Chlorination and ortho-acetoxylation of 2-arylbenzoxazoles

Article abstract of DOI:10.1039/c1ob05223c

Efficient and facile catalytic protocols for chlorination and ligand-directed ortho-acetoxylation of 2-arylbenzoxazoles have been developed. The chlorination is not a ligand-directed ortho-functionalization, but an electrophilic substitution process in the benzo ring of the benzoxazole moiety. Meanwhile, the acetoxylation exhibited high regioselectivity for the substrates containing a meta-substituent and occurred at the less sterically hindered ortho-C-H bond of the directing group. The Royal Society of Chemistry 2011.

Full text of DOI:10.1039/c1ob05223c

View Article Online / Journal Homepage / Table of Contents for this issue
Organic &
Biomolecular
Chemistry
Dynamic Article Links
Cite this: Org. Biomol. Chem., 2011, 9, 5288
www.rsc.org/obc
PAPER
Chlorination and ortho-acetoxylation of 2-arylbenzoxazoles†
Yuting Leng, Fan Yang,* Weiguo Zhu, Yangjie Wu* and Xiang Li
Received 11th February 2011, Accepted 18th April 2011
DOI: 10.1039/c1ob05223c
Efficient and facile catalytic protocols for chlorination and ligand-directed ortho-acetoxylation of
2-arylbenzoxazoles have been developed. The chlorination is not a ligand-directed
ortho-functionalization, but an electrophilic substitution process in the benzo ring of the benzoxazole
moiety. Meanwhile, the acetoxylation exhibited high regioselectivity for the substrates containing a
meta-substituent and occurred at the less sterically hindered ortho-C–H bond of the directing group.
Table 1 Effects of chlorinating reagents, solvents and catalysts on the
Introduction
selective chlorination of 2-(3-methylphenyl)benzoxazolea
Since the discovery of s-chelation directed C–H bond cleavage,
transition metal-catalyzed ligand-directed C–H bond function-
alization has emerged as a reliable and powerful tool in the
valuable conversion of arenes into new products, and numerous
endeavours have been focused on the application of this useful
transformation.1,2,3 Recently, the combination of transition metals
and directing groups has been shown to be a useful strategy to
facilitate the cleavage of the C–H bond, affording transformations
of a sp2-hybridized C–H bond to C–O,4 C–C,5 C–N,6 C–X,7 and
C–S8 bonds. In this context, many arenes containing a directing
group such as pyridine, ketone, ester, amide, oxazoline, imine, and
nitrile can be regioselectively functionalized via cyclometalated
intermediates under Pd,9 Ru,10 or Rh11 catalysis. Among them,
palladium-mediated C–H activation of arenes is one of the most
attractive processes. Particularly, in the development of palladium-
catalyzed halogenation and acetoxylation with the use of directing
groups, significant progress has been achieved by several groups,
such as those of Sanford, Daugulis, Yu, and others.12
Entry Chlorinating reagent Palladium source Solvent Yield (%)b
1
2
3
4
5
6
7c
8
p-MeC6H4SO2Cl
NCS
NCS
NCS
NCS
NCS
PdCl2
PdCl2
PdCl2
PdCl2
PdCl2
Pd(OAc)2
Pd2(dba)3
—
CH3CN 32
CH3CN 59
DCE
22
Dioxane <5
AcOH
AcOH
AcOH
AcOH
92
45
60
24
NCS
NCS
a Reaction conditions: 1a (0.5 mmol), chlorinating reagent (0.6 mmol),
catalyst (5.0 mol%), solvent (2.0 mL), 100 ◦C for 10 h. b Isolated yields.
c With the catalyst loading of 2.5 mol%.
Benzoxazoles are an important pharmacophore with low tox-
icities, which have exhibited a variety of biological activities.13
Further extension and branching functional substituents on
the benzoxazole skeleton would have great importance for the
synthesis of pharmaceutical intermediates. In 2008, we described
the direct arylation of 2-arylbenzoxazoles.14 Inspired by the
above-mentioned and our own reports, we began to explore
palladium-catalyzed chlorination and acetoxylation using ben-
zoxazole as the directing group. Herein, we would like to report
our research results as follows: the ligand-directed acetoxylation
indeed occurred at the ortho-position of the pendant aryl group,
affording the desired products in moderate to good yields; while
the chlorination of 2-arylbenzoxazoles was not a ligand-directed
ortho-C–H activation process, but an electrophilic substitution at
the para-position to the nitrogen atom in the benzo ring of the
benzoxazole moiety.
Results and discussion
Optimization of reaction conditions of the chlorination
In our initial study, we examined the effects of chlorinating
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
p-MeC6H4SO2Cl as the chlorinating reagent in CH3CN only gave
a low yield of 32% (Table 1, entry 1). When N-chlorosuccinimide
(NCS) was used as the chlorinating reagent, the product with a
higher yield of 59% was observed (Table 1, entry 2). Then, different
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. E-mail: wyj@zzu.edu.cn, yangf@zzu.edu.cn; Fax: (+86)-371-6797-
9408
† Electronic supplementary information (ESI) available. See DOI:
10.1039/c1ob05223c
5288 | Org. Biomol. Chem., 2011, 9, 5288–5296
This journal is
The Royal Society of Chemistry 2011
©

View Article Online
Table 2 The palladium-catalyzed selective chlorination of 2-
Table 2 (Contd.)
arylbenzoxazoles with NCSa
Entry
7
R
Product
Yield (%)b
Entry
1
R
Product
Yield (%)b
m-Br (1g)
83 (2g)
m-Me (1a)
92 (2a)
8
p-F (1h)
82 (2h)
81 (2i)
72 (2j)
70 (2k)
2
3
4
5
6
o-Me (1b)
p-Me (1c)
H (1d)
85 (2b)
81 (2c)
87 (2d)
88 (2e)
82 (2f)
9
p-Cl (1i)
10
p-Br (1j)
m-F (1e)
11
o, p-Cl2 (1k)
m-Cl (1f)
a Reaction conditions: 1a–k (0.5 mmol), NCS (0.6 mmol), PdCl2
(5.0 mol%), AcOH (2.0 mL), 100 ◦C for 10 h. b Isolated yields.
other solvents were investigated, and AcOH could give the
desired product in excellent yield of 92% using PdCl2 as the
catalyst (Table 1, entries 3–5). Finally, other palladium catalysts,
such as Pd(OAc)2 and Pd2(dba)3 were examined and did
not exhibit higher catalytic activity in this reaction (Table 1,
entries 6–7). However, in the absence of palladium catalyst, the
This journal is
The Royal Society of Chemistry 2011
Org. Biomol. Chem., 2011, 9, 5288–5296 | 5289
©

View Article Online
yield of desired product was remarkably decreased (Table 1,
entry 8).
Scope of substrates of the chlorination
Under the optimized conditions, the chlorination of diverse 2-
arylbenzoxazoles was examined to explore the scope of the
reaction (Table 2). Generally, the chlorination took place at
the para-position to the nitrogen atom in the benzo ring of
benzoxazole moiety owing to its higher electronic cloud density,
and the electronic effect of the benzene ring has no significant
influence on the reactions. For the benzene ring bearing electron-
donating groups, the desired products were isolated in high
yields (Table 2, entries 1–3). The chlorination of the electron-
neutral substrate also worked well at the para-position to the
nitrogen atom in the benzo ring of benzoxazole moiety (Table
2, entry 4). The reactions of the benzene ring containing electron-
withdrawing groups also generated the products in satisfactory
yields (Table 2, entries 5–11). It is noteworthy that this catalytic
system could tolerate halogen atoms (F, Cl and Br) (Table 2, entries
5–11).
The determination of the structures of the chlorinated products by
HMBC (1H-detected heteronuclear multiple bond correlation)
spectra
Fig. 2 HMBC spectrum of 2g.
atom has two strong correlated H atoms (H2¢ and H6¢), which
indicates that both H2¢ and H6¢ atoms still exist in the benzene
ring and the chlorination did not occur at the ortho-position of
the directing group.
The HMBC spectral data of the two representative chlorinated
products (2a, 2g) were utilized to confirm that the chlorination
took place at the para-position to the nitrogen atom in the benzo
ring of the benzoxazole moiety (Fig. 1, 2).
Then, from 13C NMR we could also assign the position of the
quaternary C7a atom bonded to the O atom and the quaternary
C3a atom adjacent to the N atom, which are located at d =
150.9 ppm at lower field and 140.8 ppm at slightly higher field,
respectively. From HMBC spectra, 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 the H7 atom at d =
7.57 ppm in the 1H NMR. The coupling constant of the H7 atom
1
is 2.00 Hz in the H NMR spectrum, which indicates that there
is no H atom at the ortho-position to the C7–H7 bond. Thus, the
chlorination should take place at the C6–H6 bond.
In the same manner, the HMBC spectrum (Fig. 2) analysis of the
chlorinated product (2g) could also confirm that the chlorination
did not take place at the ortho-C–H bond to the directing group,
but at the para-position to the nitrogen atom in the benzo ring of
the benzoxazole moiety.
Optimization of reaction conditions of the acetoxylation
The effects on the direct acetoxylation of 2-arylbenzoxazoles
were also explored (Table 3). The various oxidants (e.g., K2S2O8,
oxone, Cu(OTf)2, Cu(OAc)2, O2, AgOAc, H2O2 and PhI(OAc)2)
in the acetoxylation of 2-(3-methylphenyl)benzoxazole were firstly
examined, and PhI(OAc)2 turned out to be the best choice in
the presence of AcOH/Ac2O as the solvent, affording the desired
product with a high yield of 73% (Table 3, entries 1–8). However,
other solvents, such as AcOH, Ac2O, dioxane and toluene were
also checked and did not give satisfactory results (Table 3, entries
9–12).
Fig. 1 HMBC spectrum of 2a.
The HMBC spectral analysis of the 2-aryl benzoxazole contain-
ing a meta-substituent (2a) is outlined as Fig. 1. Initially, from 13
NMR we could identify the position of the quaternary C2 atom
adjacent to N and O atoms with the lowest electronic cloud density,
which is shifted to d = 163.9 ppm at the lowest field. And the C2
C
5290 | Org. Biomol. Chem., 2011, 9, 5288–5296
This journal is
The Royal Society of Chemistry 2011
©

View Article Online
Table 3 Effects of oxidants and solvents on the selective acetoxylation of
Table 4 The palladium-catalyzed selective acetoxylation of 2-
2-(3-methylphenyl)benzoxazolea
arylbenzoxazolesa
Entry R
m-Me (1a)
Product
Yield (%)b
Entry
Oxidant
Solvent
Yield (%)b
1
2
3
4
5
6
7
73 (3a)
1
2
3
4
5
6
7
8
9
10
11c
12c
K2S2O8
oxone
Cu(OTf)2
Cu(OAc)2
O2
AgOAc
H2O2
PhI(OAc)2
PhI(OAc)2
PhI(OAc)2
PhI(OAc)2
PhI(OAc)2
AcOH/Ac2O (1 : 1)
AcOH/Ac2O (1 : 1)
AcOH/Ac2O (1 : 1)
AcOH/Ac2O (1 : 1)
AcOH/Ac2O (1 : 1)
AcOH/Ac2O (1 : 1)
AcOH/Ac2O (1 : 1)
AcOH/Ac2O (1 : 1)
Ac2O
27
35
14
20
10
17
15
73
52
<5
<5
<5
o-Me (1b)
p-Me (1c)
H (1d)
66 (3b)
75 (3c)
62 (3d)
80 (3e)
84 (3f)
<5 (3g)
AcOH
dioxane
Toluene
a Reaction conditions: 1a (0.5 mmol), Pd(OAc)2 (5.0 mol%), oxidant
(0.55 mmol), solvent (4 mL). b Isolated yields. c With the addition of AcOH
(1.0 mmol) and Ac2O (1.0 mmol).
Scope of substrates of the acetoxylation
Under the optimized conditions, the scope of the palladium-
catalyzed acetoxylation of an array of substituted 2-
arylbenzoxazoles was investigated (Table 4). As expected, the
reactions of various substrates worked well under the reaction
conditions affording the products in mostly moderate to good
yields. The electron-donating substituents on 2-arylbenzoxazoles
would enhance the transformation (Table 4, entries 1, 3, 5, 6).
Especially, when the 2-arylbenzoxazole possessed two electron-
donating groups, the corresponding product was obtained in a
higher yield of 84% (Table 4, entry 6). However, the electron-
withdrawing substituent would decrease the reactivity of the
substrate, and the desired product was nearly not observed (Table
4, entry 7). It is worthy to point out that the regioselectivity of
the substrates containing a meta-substituent in this reaction was
controlled by the steric effect and the acetoxylation occurred at
the less sterically hindered ortho-C–H bond to the directing group
(Table 4, entries 1, 5–7).
p-MeO (1l)
m, p-(MeO)2 (1m)
m-Cl (1f)
The determination of the structures of the acetoxylated products
by HMBC (1H-detected heteronuclear multiple bond correlation)
spectra
The HMBC spectral data (3a) could unambiguously confirm the
proposed structure of the acetoxylated products (Fig. 3). Initially,
we could identify the position of the quaternary C2 atom adjacent
to N and O atoms at lowest electronic cloud density, which is
shifted to d = 160.1 ppm at the lowest field. The C2 atom only
has one strong correlated signal at d = 8.10 ppm, and there is
only one H atom at d = 8.10 ppm in the 1H NMR spectrum. This
indicates that one of H2¢ and H6¢ atoms has been substituted by
the OAc group. From the 1H NMR spectrum, it could be seen that
the coupling constant of the H atom (d = 8.10 ppm) is 1.88 Hz,
a Reaction conditions: 1 (0.5 mmol), Pd(OAc)2 (5.0 mol%), PhI(OAc)2
(0.55 mmol), AcOH (2.0 mL), Ac2O (2.0 mL), 100 ◦C for 48 h. b Isolated
yields.
This journal is
The Royal Society of Chemistry 2011
Org. Biomol. Chem., 2011, 9, 5288–5296 | 5291
©

View Article Online
Pd(IV) species; (iii) elimination process, resulting in the desired
product.
Conclusions
In summary, we have successfully developed chlorination, which
is the classical aromatic electrophilic substitution, and ligand-
directed ortho-acetoxylation of 2-arylbenzoxazole derivatives
through palladium-catalyzed C–H bond activation. The ace-
toxylation showed high regioselectivity for 2-arylbenzoxazoles
containing a meta-substituent. These protocols would be bene-
ficial for the convenient, efficient and applicable synthesis of 2-
arylbenzoxazoles derivatives. Further applications of these syn-
thetic methodologies are currently underway.
Experimental section
General details
1H NMR, 13C NMR, 1H–1H COSY NMR, 1H–13C HSQC
NMR, 1H–13C HBMC 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 spec-
tra were measured on an LC-MSD-Trap-XCT instrument. High-
resolution mass spectra were measured on a MALDI-FTMS.
Elemental analyses were determined with a Carlo Erba elemental
analyzer. IR spectra were recorded on a Bruker VECTOR 22
spectrophotometer. Dichloromethane, ethyl acetate and hexane
(analytical grade) were used for column chromatography without
further purification. Other solvents were purified according to
the standard methods. Other chemicals were obtained from
commercial sources and used as-received unless otherwise noted.
Fig. 3 HMBC spectrum of 3a.
which indicates that there is no ortho-H atom to the H atom (d =
8.10 ppm). Thus, this H atom (d = 8.10 ppm) should be the H6¢
atom and the H2¢ atom was substituted by the OAc group. These
spectral studies confirm that the acetoxylation occurred at the
less sterically hindered ortho-C–H (C2¢–H2¢) bond of the directing
group.
Proposed mechanism
The mechanism for the chlorination of 2-arylbenzoxazoles is the
classical aromatic electrophilic substitution at the para-position to
the nitrogen atom in the benzo ring of the benzoxazole moiety. In
this chlorination, palladium would act as the Lewis acid catalyst.
The proposed reaction mechanism for the ligand-directed ortho-
acetoxylation of 2-arylbenzoxazoles is outlined in Scheme 1,
which includes: (i) cyclopalladation of 2-arylbenzoxazoles via C–H
activation, affording a cyclopalladated intermediate; (ii) oxidative
addition of cyclopalladated intermediate with Ac2O, leading to
General procedure for synthesis of 2-arylbenzoxazoles
To a solution of 2-aminophenol (3.274 g, 30.0 mmol) in polyphos-
phoric acid (PPA, 30 mL), arylcarboxylic acid (30 mmol) was
added. The resulting mixture was heated at 150 ◦C for 5 h. After
the reaction was complete, the mixture was added into cold water
and then the pH value was adjusted to 14 with an aqueous
solution of sodium hydroxide. The mixture was extracted with
ethyl acetate three times. The combined organic layer was dried
over anhydrous Na2SO4 and filtered. After removal of the solvent
in vacuo, the residue was purified by flash column chromatography
(ethyl acetate/hexane) to afford the pure product.
2-(3-Methylphenyl)benzoxazole (1a)15
◦
1
White solid, mp 79–80 C; H NMR (400 MHz, CDCl3): d 2.45
(s, 3H), 7.24–7.79 (m, 3H), 7.37–7.42 (m, 1H), 7.56–7.60 (m, 1H),
7.75–7.80 (m, 1H), 8.05 (d, J = 7.80 Hz, 1H), 8.08 (s, 1H); 13C NMR
(100 MHz, CDCl3): d 21.4, 110.6, 119.9, 124.6, 124.8, 125.1, 126.9,
128.2, 128.8, 132.4, 138.8, 142.0, 150.7, 163.2.
2-(2-Methylphenyl)benzoxazole (1b)16
◦
1
White solid, mp 64–66 C; H NMR (400 MHz, CDCl3): d 2.80
Scheme 1 A proposed mechanism of functionalization of 2-arylbenzo-
xazoles.
(s, 3H), 7.31–7.40 (m, 5H), 7.56–7.58 (m, 1H), 7.79–7.81 (m, 1H),
5292 | Org. Biomol. Chem., 2011, 9, 5288–5296
This journal is
The Royal Society of Chemistry 2011
©

View Article Online
8.16–8.18 (m, 1H); 13C NMR (100 MHz, CDCl3): d 22.2, 110.5,
120.1, 124.3, 125.0, 126.0, 126.2, 129.9, 130.9, 131.8, 138.8, 142.1,
150.2, 163.3.
2-(4-Bromophenyl)benzoxazole (1j)22
◦
1
White solid, mp 157–158 C; H NMR (400 MHz, CDCl3): d
7.35–7.38 (m, 2H), 7.57–7.58 (m, 1H), 7.66 (d, J = 8.4 Hz, 2H),
7.76–7.78 (m, 1H), 8.11 (d, J = 8.5 Hz, 2H); 13C NMR (100 MHz,
CDCl3): d 110.6, 120.1, 124.8, 125.4, 126.1, 126.2, 129.0, 132.2,
142.0, 150.7, 162.1.
2-(4-Methylphenyl)benzoxazole(1c)17
White solid, mp 117–118 ◦C; 1H NMR (400 MHz, CDCl3): d 2.42
(s, 3H), 7.30–7.34 (m, 4H), 7.55–7.57 (m, 1H), 7.75–7.77 (m, 1H),
8.13 (d, J = 8.2 Hz, 2H); 13C NMR (100 MHz, CDCl3): d 21.6,
110.5, 119.8, 124.4, 124.5, 124.8, 127.6, 129.6, 142.0, 142.1, 150.6,
163.3.
2-(2,4-Dichlorophenyl)benzoxazole (1k)23
White solid, mp 123–124 ◦C; 1H NMR (400 MHz, CDCl3): d 7.38–
7.44 (m, 3H), 7.58–7.65 (m, 2H), 7.83–7.87 (m, 1H), 8.13 (d, J =
8.40 Hz, 1H); 13C NMR (100 MHz, CDCl3): d 110.8, 120.6, 124.7,
124.8, 125.8, 127.4, 131.3, 132.5, 134.2, 137.5, 141.6, 150.5, 160.1.
2-Phenylbenzoxazole (1d)18
2-(3-Methoxyphenyl)benzoxazole (1l)19
White solid, mp 79–80 ◦C; 1H NMR (400 MHz, CDCl3): d 7.30–
7.40 (m, 2H), 7.40–7.60 (m, 4H), 7.72–7.80 (m, 1H), 8.26 (t, J =
2.40 Hz, 2H); 13C NMR (100 MHz, CDCl3): d 110.6, 120.0, 124.6,
125.1, 127.2, 127.6, 128.9, 131.5, 142.1, 150.8, 163.1.
White solid, mp 71.3–73.8 ◦C; 1H NMR (400 MHz, CDCl3): d3.92
(s, 3H), 7.07–7.09 (m, 1H), 7.35–7.37 (m, 2H), 7.40–7.45 (m, 1H),
7.57–7.59 (m, 1H), 7.77–7.79 (m, 2H), 7.85 (d, J = 7.5 Hz, 1H);13C
NMR (100 MHz, CDCl3): d 55.2, 110.3, 111.5, 118.07, 119.7,
119.8, 124.3, 124.9, 128.0, 129.7, 141.7, 150.4, 159.2, 162.7.
2-(3-Fluorophenyl)benzoxazole (1e)19
White solid, mp 92–94 ◦C; 1H NMR (400 MHz, CDCl3): d 7.20–
7.21 (m, 1H), 7.25–7.36 (m, 2H), 7.47–7.56 (m, 2H), 7.75–7.78 (m,
1H), 7.94–8.03 (m, 2H); 13C NMR (100 MHz, CDCl3): d 110.7,
114.6 (d, J = 23.9 Hz), 118.5 (d, J = 21.2 Hz), 120.2, 123.3 (d, J =
3.1 Hz), 124.8, 125.5, 129.2 (d, J = 8.5 Hz), 130.6 (d, J = 8.1 Hz),
141.9, 150.7, 161.7 (d, J = 3.1 Hz), 162.9 (d, J = 245.4 Hz).
2-(3,4-Dimethoxylphenyl)benzoxazole (1m)19
White solid, mp 109–111 ◦C; 1H NMR (400 MHz, CDCl3): d 3.97
(s, 3H), 4.02 (s, 3H), 6.98 (d, J = 0.88 Hz, 1H), 7.25–7.36 (m, 2H),
7.54–7.58 (m, 1H), 7.73–7.78 (m, 2H), 7.86 (d, J = 8.40 Hz, 1H);
13C NMR (100 MHz, CDCl3): d 56.1, 56.1, 110.0, 110.4, 111.0,
119.6, 119.7, 121.2, 124.5, 124.7, 142.1, 149.2, 150.7, 152.0, 163.1.
2-(3-Chlorophenyl)benzoxazole (1f)19
General procedure for direct chlorination of 2-arylbenzoxazoles
White solid, mp 124–125 ◦C; 1H NMR (400 MHz, CDCl3): d 7.35–
7.40 (m, 2H), 7.44–7.53 (m, 2H), 7.58–7.62 (m, 1H), 7.77–7.79 (m,
1H), 8.15 (dt, J = 7.60, 1.40 Hz, 1H), 8.27 (d, J = 1.60 Hz, 1H);
13C NMR (100 MHz, CDCl3): d 110.7, 120.2, 124.9, 125.6, 125.7,
127.6, 128.8, 130.3, 131.6, 135.1, 141.7, 150.7, 161.6.
Substrate 1 (0.5 mmol), chlorinating reagent (0.6 mmol) and PdCl2
(5 mol%) were dissolved in AcOH (2 mL) in a 10 mL vial under
air and heated at a specific temperature for 10 h. After the reaction
was complete, the solvent was evaporated under reduced pressure.
The residual was purified by flash chromatography on silica gel
(ethyl acetate/hexane) to give the desired product.
2-(3-Bromophenyl)benzoxazole (1g)19
6-Chloro-2-(3-methylphenyl)benzoxazole (2a)
White solid, mp 128–130 ◦C; 1H NMR (400 MHz, CDCl3): d 7.25–
7.44 (m, 3H), 7.56–7.65 (m, 1H), 7.65–7.69 (m, 1H), 7.76–7.81 (m,
1H), 8.20 (d, J = 8.02 Hz, 1H), 8.43 (s, 1H); 13C NMR (100 MHz,
CDCl3): d 110.7, 120.2, 123.0, 124.9, 125.6, 126.1, 129.0, 130.5,
130.5, 134.5, 141.8, 150.8, 161.5.
Purification by flash chromatography over silica gel, eluting with
ethyl acetate–hexane (1 : 30), provided the desired compound as a
white solid; Rf 0.40; mp 99–100 ◦C; 1H NMR (400 MHz, CDCl3):
d 2.45 (s, 3H), 7.26–7.43 (m, 3H), 7.57 (s, 1H), 7.66 (d, J = 8.5 Hz,
1H), 8.02 (m, 2H); 13C NMR (100 MHz, CDCl3): d 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): 3057, 1615, 1554, 1453, 1423, 1329,1261,
1052, 920, 864, 803, 714, 681, 593, 434 cm-1; HRMS-ESI (m/z):
calcd for C14H11ClNO (M + H): 244.0529, found 244.0530.
2-(4-Fluorophenyl)benzoxazole (1h)20
White solid, mp 94–96 ◦C; 1H NMR (400 MHz, CDCl3): d 7.16–
7.20 (m, 2H), 7.32–7.35 (m, 2H), 7.54–7.55 (m, 1H), 7.74–7.76 (m,
1H), 8.21–8.25 (m, 2H); 13C NMR (100 MHz, CDCl3): d 110.3,
115.6 (d, J = 22.1 Hz), 119.7, 123.2 (d, J = 2.9 Hz), 124.4, 124.8,
129.5 (d, J = 8.8 Hz), 141.7, 150.4, 161.8, 165.5 (d, J = 251.2 Hz).
6-Chloro-2-(2-methylphenyl)benzoxazole (2b)
Purification by flash chromatography over silica gel, eluting with
ethyl acetate–hexane (1 : 30), pr◦ovided the desired compound as a
white solid; Rf 0.42; mp 85–86 C; 1H NMR (400 MHz, CDCl3):
d 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 (100 MHz, CDCl3): d
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): 3065, 1606, 1542, 1485, 1432,
1389, 1245, 1208, 1084, 1027, 961, 913, 844, 774, 723, 673, 598,
2-(4-Chlorophenyl)benzoxazole (1i)21
white solid, mp 148–150 ◦C; 1H NMR (400 MHz, CDCl3): d 7.36–
7.39 (m, 2H), 7.51–7.57 (m, 2H), 7.57–7.59 (m, 1H), 7.76–7.78 (m,
1H), 8.18–8.20 (m, 2H); 13C NMR (100 MHz, CDCl3): d 110.6,
120.0, 124.7, 125.5, 125.6, 128.8, 129.2, 137.7, 141.9, 150.7, 162.0.
This journal is
The Royal Society of Chemistry 2011
Org. Biomol. Chem., 2011, 9, 5288–5296 | 5293
©

View Article Online
456 cm-1; HRMS-ESI (m/z): calcd for C14H11ClNO (M + H):
244.0529, found 244.0525.
white solid; Rf 0.37; mp 141–143 ◦C;1H NMR (400 MHz, CDCl3):
d 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 (100 MHz, CDCl3): d
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): 3064, 1614, 1546, 1468, 1427, 1330, 1259,
1049, 860, 804, 715, 673, 594 cm-1; Anal. Calcd for C13H7BrClNO
(306.94): C, 50.60; H, 2.29; N, 4.54, found: C, 50.76; H, 2.30; N,
4.24.
6-Chloro-2-(4-methylphenyl)benzoxazole (2c)
Purification by flash chromatography over silica gel, eluting with
ethyl acetate–hexane (1 : 30), pro◦vided the desired compound as a
white solid; Rf 0.41; mp 126–128 C; 1H NMR (400 MHz, CDCl3):
d 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 (100 MHz, CDCl3): d 21.6,
111.1, 120.2, 123.9, 125.1, 127.6, 129.6, 130.3, 140.9, 142.3, 150.8,
163.9; IR (KBr): 3035, 2921, 1617, 1555, 1496, 1457, 1418, 1326,
1281, 1254, 1173, 1117, 1047, 1011, 917, 834, 807, 725, 699, 635,
595, 501 cm-1; HRMS-ESI (m/z): calcd for C14H11ClNO (M + H):
244.0529, found 244.0526.
6-Chloro-2-(4-fluorophenyl)benzoxazole (2h)
Purification by flash chromatography over silica gel, eluting with
ethyl acetate–hexane (1 : 30), pro◦vided the desired compound as a
white solid; Rf 0.33; mp 132–133 C; 1H NMR (400 MHz, CDCl3):
d 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 (100 MHz, CDCl3): d
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-phenylbenzoxazole (2d)24
Purification by flash chromatography over silica gel, eluting with
ethyl acetate–hexane (1 : 30), pr◦ovided the desired compound as a
white solid; Rf 0.36; mp 59–61 C; 1H NMR (400 MHz, CDCl3):
d 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 (100 MHz, CDCl3): d 111.2,
120.4, 125.2, 126.6, 127.6, 128.9, 130.6, 131.7, 140.8, 150.8, 163.6;
IR (KBr): 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.
6-Chloro-2-(4-chlorophenyl)benzoxazole (2i)25
Purification by flash chromatography over silica gel, eluting with
ethyl acetate–hexane (1 : 30), pro◦vided the desired compound as a
white solid; Rf 0.35; mp 148–150 C; 1H NMR (400 MHz, CDCl3):
d 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 (100 MHz,
CDCl3): d 111.3, 120.5, 125.2, 125.5, 128.9, 129.3, 130.9, 138.1,
140.8, 150.9, 162.7.
6-Chloro-2-(3-fluorophenyl)benzoxazole (2e)
Purification by flash chromatography over silica gel, eluting with
ethyl acetate–hexane (1 : 30), pro◦vided the desired compound as a
white solid; Rf 0.38; mp 128–129 C; 1H NMR (400 MHz, CDCl3):
d 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 (100 MHz, CDCl3): d 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): 3069, 1592, 1556, 1481,
1452, 1328, 1295, 1265, 1210, 1176, 1051, 881, 811, 787, 722, 673,
596, 516 cm-1; 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.
6-Chloro-2-(4-bromophenyl)benzoxazole (2j)
Purification by flash chromatography over silica gel, eluting with
ethyl acetate–hexane (1 : 30), pro◦vided the desired compound as a
white solid; Rf 0.38; mp 168–170 C; 1H NMR (400 MHz, CDCl3):
d 7.31–7.33 (m, 1H), 7.55 (s, 1H), 7.63–7.65 (m, 3H), 8.04–8.06
(m, 2H); 13C NMR (100 MHz, CDCl3): d 111.2, 120.5, 125.4,
125.6, 126.5, 129.0, 131.0, 132.3, 140.7, 150.8, 162.7; IR (KBr):
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-(3-chlorophenyl)benzoxazole (2f)
6-Chloro-2-(2,4-dichlorophenyl)benzoxazole (2k)
Purification by flash chromatography over silica gel, eluting with
ethyl acetate–hexane (1 : 30), pro◦vided the desired compound as a
white solid; Rf 0.35; mp 148–150 C; 1H NMR (400 MHz, CDCl3):
d 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 (100
MHz, CDCl3): d 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): 3065, 1611,
1550, 1472, 1428, 1330, 1259, 1102, 1051, 921, 862, 839, 805, 756,
718, 675, 595, 433 cm-1; 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.
Purification by flash chromatography over silica gel, eluting with
ethyl acetate–hexane (1 : 30), pro◦vided the desired compound as a
white solid; Rf 0.39; mp 140–141 C; 1H NMR (400 MHz, CDCl3):
d 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 (100 MHz, CDCl3):
d 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): 3075, 1609, 1584, 1554, 1467,
1426, 1370, 1108, 1080, 1020, 919, 844, 805, 596 cm-1; HRMS-
ESI (m/z): calcd for C13H6Cl3NO (M + H): 297.9593, found
297.9602.
6-Chloro-2-(3-bromophenyl)benzoxazole (2g)
General procedure for direct acetoxylation of 2-arylbenzoxazoles
Purification by flash chromatography over silica gel, eluting with
ethyl acetate–hexane (1 : 30), provided the desired compound as a
Substrate 1 (0.5 mmol), PhI(OAc)2 (0.55 mmol), Pd(OAc)2 (5
mol%) were dissolved in AcOH (2 mL) and Ac2O (2 mL) in a
5294 | Org. Biomol. Chem., 2011, 9, 5288–5296
This journal is
The Royal Society of Chemistry 2011
©

View Article Online
10 ml vial under air and heated at a specific temperature for 48 h.
Upon completion, the solvent was evaporated to dryness in vacuo.
The residual was purified by flash chromatography on silica gel
(ethyl acetate/hexane) to give the desired product.
d 2.46 (s, 3 H), 3.89 (s, 3H), 7.05–7.14 (m, 2H), 7.34–7.36 (m,
2H), 7.53–7.54 (m, 1H), 7.74–7.77 (m, 2H); 13C NMR (100 MHz,
CDCl3): d 21.2, 55.9, 110.4, 114.0, 118.7, 120.3, 120.7, 124.6, 125.0,
125.5, 141.8, 142.8, 150.2, 157.5, 159.8, 170.4; IR (KBr): 2937,
2838, 1763, 1597, 1552, 1499, 1453, 1365, 1326, 1242, 1180, 1033,
1006, 936, 876, 827, 755, 578, 516 cm-1; HRMS-ESI (m/z): calcd
for C16H14NO4 (M + H): 284.0932, found 284.0931.
2-(Benzoxazol-2-yl)-4-methylphenyl acetate (3a)
Purification by flash chromatography over silica gel, eluting with
ethyl acetate-hexane (1 : 10), provided the desired ◦compound as
1
2-(Benzoxazol-2-yl)-4,5-dimethoxyphenyl acetate (3f)
a white solid; Rf 0.32; White solid; mp 113–114 C; H NMR
(400 MHz, CDCl3): d 2.45–2.47 (s, 3H), 2.48 (s, 3H), 7.11 (d, J =
8.2 Hz, 1H), 7.34–7.38 (m, 3H), 7.54–7.55 (m, 1 H), 7.74–7.76 (m,
1H), 8.10–8.11 (s, 1H); 13C NMR (100 MHz, CDCl3): d 20.8, 21.4,
110.4, 119.8, 120.2, 123.8, 124.5, 125.3, 130.5, 133.2, 136.3, 141.8,
147.0 150.1, 160.0, 170.2; IR (KBr): 2919, 1752, 1612, 1548, 1479,
1448, 1222, 1191, 1007, 908, 841, 739, 637, 547 cm-1; HRMS-ESI
(m/z): calcd for C16H14NO3 (M + H): 268.0973, found 268.0968.
Purification by flash chromatography over silica gel, eluting with
ethyl acetate–hexane (1 : 4), provided the desired compound as a
white solid; Rf 0.35; mp 149–151 ◦C; 1H NMR (400 MHz, CDCl3):
d 2.47 (s, 3 H), 3.95 (s, 3H), 4.01 (s, 3H), 6.71–6.72 (s, 1H), 7.27–
7.35 (m, 2 H), 7.52–7.54 (m, 1H), 7.72–7.74 (m, 2H); 13C NMR (100
MHz, CDCl3): d 21.3, 56.2, 56.4, 107.1, 110.2, 111.1, 111.8, 119.9,
124.5, 125.0, 141.9, 143.7, 147.0, 150.0, 152.1, 160.0, 170.3; IR
(KBr): 2936, 2838, 1765, 1615, 1560, 1503, 1453, 1245, 1175, 1134,
1025, 939, 877, 744 cm-1; HRMS-ESI (m/z): calcd for C17H16NO5
(M + H): 314.1028, found 314.1038.
2-(Benzoxazol-2-yl)-5-methylphenyl acetate (3b)
Purification by flash chromatography over silica gel, eluting with
ethyl acetate–hexane (1 : 10), provided the desired compound as a
white solid; Rf 0.35; mp 79–80 ◦C; 1H NMR (400 MHz, CDCl3):
d 2.45 (s, 3H), 2.49 (s, 3H), 7.04 (s, 1H), 7.21–7.35 (m, 3H), 7.53–
7.55 (m, 1H), 7.72–7.74 (m, 1H), 8.17 (d, J = 8.0 Hz, 1H); 13C
NMR (100 MHz, CDCl3): d 21.4, 21.4, 110.3, 117.5, 120.1, 124.4,
124.6, 125.2, 127.4, 130.0, 142.0, 143.6, 149.1, 150.0, 160.0, 170.0;
IR (KBr): 2928, 1758, 1618, 1557, 1497, 1459, 1245, 1196, 1017,
910, 844, 740 cm-1; HRMS-ESI (m/z): calcd for C16H14NO3 (M +
H): 268.0973, found 268.0967.
Acknowledgements
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.
Notes and references
2-(Benzoxazol-2-yl)-3-methylphenyl acetate (3c)
1 (a) A. D. Ryabov, Synthesis, 1985, 233; (b) A. J. Canty, Comprehensive
Organometallic Chemistry II, (Ed.: E. W. Abel, F. G. A. Stone and G.
Wilkinson), Pergamon: Oxford, 1995.
Purification by flash chromatography over silica gel, eluting with
ethyl acetate–hexane (1 : 10), pro◦vided the desired compound as a
white solid; Rf 0.35; mp 124–125 C; 1H NMR (400 MHz, CDCl3):
d 2.21 (s, 3H), 2.53 (s, 3H), 7.07–7.09 (m, 1H), 7.24–7.26 (m,
1H), 7.38–7.46 (m, 3H), 7.57–7.60 (m, 1H), 7.81–7.83 (m, 1H);
13C NMR (100 MHz, CDCl3): d 20.9, 21.4, 110.5, 120.3, 120.80,
121.0, 124.4, 125.3, 128.6, 131.3, 140.6, 141.40, 150.0, 150.4, 159.6,
169.6; IR (KBr): 2932, 2847, 1765, 1616, 1510, 1453, 1365, 1247,
1190, 1148, 1011, 896, 846, 753 cm-1; HRMS-ESI (m/z): calcd for
C16H14NO3 (M + H): 268.0973, found 268.0977.
2 For selected reviews on C–H functionalization, see: (a) O. Daugulis,
H.-Q. Do and D. Shabashov, Acc. Chem. Res., 2009, 42, 1074; (b) D.
A. Colby, R. G. Bergman and J. A. Ellman, Chem. Rev., 2010, 110,
624; (c) E. M. Beccalli, G. Broggini, M. Martinelli and S. Sottocornola,
Chem. Rev., 2007, 107, 5318; (d) M. M. D´ıaz-Requejo and P. J. Pe´rez,
Chem. Rev., 2008, 108, 3379; (e) N. Chatani, Directed Metallation,
Springer: Berlin, 2008; (f) D. Alberico, M. E. Scott and M. Lautens,
Chem. Rev., 2007, 107, 174.
3 (a) K. Carr and J. K. Sutherland, J. Chem. Soc., Chem. Commun., 1984,
1227; (b) J. E. Baldwin, R. H. Jones, C. Najera and M. Yus, Tetrahedron,
1985, 41, 699; (c) L. Bore, T. Honda and G. W. Gribble, J. Org. Chem.,
2000, 65, 6278; (d) H. M. L. Davies and R. E. J. Beckwith, Chem. Rev.,
2003, 103, 2861; (e) A. S. Goldman, A. H. Roy, Z. Huang, R. Ahuja,
W. Schinski and M. Brookhart, Science, 2006, 312, 257; (f) S. Das, C.
D. Incarvito, R. H. Crabtree and G. W. Brudvig, Science, 2006, 312,
1941.
4 (a) L. V. Desai, K. J. Stowers and M. S. Sanford, J. Am. Chem. Soc.,
2008, 130, 13285; (b) R. Giri, J. Liang, J. G. Lei, J. J. Li, D. H. Wang,
X. Chen, I. C. Naggar, C. Guo, B. M. Foxman and J. Q. Yu, Angew.
Chem., Int. Ed., 2005, 44, 7420; (c) X. Chen, X.-S. Hao, C. E. Goodhue
and J.-Q. Yu, J. Am. Chem. Soc., 2006, 128, 6790; (d) S. J. Gu, C. Chen
and W. Z. Chen, J. Org. Chem., 2009, 74, 7203; (e) G.-W. Wang, T.-T.
Yuan and X.-L. Wu, J. Org. Chem., 2008, 73, 4717; (f) W.-H. Wang, F.
Luo, S.-H. Zhang and J. Cheng, J. Org. Chem., 2010, 75, 2415.
5 (a) K. Dipannita, N. R. Deprez, L. V. Deprez and M. S. Sanford, J.
Am. Chem. Soc., 2005, 127, 7330; (b) H. A. Chiong, Q.-N. Pham and O.
Daugulis, J. Am. Chem. Soc., 2007, 129, 9879; (c) G. J. Deng, L. Zhao
and C.-J. Li, Angew. Chem., Int. Ed., 2008, 47, 6278; (d) X. D. Zhao
and Z. K. Yu, J. Am. Chem. Soc., 2008, 130, 8136; (e) A. S. Tsai, R. G.
Bergman and J. A. Ellman, J. Am. Chem. Soc., 2008, 130, 6316; (f) R.
Giri and J.-Q. Yu, J. Am. Chem. Soc., 2008, 130, 14082.
2-(Benzoxazol-2-yl)-phenyl acetate (3d)26
Purification by flash chromatography over silica gel, eluting with
ethyl acetate–hexane (1 : 10), p◦rovided the desired compound as a
white solid; Rf 0.33; mp 75–76 C; 1H NMR (400 MHz, CDCl3): d
2.49 (s, 3H), 7.23–7.24 (m, 1 H), 7.35–7.37 (m, 3 H), 7.42 (m, 2 H),
7.55–7.56 (m, 1H), 8.30 (dd, J = 7.9 Hz, 1.6 Hz, 1H); 13C NMR
(100 MHz, CDCl3): d 21.4, 110.4, 120.3, 120.4, 124.1, 124.6, 125.4,
126.5, 130.2, 132.4, 141.9, 149.2, 150.1, 159.8, 170.0; IR (KBr):
3070, 2920, 1754, 1612, 1547, 1480, 1446, 1367, 1185, 1032, 913,
737, 473 cm-1.
2-(Benzoxazol-2-yl)-4-methoxyphenyl acetate (3e)
Purification by flash chromatography over silica gel, eluting with
ethyl acetate–hexane (1 : 6), provided the desired compound as a
white solid; Rf 0.32; mp 106–108 ◦C; 1H NMR (400 MHz, CDCl3):
6 H.-Y. Thu, W.-Y. Yu and C.-M. Che, J. Am. Chem. Soc., 2006, 128,
9048.
This journal is
The Royal Society of Chemistry 2011
Org. Biomol. Chem., 2011, 9, 5288–5296 | 5295
©

View Article Online
7 (a) D. Kalyani, A. R. Dick, W. Q. Anani and M. S. Sanford, Org.
Lett., 2006, 8, 2523; (b) X. B. Wan, Z. X. Ma, B. J. Li, K. Y. Zhang,
S. K. Cao, S. W. Zhang and Z. J. Shi, J. Am. Chem. Soc., 2006, 128,
7416; (c) X. Chen, X.-S. Hao, C. E. Goodhue and J.-Q. Yu, J. Am.
Chem. Soc., 2006, 128, 6790; (d) T.-S. Mei, R. Giri, N. Maugel and
J.-Q. Yu, Angew. Chem., Int. Ed., 2008, 47, 5215; (e) B. R. Song, X. J.
Zheng, J. Mo and B. Xu, Adv. Synth. Catal., 2010, 352, 329; (f) R. B.
Bedford, C. J. Mitchellb and R. L. Webstera, Chem. Commun., 2010, 46,
3095.
12 (a) A. R. Dick and M. S. Sanford, Tetrahedron, 2006, 62, 2439; (b) O.
Daugulis, V. G. Zaitsev, D. Shabashov, Q.-N. Pham and A. Lazareva,
Synlett, 2006, 18, 3382; (c) J.-Q. Yu, R. Giri and X. Chen, Org. Biomol.
Chem., 2006, 4, 4041; (d) G.-W Wang and T.-T. Yuan, J. Org. Chem.,
2010, 75, 476; (e) F.-R. Gou, X.-C Wang, P.-F. Huo, H.-P. Bi, Z.-H.
Guan and Y.-M. Liang, Org. Lett., 2009, 11, 5726.
13 (a) S. M. Sondhi, N. Singh, A. Kumar, O. Lozach and L. Meijer, Bioorg.
Med. Chem., 2006, 14, 3758; (b) S. M. Rida, F. A. Ashour, S. A. M.
El-Hawash, M. M. ElSemary, M. H. Badr and M. A. Shalaby, Eur. J.
Med. Chem., 2005, 40, 949.
14 (a) F. Yang, Y.-J. Wu, Z.-W. Zhu, J.-L. Zhang and Y.-N. Li, Tetrahedron,
2008, 64, 6782; (b) F. Yang, Y.-J. Wu, Y.-N. Li, B. Wang and J.-L. Zhang,
Tetrahedron, 2009, 65, 914.
15 T. Fukuhara, C. Hasegawa and S. Hara, Synthesis, 2007, 10, 1528.
16 H. Hachiya, K. Hirano, T. Satoh and M. Miura, Org. Lett., 2009, 11,
1737.
8 X. D. Zhao, E. Dimitrijevic´ and V. M. Dong, J. Am. Chem. Soc., 2009,
131, 3466.
9 (a) W.-Y. Yu, W. N. Sit, K.-M. Lai, Z. Zhou and A. S. C. Chan, J.
Am. Chem. Soc., 2008, 130, 3304; (b) Y. Zhang, J. Feng and C.-J. Li, J.
Am. Chem. Soc., 2008, 130, 2900; (c) K. L. Hull and M. S. Sanford, J.
Am. Chem. Soc., 2007, 129, 11904; (d) L. Ackermann, R. Vicente and
A. R. Kapdi, Angew. Chem., Int. Ed., 2009, 48, 9792; (e) X. Chen, K.
M. Engle, D.-H. Wang and J.-Q. Yu, Angew. Chem., Int. Ed., 2009, 48,
5094.
17 Y. Kawashita, N. Nakamichi, H. Kawabata and M. Hayashi, Org. Lett.,
2003, 5, 3713.
10 (a) I. Ozdemir, S. Demir, B. Cetinkaya, C. Gourlaouen, F. Maseras, C.
Bruneau and P. H. Dixneuf, J. Am. Chem. Soc., 2008, 130, 1156; (b) L.
Ackermann, R. Born and P. Alvarez-Bercedo, Angew. Chem., Int. Ed.,
2007, 46, 6364; (c) L. Ackermann, A. Althammer and R. Born, Angew.
Chem., Int. Ed., 2006, 45, 2619; (d) S.-I. Murahashi, T. Nakae, H. Terai
and N. Komiya, J. Am. Chem. Soc., 2008, 130, 11005; (e) S. Inoue, H.
Shiota, Y. Fukumoto and N. Chatani, J. Am. Chem. Soc., 2009, 131,
6898.
11 (a) A. M. Berman, J. C. Lewis, R. G. Bergman and J. A. Ellman, J. Am.
Chem. Soc., 2008, 130, 14926; (b) J. C. Lewis, A. M. Berman, R. G.
Bergman and J. A. Ellman, J. Am. Chem. Soc., 2008, 130, 2493; (c) L.
Li, W. W. Brennessel and W. D. Jones, J. Am. Chem. Soc., 2008, 130,
12414; (d) J. C. Lewis, R. G. Bergman and J. A. Ellman, J. Am. Chem.
Soc., 2007, 129, 5332; (e) S. Proch and R. Kempe, Angew. Chem., Int.
Ed., 2007, 46, 3135.
18 M. Yoshifuji, R. Nagase and N. Inamoto, Bull. Chem. Soc. Jpn., 1982,
55, 873.
19 S. M. Johnson, S. Connelly, I. A. Wilson and J. W. Kelly, J. Med. Chem.,
2008, 51, 260.
20 N. Barbero, M. Carril, R. SanMartin and E. Dom´ınguez, Tetrahedron,
2007, 63, 10425.
21 J. Z. Zhang, Q. Zhu and X. Huang, Synth. Commun., 2002, 32, 2175.
22 R. S. Pottorf, N. K. Chadha, M. Katkevics, V. Ozola, E. Suna, H.
Ghane, T. Regberg and M. R. Player, Tetrahedron Lett., 2003, 44, 175.
23 L. J. Mathias and G. L. Tullos, Polymer, 1996, 37, 3771.
24 S. Ueda and H. Nagasawa, J. Org. Chem., 2009, 74, 4272.
25 K. Nakagawa, H. Onoue and J. Sugita, Chem. Pharm. Bul., 1964, 12,
1135.
26 K. Brewster, R. A. Chittenden, J. M. Harrison, T. D. Inch and C.
Brown, J. Chem. Soc., Perkin Trans. 1, 1976, 1291.
5296 | Org. Biomol. Chem., 2011, 9, 5288–5296
This journal is
The Royal Society of Chemistry 2011
©