Selective palladium-catalysed ipso arylation of α,α- disubstituted benzo[b]thien-2-ylmethanols with aryl bromides using PCy 3 as ligand

Article abstract of DOI:10.1002/ejoc.200600929

α,α-Diphenylbenzo[b]thien-2-ylmethanol was treated with a series of aryl bromides in the presence of palladium(II) acetate and tricyclohexylphosphane to give the appropriate 2-aryl-benzo[b]thiophenes in good to excellent yield with concomitant formation o

Full text of DOI:10.1002/ejoc.200600929

FULL PAPER
DOI: 10.1002/ejoc.200600929
Selective Palladium-Catalysed ipso Arylation of α,α-Disubstituted
Benzo[b]thien-2-ylmethanols with Aryl Bromides using PCy3 as Ligand
A. Beatrix Bíró[a] and András Kotschy*[a]
Keywords: Benzothiophenes / Cross-coupling / Palladium / ipso Coupling
α,α-Diphenylbenzo[b]thien-2-ylmethanol was treated with a
series of aryl bromides in the presence of palladium(II) ace-
tate and tricyclohexylphosphane to give the appropriate 2-
aryl-benzo[b]thiophenes in good to excellent yield with con-
comitant formation of benzophenone. The reaction was
successfully extended to α,α-diphenylbenzo[b]thien-3-yl-
methanol, although in certain cases the transformation was
biased by concurrent ortho arylation.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2007)
cases, however, these transformations might proceed se-
quentially to give rise to highly substituted products.[11] In
order to achieve selective ipso coupling, one typically must
block the ortho positions in the starting carbinol by substi-
tution. Exceptions to this rule are 2-thienyl and 2-furyl car-
binols that, according to Miura, give 2-phenyl heterocycles
exclusively when reacted with chlorobenzene.[12] This reac-
tion was successfully extended to the preparation of 2-aryl-
thiophenes and 5-aryl-2,2Ј-bithiophenes.[13] As part of our
ongoing studies on the palladium-catalysed functionaliza-
tion of heterocyclic compounds, we attempted to extend
Miura’s procedure to 3-thienyl carbinols and benzo[b]thio-
phenylmethanol derivatives. The principal aim of our re-
search was to establish reaction conditions for which the
ipso-arylated heterocyclic product is formed with high selec-
tivity.
Introduction
Transition-metal catalysed carbon–carbon bond forming
reactions are an indispensable tool for synthetic chem-
ists.[1,2] Processes accompanied by the cleavage of a carbon–
hydrogen or a carbon–carbon bond have attracted particu-
lar attention from the atom-economic and sustainability
points of view.[3] The selectivity of coupling reactions pro-
ceeding by C–H activation usually originates in the coordi-
nating effect of an adjacent functional group; hence, these
reactions are also known as ortho arylation reactions
(Scheme 1).[4–6]
Scheme 1. The ortho and ipso arylation of aryl carbinols.
Results and Discussion
Catalytic processes involving C–C bond cleavage by β-
carbon elimination lead to the selective introduction of the
aryl moiety into the ipso position. In such processes, the
bond to break is typically between a tertiary alcohol and
an sp2- or sp-hybridized carbon. Ethynyl carbinols, for ex-
ample, were successfully converted into diarylacetylenes
with concomitant loss of a ketone molecule in a palladium-
catalysed transformation,[7,8] whereas in the presence of
rhodium catalysts, their dimerization was selectively ob-
served.[9]
The first set of experiments were designed to establish
whether the reaction of 3-thienyl carbinols and aryl halides
proceeds at the ipso position, as in the case of the analogous
2-thienyl derivatives, and to determine if the competing or-
tho arylation reaction also takes place to a considerable ex-
tent. Our carbinol of choice was α,α-diphenylthien-3-ylme-
thanol (4) and it was treated with bromobenzene (5a) in the
presence of palladium acetate, different phosphanes, and ce-
sium carbonate (Scheme 2). The reactions were monitored
and the products were identified by GC–MS.
In the palladium-catalysed transformation of α,α-disub-
stituted arylmethanols with aryl halides, ortho arylation and
ipso coupling are usually competing reactions.[10] In certain
[a] Institute of Chemistry, Eötvös Loránd University,
Pázmány Péter s. 1/A, 1117 Budapest, Hungary
Fax: +36-1-372-2909
E-mail: kotschy@chem.elte.hu
Supporting information for this article is available on the
WWW under http://www.eurjoc.org or from the author.
Scheme 2. The coupling of α,α-diphenylthien-3-ylmethanol (4) and
bromobenzene.
1364
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2007, 1364–1368

Pd-Catalysed ipso Arylation of α,α-Disubstituted Benzo[b]thien-2-ylmethanols
FULL PAPER
Our experiments revealed that the selectivity of the coup-
The poor selectivity for ipso arylation in the reaction of
ling reaction is quite poor; a mixture of products is fur- 3-thienyl carbinols and bromobenzene prompted us to look
nished in all cases, including ortho arylated starting material for other coupling partners.[14] The next reactant of choice
6, 2,3-diphenylthiophene (7), and a triphenylthiophene, ten- was α,α-diphenylbenzo[b]thien-2-ylmethanol (9, Scheme 3),
tatively identified as 2,3,5-isomer 8 (Table 1). The fact that a compound that was easily prepared from benzo[b]thio-
3-phenylthiophene was absent from the reaction mixtures phene and benzophenone.[15] In 9, there are two possible
suggests that the primary reaction of 4 and 5a is ortho aryl- sites for coupling: the 2-position for ipso coupling and the
ation in the 2-position of the thiophene ring. This position 3-position for ortho arylation. In the first reaction (Table 2,
is activated both electronically and by the directing effect Entry 1), 9 was treated with bromobenzene (5a) in o-xylene
of the carbinol moiety through complexation to the phenyl- with the use of the same conditions as reported by Miura
palladium intermediate of the catalytic cycle. The coupling for thiophene derivatives.[12] The reaction proceeded cleanly
of 6 with another molecule of bromobenzene (5a) could and 2-phenylbenzo[b]thiophene (10a) was formed selec-
lead, in principle, to three different products: direct aryl- tively, which was separated from the byproduct (benzophe-
ation at C-5, ortho arylation at C-4, and ipso arylation at none) by column chromatography. Following this encourag-
C3; only the latter product (7) was detected. This fact also ing result, a series of other aryl bromides (5b–n) were also
underlines the importance of the coordination between the reacted with 9. All reactions were run to completion, as
phenylpalladium complex and the carbinol in the course of judged by GC, and led to the selective formation of the
the process. The presence of minor amounts of a triarylated corresponding 2-arylbenzo[b]thiophene derivatives (10b–n)
thiophene, with its amount becoming significant only at the (Table 2, Entries 2–14) in good to excellent yield. The ipso
later stages of the process, suggests that 7 can undergo di- coupling of 9 worked equally well with electron-rich and
rect arylation in the 5-position. This process, also known electron-deficient aryl halides (compare Table 2, Entries 2–
as the heteroaryl Heck reaction, is well-documented in the 6). The steric effects seemed to play only a minor role, if
literature; the arylation of 7 in the 4-position is far less any, in influencing the yield (compare Table 2, Entries 2 and
likely to take place both for steric and electronic reasons. 3, 4–6, 10–12), although they had some effect on the rate
As the data in Table 1 show, the product distribution was of the coupling. Electron rich and electron poor heterocy-
only slightly dependent on the coupling conditions. cles were also efficiently coupled (Table 2, Entries 13, 14).
Whereas PCy3 and dppf (Table 1, Entries 1–4) predomi-
nantly led to diarylation products, the use of xantphos or
PPh3 (Table 1, Entries 5 and 6) caused the relative rate of
the second (ipso) arylation to decrease, which resulted in
increased amounts of monoarylated product 6. A change in
the palladium source from Pd(OAc)2 to [(C3H5)PdCl]2 or
Pd2(dba)3 had some influence on the activity of the catalyst
but not its selectivity (Table 1, Entries 2 and 3). The choice
Scheme 3. The coupling of α,α-diphenylbenzo[b]thien-2-ylmethanol
(9) and aryl bromides.
of solvent had very little effect on the process. The coupling Table 2. The palladium-catalysed coupling of α,α-diphenylbenzo-
[b]thien-2-ylmethanol (9) and aryl bromides 5a–n.
worked equally well in high-boiling solvents of apolar (o-
xylene) or polar (DMA) nature. Preliminary experiments
on other 3-thienyl carbinols (dimethyl, pentamethylene)
were even more discouraging and usually produced more
than three products.
Entry
Reagent
Time [h]
Yield [%]
1
2
3
4
5
6
7
8
9
10
11
12
13
14
1-bromobenzene (5a)
2-chloro-1-bromobenzene (5b)
4-chloro-1-bromobenzene (5c)
2-bromotoluene (5d)
8
77 (10a)
74 (10b)
97 (10c)
76 (10d)
95 (10e)
78 (10f)
67 (10g)
91 (10h)
51 (10i)
69 (10j)
73 (10k)
68 (10l)
95 (10m)
70 (10n)
22
19
20
46
22
20
20
46
17
22
46
46
22
3-bromotoluene (5e)
4-bromotoluene (5f)
4-bromoanisole (5g)
Table 1. Product distribution in the coupling of α,α-diphenylthien-
3-ylmethanol (4) and bromobenzene (5a).
2-fluoro-1-bromobenzene (5h)
4-fluoro-1-bromobenzene (5i)
1-bromonaphthalene (5j)
2-bromonaphthalene (5k)
9-bromoanthracene (5l)
2-bromothiophene (5m)
3-bromopyridine (5n)
Entry Ligand Time [h] Conversion [%]
6
7
8
1
2[a]
3[b]
4
PCy3
4
28
4
22
4
28
4
48
4
75
90
55
85
32
61
27
81
26
58
66
100
4
6
3
2
6
52
46
52
69
26
52
12
52
8
19
38
0
14
0
9
0
13
0
6
By following the coupling reactions with GC–MS, we
were unable to detect the formation of the appropriate or-
tho-arylated or 2,3-diarylated benzo[b]thiophene deriva-
tives, a finding that underlines the excellent selectivity of
the process. We also carried out some preliminary experi-
ments on the α,α-dimethyl and α,α-pentamethylene ana-
logues of 9, but the coupling of these derivatives was far
less selective; therefore, in the next set of experiments the
0
dppf
xantphos
PPh3
15
16
18
20
42
6
5
48
4
22
32
20
52
6
4
42
[a] [(C3H5)PdCl]2 was used instead of Pd(OAc)2. [b] Pd2(dba)3 was
used instead of Pd(OAc)2.
Eur. J. Org. Chem. 2007, 1364–1368
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
1365

A. B. Bíró, A. Kotschy
FULL PAPER
diphenyl carbinol moiety was shifted to the 3-position of veals that it is difficult to establish any marked trends in the
the benzo[b]thiophene frame. α,α-Diphenylbenzo[b]thien-3- product distribution. The yield of the 3-arylbenzo[b]thio-
ylmethanol (11, Scheme 4) was prepared from 3-bro- phenes ranges from good to poor and it is interesting to
mobenzo[b]thiophene[16] and benzophenone, in a similar note that 2-fluoro-1-bromobenzene (5h) gave 2,3-bis(2Ј-
method to 9. In 11, there are also two likely sites for coup- fluorophenyl)benzo[b]thiophene (13h) exclusively. From a
ling: the electronically activated 2-position for ortho aryl- preparative point of view, the utility of this reaction is lim-
ation (the primary reaction of 3-thienyl carbinols) and the ited to selected aryl bromides. A possible future extension
3-position for ipso coupling (the only reaction route ob- of the transformation is the identification of such catalyst
served for 2-benzothienyl carbinols). The coupling experi- systems that improve its selectivity either towards ipso aryl-
ments were carried out under the same previously used con- ation, or towards the formation of 2,3-diarylbenzo[b]thio-
ditions. Mixtures of 11, 2 equiv. of the appropriate aryl ha- phenes.
lide, the catalyst consisting of 5 mol-% Pd(OAc)2 and
10 mol-% PCy3, and 2 equiv. of cesium carbonate were
heated in o-xylene (Scheme 3). The reactions were moni-
tored by GC–MS and run until 11 was consumed.
Conclusions
In summary, we reacted α,α-disubstituted thienylme-
thanol and benzo[b]thienylmethanol derivatives with a
series of aryl bromides in the presence of a palladium(II)
acetate/tricyclohexylphosphane catalyst system. Although
the coupling reactions proceeded readily, the synthetic util-
ity of some of the studied transformations is limited by the
fact that coupling through C–C bond fission (ipso aryl-
ation) and through C–H activation (ortho arylation) might
be competing processes, which can lead to product mix-
tures. Starting from α,α-diphenylbenzo[b]thien-2-ylme-
thanol, we prepared a series of 2-arylbenzo[b]thiophenes
with high selectively in good to excellent yields, whereas in
case of α,α-diphenylbenzo[b]thien-3-ylmethanol, a varying
selectivity was observed in the coupling, which decreased
the yield of 3-arylbenzo[b]thiophenes in most cases at the
expense of the formation of 2,3-diarylbenzo[b]thiophenes.
Scheme 4. The coupling of α,α-diphenylbenzo[b]thien-3-ylmethanol
(11) and aryl bromides.
Unlike the case of 2-benzothienyl carbinols, the reaction
of 11 with aryl bromides usually led to the concomitant
formation of 3-arylbenzo[b]thiophenes (12) and 2,3-di-
arylbenzo[b]thiophenes (13). In contrast to the recent re-
sults of Miura and coworkers where the palladium-cata-
lysed coupling of α,α-dimethylbenzo[b]thien-3-ylmethanol
and some aryl bromides was reported to give 2,3-di-
arylbenzo[b]thiophenes in the presence of the bulky P(bi-
phenyl-2-yl)(tBu)2 ligand,[14] in our case the major product
was generally ipso-coupled 3-aryl derivative 12, which was
separated from the byproducts by column chromatography
(Table 3). By following the coupling reactions by GC–MS,
we established that the 12/13 ratio varies only a little in the
course of the process, which suggests that ortho arylation
(at C-2) and ipso arylation (at C-3) are competing processes
for 11. In contrast to this finding, Miura’s analogous pro-
cess was reported to follow a C-2 arylation, C-3 arylation
sequence.[14] Analysis of the data presented in Table 3 re-
Experimental Section
General Remarks: Melting points were determined with a hotplate
1
and are uncorrected. The H and 13C NMR (CDCl3) spectra were
recorded with a Bruker DRX-250 spectrometer. For 1H NMR spec-
tra the residual peak of CHCl3 (δ = 7.26 ppm) was used as the
internal reference, whereas for 13C NMR spectra the central peak
of CDCl3 (δ = 77.0 ppm) was used as the reference. The IR spectra
(KBr pellet) were obtained with a Bruker IFS-55 FTIR spectrome-
ter. GC–MS measurements were carried out with an Agilent 6890N
instrument (HP-5 capillary column: 30.0 mϫ250 µmϫ0.25 µm).
Silica gel (0.040–0.063 mm) was used for flash column chromatog-
raphy.
Table 3. The palladium-catalysed coupling of α,α-diphenylbenzo-
[b]thien-3-ylmethanol (11) and aryl bromides 5b–f,h–k,m.
Entry
Reagent
12[a]
13[a]
General Procedure for the Preparation of 2-Arylbenzo[b]thiophenes
(10a–n): In a flame-dried Schlenk flask, 9 (60 mg, 0.189 mmol),
the appropriate aryl halide (2 equiv.), PCy3 (5.3 mg, 0.0189 mmol,
10 mol-%), Pd(OAc)2 (2.1 mg, 0.00949 mmol, 5 mol-%), Cs2CO3
(0.123 g, 0.378 mmol), and o-xylene (6 mL) were mixed under an
atmosphere of argon and heated in an oil bath at 110 °C. After
complete conversion of the starting material (monitored by GC)
and cooling of the mixture to ambient temperature, water (20 mL)
was added, and the reaction mixture was extracted with dichloro-
methane. The combined organic extracts were dried with MgSO4,
and the solvent was removed in vacuo. The residue was purified by
column chromatography on silica gel (hexane/ethyl acetate, gradi-
ent from 100:0 to 80:20).
1
2
3
4
5
6
7
8
9
2-chloro-1-bromobenzene (5b) 94 (91, 12b)
4-chloro-1-bromobenzene (5c) 89 (86, 12c)
6
11
29
45
2-bromotoluene (5d)
3-bromotoluene (5e)
4-bromotoluene (5f)
71 (67, 12d)
55 (51, 12e)
65 (50, 12f)
0
35
2-fluoro-1-bromobenzene (5h)
4-fluoro-1-bromobenzene (5i)
1-bromonaphthalene (5j)
2-bromonaphthalene (5k)
2-bromothiophene (5m)
100 (51, 13h)
60 (32, 12i)
85 (44, 12j)
90 (55, 12k)
47 (37, 12m)
40
0[b]
0[b]
53
10
[a] 12:13 Ratios were determined by GC–MS from the reaction
mixtures. Numbers in parentheses refer to the yield of isolated
product. [b] Dibromonaphthalene is formed as a byproduct.
1366
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© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2007, 1364–1368

Pd-Catalysed ipso Arylation of α,α-Disubstituted Benzo[b]thien-2-ylmethanols
FULL PAPER
2-Phenylbenzo[b]thiophene (10a):[17] White solid, 31 mg (77%).
2-(2-Chlorophenyl)benzo[b]thiophene (10b): White solid, 34 mg
In a flame-dried Schlenk flask, 11 (100 mg, 0.316 mmol), the ap-
propriate aryl halide (2 equiv.), PCy3·HBF4 (11.4 mg, 0.316 mmol,
10 mol-%), Pd(OAc)2 (3.5 mg, 0.0158 mmol, 5 mol-%), Cs2CO3
(0.206 g, 0.632 mmol), and o-xylene (7 mL) were mixed under an
atmosphere of argon and heated in an oil bath at 110 °C. After
complete conversion of the starting material (by GC–MS) and
cooling of the mixture to ambient temperature, water (20 mL) was
added, and the reaction mixture was extracted with dichlorometh-
ane. The combined organic extracts were dried with MgSO4, and
the solvent was removed in vacuo. The residue was purified by col-
umn chromatography on silica gel (hexane/ethyl acetate, gradient
from 100:0 to 80:20).
1
(74%). M.p. 67.5–69 °C. H NMR (250 MHz): δ = 7.30–7.43 (m,
4 H), 7.51–7.54 (m, 1 H), 7.60–7.63 (m, 2 H), 7.82–7.89 (m, 2 H)
ppm. 13C NMR (62.5 MHz): δ = 122.0, 123.8, 124.4, 124.5, 124.6,
126.9, 129.2, 130.5, 131.9, 132.8, 133.2, 139.8, 140.1, 140.3 ppm.
IR: ν = 2963, 1261, 832, 802, 747, 723 cm–1. MS (EI): m/z (%) =
˜
224 (100) [M]+, 208 (30), 133 (2), 86 (8), 63 (6), 51 (6). C14H9ClS
(209.51): calcd. C 68.71, H 3.71; found C 68.66, H 3.97.
2-(4-Chlorophenyl)benzo[b]thiophene (10c):[18] White solid, 41 mg
(97%).
2-(o-Tolyl)benzo[b]thiophene (10d):[19] White solid, 32 mg (76%).
2-(m-Tolyl)benzo[b]thiophene (10e):[17] White solid, 40 mg (95%).
3-(2Ј-Chlorophenyl)benzo[b]thiophene (12b): Colourless oil, 42 mg
(91%), 1H NMR (250 MHz): δ = 7.36–7.45 (m, 6 H), 7.52–7.58 (m,
2 H), 7.92–7.96 (m, 1 H) ppm. 13C NMR (62.5 MHz): δ = 122.7,
123.2, 124.2, 124.4, 125.4, 126.7, 128.9, 129.1, 129.9, 130.0, 132.0,
2-(p-Tolyl)benzo[b]thiophene (10f):[21] Light yellow solid, 33 mg
133.8, 138.3, 139.7 ppm. IR: ν = 3023, 1231, 827, 792, 753,
(78%).
˜
731 cm–1. MS (EI): m/z (%) = 224 (100) [M]+, 208 (35), 165 (45).
2-Anisylbenzo[b]thiophene (10g):[20] White solid, 35 mg (67%).
C14H9ClS (244.65): calcd. C 68.71, H 3.71; found C 69.04, H 4.05.
2-(2Ј-Fluorophenyl)benzo[b]thiophene (10h): White solid, 29 mg
(91%). M.p. 55–56 °C. H NMR (250 MHz): δ = 7.13–7.24 (m, 2
2,3-Bis(2Ј-chlorophenyl)benzo[b]thiophene (13b): MS (EI): m/z (%)
1
= 354 (75) [M]+, 318 (25), 284 (45), 207 (100).
H), 7.26–7.39 (m, 3 H), 7.66–7.73 (m, 2 H), 7.78–7.86 (m, 2 H)
ppm. 13C NMR (62.5 MHz): δ = 116.2, 116.6, 122.0, 123.5, 123.8,
124.5, 124.6, 129.3, 129.5, 137.3, 139.4, 140.4, 157.6, 161.6 ppm.
MS (EI): m/z (%) = 228 (100) [M]+, 208 (5), 196 (10), 183 (30), 170
(5), 157 (8), 144 (3), 133 (3). C14H9FS (228.15): calcd. C 73.45, H
3.89, S 13.85; found C 73.66, H 3.97, S 14.05.
3-(4Ј-Chlorophenyl)benzo[b]thiophene (12c): Colourless oil, 40 mg
(86%). 1H NMR (250 MHz): δ = 7.23 (s, 1 H), 7.38–7.43 (m, 3 H),
7.46–7.53 (m,
(62.5 MHz): δ = 122.6, 123.0, 123.7, 124.5, 124.6, 128.7, 128.9,
3 H), 7.84–7.93 (m, 2
H) ppm. 13C NMR
129.1, 129.9, 130.8, 131.7, 134.4, 136.8, 140.7 ppm. IR: ν = 3052,
˜
1523, 1190, 829, 782, 751, 727, 677 cm–1. MS (EI): m/z (%) = 244
(100) [M]+, 208 (30), 165 (30). C14H9ClS (244.65): calcd. C 68.71,
H 3.71; found C 68.88, H 3.59.
2-(4Ј-Fluorophenyl)benzo[b]thiophene (10i): White solid, 39 mg
(51%). M.p. 162–164 °C. 1H NMR (250 MHz): δ = 6.91 (t, J =
8.6 Hz, 2 H), 7.05–7.16 (m, 3 H), 7.46 (dd, J1 = 5.1 Hz, J2 = 8.8 Hz,
2 H), 7.55 (d, J = 6.9 Hz, 1 H), 7.61 (d, J = 7.0 Hz, 1 H) ppm. 13C
NMR (62.5 MHz): δ = 115.8, 116.1, 119.4, 122.2, 123.5, 124.4,
2,3-Bis(4Ј-chlorophenyl)benzo[b]thiophene (13c): MS (EI): m/z (%)
= 354 (100) [M]+, 318 (20), 305 (5), 284 (70), 253 (10), 207 (25).
124.6, 128.2, 130.5, 139.4, 140.6, 143.0 ppm. IR: ν = 3059, 1510,
˜
3-(o-Tolyl)benzo[b]thiophene (12d): White solid, 28 mg (67%). M.p.
1261, 821, 744 cm–1. MS (EI): m/z (%) = 228 (100) [M]+, 208 (5),
183 (30). C14H9FS (228.15): C 73.66, H 3.97; found C 73.38, H
4.12.
1
178–179 °C. H NMR (250 MHz): δ = 2.20 (s, 3 H), 7.30–7.48 (m,
8 H), 7.92–7.96 (d, J = 7.4 Hz, 1 H) ppm. 13C NMR (62.5 MHz):
δ = 20.2, 122.7, 123.2, 123.7, 124.1, 124.2, 125.7, 127.9, 130.2,
130.5, 135.4, 137.1, 137.5, 139.0, 139.9 ppm. IR: ν = 3031, 1521,
˜
2-(1Ј-Naphthyl)benzo[b]thiophene (10j):[21] White solid, 34 mg
(69%).
1483, 802 cm–1. MS (EI): m/z (%)
=
224 (100)
[M]+, 208 (35), 76 (10). C15H12S (224.17): calcd. C 80.31, H 5.39;
found C 79.83, H 5.15.
2-(2Ј-Naphthyl)benzo[b]thiophene (10k):[23] White solid, 36 mg
(73%).
2,3-Bis(o-tolyl)benzo[b]thiophene (13d): MS (EI): m/z (%) = 314
(100) [M]+, 221 (32), 207 (29), 142 (20).
2-(9Ј-Anthryl)benzo[b]thiophene (10l): Light yellow solid, 43 mg
(68%). M.p. 226.5–228 °C. 1H NMR (250 MHz): δ = 7.41–7.52 (m,
7 H), 7.90–7.97 (m, 4 H), 8.06 (d, J = 8.3 Hz, 2 H), 8.57 (s, 1 H)
ppm. 13C NMR (62.5 MHz): δ = 122.2, 123.6, 124.3, 124.5, 125.3,
126.1, 126.2, 126.5, 127.2, 128.3, 128.3, 128.4, 131.1, 131.4, 134.1,
3-(m-Tolyl)benzo[b]thiophene (12e): Colourless oil, 22 mg (51%). 1H
NMR (250 MHz): δ = 2.44 (s, 3 H), 7.22–7.23 (m, 1 H), 7.38–7.12
(m, 6 H), 7.89–7.94 (m, 2 H) ppm. 13C NMR (62.5 MHz): δ = 21.5,
122.9, 123.0, 123.2, 124.3, 124.4, 125.8, 128.3, 128.6, 129.4, 135.9,
140.1 ppm. IR: ν = 3050, 3027, 1440, 886, 824, 746 cm–1. MS (EI):
˜
137.9, 138.2, 138.4, 140.6 ppm. IR: ν = 3029, 1539, 1499, 828,
˜
m/z (%) = 310 (100) [M]+, 276 (10), 154 (50). C22H14S (310.24): C
742 cm–1. MS (EI): m/z (%) = 224 (100) [M]+, 208 (20), 76 (5).
85.12, H 4.55; found C 85.04, H 4.38.
C15H12S (224.17): calcd. C 80.31, H 5.39; found C 79.90, H 5.45.
2-(2Ј-Thienyl)benzo[b]thiophene (10m):[22] White solid, 38 mg
(95%).
2,3-Bis(m-tolyl)benzo[b]thiophene (13e): MS (EI): m/z (%) = 314
(100) [M]+, 298 (20), 284 (30), 134 (15).
2-(3Ј-Pyridyl)benzo[b]thiophene (10n): Light yellow solid, 28 mg
(70%). M.p. 118.5–120.5 °C. 1H NMR (250 MHz): δ = 7.33–7.39
(m, 3 H), 7.61 (s, 1 H), 7.92–7.87 (m, 2 H), 7.96 (d, J = 9.5 Hz, 1
H), 8.58 (d, J = 5.0 Hz, 1 H), 8.99 (d, J = 2.0 Hz, 1 H) ppm. 13C
NMR (62.5 MHz): δ = 120.7, 122.3, 123.6, 123.8, 124.8, 124.9,
3-(p-Tolyl)benzo[b]thiophene (12f): White solid, 22 mg (50%). M.p.
122.5–123.5 °C. H NMR (250 MHz): δ = 2.46 (s, 3 H), 7.25 (d, J
= 7.5, 2 H), 7.39–7.43 (m, 3 H), 7.52 (d, J = 8.0 Hz, 2 H), 7.92–
7.97 (m 2 H) ppm. 13C NMR (62.5 MHz): δ = 21.3, 122.9, 123.0,
124.2, 124.3, 126.8, 128.6, 129.4, 133.1, 137.3, 138.0, 138.1,
1
130.3, 133.5, 139.7, 140.2, 140.4, 147.4, 149.1 ppm. IR: ν = 3052,
˜
140.7 ppm. IR: ν = 3025, 2918, 1541, 1494, 845, 822, 805, 761,
˜
1662, 1524, 831, 803, 745, 726 cm–1. MS (EI): m/z (%) = 211 (100)
[M]+, 79 (25), 51 (4). C13H9NS (211.14): C 73.90, H 4.29, N 6.63;
found C 73.66, H 4.33, N 6.30.
733 cm–1. MS (EI): m/z (%) = 224 (100) [M]+, 208 (15), 134 (5).
C15H12S (224.17): calcd. C 80.31, H 5.39; found C 79.98, H 5.05.
2,3-Bis(p-tolyl)benzo[b]thiophene (13f): MS (EI): m/z (%) = 314
General Procedure for the Preparation of 3-Arylbenzo[b]thiophenes
(100) [M]+, 298 (30), 284 (35), 207 (65).
Eur. J. Org. Chem. 2007, 1364–1368
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
1367

A. B. Bíró, A. Kotschy
FULL PAPER
[2]
[3]
A. Kotschy, G. Timári, Heterocycles from Transition Metal Ca-
talysis, Springer, Dordrecht, 2005.
2,3-Bis(2ЈЈ-Fluorophenyl)benzo[b]thiophene (13h): White solid,
31 mg (51%). M.p. 95–96 °C. H NMR (250 MHz): δ = 6.96 (t, J
1
M. Miura, M. Nomura, Topics in Current Chemistry (Ed.: N.
Miyaura), Springer, Dordrecht, 2002, vol. 219, pp. 212–240.
G. D. Cuny, Tetrahedron Lett. 2003, 44, 8149–8152.
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8862.
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= 8.7 Hz, 1 H), 7.06–7.30 (m, 4 H), 7.34–7.43 (m, 3 H), 7.49–7.57
(m, 2 H), 7.83–7.93 (m, 2 H) ppm. 13C NMR (62.5 MHz): δ =
115.7, 116.1, 121.9, 122.1, 123.2, 123.3, 123.8, 123.9, 124.0, 124.1,
124.5, 124.8, 129.5, 129.7, 129.8, 130.1, 130.2, 132.3, 139.4,
139.5 ppm. MS (EI): m/z (%) = 322 (100) [M]+, 302 (30), 257 (15).
C14H9FS (228.15): calcd. C 73.66, H 3.97; found C 73.19, H 4.05.
[4]
[5]
[6]
3-(4Ј-Fluorophenyl)benzo[b]thiophene (12i): Colourless oil, 14 mg
(32%). 1H NMR (250 MHz): δ = 7.21–7.29 (m, 2 H), 7.35–7.57
(m, 5 H), 7.67–7.71 (m, 1 H), 8.03–8.07 (m, 1 H) ppm. 13C NMR
(62.5 MHz): δ = 115.5, 115.8, 122.1, 122.7, 123.0, 123.4, 124.4,
[7]
[8]
A. Nagy, Z. Novák, A. Kotschy, J. Organomet. Chem. 2005,
690, 4453–4461.
124.5, 130.2, 130.3, 131.1, 137.8, 140.6, 164.3 ppm. IR: ν = 2924,
[9]
˜
A. Funayama, T. Satoh, M. Miura, J. Am. Chem. Soc. 2005,
127, 15354–15355.
Y. Terao, H. Wakui, T. Satoh, M. Miura, M. Nomura, J. Am.
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2004, 60, 6757–6763.
1509, 1217, 820, 806, 736 cm–1. MS (EI): m/z (%) = 228 (100)
[M]+, 208 (3) 183 (70). C14H9FS (228.15): calcd. C 73.66, H 3.97;
found C 73.30, H 4.25.
[10]
[11]
[12]
[13]
2,3-Bis(4Ј-fluorophenyl)benzo[b]thiophene (13i): MS (EI): m/z (%) =
322 (100) [M]+, 302 (15), 257 (10), 207 (15).
3-(1Ј-Naphthyl)benzo[b]thiophene (12j):[23] White solid, 22 mg
(44%).
3-(2Ј-Naphthyl)benzo[b]thiophene (12k):[24] White solid, 27 mg
(55%).
3-(2Ј-Thienyl)benzo[b]thiophene (12m):[23] White solid, 15 mg
(37%).
[14] Similar selectivity was observed by Miura et al. who were also
able to drive the process to selective 2,3-diarylation by chang-
ing the ligand: M. Nakano, T. Satoh, M. Miura, J. Org. Chem.
2006, 71, 8309–8311.
[15] C. Avendao, C. de Diego, J. Elguero, Magn. Reson. Chem.
1990, 28, 1011–1017.
2,3-Bis(2Ј-thienyl)benzo[b]thiophene (13m): MS (EI): m/z (%) = 298
(100) [M]+, 253 (45), 240 (5), 195 (5).
[16] H. Arnault, Synthesis 2002, 213–216.
Supporting Information (see footnote on the first page of this arti-
cle): Experimental procedures and characterization data for known
compounds.
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Acknowledgments
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[22] B. D. Tilak, Tetrahedron 1960, 9, 76–95.
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The authors thank Dr. K. Torkos for providing the necessary ana-
lytical background. The financial support of the Hungarian Scien-
tific Research Fund (OTKA F47125) and KPI (GVOP-3.2.1–358/
2004) is gratefully acknowledged.
[1] a) M. Beller, C. Bolm (Eds.), Transition Metals for Organic Syn-
thesis, 2nd ed., Wiley-VCH, Weinheim, 2004.
Received: October 24, 2006
Published Online: January 12, 2007
1368
www.eurjoc.org
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2007, 1364–1368