Direct arylation of benzoxazole C-H bonds with iodobenzene diacetates

Article abstract of DOI:10.1016/j.tetlet.2012.06.076

A Pd (OAc)₂-catalyzed direct arylation of benzoxazole C-H bonds has been achieved with iodobenzene diacetates as the arylation reagent in moderate to good yields. The procedure tolerates a series of functional groups, such as methoxy, nitro, cyano, chloro, and bromo groups.

Full text of DOI:10.1016/j.tetlet.2012.06.076

Tetrahedron Letters 53 (2012) 4588–4590
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Tetrahedron Letters
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Direct arylation of benzoxazole C–H bonds with iodobenzene diacetates
Peng Yu a, Guangyou Zhang a, Fan Chen a, , Jiang Cheng b,
⇑
⇑
a College of Chemistry and Materials Engineering, Wenzhou University, Wenzhou 325035, PR China
b School of Petrochemical Engineering, Changzhou University, Changzhou 213164, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
A Pd (OAc)2-catalyzed direct arylation of benzoxazole C–H bonds has been achieved with iodobenzene
diacetates as the arylation reagent in moderate to good yields. The procedure tolerates a series of func-
tional groups, such as methoxy, nitro, cyano, chloro, and bromo groups.
Received 26 April 2012
Revised 13 June 2012
Accepted 15 June 2012
Available online 20 June 2012
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
Arylation
C–H Bond activation
Benzoxazole
Table 1
Heteroaromatics are important structural units frequently found
in natural products, pharmaceuticals, and other functional com-
pounds.1 Recently, direct functionalization of heteroarenes C–H bond
represents an environmentally and economically attractive strategy,
which isa potential alternative totraditional cross-coupling reactions
because it avoids the extra introduction of functional groups at one of
the coupling partners.2 Among the direct arylation of C–H bonds,3
much progress has been made on employing convenient electro-
philes, such as ArX4 (X = I, Br, Cl, OTf and OMs), ArSO2Cl, ArSO2Na,5
and ArM (M = Mg, B, Si etc.).6 Meanwhile, the employment of diaryli-
odonium salts (usually Ar2IBF4) as the arylation reagents in the C–H
activation received great attentions.7 For example, in 2006, Sanford
developed Pd-catalyzed direct 2-arylation of indoles with Ar2IBF4.8
Subsequently, Gaunt reported a site-selective Cu(II)-catalyzed C–H
bond functionalization of indoles with Ar2IBF4 or Ar2IOTf.9 Recently,
Liu described a Pd(II)-catalyzed ortho C–H arylation of phenol esters
with Ph2IOTf.10 However, to our surprise, iodobenzene diacetate
(PhI(OAc)2) was not found to be arylating reagent for these C–H bond
functionalizations. As we know, iodobenzene diacetates mainly
served as oxidant11 and acetoxylation reagent in the C–H bond func-
tionalization.12 Herein, we report our study in the direct arylation of
benzoxazole with iodobenzene diacetate as the arylating reagent.
At the outset of the investigation, benzo[d]oxazole was em-
ployed as the substrate to react with PhI(OAc)2 in the presence of
Pd(OAc)2, PPh3, and Na2CO3 in DMSO at 150 °C under nitrogen.
To our delight, 2-phenylbenzoxazole (3aa) was detected by GC–
MS and isolated in 22% yield (Table 1, entry 1). The preliminary re-
sult encouraged us to optimize the reaction conditions. Among the
Selected results of screening the optimal conditions
O
O
Pd(OAc)2, Ligand
base, solvent
PhI(OAc)2
+
Ph
N
N
2a
1a
3aa
Entry
Ligand
Base
Solvent
Yielda (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
dppb
dppf
dppe
dppp
2,20-Bipyridine
2,20-Biquinoline
Phen
Phen
Phen
Na2CO3
LiOH
t-BuOLi
NaOH
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
THF
22
25
<5
<5
21
17
53
53
<5
54
31
57
K2CO3
K3PO4ꢀ3H2O
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
t-BuOK
27
84(46)b(60)c
26
52
39
44
20
<5
38
DMF
Toluene
NMP
Acetonitrile
Dioxane
DMSO
Phen
Phen
Phen
Phen
Phen
a
Reaction conditions: 1a (0.2 mmol), 2a (0.25 mmol), Pd(OAc)2 (5 mol %), ligand
(10 mol %), base (0.2 mmol), dry solvent (2 mL), 150 °C, under N2, 20 h, sealed tube.
Isolated yield.
b
Under air.
130 °C. Phen = 1,10-phenanthroline.
c
⇑
Corresponding authors.
E-mail addresses: fanchen@wzu.edu.cn (F. Chen), jiangcheng@cczu.edu.cn
bases tested, such as LiOH, t-BuOLi, NaOH, K2CO3, K3PO4ꢀ3H2O, and
Cs2CO3, Cs2CO3 was the best (Table 1, entries 2–8). Next, a variety
(J. Cheng).
0040-4039/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2012.06.076

P. Yu et al. / Tetrahedron Letters 53 (2012) 4588–4590
4589
Table 2
Table 3
Palladium-catalyzed arylation of benzoxazole derivatives with iodobenzene diace-
Palladium-catalyzed arylation of benzoxazole derivatives with iodobenzene diace-
tatesa
tatesa
O
N
O
N
O
O
Pd(OAc)2, 1,10-phen.
Cs2CO3, DMSO
Pd(OAc)2, 1,10-phen.
Cs2CO3, DMSO
ArI(OAc)2
+
ArI(OAc)2
+
R
Ar
Ar
R
N
N
2a-2h
2a-2d,2f,2g
1a
3aa-3ah
1b-1f
4ba-4fb
O
N
O
O
O
Me
N
N
ba
N
3aa, 80%
3ab
4
, 74%
, 78%
4bb, 52%
O
N
O
N
Cl
O
N
4bf
N
O
3ad
3ac
, 76%
, 71%
, 92%
4bc, 60%
N
N
O
O
OMe
Br
Cl
O
O
N
N
3ae
, 82%
3af
, 90%
N
4ca, 52%
4cb, 37%
N
O
O
O
O
N
N
t-Bu
Cl
t-Bu
3ag, 60%
CN
3ah, 67%
4da, 87%
4db, 68%
a
O
O
Reaction conditions: 1a (0.2 mmol), 2 (0.25 mmol), Pd(OAc)2 (5 mol %), Phen
(10 mol %), Cs2CO3 (0.2 mmol), DMSO (2 mL), 150 °C, 20 h, under N2, isolated yield.
N
N
Cl
4eb
, 42%
O
4ea
, 67%
O
of bidentate phosphine and nitrogen ligands were screened, and
1,10-phenanthroline (Phen) gave the optimal result (Table 1, entry
14). The solvents were significant to this reaction and the initially
used DMSO provided the optimal result (Table 1, entries 17–20).
Only 60% yield was obtained when the temperature was decreased
to 130 °C (Table 1, entry 14). Finally, we found that the combina-
tion of 5 mol % of Pd(OAc)2, 10 mol % of Phen, and 1 equiv of Cs2CO3
in DMSO at 150 °C under nitrogen for 24 h served as the optimal
conditions for this transformation.
With acceptable conditions in hand (Table 1, entry 14), we first
tested the scope of this methodology for different iodobenzene
diacetates, as shown in Table 2. As expected, a series of functional
groups on the phenyl ring of iodobenzene diacetates, such as
methoxy, bromo, chloro, and cyano groups, were compatible for
the procedure, providing the arylated products in moderate to
good yields (3aa–3ah, Table 2). Generally, the reaction was not
sensitive to the electronic properties of the substituents on the
phenyl ring of iodobenzene diacetates, as both electron-donating
groups and electron-withdrawing groups were well-tolerated.
Except 3af, electron-donating groups gave slight higher yields
than those electron-withdrawing groups analogs (3aa and 3ab vs
3ag and 3ah, Table 2). Notably, 1-(diacetoxyiodo)-4-chloroben-
zene gave the corresponding arylating products in excellent yields
(3af, Table 2).
N
N
O2N
O2N
4fa, 40% (36h)
4fb
, 32%
a
Reaction conditions: 1 (0.2 mmol), 2 (0.25 mmol), Pd(OAc)2 (5 mol %), Phen
(10 mol %), Cs2CO3 (0.2 mmol), DMSO (2 mL), 150 °C, 20 h, under N2, isolated yield.
OAc
Pd
O
N
PhI(OAc)2
O
N
A
H
1
I
PdIV
Ph
OAc
O
Pd(II)
N
B
O
N
After a broad scope of electrophiles established, we were
particularly interested in extending the direct arylation to
benzo[d]oxazole derivatives (Table 3). 5-Methyl, 6-methyl, 5-tert-
butyl, 5-chloro and 5-nitro analogs could be selectively arylated
with an acceptable efficiency. However, the electron-withdrawing
groups on the phenyl ring of benzo[d]oxazole slightly decreased
the reaction efficiency.
Ph
ligand was ommitted for clarity
3
Scheme 1. Possible mechanism.
When PhI instead of PhI(OAc)2 was subjected to the procedure,
only trace of arylation products was detected by GC–MS. This re-
sult ruled out the possibility of ArI as the intermediate in the
reaction.
The mechanism of the arylation reaction may involve a Pd(II)
insertion into the benzoxazole 2-C–H bond in the presence of base
and subsequent oxidation of the Pd(II) complex A to a Pd(IV)
intermediate B by PhI(OAc)2 (Scheme 1).8,10 Then, reductive
elimination from the Pd(IV) complex affords the desired product
and regenerates the Pd(II) species.
In conclusion, we have developed a palladium-catalyzed aryla-
tion of benzo[d]oxazole C–H bond with iodobenzene diacetates.13
The reaction provides a novel methodology allowing for a wide
functional group tolerance. Further mechanistic studies of this pro-
cess and its application to the synthesis of functional materials are
currently underway in our laboratory.

4590
P. Yu et al. / Tetrahedron Letters 53 (2012) 4588–4590
Cheng, Y.; Lan, J.; You, J. Chem. Eur. J. 2011, 17, 13415; (f) Wang, M.; Li, D.; Zhou,
Acknowledgments
W.; Wang, L. Tetrahedron 2012, 68, 1926.
6. (a) Chen, X.; Engle, K. M.; Wang, D.-H.; Yu, J.-Q. Angew. Chem., Int. Ed. 2009, 48,
5094; (b) Jana, R.; Pathak, T. P.; Sigman, M. S. Chem. Rev. 2011, 111, 1417; (c)
Tredwell, M. J.; Gulias, M.; Bremeyer, N. G.; Johansson, C. C. C.; Collins, B. S. L.;
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We thank the National Natural Science Foundation of China
(No. 209072115) and the Natural Science Foundation of Zhejiang
Province (No. R4110294 and LY12B02010) and the Priority Aca-
demic Program Development of Jiangsu Higher Education Institu-
tions for financial support.
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Supplementary data
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.tetlet.2012.06.076.
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phenanthroline (7.9 mg, 10 mol %) and DMSO (2 mL). The mixture was stirred
at 150 °C for 20 h. After the completion of the reaction, as monitored by TLC,
10 mL of ethyl acetate was added and the mixture was washed with water
(3 ꢁ 5 mL). Then the organic layer was concentrated in vacuo and the residue
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