A simple and efficient synthesis of (hetero)aryl-substituted benzothiazolyl or benzoxazolyl furan, thiophene and N -methylpyrrole derivatives through a palladium-catalyzed regioselective C-H bond arylation

Article abstract of DOI:10.1055/s-0034-1379021

The synthesis of 2-(hetero)aryl-5-benzothiazol-2-yl or -benzoxazol-2-ylfuran, -thiophene, and -1-methylpyrrole derivatives was accomplished in two steps. 2-(Benzothiazol-2-yl)- or 2-benzoxazol-2-ylfuran, -thiophene, or -1-methylpyrrole were synthesized by

Full text of DOI:10.1055/s-0034-1379021

PAPER
▌3341
paper
A Simple and Efficient Synthesis of (Hetero)Aryl-Substituted Benzothiazolyl
or Benzoxazolyl Furan, Thiophene and N-methylpyrrole Derivatives through
a Palladium-Catalyzed Regioselective C–H Bond Arylation
Palladium-Catalyzed Regioselective C–H Bond Arylation
Fatma Abdellaoui,a,b Chiraz Youssef,c Hamed Ben Ammar,*b Jean-François Soulé,a Henri Doucet*a
a
Institut des Sciences Chimiques de Rennes, UMR 6226 CNRS-Université de Rennes 1 ‘Organométalliques, Matériaux et Catalyse’,
Campus de Beaulieu, 35042 Rennes, France
Fax +33(2)23236939; E-mail: henri.doucet@univ-rennes1.fr
b
Laboratoire de Synthèse Organique Asymétrique et Catalyse Homogène, (UR 11ES56) Université de Monastir, Faculté des Sciences de
Monastir, Avenue de l’Environnement, Monastir 5000, Tunisia
c
Laboratoire de Chimie Organique Physique (UR11ES74) Université de Sfax, Faculté des Sciences de Sfax, Route de la Soukra, 3038 Sfax,
Tunisia
Received: 13.06.2014; Accepted after revision: 04.08.2014
Until now, the preparation of these derivatives involved
Abstract: The synthesis of 2-(hetero)aryl-5-benzothiazol-2-yl or
multistep synthesis including transition-metal-catalyzed
-benzoxazol-2-ylfuran, -thiophene, and -1-methylpyrrole deriva-
arylation from organometallic reagents earlier synthe-
sized (e.g., Suzuki, Stille, Negishi, Kumada, Hiyama, etc.)
tives was accomplished in two steps. 2-(Benzothiazol-2-yl)- or 2-
benzoxazol-2-ylfuran, -thiophene, or -1-methylpyrrole were syn-
thesized by coupling a heteroaryl aldehyde and either 2-mercap- or they were synthesized using highly functionalized
starting materials.6g,8 These procedures can not be consid-
ered as ecofriendly and they should be replaced by more
tophenol or 2-aminophenol. Then, they were successfully arylated
with a wide range of aryl bromides using a phosphine-free palladi-
um protocol; regioselective arylation at C5 of furan, thiophene, or
sustainable chemistry.
1-methyl-1H-pyrrole was observed in all cases. This reaction toler-
In the last two decades, the area of the transition-metal-
catalyzed direct C–H bond (hetero)arylation reactions
with (hetero)aryl halides or pseudohalides, which gener-
ate less waste compared to traditional methods, has earned
significant attention.9 The direct functionalization of het-
eroarenes has been well studied and several protocols for
the direct arylation of furans, thiophenes, or pyrroles have
emerged in the literature,10 including low catalyst load-
ing,11 using green solvents,12 or less reactive aryl chlo-
rides as coupling partners.13 The major contribution was
made using palladium chemistry, however, some reports
focused on alternative metals such as copper,14 iridium,15
or cobalt.16 To the best of our knowledge, to date there is
no general method for the direct arylation of furans, thio-
phenes, and 1-methylpyrroles bearing a benzothiazole or
benzoxazole substituent.
ates a wide variety of substituents on the aryl bromides as well as
heteroaryl bromides.
Key words: arylation, catalysis, C–H bond activation, heterocy-
cles, palladium
Benzothiazol-2-yl- or benzoxazol-2-yl-substituted furan,
thiophene, and 1-methylpyrrole derivatives have a similar
structure, which is composed of a heteroaromatic core
linked to either a benzothiazole or a benzoxazole moiety.
They have multiple applications, and have long been
known to be biologically active (Scheme 1). As examples,
benzoxazolyl-heteroaryl derivatives such as DB828 or
DB320 with furan or 1-methylpyrrole frameworks, re-
spectively, are chemotherapeutic agents for the treatment
of Trypanosoma evansi, which causes surra, an animal
pathogenic protozoan infection.1 Similar structures could
also be used for specific recognition of DNA sequences,2
or as cysteine proteases inhibitors.3 2-[2-(5-Heteroaryl-
thiophen-2-yl)benzoxazol-5-yl]propanoic acid deriva-
tives I have anti-inflammatory activity.4 The bis-
substituted amidinobenzothiazoles II have anti-HIV ac-
tivity.5 Moreover, benzothiazolylfuran, -thiophene, or -1-
methylpyrrole derivatives III or IV also have physically
interesting characteristics due to their specific phospho-
rescence properties.6 In addition, these structures might be
used as polydentate ligands, when arylated with suitable
aryls containing nitrogen or other coordinating atoms.7
Due to the wide and interesting properties of aryl-substi-
tuted benzothiazolyl- or benzoxazolylfuran, -thiophene,
and -1-methylpyrrole derivatives, the development of a
simple and efficient synthesis is necessary in order to fa-
cilitate the construction of libraries of compounds. Here-
in, we described a convergent synthesis of these
derivatives from simple and inexpensive starting materi-
als (Scheme 1, bottom). These syntheses include regiose-
lective C–H bond activation as the key step to build up the
molecular diversity.
We started our investigation by the preparation of het-
eroarenes substituted by a benzothiazole or a benzoxazole
(Scheme 2). Several methods for the preparation of such
structures are reported in the literature.17 The most conve-
nient pathway is the condensation of either 2-mercap-
tophenol or 2-aminophenol with diverse heteroaromatic
aldehydes under oxidative conditions.18 Indeed, the ben-
SYNTHESIS 2014, 46, 3341–3350
Advanced online publication: 10.09.2014
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X
DOI: 10.1055/s-0034-1379021; Art ID: ss-2014-z0365-op
© Georg Thieme Verlag Stuttgart · New York

3342
F. Abdellaoui et al.
PAPER
HN
HN
R
O
N
S
NH2
NH2
NH
NH
HO2C
Me
O
N
O
O
N
N
H2N
H2N
I
N
R
DB828
DB320
R
N
H.HCl
Me
N
S
N
N
S
N
X
S
N
X
HCl•HN
II
X = S or O
III
IV
X = S or O
retrosynthetic pathway
X
selective
C–H arylation
XH
Ar
Y
H
Y
Y
X
N
OHC
NH2
N
X = S or O
Y = S or O or NMe
Scheme 1 Relevant structures in the literature and retrosynthesis analysis of benzothiazolyl- or benzoxazolylfuran, -thiophene, and -1-meth-
ylpyrrole derivatives
zothiazolylfuran derivatives 1, 3, and 5 were obtained by With these starting materials in hands, we started to study
the condensation of 2-mercaptophenol with furfural, 3-fu- their palladium-catalyzed direct arylations using aryl bro-
raldehyde, or 5-methylfurfural in dimethyl sulfoxide at mides as coupling partners. We decided to employ our
high temperature, following a reported procedure.19 All previous conditions, a phosphine-free palladium proce-
these compounds were isolated in high yields after simple dure10b using palladium(II) acetate at low loading (only
recrystallization. Following the conditions reported by 0.5 mol%) in the presence of potassium acetate as base (2
Reyes,20 the corresponding benzoxazolylfurans 2 and 4 equiv) in N,N-dimethylacetamide (DMA) at 150 °C. First-
were synthesized in N,N-dimethylformamide with the as- ly, the direct arylation of 2-(furan-2-yl)benzothiazole (1)
sistance of one equivalent of potassium cyanide. Similar was investigated (Table 1). We found that the reaction
procedures were applied using thiophene-2-carbaldehyde proceed regioselectively at C5 of the furan and is tolerant
or 1-methyl-1H-pyrrole-2-carbaldehyde instead of furfu- of a wide range of functional groups on the aryl bromide
ral to allow the formation of the desired products 6, 8, and (e.g., cyano, nitro, formyl, ketone, and ester) (entries 1–4
9 in high yields. Under these conditions, 2-(thiophen-2- and 6). On the other hand, the reaction was completely in-
yl)benzoxazole (7) was obtained in low yield, so we syn- hibited with methoxy group in the meta position. This is
thesized it from thiophene-2-carbonyl chloride in N-meth- probably due to the more difficult oxidative addition of
ylpyrrolidin-2-one at 200 °C, following a reported this aryl bromide (entry 7). The reaction proceeded very
procedure.21
well with ortho-substituted aryl bromide 2-bromobenzo-
nitrile giving the desired coupling product 16 in 87% yield
(entry 8). Heteroaryl bromides 3-bromopyridine, 3-bro-
moquinoline, and 5-bromopyrimidine also reacted with 2-
(furan-2-yl)benzothiazole (1) to give 17–19 in 62%, 71%,
and 72% yields, providing an efficient synthesis for new
ligands with multicoordination sites (entries 9–11).
Recently, we have reported the direct arylation of
thiophenes,22 benzofurans,23 or furans24 using benzenesul-
fonyl chlorides as coupling partners. The optimized con-
SH
(a) or (b)
X
N
X
X
+
•
OHC
NH2
X
N
O
X
N
O
X
N
O
3, X = S (a) 88%
4, X = O (b) 79%
1, X = S (a) 87%
2, X = O (b) 92%
5, X = S (a) 90%
ditions
for
this
desulfitative
cross-coupling,
X
N
S
X
N
N
PdCl2(MeCN)2 (5 mol%) in the presence of three equiva-
lents of lithium carbonate in dioxane at 140 °C for 40
hours, allowed the formation of the coupling product 13
between 1 and 4-nitrobenzenesulfonyl chloride (entry 5);
the same regioisomer was obtained as under the previous
reaction conditions, however the desired product 13 was
isolated in slightly higher yield.
8, X = S (a) 94%
9, X = O (c) 76%
6, X = S (a) 68%
7, X = O (c) 77%
Scheme 2 Preparation of heteroarenes substituted by benzothiazole
or benzoxazole. Reagents and conditions: (a) DMSO, 195 °C, 2 h; (b)
KCN (1 equiv), DMF, r.t., 12 h; (c) corresponding acyl chloride was
used instead of aldehyde, NMP, 200 °C, 12 h.
Synthesis 2014, 46, 3341–3350
© Georg Thieme Verlag Stuttgart · New York

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Palladium-Catalyzed Regioselective C–H Bond Arylation
3343
Table 1 Palladium-Catalyzed Direct C5-Arylation of 2-(Furan-2-
yl)benzothiazole (1)a
Table 2 Palladium-Catalyzed Direct C5-Arylation of 2-(Furan-2-
yl)benzoxazole (2)a
S
O
S
O
(het)
Ar
(het)
Ar
+
+ Br
Br
O
O
O
O
N
N
N
N
(het)
Ar
(het)
Ar
2 (1.5 equiv)
1 (1.5 equiv)
Entry
Ar
4-NCC6H4
Product
Yield (%)
Entry
Ar
Product
Yield (%)
1
2
3
4
5
6
7
20
21
22
23
24
25
26
77
52
68
64
58
76
71
1
2
3
4
5b
6
7
8
9
4-NCC6H4
4-AcC6H4
10
11
12
13
13
14
15
16
17
18
19
67
57
64
59
69
66
0
4-MeO2CC6H4
4-HOCC6H4
4-AcC6H4
4-HOCC6H4
4-O2NC6H4
4-O2NC6H4
4-MeO2CC6H4
3-MeOC6H4
2-NCC6H4
4-O2NC6H4
2-NCC6H4
pyridin-3-yl
a Reaction conditions: Pd(OAc)2 (0.5 mol%), KOAc (2 equiv), 150
°C, 16 h.
87
62
71
72
pyridin-3-yl
quinolin-3-yl
pyrimidin-5-yl
10
11
X
N
O
(a) or (b)
Z
R
+
a Reaction conditions: Pd(OAc)2 (0.5 mol%), KOAc (2 equiv), 150
°C, 16 h.
Z = Br, R = CHO
or
Z = SO2Cl, R = NO2
3 X = S, (1.5 equiv)
or
4 X = O, (1.5 equiv)
b Reaction conditions: PdCl2(MeCN)2 (5 mol%), 4-O2NC6H4SO2Cl
(1.5 equiv), 1 (1 equiv), Li2CO3 (3 equiv), dioxane, 140 °C, 40 h.
Scheme 3 Reactivity of 2-(5-methylfuran-2-yl)benzoxazothizole (3)
and 2-(5-methylfuran-2-yl)benzoxazole (4) in palladium-catalyzed
direct arylations. Reagents and conditions: (a) ArBr (1 equiv),
Pd(OAc)2 (0.5 mol%), KOAc (2 equiv), 150 °C, 16 h; (b) ArSO2Cl
(1.5 equiv), PdCl2(MeCN)2 (5 mol%), Li2CO3 (3 equiv), dioxane, 140
°C, 40 h.
We investigated next the reactivity of 2-(furan-2-yl)benz-
oxazole (2) in the palladium-catalyzed direct arylation
with aryl bromides (Table 2). Again, 0.5 mol% of palladi-
um(II) acetate was able to promote the direct arylation of
2 in the presence of two equivalents of potassium acetate
in N,N-dimethylacetamide. The substrate scope of the re-
action with 2 as the heteroarene was similar to the scope
with compound 1. Again, functional groups such as cya-
no, ester, formyl, ketone, and nitro were tolerated (entries
1–5). The ortho-substituted aryl bromide 2-bromobenzo-
nitrile afforded the desired coupling product 25 in 76%
yield (entry 6). The heteroaryl bromide 3-bromopyridine
gave the desired coupling product 26 in high yield (entry
7).
amounts of a monoarylated product by GC-MS analysis,
which could not be isolated and identified.
Having successfully arylated 2-(furan-2-yl)benzothiazole
(1) using different aryl bromides, we attempted to extend
the scope of the reaction to 3-substituted furans such as 2-
(furan-3-yl)benzothiazole (5). However, 5 was complete-
ly unreactive under our conditions with both an aryl bro-
mide and an arenesulfonyl chloride as the coupling
partners; only starting materials were recovered at the end
of the reaction (Scheme 4, top). In order to get more infor-
mation on the reactivity of 5, we performed a competitive
reaction between one equivalent of both 2-(furan-3-
yl)benzothiazole (5) and 2-(furan-2-yl)benzothiazole (1)
in the presence of one equivalent of 4-bromobenzalde-
hyde or one equivalent of 4-nitrobenzenesulfonyl chlo-
ride; no reaction occurred, and even 1 was not arylated
(Scheme 4, bottom). This result suggests that 5 is a poi-
soning agent for the palladium catalyst.
We next explored the reactivity of 5-methylfuran bearing
a benzothiazole or a benzoxazole at C2 in the palladium-
catalyzed direct arylation (Scheme 3). It is important to
note that with the previous substrates, the arylation took
place selectively at C5, which is now blocked by a methyl
substituent, hence the arylation might occur at C3 or/and
C4 as we have previously shown using simpler 2,5-disub-
stituted furans.25 However, using 2-(5-methylfuran-2-
yl)benzothiazole (3) as the substrate did not give arylated
product whatever the coupling partners (i.e., aryl bromide
or benzenesulfonyl chloride). Using 2-(5-methylfuran-2-
yl)benzoxazole (4) as the substrate gave only trace
Next, we turned our attention to the reactivity of thio-
phene derivatives. Firstly, we attempted to arylate 2-(thio-
phen-2-yl)benzothiazole (6) with 4-bromobenzaldehyde
© Georg Thieme Verlag Stuttgart · New York
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3344
F. Abdellaoui et al.
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Table 3 Palladium-Catalyzed Direct C5-Arylation of 2-(Thiophen-
2-yl)benzoxazole (7)a
(a) or (b)
S
+
Z
R
N
O
O
O
(het)
Ar
+ Br
S
S
5 (1.5 equiv)
N
N
Z = Br, R = CHO
or
(het)
Ar
Z = SO2Cl, R = NO2
7 (1.5 equiv)
(a) or (b)
5
1
+
+
Z
R
(1 equiv)
(1 equiv)
Entry
Ar
Product
Yield (%)
Scheme 4 Reactivity of 2-(furan-3-yl)benzothiazole (5) in palladi-
um-catalyzed direct arylations. Reagents and conditions: (a)
Pd(OAc)2 (0.5 mol%), KOAc (2 equiv), 150 °C, 16 h; (b) ArSO2Cl
(1.5 equiv), PdCl2(MeCN)2 (5 mol%), Li2CO3 (3 equiv), dioxane, 140
°C, 16 h.
1
2
3b
4
5
6
7
4-OHCC6H4
4-O2NC6H4
27
28
28
29
30
31
32
54
48
0
4-O2NC6H4SO2Cl
2-NCC6H4
63
71
73
67
as the coupling partner. However, no reaction occurred
using the previous palladium catalytic system (Scheme 5,
top). Other conditions, such as higher catalyst loading [2
mol% of Pd(OAc)2], or with other sources of palladium
such as PdCl(allyl)(dppb) (2 mol%), were also unsuccess-
ful in this transformation. A competitive reaction between
2-(furan-2-yl)benzothiazole (1) and 2-(thiophen-2-
yl)benzothiazole (6) gave the arylated product 12 in 51%
yield, while 6 was fully recovered at the end of the reac-
tion (Scheme 5, bottom). This result suggested that 6 does
not poison the catalytic system but its reactivity is poor in
this palladium-catalyzed direct arylation.
pyrimidin-5-yl
pyridin-3-yl
quinolin-3-yl
a Reaction conditions: (a) Pd(OAc)2 (0.5 mol%), KOAc (2 equiv), 150
°C, 16 h.
b PdCl2(MeCN)2 (5 mol%), 4-O2NC6H4SO2Cl (1.5 equiv), 7 (1 equiv)
Li2CO3 (3 equiv), dioxane, 140 °C, 40 h.
Finally, we investigated the direct arylation of 1-methyl-
1H-pyrrole substituted by either benzothiazole or benzox-
azole at C2 (Table 4). In the case of 2-(1-methyl-1H-pyr-
rol-2-yl)benzothiazole (8), the regioselective arylation at
C5 proceeded smoothly with a wide range of aryl bro-
mides including quite sensitive functional groups such as
ketone or cyano and also with heteroaryl bromide deriva-
tives (entries 1–4). With 2-(1-methyl-1H-pyrrol-2-yl)ben-
zoxazole (9), the desired arylated products were obtained
in moderate to high yields. Again, nitro, aldehyde, or
cyano functional groups were tolerated (entries 5–7). He-
teroaryl bromides such as 3-bromoquinoline or 5-bromo-
pyrimidine allowed the formation of the desired coupling
products 40 and 41 in 56% and 61% yields, respectively
(entries 8 and 9).
(a) or (b) or (c) or (d)
S
Z
R
+
S
N
Z = Br, R = CHO
or
Z = SO2Cl, R = NO2
6 (1.5 equiv)
6 (100% recovered)
1 (35% recovered)
12 (51% based on 1)
(a)
6
+
1
Br
CHO
+
(1 equiv)
(1 equiv)
(1 equiv)
Scheme 5 Reactivity of 2-(thiophen-2-yl)benzothiazole (6) in palla-
dium-catalyzed direct arylations. Reagents and conditions: (a) ArBr
(1 equiv), Pd(OAc)2 (0.5 mol%), KOAc (2 equiv), 150 °C, 16 h; (b)
ArSO2Cl (1.5 equiv), PdCl2(MeCN)2 (5 mol%), Li2CO3 (3 equiv), di- In summary, we report here a very efficient method for the
oxane, 140 °C, 40 h; (c) ArBr (1 equiv), Pd(OAc)2 (2 mol%), KOAc
(2 equiv), 150 °C, 16 h; (d) ArBr (1 equiv), PdCl(allyl)(dppb) (2
mol%), KOAc (2 equiv), 150 °C, 16 h.
synthesis of C5-(hetero)arylated furan, thiophene, and 1-
methylpyrrole derivatives bearing benzothiazolyl or
benzoxazolyl moieties at C2. These syntheses involve two
steps from inexpensive and commercially available start-
In contrast to the thiophene bearing a benzothiazole moi-
ety at C2, the thiophene derivative 7, which has a benzox-
azole moiety, reacted well in direct arylations using aryl
bromides as coupling partners (Table 3). Under the previ-
ous conditions, a wide variety of 5-arylated 2-(thiophen-
2-yl)benzoxazole derivatives were synthesized in moder-
ate to high yields (entries 1, 2, and 4–7). The direct aryl-
ation via desulfitative coupling from 4-nitrobenzene-
sulfonyl chloride was also tested. However, no arylated
product was observed, and only the starting materials
were recovered (entry 3).
ing materials. The C–H bond functionalization key step
proceeds with ligand-free palladium(II) acetate catalyst
and potassium acetate as base in N,N-dimethylacetamide,
and affords regioselectively the C5-arylated furans, thio-
phenes, and 1-methylpyrroles. This procedure tolerates a
wide variety of substituents on the aryl bromides such as
nitro, cyano, ester, ketone, formyl, and also pyridines de-
rivatives. Generally, the heteroarenes substituted by a
benzoxazole moiety display better reactivity than those
substituted by a benzothiazole unit. Moreover, palladium-
catalyzed desulfitative arylations of furan derivatives
have been also demonstrated. Thirty new products have
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Palladium-Catalyzed Regioselective C–H Bond Arylation
3345
6 (1.47 g, 68%). This is a known compound and the spectral data are
Table 4 Palladium-Catalyzed Direct C5-Arylation of 2-(1-Methyl-
1H-pyrrol-2-yl)benzothiazole (8) and 2-(1-Methyl-1H-pyrrol-2-
yl)benzoxazole (9)a
identical to those reported in the literature.26
2-(1-Methyl-1H-pyrrol-2-yl)benzothiazole (8)
Following the general procedure from 2-aminothiophenol (1.63 g,
13 mmol) and 1-methyl-1H-pyrrole-2-carbaldehyde (0.92 mL, 10
mmol) gave 8 (2.01 g, 94%) as a white solid; mp 62–66 °C.
1H NMR (400 MHz, CDCl3, 25 °C): δ = 8.0 (dd, J = 2.0, 8.0 Hz, 1
H), 7.86 (d, J = 8.0 Hz, 1 H), 7.48 (t, J = 8.0 Hz, 1 H), 7.36 (t, J =
7.5 Hz, 1 H), 6.88 (td, J = 2.0, 4.0 Hz, 1 H), 6.85 (t, J = 2.0 Hz, 1
H), 6.26 (ddd, J = 1.5, 2.5, 4.0 Hz, 1 H), 4.19 (s, 3 H).
X
X
Me
Me
(het)
Ar
+ Br
N
N
N
N
(het)
Ar
8 X = S, (1.5 equiv)
9 X = O, (1.5 equiv)
13C NMR (100 MHz, CDCl3, 25 °C): δ = 160.2, 154.1, 133.7, 127.7,
126.3, 125.6, 124.2, 122.2, 120.8, 114.6, 108.5, 36.9.
Entry
X
Ar
Product
Yield (%)
Anal. Calcd for C12H10N2S (214.29): C, 67.26; H, 4.70. Found: C,
67.47; H, 4.33.
1
2
3
4
5
6
7
8
9
S
4-AcC6H4
33
34
35
36
37
38
39
40
41
65
77
64
53
62
67
83
56
61
S
2-NCC6H4
2-Heteroarylbenzoxazoles; General Procedure
S
pyridin-3-yl
pyrimidin-5-yl
4-O2NC6H4
4-HOCC6H4
2-NCC6H4
A mixture of 2-aminophenol (10 mmol), aldehyde (10 mmol), and
KCN (10 mmol) in DMF (25 mL) was stirred at r.t. Once the reac-
tion was complete, the mixture was diluted with water (30 mL) and
extracted with EtOAc (2 × 30 mL). The extracts were combined and
the solvent was removed under reduced pressure. The obtained sol-
id was then recrystallized (boiling EtOH–H2O, 50:50) to give the
pure compound.
S
O
O
O
O
O
2-(Furan-2-yl)benzoxazole (2)
quinolin-3-yl
pyrimidin-5-yl
Following the general procedure from 2-aminophenol (1.09 g, 10
mmol) and furfural (0.80 mL, 10 mmol) gave 2 (1.70 g, 92%). This
is a known compound and the spectral data are identical to those re-
ported in the literature.28
a Reaction conditions: (a) Pd(OAc)2 (0.5 mol%), KOAc (2 equiv), 150
°C, 16 h.
2-(5-Methylfuran-2-yl)benzoxazole (4)
Following the general procedure from 2-aminophenol (1.09 g, 10
mmol) and 5-methylfurfural (1 mL, 10 mmol) gave 4 (1.57 g, 79%)
as an orange solid; mp 68–72 °C.
1H NMR (400 MHz, CDCl3, 25 °C): δ = 7.72 (d, J = 7.0 Hz, 1 H),
7.53–7.50 (m, 1 H), 7.33–7.30 (m, 2 H), 7.15 (d, J = 4.0 Hz, 1 H),
6.19 (d, J = 4.0 Hz, 1 H), 2.44 (s, 3 H).
been synthesized by this procedure, which could find fur-
ther applications in diverse fields of chemistry such as
medicine, or materials chemistry.
13C NMR (100 MHz, CDCl3, 25 °C): δ = 157.1, 156.1, 150.6, 142.3,
141.4, 125.4, 125.2, 120.4, 116.1, 110.9, 109.2, 14.4.
DMA (99%) was purchased from Acros. KOAc (99%) and
Pd(OAc)2 (98%) were purchased from Alfa Aesar. These com-
pounds were not purified before use.
Anal. Calcd for C12H9NO2 (199.21): C, 72.35; H, 4.55. Found: C,
71.98; H, 4.87.
2-Heteroarylbenzothiazoles; General Procedure
A mixture of aldehyde (10 mmol), 2-aminothiophenol (13 mmol),
and DMSO (27 mL) was heated at 195 °C for 2 h. The mixture was
cooled to 50 °C and then poured into cold water, and the precipitate
was collected. The pale-brown solid was obtained after column
chromatography.
2-(Thiophen-2-yl)benzoxazole (7)
A mixture 2-aminophenol (1.09 g, 10 mmol) and thiophene-2-car-
bonyl chloride (1.1 mL, 10 mmol) was stirred in NMP (10 mL) at
200 °C for 2 h. Once the reaction was complete, the mixture was di-
luted with water (30 mL) and extracted with EtOAc (2 × 30 mL).
The extracts were combined and the solvent was removed under re-
duced pressure. The obtained solid was then recrystallized (boiling
EtOH–H2O, 50:50) to give pure 7 (1.55 g, 77%). This is a known
compound and the spectral data are identical to those reported in the
literature.29
2-(Furan-2-yl)benzothiazole (1)
Following the general procedure from 2-aminothiophenol (1.63 g,
13 mmol) and furfural (0.80 mL, 10 mmol) gave 1 (1.74 g, 87%).
This is a known compound and the spectral data are identical to
those reported in the literature.26
2-(1-Methyl-1H-pyrrol-2-yl)benzoxazole (9)
2-(5-Methylfuran-2-yl)benzothiazole (3)
A mixture 2-aminophenol (1.09 g, 10 mmol) and 1-methyl-1H-pyr-
role-2-carbonyl chloride (1.16 mL, 10 mmol) was stirred in NMP
(10 mL) at 200 °C for 2 h. Once the reaction was complete, the mix-
ture was diluted with water (30) and extracted with EtOAc (2 × 30
mL). The extracts were combined and the solvent was removed un-
der reduced pressure. The obtained solid was then recrystallized
(boiling EtOAc–H2O, 50:50) to give pure 9 (1.50 g, 76%) as a
brown solid; mp 90–94 °C.
1H NMR (400 MHz, CDCl3, 25 °C): δ = 7.70 (d, J = 8.0 Hz, 1 H),
7.54 (d, J = 8.0 Hz, 1 H), 7.36–7.32 (m, 2 H), 7.12 (d, J = 3.0 Hz, 1
H), 6.89 (br s, 1 H), 6.29 (d, J = 3.0 Hz, 1 H), 4.18 (s, 3 H).
Following the general procedure from 2-aminothiophenol (1.63 g,
13 mmol) and 5-methylfurfural (1 mL, 10 mmol) gave 3 (1.89 g,
88%). This is a known compound and the spectral data are identical
to those reported in the literature.27
2-(Furan-3-yl)benzothiazole (5)
Following the general procedure from 2-aminothiophenol (1.63 g,
13 mmol) and 3-furaldehyde (0.86 mL, 10 mmol) gave 5 (1.81 g,
90%). This is a known compound and the spectral data are identical
to those reported in the literature.27
2-(Thiophen-2-yl)benzothiazole (6)
Following the general procedure from 2-aminothiophenol (1.63 g,
13 mmol) and thiophene-2-carbaldehyde (0.92 mL, 10 mmol) gave
13C NMR (75 MHz, CDCl3, 25 °C): δ = 157.4, 149.1, 141.9, 128.0,
123.7, 120.2, 118.8, 114.6, 109.5, 108.3, 36.5.
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2014, 46, 3341–3350

3346
F. Abdellaoui et al.
PAPER
Anal. Calcd for C12H10N2O (198.23): C, 72.71; H, 5.09. Found: C,
72.44; H, 5.28.
2-{5-[4-(Methoxycarbonyl)phenyl]furan-2-yl}benzothiazole
(14)
Following the general procedure from 1 (0.302 g, 1.5 mmol) and
methyl 4-bromobenzoate (0.215 g, 1 mmol) gave 14 (0.221 g, 66%)
as a yellow solid; mp 174–178 °C.
1H NMR (400 MHz, CDCl3, 25 °C): δ = 8.11 (d, J = 8.0 Hz, 2 H),
8.07 (d, J = 8.0 Hz, 1 H), 7.92 (d, J = 8.0 Hz, 1 H), 7.86 (d, J = 8.0
Hz, 2 H), 7.51 (t, J = 7.5 Hz, 1 H), 7.40 (t, J = 7.5 Hz, 1 H), 7.32 (d,
J = 3.5 Hz, 1 H), 6.97 (d, J = 3.5 Hz, 1 H), 3.95 (s, 3 H).
13C NMR (100 MHz, CDCl3, 25 °C): δ = 166.8, 157.3, 155.1, 154.1,
149.2, 134.6, 133.7, 130.4, 129.8, 126.8, 125.6, 124.3, 123.4, 121.8,
113.8, 110.1, 52.4.
Direct Arylation Reaction; General Procedure
A mixture of aryl bromide (1 mmol), benzothiazolyl- or benzoxaz-
olyl-substituted furan, thiophene, or 1-methyl-1H-pyrrole deriva-
tives (1.5 mmol), and KOAc (0.196 g, 2 mmol) in DMA (2 mL) in
the presence of Pd(OAc)2 (0.56 mg, 0.0025 mmol) was heated at
150 °C for 16 h under argon to afford the arylation product after
evaporation of the solvent and filtration (silica gel).
2-[5-(4-Cyanophenyl)furan-2-yl]benzothiazole (10)
Following the general procedure from 1 (0.302 g, 1.5 mmol) and 4-
bromobenzonitrile (0.80 g, 1 mmol) gave 10 (0.202 g, 67%) as an
orange solid; mp 190–194 °C.
1H NMR (400 MHz, CDCl3, 25 °C): δ = 8.08 (d, J = 8.0 Hz, 1 H),
7.91 (d, J = 8.0 Hz, 1 H), 7.89 (d, J = 8.5 Hz, 2 H), 7.72 (d, J = 8.5
Hz, 2 H), 7.52 (t, J = 7.5 Hz, 1 H), 7.42 (t, J = 7.5 Hz, 1 H), 7.32 (d,
J = 3.5 Hz, 1 H), 7.00 (d, J = 3.5 Hz, 1 H).
Anal. Calcd for C19H13NO3S (335.38): C, 68.05; H, 3.91. Found: C,
67.98; H, 4.12.
2-[5-(2-Cyanophenyl)furan-2-yl]benzothiazole (16)
Following the general procedure from 1 (0.302 g, 1.5 mmol) and 2-
bromobenzonitrile (0.181 g, 1 mmol) gave 16 (0.263 g, 87%) as a
pale yellow solid; mp 178–182 °C.
1H NMR (400 MHz, CDCl3, 25 °C): δ = 8.07 (dd, J = 8.0, 11.0 Hz,
2 H), 7.93 (d, J = 8.0 Hz, 1 H), 7.77 (dd, J = 1.5, 8.0 Hz, 1 H), 7.69
(ddd, J = 1.5, 7.5, 8.0 Hz, 1 H), 7.52 (ddd, J = 1.5, 7.0, 8.0 Hz, 1 H),
7.47 (d, J = 4.0 Hz, 1 H), 7.42 (dt, J = 5.0, 8.0 Hz, 2 H), 7.36 (d, J =
4.0 Hz, 1 H).
13C NMR (100 MHz, CDCl3, 25 °C): δ = 157.0, 154.1, 154.0, 149.8,
134.6, 133.7, 133.0, 132.9, 127.0, 125.8, 124.8, 123.5, 119.0, 113.8,
111.7, 111.0.
Anal. Calcd for C18H10N2OS (302.35): C, 71.51; H, 3.33. Found: C,
71.68; H, 3.17.
13C NMR (100 MHz, CDCl3, 25 °C): δ = 156.9, 154.0, 151.6, 149.3,
134.6, 134.5, 133.2, 132.1, 128.2, 126.7, 126.6, 125.5, 123.3, 121.8,
118.8, 113.4, 112.9, 107.5.
2-[5-(4-Acetylphenyl)furan-2-yl]benzothiazole (11)
Following the general procedure from 1 (0.302 g, 1.5 mmol) and 4-
bromoacetophenone (0.199 g, 1 mmol) gave 11 (0.182 g, 57%) as a
yellow solid; mp 170–174 °C.
1H NMR (400 MHz, CDCl3, 25 °C): δ = 8.06 (d, J = 8.0 Hz, 1 H),
8.02 (d, J = 8.5 Hz, 2 H), 7.91 (d, J = 8.0 Hz, 1 H), 7.86 (d, J = 8.5
Hz, 2 H), 7.50 (t, J = 7.5 Hz, 1 H), 7.39 (t, J = 7.5 Hz, 1 H), 7.30 (d,
J = 3.5 Hz, 1 H), 6.97 (d, J = 3.5 Hz, 1 H), 2.62 (s, 3 H).
Anal. Calcd for C18H10N2OS (302.35): C, 71.51; H, 3.33. Found: C,
71.68; H, 3.67.
2-[5-(Pyridin-3-yl)furan-2-yl]benzothiazole (17)
Following the general procedure from 1 (0.302 g, 1.5 mmol) and 3-
bromopyridine (96 μL, 1 mmol) gave 17 (0.172 g, 62%) as a brown
solid; mp 182–186 °C.
1H NMR (400 MHz, CDCl3, 25 °C): δ = 9.03 (s, 1 H), 8.55 (d, J =
4.5 Hz, 1 H), 8.07–8.03 (m, 2 H), 7.89 (d, J = 8.0 Hz, 1 H), 7.49 (t,
J = 7.5 Hz, 1 H), 7.40–7.33 (m, 2 H), 7.29 (d, J = 3.5 Hz, 1 H), 6.91
(d, J = 3.5 Hz, 1 H).
13C NMR (100 MHz, CDCl3, 25 °C): δ = 198.0, 157.8, 155.6, 154.7,
150.0, 127.2, 135.3, 134.4, 129.8, 127.4, 126.2, 125.0, 124.0, 122.4,
114.4, 110.8, 27.4.
Anal. Calcd for C19H13NO2S (319.38): C, 71.45; H, 4.10. Found: C,
71.62; H, 4.33.
13C NMR (100 MHz, CDCl3, 25 °C): δ = 156.4, 153.3, 152.4, 148.5,
148.4, 145.2, 134.0, 130.7, 126.0, 125.3, 124.7, 123.0, 122.6, 121.0,
112.8, 108.5.
2-[5-(4-Formylphenyl)furan-2-yl]benzothiazole (12)
Following the general procedure from 1 (0.302 g, 1.5 mmol) and 4-
bromobenzaldehyde (0.185 g, 1 mmol) gave 12 (0.195 g, 64%) as
an orange solid; mp 180–184 °C.
1H NMR (400 MHz, CDCl3, 25 °C): δ = 10.03 (s, 1 H), 8.08 (d, J =
8.0 Hz, 1 H), 7.95 (s, 4 H), 7.92 (d, J = 8.0 Hz, 1 H), 7.52 (t, J = 8.0
Hz, 1 H), 7.41 (t, J = 8.0 Hz, 1 H), 7.33 (d, J = 3.5 Hz, 1 H), 7.02 (d,
J = 3.5 Hz, 1 H).
Anal. Calcd for C16H10N2OS (278.33): C, 69.05; H, 3.62. Found: C,
68.87; H, 4.01.
2-[5-(Quinolin-3-yl)furan-2-yl]benzothiazole (18)
Following the general procedure from 1 (0.302 g, 1.5 mmol) and 3-
bromoquinoline (136 μL, 1 mmol) gave 18 (0.233 g, 71%) as a dark
red solid; mp 128–132 °C.
1H NMR (400 MHz, CDCl3, 25 °C): δ = 9.25 (s, 1 H), 8.89 (s, 1 H),
8.50 (d, J = 8.5 Hz, 1 H), 8.06 (dd, J = 8.0, 12.0 Hz, 2 H), 7.91 (d,
J = 8.0 Hz, 1 H), 7.83 (t, J = 7.5 Hz, 1 H), 7.68 (t, J = 7.5 Hz, 1 H),
7.51 (t, J = 7.5 Hz, 1 H), 7.42–7.37 (m, 2 H), 7.00 (d, J = 3.0 Hz, 1
H).
13C NMR (100 MHz, CDCl3, 25 °C): δ = 191.6, 157.1, 154.7, 154.1,
149.6, 135.9, 135.0, 134.6, 130.6, 126.9, 125.7, 124.8, 123.4, 121.8,
113.8, 110.9.
Anal. Calcd for C18H11NO2S (305.35): C, 70.80; H, 3.63. Found: C,
71.04; H, 3.59.
2-[5-(4-Nitrophenyl)furan-2-yl]benzothiazole (13)
Following the general procedure from 1 (0.302 g, 1.5 mmol) and 1-
bromo-4-nitrobenzene (0.202 g, 1 mmol) gave 13 (0.190 g, 59%) as
a brown solid; mp 230–234 °C.
13C NMR (100 MHz, CDCl3, 25 °C): δ = 157.4, 154.1, 153.5, 153.3,
149.6, 142.7, 134.6, 132.6, 131.7, 128.7, 128.5, 127.8, 126.8, 125.5,
124.6, 123.4, 121.8, 121.5, 113.2, 112.8.
1H NMR (400 MHz, CDCl3, 25 °C): δ = 8.31 (d, J = 8.0 Hz, 2 H),
8.08 (d, J = 8.5 Hz, 1 H), 7.93 (d, J = 8.0 Hz, 3 H), 7.53 (t, J = 7.5
Hz, 1 H), 7.43 (t, J = 7.5 Hz, 1 H), 7.34 (d, J = 3.5 Hz, 1 H), 7.05 (d,
J = 3.5 Hz, 1 H).
13C NMR (100 MHz, CDCl3, 25 °C): δ = 156.9, 154.2, 153.8, 150.2,
147.4, 135.5, 134.7, 127.1, 125.9, 125.0, 124.7, 123.6, 121.97,
114.0, 111.7.
Anal. Calcd for C20H12N2OS (328.39): C, 73.15; H, 3.68. Found: C,
72.98; H, 3.99.
2-[5-(Pyrimidin-5-yl)furan-2-yl]benzothiazole (19)
Following the general procedure from 1 (0.302 g, 1.5 mmol) and 5-
bromopyrimidine (0.159 g, 1 mmol) gave 19 (0.201 g, 72%) as a
yellow solid; mp 212–216 °C.
1H NMR (400 MHz, CDCl3, 25 °C): δ = 9.18 (s, 1 H), 9.13 (s, 2 H),
8.07 (d, J = 8.0 Hz, 1 H), 7.92 (d, J = 8.0 Hz, 1 H), 7.52 (t, J = 8.0
Anal. Calcd for C17H10N2O3S (322.34): C, 63.35; H, 3.13. Found: C,
63.28; H, 2.94.
Synthesis 2014, 46, 3341–3350
© Georg Thieme Verlag Stuttgart · New York

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Palladium-Catalyzed Regioselective C–H Bond Arylation
3347
Hz, 1 H), 7.41 (t, J = 8.0 Hz, 1 H), 7.33 (d, J = 3.0 Hz, 1 H), 7.01 (d,
J = 3.0 Hz, 1 H).
13C NMR (100 MHz, CDCl3, 25 °C): δ = 157.7, 156.5, 153.8, 152.3,
150.0, 149.8, 134.4, 126.8, 125.6, 124.2, 123.3, 121.7, 113.2, 110.5.
1H NMR (400 MHz, CDCl3, 25 °C): δ = 8.31 (d, J = 8.0 Hz, 2 H),
8.00 (d, J = 8.0 Hz, 2 H), 7.81 (dd, J = 3.0, 6.0 Hz, 1 H), 7.61 (dd,
J = 3.0, 6.0 Hz, 1 H), 7.41–7.39 (m, 3 H), 7.07 (d, J = 4.0 Hz, 1 H).
13C NMR (100 MHz, CDCl3, 25 °C): δ = 155.0, 154.8, 150.6, 147.6,
143.9, 142.0, 135.3, 126.1, 125.5, 125.3, 124.7, 120.7, 116.8, 111.2,
111.0.
Anal. Calcd for C15H9N3OS (279.32): C, 64.50; H, 3.25. Found: C,
64.38; H, 3.51.
Anal. Calcd for C17H10N2O4 (306.27): C, 66.67; H, 3.29. Found: C,
66.34; H, 3.41.
2-[5-(4-Cyanophenyl)furan-2-yl]benzoxazole (20)
Following the general procedure from 2 (0.277 g, 1.5 mmol) and 4-
bromobenzonitrile (0.182 g, 1 mmol) gave 20 (0.220 g, 77%) as a
yellow solid; mp 222–226 °C.
1H NMR (400 MHz, CDCl3, 25 °C): δ = 7.80 (d, J = 8.5 Hz, 2 H),
7.68 (dd, J = 3.0, 6.0 Hz, 1 H), 7.59 (d, J = 8.5 Hz, 2 H), 7.47 (dd,
J = 3.0, 6.0 Hz, 1 H), 7.29–7.24 (m, 3 H), 6.87 (d, J = 4.0 Hz, 1 H).
13C NMR (100 MHz, CDCl3, 25 °C): δ = 154.7, 154.6, 150.2, 143.1,
141.6, 133.2, 132.6, 125.6, 125.0, 124.8, 120.2, 118.4, 116.4, 111.7,
110.6, 110.1.
2-[5-(2-Cyanophenyl)furan-2-yl]benzoxazole (25)
Following the general procedure from 2 (0.277 g, 1.5 mmol) and 2-
bromobenzonitrile (0.181 g, 1 mmol) gave 25 (0.217 g, 76%) as a
pale yellow solid; mp 159–163 °C.
1H NMR (400 MHz, CDCl3, 25 °C): δ = 8.20 (d, J = 8.0 Hz, 1 H),
7.81–7.79 (m, 1 H), 7.76 (d, J = 8.0 Hz, 1 H), 7.70 (t, J = 8.0 Hz, 1
H), 7.61–7.59 (m, 1 H), 7.50 (d, J = 4.0 Hz, 1 H), 7.42 (d, J = 8.0
Hz, 1 H), 7.42 (d, J = 4.0 Hz, 1 H), 7.40–7.38 (m, 2 H).
13C NMR (100 MHz, CDCl3, 25 °C): δ = 154.8, 152.5, 150.3, 142.8,
141.8, 134.3, 133.2, 132.0, 128.4, 126.9, 125.7, 125.1, 120.4, 118.7,
116.5, 112.6, 110.7, 107.8.
Anal. Calcd for C18H10N2O2 (286.28): C, 75.52; H, 3.52. Found: C,
75.38; H, 3.79.
2-{5-[4-(Methoxycarbonyl)phenyl]furan-2-yl}benzoxazole (21)
Following the general procedure from 2 (0.277 g, 1.5 mmol) and
methyl 4-bromobenzoate (0.215 g, 1 mmol) gave 21 (0.166 g, 52%)
as a pale yellow solid; mp 208–212 °C.
1H NMR (400 MHz, CDCl3, 25 °C): δ = 8.09 (d, J = 8.0 Hz, 2 H),
7.90 (d, J = 8.0 Hz, 2 H), 7.78 (dd, J = 3.0, 6.0 Hz, 1 H), 7.57 (dd,
J = 3.0, 6.0 Hz, 1 H), 7.38–7.34 (m, 3 H), 6.95 (d, J = 3.5 Hz, 1 H),
3.93 (s, 3 H).
Anal. Calcd for C18H10N2O2 (286.28): C, 75.52; H, 3.52. Found: C,
75.87; H, 3.41.
2-[5-(Pyridin-3-yl)furan-2-yl]benzoxazole (26)
Following the general procedure from 2 (0.277 g, 1.5 mmol) and 3-
bromopyridine (96 μL, 1 mmol) gave 26 (0.186 g, 71%) as a dark
red solid; mp 127–131 °C.
1H NMR (400 MHz, CDCl3, 25 °C): δ = 9.05 (s, 1 H), 8.56 (br s, 1
H), 8.10 (d, J = 7.5 Hz, 1 H), 7.77 (dd, J = 3.0, 6.0 Hz, 1 H), 7.57–
7.53 (m, 1 H), 7.38–7.30 (m, 4 H), 6.92 (d, J = 4.0 Hz, 1 H).
13C NMR (100 MHz, CDCl3, 25 °C): δ = 155.0, 154.2, 150.3, 149.5,
146.1, 142.8, 141.8, 131.8, 125.8, 125.6, 125.1, 123.8, 120.3, 116.5,
110.7, 108.8.
13C NMR (100 MHz, CDCl3, 25 °C): δ = 166.8, 156.1, 155.2, 150.4,
142.8, 141.9, 133.5, 130.4, 130.0, 125.7, 125.2, 124.5, 120.4, 116.7,
110.8, 109.5, 52.4.
Anal. Calcd for C19H13NO4 (319.31): C, 71.47; H, 4.10. Found: C,
71.69; H, 4.33.
Anal. Calcd for C16H10N2O2 (262.26): C, 73.27; H, 3.84. Found: C,
73.61; H, 3.99.
2-[5-(4-Formylphenyl)furan-2-yl]benzoxazole (22)
Following the general procedure from 2 (0.277 g, 1.5 mmol) and 4-
bromobenzaldehyde (0.185 g, 1 mmol) gave 22 (0.196 g, 68%) as a
yellow solid; mp 188–192 °C.
1H NMR (400 MHz, CDCl3, 25 °C): δ = 10.0 (s, 1 H), 7.97 (d, J =
8.0 Hz, 2 H), 7.91 (d, J = 8.0 Hz, 2 H), 7.79–7.77 (m, 1 H), 7.57–
7.55 (m, 1 H), 7.37–7.33 (m, 3 H), 6.89 (d, J = 4.0 Hz, 1 H).
13C NMR (100 MHz, CDCl3, 25 °C): δ = 191.7, 155.8, 155.1, 150.5,
143.3, 142.0, 136.1, 134.9, 130.6, 125.9, 125.3, 125.1, 120.5, 116.8,
110.9, 110.4.
2-[5-(4-Formylphenyl)thiophen-2-yl]benzoxazole (27)
Following the general procedure from 7 (0.302 g, 1.5 mmol) and 4-
bromobenzaldehyde (0.185 g, 1 mmol) gave 27 (0.165 g, 54%) as a
yellow solid; mp 186–190 °C.
1H NMR (400 MHz, CDCl3, 25 °C): δ = 10.0 (s, 1 H), 7.91 (d, J =
7.5 Hz, 2 H), 7.88 (d, J = 4.0 Hz, 1 H), 7.79 (d, J = 7.5 Hz, 2 H),
7.75–7.72 (m, 1 H), 7.54–7.52 (m, 1 H), 7.48 (d, J = 4.0 Hz, 1 H),
7.36–7.34 (m, 2 H).
13C NMR (100 MHz, CDCl3, 25 °C): δ = 191.2, 158.4, 150.5, 147.1,
142.0, 138.9, 135.9, 130.9, 130.6, 130.5, 126.3, 125.9, 124.4, 124.9,
120.0, 110.5.
Anal. Calcd for C18H11NO3 (289.28): C, 74.73; H, 3.83. Found: C,
75.02; H, 3.79.
2-[5-(4-Acetylphenyl)furan-2-yl]benzoxazole (23)
Following the general procedure from 2 (0.277 g, 1.5 mmol) and 4-
bromoacetophenone (0.199 g, 1 mmol) gave 23 (0.194 g, 64%) as a
brown solid; mp 185–189 °C.
1H NMR (400 MHz, CDCl3, 25 °C): δ = 8.03 (d, J = 8.0 Hz, 2 H),
7.93 (d, J = 8.0 Hz, 2 H), 7.82–7.78 (m, 1 H), 7.60–7.57 (m, 1 H),
7.39–7.37 (m, 3 H), 6.99 (d, J = 4.0 Hz, 1 H), 2.63 (s, 3 H).
13C NMR (100 MHz, CDCl3, 25 °C): δ = 197.4, 156.2, 155.3, 150.6,
143.2, 142.1, 137.1, 133.8, 129.3, 125.8, 125.2, 124.9, 120.5, 116.8,
110.8, 109.8, 31.1.
Anal. Calcd for C18H11NO2S (305.35): C, 70.80; H, 3.63. Found: C,
71.03; H, 3.42.
2-[5-(4-Nitrophenyl)thiophen-2-yl]benzoxazole (28)
Following the general procedure from 7 (0.302 g, 1.5 mmol) and 1-
bromo-4-nitrobenzene (0.202 g, 1 mmol) gave 28 (0.154 g, 48%) as
a yellow solid; mp 198–202 °C.
1H NMR (400 MHz, CDCl3, 25 °C): δ = 8.31 (d, J = 9.0 Hz, 2 H),
7.94 (d, J = 4.0 Hz, 1 H), 7.83 (d, J = 9.0 Hz, 2 H), 7.80–7.77 (m, 1
H), 7.56 (d, J = 4.0 Hz, 1 H), 7.51 (dd, J = 2.0, 9.0 Hz, 1 H), 7.41–
7.39 (m, 2 H).
Anal. Calcd for C19H13NO3 (303.31): C, 75.24; H, 4.32. Found: C,
75.52; H, 3.99.
13C NMR (100 MHz, CDCl3, 25 °C): δ = 150.6, 145.7, 142.0, 139.4,
131.1, 130.9, 130.0, 129.9, 126.5, 126.4, 125.6, 125.0, 124.6, 120.0,
110.6.
2-[5-(4-Nitrophenyl)furan-2-yl]benzoxazole (24)
Following the general procedure from 2 (0.277 g, 1.5 mmol) and 1-
bromo-4-nitrobenzene (0.202 g, 1 mmol) gave 24 (0.177 g, 58%) as
a yellow solid; mp 240–244 °C.
Anal. Calcd for C17H10N2O3S (322.34): C, 63.35; H, 3.13. Found: C,
63.67; H, 3.49.
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2014, 46, 3341–3350

3348
F. Abdellaoui et al.
PAPER
2-[5-(2-Cyanophenyl)thiophen-2-yl]benzoxazole (29)
Following the general procedure from 7 (0.302 g, 1.5 mmol) and 2-
bromobenzonitrile (0.181 g, 1 mmol) gave 29 (0.190 g, 63%) as a
pale yellow solid; mp 151–155 °C.
1H NMR (400 MHz, CDCl3, 25 °C): δ = 7.94 (d, J = 4.0 Hz, 1 H),
7.80 (d, J = 8.0 Hz, 1 H), 7.77–7.65 (m, 4 H), 7.59–7.56 (m, 1 H),
7.48 (dt, J = 1.5, 7.5 Hz, 1 H), 7.37 (dd, J = 3.0, 6.0 Hz, 2 H).
13C NMR (100 MHz, CDCl3, 25 °C): δ = 158.9, 151.1, 144.3, 142.5,
136.9, 135.1, 133.8, 131.5, 131.2, 130.3, 129.15, 129.1, 126.0,
125.5, 120.5, 119.0, 111.1, 110.8.
13C NMR (100 MHz, CDCl3, 25 °C): δ = 197.6, 160.4, 154.4, 139.3,
137.0, 136.0, 134.0, 129.3, 128.9, 128.7, 126.2, 124.8, 122.7, 121.3,
115.2, 110.1, 35.6, 26.7.
Anal. Calcd for C20H16N2OS (332.10): C, 72.26; H, 4.85. Found: C,
72.47; H, 4.90.
2-[5-(2-Cyanophenyl)-1-methyl-1H-pyrrol-2-yl]benzothiazole
(34)
Following the general procedure from 8 (0.321 g, 1.5 mmol) and 2-
bromobenzonitrile (0.181 g, 1 mmol) gave 34 (0.243 g, 77%) as a
pale yellow solid; mp 175–179 °C.
1H NMR (400 MHz, CDCl3, 25 °C): δ = 7.97 (d, J = 8.0 Hz, 1 H),
7.85 (d, J = 8.0 Hz, 1 H), 7.80 (dd, J = 1.5, 8.0 Hz, 1 H), 7.67 (dt,
J = 1.5, 8.0 Hz, 1 H), 7.50 (dt, J = 1.0, 7.0 Hz, 2 H), 7.45 (dt, J =
1.0, 7.0 Hz, 1 H), 7.34 (t, J = 7.5 Hz, 1 H), 6.93 (d, J = 4.0 Hz, 1 H),
6.50 (d, J = 4.0 Hz, 1 H), 4.05 (s, 3 H).
13C NMR (100 MHz, CDCl3, 25 °C): δ = 160.4, 154.4, 136.1, 135.5,
134.2, 133.8, 132.7, 131.3, 129.1, 128.5, 126.2, 124.9, 122.9, 121.4,
118.3, 115.0, 113.4, 112.4, 35.4.
Anal. Calcd for C18H10N2OS (302.35): C, 71.51; H, 3.33. Found: C,
71.22; H, 3.19.
2-[5-(Pyrimidin-5-yl)thiophen-2-yl]benzoxazole (30)
Following the general procedure from 7 (0.302 g, 1.5 mmol) and 5-
bromopyrimidine (0.159 g, 1 mmol) gave 30 (0.198 g, 71%) as a
yellow solid; mp 228–232 °C.
1H NMR (400 MHz, CDCl3, 25 °C): δ = 9.18 (s, 1 H), 9.01 (s, 2 H),
7.90 (d, J = 8.0 Hz, 1 H), 7.76–7.73 (m, 1 H), 7.57–7.55 (m, 1 H),
7.47 (d, J = 4.0 Hz, 1 H), 7.36 (dd, J = 3.0, 6.0 Hz, 2 H).
Anal. Calcd for C19H13N3S (315.39): C, 72.36; H, 4.15. Found: C,
72.55; H, 4.47.
13C NMR (100 MHz, CDCl3, 25 °C): δ = 158.0, 153.5, 150.4, 141.8,
140.4, 130.9, 130.7, 127.7, 126.1, 135.5, 124.9, 124.7, 119.9, 110.5.
2-[1-Methyl-5-(pyridin-3-yl)-1H-pyrrol-2-yl]benzothiazole (35)
Following the general procedure from 8 (0.321 g, 1.5 mmol) and 3-
bromopyridine (96 μL, 1 mmol) gave 35 (0.186 g, 64%) as an or-
ange solid; mp 138–142 °C.
Anal. Calcd for C15H9N3OS (279.32): C, 64.50; H, 3.25. Found: C,
64.38; H, 3.56.
2-[5-(Pyridin-3-yl)thiophen-2-yl]benzoxazole (31)
Following the general procedure from 7 (0.302 g, 1.5 mmol) and 3-
bromopyridine (96 μL, 1 mmol) gave 31 (0.203 g, 73%) as a yellow
solid; mp 179–183 °C.
1H NMR (400 MHz, CDCl3, 25 °C): δ = 8.92 (d, J = 2.5 Hz, 1 H),
8.56 (dd, J = 1.5, 5.0 Hz, 1 H), 7.88 (td, J = 2.0, 8.0 Hz, 1 H), 7.86
(d, J = 4.0 Hz, 1 H), 7.72 (dd, J = 3.0, 6.0 Hz, 1 H), 7.54–7.50 (m,
1 H), 7.39 (d, J = 4.0 Hz, 1 H), 7.35–7.31 (m, 3 H).
1H NMR (400 MHz, CDCl3, 25 °C): δ = 8.76 (br s, 1 H), 8.62 (dd,
J = 1.5, 5.0 Hz, 1 H), 7.98 (d, J = 8.0 Hz, 1 H), 7.85 (d, J = 8.0 Hz,
1 H), 7.79 (td, J = 2.0, 8.0 Hz, 1 H), 7.46 (dt, J = 1.5, 7.5 Hz, 1 H),
7.40 (dd, J = 5.0, 7.5 Hz, 1 H), 7.34 (t, J = 7.5 Hz, 1 H), 6.91 (d, J =
4.0 Hz, 1 H), 6.37 (d, J = 4.0 Hz, 1 H), 4.11 (s, 3 H).
13C NMR (100 MHz, CDCl3, 25 °C): δ = 160.6, 154.5, 150.0, 148.9,
136.8, 136.4, 134.1, 129.0, 128.8, 126.3, 124.9, 123.6, 122.8, 121.4,
115.2, 111.0, 35.4.
13C NMR (100 MHz, CDCl3, 25 °C): δ = 158.6, 150.6, 149.6, 147.2,
145.1, 142.1, 133.2, 131.0, 129.8, 129.6, 125.5, 125.3, 125.0, 124.0,
120.0, 110.6.
Anal. Calcd for C17H13N3S (291.37): C, 70.08; H, 4.50. Found: C,
69.89; H, 4.88.
Anal. Calcd for C16H10N2OS (278.33): C, 69.05; H, 3.62. Found: C,
68.79; H, 3.85.
2-[1-Methyl-5-(pyrimidin-5-yl)-1H-pyrrol-2-yl]benzothiazole
(36)
Following the general procedure from 8 (0.321 g, 1.5 mmol) and 5-
bromopyrimidine (0.159 g, 1 mmol) gave 36 (0.155 g, 53%) as a
yellow solid; mp 214–218 °C.
1H NMR (400 MHz, CDCl3, 25 °C): δ = 9.22 (s, 1 H), 8.88 (s, 2 H),
7.99 (d, J = 8.0 Hz, 1 H), 7.86 (d, J = 8.0 Hz, 1 H), 7.47 (dt, J = 1.5,
7.5 Hz, 1 H), 7.36 (t, J = 7.5 Hz, 1 H), 6.93 (d, J = 4.0 Hz, 1 H), 6.43
(d, J = 4.0 Hz, 1 H), 4.14 (s, 3 H).
13C NMR (100 MHz, CDCl3, 25 °C): δ = 160.1, 157.6, 156.3, 154.4,
134.2, 132.8, 130.0, 127.1, 126.4, 125.2, 123.0, 121.4, 115.3, 111.8,
35.3.
2-[5-(Quinolin-3-yl)thiophen-2-yl]benzoxazole (32)
Following the general procedure from 7 (0.302 g, 1.5 mmol) and 3-
bromoquinoline (136 μL, 1 mmol) gave 32 (0.220 g, 67%) as a yel-
low solid; mp 198–202 °C.
1H NMR (400 MHz, CDCl3, 25 °C): δ = 9.25 (d, J = 2.5 Hz, 1 H),
8.36 (d, J = 2.5 Hz, 1 H), 8.13 (d, J = 8.5 Hz, 1 H), 7.94 (d, J = 4.0
Hz, 1 H), 7.88 (d, J = 8.0 Hz, 1 H), 7.77–7.72 (m, 2 H), 7.62–7.54
(m, 3 H), 7.39–7.35 (m, 2 H).
13C NMR (100 MHz, CDCl3, 25 °C): δ = 158.7, 150.7, 148.3, 148.0,
145.5, 142.3, 132.2, 131.2, 130.2, 129.9, 129.6, 128.3, 128.0, 127.8,
126.8, 125.6, 125.5, 125.1, 120.1, 110.7.
Anal. Calcd for C16H12N4S (292.36): C, 65.73; H, 4.14. Found: C,
65.36; H, 4.23.
Anal. Calcd for C20H12N2OS (328.39): C, 73.15; H, 3.68. Found: C,
73.47; H, 3.31.
2-[1-Methyl-5-(4-nitrophenyl)-1H-pyrrol-2-yl]benzoxazole (37)
Following the general procedure from 9 (0.297 g, 1.5 mmol) and 1-
bromo-4-nitrobenzene (0.202 g, 1 mmol) gave 37 (0.198 g, 62%) as
a yellow solid; mp 185–189 °C.
1H NMR (400 MHz, CDCl3, 25 °C): δ = 8.34 (dd, J = 8.5, 12.5 Hz,
2 H), 7.78 (d, J = 9.0 Hz, 1 H), 7.73–7.70 (m, 1 H), 7.64 (d, J = 9.0
Hz, 2 H), 7.56–7.53 (m, 1 H), 7.34–7.32 (m, 1 H), 7.19 (d, J = 4.0
Hz, 1 H), 6.48 (d, J = 4 Hz, 1 H), 4.17 (s, 3 H).
2-[5-(4-Acetylphenyl)-1-methyl-1H-pyrrol-2-yl]benzothiazole
(33)
Following the general procedure from 8 (0.321 g, 1.5 mmol) and 4-
bromoacetophenone (0.199 g, 1 mmol) gave 33 (0.216 g, 65%) as a
pale yellow solid; mp 163–167 °C.
1H NMR (400 MHz, CDCl3, 25 °C): δ = 8.05 (d, J = 8.0 Hz, 2 H),
7.98 (d, J = 8.0 Hz, 1 H), 7.85 (d, J = 8.0 Hz, 1 H), 7.58 (d, J = 8.0
Hz, 2 H), 7.46 (t, J = 7.5 Hz, 1 H), 7.35 (t, J = 7.5 Hz, 1 H), 6.91 (d,
J = 4.0 Hz, 1 H), 6.4 (d, J = 4.0 Hz, 1 H), 4.14 (s, 3 H), 2.65 (s, 3 H).
13C NMR (100 MHz, CDCl3, 25 °C): δ = 157.6, 149.9, 147.2, 142.4,
138.8, 138.5, 129.4, 128.6, 124.7, 124.6, 124.3, 119.8, 115.5, 112.0,
110.4, 35.6.
Anal. Calcd for C18H13N3O3 (319.31): C, 67.71; H, 4.10. Found: C,
67.88; H, 4.31.
Synthesis 2014, 46, 3341–3350
© Georg Thieme Verlag Stuttgart · New York

PAPER
Palladium-Catalyzed Regioselective C–H Bond Arylation
3349
2-[5-(4-Formylphenyl)-1-methyl-1H-pyrrol-2-yl]benzoxazole
(38)
Following the general procedure from 9 (0.297 g, 1.5 mmol) and 4-
bromobenzaldehyde (0.185 g, 1 mmol) gave 38 (0.202 g, 67%) as
an orange solid; mp 177–181 °C.
Supporting Information for this article is available online
at http://www.thieme-connect.com/products/ejournals/journal/
10.1055/s-00000084.SunogIpimrfiantoSuIpg
n
fonirtat
ori
1H NMR (400 MHz, CDCl3, 25 °C): δ = 10.14 (s, 1 H), 8.05 (d, J =
8.0 Hz, 2 H), 7.80–7.76 (m, 1 H), 7.72 (d, J = 8.0 Hz, 2 H), 7.62–
7.59 (m, 2 H), 7.41–7.39 (m, 1 H), 7.26 (d, J = 4.0 Hz, 1 H), 6.53
(d, J = 4.0 Hz, 1 H), 4.24 (s, 3 H).
References
(1) (a) Gillingwater, K.; Kumar, A.; Anbazhagan, M.; Boykin,
D. W.; Tidwell, R. R.; Brun, R. Antimicrob. Agents
Chemother. 2009, 53, 5074. (b) Gillingwater, K.; Kumar,
A.; Ismail, M. A.; Arafa, R. K.; Stephens, C. E.; Boykin, D.
W.; Tidwell, R. R.; Brun, R. Vet. Parasitol. 2010, 169, 264.
(2) (a) Munde, M.; Kumar, A.; Nhili, R.; Depauw, S.; David-
Cordonnier, M.-H.; Ismail, M. A.; Stephens, C. E.; Farahat,
A. A.; Batista-Parra, A.; Boykin, D. W.; Wilson, W. D.
J. Mol. Biol. 2010, 402, 847. (b) Bailly, C.; Tardy, C.; Wang,
L.; Armitage, B.; Hopkins, K.; Kumar, A.; Schuster, G. B.;
Boykin, D. W.; Wilson, W. D. Biochemistry 2001, 40, 9770.
(c) Bachhav, H. M.; Bhagat, S. B.; Telvekar, V. N.
Tetrahedron Lett. 2011, 52, 5697.
13C NMR (100 MHz, CDCl3, 25 °C): δ = 191.8, 157.7, 149.8, 142.4,
139.5, 138.3, 135.5, 130.2, 129.5, 124.8, 124.6, 123.7, 119.6, 115.4,
111.5, 110.3, 35.6.
Anal. Calcd for C19H14N2O2 (302.33): C, 75.48; H, 4.67. Found: C,
75.66; H, 4.89.
2-[5-(2-Cyanophenyl)-1-methyl-1H-pyrrol-2-yl]benzoxazole
(39)
Following the general procedure from 9 (0.297 g, 1.5 mmol) and 2-
bromobenzonitrile (0.181 g, 1 mmol) gave 39 (0.248 g, 83%) as a
white solid; mp 159–163 °C.
1H NMR (400 MHz, CDCl3, 25 °C): δ = 7.79 (d, J = 7.5 Hz, 1 H),
7.71–7.65 (m, 2 H), 7.53–7.47 (m, 3 H), 7.30 (t, J = 4.0 Hz, 2 H),
7.19 (d, J = 4.0 Hz, 1 H), 6.50 (d, J = 4.0 Hz, 1 H), 3.97 (s, 3 H).
(3) Szabelski, M.; Rogiewicz, M.; Wiczk, W. Anal. Biochem.
2005, 342, 20.
(4) Dunwell, D. W.; Evans, D.; Hicks, T. A. J. Med. Chem.
1975, 18, 1158.
13C NMR (100 MHz, CDCl3, 25 °C): δ = 158.1, 150.2, 142.8, 136.4,
136.3, 134.2, 133.1, 131.8, 129.1, 125.1, 124.9, 123.6, 120.0, 118.6,
115.5, 114.0, 112.6, 110.7, 35.5.
(5) Racane, L.; Tralic-Kulenovic, V.; Fiser-Jakic, L.; Boykin,
D. W.; Karminski-Zamola, G. Heterocycles 2001, 55, 2085.
(6) (a) Tralic-Kulenovic, V.; Fiser-Jakic, L.; Lazarevic, Z.
Monatsh. Chem. 1994, 125, 209. (b) Racane, L.; Tralic-
Kulenovic, V.; Karminski-Zamola, G.; Fiser-Jakic, L.
Monatsh. Chem. 1995, 126, 1375. (c) Karminiski-Zamola,
G.; Tralic-Kulenovic, V.; Fiser-Jakic, L. Rapid Commun.
Mass Spectrom. 1996, 10, 1621. (d) Racane, L.; Tralic-
Kulenovic, V.; Karminski-Zamola, G.; Fiser-Jakic, L.
Monatsh. Chem. 1996, 127, 579. (e) Tralic-Kulenovic, V.;
Racane, L.; Karminski-Zamola, G. Spectrosc. Lett. 2003, 36,
43. (f) Zajac, M.; Hrobarik, P.; Magdolen, P.; Foltinova, P.;
Zahradnik, P. Tetrahedron 2008, 64, 10605. (g) Batista, R.
M. F.; Costa, S. P. G.; Malheiro, E. L.; Belsley, M.; Raposo,
M. M. M. Tetrahedron 2007, 63, 4258.
Anal. Calcd for C19H13N3O (299.33): C, 76.24; H, 4.38. Found: C,
76.59; H, 4.22.
2-[1-Methyl-5-(quinolin-3-yl)-1H-pyrrol-2-yl]benzoxazole (40)
Following the general procedure from 9 (0.297 g, 1.5 mmol) and 3-
bromoquinoline (136 μL, 1 mmol) gave 40 (0.182 g, 56%) as a yel-
low solid; mp 122–126 °C.
1H NMR (400 MHz, CDCl3, 25 °C): δ = 7.76 (br s, 1 H), 8.63 (d, J =
4.0 Hz, 1 H), 7.79 (td, J = 2.0, 8.0 Hz, 1 H), 7.73–7.69 (m, 1 H), 7.53
(d, J = 9.0 Hz, 1 H), 7.41 (dd, J = 5.0, 8.0 Hz, 1 H), 7.37–7.34 (m,
1 H), 7.34–7.30 (m, 2 H), 7.19 (d, J = 4.0 Hz, 1 H), 6.99 (s, 1 H),
6.41 (d, J = 4.0 Hz, 1 H), 4.13 (s, 3 H).
(7) Li, Y.; Cao, R.; Lippard, S. J. Org. Lett. 2011, 13, 5052.
(8) (a) Ryabukhin, S. V.; Plaskon, A. S.; Volochnyuk, D. M.;
Tolmachev, A. A. Synthesis 2006, 3715. (b) Mamada, M.;
Nishida, J.-i.; Tokito, S.; Yamashita, Y. Chem. Lett. 2008,
37, 766. (c) Batista, R. M. F.; Oliveira, E.; Costa, S. P. G.;
Lodeiro, C.; Raposo, M. M. M. Tetrahedron 2011, 67, 7106.
(d) Inouchi, T.; Nakashima, T.; Toba, M.; Kawai, T. Chem.
Asian J. 2011, 6, 3020. (e) Molander, G. A.; Ajayi, K. Org.
Lett. 2012, 14, 4242. (f) Zhang, Y.; Lai, S.-L.; Tong, Q.-X.;
Lo, M.-F.; Ng, T.-W.; Chan, M.-Y.; Wen, Z.-C.; He, J.; Kc-
Sham, J.; Tang, X.-L.; Liu, W.-M.; Ko, C.-C.; Wang, P.-F.;
Lee, C.-S. Chem. Mater. 2012, 24, 61. (g) Dessi, A.;
Barozzino Consiglio, G.; Calamante, M.; Reginato, G.;
Mordini, A.; Peruzzini, M.; Taddei, M.; Sinicropi, A.; Parisi,
M. L.; Fabrizi de Biani, F.; Basosi, R.; Mori, R.; Spatola, M.;
Bruzzi, M.; Zani, L. Eur. J. Org. Chem. 2013, 1916. (h) Shi,
B.; Zhang, P.; Wei, T.; Yao, H.; Lin, Q.; Liu, J.; Zhang, Y.
Tetrahedron 2013, 69, 7981.
13C NMR (100 MHz, CDCl3, 25 °C): δ =173.6, 157.8, 152.3, 150.1,
149.8, 149.1, 142.3, 137.1, 136.4, 128.5, 125.0, 124.7, 124.6, 123.6,
123.2, 119.6, 115.3, 114.2, 111.0, 110.3, 35.4.
Anal. Calcd for C21H15N3O (325.36): C, 77.52; H, 4.65. Found: C,
77.24; H, 4.98.
2-[1-Methyl-5-(pyrimidin-5-yl)-1H-pyrrol-2-yl]benzoxazole
(41)
Following the general procedure from 9 (0.297 g, 1.5 mmol) and 5-
bromopyrimidine (0.159 g, 1 mmol) gave 41 (0.168 g, 61%) as a
pale yellow solid; mp 190–194 °C.
1H NMR (400 MHz, CDCl3, 25 °C): δ = 9.22 (s, 1 H), 8.87 (s, 2 H),
7.73–7.69 (m, 1 H), 7.55–7.51 (m, 1 H), 7.35–7.30 (m, 2 H), 7.19
(d, J = 4.0 Hz, 1 H), 6.46 (d, J = 4.0 Hz, 1 H), 4.16 (s, 3 H).
13C NMR (100 MHz, CDCl3, 25 °C): δ = 157.4, 157.1, 156.1, 149.5,
142.0, 133.0, 126.7, 124.7, 124.4, 123.9, 119.5, 115.1, 111.4, 110.1,
34.9.
(9) (a) Campeau, L.-C.; Stuart, D. R.; Fagnou, K. Aldrichimica
Acta 2007, 40, 35. (b) Alberico, D.; Scott, M. E.; Lautens,
M. Chem. Rev. 2007, 107, 174. (c) Satoh, T.; Miura, M.
Chem. Lett. 2007, 36, 200. (d) Seregin, I. V.; Gevorgyan, V.
Chem. Soc. Rev. 2007, 36, 1173. (e) Fairlamb, I. J. S. Chem.
Soc. Rev. 2007, 36, 1036. (f) Ackermann, L.; Vicente, R.;
Kapdi, A. R. Angew. Chem. Int. Ed. 2009, 48, 9792.
(g) Daugulis, O. In C-H Activation; Vol. 292; Yu, J.-Q.; Shi,
Z., Eds.; Springer: Berlin, 2010, 57. (h) Yamaguchi, J.;
Yamaguchi, A. D.; Itami, K. Angew. Chem. Int. Ed. 2012,
51, 8960. (i) Neufeldt, S. R.; Sanford, M. S. Acc. Chem. Res.
Anal. Calcd for C16H12N4O (276.29): C, 69.55; H, 4.38. Found: C,
69.31; H, 4.11.
Acknowledgment
F.A. is grateful to ‘UTIQUE’ for a grant. We thank the CNRS,
‘Rennes Metropole’ and Scientific Ministry of Higher Education
and Research of Tunisia for providing financial support.
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2014, 46, 3341–3350

3350
F. Abdellaoui et al.
PAPER
2012, 45, 936. (j) Kuhl, N.; Hopkinson, M. N.; Wencel-
Delord, J.; Glorius, F. Angew. Chem. Int. Ed. 2012, 51,
10236. (k) Wencel-Delord, J.; Glorius, F. Nat. Chem. 2013,
5, 369.
(17) (a) Altenhoff, G.; Glorius, F. Adv. Synth. Catal. 2004, 346,
1661. (b) Viirre, R. D.; Evindar, G.; Batey, R. A. J. Org.
Chem. 2008, 73, 3452. (c) Terashima, M.; Ishii, M.;
Kanaoka, Y. Synthesis 1982, 484.
(10) (a) Bellina, F.; Rossi, R. Tetrahedron 2009, 65, 10269.
(b) Dong, J. J.; Roger, J.; Pozgan, F.; Doucet, H. Green
Chem. 2009, 11, 1832. (c) Liégault, B.; Lapointe, D.; Caron,
L.; Vlassova, A.; Fagnou, K. J. Org. Chem. 2009, 74, 1826.
(d) Roger, J.; Pozgan, F.; Doucet, H. Green Chem. 2009, 11,
425. (e) Gryko, D. T.; Vakuliuk, O.; Gryko, D.; Koszarna, B.
J. Org. Chem. 2009, 74, 9517. (f) Roger, J.; Gottumukkala,
A. L.; Doucet, H. ChemCatChem 2010, 2, 20. (g) Fu, H. Y.;
Doucet, H. Eur. J. Org. Chem. 2011, 7163. (h) Yanagisawa,
S.; Itami, K. Tetrahedron 2011, 67, 4425. (i) Gorelsky, S. I.;
Lapointe, D.; Fagnou, K. J. Org. Chem. 2012, 77, 658.
(j) Ghosh, D.; Lee, H. M. Org. Lett. 2012, 14, 5534.
(k) Zhao, L.; Bruneau, C.; Doucet, H. ChemCatChem 2013,
5, 255. (l) Rossi, R.; Bellina, F.; Lessi, M.; Manzini, C. Adv.
Synth. Catal. 2014, 356, 17. (m) He, M.; Soulé, J.-F.;
Doucet, H. ChemCatChem 2014, 6, 1824.
(11) (a) Požgan, F.; Roger, J.; Doucet, H. ChemSusChem 2008, 1,
404. (b) Ionita, M.; Roger, J.; Doucet, H. ChemSusChem
2010, 3, 367.
(12) Beydoun, K.; Doucet, H. ChemSusChem 2011, 4, 526.
(13) (a) Roy, D.; Mom, S.; Beaupérin, M.; Doucet, H.; Hierso, J.-
C. Angew. Chem. Int. Ed. 2010, 49, 6650. (b) Nadres, E. T.;
Lazareva, A.; Daugulis, O. J. Org. Chem. 2011, 76, 471.
(14) Barbero, N.; SanMartin, R.; Domínguez, E. Tetrahedron
Lett. 2009, 50, 2129.
(18) (a) Cho, Y.-H.; Lee, C.-Y.; Cheon, C.-H. Tetrahedron 2013,
69, 6565. (b) Chen, Y.-X.; Qian, L.-F.; Zhang, W.; Han, B.
Angew. Chem. Int. Ed. 2008, 47, 9330. (c) Varma, R. S.;
Saini, R. K.; Prakash, O. Tetrahedron Lett. 1997, 38, 2621.
(d) Yoo, W.-J.; Yuan, H.; Miyamura, H.; Kobayashi, S. Adv.
Synth. Catal. 2011, 353, 3085.
(19) Fu, H.-y.; Gao, X.-d.; Zhong, G.-y.; Zhong, Z.-y.; Xiao, F.;
Shao, B.-x. J. Lumin. 2009, 129, 1207.
(20) Reyes, H.; Beltran, H. I.; Rivera-Becerril, E. Tetrahedron
Lett. 2011, 52, 308.
(21) Aleksandrov, A. A.; Vlasova, E. V.; El’chaninov, M. M.
Russ. J. Org. Chem. 2010, 46, 898.
(22) Yuan, K.; Doucet, H. Chem. Sci. 2014, 5, 392.
(23) Loukotova, L.; Yuan, K.; Doucet, H. ChemCatChem 2014,
6, 1303.
(24) Beladhria, A.; Yuan, K.; Ben Ammar, H.; Soulé, J.-F.; Ben
Salem Ridha, ; Henri, D. Synthesis 2014, 46, 2515.
(25) (a) Gottumukkala, A. L.; Doucet, H. Adv. Synth. Catal.
2008, 350, 2183. (b) Li, P.; Chai, Z.; Zhao, G.; Zhu, S.-Z.
Tetrahedron 2009, 65, 1673.
(26) Chakraborti, A. K.; Rudrawar, S.; Jadhav, K. B.; Kaur, G.;
Chankeshwara, S. V. Green Chem. 2007, 9, 1335.
(27) Fiser-Jakic, L.; Karaman, B.; Jakopcic, K. Croat. Chem.
Acta 1980, 53, 69.
(28) Marsden, S. P.; McGonagle, A. E.; McKeever-Abbas, B.
Org. Lett. 2008, 10, 2589.
(29) Guru, M. M.; Ali, M. A.; Punniyamurthy, T. Org. Lett. 2011,
13, 1194.
(15) (a) Join, B.; Yamamoto, T.; Itami, K. Angew. Chem. Int. Ed.
2009, 48, 3644. (b) García-Melchor, M.; Gorelsky, S. I.;
Woo, T. K. Chem. Eur. J. 2011, 17, 13847.
(16) Qian, Y. Y.; Wong, K. L.; Zhang, M. W.; Kwok, T. Y.; To,
C. T.; Chan, K. S. Tetrahedron Lett. 2012, 53, 1571.
Synthesis 2014, 46, 3341–3350
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