Synthesis of 2-aryl- and 2,5-diarylfurans and thiophenes by Suzuki-Miyaura reactions using potassium trifluoroborate salts and heteroaryltellurides

Article abstract of DOI:10.1071/CH08255

The Suzuki-Miyaura cross-coupling reaction of 2-(butyltellanyl) or 2,5-bis-(butyltellanyl)furans and thiophenes with potassium aryltrifluoroborate salts catalyzed by palladium afforded 2-aryl- or 2,5-diaryl-furans and thiophenes in moderate to good yields.

Full text of DOI:10.1071/CH08255

Full Paper
CSIRO PUBLISHING
Aust. J. Chem. 2008, 61, 870–873
www.publish.csiro.au/journals/ajc
Synthesis of 2-Aryl- and 2,5-Diarylfurans and Thiophenes by
Suzuki–Miyaura Reactions Using Potassium Trifluoroborate
Salts and Heteroaryltellurides
Giancarlo V. Botteselle,A Thomas L. S. Hough,A Raphael C. Venturoso,A
Rodrigo Cella,C Adriano S. Vieira,A and Helio A. StefaniA,B,C,D
AFaculdade de Ciências Farmacêuticas, Universidade de São Paulo, São Paulo, Brazil.
BDeparmento de Biofísica, Universidade Federal de São Paulo, São Paulo, Brazil.
CInstituto de Química, Universidade de São Paulo, São Paulo, Brazil.
DCorresponding author. Email: hstefani@usp.br
The Suzuki–Miyaura cross-coupling reaction of 2-(butyltellanyl) or 2,5-bis-(butyltellanyl)furans and thiophenes with
potassium aryltrifluoroborate salts catalyzed by palladium afforded 2-aryl- or 2,5-diaryl-furans and thiophenes in moderate
to good yields.
Manuscript received: 12 June 2008.
Final version: 27 August 2008.
Introduction
Due to the important and advantageous features of potassium
organotrifluoroborate salts and organotellurium compounds in
Suzuki–Miyaura cross-coupling reactions, we have endeavoured
to develop new methods for construction of biaryls, enynes,
stilbenes, and 1,3-diene systems.[29–32] Extending our research
interest in the preparation and reactivity of potassium organo-
trifluoroborate salts, we report herein a new approach for the
synthesis of 2-aryl- or 2,5-diarylfurans and thiophenes com-
pounds by the palladium-catalyzed cross-coupling reaction of
heteroaryl tellurides and potassium aryltrifluoroborate salts.
Heterobiaryls have important biological properties, and the
biaryl unit is present in several types of compounds of current
interest including natural products, polymers, advanced mate-
rials, liquid crystals, luminescent molecular chemosensors, and
molecules of medicinal interest.[1,2] The preparation of hetero-
biaryls using the Suzuki–Miyaura coupling reaction, in which
the aryl moieties comprise either one or both of the hetero-
cyclic rings, has attracted considerable attention, and there are
examples of this type of synthesis.[1–3]
2,5-Diphenylfurans have already been prepared by Stille
coupling,[4–6] Suzuki–Miyaura coupling,[6] Paal–Knoor
synthesis,[7] and from phenacyl bromides[8] as well as from
butane or butyndiones by microwave irradiation.[9] The struc-
tural feature of furans with conjugated aromatic substituents
at the 2- and 5-positions should be associated with useful and
specific fluorescent properties.[10,11]
Boronic acids and boronate esters are the most commonly
used derivatives in Suzuki–Miyaura cross-coupling reactions.
Recently, potassium organotrifluoroborate salts have been used
as an alternative to these boron reagents in Suzuki–Miyaura
cross-coupling reactions.[12–15] These salts are easily prepared
by the addition of a saturated aqueous solution of inexpensive,
widely available KHF2 to a great variety of organoboron inter-
mediates. Organotrifluoroborates are stable, non-hygroscopic,
relatively nucleophilic compounds and their inorganic byprod-
ucts are environmentally benign and easily removed in the
workup step.[16,17]
Results and Discussion
Our initial studies focussed on the development of an
optimum set of reaction conditions for the coupling reac-
tion of 2,5-bis(butyltellanyl)furans[33] and 2,5-bis(butyltellanyl)
thiophenes[34] with potassium aryltrifluoroborate salts. In pre-
liminary experiments, we investigated the catalyzed cross-
coupling reaction between 2,5-bis(butyltellanyl)furan 1 and
phenyltrifluoroborate salt 2a in methanol, using Pd(OAc)2 as
catalyst and 1,1ꢀ-bis-(diphenylphosphino)ferrocene (dppf) as
the ligand at room temperature in one step, which produced
2,5-diphenylfuran 3a in 73% yield (Table 1; entry 11).
As we reported earlier,[29–31] the influence of silver salt
as an additive was noteworthy in this cross-coupling reaction.
When the reaction was performed in the absence of Ag2O, no
cross-coupling product was isolated and the starting material 1
was recovered unchanged (Table 1, entry 12). Also tested were
AgOAc and CuI (Table 1, entries 16 and 17, respectively) as
additives, and no product formation was observed in either case.
The use of PdCl2, Pd(PPh3)4, and Pd(dppf)Cl2 in the pres-
ence of Ag2O yielded the desired product, but in unsatisfactory
amounts (Table 1, entries 2–4). Among the several catalyst sys-
tems tested, Pd(OAc)2 (10 mol%), using dppf (0.1 mmol) as
ligand and Ag2O as additive, was found to be ideal and the
product was obtained in 73% isolated yield (Table 1, entry 11).
Over the past decade, organotellurium chemistry has
been extensively explored, and many methods employing tel-
lurium compounds have been developed.[18,19] Among these
methods, organotellurium reagents were successfully used as
the electrophilic partner[20] in several metal-catalyzed cross-
coupling reactions, such as the Sonogashira,[21–24] Negishi,[25]
Heck,[26–28] and Suzuki–Miyaura reactions.[29–32]
© CSIRO 2008
10.1071/CH08255
0004-9425/08/110870

Suzuki–Miyaura Reactions
871
Table 1. Screening for the best Suzuki–Miyaura cross-coupling reaction conditions
Reaction
conditions
Bun Te
Ph
ϩ
PhBF3K
TeBun
MeOH
O
O
Ph
2a
1
3a
Entry
Catalyst (mol%)
Ligand (mmol)
Base (equiv.)
YieldA [%]
1
2
3
4
5
6
7
8
Pd(OAc)2 (10)
PdCl2 (10)
Pd(PPh3)4 (10)
Pd(dppf)Cl2 (10)
PdCl2 (10)
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
34
36
38
48
48
50
45
50
53
55
73
—
75
50
30
—
—
—
—
—
45
—
—
PPh3 (0.2)
PPh3 (0.2)
BINAP (0.05)
Tri(o-tolyl)phosphine (0.1)
Tri(2-furyl)phosphine (0.1)
dppe (0.1)
dppf (0.1)
dppf (0.1)
dppf (0.1)
dppf (0.1)
dppf (0.1)
dppf (0.1)
dppf (0.1)
dppf (0.1)
dppf (0.1)
dppf (0.1)
dppf (0.1)
dppf (0.1)
Pd(OAc)2 (10)
Pd(OAc)2 (10)
Pd(OAc)2 (10)
Pd(OAc)2 (10)
Pd(OAc)2 (10)
Pd(OAc)2 (10)
Pd(OAc)2 (10)
Pd(OAc)2 (20)
Pd(OAc)2 (5)
Pd(OAc)2 (1)
Pd(OAc)2 (10)
Pd(OAc)2 (10)
Pd(OAc)2 (10)
Pd(OAc)2 (10)
Pd(OAc)2 (10)
Pd(OAc)2 (10)
Pd(OAc)2 (10)
Pd(OAc)2 (10)
9
10
11
12B
13
14
15
16C
17D
18
19
20
21
22
23
—
Et3N (3)
K2CO3 (3)
Cs2CO3 (3)
DIPEA (3)
DMAP (3)
Pyridine (3)
dppf (0.1)
AIsolated yield.
BNo additive was employed.
CAgOAc was employed instead of Ag2O.
DCuI was employed instead of Ag2O.
No significant improvement on the yield occurred with either
higher stoichiometry of Pd(OAc)2 (20 mol%) (Table 1, entry 13)
or when lower catalyst loadings were used (Table 1, entries
14 and 15). The reactions were monitored by consumption of
starting material and appearance of the desired product by TLC
analysis.
In addition, other ligands such as triphenylphosphine, 2,2-
bis(diphenylphosphino)-1,1ꢀ-binaphthyl (BINAP), tri(o-tolyl)
phosphine, tri(2-furyl)phosphine, and dppe (Table 1, entries
6–10 respectively) were tested and in all cases the desired
product formed, but in unsatisfactory yields.
salts 2a–e afforded low to medium yields (15–55%) and the
homocoupling product was also observed.
The effect of substituents was also studied, as shown in
Table 2. When potassium aryltrifluoroborate salts contain-
ing electron-withdrawing groups were used no reaction was
observed (Table 2, entries 6 and 7) except when fluorine was
attached in the para-position (Table 2, entry 3). Electron-
donating groups were also used, but with no further bene-
fit. When potassium heteroaryltrifluoroborate salts, such as
pyridinyl or thiophenyl were employed, no reaction was observed
(Table 2, entries 8 and 9).
Finally, to optimize the reaction several bases such as
Et3N, K2CO3, Cs2CO3, dimethylaminopyridine (DMAP), N,N-
diisopropylethylamine (DIPEA), and pyridine (Table 1, entries
18–21) were used. Only the use of DIPEA afforded the desired
product, but in a modest yield of 45% (Table 1, entry 21).
Todemonstrate theefficiency of this reaction, we explored the
method by extending these conditions to other potassium aryl-
trifluoroborate salts and to 2,5-bis(butyltellanyl)thiophene 4,
to afford the 2,5-diarylfurans 3 and thiophenes 5 (Table 2).
However, when other potassium aryltrifluoroborate salts
were employed, only reasonable yields to 2,5-diarylfurans were
achieved (35–73%). In all cases we observed a homocoupling
reaction of the potassium aryltrifluoroborate salts, which led to
the formation of the respective biaryl products. Even the use of
an excess of potassium aryltrifluoroborate did not afford better
yields.
When the same standard catalyst systems were employed
with 2-(butyltellanyl)furan 6 and 2-(butyltellanyl)thiophene 7,
the corresponding 2-arylfurans 8 and 2-arylthiophenes 9 were
obtained in better yields as compared with the 2,5-diaryl
derivatives (Table 3).
The effects of substituents with these substrates were
comparable to those observed with the 2,5-bis(butyltellanyl)
derivatives. When potassium aryltrifluoroborate salts contain-
ing electron-withdrawing substituents were used, no reaction
was observed (Table 3, entries 6 and 7) except when fluorine
was located in the para-position (Table 3, entry 5). However,
whenpotassium2-thiophenyltrifluoroboratewascoupledwith 6,
the corresponding product was achieved in 34% yield (Table 3,
entry 9).
Conclusions
In the same manner, the cross-coupling between 2,5-
bis(butyltellanyl)thiophene 4 and potassium aryltrifluoroborate
We have presented here a new approach to the synthe-
sis of 2,5-diarylfurans and 2,5-diarylthiophenes, as well as

872
G. V. Botteselle et al.
Table 2. Synthesis of 2,5-diarylfurans and thiophenes by
Suzuki–Miyaura cross-coupling reaction
Pd(OAc)2, dppf,
a
Table 3. Synthesis of 2,5-diarylfurans and thiophenes by
Suzuki–Miyaura cross-coupling reaction
Pd(OAc)2, dppf,
a
room temp.
room temp.
BunTe
ϩ
2ArBF3K
Ar
ϩ ArBF3K
TeBun
X
TeBun
X
MeOH, Ag2O
X
MeOH, Ag2O
Ar
X
Ar
X ϭ O 8a–i
X ϭ S 9a–i
X ϭ O 6
X ϭ S 7
2a–i
X ϭ O 1
X ϭ S 4
2a–i
X ϭ O 3a–i
X ϭ S 5a–i
Entry
Compound
X
Yield [%]A
Entry
1
Compound
X
Yield [%]A
1
2
O 8a
S 9a
68B
55B
O 3a
S 5a
73B
45C
X
X
55B
64C
2
3
4
O 3b
S 5b
60C
15
O 8b
S 9b
X
X
X
Me
O 3c
S 5c
55B
32C
X
3D
O 8c
S 9c
50C
71B
F
F
NH2
O 3d
S 5d
55C
55B
X
OMe
65B
60B
MeO
H2N
4
5
6
O 8d
S 9d
X
OMe
5D
O 3e
S 5e
35C
50C
NH2
X
X
O 8e
S 9e
30B
56C
X
F
6
O 3f
S 5f
n.r.E
n.r.
CO2H
CF3
HO2C
F3C
O 8f
S 9f
n.r.E
n.r.
X
CO2H
CF3
7
X
O 3g
S 5g
n.r.
n.r.
CF3
CF3
X
7
O 8g
S 9g
n.r.
n.r.
CF3
8
9
O 3h
S 5h
n.r.
n.r.
X
X
N
S
N
8
9
O 8h
S 9h
n.r.
n.r.
X
O 3i
S 5i
n.r.
n.r.
N
S
O 8i
S 9i
34
n.r.
S
AIsolated yield.
X
BReaction time: 1.5 h.
CReaction time: 2.0 h.
AIsolated yield.
DUsing (3-aminophenyl)boronic acid.
En.r. = no reaction.
BReaction time: 1.5 h.
CReaction time: 1.5 h.
DUsing (3-aminophenyl)boronic acid.
En.r. = no reaction.
2-arylfurans and 2-arylthiophenes. Our methodology consists of
a palladium-catalyzed cross-coupling reaction between organo-
tellurium compounds and potassium aryltrifluoroborate salts.
More than 20 examples of 2,5-diaryl and 2-arylheteroaryl
species were prepared in 30–73% overall yield. Studies aimed
towards the template-directed synthesis of more complex struc-
tures are in progress in our laboratory.
(0.5 mmol), silver(i) oxide (1 mmol), dppf (20 mol%, 0.1 mmol),
and palladium(ii) acetate (10 mol%, 0.05 mmol) in dry methanol
(4 mL), after which was added potassium aryltrifluoroborate
(1.1 mmol). The reaction mixture was stirred at room tempera-
ture and the consumption of the starting materials was followed
by TLC. Fluorescent side products that formed as the reaction
proceeded were visible on the TLC plate under long-wavelength
UV light. The reaction mixture was filtered through a pad of
Celite and the filtrate partitioned between ethyl acetate and sat-
urated NH4Cl. The organic layer was washed with saturated
NH4Cl(3 × 10 mL), driedoverMg2SO4, andconcentratedunder
Experimental
General Procedure for 2,5-Diarylfurans and Thiophenes
In a two-necked round-bottomed flask (15 mL), under a nitrogen
atmosphere, were added 2,5-bis(butyltellanyl)furan or thiophene

Suzuki–Miyaura Reactions
873
vacuum. The product was purified by silica gel chromatography
(100% hexane).
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δH (300 MHz, CDCl3) 3.87 (s, 6H), 6.61 (s, 2H), 6.97 (d, J 7.83,
4H), 7.69 (d, J 7.95, 4H). δC (75 MHz, CDCl3) 158.9, 152.8,
125.0, 124.0, 114.2, 105.6, 55.4. m/z 1H and 3C 280 (100%),
265 (93), 194 (10), 140 (31), 77 (5), 43 (4).
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δH (300 MHz, CDCl3) 3.83 (s, 6H), 6.91 (d, J 8.76, 4H), 7.13
(s, 2H), 7.53 (d, J 8.73, 4H). δC (75 MHz, CDCl3) 159.1, 142.6,
126.8, 122.9, 114.3, 114.2, 55.4. m/z 296 (100%), 281 (77),
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General Procedure for 2-Arylfurans and Thiophenes
In a two-necked round-bottomed flask (15 mL), under a nitro-
gen atmosphere, were added 2-(butyltellanyl)furan or thiophene
(0.5 mmol), silver(i) oxide (1 mmol), dppf (20 mol%, 0.1 mmol),
and palladium(ii) acetate (10 mol%, 0.05 mmol) in dry methanol
(4 mL), after which was added potassium aryltrifluoroborate
(0.55 mmol). The reaction mixture was stirred at room tem-
perature and the consumption of the starting materials was
followed by TLC. Fluorescent side products, that formed as
the reaction proceeded, were visible on the TLC plate under
long-wavelength UV light. The reaction mixture was filtered
through a pad of Celite and the filtrate partitioned between ethyl
acetate and saturated NH4Cl.The organic layer was washed with
saturated NH4Cl (3 × 10 mL), dried over Mg2SO4, and concen-
trated under vacuum. Purification was performed by silica gel
chromatography (100% hexane).
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2-(Anisole)furan 8d
δH (300 MHz, CDCl3) 3.85 (s, 3H), 6.47 (dd, J 3.21, 1.8, 1H),
6.54 (d, J 3.3, 1H), 6.94 (d, J 8.79, 2H), 7.45 (d, J 0.96, 1H), 7.63
(d, J 8.79). δC (75 MHz, CDCl3) 159.0, 154.1, 141.4, 125.2 (2C),
124.1, 114.1 (2C), 111.5, 103.4, 55.3. m/z 174 (78%), 159 (67),
131 (16), 77 (14), 43 (100).
2-(Anisole)thiophene 9d
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δH (300 MHz, CDCl3) 3.81 (s, 3H), 6.89 (d, J 8.73, 2H), 7.01–
7.03 (m, 1H), 7.17–7.23 (m, 2H), 7.52 (d, J 8.73, 2H). δC
(75 MHz, CDCl3) 159.2, 144.4, 127.9, 127.3, 127.2 (2C), 123.8,
122.1, 114.3 (2C), 55.4. m/z 190 (98%), 175 (100), 147 (48),
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Acknowledgement
The authors are grateful to Fundação de Amparo
do Estado de São Paulo (FAPESP) (07/59404-2, 07/51466-9, and
05/59141-6) and Conselho Nacional de Desenvolvimento Científico e
Tecnológico (CNPq) (154976/2006-7) for financial support.
à Pesquisa
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