Facile synthesis of arylboronic esters by palladacycle-catalyzed bromination of 2-arylbenzoxazoles and subsequent borylation of the brominated products

Article abstract of DOI:10.1016/j.tet.2011.06.057

An efficient and facile synthesis of arylboronic esters bearing the benzoxazole moiety has been described using a new family of palladacycle: cyclopalladated ferrocenylimines as the catalysts. This reaction includes two concessive steps: bromination of 2-arylbenzoxazoles and subsequent borylation. The bromination of para-C-H bond was an electrophilic substitution process by using NBS as the brominating reagent, and the brominated products were determined by HMBC (¹H-detected heteronuclear multiple bond correlation) spectra. Particularly, the borylation step could be carried out successively only after removal of the solvent to afford the arylboronic esters in moderate to good yields.

Full text of DOI:10.1016/j.tet.2011.06.057

Tetrahedron 67 (2011) 6191e6196
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Tetrahedron
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Facile synthesis of arylboronic esters by palladacycle-catalyzed bromination of
2-arylbenzoxazoles and subsequent borylation of the brominated products
*
*
Yuting Leng, Fan Yang , Weiguo Zhu, Dapeng Zou, Yangjie Wu , Ranran Cai
Chemistry Department, Henan Key Laboratory of Chemical Biology and Organic Chemistry, Key Laboratory of Applied Chemistry of Henan Universities, Zhengzhou University,
Zhengzhou 450052, People’s Republic of China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 7 May 2011
Received in revised form 10 June 2011
Accepted 21 June 2011
Available online 25 June 2011
An efficient and facile synthesis of arylboronic esters bearing the benzoxazole moiety has been described
using a new family of palladacycle: cyclopalladated ferrocenylimines as the catalysts. This reaction in-
cludes two concessive steps: bromination of 2-arylbenzoxazoles and subsequent borylation. The bro-
mination of para-CeH bond was an electrophilic substitution process by using NBS as the brominating
reagent, and the brominated products were determined by HMBC (1H-detected heteronuclear multiple
bond correlation) spectra. Particularly, the borylation step could be carried out successively only after
removal of the solvent to afford the arylboronic esters in moderate to good yields.
Keywords:
Bromination
Borylation
Ó 2011 Elsevier Ltd. All rights reserved.
Palladium catalysis
HMBC spectra
1. Introduction
oxidative aminations, and additions to imines and iminiumions.10
However, the classical preparation of arylboronic esters is often
Transition-metal-catalyzed CeH bond functionalization has
become a valuable synthetic tool for the selective oxidation of or-
ganic molecules.1 Currently, remarkable progress has been made in
the development of catalytic C-heteroatom bond forming re-
actions.2 The halogenated arenes are extremely valuable starting
materials for synthetic elaboration especially on the aspect of
a variety of biologically active molecules and pharmaceutical
agents.3 Notably, Sanford and Yu developed the catalytic versions
for directed CeH bond halogenation.4,5 Wang reported a protocol
for the bromination of arenes with NBS under AuCl3 catalysis.6 Very
recently, Gaunt and co-workers reported a highly para-selective
copper(II)-catalyzed direct arylation of aniline and phenol de-
rivatives, which underwent a typically electrophilic substitution
process.7 Zhang also described palladium-catalyzed para-CeH
aminations of anilides with N-fluorobenzenesulfonimide.8 From
these points of view, we consider it highly fascinating and desirable
to apply this efficient para-CeH halogenation to the synthesis of
arylboronic esters.
with the aid of stoichiometric organometallic reagents, such as
magnesium or lithium alkyl reagents.11 To overcome the limita-
tion, two distinct approaches have been pursued by a number of
groups. On the one hand, the pre-functionalized aryl halides could
be utilized as starting materials under palladium catalysis
(Scheme 1a).12 On the other hand, several groups achieved the
direct conversion of CeH bonds to CeB bonds catalyzed by Ir and
Rh through selective CeH bond functionalization(Scheme 1b).13
Our interests focused on the combined strategy of the afore-
mentioned approaches by seeking for the possibility of developing
a significant practical improvement over palladium-catalyzed
CeH borylation (Scheme 1c).
X
+
Bpin
Bpin
[Pd]
R
HBpin / B2pin2
(a)
(b)
R
R
Ligand
H
+
[Ir] or [Rh]
Ligand
HBpin / B2pin2
[Pd]
R
Arylboronic esters as a kind of versatile reagent are now widely
used in organic synthesis.9 They undergo metal-catalyzed cross-
coupling reactions, 1,2- and 1,4-additions to carbonyl compounds,
Br
Bpin
[Pd]
(c)
NBS etc
FG
B2pin2
FG
FG
* Corresponding authors. Fax: þ86 371 6797 9408; e-mail addresses: yangf@
Scheme 1. Strategies for the synthesis of arylboronic esters.
zzu.edu.cn (F. Yang), wyj@zzu.edu.cn (Y. Wu).
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.06.057

6192
Y. Leng et al. / Tetrahedron 67 (2011) 6191e6196
Cyclopalladated ferrocenylimines as a family of versatile palla-
palladacycle catalyst, the reaction proceeded very slowly and only
a low yield of 28% was observed (Table 1, entry 11). It indicated that
the palladacycle indeed played an important role for the successful
bromination. Finally, some other brominating reagents were also
examined, but the results were not satisfactory (Table 1, entries
12e14).
Under the optimized conditions, the bromination of diverse 2-
arylbenzoxazoles was examined to explore the scope of the re-
action. Generally, the bromination of 2-arylbenzoxazoles is a clas-
sical electrophilic aromatic substitution at the para-position of the
nitrogen atom in the benzene ring of benzoxazole affording the
desired products in moderate to good yields, and the substituent
effect has no significant influence on the reactions (Table 2). In this
dacycle catalysts (Fig. 1), which were developed by our research
group, have been applied to various reactions.14 Herein we report
for the first time the facile synthesis of arylboronic esters through
catalytic para-bromination using NBS as a brominating reagent and
following borylation of the new formed CeBr bond. The borylation
step could be performed directly without any special treatments
but removal of the solvent. It should be noted that this bromination
of 2-arylbenzoxazoles was not the ligand-directed ortho-CeH ac-
tivation process, but an electrophilic substitution at the para-po-
sition of the nitrogen atom in the benzene ring of benzoxazole,
which could be determined by HMBC (1H-detected heteronuclear
multiple bond correlation) spectra.
N
N
N
Fe Pd
Fe Pd Cl
Fe Pd
Cl
PPh3
II
Cl
PCy3
III
2
I
Fig. 1. Palladacycle IeIII.
2. Result and discussion
bromination, palladium species would act as the lewis acid catalyst.
For the 2-arylbenzoxazoles bearing electron-donating groups, the
desired products were isolated in high yields (Table 2, entries 1e3),
and the bromination of the electron-neutral substrate also worked
well at the para-position of nitrogen atom in benzene ring of
benzoxazole with higher electronic cloud density (Table 2, entry 4).
The reactions of 2-arylbenzoxazoles bearing electron-withdrawing
groups also generated the products in satisfactory yields (Table 2,
entries 5e11). Undoubtedly, all of the derived brominated products
have at least one halogen atom and could be functionalized further
to construct the complicated molecules.
In our initial study, we examined the effects on various catalysts,
brominating reagents and solvents in the bromination of 2-(3-
methylphenyl) benzoxazole. The results are summarized in Table 1.
Thereactionof2-(3-methylphenyl)benzoxazoleandNBSwascarried
out in the presence of Pd(OAc)2 as the catalyst, and the bromination
took place at the para-position of the nitrogen atom in the benzene
ring of benzoxazole owing to its higher electronic cloud density
(Table 1, entry 1). After screening the solvents, we found that the
AcOH appeared to be the best choice (Table 1, entries 1e3). Then,
different palladiumcatalystswere investigated(Table 1, entries 4e8),
and palladacycle I as the catalyst gave the desired product in 89%
yield (Table 1, entry 6). However, when the loading of catalyst or
reaction temperature was reduced, low yields of products were iso-
lated (Table 1, entries 9 and 10). Particularly, in the absence of the
Table 2
Palladacycle-catalyzed the bromination of 2-arylbenzoxazoles with NBSa
Br
R
O
O
N
R
NBS, palladacycle I
AcOH, 100 o
N
C
1a-1k
2a-2k
Table 1
Entry
1
R
Product
Yield (%)b
89
Effects of solvents, catalysts and brominating reagents on the bromination of 2-(3-
methylphenyl)benzoxazole (1a)a
Me
Br
2a
O
N
O
N
Br
m-Me
O
N
Palladacycle, solvent
Brominating reagent
Me
2a
1a
Br
2b
O
N
2
o-Me
86
Entry Brominating
reagent
Palladium source
T (ꢀC) Solvent Yield (%)b
1
2
3
4
5
6
7
8
NBS
NBS
NBS
NBS
NBS
NBS
NBS
NBS
NBS
NBS
NBS
Pd(OAc)2 (5 mol %)
Pd(OAc)2 (5 mol %)
Pd(OAc)2 (5 mol %)
PdCl2 (5 mol %)
Pd2(dba)3 (2.5 mol %)
Palladacycle I (1 mol %)
Palladacycle II (2 mol %) 100
Palladacycle III (2 mol %) 100
Palladacycle I (0.5 mol %) 100
Palladacycle I (1 mol %)
d
Reflux CH3CN 19
Br
2c
O
N
Reflux DCE
22
67
36
62
89
81
30
46
54
28
38
20
21
3
4
5
p-Me
H
90
90
92
Me
100
100
100
100
AcOH
AcOH
AcOH
AcOH
AcOH
AcOH
AcOH
AcOH
AcOH
AcOH
AcOH
AcOH
Br
2d
O
N
9
F
10
11
12c
13
14
50
Br
O
N
100
100
100
100
m-F
Br2/PhI(OAc)2 Palladacycle I (1 mol %)
CuBr2
Br2
2e
Palladacycle I (1 mol %)
Palladacycle I (1 mol %)
a
Cl
Reaction conditions: 1a (0.5 mmol), brominating reagent (0.75 mmol), solvent
70
Br
2f
O
N
(2 mL), palladium catalyst, 8 h.
6
m-Cl
b
Isolated yields based on 1a.
c
PhI(OAc)2 (0.75 mmol).
Bold indicates the optimized conditions.

Y. Leng et al. / Tetrahedron 67 (2011) 6191e6196
6193
Table 2 (continued )
did not occur at the ortho-position of the directing group. Then,
from 13C NMR we could also assign the position of C7a bonded to
the O atom and C3a adjacent to the N atom, which are located at
151.1 ppm in lower field and 141.3 ppm in a little higher field, re-
spectively. From the HMBC spectrum, the C7a atom has one strong
correlated H atom (H4) and one weak correlated atom (H7), and the
C3a atom has two strong correlated H atoms (H5 and H7). Given
this, we could assign the position of H7 atom with the chemical
shift of 7.60 ppm in the 1H NMR spectrum. The coupling constant of
the H7 atom is 1.40 Hz in the 1H NMR spectrum, which indicates
that there is no H atom at the ortho-position of the C7eH7 bond.
Thus, the bromination should take place at the C6eH6 bond.
Subsequently, we pursued the SuzukieMiyaura/borylation of
the obtained brominated products. The following borylation turned
out to be compatible with the palladium-catalyzed halogenation
conditions. In the typical procedure, the 2-arylbenzoxazoles were
first converted into the corresponding brominated products. After
the completion of bromination, the solvent was evaporated and the
crude products were directly subjected to the following borylation
couplings. The results of this palladacycle-catalyzed borylation of
brominated 2-arylbenzoxazoles were summarized in Table 3. The
reactions proceeded smoothly to afford the borylated products
with moderate to good yields. The electronic effect has no influence
on the borylation, and both electron-poor and electron-rich func-
tional groups could be tolerated in these couplings. Notably, when
the substrates possessed other halogen atoms, such as F, Cl, the
borylation would chemoselectively occurr on the CeBr bond.
Entry
R
Product
Yield (%)b
73
Br
Br
O
N
7
m-Br
2g
Br
O
N
8
p-F
90
F
2h
Br
O
N
9
p-Cl
p-Br
79
75
Cl
Br
2i
Br
O
N
10
2j
Cl
Br
O
N
11
o,p-Cl2
66
Cl
2k
a
Reaction conditions: 1aek (0.5 mmol), NBS (0.75 mmol), palladacycle
I
(1 mol %), AcOH (2 mL), 100 ꢀC, 8 h.
b
Isolated yield.
The HMBC (1H-detected heteronuclear multiple bond correla-
tion) spectral data of the representative brominated product (2a)
were utilized to confirm the assumption that the bromination took
place at the para-position of nitrogen atom in the benzene ring of
benzoxazole (Fig. 2).
3. Conclusion
In summary, we have developed an efficient protocol for
palladacycle-catalyzed direct bromination of 2-arylbenzoxazoles
with NBS through an electrophilic substitution process, and the
bromination took place at the para-position of the nitrogen atom in
benzene ring of benzoxazole. Moreover, as demonstrated by Suzuki
borylation, the reactions allow the combination of bromination of
CeH bonds and subsequent borylation in an efficient manner. The
borylated products would be applied to traditional Pd(0)/Pd(II)
coupling reactions to afford the complicated
with benzoxazoles moieties.
p-conjugated systems
4. Experimental section
4.1. General
1H NMR, 13C NMR, 1He1H COSY NMR, 1He13C HSQC NMR,
1He13C HMBC NMR spectra were recorded on a Bruker DPX-400
spectrometer with CDCl3 as the solvent and TMS as an internal
standard. Melting points were measured using a WC-1 microscopic
apparatus and are uncorrected. GC analysis was performed on
Agilent 4890D gas chromatograph. Mass spectra were measured on
an LC-MSD-Trap-XCT instrument. High-resolution mass spectra
were measured on a MALDI-FTMS. Elemental analyses were de-
termined with a Carlo Erba elemental analyzer. Dichloromethane,
ethyl acetate and hexane (analytical grade) were used for column
chromatography without further purification. Other solvents were
purified according to the standard methods. All the 2-
arylbenzoxazoles were prepared according to the previously pub-
lished procedures.15 The other chemicals were obtained from
commercial sources and used as-received unless otherwise noted.
Fig. 2. HMBC spectrum of 2a.
The HMBC spectral analysis of the 2-aryl benzoxazole contain-
ing a meta-substituent (2a) was outlined (Fig. 2). Initially, from 13C
NMR we could locate the position of the C2 atom adjacent to N and
O atoms with the lowest electronic cloud density, which is shifted
to 163.7 ppm in the lower field. And the C2 atom has two strong
correlated H atoms (H20 and H60), which indicates that both the H20
and H60 atoms still exist in the benzene ring and the bromination
4.2. General procedure for direct bromination
Substrate (0.5 mmol), brominating reagent (0.75 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 8 h. After the

Table 3
Palladacycle-catalyzed bromination and subsequent borylation of 2-arylbenzoxazolesa
Br
O
O
B
O
O
O
O
O
O
B
B
O
N
NBS, palladacycle I
N
R
R
AcOH, 100 o
C
N
palladacycle III (1 mol%), 6 h
R
dioxane, 80 oC, KOAc
1a-1k
2a-2k
3a-3k
Entry
1
R
Product
Yield (%)b
70
O
B
m-Me
O
N
O
3a
O
B
2
3
4
o-Me
p-Me
H
62
56
73
O
O
N
3b
O
B
O
O
N
3c
O
B
O
O
N
3d
O
B
F
5
m-F
81
52
73
O
N
O
3e
O
B
Cl
6
m-Cl
m-Br
O
O
N
3f
O
B
O
B
7c
O
O
N
O
3g
O
B
8
9
p-F
89
77
O
O
F
N
3h
O
B
p-Cl
O
O
Cl
N
3i
O
B
10c
p-Br
70
68
O
O
O
N
O
B
3j
O
B
Cl
11
o,p-Cl2
O
O
Cl
N
3k
a
Reaction conditions: 1aek (0.5 mmol), NBS (0.75 mmol), palladacycle I (1 mol %), AcOH (2 mL), 100 ꢀC; after the reaction was analyzed by TCL and GC, the solvent was
evaporated in vacuo, the mixture of B2pin2 (0.6 mmol), KOAc (1 mmol), palladacycle III (1 mol %), 1,4-dioxane (2 mL) was added under N2 and the reaction was carried out at
80 ꢀC for 6 h.
b
Isolated yields based on 1aek.
B2pin2 (1.2 mmol).
c

Y. Leng et al. / Tetrahedron 67 (2011) 6191e6196
6195
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.
(m, 3H), 7.61 (d, J¼8.4 Hz, 1H), 7.73 (s, 1H), 8.09 (d, J¼7.6 Hz, 1H),
8.20 (s, 1H); 13C NMR (100 MHz, CDCl3):
131.8, 130.3, 128.3, 128.3, 127.6, 125.7, 121.1, 118.4, 114.2; Anal. Calcd
for C13H7BrClNO: C 50.60, H 2.29, N 4.54; found: C 50.60, H 2.33,
N 4.40.
d
¼162.1, 151.2, 141.1, 135.1,
4.3.7. 6-Bromo-2-(3-bromophenyl)benzoxazole (2g). White solid,
4.3. General procedure for bromination and borylation of the
brominated products
mp 129e131 ꢀC, yield 73%; 1H NMR (400 MHz, CDCl3):
d
¼7.26e7.40
(m, 1H), 7.46e7.48 (m, 1H), 7.60e7.66 (m, 2H), 7.72 (s, 1H), 8.12 (d,
J¼7.8 Hz, 1H), 8.35 (s, 1H); 13C NMR (100 MHz, CDCl3):
¼161.9,
d
Substrate 1 (0.5 mmol), brominating reagent (0.75 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. After the re-
action was complete monitored by TCL and GC, the solvent was
evaporated under reduced pressure and a mixture of B2pin2
(0.6 mmol), (1.2 mmol for Table 3, entries 7 and 10), KOAc
(1 mmol), palladacycle III (1 mol %) and 1,4-dioxane (2 mL) was
added under N2. The reaction was carried out at 80 ꢀC for 6 h, and
then quenched with water. The mixture was diluted with ethyl
acetate (10 mL), filtered through a pad of Celite, and followed by
extraction with ethyl acetate for three times. The combined or-
ganic layer was dried over anhydrous Na2SO4 and filtered. After
removal of the solvent in vacuum, the residue was purified by
flash chromatography on silica gel (ethyl acetate/hexane) to give
the pure product.
151.1, 141.0, 134.7, 130.5, 130.4, 128.5, 128.3, 126.1, 123.0, 121.1, 118.4,
114.2; Anal. Calcd for C13H7Br2NO: C 44.23, H 2.00, N 3.97; found: C
44.51, H 2.04, N 3.93.
4.3.8. 6-Bromo-2-(4-fluorophenyl)benzoxazole (2h). White solid,
mp 123e124 ꢀC, yield 90%; 1H NMR (400 MHz, CDCl3):
d
¼7.17e7.27
(m, 2H), 7.44 (dd, J¼1.7 Hz, 8.5 Hz,1H), 7.58 (d, J¼8.5 Hz,1H), 7.70 (s,
1H), 8.17e8.20 (m, 2H); 13C NMR (100 MHz, CDCl3):
d
¼164.9 (d,
J¼252.0 Hz), 162.6, 151.1, 141.2, 129.9 (d, J¼8.9 Hz), 128.1, 122.9 (d,
J¼3.2 Hz), 120.8, 117.9, 116.1 (d, J¼22.1 Hz), 116.2 (d, J¼22.1 Hz),
114.0; HRMS-ESI (m/z): [MþH]þ calcd for C13H7BrFNO: 291.9773;
found 291.9772.
4.3.9. 6-Bromo-2-(4-chlorophenyl)benzoxazole (2i). White solid,
mp 146e148 ꢀC, yield 79%; 1H NMR (400 MHz, CDCl3):
d
¼7.45e7.49
(m, 3H), 7.59 (d, J¼8.3 Hz, 1H), 7.71 (s, 1H), 8.11e8.13 (m, 2H); 13C
4.3.1. 6-Bromo-2-(3-methylphenyl)benzoxazole (2a). White solid,
NMR (100 MHz, CDCl3):
128.9, 129.2, 129.3, 138.1, 141.2, 151.1, 162.5; Anal. Calcd for
C13H7BrClNO: C 50.60, H 2.29, N 4.54; found: C 50.93, H 2.38, N 4.53.
d
¼114.1, 118.2, 121.0, 125.1, 128.2, 128.8,
mp 92e93 ꢀC, yield 89%; 1H NMR (400 MHz, CDCl3):
d
¼2.45 (s, 3H),
7.34e7.47 (m, 3H), 7.61 (d, J¼8.4 Hz, 1H), 7.73 (s, 1H), 8.01 (d,
J¼3.6 Hz, 1H), 8.05 (s, 1H); 13C NMR (100 MHz, CDCl3):
¼163.7,
d
151.2, 141.3, 138.8, 132.7, 128.9, 128.2, 128.0, 126.5, 124.8, 120.9,
117.9, 114.1, 21.4; HRMS-ESI (m/z): [MþH]þ calcd for C14H11BrNO:
288.0024; found 288.0022.
4.3.10. 6-Bromo-2-(4-bromophenyl)benzoxazole (2j). White solid,
mp 154e156 ꢀC, yield 75%; 1H NMR (400 MHz, CDCl3):
d
¼7.26e7.48
(m,1H), 7.60e7.66 (m, 3H), 7.72 (s, 1H), 8.05e8.07 (m, 2H); 13C NMR
(100 MHz, CDCl3):
d
¼162.6, 151.1, 141.2, 132.3, 129.0, 129.0, 128.2,
4.3.2. 6-Bromo-2-(2-methylphenyl)benzoxazole (2b). White solid,
126.6, 125.5, 121.0, 118.3, 114.1; HRMS-ESI (m/z): [MþH]þ calcd for
mp 91e92 ꢀC, yield 86%; 1H NMR (400 MHz, CDCl3):
d
¼2.80 (s, 3H),
7.38 (m, 4H), 7.65 (d, J¼8.4 Hz, 1H), 7.75 (s, 1H), 8.15 (d, J¼1.4 Hz,
1H); 13C NMR (100 MHz, CDCl3):
C13H7Br2NO: 351.8972; found 351.8971.
d
¼163.8, 150.7, 141.3, 139.0, 131.9,
4.3.11. 6-Bromo-2-(2,4-dichlorophenyl)benzoxazole
(2k). White
131.2, 129.9, 127.8, 126.1, 125.6, 121.0, 117.8, 114.0, 22.3; HRMS-ESI
solid, mp 126e127 ꢀC, yield 66%; 1H NMR (400 MHz, CDCl3):
(m/z): [MþH]þ calcd for C14H11BrNO: 288.0024; found 288.0019.
d
¼7.38e7.51 (m, 2H), 7.58 (s, 1H), 7.67e7.70 (m, 1H), 7.77 (s, 1H),
8.08 (d, J¼8.48 Hz, 1H); 13C NMR (100 MHz, CDCl3):
¼160.5, 150.9,
d
4.3.3. 6-Bromo-2-(4-methylphenyl)benzoxazole (2c). White solid,
140.8, 137.9, 134.3, 132.5, 131.4, 128.3, 127.5, 124.2, 121.5, 118.8,
114.3; HRMS-ESI (m/z): [MþH]þ calcd for C13H6BrCl2NO: 341.9088;
found 341.9083.
mp 121e123 ꢀC, yield 90%; 1H NMR (400 MHz, CDCl3):
d
¼2.43 (s,
3H), 7.25e7.31 (m, 2H), 7.43 (dd, J¼1.7 Hz, 8.4 Hz, 1H), 7.58 (d,
J¼8.4 Hz, 1H), 7.70 (s, 1H), 8.08 (d, J¼8.2 Hz, 2H); 13C NMR
(100 MHz, CDCl3):
d
¼163.7, 151.1, 142.4, 141.3, 129.7, 129.7, 129.6,
4.3.12. 6-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolane-2-yl)-2-(3-
methylphenyl)benzoxazole (3a). White solid, mp 74e75 ꢀC, yield
127.9,127.6, 123.8, 120.7, 117.6,114.0, 21.7; HRMS-ESI (m/z): [MþH]þ
calcd for C14H11BrNO: 288.0024; found 288.0023.
70%; 1H NMR (400 MHz, CDCl3):
d
¼1.37 (s, 12H), 2.44 (s, 3H),
7.32e7.41 (m, 2H), 7.75e7.83 (m, 2H), 8.03e8.09 (m, 3H); 13C NMR
(100 MHz, CDCl3):
4.3.4. 6-Bromo-2-phenylbenzoxazole (2d)16. White solid, mp
d
¼163.8, 150.3, 144.4, 138.4, 132.3, 130.7, 128.5,
89e91 ꢀC, yield 90%; 1H NMR (400 MHz, CDCl3):
d
¼7.27e7.54 (m,
128.0, 126.0, 124.6, 119.0, 116.4, 83.7, 24.7, 21.1; HRMS-ESI (m/z):
4H), 7.60e7.62 (m, 1H), 7.72 (s, 1H), 8.21 (d, J¼8.4 Hz, 2H); 13C NMR
[MþH]þ calcd for C20H23BNO3: 336.1771; found 336.1770.
(100 MHz, CDCl3):
d
¼163.5, 151.2, 141.3, 131.8, 128.9, 128.0, 127.7,
126.6, 120.9, 117.9, 114.1.
4.3.13. 6-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolane-2-yl)-2-(2-
methylphenyl)benzoxazole (3b). White solid, mp 80e82 ꢀC, yield
4.3.5. 6-Bromo-2-(3-fluorophenyl)benzoxazole (2e). White solid,
62%; 1H NMR (400 MHz, CDCl3):
d
¼1.39 (s, 12H), 2.82 (s, 3H),
7.34e7.42 (m, 3H), 7.79e7.85 (m, 2H), 8.06 (s, 1H), 8.20e8.21 (m,
1H); 13C NMR (100 MHz, CDCl3):
mp 107e108 ꢀC, yield 92%; 1H NMR (400 MHz, CDCl3):
d
¼7.24e7.28
(m, 1H), 7.49e7.52 (m, 2H), 7.63e7.65 (m, 1H), 7.75e7.76 (m, 1H),
d
¼164.3, 150.2, 144.7, 139.0, 131.8,
7.91e7.93 (m, 1H), 8.01e8.03 (m, 1H); 13C NMR (100 MHz, CDCl3):
131.1, 130.8, 130.1, 126.1, 126.1, 119.5, 116.6, 84.0, 24.9, 22.2; HRMS-
d
¼162.9 (d, J¼245.7 Hz), 162.2 (d, J¼3.2 Hz), 151.2, 141.1, 130.7 (d,
ESI (m/z): [MþH]þ calcd for C20H23BNO3: 336.1771; found 336.1766.
J¼8.0 Hz), 128.3, 123.4 (d, J¼3.1 Hz), 121.1, 118.8 (d, J¼21.2 Hz), 118.4,
114.6 (d, J¼24.0 Hz), 114.2; HRMS-ESI (m/z): [MþH]þ calcd for
C13H7BrFN: 291.9773; found 291.9773.
4.3.14. 6-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolane-2-yl)-2-(4-
methylphenyl)benzoxazole (3c). White solid, mp 144e145 ꢀC, yield
56%; 1H NMR (400 MHz, CDCl3):
d
¼1.38 (s, 12H), 2.44 (s, 3H), 7.33
(d, J¼8.1 Hz, 2H), 7.73e7.82 (m, 2H), 8.02 (s, 1H), 8.15e8.17 (m, 2H);
13C NMR (100 MHz, CDCl3):
¼164.2, 150.6, 144.8, 142.2, 130.9,
4.3.6. 6-Bromo-2-(3-chlorophenyl)benzoxazole (2f). White solid,
mp 112e114 ꢀC, yield 70%; 1H NMR (400 MHz, CDCl3):
d¼7.43e7.52
d

6196
Y. Leng et al. / Tetrahedron 67 (2011) 6191e6196
129.6, 127.8, 124.3, 119.2, 116.5, 84.0, 24.9, 21.6; HRMS-ESI (m/z):
[MþH]þ calcd for C20H23BNO3: 336.1771; found 336.1770.
7.57 (s, 1H) 7.80e7.85 (m, 2H), 8.06e8.14(m, 2H); 13C NMR
(100 MHz, CDCl3):
d
¼160.9, 150.4, 144.0, 137.6, 134.4, 132.6, 131.3,
131.1, 127.4, 124.7, 119.8, 116.9, 84.0, 24.9; HRMS-ESI (m/z): [MþH]þ
4.3.15. 6-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolane-2-yl)-2-
calcd for C19H19BCl2NO3: 390.0840; found 390.0835.
phenylbenzoxazole (3d). White solid, mp 95e96 ꢀC, yield 73%; 1H
Acknowledgements
NMR (400 MHz, CDCl3):
d
¼1.37 (s, 12H), 7.50e7.52 (m, 3H),
7.76e7.84 (m, 2H), 8.04 (s, 1H), 8.26e8.28 (m, 2H); 13C NMR
We are grateful to the National Natural Science Foundation of
China (No. 20772114) and the Innovation Fund for Outstanding
Scholar of Henan Province (No. 0621001100) for financial support of
this research. We also thank Professor Jianhua Xu for his valuable
comments on this paper.
(100 MHz, CDCl3):
d
¼163.9, 150.6, 144.7, 131.7, 131.0, 128.9, 127.8,
127.1, 119.4, 116.7, 84.0, 24.9; HRMS-ESI (m/z): [MþH]þ calcd for
C19H21BNO3: 322.1614; found 322.1607.
4.3.16. 6-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolane-2-yl)-2-(3-
fluorophenyl)benzoxazole (3e). White solid, mp 147e149 ꢀC, yield
81%; 1H NMR (400 MHz, CDCl3):
d
¼1.38 (s, 12H), 7.20e7.23 (m, 1H),
7.47e7.50 (m, 1H), 7.75e7.84 (m, 2H), 7.95 (d, 1H, J¼9.3 Hz),
8.03e8.06 (m, 2H); 13C NMR (100 MHz, CDCl3):
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tet.2011.06.057.
d¼162.8 (d,
J¼245.5 Hz), 162.6 (d, J¼3.3 Hz), 150.6, 144.4, 131.1, 130.6 (d,
J¼8.1 Hz), 129.0 (d, J¼8.5 Hz), 123.4 (d, J¼3.1 Hz), 119.5, 118.6 (d,
J¼21.1 Hz), 116.7, 114.6 (d, J¼23.9 Hz), 114.5, 84.1, 24.9; HRMS-ESI
(m/z): [MþH]þ calcd for C19H20BFNO3: 340.1520; found 340.1516.
References and notes
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G.; Ellman, J. A. J. Am. Chem. Soc. 2001, 123, 9692.
4.3.17. 6-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolane-2-yl)-2-(3-
chlorophenyl)benzoxazole (3f). White solid, mp 122e123 ꢀC, yield
52%; 1H NMR (400 MHz, CDCl3):
d
¼1.38 (s, 12H), 7.45e7.52 (m, 2H),
7.75e7.84 (m, 2H), 8.01 (s, 1H), 8.20 (d, J¼6.72 Hz, 1H), 8.26 (s, 1H);
13C NMR (100 MHz, CDCl3):
2. (a) Kalyani, D.; Sanford, M. S. Top. Organomet. Chem. 2007, 24, 85; (b) Kakiuchi, F.;
Murai, S. Top. Organomet. Chem.1999, 3, 47; (c) Powers, D. C.; Geibel, M. A. L.; Klein,
J. E. M. N.; Ritter, T. J. Am. Chem. Soc. 2009,131,17050; (d) Bedford, R. B.; Mitchellb,
C. J.; Webster, R. L. Chem. Commun. 2010, 3095; (e) Song, B. R.; Zheng, X. J.; Mo, J.;
Xu, B. Adv. Synth. Catal. 2010, 352, 329; (f) Niedermann, K.; Welch, J. M.; Koller, R.;
d
¼162.5, 150.6, 144.4, 135.1, 131.6, 131.2,
130.2, 128.8, 127.7, 125.8, 119.5, 116.7, 84.1, 24.9; HRMS-ESI (m/z):
[MþH]þ calcd for C19H20BClNO3: 356.1225; found 356.1220.
ꢀ
Cvengros, J.; Santschi, N.; Battaglia, P.; Togni, A. Tetrahedron 2010, 66, 5753.
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4.3.18. 6-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolane-2-yl)-2-[3-
(4,4,5,5-tetramethyl-1,3,2-dioxaborolane-2-yl)phenyl]benzoxazole
(3g). White solid, mp 203e204 ꢀC, yield 73%; 1H NMR (400 MHz,
4. (a) Kalyani, D.; Dick, A. R.; Anani, W. Q.; Sanford, M. S. Org. Lett. 2006, 8, 2523; (b)
Kalyani, D. A.; Dick, R. W.; Anani, Q.; Sanford, M. S. Tetrahedron 2006, 62, 11483.
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9. Hall, D. G. In Boronic Acids: Preparation and Applications in Organic Synthesis and
Medicine; Hall, D. G., Ed.; Wiley-VCH: Weinheim, 2005; p 1.
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CDCl3):
d
¼1.37 (s, 24H), 7.51e7.55 (m, 1H), 7.75e7.83 (m, 2H) 7.97
(d, J¼7.3 Hz, 1H), 8.03 (s, 1H), 8.36 (d, J¼7.9 Hz, 1H), 8.72 (s, 1H); 13C
NMR (100 MHz, CDCl3):
130.4, 128.3, 126.5, 119.3, 116.6, 84.1, 84.0, 24.9; HRMS-ESI (m/z):
[MþH]þ calcd for C25H32B2NO5: 448.2466; found 448.2461.
d
¼164.0, 150.7, 144.7, 137.9, 134.1, 131.0,
4.3.19. 6-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolane-2-yl)-2-(4-
fluorophenyl)benzoxazole (3h). White solid, mp 152e153 ꢀC, yield
89%; 1H NMR (400 MHz, CDCl3):
d
¼1.38 (s, 12H), 7.18e7.26 (m, 2H),
7.73e7.82(m, 2H), 8.01 (s,1H), 8.24e8.28 (m, 2H); 13C NMR (100 MHz,
CDCl3):
d¼164.9 (d, J¼251.5 Hz), 163.0, 150.6, 144.6, 131.1, 130.0 (d,
J¼8.8 Hz), 123.4 (d, J¼3.1 Hz), 119.3, 116.6, 116.1 (d, J¼22.0 Hz), 84.0,
24.9; HRMS-ESI (m/z): [MþH]þ calcd for C19H20BFNO3: 340.1520;
found 340.1523.
12. (a) Miyarura, N. Top. Curr. Chem. 2002, 219, 11; (b) Billingsley, K. L.; Barder, T. E.;
Buchwald, S. L. Angew. Chem., Int. Ed. 2007, 46, 5359; (c) Billingsley, K. L.;
Buchwald, S. L. J. Org. Chem. 2008, 73, 5589; (d) Duong, H. A.; Chua, S.; Huleatt,
P. B.; Chai, C. L. L. J. Org. Chem. 2008, 73, 9177; (e) Martin, T.; Laguerre, C.;
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4.3.20. 6-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolane-2-yl)-2-(4-
chlorophenyl)benzoxazole (3i). White solid, mp 171e172 ꢀC, yield
77%; 1H NMR (400 MHz, CDCl3):
d
¼1.38 (s, 12H), 7.47e7.50 (m, 2H),
7.73e7.83 (m, 2H), 8.01 (s, 1H), 8.17e8.20 (m, 2H); 13C NMR
~
Olivero, S.; Gimbert, Y.; Chavant, P. Y.; Dunach, E. J. Am. Chem. Soc. 2010, 132,
(100 MHz, CDCl3):
d
¼162.9, 150.6, 144.5, 137.9, 131.1, 129.2, 129.0,
11825; (h) Merino, P.; Tejero, T. Angew. Chem., Int. Ed. 2010, 49, 7164.
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Miyaura, N. Angew. Chem., Int. Ed. 2002, 41, 3056; (d) Ishiyama, T.; Takagi, J.;
Ishida, K.; Miyaura, N.; Anastasi, N. R.; Hartwig, J. F. J. Am. Chem. Soc. 2002, 124,
390; (e) Whisler, M. C.; MacNeil, S.; Snieckus, V.; Beak, P. Angew. Chem., Int. Ed.
2004, 43, 2206; (f) Mertins, K.; Zapf, A.; Beller, M. J. Mol. Catal. A: Chem. 2004,
207, 21; (g) Boller, T. M.; Murphy, J. M.; Hapke, M.; Ishiyama, T.; Miyaura, N.;
Hartwig, J. F. J. Am. Chem. Soc. 2005, 127, 14263; (h) Murphy, J. M.; Lawrence, J.
D.; Kawamura, K.; Incarvito, C.; Hartwig, J. F. J. Am. Chem. Soc. 2006, 128, 13684;
(i) Boebel, T. A.; Hartwig, J. F. J. Am. Chem. Soc. 2008, 130, 7534.
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Song, M. P. J. Organomet. Chem. 2001, 637e639, 27; (b) Xu, C.; Gong, J. F.; Yue, S. F.;
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125.6, 119.4, 116.7, 84.1, 24.9; HRMS-ESI (m/z): [MþH]þ calcd for
C19H20BClNO3: 356.1225; found 356.1215.
4.3.21. 6-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolane-2-yl)-2-[4-
(4,4,5,5-tetramethyl-1,3,2-dioxaborolane-2-yl)phenyl]benzoxazole
(3j). White solid, mp 248e249 ꢀC, yield 70%; 1H NMR (400 MHz,
CDCl3):
d
¼1.37 (s, 24H), 7.76e7.83 (m, 2H), 7.96e7.98 (m, 2H), 8.04 (s,
1H), 8.27 (d, J¼8.0 Hz, 2H);13C NMR(100 MHz, CDCl3):
¼163.8,150.6,
d
144.6,135.2,131.1,129.2,126.8,119.4,116.7, 84.1, 84.0, 24.9; HRMS-ESI
(m/z): [MþH]þ calcd for C25H32B2NO5: 448.2466; found 448.2456.
4.3.22. 6-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolane-2-yl)-2-(2,4-
dichlorophenyl)benzoxazole (3k). White solid, mp 126e127 ꢀC, yield
68%; 1H NMR (400 MHz, CDCl3):
d
¼1.37 (s, 12H), 7.38e7.40 (m, 1H),