Palladium-catalyzed selective decarboxylative coupling reaction versus direct C - H arylation for arylation of heteroaromatics

Article abstract of DOI:10.1002/aoc.3037

Conditions for selective palladium-catalyzed decarboxylative 2-arylation of 3-substituted thiophene and furan derivatives bearing an ester at C2 position have been established. By using 2 mol% phosphine-free Pd(OAc)₂ as the catalyst and a mixture of KOH and K₂CO₃ as the bases, in dimethylacetamide, moderate to good yields of the desired 2-arylated products were obtained. A range of functional groups such as nitrile, nitro, formyl or acetyl on the aryl bromides was tolerated. This method allows us to employ in some cases more convenient reactants in terms of cost or physical properties (boiling point) for arylations. Copyright

Full text of DOI:10.1002/aoc.3037

Full Paper
Received: 24 June 2013
Revised: 26 June 2013
Accepted: 29 June 2013
Published online in Wiley Online Library: 23 August 2013
(wileyonlinelibrary.com) DOI 10.1002/aoc.3037
Palladium-catalyzed selective decarboxylative
coupling reaction versus direct C―H arylation
for arylation of heteroaromatics
Haiyan Fua,b, Hua Chena* and Henri Doucetb*
Conditions for selective palladium-catalyzed decarboxylative 2-arylation of 3-substituted thiophene and furan derivatives
bearing an ester at C2 position have been established. By using 2 mol% phosphine-free Pd(OAc)2 as the catalyst and a mixture
of KOH and K2CO3 as the bases, in dimethylacetamide, moderate to good yields of the desired 2-arylated products were
obtained. A range of functional groups such as nitrile, nitro, formyl or acetyl on the aryl bromides was tolerated. This method
allows us to employ in some cases more convenient reactants in terms of cost or physical properties (boiling point) for
arylations. Copyright © 2013 John Wiley & Sons, Ltd.
Keywords: palladium; catalysis; thiophenes; furans; arylation; decarboxylative coupling
improving the regioselectivity for a selective access to 2-arylated
Introduction
3-substituted thiophenes or furans.
Since the pioneering studies of Myers and Goossen,[11,12] using
2-Arylated thiophenes and furans continue to attract the attention
of synthetic organic chemists due to the biological properties of
some of these derivatives. For example, raloxifene is a drug used
to prevent and treat osteoporosis, dantrolene is a muscle relaxant,
and lapatinib is employed against breast cancer (Fig. 1).
carboxylic acids as cross-coupling partners for metal-mediated
decarboxylation reactions, several exciting results on this
research area have been reported.[13,14] However, little is known
on the reactivity of heteroarenes bearing an ester at C2 for
decarboxylation versus direct arylation reactions. From this
consideration, we decided to explore the reactivity of two
types of five-membered ring heteroarenes bearing an ester
at C2: methyl 3-chlorothiophene-2-carboylate and methyl
3-methylfuran-2-carboxylate. They were used as model substrates
to evaluate the regioselectivity of the arylation and to determine
conditions for the selective decarboxylative coupling at C2.
Traditional methods for arylations of thiophenes or furans are
the metal-catalyzed Suzuki, Negishi, Stille or Kumada cross-
coupling reactions.[1] However, these methods required prelimi-
nary synthesis of organometallic compounds, and stoichiometric
amount of metal salts were produced as by-products. In this con-
text, the catalytic direct C―H arylation provides a cost-effective
and environmentally attractive method for the synthesis of such
compounds.[2,3] However, the control of the regioselectivity
remains an essential issue due to the presence of several C―H
bonds with similar reactivity on several heterocycles. For exam-
ple, the direct arylation of 3-substituted thiophenes or furans to
provide the mono-2-arylated products are less effective owing
to the presence of two reactive positions C2 and C5.[4–10] In
2003, Sharp and co-workers demonstrated that the use of Pd
(PPh3)4 in toluene allowed the regioselective arylation at the
2-position of methyl 3-thiophene carboxylate.[4] The reactivity of
3-methoxythiophene for direct C―H arylation was explored by
Borghese and co-workers. They obtained selectively the 2-arylated
thiophenes in 28–60% yields.[5] On the other hand, Bilodeau and
co-workers reported that a mixture of the 2- and 5-phenylated
thiophenes in a 3.3:1 ratio was obtained by using Pd[P(tBu)3]2 as
the catalyst for the arylation of 3-methylthiophene.[6] Similarly,
we have reported examples of palladium-catalyzed arylation of
3-formylthiophene, in which the 2-arylated thiophenes were
produced in 76–86% regioselectivity, together with 5-arylated
thiophenes.[7,8] In 2011, Mori and co-workers reported that the
reaction of 3-hexylthiophene with 4-bromotoluene also gives a
mixture of the C2- and C5-monoarylated thiophenes as well as
the C2,C5-diarylated thiophene.[9] Therefore, there is still room for
Results and Discussion
The reaction of 1-bromonaphthalene with 2 equiv. of methyl
3-chlorothiophene-2-carboxylate was employed as the model
reaction for the optimization of the conditions (Scheme 1 and
Table 1). Based on our previously established conditions for
decarboxylative arylation of 2-arylfuroates,[15] we performed the
reaction at 150°C in the presence of a mixture of 2 equiv. of
KOH associated with 2 equiv. of another base. Initially, the
reaction was carried out in dimethylacetamide (DMA) with
*
Correspondence to: H. Doucet, Institut Sciences Chimiques de Rennes, UMR 6226
CNRS – Université de Rennes ‘Organométalliques, Matériaux et Catalyse’, Campus
de Beaulieu, 35042 Rennes, France. Email: henri.doucet@univ-rennes1.fr;
scuhchen@163.com
a Key Laboratory of Green Chemistry and Technology, Ministry of Education,
College of Chemistry, Sichuan University, Chengdu 610064, China
b Institut Sciences Chimiques de Rennes, UMR 6226 CNRS-Université de Rennes
‘Organométalliques, Matériaux et Catalyse’, 35042 Rennes, France
Appl. Organometal. Chem. 2013, 27, 595–600
Copyright © 2013 John Wiley & Sons, Ltd.

H. Fu et al.
N
N
Cl
O
NH
N
O
O
HN
O
SO2Me
F
O
Lapatinib
HO
N
S
N
O
OH
O
NH
O2N
Raloxifene
Dantrolene
Figure 1. Examples of bioactive thiophene or furan derivatives.
S
[Pd]
S
+
KOH (2 equiv.), base (2
equiv.), solvent, 150°C,
18h
O
S
Cl
3a
Br
Cl
+
OMe
3b
Cl
2
S
1
3d
+
1 equiv.
2 equiv.
Cl
3c
Scheme 1. Palladium-catalyzed arylation of methyl 3-chlorothiophene-2-carboxylate with 1-bromonaphthalene.
1 mol% of PdCl(C3H5)(dppb) [dppb: 1,4-bis(diphenylphosphino)
butane][16] as the catalyst. With K2CO3 or KOAc as the second
base, the 1-bromonaphthalene was completely converted, with
about 11% and 16% naphthalene-homocoupling by-product 3d
produced, respectively, and more than 80% yields of arylation
products 3a and 3b were obtained in both cases (Table 1, entries
1 and 2). Only trace amounts of 2,5-diarylated product 3c were
detected. Although the competing formation of 2- or 5-arylation
products coexists, the decarboxylative arylation at C2 position to
form 3a prevailed over the direct C―H arylation at C5 to give 3b.
However, the amount of C5 arylation product 3b was significant,
as it was produced in 18% and 24% yields, respectively. Interest-
ingly, K2CO3 as the second base seems to be more beneficial
for the decarboxylative arylation at C2 position than KOAc.
1-Bromonaphthalene conversion decreased when Pd(OAc)2 was
employed in place of PdCl(C3H5)(dppb) as the catalyst, but the
regioselectivity was improved with an increase of the C2:C5 ratio
from 3.6 to 7.4 (Table 1, entries 1 and 4). Therefore, in the subse-
quent experiments, Pd(OAc)2 was selected as the catalyst and
K2CO3 as the second base. Increasing the Pd(OAc)2 loading from
1% to 2 mol% enhanced the 1-bromonaphthalene conversion
from 75% to 90% (Table 1, entries 4 and 5). Further optimization
of the condition revealed that both Cs2CO3 and CsOAc as the
second base resulted in relatively lower conversions with about
44–79% substrate recovery. Again, the carbonate base proved
to be more effective than acetate, affording a C2:C5 ratio of 3.0
versus 0.7 with CsOAc. The solvent nature usually plays an impor-
tant role for such reactions. Employing the non-polar solvent
xylene failed to give any substrate conversion (Table 1, entry 8).
Although full conversion was obtained with DMF as the solvent,
a large amount of homocoupling 1-bromonaphthalene 3d
by-product was formed (Table 1, entry 9). It should be noted that,
in all cases, no cleavage of the C―Cl thiophene bond was
detected. Consequently, we employed the following conditions
for the subsequent reactions: 2 mol% Pd(OAc)2 as the catalyst,
a mixture of 2 equiv. of KOH and 2 equiv. of K2CO3 as the bases,
DMA as the solvent, at 150°C.
Having the decarboxylation reaction conditions in hand,
we next explored the scope of this protocol (Tables 2 and 3).
Firstly, the influence of the nature of the aryl bromides for
coupling with methyl 3-chlorothiophene-2-carboxylate was
investigated (Table 2). The system proved to be tolerant to several
functional groups. 4-Bromobenzonitrile, 4-bromoacetophenone,
4-bromobenzaldehyde and 4-bromonitrobenzene were success-
fully coupled with methyl 3-chlorothiophene-2-carboxylate, giving
the corresponding C2-arylated products 4a–7a in moderate to
good yields, from 44% to 66%, with ratios of C2:C5 arylations from
8.8 to 14.5 (Table 2, entries 1–4). The use of electron-rich aryl
bromide, 4-tert-butylbromobenzene, led to a lower conversion of
43%. It is noteworthy that, although only 30% yield of desired
product 8a was obtained, a relatively high regioselectivity could
be achieved with a ratio C2:C5 of 10 (Table 2, entry 5). Selective
2-arylations were also observed using 2-bromonaphthalene and
9-bromoanthracene, resulting in 58% and 73% yields of the
products 9a, 11a respectively (Table 2, entries 6 and 8). The
ortho-substituted aryl bromide, 2-bromobenzonitrile, is less selec-
tive for decarboxylative arylation at the C2 position, as a 48:19 ratio
of C2:C5-arylated products 10a and 10b was obtained (Table 2,
entry 7). Pyridines or quinolines are π-electron-deficient heterocycles
and therefore their oxidative addition to the palladium is, in
general, relatively easy. From such heteroaryl bromides, a similar
reactivity to that of the electron-deficient aryl bromides was expected.
As anticipated, using 3- or 4-bromopyridines, 3-bromoquinoline
and 4-bromoisoquinoline, the decarboxylative coupling products
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Copyright © 2013 John Wiley & Sons, Ltd.
Appl. Organometal. Chem. 2013, 27, 595–600

Palladium-catalyzed selective decarboxylative coupling of heteroarenes
Table 1. Influence of the reaction conditions for palladium-catalysed arylation of methyl 3-chlorothiophene-2-carboxylate with
1-bromonaphthalene (Scheme 1)
Entry
Catalyst (mol%)
Second base
Solvent
Conv. (%)
Yield 3a (%)
Yield 3b (%)
Ratio 3a/3b
1
2
3
4
5
6
7
8
9
PdCl(C3H5)(dppb) (1)
PdCl(C3H5)(dppb) (1)
Pd(OAc)2 (1)
K2CO3
KOAc
DMA
DMA
DMA
DMA
DMA
DMA
DMA
xylene
DMF
100
100
92
65
64
18
24
21
7
3.6
2.6
3.4
7.4
10.1
3.0
0.7
—
KOAc
71 (61)
52
Pd(OAc)2 (1)
K2CO3
K2CO3
Cs2CO3
CsOAc
KOAc
75
Pd(OAc)2 (2)
90
61
6
Pd(OAc)2 (2)
56
21
7
Pd(OAc)2 (2)
21
8
11
—
5
Pd(OAc)2 (2)
0
—
Pd(OAc)2 (2)
K2CO3
100
43
8.6
Conditions: 1-bromonaphthalene (1 mmol), methyl 3-chlorothiophene-2-carboxylate (2 mmol), KOH (2 mmol), second base (2 mmol), 150°C, 18 h,
argon, conversion of 1-bromonaphthalene, gas chromatographic and NMR yields; yield in parenthesis is isolated.
12a–15a were obtained as the major products in 50–89% yields
(Table 2, entries 9–12). Compared with 3- or 4-bromopyridines,
3-bromoquinoline or 4-bromoisoquinoline was expected to give
lower regioselectivities towards C2 arylation due to their steric
hindrance. To our surprise, they exhibited unexpectedly higher C2:
C5 ratios of 17.6 and 22.2, respectively (Table 2, entries 11 and 12).
For comparison, we also carried out the direct C―H arylation
reaction starting from 3-chlorothiophene and 4-bromoisoquinoline.
In this case, a lower C2:C5 ratio of 8 was obtained (Table 2, entry 13).
These results confirm that the presence of the carboxylate group
at the C2 position seems advantageous for improving the
regioselectivity towards C2 arylations.
3-methylfuran, for the synthesis of 2-arylated 3-methylfurans is
particularly attractive as: (i) the much higher boiling point for
methyl 3-methylfuran-2-carboxylate than for 3-methylfuran (b.p.
195°C vs. 65°C) allows reactions to be carried out in classical glass-
ware instead of autoclaves; (ii) methyl 3-methylfuran-2-carboxylate
is available at a more affordable cost than 3-methylfuran.
We were pleased to find that, again, the desired 2-arylated
products 16–21 were regioselectively obtained in all cases. With
this substrate, it should be noted that no significant amounts of
C5-arylation products were detected by gas chromatographic–
mass spectrometric analysis of the crude mixtures. The products
16–21 were obtained in moderate to good yields ranging from
49% to 72% using 2 mol% Pd(OAc)2 catalyst. Again, the reaction
tolerates electron-withdrawing substituents, congested aryl
bromides or pyridyl bromides.
To evaluate the substrate scope with respect to the heteroarene,
the reactivity of methyl 3-methylfuran-2-carboxylate was exam-
ined (Fig. 2 and Table 3). The use of this substrate, instead of
Table 2. Scope of the palladium-catalyzed decarboxylative coupling of methyl 3-chlorothiophene-2-carboxylate with aryl bromides
Entry
Aryl bromide or R
Conv. (%)
Yield in 2-arylated product a (%)
Ratio a/b
1
4-CN
100
100
100
93
4a 58
5a 44
11.6
8.8
2
4-COMe
4-CHO
4-NO2
4-tBu
3
6a 58
14.5
13.2
10
4
7a 66
5
43
8a 30
6
2-Bromonaphthalene
2-CN
81
9a 58
11.6
2.5
7
100
100
100
89
10a 48
11a 73
12a 60
13a 50
14a 88
15a 89
15a 88
8
9-Bromoanthracene
4-Bromopyridine, hydrochloride
3-Bromopyridine
6.1
9
15
10
11
12
13
5
3-Bromoquinoline
4-Bromoisoquinoline
4-Bromoisoquinoline
100
100
100
17.6
22.2
8a
Conditions: Pd(OAc)2 (0.02 mmol), aryl bromide (1 mmol), methyl 3-chlorothiophene-2-carboxylate (2 mmol), KOH (2 mmol), KOAc (2 mmol), 18h,
150°C, conversion of the aryl bromide.
aPd(OAc)2 (0.1 mmol), 4-bromoisoquinoline (1 mmol), 3-chlorothiophene (2.0 mmol), KOAc (2 mmol), 18 h, 130°C.
Appl. Organometal. Chem. 2013, 27, 595–600
Copyright © 2013 John Wiley & Sons, Ltd.
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H. Fu et al.
Table 3. Scope of the palladium-catalysed decarboxylative coupling of methyl 3-methylfuran-2-carboxylate with aryl bromides
Entry
Aryl bromide or R
Conv. (%)
Yield in 2-arylated product (%)
1
2
3
4
5
6
4-NO2
100
100
100
100
100
76
16 49
17 50
18 72
19 59
20 50
21 52
1-Bromonaphthalene
9-Bromoanthracene
4-Bromopyridine, hydrochloride
3-Bromoquinoline
4-Bromoisoquinoline
Conditions: Pd(OAc)2 (0.02 mmol), aryl bromide (1 mmol), methyl 3-methylfuran-2-carboxylate (2 mmol), KOH (2 mmol), KOAc (2 mmol), 18h, 150°C,
conversion of the aryl bromide.
Preparation of the PdCl(C3H5)(dppb) catalyst[16]
Mp: 36°C
CO2Me
Expensive
Bp: 65°C
requires
An oven-dried 40 ml Schlenk tube equipped with a magnetic
stirring bar under argon atmosphere was charged with [Pd(C3H5)Cl]2
(0.182 g, 0.5 mmol) and dppb (0.426 g, 1 mmol). Anhydrous
dichloromethane (10 ml) was added, and the solution was stirred
at room temperature for 20 min. The solvent was removed under
vacuum. The yellow powder obtained was used without purifica-
tion. 31P NMR (81 MHz, CDCl3) δ = 19.3 (s).
O
O
autoclave
Figure 2. Reactions with 3-methylfuran-2-carboxylate do not require use
of autoclaves.
Conclusion
General Procedure for Coupling Reactions
We have investigated the palladium-catalyzed decarboxylative
coupling reaction versus direct arylation of 3-substituted thio-
phene- or furan-2-carboxylates. We found that, using a mixture
of KOH and K2CO3 as the bases in DMA with 2 mol% Pd(OAc)2
as the catalyst and under argon atmosphere at 150°C, a
decarboxylative arylation reaction occurred preferentially to give
the C2-arylated products. With various aryl bromides, the desired
2-arylated products were obtained in moderate to good yields.
These results demonstrated that these heteroaryl 2-carboxylates
can be employed as the coupling partners for selective palla-
dium-catalyzed 2-arylation of heteroarenes. Owing to the higher
boiling point of the ester-substituted heteroarenes, the handling
of some of these heteroarenes is more convenient. Finally, this
strategy proved to display a good functional group tolerance
on the aryl bromide coupling partner.
In a typical experiment, the aryl bromide (1 mmol), methyl
3-chlorothiophene-2-carboxylate (0.354 g, 2 mmol) or methyl
3-methylfuran-2-carboxylate (0.280 g, 2 mmol), KOH (0.112 g,
2 mmol), K2CO3 (0.276 g, 2 mmol) and Pd(OAc)2 (see tables) were
dissolved in DMA (3 ml) under an argon atmosphere. The reaction
mixture was stirred at 150°C (see tables) for 16 h. The solution
was diluted with water (15 ml) and the product was then
extracted three times with ethyl acetate or dichloromethane. The
combined organic layer was dried over MgSO4 and the solvent
was removed in vacuum. The products were purified by silica gel
column chromatography.
3-Chloro-2-(1-naphthyl)thiophene (3a)
1H NMR (400 MHz, CDCl3): δ 7.95–7.88 (m, 2H, CCCHCHCHCH),
7.79 (d, J = 7.7 Hz, 1H, CCHCHCHC), 7.58-7.45 (m, 4H,
CCHCHCHCCHCHCHCHC), 7.41 (d, J = 5.3 Hz, 1H, SCH), 7.09 (d,
J = 5.3 Hz, 1H, SCHCH). 13C NMR (100 MHz, CDCl3): δ 134.4 (SCCCl),
133.6 (CCHCHCHC), 132.1 (CCHCHCHC), 129.4 (CCHCHCHCCHCHCHCH),
129.3 (CCCCHCHCHCH), 128.3 (CCHCHCHCCHCHCH), 128.0 (SCHCH),
126.5 (SCHCH), 126.1 (CCHCHCHCCHCHCH), 126.0 (CCHCHCHCCHCHCH),
125.1 (CCHCHCHCCHCHCHCH), 124.2 (C―Cl). Elemental analysis:
calcd (%) for C14H9ClS (244.74): C 68.71, H 3.71; found: C 68.88, H 3.94.
Experimental
General
All reactions were run under argon in Schlenk tubes using
vacuum lines. DMA, DMF or xylene, analytical grade, were not
distilled before use. The bases Cs2CO3, CsOAc, K2CO3, KOAc and
Pd(OAc)2 were used as received. Commercial aryl bromides,
methyl 3-chlorothiophene-2-carboxylate and methyl 3-methylfuran-
3-Chloro-2,5-di(1-naphthyl)thiophene (3c)
1
2-carboxylate were used without purification. H and 13C spectra
This compound was obtained in low yield.
were recorded with a Bruker 400 MHz spectrometer in CDCl3
solutions. Chemical shifts are reported in ppm relative to CDCl3
1H NMR (400 MHz, CDCl3): δ 8.43 (d, J = 7.7 Hz, 1H, naphthyl),
8.03 (d, J = 7.7 Hz, 1H, naphthyl), 8.00–7.88 (m, 4H, naphthyl),
7.70–7.65 (m, 2H, naphthyl), 7.64–7.50 (m, 6H, naphthyl), 7.31 (s,
1H, thiophene). 13C NMR (100 MHz, CDCl3): δ 141.3 (SCC), 134.6
1
(7.25 for H NMR and 77.0 for 13C NMR). Flash chromatography
was performed on silica gel (230–400 mesh).
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Appl. Organometal. Chem. 2013, 27, 595–600

Palladium-catalyzed selective decarboxylative coupling of heteroarenes
(Ar), 133.9 (Ar), 133.7 (Ar), 132.0 (Ar), 131.4 (Ar), 131.3 (Ar), 129.5
(Ar), 129.4 (naphthyl CH), 129.2 (Ar), 129.0 (naphthyl CH), 128.5
(naphthyl CH), 128.4 (naphthyl CH), 128.1 (naphthyl CH), 127.8
(naphthyl CH), 126.8 (naphthyl CH), 126.6 (naphthyl CH), 126.3
(naphthyl CH), 126.2 (naphthyl CH), 126.1 (naphthyl CH), 125.4
(naphthyl CH), 125.3 (naphthyl CH), 125.1 (naphthyl CH), 123.7
(SCCH).
126.6 (CCHCHCCHCH), 126.5 (CCHCCHCH), 126.4 (CCHCCHCH),
124.1 (CCHCHC), 121.2 (SCCCl). Elemental analysis: calcd (%) for
C14H9ClS (244.74): C 68.71, H 3.71; found: C 68.71, H 3.58.
2-(3-Chlorothiophen-2-yl)-benzonitrile (10a)
1H NMR (400 MHz, CDCl3): δ 7.71 (d, J = 7.9 Hz, 1H, CCHCHCH),
7.59 (t, J = 7.5 Hz, 1H, CCHCHCH), 7.50 (d, J = 7.9 Hz, 1H,
CNCCHCH), 7.46 (t, J = 7.5 Hz, 1H, CNCCHCH), 7.35 (d, J = 5.3
Hz, 1H, SCH), 6.9 (d, J = 5.3 Hz, 1H, SCHCH). 13C NMR (100 MHz,
CDCl3): δ 135.6 (SCCCl), 133.5 (CCHCHCH), 132.5 (CNCCHCH),
131.9 (CNCCHCH), 131.7 (CCCN), 128.9 (CCHCHCH), 128.5
(SCHCH), 126.2 (SCHCH), 124.9 (SCCCl), 117.7 (CCN), 113.8 (CHCN).
Elemental analysis: calcd (%) for C11H6ClNS (219.69): C 60.14, H
2.75; found: C 60.31, H 2.88.
4-(3-Chlorothiophen-2-yl)-benzonitrile (4a)
1H NMR (400 MHz, CDCl3): δ 7.74 (d, J = 8.5 Hz, 2H, CHCHCCN),
7.63 (d, J = 7.5 Hz, 2H, CHCHCCN), 7.29 (d, J = 5.3 Hz, 1H, SCHCH),
6.97 (d, J = 5.3 Hz, 1H, SCHCH). 13C NMR (100 MHz, CDCl3): δ 136.8
(C-1′ on phenyl), 133.9 (SCCCl), 132.4 (CHCHCCN), 129.8 (SCHCH),
128.9 (CHCHCCN), 125.5 (SCHCH), 123.0 (SCH), 118.6 (CN), 111.4
(CHCN). Elemental analysis: calcd (%) for C11H6ClNS (219.69): C 60.14,
H 2.75; found: C 60.07, H 2.87.
2-(9-Anthryl)-3-chlorothiophene (11a)
1H NMR (400 MHz, CDCl3): δ 8.46 (s, 1H, CHCCHCCH), 7.95 (d, J = 8.0 Hz,
2H, CHCHCCHCCHCH), 7.63 (d, J = 8.0 Hz, 2H, CHCHCCCCHCH), 7.47
(d, J = 5.3 Hz, 1H, SCHCH), 7.40–7.32 (m, 4H, CHCHCHCCCCHCHCH),
7.13 (d, J = 5.3 Hz, 1H, SCHCH). 13C NMR (100 MHz, CDCl3): δ 132.5
(SCCCl), 131.7 (CHCHCCHCCHCH), 131.3 (Ar), 128.9 (SCHCH), 128.6
(Ar), 128.0 (SCHCH), 126.4 (Ar), 126.3 (Ar), 126.1 (Ar), 126.0 (Ar),
125.4 (Ar), 125.2 (SCCCl). Elemental analysis: calcd (%) for C18H11ClS
(294.80): C 73.34, H 3.76; found: C 73.50, H 3.59.
2-(4-Acetylphenyl)-3-chlorothiophene (5a)
1H NMR (400 MHz, CDCl3): δ 7.94 (d, J = 8.5 Hz, 2H, CHCHCCOCH3),
7.72 (d, J = 7.5 Hz, 2H, CHCHCCOCH3), 7.27 (d, J = 5.3 Hz, 1H, SCH),
6.96 (d, J = 5.3 Hz, 1H, SCHCH), 2.56 (s, 3H, COCH3). 13C NMR (100
MHz, CDCl3): δ 196.0 (COMe), 136.8 (C-1′ on phenyl), 136.2 (SCCCl),
134.9 (CCOCH3), 129.7 (SCHCH), 128.8 (CHCHCCOCH3), 128.7
(CHCHCCOCH3), 125.0 (SCHCH2), 122.5 (SCCCl), 26.0 (COCH3).
Elemental analysis: calcd (%) for C12H9ClOS (236.72): C 60.89, H 3.83;
found: C 60.99, H 3.74.
4-(3-Chlorothiophen-2-yl)-pyridine (12a)
1H NMR (400 MHz, CDCl3): δ 8.59 (d, J = 4.8 Hz, 2H, CHN), 7.56 (d,
J = 4.8 Hz, 2H, CHCHN), 7.31 (d, J = 5.3 Hz, 1H, SCH), 6.98 (d, J = 5.3 Hz,
1H, SCHCH). 13C NMR (100 MHz, CDCl3): δ 150.2 (CHN), 139.8 (C-1′
on pyridyl), 133.0 (SCCCl), 130.1 (SCHCH), 125.7 (SCH), 123.6 (SCCCl),
122.3 (CHCHN). Elemental analysis: calcd (%) for C9H6ClNS (195.67):
C 55.24, H 3.09; found: C 55.14, H 3.04.
2-(4-Formylphenyl)-3-chlorothiophene (6a)
1H NMR (400 MHz, CDCl3): δ 9.95 (s, 1H, CHO), 7.88 (d, J = 8.5 Hz,
2H, CHCHCCHO), 7.79 (d, J = 8.5 Hz, 2H, CHCHCCHO), 7.29
(d, J = 5.3 Hz, 1H, SCH), 6.97 (d, J = 5.3 Hz, 1H, SCHCH). 13C NMR
(100 MHz, CDCl3): δ 191.6 (CHO), 138.2 (C-1′ on phenyl), 135.4
(SCCCl), 134.7 (CCHO), 130.0 (CHCHCCHO), 129.8 (SCHCH), 129.0
(CHCHCCHO), 125.4 (SCH), 122.9 (SCCCl). Elemental analysis: calcd
(%) for C11H7ClOS (222.69): C 59.33, H 3.17; found: C 59.27, H 3.29.
3-(3-Chlorothiophen-2-yl)-pyridine (13a)
1H NMR (400 MHz, CDCl3): δ 8.82 (s, 1H, CCHN), 8.53 (d, J = 4.8 Hz,
1H, NCHCH), 7.93 (d, J = 7.9 Hz, 1H, CCHCHCHN), 7.30 (dd, J = 7.9,
4.8 Hz, 1H, CCHCHCHN), 7.28 (d, J = 5.3 Hz, 1H, SCH), 6.98 (d,
J = 5.3 Hz, 1H, SCHCH). 13C NMR (100 MHz, CDCl3): δ 149.3 (CCHN),
149.0 (NCHCH), 135.8 (CCHCHCHN), 132.4 (SCCCl), 129.5 (SCHCH),
128.5 (CCHCHCHN), 125.0 (SCHCH), 123.3 (CCHCHCHN), 122.8
(SCCCl). Elemental analysis: calcd (%) for C9H6ClNS (195.67): C
55.24, H 3.09; found: C 55.08, H 3.32.
2-(4-Nitrophenyl)-3-chlorothiophene (7a)
1H NMR (400 MHz, CDCl3): δ 8.20 (d, J = 8.5 Hz, 2H, CHCHCNO2),
7.78 (d, J = 8.5 Hz, 2H, CHCHCNO2), 7.32 (d, J = 5.3 Hz, 1H, SCH),
6.99 (d, J = 5.3 Hz, 1H, SCHCH). 13C NMR (100 MHz, CDCl3): δ
147.1 (CNO2), 138.7 (C-1′ on phenyl), 133.5 (SCCCl), 130.0
(SCHCH), 129.1 (CHCHCNO2), 125.9 (SCHCH), 123.9 (CHCHCNO2),
123.5 (SCCCl). Elemental analysis: calcd (%) for C10H6ClNO2S
(239.68): C 50.11, H 2.52; found: C 50.04, H 2.41.
3-(3-Chlorothiophen-2-yl)-quinoline (14a)
1H NMR (400 MHz, CDCl3): δ 9.10 (s, 1H, CCHNC), 8.32 (s, 1H,
CCHC), 8.04 (d, J = 8.0 Hz, 1H, NCCHCH), 7.76 (d, J = 8.0 Hz, 1H,
CCHCCHCH), 7.64 (t, J = 7.9 Hz, 1H, NCCHCHCHCH), 7.48 (t,
J = 7.9 Hz, 1H, NCCHCHCHCH), 7.26 (d, J = 5.3 Hz, 1H, SCH), 6.98
(d, J = 5.3 Hz, 1H, SCHCH). 13C NMR (75 MHz, CDCl3): δ 150.7 (Ar),
147.2 (Ar), 136.9 (Ar), 134.4 (Ar), 125.3 (Ar), 123.4 (Ar), 123.0 (Ar),
121.0 (Ar), 118.6 (Ar), 113.4 (Ar). Elemental analysis: calcd (%) for
C13H8ClNS (245.73): C 63.54, H 3.28; found: C 63.67, H 3.18.
2-(4-tert-Butylphenyl)-3-chlorothiophene (8a)
1H NMR (400 MHz, CDCl3): δ 7.53 (d, J = 7.5 Hz, 2H, CHCHCtBu),
7.37 (d, J = 7.5 Hz, 2H, CHCHCtBu), 7.16 (d, J = 5.3 Hz, 1H, SCHCH),
6.90 (d, J = 5.3 Hz, 1H, SCHCH), 1.28 (s, 9H, tBu). 13C NMR (100
MHz, CDCl3): δ 151.2 (CtBu), 136.3 (SCCCl), 129.3 (C-1′ on phenyl),
129.2 (SCHCH), 128.3 (CHCHCtBu), 125.6 (SCHCH), 123.5
(CHCHCtBu), 121.0 (SCCCl), 34.7 (CtBu), 31.3 (―C(CH3)3). Elemental
analysis: calcd (%) for C14H15ClS (250.79): C 67.05, H 6.03; found: C
67.00, H 5.89.
4-(3-Chlorothiophen-2-yl)-isoquinoline (15a)
1H NMR (400 MHz, CDCl3): δ 9.29 (s, 1H, CCHNCHCCH), 8.55 (s, 1H,
CCHNCHCCH), 8.02 (d, J = 8.0 Hz, 1H, CCHNCHCCH), 7.78 (d,
J = 8.0 Hz, 1H, CCCHCHCHCHCCHNC), 7.60 (t, J = 7.9 Hz, 1H,
CCCHCHCHCHCCHNC), 7.62 (t, J = 7.9 Hz, 1H, CCCHCHCHCHCCHNC),
7.44 (d, J = 5.3 Hz, 1H, SCHCH), 7.10 (d, J = 5.3 Hz, 1H, SCHCH).
13C NMR (100 MHz, CDCl3): δ 153.5 (CCHNCHCCH), 144.9
(CCHNCHCCH), 134.6 (SCCCl), 131.0 (CCCHCHCHCHCCHNC), 130.7
(CCCHCHCHCHCCHNC), 128.4 (SCHCH), 128.3 (CCCHCHCHCHCCHNC),
3-Chloro-2-(2-naphthyl)thiophene (9a)
1H NMR (400 MHz, CDCl3): δ 8.03 (s, 1H, CCHCCHCH), 7.80–7.62 (m, 4H,
CCHCCHCHCHCHCCHCH), 7.40–7.35 (m, 2H, CCHCCHCHCHCHCCHCH),
7.16 (d, J = 5.3 Hz, 1H, SCH), 6.90 (d, J = 5.3 Hz, 1H, SCHCH). 13C NMR
(100 MHz, CDCl3): δ 136.2 (SCCCl), 133.2 (CCHCCCHCH), 132.8
(CCHCCCHCH), 129.7 (CCHCCCHCH), 129.4 (CCHCHCC), 128.3
(CCHCHCCHCH), 128.2 (CCHCCHCH), 127.8 (SCHCH), 127.7 (SCHCH),
Appl. Organometal. Chem. 2013, 27, 595–600
Copyright © 2013 John Wiley & Sons, Ltd.
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H. Fu et al.
128.0 (SCHCH), 127.6 (CCCHCHCHCHCCHN), 126.0 (CCCHCHCHCHCCHN),
125.2 (CCCHCHCHCHCCHNC), 125.0 (CCCHCHCHCHCCHNC), 123.5
(SCCCl). Elemental analysis: calcd (%) for C13H8ClNS (245.73): C
63.54, H 3.28; found: C 63.50, H 3.09.
146.4 (OCCCH3), 143.7 (CCHNCHCCHCHCHCH), 142.4 (OCHCH), 134.3
(CCHNCHCCHCHCHCH), 130.7 (CCHNCHCCHCHCHCH), 128.6
(CCHNCHCCHCHCHCHC), 127.9 (CCHNCHCCHCHCHCHC), 127.3
(CCHNCHCCHCHCHCHC), 125.3 (CCHNCHCCHCHCHCHC), 122.4
(CCHNCHCCHCHCHCHC), 119.3 (OCCCH3), 114.1 (OCHCH), 11.0
(CCH3). Elemental analysis: calcd (%) for C14H11NO (209.24):
C 80.36, H 5.30; found: C 80.27, H 5.44.
3-Methyl-2-(4-nitrophenyl)-furan (16)
1H NMR (400 MHz, CDCl3): δ 8.19 (d, J = 8.5 Hz, 2H, CHCHCNO2),
7.69 (d, J = 8.5 Hz, 2H, CHCHCNO2), 7.19 (s, 1H, OCH), 6.32 (s,
1H, OCHCH), 2.22 (s, 3H, CCH3). 13C NMR (100 MHz, CDCl3): δ
146.6 (CNO2), 145.4 (OCCCH3), 142.6 (OCHCH), 137.6 (C-1′ on
phenyl), 124.9 (CHCHCNO2), 124.1 (CHCHCNO2), 120.8 (OCCCH3),
116.1 (OCHCH), 12.4 (CCH3). Elemental analysis: calcd (%) for
C11H9NO3 (203.19): C 65.02, H 4.46; found: C 65.11, H 4.37.
Acknowledgments
We are grateful to the Chinese Scholarship Council for a grant
to H.Y.F. We thank CNRS and ‘Rennes Metropole’ for providing
financial support.
3-Methyl-2-(1-naphthyl)furan (17)
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δ
7.90–7.76 (m, 3H,
CCCHCHCHCHCCHCHCH), 7.50–7.38 (m, 5H, CCCHCHCHCHCCHCHCH
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2-(9-Anthryl)-3-methylfuran (18)
1H NMR (400 MHz, CDCl3): δ 8.54 (s, 1H, anthryl), 8.04 (d, J = 8.0 Hz,
2H, anthryl), 7.74 (d, J = 8.0 Hz, 2H, anthryl), 7.66 (s, 1H, furan),
7.50–7.40 (m, 4H, anthryl), 6.57 (s, 1H, furan), 1.88 (s, 3H, Me).
13C NMR (100 MHz, CDCl3): δ 146.7 (Ar), 142.3 (Ar), 131.8 (Ar),
131.3 (Ar), 128.5 (Ar), 128.4 (Ar), 126.3 (Ar), 126.1 (Ar), 126.0 (Ar),
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1H NMR (400 MHz, CDCl3): δ 8.53 (d, J = 4.8 Hz, 2H, CHN), 7.43
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3-(3-Methylfuran-2-yl)-quinoline (20)
1H NMR (400 MHz, CDCl3): δ 9.19 (s, 1H, CHN), 8.22 (s, 1H,
NCHCCHC), 8.02 (d, J = 8.0 Hz, 1H, NCCH), 7.77 (d, J = 8.0 Hz,
1H, NCCCHCH), 7.60 (t, J = 7.9 Hz, 1H, NCCHCH), 7.48 (t, J = 7.9
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127.0 (NCCCHCH), 125.2 (NCCCH), 118.4 (CCH3), 115.4 (OCHCH),
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C 80.36, H 5.30; found: C 80.49, H 5.19.
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4-(3-Methylfuran-2-yl)-isoquinoline (21)
1H NMR (400 MHz, CDCl3): δ 9.16 (s, 1H, CCHNCHCCHCHCHCH), 8.47 (s,
1H, CCHNCHCCHCHCHCH), 7.97–7.90 (m, 2H, CCHNCHCCHCHCHCH),
7.62 (t, J = 8.0 Hz, 1H, CCHNCHCCHCHCHCH), 7.55 (t, J = 8.0 Hz, 1H,
CCHNCHCCHCHCHCH), 7.49 (s, 1H, OCHCH), 6.40 (s, 1H, OCHCH), 2.07
(s, 3H, CCH3). 13C NMR (100 MHz, CDCl3): δ 152.6 (CCHNCHCCHCHCHCH),
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Copyright © 2013 John Wiley & Sons, Ltd.
Appl. Organometal. Chem. 2013, 27, 595–600