Cyclopalladated ferrocenylimine catalyzed chlorination of 2-arylbenzoxazoles

Article abstract of DOI:10.1002/cjoc.201180245

An efficient and facile protocol for palladacycle-catalyzed chlorination of 2-arylbenzoxazoles was developed. The results represent the first examples involving the palladacycle as the catalyst for such chlorination. This chlorination was not a ligand-directed ortho-Ci-H activation, but an electrophilic substitution process at the para-position of the nitrogen atom in the benzo ring of benzoxazole moiety, the regiochemistry of which had been confirmed by HMBC spectral analysis. The catalytic system could tolerate various halogen atoms, such as F, Cl and Br, affording the corresponding products in moderate to excellent yields.

Full text of DOI:10.1002/cjoc.201180245

FULL PAPER
Cyclopalladated Ferrocenylimine Catalyzed Chlorination of
2-Arylbenzoxazoles
Leng, Yuting(冷瑜婷)
Yang, Fan*(杨帆)
Wu, Yangjie*(吴养洁)
Li, Ke(李克)
Chemistry Department, Henan Key Laboratory of Chemical Biology and Organic Chemistry, Key Laboratory of
Applied Chemistry of Henan Universities, Zhengzhou University, Zhengzhou, Henan 450052, China
An efficient and facile protocol for palladacycle-catalyzed chlorination of 2-arylbenzoxazoles was developed.
The results represent the first examples involving the palladacycle as the catalyst for such chlorination. This chlori-
nation was not a ligand-directed ortho-C — H activation, but an electrophilic substitution process at the
para-position of the nitrogen atom in the benzo ring of benzoxazole moiety, the regiochemistry of which had been
confirmed by HMBC spectral analysis. The catalytic system could tolerate various halogen atoms, such as F, Cl and
Br, affording the corresponding products in moderate to excellent yields.
Keywords chlorination, arylbenzoxales, cyclopalladated ferrocenylimines, HMBC spectra
Introduction
N
Aryl or heteroaryl halides are important starting ma-
terials to construct complicated structures and notable
structural motifs in natural products and manufactured
drugs.1 Recently, halogenated arenes were selectively
synthesized by metal-catalyzed halogenation of C— H
bonds.2 Particularly, Sanford, Yu and Shi have demon-
strated that the directing group could act as an effective
strategy for the halogenation of ortho-C— H bond of the
directing group.3 Benzoxazoles are the important phar-
macophore with lower toxicities and have exhibited a
variety of biological activities.4 The direct arylation of
2-aryl benzoxazoles was successfully developed using
benzoxazoles as the directing group in our research
group.5 Further extension and branching functional sub-
stituents on them such as chlorination, would have great
importance for the facile synthesis of pharmaceutical
intermediates bearing the benzoxazole moiety.
Cyclopalladated ferrocenylimines as a family of
versatile palladacycle catalysts were developed by our
research group and had been applied to diverse catalytic
coupling reactions (Figure 1).6 They are often stable,
convenient to be prepared and easy to handle, and can
be used as important alternatives to simple palladium
species. Inspired by the above-mentioned and our own
reports, we explored the palladacycle-catalyzed chlorin-
ation of 2-arylbenzoxazoles and found that this reaction
was not a ligand-directed ortho-C— H activation process,
but a classic electrophilic substitution at the para-posi-
tion of the nitrogen atom in the benzo ring of benzoxa-
zole moiety.
Fe Pd
Cl
PPh3
Figure 1 Palladacycle I.
Results and discussion
In our initial study, we examined the effects of chlo-
rinating reagents, solvents and various catalysts on the
chlorination of 2-(3-methylphenyl)benzoxazole. The
results are summarized in Table 1. The reaction of
2-(3-methylphenyl)benzoxazole with CuCl2 was carried
out in the presence of PdCl2, and only a very low yield
was obtained (Table 1, Entry 1). After screening the
chlorinating reagents, we found that N-chlorosuccin-
imide (NCS) appeared to be the better choice (Table 1,
Entries 1— 3). Then, different solvents were investi-
gated, and AcOH could give the desired product in
moderate yield of 42% (Table 1, Entries 3— 6). Finally,
among palladium catalysts, palladacycle I as the catalyst
gave the desired product in 89% yield (Table 1, Entry 7).
However, Pd(OAc)2 and Pd2(dba)3 did not exhibit
higher catalytic activity in this reaction (Table 1, Entries
8, 9).
Under the optimized conditions, the chlorination of
diverse 2-arylbenzoxazoles was examined to explore the
scope of the reaction (Table 2). Generally, the reaction
proceeded well to afford the desired products in moder-
ate to good yields, and the electronic effect has no sig-
*
E-mail: yangf@zzu.edu.cn; wyj@zzu.edu.cn; Fax: 0086-371-6797-9408
Received March 13, 2011; revised and accepted April 15, 2011.
Project supported by the National Natural Science Foundation of China (No. 20772114) and the Innovation Fund for Outstanding Scholar of Henan
Province (No. 0621001100).
Chin. J. Chem. 2011, 29, 1703— 1708
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Leng et al.
FULL PAPER
Table 1 Effects of catalysts, chlorinating reagents and solvents
on the chlorination of 2-(3-methylphenyl) benzoxazolea
1
7.57 in H NMR. The coupling constant of the H-7
Table 2 Palladacycle-catalyzed chlorination of 2-arylbenzo-
Palladium source
chlorinating reagent
xazoles with NCSa
Cl
O
N
O
N
Solvent, 100 oC, 4 h
Palladacycle I (1 mol%)
Cl
O
N
R
O
N
R
NCS (0.6 mmol)
2a
1a
AcOH, 100 oC, 4 h
Chlorinating
reagent
2
1
Entry
Palladium source Solvent Yieldb/%
Entry
R
Product
Yieldb/%
1
2
3
4
5
6
CuCl2
PdCl2 (5 mol%) CH3CN
17
12
p-Me-C6H4SO2Cl PdCl2 (5 mol%) CH3CN
Cl
Cl
O
NCS
NCS
NCS
NCS
PdCl2 (5 mol%) CH3CN
PdCl2 (5 mol%) DCE
PdCl2 (5 mol%) Dioxane
PdCl2 (5 mol%) HOAc
37
1
2
m-Me
89
85
84
80
78
82
72
80
75
83
73
N
2a
22
＜5
O
42
o-Me
p-Me
H
Palladacycle I
HOAc
N
2b
7
8
9
NCS
NCS
NCS
89
35
30
(1 mol%)
Pd(OAc)2
HOAc
Cl
O
(5 mol%)
3
Pd2(dba)3
HOAc
N
2c
(2.5 mol%)
a Reaction conditions: 1a (0.5 mmol), chlorinating reagent (0.6
mmol), palladium catalyst, solvent (2 mL), 100 ℃ for 4 h.
b Isolated yields.
Cl
Cl
O
4
N
2d
nificant influence on the reactions. It is noteworthy to
point out that this catalytic system could tolerate halo-
gen atoms (F, Cl and Br) (Table 2, Entries 5— 11), and
the chlorination took place at the para-position of the
nitrogen atom in the benzo ring of benzoxazole moiety.
F
O
5
m-F
m-Cl
m-Br
p-F
N
2e
Cl
Cl
O
Determination of the structures of the chlorinated
products by HMBC (1H-detected heteronuclear mul-
tiple bond correlation) spectra
6
N
2f
Br
The HMBC spectral data of the 2-aryl benzoxazole
containing a meta-substituent (2a) as the representative
chlorinated products was utilized to confirm that the
chlorination took place at the para-position of the ni-
trogen atom in the benzo ring of benzoxazole moiety
(Figure 2).
Cl
O
7
N
2g
Cl
O
F
8
N
2h
Initially, from 13C NMR we could identify the posi-
tion of the quaternary C-2 atom adjacent to N and O
atoms with the lowest electronic cloud density, which is
shifted to δ 163.9 at lower field. And the C-2 atom has
two strong correlated H atoms (H-2' and H-6'), which
indicates that both H-2' and H-6' atoms still exist in the
benzene ring and the chlorination did not occur at the
ortho-position of the directing group.
Cl
O
Cl
9
p-Cl
p-Br
N
2i
Cl
Cl
O
Br
10
N
2j
13
Then, from C NMR we could also assign the posi-
tion of the quaternary C-7a atom bonded to the O atom
and the quaternary C-3a atom adjacent to the N atom,
which are located at δ 150.9 at lower field and δ 140.8
at a little higher field, respectively. From HMBC spectra,
the C-7a atom has one strong correlated H atom (H-4)
and one weak correlated atom (H-7), and the C-3a atom
has two strong correlated H atoms (H-5 and H-7). Given
this, we could assign the position of the H-7 atom at δ
Cl
O
11 o,p-Cl2
Cl
N
2k
a
Reaction conditions: 1a—1k (0.5 mmol), NCS (0.6 mmol),
palladacycle I (1 mol%), AcOH (2 mL), 100 ℃ for 4 h. b Iso-
lated yields.
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© 2011 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2011, 29, 1703— 1708

Cyclopalladated Ferrocenylimine Catalyzed Chlorination of 2-Arylbenzoxazoles
4
3
N
4
3
N
6'
3a
7a
5'
6'
2'
3a
7a
5'
5
6
5
2
1'
2
1'
4'
3'
4'
3'
O1
O1
6
Cl
2'
7
7
Figure 2 HMBC spectrum of 2a.
1
atom is 2.00 Hz in the H NMR spectrum, which indi-
cates that there is no H atom at the ortho-position of the
C-7—H-7 bond. Thus, the chlorination should take
place at the C-6—H-6 bond.
Melting points were measured using a WC-1 micro-
scopic apparatus and are uncorrected. GC analysis was
performed on Agilent 4890D gas chromatograph. Mass
spectra were measured on an LC-MSD-Trap-XCT in-
strument. High-resolution mass spectra were measured
on a MALDI-FTMS. Elemental analyses were deter-
mined with a Carlo Erba elemental analyzer. IR spectra
were recorded on a Bruker VECTOR 22 spectropho-
tometer. Dichloromethane, ethyl acetate and hexane
(analytical grade) were used for column chromatogra-
phy without further purification. Other solvents were
purified according to the standard methods. All the
2-arylbenzoxazoles were prepared according to the pre-
viously published procedures.7 The other chemicals
were obtained from commercial sources and used
as-received unless otherwise noted.
Conclusions
In summary, the palladacycle-catalyzed chlorination
of 2-arylbenzoxazoles derivatives has been developed,
which is not the ligand-directed ortho-functionalization,
but a typical electrophilic substitution process. This
protocol would be beneficial for the convenient and ef-
ficient synthesis of benzoxazoles derivatives. Further
investigation on the application of this synthetic meth-
odology is currently underway.
Experimental
General procedure for the palladacycle I6a
General details
After a solution of lithium tetrachloropalladate(II) in
10 mL of methanol (1 mmol Li2PdCl4) was added to a
solution of mole equivalents of NaOAc and ferro-
cenylimine in 30 mL of methanol, the resulting red so-
1H NMR, 13C NMR, H-13C HBMC NMR spectra
1
were recorded on a Bruker DPX-400 spectrometer with
CDCl3 as the solvent and TMS as an internal standard.
Chin. J. Chem. 2011, 29, 1703— 1708
© 2011 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
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Leng et al.
FULL PAPER
lution was stirred at room temperature for about 24 h
and filtered. The obtained solid without further purifica-
tion was treated with PPh3 (2 mmol) in CH2Cl2 at room
temperature for 0.5 h and then filtered. The filtrate was
concentrated in vacuo and the residue was purified by
flash chromatography on silica gel (ethyl acetate/hexane)
to give the red solid. Finally, the red solid was crystal-
lized from CH2Cl2-petroleum ether (60—90 ℃) to pro-
duce the pure cyclopalladated compound I.
129.6, 130.3, 140.9, 142.3, 150.8, 163.9; IR (KBr) ν:
3035, 2921, 1617, 1555, 1496, 1457, 1418, 1326, 1281,
1254, 1173, 1117, 1047, 1011, 917, 834, 807, 725, 699,
－
1
635, 595, 501 cm ; HRMS-ESI calcd for C14H11ClNO
(M＋H) 244.0529, found 244.0526.
6-Chloro-2-phenylbenzoxazole (2d)8 Purification
by flash chromatography over silica gel, eluting with
ethyl acetate-hexane (V∶V＝1∶30), provided the de-
sired compound as a white solid; Rf＝0.36; m.p. 59—61
℃; 1H NMR (CDCl3, 400 MHz) δ: 7.25—7.32 (m, 1H),
7.48—7.56 (m, 4H), 7.64 (d, J＝8.5 Hz, 1H), 8.18—
8.21 (m, 2H); 13C NMR (CDCl3, 100 MHz) δ: 111.2,
120.4, 125.2, 126.6, 127.6, 128.9, 130.6, 131.7, 140.8,
150.8, 163.6; IR (KBr) ν: 3057, 2924, 2854, 1618, 1552,
1483, 1451, 1426, 1331, 1263, 1121, 1052, 1022, 919,
876, 809, 693, 595, 487 cm － 1. Anal. calcd for
C13H8ClNO (229.03): C 67.99, H 3.51, N 6.10; found C
68.37, H 3.61, N 5.94.
General procedure for the chlorination of 2-aryl-
benzoxazoles
Substrate (0.5 mmol), chlorinating reagent (0.6
mmol) and palladacycle I (1 mol%) were dissolved in
AcOH (2 mL) in a 10 mL vial under air and heated at a
specific temperature for 4 h. After the reaction was
complete, the mixture was diluted with CH2Cl2 (10 mL),
filtered through a pad of Celite, and washed multiple
times with CH2Cl2. The combined organic solutions
were evaporated under reduced pressure and the residue
was purified by flash chromatography on silica gel
(ethyl acetate/hexane) to give the pure product.
6-Chloro-2-(3-fluorophenyl)benzoxazole
(2e)
Purification by flash chromatography over silica gel,
eluting with ethyl acetate-hexane (V ∶ V ＝ 1 ∶ 30),
provided the desired compound as a white solid; Rf＝
0.38; m.p. 128—129 ℃; 1H NMR (CDCl3, 400 MHz) δ:
7.18—7.24 (m, 1H), 7.24—7.26 (m, 1H), 7.32—7.35
(m, 1H) 7.48—7.50 (m, 1H), 7.58 (s, 1H), 7.65—7.68
(m, 1H), 8.00 (d, J＝7.9 Hz, 1H); 13C NMR (CDCl3,
100 MHz) δ: 111.3, 114.5 (d, J＝24.4 Hz), 118.8 (d,
J＝21.2 Hz), 120.7, 123.3 (d, J＝3.1 Hz), 125.5, 129.9
(d, J＝8.9 Hz), 130.7 (d, J＝8.1 Hz), 130.7, 140.7,
150.9, 162.4 (d, J＝3.4 Hz), 162.9 (d, J＝245.8 Hz); IR
(KBr) ν: 3069, 1592, 1556, 1481, 1452, 1328, 1295,
1265, 1210, 1176, 1051, 881, 811, 787, 722, 673, 596,
Characterization data for all the compounds
6-Chloro-2-(3-methylphenyl)benzoxazole
(2a)
Purification by flash chromatography over silica gel,
eluting with ethyl acetate-hexane (V∶V＝1∶30), pro-
vided the desired compound as a white solid; Rf＝0.40;
1
m.p. 99—100 ℃; H NMR (CDCl3, 400 MHz) δ: 2.45
(s, 3H), 7.26—7.43 (m, 3H), 7.57 (s, 1H), 7.66 (d, J＝
8.5 Hz, 1H), 8.00—8.02 (m, 2H); 13C NMR (CDCl3,
100 MHz) δ: 21.4, 111.2, 120.4, 124.8, 125.2, 126.5,
128.2, 128.9, 130.6, 132.7, 138.8, 140.9, 150.9, 163.9;
IR (KBr) ν: 3057, 1615, 1554, 1453, 1423, 1329, 1261,
－
1
516 cm . Anal. calcd for C13H7ClFNO (247.02): C
63.05, H 2.85, N 5.66; found C 63.16, H 2.98, N 5.46.
－
1
1052, 920, 864, 803, 714, 681, 593, 434 cm ; HRMS-
ESI calcd for C14H11ClNO (M＋H) 244.0529, found
244.0530.
6-Chloro-2-(3-chlorophenyl)benzoxazole
(2f)
Purification by flash chromatography over silica gel,
eluting with ethyl acetate-hexane (V ∶ V ＝ 1 ∶ 30),
provided the desired compound as a white solid; Rf＝
0.35; m.p. 148—150 ℃; 1H NMR (CDCl3, 400 MHz) δ:
7.26—7.33 (m, 1H), 7.43—7.48 (m, 2H), 7.55 (s, 1H),
7.64 (d, J＝8.5 Hz, 1H), 8.06 (d, J＝7.7 Hz, 1H), 8.17
(s, 1H); 13C NMR (CDCl3, 100 MHz) δ: 111.3, 120.6,
125.5, 125.6, 127.6, 128.3, 130.21, 131.1, 131.7, 135.1,
140.6, 150.8, 162.2; IR (KBr) ν: 3065, 1611, 1550, 1472,
1428, 1330, 1259, 1102, 1051, 921, 862, 839, 805, 756,
6-Chloro-2-(2-methylphenyl)benzoxazole
(2b)
Purification by flash chromatography over silica gel,
eluting with ethyl acetate-hexane (V∶V＝1∶30), pro-
vided the desired compound as a white solid; Rf＝0.42;
m.p. 85—86 ℃; 1H NMR (CDCl3, 400 MHz) δ: 2.79 (s,
3H), 7.30—7.42 (m, 4H), 7.57 (s, 1H), 7.68 (d, J＝8.4
Hz, 1H), 8.13 (d, J＝8.3 Hz, 1H); 13C NMR (CDCl3,
100 MHz) δ: 22.2, 111.0, 120.5, 125.0, 125.60, 126.0,
129.8, 130.50, 131.1, 131.8, 138.9, 140.7, 150.3, 163.9;
IR (KBr) ν: 3065, 1606, 1542, 1485, 1432, 1389, 1245,
1208, 1084, 1027, 961, 913, 844, 774, 723, 673, 598,
－
1
718, 675, 595, 433 cm . Anal. calcd for C13H7Cl2NO
(262.99): C 59.12, H 2.67, N 5.30; found C 59.23, H
2.64, N 5.22.
－
1
456 cm ; HRMS-ESI calcd for C14H11ClNO (M＋H)
6-Chloro-2-(3-bromophenyl)benzoxazole
(2g)
244.0529, found 244.0525.
Purification by flash chromatography over silica gel,
eluting with ethyl acetate-hexane (V ∶ V ＝ 1 ∶ 30),
provided the desired compound as a white solid; Rf＝
0.37; m.p. 141—143 ℃; 1H NMR (CDCl3, 400 MHz) δ:
7.26—7.39 (m, 2H), 7.56 (s, 1H), 7.63—7.66 (m, 2H),
8.11 (d, J＝7.7 Hz, 1H), 8.34 (s, 1H); 13C NMR (CDCl3,
100 MHz) δ: 111.3, 120.6, 123.0, 125.5, 126.0, 128.5,
130.4, 131.1, 134.6, 140.6, 150.8, 162.0; IR (KBr) ν:
3064, 1614, 1546, 1468, 1427, 1330, 1259, 1049, 860,
6-Chloro-2-(4-methylphenyl)benzoxazole
(2c)
Purification by flash chromatography over silica gel,
eluting with ethyl acetate-hexane (V∶V＝1∶30), pro-
vided the desired compound as a white solid; Rf＝0.41;
m.p. 126—128 ℃; 1H NMR (CDCl3, 400 MHz) δ: 2.42
(s, 3H), 7.26—7.30 (m, 3H), 7.53 (s, 1H), 7.62 (d, J＝
8.5 Hz, 1H), 8.12—8.14 (m, 2H); 13C NMR (CDCl3,
100 MHz) δ: 21.6, 111.1, 120.2, 123.9, 125.1, 127.6,
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© 2011 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2011, 29, 1703— 1708

Cyclopalladated Ferrocenylimine Catalyzed Chlorination of 2-Arylbenzoxazoles
－
1
804, 715, 673, 594 cm . Anal. calcd for C13H7BrClNO
(306.94): C 50.60, H 2.29, N 4.54; found C 50.76, H
(c) Littke, A. F.; Fu, G. C. Angew. Chem., Int. Ed. 2002, 41,
4176.
2.30, N 4.24.
6-Chloro-2-(4-fluorophenyl)benzoxazole
2
For selective examples, see:
(a) Bedford, R. B.; Mitchellb, C. J.; Webster, R. L. Chem.
Commun. 2010, 3095.
(b) Song, B. R.; Zheng, X. J.; Mo, J.; Xu, B. Adv. Synth.
Catal. 2010, 352, 329.
(c) Niedermann, K.; Welch, J. M.; Koller, R.; Cvengroš, J.;
Santschi, N.; Battaglia, P.; Togni, A. Tetrahedron 2010, 66,
5753.
(d) Powers, D. C.; Geibel, M. A. L.; Klein, J. E. M. N.;
Ritter, T. J. Am. Chem. Soc. 2009, 131, 17050.
(e) Ackermann, L.; Vicente, R.; Kapdi, A. R. Angew. Chem.,
Int. Ed. 2009, 48, 9792.
(f) Chen, X.; Engle, K. M.; Wang, D.-H.; Yu, J.-Q. Angew.
Chem., Int. Ed. 2009, 48, 5094.
(2h)
Purification by flash chromatography over silica gel,
eluting with ethyl acetate-hexane (V ∶ V ＝ 1 ∶ 30),
provided the desired compound as a white solid; Rf＝
0.33; m.p. 132—133 ℃; 1H NMR (CDCl3, 400 MHz) δ:
7.17—7.21 (m, 2H), 7.30—7.32 (m, 1H), 7.54 (s, 1H),
7.63 (d, J＝8.5 Hz, 1H), 8.17—8.21 (m, 2H); 13C NMR
(CDCl3, 100 MHz) δ: 111.2, 116.2 (d, J＝22.1 Hz),
120.4, 123.0 (d, J＝3.3 Hz), 125.3, 130.0 (d, J＝8.9 Hz),
130.7, 140.8, 150.9, 162.7, 164.9 (d, J＝251.8 Hz).
Anal. calcd for C13H7ClFNO (247.02): C 63.05, H 2.85,
N 5.66; found C 63.22, H 2.87, N 5.59.
6-Chloro-2-(4-chlorophenyl)benzoxazole
(2i)9
Purification by flash chromatography over silica gel,
eluting with ethyl acetate-hexane (V ∶ V ＝ 1 ∶ 30),
provided the desired compound as a white solid; Rf＝
0.35; m.p. 148—150 ℃; 1H NMR (CDCl3, 400 MHz) δ:
7.32—7.35 (m, 1H), 7.48—7.51 (m, 2H), 7.57 (d, J＝
1.8 Hz, 1H), 7.66 (d, J＝8.5 Hz, 1H), 8.13—8.15 (m,
2H); 13C NMR (CDCl3, 100 MHz) δ: 111.3, 120.5,
125.2, 125.5, 128.9, 129.3, 130.9, 138.1, 140.8, 150.9,
162.7.
(g) Wang, X. S.; Mei, T.-S.; Yu, J.-Q. J. Am. Chem. Soc.
2009, 131, 7520.
(h) Ball, N. D.; Sanford, M. S. J. Am. Chem. Soc. 2009, 131,
3796.
(i) Zhao, X. D.; Dimitrijević, E.; Dong, V. M. J. Am. Chem.
Soc. 2009, 131, 3466.
(j) Mei, T.-S.; Giri, R.; Maugel, N.; Yu, J.-Q. Angew. Chem.,
Int. Ed. 2008, 47, 5215.
(k) Yu, W.-Y.; Sit, W. N.; Lai, K.-M.; Zhou, Z.; Chan, A. S.
C. J. Am. Chem. Soc., 2008, 130, 3304.
6-Chloro-2-(4-bromophenyl)benzoxazole
(2j)
Purification by flash chromatography over silica gel,
eluting with ethyl acetate-hexane (V∶V＝1∶30), pro-
vided the desired compound as a white solid; Rf＝0.38;
m.p. 168—170 ℃; 1H NMR (CDCl3, 400 MHz) δ: 7.31
—7.33 (m, 1H), 7.55 (s, 1H), 7.63—7.65 (m, 3H), 8.04
(l) Zhang, Y.; Feng, J.; Li, C.-J. J. Am. Chem. Soc. 2008,
130, 2900.
(m) Ozdemir, I.; Demir, S.; Cetinkaya, B.; Gourlaouen, C.;
Maseras, F.; Bruneau, C.; Dixneuf, P. H. J. Am. Chem. Soc.
2008, 130, 1156.
(n) Murahashi, S.-I.; Nakae, T.; Terai, H.; Komiya, N. J. Am.
Chem. Soc. 2008, 130, 11005.
(o) Berman, A. M.; Lewis, J. C.; Bergman, R. G.; Ellman, J.
A. J. Am. Chem. Soc. 2008, 130, 14926.
(p) Lewis, J. C.; Berman, A. M.; Bergman, R. G.; Ellman, J.
A. J. Am. Chem. Soc. 2008, 130, 2493.
(q) Li, L.; Brennessel, W. W.; Jones, W. D. J. Am. Chem.
Soc. 2008, 130, 12414.
(a) Hull, K. L.; Sanford, M. S. J. Am. Chem. Soc. 2007, 129,
11904.
(b) Wan, X. B.; Ma, Z. X.; Li, B. J.; Zhang, K. Y.; Cao, S.
K.; Zhang, S. W.; Shi, Z. J. J. Am. Chem. Soc. 2006, 128,
7416.
(c) Kalyani, D.; Dick, A. R.; Anani, W. Q.; Sanford, M. S.
Org. Lett. 2006, 8, 2523.
(d) Chen, X.; Hao, X.-S.; Goodhue, C. E.; Yu, J.-Q. J. Am.
Chem. Soc. 2006, 128, 6790.
(a) Sondhi, S. M.; Singh, N.; Kumar, A.; Lozach, O.; Meijer,
L. Bioorg. Med. Chem. 2006, 14, 3758.
(b) Rida, S. M.; Ashour, F. A.; El-Hawash, S. A. M.; Else-
mary, M. M.; Badr, M. H.; Shalaby, M. A. Eur. J. Med.
Chem. 2005, 40, 949.
(a) Yang, F.; Wu, Y.-J.; Zhu, Z.-W.; Zhang, J.-L.; Li, Y.-N.
Tetrahedron 2008, 64, 6782.
13
—8.06 (m, 2H); C NMR (CDCl3, 100 MHz) δ: 111.2,
120.5, 125.4, 125.6, 126.5, 129.0, 131.0, 132.3, 140.7,
150.8, 162.7; IR (KBr) ν: 3078, 2924, 1612, 1584, 1457,
1427, 1394, 1327, 1256, 1233, 1066, 1046, 1003, 918,
837, 814, 723, 559, 499 cm － 1. Anal. calcd for
C13H7BrClNO (306.94): C 50.60, H 2.29, N 4.54; found
C 50.78, H 2.24, N 4.34.
6-Chloro-2-(2,4-dichlorophenyl)benzoxazole (2k)
Purification by flash chromatography over silica gel,
eluting with ethyl acetate-hexane (V∶V＝1∶ 30),
provided the desired compound as a white solid; Rf＝
0.39; m.p. 140—141 ℃; 1H NMR (CDCl3, 400 MHz) δ:
7.37—7.40 (m, 2H), 7.57—7.61 (m, 2H), 7.73 (d, J＝
8.5 Hz, 1H), 8.08 (d, J＝8.5 Hz, 1H); 13C NMR (CDCl3,
100 MHz) δ: 111.4, 121.0, 124.2, 125.6, 127.5, 131.4,
131.5, 132.4, 134.3, 137.8, 140.3, 150.6, 160.6; IR (KBr)
ν: 3075, 1609, 1584, 1554, 1467, 1426, 1370, 1108,
3
－
1
1080, 1020, 919, 844, 805, 596 cm ; HRMS-ESI calcd
4
5
for C13H6Cl3NO (M＋H) 297.9593, found 297.9602.
References
1
(a) Nicolaou, K. C.; Bulger, P. G.; Sarlah, D. Angew. Chem.,
Int. Ed. 2005, 44, 4442.
(b) Yang, F.; Wu, Y.-J.; Li, Y.-N.; Wang, B.; Zhang, J.-L.
Tetrahedron 2009, 65, 914.
(c) Li, Y.-N.; Yang, F.; Wu, Y.-J. Chem. J. Chin. Univ.
(b) Hassan, J.; Sévignon, M.; Gozzi, C.; Schulz, E.; Lemaire,
M. Chem. Rev. 2002, 102, 1359.
Chin. J. Chem. 2011, 29, 1703— 1708
© 2011 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
1707

Leng et al.
FULL PAPER
2008, 29, 2535.
(e) Leng, Y.-T.; Yang, F.; Wei, K.; Wu, Y.-J. Tetrahedron
2010, 66, 1244.
Yoshifuji, M.; Nagase, R.; Inamoto, N. Bull. Chem. Soc.
Jpn. 1982, 55, 873.
Ueda, S.; Nagasawa, H. J. Org. Chem. 2009, 74, 4272.
Nakagawa, K.; Onoue, H.; Sugita, J. Chem. Pharm. Bull.
1964, 12, 1135.
6
(a) Huo, S.-Q.; Wu, Y.-J.; Du, C.-X.; Zhu, Y.; Yuan, H.-Z.;
Mao, X.-A. J. Organomet. Chem. 1994, 483, 139.
(b) Wu, Y.-J.; Hou, J.-J.; Yun, H.-Y.; Cui, X.-L.; Yuan, R.-J.
J. Organomet. Chem. 2001, 637— 639, 793.
(c) Yang, F.; Cui, X.-L.; Li, Y.-N.; Zhang, J.-L.; Ren, G.-R.;
Wu, Y.-J. Tetrahedron 2007, 63, 1963.
7
8
9
(d) Yang, F.; Wu, Y.-J. Eur. J. Org. Chem. 2007, 3476.
(E1103139 Pan, B.)
1708
www.cjc.wiley-vch.de
© 2011 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2011, 29, 1703— 1708