O-aryloxime ethers from the copper(II)-mediated cross-coupling of oximes and phenylboronic acids

Article abstract of DOI:10.1055/s-0028-1088199

A direct approach to O-aryloxime ethers by means of the first copper-mediated cross-coupling of aromatic oximes and phenylboronic acids is reported. The O-arylation of acetophenone oximes with phenylboronic acids typically furnished O-aryloxime ethers in

Full text of DOI:10.1055/s-0028-1088199

LETTER
955
O-Aryloxime Ethers from the Copper(II)-Mediated Cross-Coupling of Oximes
and Phenylboronic Acids
Synthesis of
O
-Ary
b
loxime
E
the
d
rs elselam Ali,a,b Adam G. Meyer,*a Kellie L. Tuckb
a
CSIRO Molecular and Health Technologies, Bag 10, Clayton South, Vic 3169, Australia
Fax +61(3)95452376; E-mail: adam.meyer@csiro.au
b
School of Chemistry, Monash University, Clayton, Vic 3800, Australia
Received 28 October 2008
conditions required for their copper-mediated cross-
coupling (Table 1).
Abstract: A direct approach to O-aryloxime ethers by means of the
first copper-mediated cross-coupling of aromatic oximes and phe-
nylboronic acids is reported. The O-arylation of acetophenone
oximes with phenylboronic acids typically furnished O-aryloxime
ethers in good to moderate yields.
The conditions chosen were based upon those reported for
the copper(II)-mediated cross-coupling of phenylboronic
acids with phenols.8 Thus, 1 equivalent of both acetophe-
none oxime (1a) and Cu(OAc)2, and 2 equivalents of both
the phenylboronic acid 2a and an amine base, were al-
lowed to react at room temperature in 1,2-dichloroethane
with 4 Å molecular sieves for a period of 72 hours under
an ambient atmosphere.
Key words: O-aryloxime ether, oxime, phenylboronic acid, cop-
per(II) acetate, cross-coupling
O-Aryloxime ethers are not only useful synthetic interme-
diates, being precursors to benzofurans1 and benzisox-
azoles,2 but are present in a growing number of bioactive
compounds. Examples include potent inhibitors of trans-
thyretin amyloid fibril formation3 and agents with signifi-
cant in vitro activity against ecto- and endoparasites that
afflict companion and production animals.4
Table 1 Optimization of Bases, Solvents, and Copper Saltsa
OH
B(OH)2
N
Cu(OAc)2
DCE
O
N
+
base, 4 Å MS
air, 72 h, r.t.
Cl
The O-aryloxime ether moiety is commonly prepared
from a condensation reaction between aldehydes or ke-
tones and O-aryloxyamines.5 Although large numbers of
aldehydes and ketones are commercially available, the O-
aryloxyamines are not and in general must be prepared
prior to use. A more direct approach to O-aryloxime
ethers is based upon the O-arylation of alkali metal oxime
salts with nitro- or fluoroarene derivatives,6 although a
limitation of this strategy is that haloarenes such as iodo-
and bromobenzenes cannot be used.7 Despite these meth-
ods, there is an ongoing need to develop general synthetic
approaches to prepare O-aryloxime ethers.
1a
3a
Cl
2a
Entry
1
Base
Equiv
Yield of 3a (%)b
pyridine
pyridine
pyridine
Et3N
1.1
2
36
2
59
3
5
27
4
2
22
5
DBU
2
55
An O-arylation process conducted under very mild reac-
tion conditions is the oxidative cross-coupling of OH-
containing substrates with phenylboronic acids, simulta-
neously reported by Chan8 and Evans et al.9 This process
is mediated by a stoichiometric amount of a copper(II) salt
in the presence of a weak base and atmospheric oxygen.
We envisaged that such an O-arylation process between
oximes and phenylboronic acids would provide a simple
and general method for the synthesis of O-aryloxime
ethers.
6
DMAP
2
40
7
pyridine–Et3N (1:1)
pyridine–DBU (1:1)
Cs2CO3
2
30
8
2
30
9
1.1
2
no reaction
traced
traced
35
10c
11e
12f
pyridine
pyridine
2
pyridine
2
Acetophenone oxime (1a), readily obtained from ace-
tophenone and hydroxylamine, and 4-chlorophenylboron-
ic acid (2a) were used as model substrates to explore the
a Conditions: 1a (1.5 mmol), 2a (3.0 mmol), Cu(OAc)2 (1.5 mmol).
b Isolated yield (in some cases minor amounts of biaryl ether and/or
phenol products were also isolated).
c MeOH as solvent.
d Deoximation of 1a observed.
e DMF as solvent.
SYNLETT 2009, No. 6, pp 0955–0959
x
x.
x
x.
2
0
0
9
f Amount of CuCl used: 1.5 mmol.
Advanced online publication: 16.03.2009
DOI: 10.1055/s-0028-1088199; Art ID: D37508ST
© Georg Thieme Verlag Stuttgart · New York

956
A. Ali et al.
LETTER
It is known that the amine plays a crucial role, acting as
both a base and a ligand, and varies according to the spe-
cific copper-mediated cross-coupling process.8–10 In this
case, pyridine was found to be the best amine, with 2
equivalents required for optimal yields of 3a (Table 1, en-
try 2).11 Using either 1.1 or 5 equivalents of pyridine re-
sulted in diminished yields (Table 1, entries 1 and 3).
Amines such as triethylamine, DBU, and DMAP either
suppressed or did not improve the cross-coupling reaction
(Table 1, entries 4–6). It has also been reported that mix-
tures of amines can improve carbon–heteroatom cross-
coupling processes.9,10c However, when 2 equivalents of
an equimolar mixture of pyridine and triethylamine (or
pyridine and DBU) was used no improvement in the yield
of 3a occurred (Table 1, entries 7 and 8). Furthermore, no
reaction was observed when an inorganic base such as
Cs2CO3 was used (Table 1, entry 9). A limited examina-
tion of solvents revealed that 1,2-dichloroethane was op-
timal when compared to methanol or DMF, which both
gave only traces of 3a and resulted in considerable deoxi-
mation of 1a to the corresponding ketone (Table 1, entries
10 and 11). Finally, cuprous chloride was evaluated as a
copper source, but failed to improve the yield of 3a
(Table 1, entry 12), despite this copper(I) salt being
shown to effectively promote the O-arylation of N-
hydroxyphthalimide with phenylboronic acids.10a
Table 2 Cu(OAc)2-Mediated O-Arylation of Acetophenone Oxime
(1a) with Arylboronic Acids 2a–i11
OH
N
Cu(OAc)2
O
DCE
N
Ar
ArB(OH)2
+
py, 4 Å MS
air, 72 h, r.t.
1a
2a–i
3a–i
Entry Arylboronic acid
Product
Yield
(%)a
1
2
2a
3a
59
(HO)2B
Cl
O
O
Cl
N
N
59
2b
3b
(HO)2B
3
42
CF3
CF3
2c
3c
3d
3e
3f
(HO)2B
O
O
O
O
N
N
N
N
4
70
50
50
18
10
3
2d
With a suitable set of cross-coupling conditions in hand,11
we investigated the Cu(OAc)2-mediated O-arylation of
acetophenone oxime (1a) with a set of structurally and
electronically diverse arylboronic acids (Table 2).
(HO)2B
OMe
OMe
5
2e
As discussed, 1a and 4-chlorophenylboronic acid (2a) ef-
ficiently cross-coupled to give O-aryloxime ether 3a
(Table 2, entry 1). Similarly, 1a reacted with 3-chlorophe-
nylboronic acid (2b) to afford O-(3-chlorophenyl)ace-
tophenone oxime (3b) in a satisfactory yield (Table 2,
entry 2). Use of the more electron-deficient 4-trifluoro-
methylphenylboronic acid (2c) resulted in a slight de-
crease in yield (Table 2, entry 3). A significantly better O-
arylating agent was phenylboronic acid (2d), which af-
forded O-aryloxime ether 3d in 70% isolated yield
(Table 2, entry 4). When the cross-coupling of 1a with 3-
methoxyphenylboronic acid (2e) and 4-methylphenylbo-
ronic acid (2f) was examined, it was found that the corre-
sponding O-arylated products 3e and 3f, respectively,
were formed in moderate yields (Table 2, entries 5 and 6).
In contrast oxime 1a did not efficiently cross-couple with
2-methylphenylboronic acid (2g, Table 2, entry 7) or 2-
chlorophenylboronic acid (2h, Table 2, entry 8), and the
isolated yields of O-aryloxime ethers 3g and 3h, respec-
tively, were significantly depressed.12 Lastly, the cross-
coupling of 1a and 3-thienylboronic acid (2i) resulted in
the O-aryloxime ether product 3i being isolated in very
low yield (Table 2, entry 9).12
(HO)2B
6
2f
(HO)2B
7
2g
3g
Cl
Cl
O
O
(HO)2B
8b
N
N
2h
3h
3i
(HO)2B
9b
S
S
2i
a See Table 1.
b DBU as the amine and 7 d reaction time.
it was apparent that the O-arylation of oxime 1a was sen-
sitive to the presence of electron-withdrawing and -donat-
ing substituents on the phenylboronic acid. For example,
the O-arylation of 1a became progressively less efficient
as the phenylboronic acid coupling partner became in-
creasingly electron deficient. Thus, yields from cross-
As shown in Table 2, acetophenone oxime (1a) most ef-
fectively cross-coupled with the parent phenylboronic
acid (2d), which is somewhat unexpected given that 2d is
reputed to be relatively inefficient in copper-mediated
carbon–heteroatom cross-coupling reactions.13 Moreover,
Synlett 2009, No. 6, 955–959 © Thieme Stuttgart · New York

LETTER
Synthesis of O-Aryloxime Ethers
957
couplings involving 4- and 3-chlorophenylboronic acids
(2a and 2b) were somewhat diminished in comparison to
the parent phenylboronic acid (2d), whereas the yield
from the reaction of the highly electron-deficient phenyl-
boronic acid 2c was significantly reduced. It was also no-
ticeable that the cross-coupling of phenylboronic acids
bearing electron-donating substituents, 3-methoxyphe-
nylboronic acid (2e) and 4-methylphenylboronic acid
(2f), were also less efficient when compared to phenylbo-
ronic acid (2d). Furthermore, the ortho-substituted phe-
nylboronic acids 2g and 2h, and the heteroarylboronic
acid 2i, appear not to be tolerated. It should be noted that
the poor yield obtained when using 2-chlorophenylboron-
ic acid (2h) was not surprising since it has been reported
that 2-halophenylboronic acids do not participate in cop-
per-mediated carbon–heteroatom cross-couplings.9,10a,14
Table 3 Cu(OAc)2-Mediated O-Arylation of 4¢-Substituted Aceto-
phenone Oximes 1b–d with Phenylboronic Acids 2a–f11
O
OH
B(OH)2
N
N
Cu(OAc)2
DCE
R2
+
py, 4 Å MS
air, 72 h, r.t.
R1
R1
R2
2a–f
1b, R1 = Cl
4a–r
1c, R1 = NO2
1d, R1 = OMe
Entry
R1
R2
Product
4a
Yield (%)a
52
1
Cl
4-Cl
3-Cl
4-CF3
H
2
Cl
4b
4c
52
3
Cl
32
In all cases the O-aryloxime ethers shown in Table 2 were
found to be single isomers about the C=N bond by analy-
sis of the associated NMR spectroscopic data. However,
by virtue of insufficient through-space correlations,
NOESY NMR experiments failed to indicate if these com-
pounds existed as E- or Z-isomers about the C=N bond.
The O-aryloxime ethers were subsequently confirmed as
being E-isomers about the C=N bond by single-crystal X-
ray diffraction (Figure 1).
4
Cl
4d
4e
53
5
Cl
3-OMe
4-Me
4-Cl
3-Cl
4-CF3
H
40
6
Cl
4f
53
7
O2N
O2N
O2N
O2N
O2N
O2N
4g
56b
62b
40
8
4h
4i
9
10
4j
63b
60
11
3-OMe
4-Me
4-Cl
3-Cl
4-CF3
H
4k
4l
12
50
13
MeO
MeO
MeO
MeO
MeO
MeO
4m
4n
4o
66
14
54
15
39
16
4p
4q
4r
65
Figure 1 ORTEP diagram of the single-crystal X-ray structure of
(E)-O-(4-trifluoromethylphenyl)acetophenone oxime (3c)
17
3-OMe
4-Me
49
18
49
a See Table 1.
To probe the reaction scope further, we investigated the
O-arylation of acetophenone oximes containing both elec-
tron-withdrawing and -donating substituents. Thus, the O-
arylation of 4¢-chloro-, 4¢-nitro- and 4¢-methoxyacetophe-
none oximes 1b–d with phenylboronic acids 2a–f was ex-
plored, with the overall results tending to mirror those
involving acetophenone oxime (1a, Table 3).
b Includes the isolation of a minor amount (ca. 5%) of the correspond-
ing (Z)-isomer.
that obtained from the reaction of 1a and 2f (Table 3, en-
tries 6, 12, and 18). Overall, these results suggest that the
efficacy of this copper-mediated cross-coupling process is
not greatly influenced by the electronic nature of the ace-
tophenone oxime, but significantly affected by the pres-
ence of electron-withdrawing and -donating substituents
on the phenylboronic acid coupling partner.
Once again the best yields were generally obtained when
using 4- and 3-chlorophenylboronic acids (2a and 2b,
Table 3, entries 1, 2, 7, 8, 13, and 14) and phenylboronic
acid (2d, Table 3, entries 4, 10, and 16), with the O-aryla-
tion process being less efficient when 4-trifluorometh-
ylphenylboronic acid (2c) was employed (Table 3, entries
3, 9, and 15). In a similar manner to 1a, acetophenone
oximes 1b–d cross-coupled with 3-methoxyphenylboron-
ic acid (2e) to afford the corresponding O-aryloxime
ethers in modest (Table 3, entries 5 and 17) or good isolat-
ed yield (Table 3, entry 11). Cross-couplings of 1b–d with
4-methylphenylboronic acid (2f) gave yields analogous to
In contrast to the O-arylation of acetophenone oximes, the
cross-coupling of benzaldehyde oxime (5a) with a select
group of phenylboronic acids was considerably less effi-
cient (Table 4). The best isolated yield was obtained from
the cross-coupling reaction involving phenylboronic acid
(2d, Table 4, entry 3), whereas the electron-deficient phe-
nylboronic acids 2a and 2b, and also 3-methoxyphenylbo-
ronic acid (2e), all gave O-arylated products in poor yields
Synlett 2009, No. 6, 955–959 © Thieme Stuttgart · New York

958
A. Ali et al.
LETTER
(2) (a) Shutske, G. M. J. Org. Chem. 1984, 49, 180.
(Table 4, entries 1, 2, and 4). Similarly, benzophenone
oxime (5b) cross-coupled poorly with 4-chlorophenylbo-
ronic acid (2a, Table 4, entry 5), although the O-arylation
of 5b with phenylboronic acid (2d) was somewhat more
efficacious (Table 4, entry 6). Moreover, in both cases
significant deoximation of benzophenone oxime (5b) oc-
curred under the reaction conditions [the deoximation of
oximes by Cu(II) salts has been reported previously].7,15
(b) Shutske, G. M.; Kapples, K. J. J. Heterocycl. Chem.
1989, 26, 1293.
(3) Johnson, S. M.; Petrassi, H. M.; Palaninathan, S. K.;
Mohamedmohaideen, N. N.; Purkey, H. E.; Nichols, C.;
Chiang, K. P.; Walkup, T.; Sacchettini, J. C.; Sharpless,
K. B.; Kelly, J. W. J. Med. Chem. 2005, 48, 1576.
(4) (a) Meyer, A. G.; Winzenberg, K. N.; Sawutz, D. G.; Liepa,
A. J. US 7 312 248, 2007. (b) Ali, A.; Altamore, T. M.;
Bliese, M.; Fisara, P.; Liepa, A. J.; Meyer, A. G.; Nguyen,
O.; Sargent, R. M.; Sawutz, D. G.; Winkler, D. A.;
Winzenberg, K. N.; Ziebell, A. Bioorg. Med. Chem. Lett.
2008, 18, 252.
(5) Ãbele, E.; Lukevics, E. Org. Prep. Proced. Int. 2000, 32,
235.
(6) (a) Mooradian, A.; DuPont, P. E. J. Heterocycl. Chem. 1967,
4, 441. (b) Jacob, B. B. Synthesis 1975, 782.
(7) A copper-catalyzed cross-coupling of aromatic oximes with
iodoarenes has recently been reported. See: De Nonappa,
P.; Pandurangan, K.; Maitra, U.; Wailes, S. Org. Lett. 2007,
9, 2767.
(8) Chan, D. M. T.; Monaco, K. L.; Wang, R.-P.; Winters, M. P.
Tetrahedron Lett. 1998, 39, 2933.
(9) Evans, D. A.; Katz, J. L.; West, T. R. Tetrahedron Lett.
1998, 39, 2937.
(10) (a) Petrassi, H. M.; Sharpless, K. B.; Kelly, J. W. Org. Lett.
2001, 3, 139. (b) Wang, Z.; Zhang, J. Tetrahedron Lett.
2005, 46, 4997. (c) Singh, B. K.; Appukkuttan, P.;
Claerhout, S.; Parmar, V. S.; Van der Eycken, E. Org. Lett.
2006, 8, 1863.
Table 4 Cu(OAc)2-Mediated O-Arylation of Benzaldehyde Oxime
(5a) or Benzophenone Oxime (5b) with Phenylboronic Acids
2a,b,d,e11
OH
N
R1
B(OH)2
Cu(OAc)2
DCE
O
R1
N
+
py, 4 Å MS
air, 72 h, r.t.
R2
R2
5a, R1 = H
2a,b,d,e
6a–f
5b, R1 = Ph
Entry
R1
R2
Product
6a
Yield (%)a
1
H
4-Cl
3-Cl
H
28
30
43
29b
32
51
2
H
6b
3
H
6c
4
H
3-MeO
4-Cl
H
6d
(11) All products showed analytical and spectral characteristics
consistent with their structure.
5
Ph
Ph
6e
Representative Pocedure for the Copper-Mediated
Cross-Coupling of Aromatic Oximes and Phenylboronic
Acids
6
6f
a See Table 1.
To a mixture of acetophenone oxime (1a, 200 mg, 1.48
mmol), Cu(OAc)2 (269 mg, 1.48 mmol) and 4-chloro-
phenylboronic acid (2a, 463 mg, 2.96 mmol) in DCE (12
mL) was added pyridine (239 mL, 2.96 mmol). This resulted
in a light green colored solution to which freshly activated,
and partially crushed, 4 Å MS (ca. 350 mg) were added. The
reaction was open to the atmosphere. The progress of the
reaction was followed by TLC. The color of the reaction
mixture changed from light to deep green as the reaction
proceeded. After stirring at r.t. for 72 h the reaction mixture
was filtered through a small pad of silica gel (eluting with
CH2Cl2) and the solvent removed under reduced pressure.
The resulting brown oil was purified by radial
chromatography (eluting with 5–10% CH2Cl2–PE) to afford
(E)-O-(4-chlorophenyl)acetophenone oxime (3a, 215 mg,
59%) as a white solid; mp 69–71 °C (lit.7 54–56 °C). 1H
NMR (400 MHz, CDCl3): d = 7.76 (m, 2 H), 7.43 (m, 3 H),
7.29 (d, J = 9.2 Hz, 2 H), 7.23 (d, J = 9.2 Hz, 2 H), 2.45 (s,
3 H). 13C NMR (100 MHz, CDCl3): d = 158.2 (C), 158.1 (C),
135.7 (C), 129.9 (CH), 129.1 (CH), 128.5 (CH), 126.9 (C),
126.5 (CH), 116.0 (CH), 13.4 (CH3). HRMS: m/z calcd for
C14H12ClNO: 245.0607; found: 245.0599.
b Slowly isomerizes in CDCl3 to give a mixture of E- and Z-isomers.
In summary, we report a concise method to prepare O-aryl-
oxime ethers by means of the first copper-mediated cross-
coupling of aromatic oximes and phenylboronic acids us-
ing stoichiometric Cu(OAc)2 with pyridine as base. In
most cases the O-arylation of acetophenone oximes with
phenylboronic acids furnished O-aryloxime ethers in
good to moderate yields, although when the phenylboron-
ic acid coupling partner contained a highly electron-defi-
cient moiety the reaction did not proceed as smoothly. It
was also found that the cross-coupling was not greatly in-
fluenced by the electronic nature of the acetophenone
oxime. Studies to optimize and improve the scope of this
method are being actively investigated within our labora-
tories and will be reported in due course.
Acknowledgment
Data for Selected Compounds
The authors wish to thank Dr. Craig Forsyth, School of Chemistry,
Monash University, for X-ray crystallographic analysis.
(E)-O-(3-Chlorophenyl)acetophenone Oxime (3b)
Colorless oil. 1H NMR (400 MHz, CDCl3): d = 7.77 (m,
2 H), 7.43 (m, 3 H), 7.35 (m, 1 H), 7.24 (m, 1 H), 7.15 (m,
1 H), 7.01 (m, 1 H), 2.45 (s, 3 H). 13C NMR (100 MHz,
CDCl3): d = 160.2 (C), 158.5 (C), 135.6 (C), 134.7 (C), 130.0
(CH), 129.9 (CH), 128.5 (CH), 126.5 (CH), 122.2 (CH),
115.2 (CH), 113.0 (CH), 13.4 (CH3). HRMS: m/z calcd for
C14H12ClNO: 245.0607; found: 245.0606.
References and Notes
(1) (a) Sheradsky, T. Tetrahedron Lett. 1966, 43, 5225.
(b) Castellino, A. J.; Rapoport, H. J. Org. Chem. 1984, 49,
4399. (c) Takeda, N.; Miyata, O.; Naito, T. Eur. J. Org.
Chem. 2007, 1491.
Synlett 2009, No. 6, 955–959 © Thieme Stuttgart · New York

LETTER
Synthesis of O-Aryloxime Ethers
959
(E)-O-(4-Chlorophenyl)-4¢-chloroacetophenone Oxime
(4a)
(E)-O-(3-Methoxyphenyl)-4¢-nitroacetophenone Oxime
(4k)
Colorless solid; mp 81–83 °C. 1H NMR (400 MHz, CDCl3):
d = 7.70 (d, J = 8.4 Hz, 2 H), 7.39 (d, J = 8.4 Hz, 2 H), 7.29
(d, J = 8.8 Hz, 2 H), 7.21 (d, J = 8.8 Hz, 2 H), 2.42 (s, 3 H).
13C NMR (50 MHz, CDCl3): d = 158.0 (C), 157.1 (C), 136.0
(C), 134.1 (C), 129.2 (CH), 128.8 (CH), 127.7 (CH), 127.1
(C), 116.0 (CH), 13.3 (CH3). HRMS: m/z calcd for
C14H11Cl2NO: 279.0218; found: 279.0207.
Colorless solid; mp 76–78 °C. 1H NMR (400 MHz, CDCl3):
d = 8.28 (d, J = 8.8 Hz, 2 H), 7.96 (d, J = 8.8 Hz, 2 H), 7.26
(m, 1 H), 6.89 (m, 2 H), 6.64 (m, 1 H), 3.84 (s, 3 H), 2.50 (s,
3 H). 13C NMR (50 MHz, CDCl3): d = 160.7 (C), 160.3 (C),
155.7 (C), 148.5 (C), 141.9 (C), 129.9 (CH), 127.2 (CH),
123.7 (CH), 108.2 (CH), 107.2 (CH), 101.1 (CH), 55.4
(CH3), 13.2 (CH3). HRMS: m/z calcd for C15H14N2O4:
286.0954; found: 286.0945.
(E)-O-(4-Methylphenyl)-4¢-chloroacetophenone Oxime
(4f)
(E)-O-(4-Chlorophenyl)-4′-methoxyacetophenone
Oxime (4m)
Yellow solid; mp 103–104 °C. 1H NMR (400 MHz, CDCl3):
d = 7.71 (d, J = 8.8 Hz, 2 H), 7.38 (d, J = 8.8 Hz, 2 H), 7.14
(m, 4 H), 2.42 (s, 3 H), 2.32 (s, 3 H). 13C NMR (125 MHz,
CDCl3): d = 157.4 (C), 156.2 (C), 135.6 (C), 134.5 (C), 131.7
(C), 129.7 (CH), 128.7 (CH), 127.7 (CH), 114.7 (CH), 20.6
(CH3), 13.1 (CH3). HRMS: m/z calcd for C15H14ClNO:
259.0764; found: 259.0766.
Colorless solid; mp 78–80 °C. 1H NMR (400 MHz, CDCl3):
d = 7.72 (d, J = 8.8 Hz, 2 H), 7.27 (d, J = 9.2 Hz, 2 H), 7.21
(d, J = 9.2 Hz, 2 H), 6.94 (d, J = 8.8 Hz, 2 H), 3.85 (s, 3 H),
2.41 (s, CH3). 13C NMR (100 MHz, CDCl3): d = 161.0 (C),
158.2 (C), 157.8 (C), 129.1 (CH), 128.1 (C), 127.9 (CH),
126.7 (C), 116.0 (CH), 113.9 (CH), 55.3 (CH3), 13.3 (CH3).
HRMS: m/z calcd for C15H14ClNO2: 275.0713; found:
275.0698.
(E)-O-(4-Chlorophenyl)-4¢-nitroacetophenone Oxime
(4g)
Colorless solid; mp 101–103 °C. 1H NMR (400 MHz,
CDCl3): d = 8.26 (d, J = 9.2 Hz, 2 H), 7.93 (d, J = 9.2 Hz, 2
H), 7.30 (d, J = 9.2 Hz, 2 H), 7.22 (d, J = 9.2 Hz, 2 H), 2.49
(s, 3 H). 13C NMR (100 MHz, CDCl3): d = 157.8 (C), 156.2
(C), 148.5 (C), 141.6 (C), 129.3 (CH), 127.6 (C), 127.2
(CH), 123.7 (CH), 116.1 (CH), 13.3 (CH3). HRMS: m/z
calcd for C14H11ClN2O3: 290.0458; found: 290.0446.
(12) In the case of compounds 3h and 3i, DBU (2.0 equiv) was
found to be a more effective amine than pyridine.
(13) Chan, D. M. T.; Monaco, K. L.; Li, R.; Bonne, D.; Clark, C.
G.; Lam, P. Y. S. Tetrahedron Lett. 2003, 44, 3863.
(14) 2-Halophenylboronic acids are presumably susceptible to
‘proto-deboronation’. See: Kuivila, H. G.; Reuwer, J. F.;
Mangravite, J. A. Jr. J. Am Chem. Soc. 1964, 86, 2666.
(15) (a) Kaminskaia, N. V.; Kostic, N. M. J. Chem. Soc., Dalton
Trans. 2001, 1083. (b) Onindo, C. O.; Kozlowski, H.; Kiss,
T. J. Chem. Soc., Dalton Trans. 1995, 3911.
Synlett 2009, No. 6, 955–959 © Thieme Stuttgart · New York