as yellow solid: mp 136ꢀ138 °C; 1H NMR (400 MHz, CDCl3) δ
7.86 (d, J = 8.2 Hz, 2H), 7.85 (d, J = 8.2 Hz, 2H), 7.50 (dd, J = 8.2, 7.1 Hz,
2H), 7.41 (dd, J = 7.1, 1.2 Hz, 2H) 7.38 (ddd, J = 8.2, 7.1, 1.2 Hz, 2H),
7.31 (d, J = 8.2 Hz, 2H), 7.20 (ddd, J = 8.2, 7.1, 1.2 Hz, 2H) ppm; 13C
NMR (100 MHz, CDCl3) δ 138.4, 133.5, 132.8, 128.1 (2C), 127.9,
127.8, 126.5, 125.9 (2C), 125.8, 125.4 ppm; IR (KBr) 3042, 2922, 1588,
1504, 1379, 1135, 804, 769 cmꢀ1; m/z (70 ev) 491.8 [M+]. Anal. Calcd
for C24H14Br2S: C, 58.32; H, 2.86. Found: C, 58.48; H, 2.87.
3,4-Dibromo-2,5-bis(4-methoxyphenyl)thiophene (5e):
Into a 10 mL oven-dried flask were placed tetrabromothiophene (0.5
mmol, 199.8 mg), 4-methoxybenzeneboronic acid (1.2 mmol, 182.5
mg), K3PO4 (2.5 mmol, 530.6 mg), 4 mol % of [Pd(OAc)2 + ligand]
(0.02 mmol, 16.6 mg), 3 mL of toluene plus 2 mL of dioxane. The
reaction mixture was then heated and stirred at 80 °C for 12 h. Column
chromatography (petroleum ether/ethyl acetate 40:1) resulted 188.4
mg (83%) of the title compound as yellow solid: mp 163ꢀ164 °C, mp23
171ꢀ173 °C; 1H NMR (400 MHz, CDCl3) δ 7.58 (d, J = 8.8 Hz, 4H),
6.97 (d, J = 8.8, 4H), 3.85(s, 6H) ppm; 13C NMR (100 MHz, CDCl3) δ
160.0, 137.4, 130.3, 125.3, 114.0, 111.5, 55.4 ppm; IR (KBr) 3029, 2996,
2961, 2835, 1607, 1535, 1491, 1439, 1299, 1253, 1031, 828, 803,
755 cmꢀ1; m/z (70 ev) 453.9 [M+]. Anal. Calcd for C18H14Br2 O2S:
C, 47.60; H, 3.11. Found: C, 47.51; H, 3.12.
3,4-Dibromo-2,5-bis(4-(trifluoromethoxy)phenyl)thiophene
(5f): A mixture of tetrabromothiophene (0.5 mmol, 199.8 mg), 4-tri-
fluoromethoxyphenylboronic acid (1.2 mmol, 163.2 mg), K3PO4 (2.5
mmol, 530.6 mg), and 4 mol % of [Pd(OAc)2 + ligand] (0.02 mmol, 16.6
mg) in toluene (5 mL) was stirred at 80 °C for 12 h. After extraction and
column chromatography, a colorless solid was obtained in 62% yield
(174.2 mg): mp 92ꢀ94 °C; 1H NMR (400 MHz, CDCl3) δ 7.63 (d, J =
8.8 Hz, 4H), 7.32 (d, J = 8.8 Hz, 4H) ppm; 13C NMR (100 MHz,
CDCl3) δ 149.0 (d, J = 1.6 Hz), 137.7, 129.9, 120.5, 119.7 (q, J = 256
Hz), 110.5, 110.0 ppm; IR (KBr) 2973, 2931, 1601, 1525, 1471, 1289,
1201, 1147, 837 cmꢀ1; m/z (70 ev) 561.7 [M+]. Anal. Calcd for
C18H8Br2F6O2S: C, 38.46; H, 1.43. Found: C, 38.38; H, 1.43.
3,4-Dibromo-2,5-diphenylthiophene (5a): A mixture of tetra-
bromothiophene (0.5 mmol, 199.8 mg), phenylboronic acid (1.20
mmol, 146.5 mg), K3PO4 (2.5 mmol, 530.6 mg), and 5 mol % of
[Pd(OAc)2 + ligand] (0.02 mmol, 16.6 mg) in toluene (5 mL) was
stirred at 75 °C for 10 h. After extraction and column chromatography a
colorless solid was obtained in 69% yield (136 mg): mp 103ꢀ104 °C
(mp35 101.5ꢀ102.5 °C, mp36 95ꢀ96 °C); 1H NMR (400 MHz,
CDCl3) δ = 7.67ꢀ7.64 (m, 4H), 7.47ꢀ7.40 (m, 6H) ppm; spectro-
scopic data are identical to those reported;23 HRMS (70 eV) calcd for
C16H10Br2S 391.88700, found 391.88717.
3,4-Dibromo-2,5-di-m-tolylthiophene (5g): A mixture of
polybromothiophene (0.5 mmol, 199.8 mg), 3-methylphenylboronic
acid (1.2 mmol, 153.6 mg), K3PO4 (2.5 mmol, 530.6 mg), and 4 mol %
of [Pd(OAc)2 + ligand] (0.02 mmol, 16.6 mg) in 5 mL of toluene was
stirred at 75 °C for 12 h. Column chromatography (petroleum ether)
provided 162.5 mg (77%) of the title compound as colorless solid: mp
86ꢀ87 °C; 1H NMR (400 MHz, CDCl3) δ 7.48ꢀ7.46 (m, 4H),
7.36ꢀ7.33 (m, 2H),7.25ꢀ7.21 (m, 2H), 2.41 (s, 6H) ppm; 13C NMR
(100 MHz, CDCl3) δ 138.5, 138.2, 132.8, 129.7, 129.6, 128.6, 126.1,
112.1, 21.5 ppm; IR (KBr) 3015, 2918, 2854, 1602, 1581, 1406, 1271,
1020, 889, 785, 742 cmꢀ1; m/z (70 ev) 422.0 [M+]. Anal. Calcd for
C18H14Br2S: C, 51.21; H, 3.34. Found: C, 51.31; H, 3.35.
3,4-Dibromo-2,5-di-p-tolylthiophene (5b): A mixture of tet-
rabromothiophene (0.5 mmol, 199.8 mg), 4-methylphenylboronic acid
(1.20 mmol, 163.2 mg), K3PO4 (2.5 mmol, 530.6 mg), and 4 mol % of
[Pd(OAc)2 + ligand] (0.02 mmol, 16.6 mg) in toluene (5 mL) was
stirred at 75 °C for 12 h. After extraction and column chromatography
(petroleum ether), a colorless solid was obtained in 82% yield (173 mg):
mp 146ꢀ147 °C (mp23 152ꢀ155 °C); 1H NMR (400 MHz, CDCl3) δ
7.54 (d, J = 8.0 Hz, 4H), 7.26 (d, J = 8.0 Hz, 4H), 2.4 (s, 6H) ppm; 13C
NMR (100 MHz, CDCl3) δ 138.9, 137.9, 130.1, 129.4, 128.9, 111.8,
21.4 ppm; IR (KBr) 3020, 2917, 1636, 1489, 1265, 863, 797 cmꢀ1
HRMS (70 eV) calcd for C18H14Br2S 419.91830, found 419.91843.
;
7322
dx.doi.org/10.1021/jo201317t |J. Org. Chem. 2011, 76, 7316–7325

The Journal of Organic Chemistry
FEATURED ARTICLE
3,4-Dibromo-2,5-bis(2,6-dimethylphenyl)thiophene (5h):
To a mixture of tetrabromothiophene (0.5 mmol, 199.8 mg), 2,6-
dimethylphenylboronic acid (1.2 mmol, 180 mg), K3PO4 (2.5 mmol,
530.6 mg), 4 mol % of [Pd(OAc)2 + ligand] (0.02 mmol, 16.6 mg) was
added 5 mL of toluene. The reaction mixture was then heated and stirred
at 80 °C for 14 h. Column chromatography (petroleum ether) resulted
m/z (70 ev) 413.9 [M+]. Anal. Calcd for C15H10Br2S2: C, 43.50; H, 2.43.
Found: C, 43.42; H, 2.44.
3-Bromo-4-(4-methoxyphenyl)-2,5-diphenylthiophene (7a):
To a mixture of 3,4-dibromo-2,5-diphenylthiophene (0.3 mmol, 118.2 mg),
4-methoxybenzeneboronic acid (0.35 mmol, 53.2 mg), K3PO4 (1.2 mmol,
254.7 mg), and 5 mol % of [Pd(OAc)2 + ligand] (0.015 mmol, 12.44 mg)
was added 5 mL of toluene. The reaction mixture was then heated and stirred
at 80 °C for 12 h. Column chromatography (petroleum ether/ethyl acetate =
60:1) gave 89 mg (71%) of 7a as yellow solid: mp 162ꢀ163 °C; 1H NMR
(400 MHz, CDCl3) δ = 7.72 (d, J = 7.9 Hz, 2H), 7.48ꢀ7.39 (m, 3H),
7.22ꢀ7.19 (m, 7H), 6.90 (d, J = 7.9 Hz, 2H) ppm; 13C NMR (100 MHz,
CDCl3) δ = 159.1, 139.0, 138.6, 136.9, 133.8, 133.4, 131.9, 129.4, 128.8,
128.6, 128.5, 128.3, 128.2, 127.6, 113.7, 111.6, 55.2 ppm; IR (KBr) 3055,
1
139.5 mg (62%) of 5h as colorless solid: mp 181ꢀ182 °C; H NMR
(400 MHz, CDCl3) δ 7.25 (t, J = 7.5 Hz, 2H), 7.13 (d, J = 7.5 Hz, 4H),
2.14 (s, 12H) ppm; 13C NMR (100 MHz, CDCl3) δ 138.8, 138.5, 131.1,
129.6, 127.6, 117.2, 112.8, 110.7, 20.3 ppm; IR (KBr) 3061, 3022, 2918,
2854, 1462, 1377, 1281, 1094, 855, 768 cmꢀ1; m/z (70 ev) 450.0 [M+].
Anal. Calcd for C20H18Br2S: C, 53.35; H, 4.03. Found: C, 53.44; H, 4.04.
3,4-Dibromo-2-o-tolyl-5-p-tolylthiophene (6a): Five milli-
liters of toluene was added to a mixture of 2,3,4-tribromo-5-p-tolylthio-
phene (0.5 mmol, 205.5 mg), 2-methylphenylboronic aicd (0.55 mmol,
74.8 mg), K3PO4 (1.5 mmol, 318.4 mg), and 4 mol % of [Pd(OAc)2 +
ligand] (0.02 mmol, 16.6 mg). The mixture was heated at 80 °C for 10 h.
Column chromatography (petroleum ether) gave 6a as colorless oil in
58% (122.4 mg): 1H NMR (400 MHz, CDCl3) δ = 7.54 (d, J = 8.1 Hz,
2H), 7.47 (d, J = 8.1 Hz, 2H), 7.27ꢀ7.21 (m, 4H), 2.4 (s, 3H), 2.38 (s,
3H) ppm; 13C NMR (100 MHz, CDCl3) δ = 138.9, 138.3, 137.9, 136.7,
130.0, 129.5 (2C), 129.4 (2C), 128.9 (2C), 126.8 (2C), 111.8, 21.4, 21.1
ppm; IR (NaCl) 3061, 3023, 2921, 2864, 1638, 1515, 1482, 1265, 1115,
860, 810, 705 cmꢀ1; HRMS (70 eV) calcd for C18H14Br2S 419.91830,
found 419.91863.
3018, 2953, 2833, 1597, 1540, 1483, 1287, 1245, 1147, 1027, 754, 693 cmꢀ1
;
HRMS (70 eV) calcd for C23H17BrOS 420.01835, found 420.01822.
3-Bromo-4-(4-(methylthio)phenyl)-2,5-diphenylthiophene
(7b): A mixture of 3,4-dibromo-2,5-diphenylthiophene (0.3 mmol,
118.2 mg), 4-(methylthio)phenylboronic acid (0.35 mmol, 58.8 mg),
K3PO4 (1.2 mmol, 254.7 mg), and 6 mol % of [Pd(OAc)2 + ligand]
(0.018 mmol, 14.93 mg) in toluene (5 mL) was stirred at 90 °C for 14 h.
Column chromatography (petroleum ether/ethyl acetate 100:1) af-
forded the title compound as yellow solid in 53.8 mg (41%): mp
1
120ꢀ122 °C; H NMR (400 MHz, CDCl3) δ 7.71 (d, J = 8.0 Hz,
2H), 7.45 (d, J = 8.0, 2H), 7.25ꢀ7.19 (m, 10H), 2.50 (s, 3H) ppm; 13C
NMR (100 MHz, CDCl3) δ 139.3, 138.3, 138.2, 137.2, 133.6, 133.3,
132.4, 131.2, 129.4, 128.8, 128.6, 128.5, 128.4, 127.8, 125.9, 111.1, 15.4
ppm; IR (KBr) 3062, 3020, 2923, 2851, 1597, 1480, 1419, 1238, 1089,
969, 880, 755, 648 cmꢀ1; HRMS (70 eV) calcd for C23H17BrS2
435.99550, found 435.99561.
2-(3,4-Dibromo-5-(p-tolyl)thiophen-2-yl)furane (6b): To a
mixture of 2,3,4-tribromo-5-(p-tolyl)thiophene (0.4 mmol, 164.4 mg),
2-furanylboronic acid (0.45 mmol, 50.4 mg), K3PO4 (1.2 mmol, 254.7
mg), and 6 mol % of [Pd(OAc)2 + ligand] (0.024 mmol, 19.92 mg) was
added a mixture of 2 mL of toluene plus 3 mL of dioxane. The reaction
mixture was then heated and stirred at 80 °C for 16 h. Column
chromatography (petroleum ether/EtOAc = 60: 1) gave 81.2 mg
3-Bromo-4-phenyl-2,5-di-p-tolylthiophene (7c): To a mix-
ture of 3,4-dibromo-2,5-di-p-tolylthiophene (0.3 mmol, 126.65 mg),
phenylboronic acid (0.35 mmol, 42.7 mg), K3PO4 (1.2 mmol, 254.7
mg), and 5 mol % of [Pd(OAc)2 + ligand] (0.015 mmol, 12.44 mg) was
added 5 mL of toluene. The reaction mixture was then heated and stirred
at 80 °C for 14 h. Column chromatography (petroleum ether/ethyl
acetate 60:1) gave 86.8 mg (69%) of title compound as light yellow solid:
mp 128ꢀ129 °C; 1H NMR (400 MHz, CDCl3) δ 7.61 (d, J = 8.0 Hz,
2H), 7.36 (d, J = 8.0 Hz, 2H), 7.33ꢀ7.23 (m, 5H), 7.08 (d, J = 8.0 Hz,
2H), 7.00 (d, J = 8.0 Hz, 2H), 2.40 (s, 3H), 2.28 (s, 3H) ppm; 13C NMR
(100 MHz, CDCl3) δ 139.1, 138.5, 138.3, 137.6, 136.8, 136.2, 130.8,
130.5, 129.4, 129.3, 129.2, 128.6, 128.3, 127.7, 125.5, 110.8, 21.4, 21.2
ppm; IR (KBr) 3061, 3023, 2918, 2859, 1692, 1603, 1506, 1486, 1281,
1247, 1021, 818, 764 cmꢀ1; m/z (70 ev) 418.1 [M+]. Anal. Calcd for
C24H19BrS: C, 68.73; H, 4.57. Found: C, 68.58; H, 4.59.
3-Bromo-4-(4-methoxyphenyl)-2,5-di-p-tolylthiophene (7d):
To a mixture of 3,4-dibromo-2,5-di-p-tolylthiophene (0.3 mmol, 126.65 mg),
4-methoxyphenylboronic acid (0.35 mmol, 53.2 mg), K3PO4 (1.2 mmol,
254.7 mg), 5 mol % of [Pd(OAc)2 + ligand] (0.015 mmol, 12.44 mg) were
added 3 mL of toluene and 2 mL of dioxane. The reaction mixture was then
heated and stirred at 80 °C for 13 h. Column chromatography (petroleum
ether/ethyl acetate 45:1) resulted 83.6 mg (62%) of title compound as yellow
solid: mp 121ꢀ122 °C; 1H NMR (400 MHz, CDCl3) δ 7.61 (d, J = 8.0 Hz,
2H), 7.26 (d, J = 8.2 Hz, 2H), 7.20 (d, J = 8.8, 2H), 7.09 (d, J = 8.2 Hz, 2H),
7.00 (d, J = 8.0 Hz, 2H), 6.90 (d, J = 8.8 Hz, 2H), 3.83 (s, 3H), 2.40 (s, 3H),
2.29 (s, 3H) ppm; 13C NMR (100 MHz, CDCl3) δ 159.0, 138.8, 138.3,
138.1, 137.5, 136.6, 131.9, 131.0, 130.6, 129.3, 129.2, 129.1, 128.6, 128.4,
113.7, 111.2, 55.2, 21.4, 21.2 ppm; IR (KBr) 3022, 2956, 2930, 2855, 1609,
1514, 1492, 1452, 1287, 1246, 1176, 1034, 880, 802, 756 cmꢀ1; HRMS
(70 eV) calcd for C25H21BrOS 448.04965, found 448.04939.
1
(51%) of a light brown solid: mp 58ꢀ59 °C; H NMR (400 MHz,
CDCl3) δ = 7.55 (d, J = 7.8 Hz, 2H), 7.47 (dd, J = 3.5, 1.8 Hz, 1H), 7.27
(d, J = 7.8 Hz, 2H), 7.15 (dd, J = 3.5, 0.8 Hz, 1H), 6.54 (dd, J = 3.5, 1.8
Hz, 1H) ppm; 13C NMR (100 MHz, CDCl3) δ = 147.2, 142.2, 139.0,
137.1, 129.8, 129.4, 128.8, 128.5, 112.1, 111.9, 110.1, 108.6, 21.4 ppm;
IR (KBr) 3022, 2918, 1647, 1509, 1483, 1273, 1019, 811, 735 cmꢀ1
HRMS (70 eV) calcd for C15H10Br2OS 395.88191, found 395.88209.
;
3,4-Dibromo-5-phenyl-2,20-bithiophene (6c): To a mixture
of 2,3,4-tribromo-5-phenylthiophene (0.4 mmol, 158.8 mg), 2-thiophe-
neboronic acid (0.45 mmol, 57.6 mg), K3PO4 (1.2 mmol, 254.7 mg),
and 6 mol % of [Pd(OAc)2 + ligand] (0.024 mmol, 19.92 mg) was added
3 mL of toluene plus 2 mL of dioxane. The reaction mixture was then
heated and stirred at 80 °C for 16 h. Column chromatography
(petroleum ether) gave 67.2 mg (42%) of title compound as yellow
solid: mp 73ꢀ74 °C; 1H NMR (400 MHz, CDCl3) δ 7.64 (dd, J = 8.1,
1.6 Hz, 2H), 7.47ꢀ7.38 (m, 5H), 7.10 (dd, J = 5.1, 1.6 Hz, 1H) ppm; 13C
NMR (100 MHz, CDCl3) 137.2, 134.3, 132.6, 132.1, 129.0, 128.9, 128.7,
127.4, 127.0, 126.7, 112.5,112.4 ppm; IR (KBr) 3108, 3058, 3023, 1598,
1480, 1279, 1242, 860, 747 cmꢀ1; HRMS (70 eV) calcd for C14H8Br2S2
397.84342, found 397.84323.
3,4-Dibromo-5-(m-tolyl)-2,20-bithiophene (6d): To a mix-
ture of 2,3,4-tribromo-5-(m-tolyl)thiophene (0.4 mmol, 164.4 mg),
2-thiopheneboronic acid (0.45 mmol, 57.6 mg), K3PO4 (1.2 mmol,
254.7 mg), and 6 mol % of [Pd(OAc)2 + ligand] (0.024 mmol, 19.92
mg) were added 3 mL of toluene and 2 mL of dioxane. The reaction
mixture was then heated and stirred at 80 °C for 16 h. Column
chromatography (petroleum ether) provided 77.8 mg (47%) of 6d as
green solid: mp 46ꢀ47 °C; 1H NMR (400 MHz, CDCl3) δ 7.47ꢀ7.44
(m, 3H), 7.40 (dd, J = 5.1, 1.2 Hz, 1H), 7.36ꢀ7.21 (m, 2H), 7.11 (dd, J =
5.1, 3.6 Hz, 1H) ppm; 13C NMR (100 MHz, CDCl3) 138.5, 137.4, 134.3,
132.5, 131.9, 129.7, 129.6, 128.0, 127.7, 127.4, 127.0, 126.7, 126.1, 112.3,
3-Bromo-4-(4-methoxyphenyl)-2-(o-tolyl)-5-(p-tolyl)thio-
phene (8): A mixture of 3,4-dibromo-2-(o-tolyl)-5-(p-tolyl)thiophene
(0.3 mmol, 118.2 mg), 4-methoxyphenylboronic acid (0.35 mmol, 58.8
mg), K3PO4 (1.2 mmol, 254.7 mg), 5 mol % of [Pd(OAc)2 + ligand]
(0.015 mmol, 12.44 mg) in 3 mL of toluene plus 2 mL of dioxane was
21.5 ppm; IR (KBr) 3097, 3008, 2957, 1578, 1257, 1186, 874, 747 cmꢀ1
;
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FEATURED ARTICLE
stirred at 80 °C for 14 h. Flash chromatography (petroleum ether/
1597, 1524, 1504, 1482, 1285, 1244, 1173, 1031, 833, 764, 753 cmꢀ1
HRMS (70 eV) calcd for C30H24OS 432.15479, found 432.15482.
3-(4-Methoxyphenyl)-4-phenyl-5-(o-tolyl)-2-(p-tolyl)thio-
phene (13): A mixture of 3-bromo-4-(4-methoxyphenyl)-2-(o-tolyl)-
5-(p-tolyl)thiophene (0.3 mmol, 134.8 mg), phenylboronic acid (0.4
mmol, 49 mg), K3PO4 (1.2 mmol, 254.7 mg), and 8 mol % of
[Pd(OAc)2 + ligand] (0.024 mmol, 19.9 mg) in a mixture of 3 mL of
toluene plus 2 mL of dioxane was stirred at 90 °C for 16 h. Chroma-
tography (petroleum ether/ethyl acetate 45:1) provided 13 as colorless
solid in 68.3 mg (51%): mp 161ꢀ163 °C; 1H NMR (600 MHz, CDCl3)
δ = 7.37ꢀ7.35 (m, 1H), 7.21ꢀ7.20 (m, 1H), 7.17ꢀ7.14 (m, 3H),
7.13ꢀ7.12 (m, 1H), 7.08ꢀ7.06 (m, 2H), 7.05ꢀ7.02 (m, 3H), 6.94 (d,
J = 8.8 Hz, 2H), 6.85 (dd, J = 8.1, 1.6 Hz, 2H), 6.71 (d, J = 8.8 Hz, 2H),
3.78 (s, 3H), 2.34 (s, 3H), 2.06 (s, 3H) ppm; 13C NMR (150 MHz,
CDCl3) δ = 158.2, 140.6, 138.4, 137.6, 137.5, 137.3, 136.8, 136.6, 133.8,
132.0, 131.9, 131.6, 131.0, 130.4, 130.0, 129.1, 129.0, 128.0, 127.4, 126.0,
125.3, 113.4, 55.0, 21.2, 20.4 ppm; IR (KBr) 3057, 2993, 2923, 1609,
1575, 1486, 1246, 1176, 1100, 1033, 815, 727 cmꢀ1; m/z (70 eV) 446.2
[M+]. Anal. Calcd for C31H26OS: C, 83.37; H, 5.87. Found: C, 83.22;
H, 5.89.
;
EtOAc 45:1) to provide the title compound as a colorless solid in
1
71.5 mg (53%): mp 165ꢀ166 °C; H NMR (600 MHz, CDCl3) δ =
7.42ꢀ7.37 (m, 3H), 7.33ꢀ7.31 (m, 1H), 7.28 (d, J = 8.5 Hz, 2H), 7.16
(d, J = 8.1 Hz, 2H), 7.08 (d, J = 8.1 Hz, 2H), 6.95 (d, J = 8.5 Hz, 2H), 3.88
(s, 3H), 2.42 (s, 3H), 2.35 (s, 3H) ppm; 13C NMR (150 MHz, CDCl3)
δ = 158.3, 138.7, 137.9, 137.3, 136.2, 135.7, 132.4, 131.6, 131.0, 130.4,
130.0, 129.1, 128.9, 128.3, 127.5, 125.4, 113.3, 113.2, 55.0, 21.2, 20.4
ppm; IR (KBr) 3005, 2954, 2835, 1610, 1514, 1485, 1288, 1249, 1175,
1033, 799, 719 cmꢀ1; HRMS (70 eV) calcd for C25H21BrOS 448.04965,
found 448.04957.
3,4-Bis(4-methoxyphenyl)-2,5-diphenylthiophene (10a):
Five milliliters of solvent (toluene 2 mL + dioxane 3 mL) was added
to a mixture of 3,4-dibromo-2,5-diphenylthiophene (0.3 mmol, 118.2
mg), 4-methoxybenzeneboronic acid (0.7 mmol, 106.4 mg), K3PO4
(1.75 mmol, 371.5 mg), and 8 mol % of [Pd(OAc)2 + ligand] (0.024
mmol, 19.90 mg). The mixture was heated at 80 °C for 14 h. Column
chromatography (petroleum ether/ethyl acetate 60:1) afforded 101 mg
(75%) of 10a as yellow solid: mp 207ꢀ208 °C, mp26 210ꢀ211 °C; 1H
NMR (400 MHz, CDCl3) δ 7.25ꢀ7.18 (m, 10H), 6.87 (d, J = 8.6 Hz,
4H), 6.66 (d, J = 8.6, 4 Hz), 3.74 (s, 6H) ppm; spectroscopic data are
identical to those reported; HRMS (70 eV) calcd for C30H24O2S
448.14970, found 448.14953.
3,4-Bis(4-methoxyphenyl)-2,5-di-p-tolylthiophene (10b):
A mixture of 3,4-dibromo-2,5-di-p-tolylthiophene (0.3 mmol, 126.65
mg), 4-methoxyphenylboronic acid (0.7 mmol, 106.4 mg), K3PO4 (1.75
mmol, 371.5 mg), and 8 mol % of [Pd(OAc)2 + ligand] (0.024 mmol,
19.90 mg) in 3 mL of toluene plus 2 mL of dioxane was stirred at 80 °C
for 14 h. Column chromatography (petroleum ether/ethyl acetate 40:1)
provided the title compound as colorless solid in 110.1 mg (77%): mp
203ꢀ204 °C, mp23 230ꢀ231 °C; 1H NMR (400 MHz, CDCl3) δ 7.12
(d, J = 8.0 Hz, 4H), 7.02 (d, J = 8.0 Hz, 4H), 6.87 (d, J = 8.8 Hz, 4H), 6.66
(d, J = 8.8 Hz, 4H), 3.74 (s, 6H), 2.30 (s, 6H) ppm; spectroscopic data
are identical to those reported. Anal. Calcd for C32H28O2S: C, 80.64; H,
5.92. Found: C, 80.48; H, 5.94.
3,4-Bis(4-methoxyphenyl)-2-(o-tolyl)-5-(p-tolyl)thiophene (11):
A mixture of 2 mL of toluene plus 3 mL of dioxane was added to a mixture of 3,4-
dibromo-2-(o-tolyl)-5-(p-tolyl)thiophene (0.3 mmol, 126.65 mg), 4-methox-
ybenzeneboronic acid (0.7 mmol, 106.4 mg), K3PO4 (1.75 mmol, 371.5 mg),
and 8 mol % of [Pd(OAc)2 + ligand] (0.024 mmol, 19.90 mg). The mixture was
heated at 90 °C for 15 h. Chromatography (petroleum ether/EtOAc 40:1) gave
the title compound as colorless solid: yield 90.2 mg (63%); mp 144ꢀ145 °C;
1H NMR (400 MHz, CDCl3) δ = 7.34ꢀ7.32 (m, 1H),7.23ꢀ7.08 (m, 3H),
7.12 (d, J= 7.8 Hz, 2H), 7.02 (d, J = 7.8 Hz, 2H), 6.91 (d, J = 8.4 Hz, 2H), 6.72
(d,J= 8.4 Hz, 2H), 6.67 (d, J=8.6,2Hz),6.54(d,J= 8.6 Hz, 2H), 3.74 (s, 3H),
3.66 (s, 3H), 2.29 (s, 3H), 2.02 (s, 3H) ppm; 13C NMR (100 MHz, CDCl3)
δ = 158.2, 157.8, 140.2, 138.3, 137.6, 137.3, 137.0, 136.8, 134.0, 132.1, 132.0,
131.8, 131.5, 130.1, 129.2, 129.16, 129.11, 129.0, 128.0, 125.4, 113.4, 113.0, 55.1,
55.0, 21.2, 20.5 ppm; IR (KBr) 3008, 2954, 2923, 2835, 1609, 1524, 1506, 1303,
1287, 1246, 1110, 889, 869, 769 cmꢀ1;m/z(70 eV) 476.3 [M+]. Anal. Calcd for
C32H28O2S: C, 80.64; H, 5.92. Found: C, 80.81; H, 5.94.
3-(4-Methoxyphenyl)-2,5-diphenyl-4-p-tolylthiophene (12):
To a mixture of 3-bromo-4-(4-methoxyphenyl)-2,5-diphenylthiophene
(0.2 mmol, 84.26 mg), 4-methylbenzeneboronic acid (0.24 mmol, 32.6
mg), K3PO4 (0.6 mmol, 127.36 mg), 8 mol % of [Pd(OAc)2 + ligand]
(0.016 mmol, 13.27 mg) was added 5 mL of toluene. The reaction mixture
was then heated and stirred at 90 °C for 16 h. Column chromatography
(petroleum ether/ethyl acetate 50:1) gave 39.8 mg (46%) of a yellow solid:
mp 177ꢀ179 °C; 1H NMR (400 MHz, CDCl3) δ = 7.26ꢀ7.18 (m, 10H),
6.92 (d, J = 8.0 Hz, 2H), 6.87 (d, J = 8.8 Hz, 2H), 6.84 (d, J = 8.0 Hz, 2H),
6.66 (d, J = 8.8, 2 Hz), 3.73 (s, 6H), 2.26 (s, 3H) ppm; 13C NMR (100
MHz, CDCl3) δ = 158.1, 139.5, 139.1, 138.1, 138.0, 136.0, 134.4, 133.4,
131.9, 130.6, 129.1 (2C), 128.8, 128.5, 128.3 (2C), 128.2, 127.0, 126.9,
113.2, 55.0, 21.2 ppm; IR (KBr) 3055, 3025, 3001, 2950, 2932, 2833, 1607,
Debromination34 Procedure of 3-Bromo-4-(4-meth-
oxyphenyl)-2-(o-tolyl)-5-(p-tolyl)thiophene (9): Five milliliters
of dry CH3CN was added to an oxygen-free mixture of bromothiophene
(022 mmol, 100 mg) and Pd(PPh3)4 (0.022 mmol,25.7 mg) and stirred
for about 20 min. After that, NaBH4 (0.55 mmol, 21.2 mg) was added.
The mixture was stirred at 75 °C under inert atmosphere for 24 h. Then,
the solvent was evaporated, and the residue was extracted by dichlor-
omethane (3 ꢁ 30 mL). Organic phase was combined and dried over
MgSO4 and concentrated under vacuum. The crude product was
purified via flash chromatography on silica gel (petroleum ether/ethyl
acetate 40:1) to provide the title compound as colorless viscous oil in 66
mg (81%): 1H NMR (600 MHz, C6D6) δ 7.58ꢀ7.53 (m, 1H), 7.41 (d,
J = 7.9 Hz,2H), 7.33 (d, J = 8.7 Hz, 2H), 7.15 (s, 1H), 7.09ꢀ7.08 (m,
3H), 6.87 (d, J = 7.9 Hz, 2H), 6.71 (d, J = 8.7 Hz, 2H), 3.27 (s, 3H), 2.41
(s, 3H), 2.02 (s, 3H) ppm; 13C NMR (150 MHz, C6D6) δ 159.9, 142.5,
138.9, 138.8, 137.9, 136.8, 135.2, 132.9, 131.9, 131.3, 131.0, 130.33,
130.30, 130.2, 129.0, 128.8, 127.1, 115.0, 55.4, 22.0, 21.7 ppm; IR
(NaCl) 3049, 2955, 2925, 1610, 1488, 1462, 1442, 1291, 1247, 1177,
1035, 835, 738 cmꢀ1; m/z (70 ev) 370.2 [M+]. Anal. Calcd for
C25H22OS: C, 81.04; H, 5.98. Found: C, 81.20; H, 6.00.
’ ASSOCIATED CONTENT
S
Supporting Information. Reaction optimization condi-
b
tions, X-ray data, results of calculations, and NMR spectra. This
material is available free of charge via the Internet at http://pubs.
acs.org.
’ AUTHOR INFORMATION
Corresponding Author
*E-mail: schmidt@ioc.tu-clausthal.de.
’ ACKNOWLEDGMENT
Dr. Gerald Dr€ager, University of Hannover (Germany), is
gratefully acknowledged for measuring the HRMS spectra.
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