Synthesis of functionalized thiophenes and oligothiophenes by selective and iterative cross-coupling reactions using indium organometallics

Article abstract of DOI:10.1039/c2ob25123j

The synthesis of unsymmetrical 2,5-disubstituted thiophenes by selective and sequential palladium-catalyzed cross-coupling reactions of indium organometallics with 2,5-dibromothiophene is reported. Following an iterative coupling sequence, α-oligothiophenes were synthesized in good yields and with high atom economy.

Full text of DOI:10.1039/c2ob25123j

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PAPER
Synthesis of functionalized thiophenes and oligothiophenes by selective and
iterative cross-coupling reactions using indium organometallics†
M. Montserrat Martínez, Miguel Peña-López, José Pérez Sestelo* and Luis A. Sarandeses*
Received 16th January 2012, Accepted 9th March 2012
DOI: 10.1039/c2ob25123j
The synthesis of unsymmetrical 2,5-disubstituted thiophenes by selective and sequential palladium-
catalyzed cross-coupling reactions of indium organometallics with 2,5-dibromothiophene is reported.
Following an iterative coupling sequence, α-oligothiophenes were synthesized in good yields and with
high atom economy.
Introduction
The thiophene ring is present in a wide variety of natural pro-
ducts and pharmaceuticals,1 and functionalized thiophenes such
as α-linked linear oligothiophenes are among the most promising
polymers for the development of electronic devices such as
organic field-effect transistors (OFETs), organic light-emitting
diodes (OLEDs) and solar cells.2 The synthesis of linear
α-coupled thiophenes is usually performed from 2,5-dihalothio-
phenes by two-fold cross-coupling reactions to afford symmetri-
Scheme 1 Iterative and selective cross-coupling reactions using
cally α,α′-disubstituted oligothiophenes.3 Unfortunately, there is
2,5-dibromothiophene (1).
a low differentiation between the two reactive positions and a
second cross-coupling can occur readily, limiting the structural
diversity provided by selective cross-coupling reactions.4 To
by metallation of the remaining bromine atom and further coup-
avoid this limitation, the synthesis of thiophenes furnished with
two different halogens has been pursued to perform chemoselec-
tive cross-coupling reactions.5
ling processes (Scheme 1).
Results and discussion
In recent years we have shown that indium organometallics
are useful reagents in metal-catalyzed cross-coupling reactions.6
Besides the high efficiency, versatility, and selectivity in cross-
coupling reactions, triorganoindium reagents (R3In) are particu-
larly effective in the synthesis of functionalized heterocyclic
compounds7 and highly selective in coupling reactions with 3,4-
dihalomaleimides.8 Herein, we report the novel use of indium
organometallics in selective and iterative cross-coupling reac-
tions applied to the synthesis of functionalized thiophenes and
oligothiophenes. Using the commercially available 2,5-dibro-
mothiophene as an electrophile, selective reactions should allow
the successive incorporation of organic residues to afford non-
symmetrically α,α′-disubstituted thiophenes and also enable
iterative coupling reactions, after the first monocoupling reaction,
Our research started studying the reactivity of triorganoindium
reagents in palladium-catalyzed cross-coupling with 2,5-dibro-
mothiophene (1). Based on our experience in aryl–aryl coupling
with indium reagents, PdCl2(dppf) complex was selected as pal-
ladium source.7 In this way, the reaction of 1 with tri-(2-thienyl)
indium (40 mol%), prepared in solution from 2-bromothiophene,
in the presence of PdCl2(dppf) (4 mol%) provided the bromo-
bithiophene 2a selectively in 78% yield as the only isolated
product, the dicoupling product being undetected (Table 1,
entry 1). Analogously, the reaction using tri(benzo[b]thien-2-yl)-
indium also gave the monocoupling product 2b in 77% yield in
a similar reaction time (entry 2). The growing interest of mixed
heterocyclic polymers,9 led us to try the reaction with a different
heteroarylindium reagent. Under the same conditions, we found
that the reaction of tri(2-furanyl)indium with 1 gave the cross-
coupling product 2c selectively in good yield (70%, entry 3).
Since α-styrylthiophenes have been proposed as materials for
new organic electronic devices,10 we also assayed the monocou-
pling reaction with the conjugated alkenylindium derivative from
Departamento de Química Fundamental, Universidade da Coruña,
E-15071 A Coruña, Spain. E-mail: qfsarand@udc.es, sestelo@udc.es;
Fax: +34 981 167 065; Tel: +34 981 167 000
†Electronic supplementary information (ESI) available: Copies of NMR
spectra for compounds prepared. See DOI: 10.1039/c2ob25123j
3892 | Org. Biomol. Chem., 2012, 10, 3892–3898
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Table 1 Selective cross-coupling reactions of triorganoindium reagents
with 2,5-dibromothiophene (1)
(50 mol%) with 5-bromo-2,2′-bithiophene (2a) using the
same catalytic system as for the first coupling [PdCl2(dppf),
(4 mol%)] afforded the corresponding non-symmetrically substi-
tuted thiophene 3a in excellent 96% yield after 12 h at reflux
(Table 2, entry 1). On the other hand, the reaction of 2a with
trialkynylindium reagents afforded the corresponding alkynyl-
bithiophenes 3b and 3c in good yields (73% and 82%, respect-
ively, entries 2 and 3). Interestingly, the bithiophene 3b has
shown antiviral activity12 and the alcohol derived from the desi-
lylation of 3c has been reported as an antifungal metabolite.13
Under the same conditions, the reaction of tri(2-thienyl)indium
with 2b afforded the trithienyl derivative 4 in 80% yield (entry
4). In a similar manner, 2-bromo-5-ethynylthiophenes 2e and 2f
reacted with thienylindium derivatives providing a new series of
bithienyl analogs 5 and 6a (95% and 63% yield, respectively,
entries 5 and 6). Compound 5 is a key precursor in the synthesis
of arctic acid, a natural product that is of pharmacological inter-
est.14 As previously, we were also interested in the introduction
of other heteroaryl groups in the second coupling. In this
context, the reaction of the 2-furanylindium reagent with 2f
under the standard conditions gave 6b in a good 75% yield
(entry 7). Overall, these results demonstrate the efficiency and
versatility of indium organometallics in the selective and sequen-
tial cross-coupling reactions for the synthesis of non-symmetrical
2,5-disubstituted thiophenes.
Entry
1
R1
Product
Yielda (%)
78
2
77
3
4
5
6
70
55
53b,c
52b,c
The next step in our study about the selectivity of triorgano-
indium reagents in the coupling reactions with 2,5-dibromothio-
phene involved the assessment of monocoupling products 2 in
iterative cross-coupling reactions. The application of iterative
processes is a powerful strategy that is commonly used in bio-
synthesis and has been recently extended to cross-coupling reac-
tions,15,16 and to the synthesis of oligothiophenes.17 These
sequences start with a molecule that contains a reactive func-
tional group (“on”) and other groups that are unreactive or pro-
tected (“off”) to suppress uncontrolled polymerizations. After a
selective coupling through the reactive group, the unreactive one
is activated or deprotected (“on”) to repeat the coupling
sequence. The high selectivity obtained in the first coupling reac-
tions reveals compounds 2 as indium pronucleophiles, thus
avoiding the protection–deprotection steps usually required in
iterative sequences.
The first step in these iterative reactions involved the mono-
coupling reactions to afford 2a and 2b (Scheme 2). With these
compounds in hand, the activation step was carried out by
lithium–bromine exchange with n-BuLi and subsequent trans-
metallation with InCl3 to give the corresponding thienylindium
reagents that were used without isolation. A new selective mono-
coupling of these compounds with 1, in the presence of
PdCl2(dppf) (4%) as palladium source, afforded 7a and 7b in
good yields (73% and 85%, respectively). Gratifyingly, a new
iteration was also possible and proceeded in good yields to
provide, after activation and cross-coupling, compounds 8a and
8b in satisfactory yields (59% and 50%, respectively).
a Isolated yield. b Using Pd(PPh3)4 (4 mol%). c The dicoupling product
was isolated as byproduct (<15%).
β-bromostyrene, giving rise to the α-styrylthiophene 2d in 55%
yield (entry 4). Additionally, we also turned our interest towards
oligoethynylthiophenes despite their synthesis having found
important limitations.11 Initially, the reaction of tri(trimethylsilyl-
ethynyl)indium and tri(phenylethynyl)indium with 1 using
PdCl2(dppf) (4 mol%) afforded the monocoupling products 2e
and 2f in modest yields (35–40% yield). However, these results
were improved using Pd(PPh3)4 as palladium source (Table 1,
entries 5 and 6), although in this case some dicoupling product
was obtained as a byproduct (<15%). All the indium organome-
tallics were prepared as a THF solution from the corresponding
lithium derivatives using InCl3 and used without isolation. In
general, the reactivity and selectivity shown by the triorgano-
indium reagents in these palladium-catalyzed coupling reactions
is comparable to or higher than other organometallics, highlight-
ing the atom economy, since only 40 mol% of the organoindium
reagent is necessary.
With the 2-bromothiophenes 2a–f in hand, we devised that
these monocoupling products can play a dual role in further
transformations: they can be used as new electrophiles in sequen-
tial coupling reactions or as indium nucleophiles (after metalla-
tion and transmetallation) in iterative coupling processes. In
order to demonstrate the efficiency of indium organometallics in
the sequential synthesis of non-symmetrical thiophenes we tried
aryl, heteroaryl and ethynylindium organometallics as second
nucleophilic counterparts. Thus, the reaction of triphenylindium
Palladium-catalyzed cross-coupling reactions of an excess
(70 mol%) of triorganoindium reagents with 2,5-dibromothio-
phene afforded the dicoupling products in good yields. As
an example of these twofold cross-coupling reactions, we used
the thienylindium reagents in iterative coupling reactions for
the synthesis of symmetrically substituted α-oligothiophenes.
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Table 2 Synthesis of non-symmetrical 2,5-disubstituted thiophenes by sequential cross-coupling reactions with triorganoindium reagents
Entry
1
2
R2
Ph
Product
Yielda (%)
96
2a
2
2a
73
3
4
2a
2b
82
80
5
6
2e
2f
95
63
7
2f
75
a Isolated yield.
Interestingly, the reaction of the indium reagent derived from 2-
bromobithiophene (2a) with (1), in the presence of PdCl2(dppf),
afforded α-quinquethiophene (9a, Scheme 3) in 66% yield after
refluxing for 12 h. Analogously, the reaction of the indium
reagent obtained from 2b with 1 afforded the benzothienyl end-
capped oligothiophene 9b in 65% yield. These examples demon-
strate the utility of indium organometallics towards the synthesis
of α-oligothiophenes following an iterative-twofold coupling
sequence.
materials science are currently under investigation and the results
will be published in due course.
Experimental
General methods
All reactions were carried out in flame dried glassware, under an
argon atmosphere, using standard gastight syringes, cannulae,
and septa. Tetrahydrofuran (THF) was dried by distillation from
the sodium ketyl of benzophenone. Reaction temperatures refer
to external bath temperatures. 1-[(tert-Butyldimethylsilyl)oxy]-3-
butyne18 and 2-(5-bromothiophen-2-yl)-1,3-dioxolane19 were
prepared according to the literature procedures. Butyllithium and
phenyllithium were titrated prior to use. All other commercially
available reagents were used as received. Organic extracts were
dried over anhydrous MgSO4, filtered, and concentrated using a
rotary evaporator at aspirator pressure. Reactions were monitored
by TLC using precoated silica gel plates (Alugram® Xtra SIL
G/UV254, 0.20 mm thick) using UV light as visualizing agent
and ethanolic phosphomolybdic acid as developing agent. Flash
column chromatography was performed using 230–400 mesh
Conclusions
In conclusion, we have studied the usefulness of indium organo-
metallics in selective palladium-catalyzed cross-coupling reac-
tions with 2,5-dibromothiophene. The reactions proceed in good
yields and with high selectivity, and the monocoupling products
were used further both as electrophiles in sequential cross-coup-
ling syntheses and as pronucleophiles in iterative coupling
sequences. These examples highlight the synthetic utility of
triorganoindium reagents in cross-coupling reactions and include
the syntheses of α-coupled oligothiophene structures by iterative
coupling reactions. Further applications of this methodology in
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Scheme 3 Twofold cross-coupling reactions with triorganoindium
reagents. Reagents and conditions: (a) n-BuLi, THF, −78 °C, then
InCl3, −78 °C to rt, then 1, PdCl2(dppf) (4 mol%), THF, 80 °C, 12 h.
solids with CH2Cl2 (15 mL). The filtrate was concentrated
in vacuo and the residue was purified by flash chromatography
to afford, after concentration and high vacuum drying, the corre-
sponding cross-coupling product, except for compounds 9a and
9b, which were purified by crystallization after the filtration.
5-Bromo-2,2′-bithiophene (2a).14a Pale yellow solid (96 mg,
78%); mp 33–34 °C (MeOH) (lit.14a 32–33 °C); νmax/cm−1
(ATR) 3070, 2923, 1581, 1504 and 1199; δH (300 MHz, CDCl3)
6.93 (1 H, d, J 3.8), 6.99 (1 H, d, J 3.8), 7.03 (1 H, dd, J 5.1,
3.6), 7.13 (1 H, dd, J 3.6, 1.1) and 7.24 (1 H, dd, J 5.1, 1.1); δC
(75 MHz, CDCl3) 110.9 (C), 123.8 (CH), 124.1 (CH), 124.8
(CH), 127.9 (CH), 130.6 (CH), 136.4 (C) and 138.9 (C); MS
(EI) m/z 246 (M+, 81Br, 100%), 244 (M+, 79Br, 98), 165 (45);
HRMS (EI) m/z 243.9008 (M+). Calc. for C8H5S2Br: 243.9011.
Scheme 2 Iterative cross-coupling reactions with triorganoindium
reagents.
1
silica gel packed in glass columns. H and 13C NMR spectra
1
were recorded in CDCl3 at 300 MHz or 500 MHz for H and
75 MHz or 125 MHz for 13C, at ambient temperature, and cali-
brated to the solvent peak. DEPT data was used to assign carbon
types. Mass spectra were obtained with EI ionization at 70 eV.
Melting points are uncorrected.
2-(5-Bromothiophen-2-yl)benzo[b]thiophene
(2b). Yellow
solid (114 mg, 77%); mp 128–129 °C (CH2Cl2); Anal. Found:
C, 49.16; H, 2.03. Calc. for C12H7S2Br: C, 48.82; H, 2.39;
νmax/cm−1 (ATR) 3054, 2923, 1499, 1438, 1417, 819 and 792;
δH (300 MHz, CDCl3) 7.01 (1 H, d, J 3.9), 7.04 (1 H, d, J 3.9),
7.29–7.38 (3 H, m) and 7.71–7.79 (2 H, m); δC (75 MHz,
CDCl3) 112.2 (C), 120.0 (CH), 122.1 (CH), 123.6 (CH), 124.7
(CH), 124.8 (CH), 125.1 (CH), 130.8 (CH), 136.2 (C), 138.9
(C), 139.0 (C) and 140.1 (C); MS (EI) m/z 296 (M+, 81Br,
100%), 294 (M+, 79Br, 97), 171 (25); HRMS (EI) m/z 293.9167
(M+). Calc. for C12H7S2Br: 293.9167.
Triorganoindium reagents
Triorganoindium compounds were prepared according to pre-
viously published methods7b by treatment of the corresponding
organolithium reagents (3 equiv, ∼0.5 M in dry THF) with a sol-
ution of InCl3 (1.1 equiv, ∼0.05 M in dry THF) at −78 °C and
warming to room temperature and were used without isolation.
Phenylacetylene, trimethylsilylacetylene and furan were
lithiated by treatment with n-BuLi (1 equiv) at −78 °C and
warming to room temperature. Other organolithium reagents
were prepared by metal–halogen exchange reactions with n-BuLi
(1 equiv) at −78 °C in dry THF.
2-(5-Bromo-2-thienyl)furan (2c).20 Colorless oil (80 mg,
70%); νmax/cm−1 (ATR) 3112, 2924, 2852, 1464, 1152, 988 and
789; δH (300 MHz, CDCl3) 6.44 (1 H, dd, J 3.4, 1.8), 6.47 (1 H,
dd, J 3.5, 0.8), 6.98 (2 H, s) and 7.40 (1 H, dd, J 1.8, 0.8); δC
(75 MHz, CDCl3) 105.3 (CH), 111.1 (C), 111.7 (CH), 122.5
(CH), 130.5 (CH), 135.2 (C), 141.9 (CH) and 148.4 (C); MS
(EI) m/z 230 (M+, 81Br, 33%), 228 (M+, 79Br, 31), 77 (100);
HRMS (EI) m/z 227.9238 (M+). Calc. for C8H5OSBr: 227.9239.
General procedure for the palladium-catalyzed cross-coupling
reactions
In a Schlenk tube filled with argon, to a solution of the electro-
phile (0.5 mmol) and PdCl2(dppf) (0.02 mmol) in dry THF
(2 mL), a solution of R3In [∼0.05 M in THF, 0.2 mmol for the
selective monocoupling (Table 1 and Scheme 2), 0.25 mmol for
the sequential coupling reactions (Table 2) or 0.35 mmol for the
twofold coupling reactions (Scheme 3)] was added, and the
resulting mixture stirred at 80 °C for 12 h. The reaction was
quenched by the addition of a few drops of MeOH and the
mixture filtered through a short pad of Celite®, washing the
(E)-2-Bromo-5-styrylthiophene (2d).10 Orange solid (67 mg,
55%); mp 97–99 °C (hexanes) (lit.10 96–98 °C); νmax/cm−1
(ATR) 3023, 2921, 2852, 2362, 1430, 949 and 797; δH
(300 MHz, CDCl3) 6.80 (1 H, d, J 4.0), 6.82 (1 H, d, J 16), 6.95
(1 H, d, J 3.8), 7.10 (1 H, d, J 16.0) and 7.23–7.46 (5 H, m); δC
(75 MHz, CDCl3) 111.1 (C), 121.2 (CH), 126.2 (CH), 126.3
(2 × CH), 127.9 (CH), 128.7 (2 × CH), 128.8 (CH), 130.5 (CH),
136.6 (C) and 144.5 (C); MS (EI) m/z 266 (M+, 81Br, 100%),
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264 (M+, 79Br, 98); HRMS (EI) m/z 263.9605 (M+). Calc. for
C12H9SBr: 263.9603.
2-[(2,2′-Bithiophen)-5-yl]benzo[b]thiophene (4). Pale yellow
solid (119 mg, 80%); mp 186–187 °C (hexanes); Anal. Found:
C, 64.78; H, 3.75. Calc. for C16H10S3: C, 64.39; H, 3.38;
νmax/cm−1 (ATR) 3063, 2921, 2851, 1449, 820 and 794; δH
(300 MHz, CDCl3) 7.04 (1 H, dd, J 5.1, 3.6), 7.1 (1 H, d, J 3.6),
7.20 (1 H, d, J 3.7), 7.23 (1 H, dd, J 5.8, 1.1), 7.31–7.40 (3 H,
m), 7.50 (1 H, br s) and 7.80–7.81 (2 H, m); δC (75 MHz,
CDCl3) 119.6 (CH), 121.4 (CH), 122.1 (CH), 123.4 (CH), 124.4
(CH), 124.6 (CH), 124.7 (CH), 124.8 (CH), 125.7 (CH), 127.9
(CH), 136.1 (C), 136.9 (C), 137.4 (C), 139.1 (C), 139.4 (C) and
140.3 (C); MS (EI) m/z 298 (M+, 100%); HRMS (EI) m/z
297.9935 (M+). Calc. for C16H10S3: 297.9939.
2-Bromo-5-[2-(trimethylsilyl)ethynyl]thiophene (2e).5a Yellow
oil (69 mg, 53%); νmax/cm−1 (ATR) 3070, 2920, 2349, 1504 and
1443; δH (300 MHz, CDCl3) 0.24 (9 H, s), 6.90 (1 H, d, J 3.9)
and 6.96 (1 H, d, J 3.9); δC (75 MHz, CDCl3) −0.30 (3 × CH3),
96.4 (C), 100.1 (C), 113.1 (C), 129.8 (CH), 132.3 (C) and 132.9
(CH); MS (EI) m/z 260 (M+, 81Br, 38%), 258 (M+, 79Br, 35),
245 (M − CH3, 81Br, 100), 243 (M − CH3, 79Br, 96); HRMS
(EI) m/z 257.9521 (M+). Calc. for C9H11SiSBr: 257.9529.
2-Bromo-5-(phenylethynyl)thiophene (2f).21 White solid
(68 mg, 52%); mp 73–74 °C (hexanes) (lit.21 72–74 °C); Anal.
Found: C, 54.84; H, 2.30. Calc. for C12H7SBr: C, 54.77; H,
2.68; νmax/cm−1 (ATR) 3078, 3055, 2359, 2339, 1754, 1597,
1526 and 1442; δH (300 MHz, CDCl3) 6.97 (1 H, d, J 3.9), 7.03
(1 H, d, J 3.9), 7.35–7.38 (3 H, m) and 7.50–7.53 (2 H, m); δC
(75 MHz, CDCl3) 81.6 (C), 94.0 (C), 113.1 (C), 122.5 (C),
125.1 (C), 128.4 (2 × CH), 128.7 (CH), 130.1 (CH), 131.4 (2 ×
CH) and 132.2 (CH); MS (EI) m/z 264 (M+, 81Br, 100%), 262
(M+, 79Br, 98), 183 (33); HRMS (EI) m/z 261.9445 (M+). Calc.
for C12H7SBr: 261.9446.
5-(1,3-Dioxolan-2-yl)-5′-[2-(trimethylsilyl)ethynyl]-2,2′-bithio-
phene (5). Yellow solid (159 mg, 95%); mp 72–73 °C
(hexanes); Anal. Found: C, 57.48; H, 5.35. Calc. for
C16H18O2SiS2: C, 57.45; H, 5.42; νmax/cm−1 (ATR) 2964, 2882,
2145, 1378, 1247, 1197 and 836; δH (300 MHz, CDCl3) −0.30
(9 H, s), 4.03 (2 H, dd, J 4.6, 2.6), 4.13 (2 H, dd, J 4.6, 2.6),
6.08 (1 H, s), 7.00 (1 H, d, J 3.8), 7.06 (2 H, s) and 7.12 (1 H, d,
J 3.8); δC (75 MHz, CDCl3) −0.17 (3 × CH3), 65.3 (2 × CH2),
97.3 (C), 100.1 (CH), 122.2 (C), 123.5 (CH), 123.7 (CH), 126.2
(C), 126.9 (CH), 133.4 (CH), 137.6 (C), 138.6 (C) and 141.4
(C); MS (EI) m/z 334 (M+, 100%), 262 (M − C3H9Si, 28);
HRMS (EI) m/z 334.0514 (M+). Calc. for C16H18O2SiS2:
334.0512.
5-Phenyl-2,2′-bithiophene (3a).22 Yellow solid (117 mg,
96%); mp 119–121 °C (hexanes) (lit.22 120–121 °C); νmax/cm−1
(ATR) 3057, 2921, 1597, 1487, 1457 and 886; δH (300 MHz,
CDCl3) 7.03 (1 H, dd, J 5.1, 3.7), 7.15 (1 H, d, J 3.7), 7.20–7.23
(3 H, m), 7.30 (1 H, br d, J 7.4), 7.38 (2 H, dd, J 7.6, 1.4) and
7.61 (2 H, dd, J 7.4, 1.1); δC (75 MHz, CDCl3) 123.6 (CH),
123.7 (CH), 124.4 (CH), 124.6 (CH), 125.6 (2 × CH), 127.6
(CH), 127.8 (CH), 128.9 (2 × CH), 134.1 (C), 136.7 (C), 137.4
(C) and 143.1 (C); MS (EI) m/z 242 (M+, 55%); HRMS (EI) m/z
242.0215 (M+). Calc. for C14H10S2: 242.0218.
2-[5-(Phenylethynyl)thiophen-2-yl]benzo[b]thiophene
(6a).
Yellow solid (100 mg, 63%); mp 163–164 °C (hexanes); Anal.
Found: C, 75.58; H, 3.74. Calc. for C20H12S2: C, 75.91; H, 3.82;
νmax/cm−1 (ATR) 3049, 2921, 2199, 1441, 791 and 740; δH
(500 MHz, CDCl3) 7.20 (1 H, d, J 3.8), 7.23 (1 H, d, J 3.8),
7.32–7.40 (5 H, m), 7.43 (1 H, br s), 7.54–7.56 (2 H, m) and
7.75–7.84 (2 H, m); δC (125 MHz, CDCl3) 82.5 (C), 94.6 (C),
120.3 (CH), 122.2 (CH), 123.6 (CH), 124.8 (CH), 124.82 (CH),
124.83 (CH), 124.9 (CH), 124.92 (CH), 128.4 (CH), 128.6
(CH), 131.4 (CH), 132.8 (CH), 136.5 (C), 137.2 (C), 138.7 (C),
139.2 (C), 139.5 (C) and 140.2 (C); MS (EI) m/z 316 (M+,
100%); HRMS (EI) m/z 316.0377 (M+). Calc. for C20H12S2:
316.0375.
5-(2-Phenylethynyl)-2,2′-bithiophene (3b).23 Yellow solid
(97 mg, 73%); mp 91–92 °C (hexanes) (lit.23 89–90 °C);
νmax/cm−1 (ATR) 3054, 2920, 2201, 1441 and 802; δH
(300 MHz, CDCl3) 7.04 (1 H, dd, J 5.1, 3.6), 7.09 (1 H, d, J
3.8), 7.18–7.22 (2 H, m), 7.25 (1 H, dd, J 5.2, 1.1), 7.34–7.39 (3
H, m) and 7.51–7.54 (2 H, m); δC (75 MHz, CDCl3) 82.6 (C),
94.1 (C), 122.0 (C), 122.9 (C), 123.6 (CH), 124.2 (CH), 125.0
(CH), 128.0 (CH), 128.4 (2 × CH), 128.5 (CH), 131.4 (2 × CH),
132.8 (CH), 136.8 (C) and 138.9 (C); MS (EI) m/z 266 (M+,
100%); HRMS (EI) m/z 266.0218 (M+). Calc. for C16H10S2:
266.0218.
2-[5-(Phenylethynyl)thiophen-2-yl]furan (6b). Yellow oil
(94 mg, 75%); Anal. Found: C, 76.39; H, 4.25. Calc. for
C16H10OS: C, 76.77; H, 4.03; νmax/cm−1 (ATR) 3079, 2924,
2853, 2201, 1805, 1441, 1014 and 975; δH (500 MHz, CDCl3)
6.48 (1 H, dd, J 3.4, 1.8), 6.56 (1 H, dd, J 3.4, 0.7), 7.15 (1 H,
d, J 3.8), 7.22 (1 H, d, J 3.8), 7.36–7.39 (3 H, m), 7.44 (1 H, dd,
J 1.8, 0.7) and 7.53–7.55 (2 H, m); δC (125 MHz, CDCl3) 82.7
(C), 94.1 (C), 105.9 (CH), 111.9 (CH), 121.8 (C), 122.3 (CH),
122.9 (C), 128.4 (2 × CH), 128.5 (CH), 131.4 (2 × CH), 132.7
(CH), 135.0 (C), 142.1 (CH) and 148.9 (C); MS (EI) m/z 250
(M+, 100%); HRMS (EI) m/z 250.0445 (M+). Calc. for
C16H10OS: 250.0447.
5-[4-[(tert-Butyldimethylsilyl)oxy]but-1-yn-1-yl]-2,2′-bithiophene
(3c). Pale yellow oil (143 mg, 82%); Anal. Found: C, 62.38; H,
6.79. Calc. for C18H24OSiS2: C, 62.02; H, 6.94; νmax/cm−1
(ATR) 2953, 2927, 2855, 1470, 1251, 1101 and 834; δH
(300 MHz, CDCl3) 0.13 (6 H, s), 0.95 (9 H, s), 2.68 (2 H, t, J
7.0), 3.84 (2 H, t, J 7.0), 7.00–7.05 (3 H, m), 7.17 (1 H, dd, J
3.6, 1.1) and 7.23 (1 H, dd, J 5.1, 1.1); δC (75 MHz, CDCl3)
−5.2 (2 × CH3), 18.4 (C), 24.2 (CH2), 25.9 (3 × CH3), 61.7
(CH2), 74.7 (C), 92.5 (C), 122.7 (C), 123.3 (CH), 124.0 (CH),
124.5 (CH), 127.9 (CH), 132.0 (CH), 136.9 (C) and 137.7 (C);
MS (EI) m/z 348 (M+, 10%), 291 (M − C4H9, 100), 217 (M −
C4H9OSi, 23); HRMS (EI) m/z 348.1019 (M+). Calc. for
C18H24OSiS2: 348.1032.
5-Bromo-2,2′:5′,2′′-terthiophene (7a).24 Yellow solid (120 mg,
73%); mp 140–141 °C (hexanes) (lit.24 141–142 °C); νmax/cm−1
(ATR) 3067, 2923, 2852, 1499, 1426, 832 and 789; δH
(300 MHz, CDCl3) 6.92 (1 H, d, J 3.8), 6.98 (1 H, d, J 3.8),
7.01–7.09 (3 H, m), 7.18 (1 H, dd, J 3.6, 1.0) and 7.24 (1 H, dd,
J 5.1, 1.1); δC (75 MHz, CDCl3) 111.0 (C), 123.7 (CH), 123.9
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(CH), 124.3 (CH), 124.6 (CH), 124.7 (CH), 127.9 (CH), 130.7
(CH), 135.1 (C), 136.7 (C), 136.8 (C) and 138.6 (C); MS (EI)
m/z 328 (M+, 81Br, 100%), 326 (M+, 79Br, 97), 248 (M − Br,
10); HRMS (EI) m/z 325.8889 (M+). Calc. for C12H7S3Br:
325.8888.
INCITE08PXIB103167PR) for financial support. M.M.M.
thanks the Xunta de Galicia for an Isidro Parga Pondal contract
and M.P.L. thanks Ministerio de Ciencia e Innovación for an
FPU predoctoral fellowship.
2-[5′-Bromo-(2,2′-bithiophen)-5-yl]benzo[b]thiophene (7b).25
Yellow solid (160 mg, 85%); mp 130–132 °C (THF); νmax/cm−1
(ATR) 3065, 2924, 2853 and 817; δH (300 MHz, CDCl3) 6.95
(1 H, d, J 3.9), 7.00 (1 H, d, J 3.9), 7.05 (1 H, d, J 3.8), 7.18
(1 H, d, J 3.8), 7.28–7.38 (2 H, m), 7.39 (1 H, s) and 7.71–7.83
(2 H, m); δC (75 MHz, CDCl3) 111.4 (C), 120.0 (CH), 122.2
(CH), 123.5 (CH), 124.0 (CH), 124.65 (CH), 124.70 (CH),
124.8 (CH), 125.7 (CH), 130.8 (CH), 136.2 (C), 136.6 (C),
138.4 (C), 139.1 (C), 140.2 (C) and 140.3 (C); MS (EI) m/z 378
(M+, 81Br, 100%), 376 (M+, 79Br, 98), 298 (M − Br, 22), 216
(M − C4H2SBr, 65); HRMS (EI) m/z 375.9041 (M+). Calc. for
C16H9S3Br: 375.9044.
Notes and references
1 (a) F. Bohlmann and C. Zdero, in Chemistry of Heterocyclic Compounds,
ed. S. Gronowitz, Wiley, New York, 1985, Vol. 44: Thiophene and its
Derivatives, Part 1, pp 261–324; (b) J. B. Press, in Chemistry of Hetero-
cyclic Compounds. ed. S. Gronowitz, Wiley, New York, 1991, Vol. 44:
Thiophene and its Derivatives, Part 4, pp. 397–502.
2 (a) Handbook of Thiophene-based Materials, ed. I. F. Perepichka and
D. F. Perepichka, Wiley, Chichester, U.K., 2009; (b) A. Mishra, C.-Q. Ma
and P. Bäuerle, Chem. Rev., 2009, 109, 1141–1276.
3 (a) A. Operamolla and G. M. Farinola, Eur. J. Org. Chem., 2011, 423–
450; (b) B. Carsten, F. He, H. J. Son, T. Xu and L. Yu, Chem. Rev., 2011,
111, 1493–1528.
4 (a) S. Schröter, C. Stock and T. Bach, Tetrahedron, 2005, 61, 2245–2267;
(b) I. J. S. Fairlamb, Chem. Soc. Rev., 2007, 36, 1036–1045; (c) J.-
R. Wang and K. Manabe, Synthesis, 2009, 1405–1427.
5-Bromo-2,2′:5′,2′′:5′′,2′′′-quaterthiophene (8a).26 Yellow solid
(121 mg, 59%); mp 225–227 °C (CH2Cl2) (lit.26 226–227 °C);
νmax/cm−1 (ATR) 2955, 2922, 2852, 1728, 1455, 1284 and 789;
δH (500 MHz, CDCl3) 6.92 (1 H, d, J 3.9), 6.98 (1 H, d, J 3.9),
7.01–7.10 (5 H, m), 7.18 (1 H, dd, J 3.6, 1.1) and 7.23 (1 H, dd,
J 5.1, 3.6); δC (125 MHz, CDCl3) 111.1 (C), 123.8 (CH), 123.9
(CH), 124.2 (CH), 124.4 (CH), 124.5 (CH), 124.62 (CH),
124.66 (CH), 127.9 (CH), 130.7 (CH), 135.1 (C), 135.6 (C),
136.4 (C), 136.6 (C), 136.9 (C) and 138.5 (C); MS (EI) m/z 410
(M+, 81Br, 100%), 408 (M+, 79Br, 97); HRMS (EI) m/z 407.8767
(M+). Calc. for C16H9S4Br: 407.8765.
5 (a) E. G. A. Notaras, N. T. Lucas, M. G. Humphrey, A. C. Willis and A.
D. Rae, Organometallics, 2003, 22, 3659–3670; (b) B. Mühling,
S. Theisinger and H. Meier, Synthesis, 2006, 1009–1015.
6 Selected references: (a) I. Pérez, J. Pérez Sestelo and L. A. Sarandeses,
Org. Lett., 1999, 1, 1267–1269; (b) I. Pérez, J. Pérez Sestelo and L.
A. Sarandeses, J. Am. Chem. Soc., 2001, 123, 4155–4160; (c) M.
A. Pena, J. Pérez Sestelo and L. A. Sarandeses, Synthesis, 2003, 780–
784; (d) J. Caeiro, J. Pérez Sestelo and L. A. Sarandeses, Chem.–Eur. J.,
2008, 14, 741–746; (e) R. Riveiros, L. Saya, J. Pérez Sestelo and L.
A. Sarandeses, Eur. J. Org. Chem., 2008, 1959–1966.
7 (a) M. A. Pena, I. Pérez, J. Pérez Sestelo and L. A. Sarandeses, Chem.
Commun., 2002, 2246–2247; (b) M. A. Pena, J. Pérez Sestelo and L.
A. Sarandeses, J. Org. Chem., 2007, 72, 1271–1275; (c) A. Mosquera,
R. Riveiros, J. Pérez Sestelo and L. A. Sarandeses, Org. Lett., 2008, 10,
3745–3748.
2-[5′′-Bromo-(2,2′:5′,2′′-terthiophen)-5-yl]benzo[b]thiophene
(8b). Orange solid (115 mg, 50%); mp 190–192 °C (CH2Cl2);
νmax/cm−1 (ATR) 3065, 2920, 2851, 1731, 1517, 1453, 1426
and 822; δH (500 MHz, THF-d8) 7.10 (1 H, dd, J 7.1, 3.8),
7.19–7.21 (1 H, m), 7.24–7.26 (2 H, m), 7.32–7.44 (4 H, m),
7.55 (1 H, br s), 7.77–7.80 (1 H, m) and 7.83–7.87 (1 H, m);
MS (EI) m/z 460 (M+, 81Br, 20%), 458 (M+, 79Br, 18), 380 (M −
Br, 100); HRMS (EI) m/z 457.8921 (M+). Calc. for C20H11S4Br:
457.8921.
8 L. Bouissane, J. Pérez Sestelo and L. A. Sarandeses, Org. Lett., 2009, 11,
1285–1288.
9 (a) Y. Miyata, T. Nishinaga and K. Komatsu, J. Org. Chem., 2005, 70,
1147–1153; (b) O. Gidron, Y. Diskin-Posner and M. Bendikov, J. Am.
Chem. Soc., 2010, 132, 2148–2150; (c) U. Bunz, Angew. Chem., Int. Ed.,
2010, 49, 5037–5040; (d) K. Ono, A. Nakashima, Y. Tsuji, T. Kinoshita,
M. Tomura, J.-I. Nishida and Y. Yamashita, Chem.–Eur. J., 2010, 16,
13539–13546.
10 C. Videlot-Ackermann, J. Ackermann, H. Brisset, K. Kawamura,
N. Yoshimoto, P. Raynal, A. E. Kassmi and F. Fages, J. Am. Chem. Soc.,
2005, 127, 16346–16347.
11 (a) J.-P. Tranchier, R. Chavignon, D. Prim, A. Auffrant, Z. F. Plyta,
F. Rose-Munch and E. Rose, Tetrahedron Lett., 2000, 41, 3607–3610;
(b) N. G. Kundu and B. Nandi, J. Org. Chem., 2001, 66, 4563–4575;
(c) C. Huang, C.-G. Zhen, S. P. Su, K. P. Loh and Z.-K. Chen, Org. Lett.,
2005, 7, 391–394.
12 J. B. Hudson, E. A. Graham, N. Miki, G. H. N. Towers, L. L. Hudson,
R. Rossi, A. Carpita and D. Neri, Chemosphere, 1989, 19, 1329–1343.
13 N. Fokialakis, C. L. Cantrell, S. O. Duke, A. L. Skaltsounis and D.
E. Wedge, J. Agric. Food Chem., 2006, 54, 1651–1655.
14 (a) A. Carpita and R. Rossi, Gazz. Chim. Ital., 1985, 115, 575–583;
(b) T. Washino, M. Yoshikura and S. Obata, Agric. Biol. Chem., 1986,
50, 565–568.
15 C. Wang and F. Glorius, Angew. Chem., Int. Ed., 2009, 48, 5240–5244,
and references therein.
16 For some examples, see: (a) P. Galda and M. Rehahn, Synthesis, 1996,
614–620; (b) S. Lightowler and M. Hird, Chem. Mater., 2005, 17, 5538–
5549; (c) Y. Nakao, J. Chen, M. Tanaka and T. Hiyama, J. Am. Chem.
Soc., 2007, 129, 11694–11695; (d) N. Ishida, Y. Shimamoto and
M. Murakami, Org. Lett., 2010, 12, 3179–3181; (e) S. J. Lee, T.
M. Anderson and M. D. Burke, Angew. Chem., Int. Ed., 2010, 49, 8860–
8863; (f) K. Manabe, M. Ohba and Y. Matsushima, Org. Lett., 2011, 13,
2436–2439.
17 (a) P. R. L. Malenfant and J. M. J. Frechet, Chem. Commun., 1998,
2657–2658; (b) T. Kirschbaum, R. Azumi, E. Mena-Osteritz and
P. Bäuerle, New J. Chem., 1999, 23, 241–250; (c) C. A. Briehn,
T. Kirschbaum and P. Bäuerle, J. Org. Chem., 2000, 65, 352–359;
2,2′:5′,2′′:5′′,2′′′:5′′′,2′′′′-Quinquethiophene
(9a).27 Orange
solid (136 mg, 66%); mp 258–259 °C (toluene) (lit.27
256–257 °C); νmax/cm–1 (ATR) 3085, 3065, 1496, 1449, 1426,
1068, 1049, 831 and 790; δH (300 MHz, CDCl3) 7.03 (2 H, dd,
J 5.1, 3.6), 7.08 (6 H, s), 7.18 (2 H, dd, J 3.6, 1.1) and 7.23
(2 H, dd, J 5.1, 1.1); MS (EI) m/z 412 (M+, 100%); HRMS (EI)
m/z 411.9539 (M+). Calc. for C20H12S5: 411.9537.
5,5′′-Bis(benzo[b]thiophen-2-yl)-2,2′:5′,2′′-terthiophene (9b).25
Orange solid (toluene) (166 mg, 65%); νmax/cm−1 (ATR) 3056,
2854, 1561, 1438, 817 and 742; δH (300 MHz, CDCl3)
7.19–7.24 (2 H, m), 7.30–7.39 (8 H, m), 7.52 (2 H, br s) and
7.71–7.83 (4 H, m); MS (EI) m/z 512 (M+, 17%), 429 (M −
C4H3S, 20), 298 (100); HRMS (EI) m/z 511.9834 (M+). Calc.
for C28H16S5: 511.9850.
Acknowledgements
We are grateful to the Ministerio de Ciencia e Innovación
(Spain, CTQ2009-07180) and Xunta de Galicia (Spain,
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(d) T. Kirschbaum, C. A. Briehn and P. Bäuerle, J. Chem. Soc., Perkin
Trans. 1, 2000, 1211–1216; (e) N. Masuda, S. Tanba, A. Sugie,
D. Monguchi, N. Koumura, K. Hara and A. Mori, Org. Lett., 2009, 11,
2297–2300; (f) S. Tanaka, S. Tamba, D. Tanaka, A. Sugie and A. Mori,
J. Am. Chem. Soc., 2011, 133, 16734–16737.
22 A. Yokooji, T. Satoh, M. Miura and M. Nomura, Tetrahedron, 2004, 60,
6757–6763.
23 R. Rossi, A. Carpita and A. Lezzi, Tetrahedron, 1984, 40, 2773–2779.
24 P. Bäuerle, F. Würthner, G. Götz and F. Effenberger, Synthesis, 1993,
1099–1103.
18 T. Jensen, H. Pedersen, B. Bang-Andersen, R. Madsen and M. Jørgensen,
Angew. Chem., Int. Ed., 2008, 47, 888–890.
25 H. Tian, J. Shi, B. He, N. Hu, S. Dong, D. Yan, J. Zhang, Y. Geng and
F. Wang, Adv. Funct. Mater., 2007, 17, 1940–1951.
19 A. L. Johnson, J. Org. Chem., 1976, 41, 1320–1324.
20 A. Carpita, R. Rossi and C. A. Veracini, Tetrahedron, 1985, 41, 1919–
1929.
26 (a) S. Trabattoni, S. Laera, R. Mena, A. Papagni and A. Sassella, J.
Mater. Chem., 2004, 14, 171–178; (b) S. Trabattoni, A. Borghesi,
S. Laera, M. Moret and A. Papagni, Synth. Met., 2004, 145, 7–10.
27 A. Merz and F. Ellinger, Synthesis, 1991, 462–464.
21 A. P. Rudenko and A. Vasil’ev, Zh. Org. Khim., 1995, 31, 1502–1522.
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