Palladium-catalyzed desulfitative C-arylation of a benzo[d]oxazole C-H bond with arene sulfonyl chlorides

Article abstract of DOI:10.1039/c1cc14718h

A palladium-catalyzed direct desulfitative C-arylation of a benzo[d]oxazole C-H bond with arene sulfonyl chlorides is described. The procedure tolerates halo, cyano, nitro, trifluoromethyl, acetyl and acetylamino groups on the phenyl ring of sulfonyl chlorides, providing the arylation products in moderate to good yields. It represents a practical and attractive alternative for the synthesis of 2-aryl benzoxazoles.

Full text of DOI:10.1039/c1cc14718h

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COMMUNICATION
Palladium-catalyzed desulfitative C-arylation of a benzo[d]oxazole
C–H bond with arene sulfonyl chloridesw
Manli Zhang, Shouhui Zhang, Miaochang Liu and Jiang Cheng*
Received 31st July 2011, Accepted 5th September 2011
DOI: 10.1039/c1cc14718h
A palladium-catalyzed direct desulfitative C-arylation of a
benzo[d]oxazole C–H bond with arene sulfonyl chlorides is
described. The procedure tolerates halo, cyano, nitro, trifluoro-
methyl, acetyl and acetylamino groups on the phenyl ring of
sulfonyl chlorides, providing the arylation products in moderate
to good yields. It represents a practical and attractive alternative
for the synthesis of 2-aryl benzoxazoles.
Table 1 Selected results of screening the optimal conditionsa
Entry
Cu sources (eq)
Bases (eq)
Yield (%)b
1
2
3
4
5
6
7
8
Cu(OAc)2 (1.0)
CuF2 (1.0)
CuCl2 (1.0)
CuBr (1.0)
CuI (1.0)
—
CuI (1.0)
CuI (1.0)
CuI (1.0)
CuI (1.0)
CuI (1.0)
CuI (1.0)
CuI (1.0)
CuI (0.5)
CuI (1.0)
CuI (1.0)
K2CO3 (2.0)
K2CO3 (2.0)
K2CO3 (2.0)
K2CO3 (2.0)
K2CO3 (2.0)
K2CO3 (2.0)
—
NazCO3 (2.0)
KHCO3 (2.0)
NaHCO3 (2.0)
t-BuOK (2.0)
KOH (2.0)
o5
o5
28
20
The bis(hetero)aryl moiety is ubiquitous in many natural and
biologically active compounds as well as advanced organic
materials.1 In the past, the transition-metal-catalyzed cross-
coupling reactions were successful methods to construct these
motifs.2 Meanwhile, transition-metal-catalyzed direct arylations
of (hetero)arenes are important alternatives to traditional
cross-coupling reactions in arene synthesis.3 Direct arylation
through cleavage of C–H bonds represents an environmentally
and economically attractive strategy for such transformations,
which avoids the extra introduction of functional groups at
one of the potential coupling partners. Many elegant examples
of the C–H arylation have been achieved using ArX4 (X = I,
Br, Cl and OTf), ArI(III)5 and ArM6 (M = Mg, B and Si etc.).
Yu reported the arylation of 2-arylpyridine C–H bond
using acyl chloride.7 Similarly, arene sulfonyl chlorides are
inexpensive and readily available compounds, which were
widely applied as arylating reagents in the desulfitative C–C
coupling reaction.8 However, to the best of our knowledge,
few successful examples have been reported to date on the
arylation of heteroarene C–H bonds, utilizing arene sulfonyl
chlorides as arylation reagents. Recently, Dong reported the
desulfitative arylation of a 2-arylpyridine C–H bond.9 Our
interest in transition-metal-catalyzed C–H functionalization
spurred us to test the feasibility of desulfitative arylation for
such a transformation.10 Herein, we wish to report our study
on such transformations.
87 (68c, 40d)
o5
o5
65
11
10
9
10
11
12
13
14
15
16
o5
10
K2CO3 (3.0)
K2CO3 (2.0)
K2CO3 (2.0)
K2CO3 (2.0)
15e
o5f
o5g
o5h
a
Reaction conditions: 1a (0.2 mmol), 2a (0.4 mmol), Pd source
(10 mol%), indicated copper source and base, dry solvent (2 mL),
b
c
under air, 120 1C, 48 h, sealed tube. Isolated yields. Under O2.
Under N2. THF. DMF. toluene. without Pd.
d
e
f
g
h
and CuCl2 (1 equivalent) in 1,4-dioxane under air. The copper
salts were crucial for this transformation (entry 6, Table 1).
Among the copper examined, such as Cu(OAc)2, CuF2, CuCl2,
CuBr and CuI, CuI was the best, providing 3aa in 87% yield
(entries 1–5, Table 1). Under O2, the yield of 3aa decreased
to 68%, while under N2, only 40% yield of the product
was formed (entry 5, Table 1). The base played an important
role in the reaction since no product was detected in the
absence of any base. K2CO3 was superior to other bases, such
as Na2CO3, NaHCO3, KHCO3, t-BuOK and KOH (entries
7–12, Table 1).Meanwhile, using THF, DMF or toluene as
solvents for the arylation reaction gave less satisfactory results
(entries 13–15, Table 1). During the screening of palladium
catalysts, such as Pd(OAc)2, PdCl2, PdCl2(CH3CN)2, provided
3aa in 87%, 40%, 70% yield, respectively. No product was
formed in the absence of Pd (entry 16, Table 1). After
surveying a variety of catalysts, bases and solvents, we found
that the combination of 10 mol% of Pd(OAc)2, 1 equivalent of
CuI and 2 equivalents of K2CO3 in dioxane at 120 1C for 48 h
served as the optimal conditions for this transformation.
We initiated our investigation on the model reaction of
benzoxazole with p-tolylsulfonyl chloride to optimize the critical
reaction parameters (Table 1). To our delight, the desulfitative
C-arylation took place in the presence of Pd(OAc)2 (10 mol%)
College of Chemistry & Materials Engineering, Wenzhou University,
Wenzhou 325000, People’s Republic of China.
E-mail: jiangcheng@wzu.edu.cn
w Electronic supplementary information (ESI) available: experimental
details. See DOI: 10.1039/c1cc14718h
c
11522 Chem. Commun., 2011, 47, 11522–11524
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Importantly, this transformation is very practical as it does
not require the use of strong bases or expensive ligands and the
rigorous exclusion of air.
The halo products could easily be further modifiable. Moreover,
biphenyl, naphthyl and acetylamino groups on the phenyl ring
of the sulfonyl chlorides could also gave arylation products
in moderate yields, respectively (3al, 3am and 3an, Table 2). It is
worth noting that 5-chlorothiophene-2-sulfonyl chloride also
worked under the current conditions with moderate yield (3ao,
Table 2). Importantly, the N,N-dimethylamination product was
formed in moderate yield when dimethylsulfamoyl chloride was
subjected to the procedure (3ap, Table 2).
With the optimized reaction conditions in hand, we investigated
the effect of electronic and structural variations of the sulfonyl
chlorides. The scope of the reaction is presented in Table 2. As
expected, a series of functional groups on the phenyl ring of
sulfonyl chlorides, such as bromo, chloro, fluoro, nitro, cyano,
trifluoromethyl and acetyl were compatible under this procedure,
and the products were isolated in moderate to good yields
(3aa–3an, Table 2). Generally, the reaction efficiency was
sensitive to the electronic property of the groups on the phenyl
ring of the sulfonyl chlorides. Except for 3aj, electron-donating
groups gave a slight higher yield than electron-withdrawing
groups (3aa, 3ab and 3ac vs. 3ah, 3al and 3ak, Table 2). The
hindrance of the phenyl ring of sulfonyl chloride had slight
effect on the efficiency (3aa vs. 3ac, Table 2). It was regrettable that
2-nitrobenzene-1-sulfonyl chloride did not work under the
procedure. Notably, the halo groups on the phenyl ring of sulfonyl
chlorides survived in the procedure (3ae, 3af and 3ag, Table 2).
After a broad scope of electrophiles was established, we were
particularly interested in extending the direct arylation to
benzo[d]oxazole derivatives (Table 3). 5-methyl, 5-chloro,
6-methyl, 5-nitro and 5-tert-butyl could be selectively arylated
with an acceptable efficiency. However, the electron-withdrawing
groups on the phenyl ring of benzo[d]oxazole would slightly
decrease the reaction efficiency. Importantly, benzothiazole was
also applicable, albeit the acylation product 4ga was isolated in
moderate yield (Table 3).
A plausible mechanism is outlined in Scheme 1. Step (i)
involves the electrophilic attack of CuI on the benzoxazole
C–H bond to afford intermediate A,11 at which Cu/Pd exchange
occurs to form the Pd(II) species A0. In step (ii), the oxidative
addition of arene sulfonyl chloride to the intermediate A0
forms the Pd(IV) intermediate B. In step (iii), the intermediate
B produces intermediate C with concomitant loss of SO2 in
the presence of palladium and copper catalysts at a higher
temperature,8 and in step (iv), the reductive elimination from
the Pd(IV) complex under base affords the 2-aryl benzoxazole
and regenerates Pd(II). However, the possibility of a Pd(0)/Pd(II)
mechanism could not be thoroughly ruled out.
Table
2
Palladium-catalyzed
desulfitative
C-arylation
of
benzo[d]oxazole with arene sulfonyl chloridesa
Table
3
Palladium-catalyzed
desulfitative
C-arylation
of
benzo[d]oxazole derivatives with arene sulfonyl chloridesa
a
a
Reaction conditions: Benzoxazole derivative (0.2 mmol),
(0.4 mmol), Pd(OAc)2 (10 mol%), CuI (0.2 mmol), K2CO3 (0.4 mmol),
2
Reaction conditions: 1a (0.2 mmol), 2 (0.4 mmol), Pd(OAc)2
(10 mol%), CuI (0.2 mmol), K2CO3 (0.4 mmol), dry 1,4-dioxane
(2 mL), under air, 120 1C, 48 h, sealed tube.
dry 1,4-dioxane (2 mL), under air, 120 1C, 48 h, sealed tube.
c
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Scheme 1 Plausible mechanism.
In conclusion, we have developed a palladium-catalyzed
desulfitative C-arylation of benzo[d]oxazole C–H bond with
arene sulfonyl chlorides. The reaction provides a novel meth-
odology allowing for a wide functional group tolerance.
Further mechanistic studies of this process and its application
to the synthesis of functional materials are currently under
way in our laboratory.
Financial support was provided by the National Natural
Science Foundation of China (No. 20972115) and the Natural
Science Foundation of Zhejiang Province (No. R4110294).
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11524 Chem. Commun., 2011, 47, 11522–11524
This journal is The Royal Society of Chemistry 2011