A straightforward synthesis of N-monosubstituted α-keto amides via aerobic benzylic oxidation of amides

Article abstract of DOI:10.1016/j.tet.2011.11.005

An efficient sodium bicarbonate promoted aerobic oxidation reaction to prepare N-monosubstituted α-keto amides in the presence of n-tetrabutylammonium hydrogensulfate (TBAHS) was described. This reaction provides a very simple and convenient synthetic route to N-monosubstituted α-keto amides from easily available aryl- or heteroarylacetamides in good to high yields without using toxic reagents and harsh conditions.

Full text of DOI:10.1016/j.tet.2011.11.005

Tetrahedron 68 (2012) 573e579
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A straightforward synthesis of N-monosubstituted a-keto amides via aerobic
benzylic oxidation of amides
,
a,b,c,
*
Jun Shao a, Xiaomei Huang a, Siyuan Wang a, Bingxin Liu a , Bin Xu
*
a Department of Chemistry, College of Sciences, Shanghai University, Shanghai 200444, China
b State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, China
c Shanghai Key Laboratory of Green Chemistry and Chemical Processes, Department of Chemistry, East China Normal University, Shanghai 200062, China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 21 June 2011
Received in revised form 12 October 2011
Accepted 3 November 2011
Available online 11 November 2011
An efficient sodium bicarbonate promoted aerobic oxidation reaction to prepare N-monosubstituted a-
keto amides in the presence of n-tetrabutylammonium hydrogensulfate (TBAHS) was described. This
reaction provides a very simple and convenient synthetic route to N-monosubstituted -keto amides
a
from easily available aryl- or heteroarylacetamides in good to high yields without using toxic reagents
and harsh conditions.
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
Arylacetamides
Atmospheric oxygen
a
-Keto amides
N-Monosubstituted amides
Oxidation
1. Introduction
O
O
O
H
N
H
N
Due to their specific structures and activities, N-mono-
substituted a-keto amides have been paid great attentions. The a-
O
O
H2N
N
H
N
H
O
Bu
O
O
keto amide scaffold is widely spread in natural products and some
substances with potential bio-activities (Scheme 1). For example,
Chloropeptin I and Complestatin are proved to inhibit HIV repli-
cation, and the studies on their total synthesis, modification, and
activity attract the efforts of many chemists.1 Bestatin and PTH
Bestatin analogue
Isatin
PTH
OH
O
analogues bearing the a-keto skeletons were found to be inhibitors
HN
of the serine proteinase elastase2 and Cathepsin K,3 respectively.
Isatin and its derivatives are widely used in dye, food, and medic-
O
O
O
H
H
N
H
N
N
O
HOOC
N
N
H
inal industry.4 Besides, many other substances bearing the
a-keto
H
O
O
O
amide substructure were found to be fungicide and fungicide pre-
cursors,5 antibiotics,6 and various inhibitors.7 Moreover, their us-
ages as significant intermediates, versatile building blocks8 and
applications in NMR study9 have also been added to their
importance.
Cl
Cl Cl
Cl Cl
Cl
OH
OH
OH
Chloropeptin I
Scheme 1. Some bioactive products with
OH
a
-keto amide moiety.
The synthesis of N-monosubstituted a-keto amides could date
back to the early 1960s when Ugi and his co-workers developed the
coupling reaction of acyl chloride with isonitrile.10 After that, var-
ious synthetic methods were exploited including the direct
amidation of a
-keto acids and their derivatives,11 photooxygenation
of corresponding amides,12 amido double carbonylation,13 rear-
rangement reaction between Schiff base and isonitrile,14 oxidation
of
a a-oxidation of amides mainly
-hydroxyamides,15 and direct
using SeO2 as metal oxidants.8f,16 Recently, a copper-catalyzed ox-
* Corresponding authors. Tel./fax: þ86 21 66132065; e-mail addresses: bxliu@
idative amidationediketonization of terminal alkynes17 and a zinc
shu.edu.cn (B. Liu), xubin@shu.edu.cn (B. Xu).
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.11.005

574
J. Shao et al. / Tetrahedron 68 (2012) 573e579
Table 1
chloride promoted formal oxidative coupling of aromatic aldehydes
and isocyanides to
-keto amides18 were reported, which have
Reaction optimization of base, additive, and solventa
a
provided new routes for this class of molecules. However, for some
of the methods, the expensive and toxic reagents employed, the
harsh conditions used and low yields achieved have turned them
into limitations.
O
H
H
N
N
Base, Additive
Solvent, Air
O
O
2a
We have recently reported an efficient access to N,N-di-
1a
substituted
amides with Cs2CO3 and n-Bu4NBr in the presence of atmospheric
air.19 However, the same reaction conditions failed to afford
-ox-
idized N-monosubstituted amides in good yields. It became a new
synthetic challenge to find an efficient and convenient access to the
a-keto amides by treatment of easily available tertiary
Entry Base (equiv) Additive (equiv) Solvent Temp (ꢀC) Time (h) Yieldb (%)
a
1
2
3
4
5
6
7
8
Cs2CO3 (1.1) TBAB (0.5)
Cs2CO3 (2.0) TBAB (1.0)
Cs2CO3 (3.0) TBAB (1.5)
Cs2CO3 (3.0) TBAHS (1.5)
Cs2CO3 (3.0) TBAHS (1.5)
Cs2CO3 (3.0) TBAHS (1.5)
Cs2CO3 (3.0) TBAHS (1.5)
Cs2CO3 (3.0) TEBAC (1.5)
Cs2CO3 (2.5) TBAHS (1.5)
Cs2CO3 (3.0) TBAHS (1.0)
DMF
DMF
DMF
DMF
Toluene 110
DCE 85
Dioxane Reflux
Dioxane Reflux
Dioxane Reflux
Dioxane Reflux
Dioxane Reflux
Dioxane Reflux
Dioxane Reflux
Dioxane Reflux
Dioxane Reflux
Dioxane Reflux
Dioxane Reflux
Dioxane Reflux
120
120
120
120
9
6
5.5
24
20
31
41
Trace
48
<5
84
7
57
53
N-monosubstituted
a-keto amides via direct a-oxidation of the
7
24
6
40
9
11
22
24
24
12
14.5
43
13
24
corresponding secondary amides without using any toxic or ex-
pensive reagents, or without employing harsh conditions. Herein,
we developed a direct method for the efficient preparation of N-
9
monosubstituted a-keto amides from readily available arylaceta-
10
11
12
13
14
15
16
17
18
mides in good to high yields (Scheme 2). The reactions are effective
in the presence of NaHCO3 and n-Bu4NHSO4 with the reactions
open to air in refluxed dioxane.
K2CO3 (3.0)
CsOAc (3.0) TBAHS (1.5)
NaOH (3.0) TBAHS (1.5)
TBAHS (1.5)
23
0
10
89
NaHCO3 (3.0) TBAHS (1.5)
NaHCO3 (3.0) TBAHS (1.0)
NaHCO3 (2.0) TBAHS (1.5)
NaHCO3 (3.0) TBAHS (1.5)
NaHCO3 (3.0) TBAB (1.5)
70
O
R1
N
22c
47d
Trace
Cs CO , -Bu NBr
n
2
3
4
previous work
Ar
R2
DMF, air, 120 oC
R1, R2 = H
O
R1
N
The bold values in the table are used for emphasizing the optimized reaction
condition.
R2
a
Ar
Reaction conditions: 1a (0.5 mmol), dioxane (2.5 mL), open to air, dried through
acalciumchloridetube, reflux. DCE¼1,2-dichloroethane, TBAB¼Tetrabutylammonium
bromide, TEBAC¼Benzyltriethyl-ammonium chloride, TBAHS¼Tetrabutylammonium
hydrogensulfate.
O
1
O
H
N
NaHCO , -Bu NHSO
n
4
3
4
this work
Ar
R2
b
Isolated yields.
With conversion of 25% based on 1a.
Reaction was run under O2 atmosphere.
dioxane, air, reflux
R2 = H
c
O
2
R1 = H,
Scheme 2. Synthesis of
d
a
-keto arylacetamides.
shown in Table 2, the
a-oxidation reaction proceeded readily to give
the corresponding -keto amides in moderate to good yields. Re-
a
markably clean reactions were observed with functionalized mol-
ecules bearing ortho, meta, and para substitutions on the N-aryl ring
(Table 2, entries 2e9). Electron-donating and electron-
withdrawing groups substituted on the aryl ring were tolerated
2. Results and discussion
Initially, based on our previous results, we speculated whether
the same conditions, which were successfully applied to give N,N-
disubstituted a-keto amides, could be also effective for the prepa-
and readily to give the corresponding a-keto amides in good yields
(Table 2, entries 11 and 12). However, substrate with strong
electron-withdrawing group, e.g., nitro group, afforded lower yield
(Table 2, entry 10). This oxidation reaction was not limited to simple
benzene-containing aromatics, substrates containing the sub-
structure of naphthalene (Table 2, entry 13), pyrimidine (Table 2,
entry 14), pyridine (Table 2, entry 15), and aliphatic chain (Table 2,
entry 16) also gave good yields. For sterically hindered or less re-
active substrates, better results could be achieved using Cs2CO3 as
base instead of NaHCO3. For example, compound 2c bearing an
ortho methoxyl group was obtained in 84% yield (Table 2, entry 3),
and 2h and 2n were obtained in both 93% yields under the same
conditions (Table 2, entries 8 and 14). Nevertheless, for substrate
with strong electron-withdrawing nitro group, amide 2j was
afforded in 29% yield even using Cs2CO3 as base (Table 2, entry 10).
To further expand the scope of the reaction, substrates 1q and 1r
with indol or thiophene moiety were investigated under standard
conditions. Gratifyingly, the corresponding oxidation products 2q
and 2r could be also well achieved in good yields, respectively
(Table 2, entries 17 and 18). However, 2-phenylacetamide and
cinnamamide derived substrate (E)-N,4-diphenylbut-3-enamide,20
ration of N-monosubstituted amides. To our disappointment, 1a in
DMF in the presence of Cs2CO3 and n-Bu4NBr gave 2a in only 20%
yield after reacted for 9 h (Table 1, entry 1). Improved yields could
be achieved by increasing the amount of Cs2CO3 and n-Bu4NBr
(Table 1, entries 2 and 3). When n-Bu4NHSO4 was used instead as
additive, the yield significantly dropped (Table 1, entry 4). However,
the change of solvent turned out to be a good solution. Dioxane was
proved to be the most favorable solvent (Table 1, entry 7). Other
solvents, such as toluene and DCE gave no better results (Table 1,
entries 5 and 6). Changing the additive from TBAHS to TEBAC gave
trace amount of product (Table 1, entry 8) and the yields dropped
with reduction of the amount of base or additive (Table 1, entries 9
and 10). No amelioration result could be afforded by using K2CO3,
CsOAc, and NaOH as base (Table 1, entries 11e13). To our delight,
the employment of NaHCO3 as base gave 2a in 89% yield after
reacted for 12 h (Table 1, entry 14). However, when reducing the
amount of n-Bu4NHSO4 to 1.0 equiv, the yield dropped to 70% (Table
1, entry 15) and less amount of NaHCO3 gave only 22% yield of the
oxidized product with a conversion of 25% after reacted for 43 h
(Table 1, entry 16). When the reaction was conducted using oxygen
atmosphere as oxidant (Table 1, entry 17) or using TBAB as additive
instead of TBAHS (Table 1, entry 18), no better results were
achieved.
which
was
prepared
from
cinnamaldehyde
and
4-
methylbenzenesulfono-hydrazide, failed to react under the same
conditions and gave no desired oxidation products.
Based on literature reports and our previous work,19,21 a possi-
To explore the scope of this method, a variety of aryl- or het-
eroarylacetamides 1aer were applied under the optimized condi-
tions (Table 1, entry 14). The results are summarized in Table 2. As
ble reaction mechanism for this direct formation of
a-keto amides
was illustrated involving deprotonation at the benzyl position of

J. Shao et al. / Tetrahedron 68 (2012) 573e579
575
Table 2
Synthesis of N-monosubstituted a
-keto amides by oxidation of amidesa
NaHCO3 (3 equiv.)
O
H
N
H
N
-Bu NSO H (1.5 equiv.)
n
4
4
Ar
R
Ar
R
O
Dioxane, air, reflux
O
2
1
Entry
1
Reactant
Product
Time (h)
12
Yieldb (%)
O
O
O
H
N
H
N
89
85
O
1a
O
O
O
2a
H
N
H
N
2
3
14.5
16
O
1b
1c
2b
2c
OMe
OMe
H
N
H
N
84c
O
O
H
H
N
N
4
5
6
7
13
81
83
80
85
O
1d
O
O
O
2d
O
H
N
H
Cl
N
Cl
12
O
O
1e
1f
2e
2f
O
H
N
H
N
14
O
H
H
N
N
11.5
O
O
OMe
Cl
1g
1h
1i
OMe
Cl
2g
2h
2i
O
H
H
N
N
8
18
18
11
93c
80
O
O
O
H
N
H
N
9
O
O
Br
Br
O
H
N
H
N
10
29c
O
O
NO2
1j
NO2
2j
2k
2l
O
H
N
H
N
11
10
83
84
64
O
O
Cl
1k
1l
Cl
O
H
N
H
N
12
11
O
O
MeO
MeO
O
H
N
H
N
13
14
12
O
O
1m
2m
O
H
H
N
N
93c
N
N
11.5
O
O
N
(continued on next page)
1n
N
2n

576
J. Shao et al. / Tetrahedron 68 (2012) 573e579
Table 2 (continued )
Entry
Reactant
Product
Time (h)
Yieldb (%)
O
H
H
N
N
N
N
15
16
17
10
52
55
59
O
O
1o
2o
O
H
H
N
N
14.5
10
O
1p
O
O
2p
H
N
H
N
O
O
N
N
1q
2q
O
H
N
H
N
18
7
44
S
O
S
O
1r
2r
a
Reaction conditions: amides (1aer, 0.5 mmol), NaHCO3 (1.5 mmol), n-Bu4NHSO4 (0.75 mmol), dioxane (2.5 mL), open to air, dried through a calcium chloride tube, reflux.
Isolated yields.
Cs2CO3 (3.0 equiv) was used instead of NaHCO3.
b
c
the amides 1 and the formation of carbanion A, which then reacted
conditions. The usage of the reaction and its applications for the
synthesis of bioactive compounds are currently under further in-
vestigation in our laboratory and will be reported in due course.
with molecule oxygen to provide peroxy anion B (Scheme 3). In-
termediate B could be assumed to exist in form C with a six-
membered ring by intermolecular hydrogen bond interaction. In-
tra or intermolecular abstraction of a proton from the benzylic site
of the intermediate B leading to loss of hydroxide ion and formation
of a carbonyl group of 2.21c The effect of ammonium salt in this
reaction may account for the deprotonation step. The detailed
mechanism is still unconfirmed at this time and need further in-
vestigation in our laboratory.
4. Experimental section
4.1. General
All solvents were purified before used.22 All melting points were
taken on a melting point tube. Infrared spectra were recorded on
a Nicolet AVATAR 370 FT-IR spectrometer. 1H and 13C NMR spectra
were obtained on a Bruker AV-500 spectrometer. Chemical shifts
H
N
H2O
O2
Ar
R
are reported relative to chloroform (
d
¼7.26 ppm) or dimethyl
O
sulfoxide (
d
¼2.50 ppm) for 1H NMR and chloroform (
¼77.16 ppm)
d
A
or dimethyl sulfoxide (
d
¼39.52 ppm) for 13C NMR. GC-MS was
BH
carried out on an Agilent 5975 N mass spectrometer (EI, 70 eV).
Elemental analyses were carried out on a VARIO EL111 elemental
analyzer. Silica gel plate GF254 were used for thin layer chroma-
tography (TLC) and silica gel H or 300e400 mesh were used for
flash column chromatography. Yields refer to chromatographically
and spectroscopically pure compounds, unless otherwise indicated.
B
R
H
N
OH
Ar
O
1
O
O
O
O
H
H
H
N
N
Ar
R
Ar
R
O
2
O
B
4.2. General procedure for synthesis of N-monosubstituted
keto amides (2aer)
a-
O
To a 25 mL round-bottom flask dried through a calcium chloride
tube, 1aer (0.5 mmol), NaHCO3 (1.5 mmol), and n-Bu4NHSO4
(0.75 mmol) in dioxane (2.5 mL) were added in the presence of
atmospheric oxygen. The reaction mixture was stirred under reflux
until 1aer was disappeared monitored by TLC. After that, the
mixture was filtered and washed with ethyl acetate. The filtrate was
concentrated under reduced pressure and the crude product was
purified by column chromatography on silica gel (eluent: petro-
leum ether/ethyl acetate) to give 2aer.
H
N
Ar
R
O
C
Scheme 3. Plausible mechanism of a-oxidation reaction.
3. Conclusion
In summary, we describe here an efficient sodium bicarbonate
promoted aerobic oxidation reaction in the presence of tetra-n-
4.2.1. 2-Oxo-N,2-diphenylacetamide (2a)23. Light yellow solid, 89%
yield, mp 43e45 ꢀC. IR (KBr): 3436, 3338, 3059, 2925, 1667, 1596,
butylammonium bisulfate to afford N-monosubstituted
amides. Compared with other reported methods, the current ap-
proach provides a very simple and convenient route to -keto
a-keto
1281 cmꢁ1. 1H NMR (500 MHz, CDCl3):
d
9.04 (s,1H), 8.40 (dd, J¼7.5,
a
1.0 Hz, 2H), 7.71 (d, J¼7.5 Hz, 2H), 7.66e7.63 (m, 1H), 7.50 (t,
amides from easily available aryl- or heteroarylacetamides in good
to high yields. This reaction avoids using toxic reagents and harsh
J¼8.0 Hz, 2H), 7.39 (t, J¼8.0 Hz, 2H), 7.19 (t, J¼7.5 Hz, 1H). 13C NMR
(125 MHz, CDCl3):
d 187.57, 159.09, 136.76, 134.71, 133.16, 131.53,

J. Shao et al. / Tetrahedron 68 (2012) 573e579
577
129.30, 128.65, 125.38, 120.06. MS (EI): m/z (%) 225 (27) [Mþ], 211
(10), 120 (10), 119 (10), 106 (21), 105 (100), 91 (18), 77 (47).
J¼9.0 Hz, 2H). 13C NMR (125 MHz, CDCl3):
d
187.19, 158.92, 135.33,
134.91,133.02,131.60,130.49,129.41,128.73,121.26. MS (EI): m/z (%)
261 (5) [Mþ
(
37Cl)], 259 (15) [Mþ
(
35Cl)], 105 (100), 77 (31).
4.2.2. 2-Oxo-2-phenyl-N-o-tolylacetamide (2b)17,24. Light yellow
solid, 85% yield, mp 89.5e91.5 ꢀC. IR (KBr): 3231, 2910, 1677,
4.2.9. N-(4-Bromophenyl)-2-oxo-2-phenylacetamide
yellow solid, 80% yield, mp 160e162 ꢀC. IR (KBr): 3340, 2925, 1488,
(2i)17. Light
1253 cmꢁ1. 1H NMR (500 MHz, CDCl3):
d 8.96 (s, 1H), 8.46e8.44 (m,
2H), 8.12 (d, J¼8.0 Hz, 1H), 7.66 (tt, J¼7.5, 1.0 Hz, 1H), 7.51 (t,
1279, 1166, 1069 cmꢁ1 1H NMR (500 MHz, CDCl3):
. d 8.98 (s, 1H),
J¼7.5 Hz, 2H), 7.31e7.24 (m, 2H), 7.15 (td, J¼7.5, 1.0 Hz, 1H), 2.37 (s,
8.40 (d, J¼7.5 Hz, 2H), 7.67 (t, J¼7.5 Hz, 1H), 7.61 (AA0 of AA0BB0,
3H). 13C NMR (125 MHz, CDCl3):
d 187.60, 158.97, 134.70, 133.19,
J¼8.5 Hz, 2H), 7.51 (BB0 of AA0BB0, J¼9.0 Hz, 2H), 7.53e7.50 (m, 2H).
131.56, 130.75, 128.82, 128.64, 127.02, 127.00, 125.75, 121.80, 17.66.
13C NMR (125 MHz, CDCl3):
d 187.14, 158.89, 135.84, 134.95, 133.04,
MS (EI): m/z (%) 239 (28) [Mþ], 106 (15), 105 (100), 77 (38).
132.40, 131.64, 128.77, 121.57, 118.22. MS (EI): m/z (%) 304 (10) [Mþ
81Br)], 303 (10) [Mþ 79Br)], 105 (100), 77 (33).
(
(
4.2.3. N-(2-Methoxyphenyl)-2-oxo-2-phenylacetamide (2c). Light
yellow solid, 84% yield, mp 81e84 ꢀC. IR (KBr): 3437, 3384, 2967,
4.2.10. N-(4-Nitro-phenyl)-2-oxo-2-phenyl-acetamide (2j)26. Light
yellow solid, 29% yield, mp 170e172 ꢀC. IR (KBr): 3329, 2958, 2925,
1693, 1663, 1524, 1280 cmꢁ1. 1H NMR (500 MHz, CDCl3):
d 9.53 (s,
1H), 8.50 (dd, J¼8.0, 1.5 Hz, 1H), 8.49e8.40 (m, 2H), 7.65 (tt, J¼7.5,
1.5 Hz, 1H), 7.53e7.50 (m, 2H), 7.14 (td, J¼7.5, 1.5 Hz, 1H), 7.02 (td,
J¼7.5, 1.0 Hz, 1H), 6.94 (dd, J¼8.5, 1.5 Hz, 1H), 3.94 (s, 3H). 13C NMR
1509, 1339, 1264 cmꢁ1. 1H NMR (500 MHz, CDCl3):
d 9.29 (br, 1H),
8.43 (d, J¼8.0 Hz, 2H), 8.30 (AA0 of AA0BB0, J¼9.0 Hz, 2H), 7.90 (BB0 of
AA0BB0, J¼9.0 Hz, 2H), 7.70 (t, J¼7.0 Hz, 1H), 7.55 (t, J¼8.0 Hz, 2H).
(125 MHz, CDCl3):
d
187.63, 159.12, 148.93, 134.60, 133.40, 131.52,
13C NMR (125 MHz, CDCl3):
d 186.39, 158.90, 142.37, 135.31, 132.69,
128.68, 126.55, 125.19, 121.17, 119.97, 110.32, 55.93. MS (EI): m/z (%)
225 (3) [Mþ], 215 (12), 214 (100), 212 (99), 133 (25), 105 (86), 77
(35). Anal. Calcd for C15H13NO3: C, 70.58; H, 5.13; N, 5.49. Found: C,
70.45; H, 4.85; N, 5.59.
131.73, 128.91, 125.39, 119.73. MS (EI): m/z (%) 270 (4) [Mþ], 105
(100), 77 (31).
4.2.11. 2-(4-Chlorophenyl)-2-oxo-N-phenylacetamide
(2k). Light
yellow solid, 83% yield, mp 127e128 ꢀC. IR (KBr): 3458, 3338, 1655,
4.2.4. 2-Oxo-2-phenyl-N-m-tolylacetamide (2d)17. Light yellow
solid, 81% yield, mp 91e93 ꢀC. IR (KBr): 3470, 3341, 1688, 1661,
1535, 1277, 1165 cmꢁ1 1H NMR (500 MHz, CDCl3):
. d 8.96 (br, 1H),
8.41 (d, J¼8.5 Hz, 2H), 7.69 (AA0 of AA0BB0, J¼7.5 Hz, 2H), 7.48 (BB0 of
1279 cmꢁ1 1H NMR (500 MHz, CDCl3):
. d 8.99 (s, 1H), 8.41 (d,
AA0BB0, J¼8.5 Hz, 2H), 7.41 (t, J¼8.0 Hz, 2H), 7.21 (t, J¼7.0 Hz, 1H).
J¼7.5 Hz, 2H), 7.65 (t, J¼7.5 Hz, 1H), 7.57 (s, 1H), 7.51 (t, J¼7.5 Hz,
13C NMR (125 MHz, CDCl3):
d 186.19, 158.66, 141.64, 136.59, 133.11,
3H), 7.28 (t, J¼7.5 Hz, 1H), 7.02 (d, J¼7.5 Hz, 1H), 2.39 (s, 3H). 13C
131.53, 129.41, 129.12, 125.60, 120.08. MS (EI): m/z (%) 261 (6) [Mþ
NMR (125 MHz, CDCl3):
d
187.58, 159.04, 139.27, 136.66, 134.67,
(
37Cl)], 259 (16) [Mþ 35Cl)], 149 (9), 105 (100), 77 (32). Anal. Calcd
(
133.19, 131.53, 129.11, 128.62, 126.19, 120.63, 117.15, 21.59. MS (EI):
for C14H10ClNO2: C, 64.75; H, 3.88; N, 5.39. Found: C, 64.55; H, 3.82;
N, 5.42.
m/z (%) 239 (30) [Mþ], 134 (14), 133 (10),106 (15), 105 (100), 77 (38).
4.2.5. N-(3-Chlorophenyl)-2-oxo-2-phenylacetamide (2e)25. Light
yellow solid, 83% yield, mp 120e121 ꢀC. IR (KBr): 3474, 3348, 1688,
4.2.12. 2-(4-Methoxyphenyl)-2-oxo-N-phenyl-acetamide
(2l)27. Light yellow solid, 84% yield, mp 110.0e111.0 ꢀC. IR (KBr):
3441, 3353, 2849, 1688, 1642, 1595, 1565, 1531, 1445, 1164 cmꢁ1. 1H
1660, 1594, 1538, 1484, 1443 cmꢁ1 1H NMR (500 MHz, CDCl3):
.
d
9.01 (s, 1H), 8.41 (dd, J¼9.5, 1.0 Hz, 2H), 7.87 (t, J¼2.0 Hz, 1H), 7.67
(tt, J¼7.5, 1.0 Hz, 1H), 7.53e7.50 (m, 3H), 7.32 (t, J¼8.0 Hz, 1H),
7.18e7.17 (m, 1H). 13C NMR (125 MHz, CDCl3):
187.09, 159.00,
NMR (500 MHz, CDCl3):
d
9.07 (s, 1H), 8.48 (d, J¼9.0 Hz, 2H), 7.70
(AA0 of AA0BB0, J¼8.0 Hz, 2H), 7.38 (t, J¼8.0 Hz, 2H), 7.18 (d, J¼7.5 Hz,
d
1H), 6.96 (BB0 of AA0BB0, J¼8.5 Hz, 2H), 3.89 (s, 3H). 13C NMR
137.88, 135.05, 134.94, 132.97, 131.61, 130.32, 128.74, 125.47, 120.16,
(125 MHz, CDCl3): d 185.35, 165.00, 159.66, 136.89, 134.35, 129.28,
118.06. MS (EI): m/z (%) 261 (4) [Mþ
(
37Cl)], 259 (12) [Mþ
(
35Cl)], 105
126.18, 125.25, 120.02, 114.02, 55.69. MS (EI): m/z (%) 255 (12) [Mþ],
(100), 77 (28).
135 (100), 77 (12).
4.2.6. 2-Oxo-2-phenyl-N-p-tolylacetamide (2f)17. Light yellow solid,
80% yield, mp 114.5e116.4 ꢀC. IR (KBr): 3444, 3340, 2923, 1671,
4.2.13. N-(Naphthalen-1-yl)-2-oxo-2-phenylacetamide
(2m)28. Light yellow solid, 64% yield, mp 102e103 ꢀC. IR (KBr):
1535, 1281 cmꢁ1. 1H NMR (500 MHz, CDCl3):
d
8.92 (s, 1H), 8.41 (d,
3441, 3178, 1667, 1656, 1594, 1535, 1502, 1442 cmꢁ1 1H NMR
.
(500 MHz, CDCl3): d 9.56 (s, 1H), 8.51e8.49 (m, 2H), 8.25 (d,
J¼7.0 Hz, 2H), 7.66 (t, J¼7.5 Hz, 1H), 7.59 (AA0 of AA0BB0, J¼8.5 Hz,
2H), 7.51 (t, J¼8.0 Hz, 2H), 7.20 (BB0 of AA0BB0, J¼8.5 Hz, 2H), 2.35 (s,
J¼7.5 Hz, 1H), 7.97 (d, J¼8.5 Hz, 1H), 7.91 (dd, J¼8.0, 0.5 Hz, 1H), 7.77
3H). 13C NMR (125 MHz, CDCl3):
d 187.66, 158.89, 135.20, 134.71,
(d, J¼8.0 Hz, 1H), 7.70e7.67 (m, 1H), 7.62e7.58 (m, 1H), 7.57e7.53
134.22, 133.28, 131.60, 129.87, 128.67, 120.03, 21.12. MS (EI): m/z (%)
(m, 4H). 13C NMR (125 MHz, CDCl3):
d 187.60, 159.45, 134.86, 134.21,
239 (37) [Mþ], 106 (17), 105 (100), 77 (38).
133.27, 131.72, 131.25, 129.04, 128.76, 126.81, 126.61, 126.41, 125.86,
120.35, 119.65. MS (EI): m/z (%) 275 (38) [Mþ], 270 (28), 150 (37),
120 (71), 105 (100), 77(64).
4.2.7. N-(4-Methoxyphenyl)-2-oxo-2-phenylacetamide (2g)17. Light
yellow solid, 85% yield, mp 94e95 ꢀC. IR (KBr): 3367, 3341, 2957,
2928, 1664, 1511, 1245 cmꢁ1. 1H NMR (500 MHz, CDCl3):
d
8.90 (s,
4.2.14. 2-Oxo-2-phenyl-N-(pyrimidin-5-yl)acetamide
yellow solid, 93% yield, mp 169e170 ꢀC. IR (KBr): 3441, 2831, 1669,
1438, 1277, 1200 cmꢁ1 1H NMR (500 MHz, CDCl3):
9.18 (s, 2H),
(2n). Light
1H), 8.41 (AA0 of AA0BB0, J¼7.0 Hz, 2H), 7.67e7.61 (m, 3H), 7.50 (t,
J¼8.0 Hz, 2H), 6.94 (BB0 of AA0BB0, J¼7.0 Hz, 2H), 3.82 (s, 3H). 13C
.
d
NMR (125 MHz, CDCl3):
d
187.74, 158.80, 157.16, 134.68, 133.32,
9.12 (s, 1H), 9.08 (s, 1H), 8.44e8.42 (m, 2H), 7.72e7.69 (m, 1H), 7.54
131.57,129.93,128.66,121.63,114.47, 55.61. MS (EI): m/z (%) 255 (46)
(t, J¼8.0 Hz, 2H). 13C NMR (125 MHz, CDCl3):
d 185.97, 159.31,
[Mþ], 149 (10), 122 (11), 105 (100), 77 (35).
155.22, 148.08, 135.40, 132.62, 131.73, 128.94. MS (EI): m/z (%) 227
(7) [Mþ], 199 (23), 105 (100), 83 (40), 77 (45). Anal. Calcd for
C12H9N3O2: C, 63.43; H, 3.99; N, 18.49. Found: C, 63.46; H, 4.03; N,
18.43.
4.2.8. N-(4-Chlorophenyl)-2-oxo-2-phenylacetamide (2h)17. Light
yellow solid, 93% yield, mp 158e160 ꢀC. IR (KBr): 3339, 1696, 1663,
1532, 1278, 1166 cmꢁ1 1H NMR (500 MHz, CDCl3):
. d 9.02 (s, 1H),
8.49 (dd, J¼8.0, 1.0 Hz, 2H), 7.66 (AA0 of AA0BB0, J¼9.0 Hz, 2H),
4.2.15. 2-Oxo-2-phenyl-N-(pyridin-2-yl)acetamide (2o). Light yel-
low solid, 52% yield, mp 69e70 ꢀC. IR (KBr): 3436, 1675, 1620, 1594,
7.68e7.64 (m, 1H), 7.51 (t, J¼8.0 Hz, 2H), 7.35 (BB0 of AA0BB0,

578
J. Shao et al. / Tetrahedron 68 (2012) 573e579
1579, 1531, 1465 cmꢁ1 1H NMR (500 MHz, CDCl3):
. d 9.55 (s, 1H),
Sabet, R.; Mohammadpour, M.; Sadeghi, A.; Fassihi, A. Eur. J. Med. Chem. 2010,
45, 1113e1118; (d) Diaz, P.; Xu, J.; Astruc-Diaz, F.; Pan, H. M.; Brown, D. L.;
Naguib, M. J. Med. Chem. 2008, 51, 4932e4947; (e) Sakamoto, M.; Iwamoto, T.;
Nono, N.; Ando, M.; Arai, W.; Mino, T.; Fujita, T. J. Org. Chem. 2002, 68, 942e946;
(f) Sekine, A.; Hori, K.; Ohashi, Y.; Yagi, M.; Toda, F. J. Am. Chem. Soc. 1989, 111,
697e699; (g) Aoyama, H.; Sakamoto, M.; Kuwabara, K.; Yoshida, K.; Omote, Y. J.
Am. Chem. Soc. 1983, 105, 1958e1964.
5. (a) Lamberth, C.; Jeanguenat, A.; Cederbaum, F.; Mesmaeker, A. D.; Zeller, M.;
Kempf, H.-J.; Zeun, R. Bioorg. Med. Chem. 2008, 16, 1531e1545; (b) Cederbaum,
F.; Lamberth, C.; Malan, C.; Naud, F.; Spindler, F.; Studer, M.; Blaser, H.-U. Adv.
Synth. Catal. 2004, 346, 842e848.
8.39e8.37 (m, 3H), 8.32 (d, J¼8.0 Hz,1H), 7.78 (td, J¼7.5, 2.0 Hz,1H),
7.66 (tt, J¼7.5, 1.5 Hz, 1H), 7.53e7.50 (m, 2H), 7.13 (dd, J¼7.5, 1.0 Hz,
1H). 13C NMR (125 MHz, CDCl3):
d 186.91, 159.84, 150.43, 148.53,
138.54, 134.75, 132.98, 131.36, 128.70, 120.77, 114.43. MS (EI): m/z
(%) 226 (9) [Mþ], 105 (100), 77 (45). Anal. Calcd for C13H10N2O: C,
69.02; H, 4.46; N, 12.38. Found: C, 69.02; H, 4.26; N, 12.42.
4.2.16. N-Butyl-2-oxo-2-phenylacetamide (2p)29. Light yellow liq-
uid, 55% yield. IR (film): 3314, 2959, 2932, 2872, 1666, 1596, 1527,
6. Salituro, G. M.; Townsend, C. A. J. Am. Chem. Soc. 1990, 112, 760e770.
7. (a) Nair, L. G.; Bogen, S.; Doll, R. J.; Shih, N. Y.; Njoroge, F. G. Tetrahedron Lett.
2010, 51, 1276e1279; (b) Nair, L. G.; Sannigrahi, M.; Bogen, S.; Pinto, P.; Chen, K.
X.; Prongay, A.; Tong, X.; Cheng, K. C.; Girijavallabhan, V.; Njoroge, F. G. Bioorg.
Med. Chem. Lett. 2010, 20, 567e570; (c) Bogen, S. L.; Arasappan, A.; Velazquez,
F.; Blackman, M.; Huelgas, R.; Pan, W. D.; Siegel, E.; Nair, L. G.; Venkatraman, S.;
Guo, Z. Y.; Doll, R.; Shih, N. Y.; Njoroge, F. G. Bioorg. Med. Chem. Lett. 2010, 18,
1854e1865; (d) Ayral-Kaloustian, S.; Gu, J. X.; Lucas, J.; Cinque, M.; Gaydos, C.;
Zask, A.; Chaudhary, I.; Wang, J. Y.; Di, L.; Young, M.; Ruppen, M.; Mansour, T. S.;
Gibbons, J. J.; Yu, K. J. Med. Chem. 2010, 53, 452e459; (e) Mavunkel, B. J.; Pe-
rumattam, J. J.; Tan, X. F.; Luedtke, G. R.; Lu, Q.; Lim, D.; Kizer, D.; Dugar, S.;
Chakravarty, S.; Xu, Y. J.; Jung, J.; Liclican, A.; Levy, D. E.; Tabora, J. Bioorg. Med.
Chem. Lett. 2010, 20, 1059e1062; (f) Montalban, A. G.; Boman, E.; Chang, C. D.;
Ceide, S. C.; Dahl, R.; Dalesandro, D.; Delaet, N. G. J.; Erb, E.; Ernst, J. T.; Gibbs, A.;
Kahl, J.; Kessler, L.; Kucharski, J.; Lum, C.; Lundstrom, J.; Miller, S.; Nakanishi, H.;
Roberts, E.; Saiah, E.; Sullivan, R.; Urban, J.; Wang, Z. J.; Larson, C. J. Bioorg. Med.
Chem. Lett. 2010, 20, 4819e4824; (g) Montalban, A. G.; Boman, E.; Chang, C. D.;
Ceide, S. C.; Dahl, R.; Dalesandro, D.; Delaet, N. G. J.; Erb, E.; Ernst, A. G.; Kahl, J.;
Kessler, L.; Lundstrom, J.; Miller, H. N.; Roberts, E. R.; Saiah, E.; Sullivan, R.;
Wang, Z. J.; Larson, C. J. Bioorg. Med. Chem. Lett. 2008, 18, 1772e1777; (h) Prasad,
C. C. C.; Zheng, M.; Vig, S.; Bergstrom, C.; Smith, D. W.; Gao, Q.; Yeola, S.; Polson,
C. T.; Corsa, J. A.; Guss, V. L.; Loo, A.; Wang, J.; Sleczka, B. G.; Dangler, C.; Rob-
ertson, B. J.; Hendrick, J. P.; Roberts, S. B.; Barten, D. M. Bioorg. Med. Chem. Lett.
2007, 17, 4006e4011; (i) Pevarello, P.; Brasca, M. G.; Orsini, P.; Traquandi, G.;
Longo, A.; Nesi, M.; Orzi, F.; Piutti, C.; Sansonna, P.; Varasi, M.; Cameron, A.;
Vulpetti, A.; Roletto, F.; Alzani, R.; Ciomei, M.; Albanese, C.; Pastori, W.; Mar-
siglio, A.; Pesenti, E.; Fiorentini, F.; Bischoff, J. R.; Mercurio, C. J. Med. Chem.
2005, 48, 2944e2956; (j) Helal, C. J.; Sanner, M. A.; Cooper, C. B.; Gant, T.; Adam,
M.; Lucas, J. C.; Kang, Z. J.; Kupchinsky, S.; Ahlijanian, M. K.; Tate, B.; Menniti, F.
S.; Kelly, K.; Peterson, M. Bioorg. Med. Chem. Lett. 2004, 14, 5521e5525; (k)
Sakowski, J.; Bohm, M.; Sattler, I.; Dahse, H. M.; Schlitzer, M. J. Med. Chem. 2001,
44, 2886e2899.
8. (a) Solomon, V. R.; Hu, C. K.; Lee, H. Bioorg. Med. Chem. Lett. 2010, 18,
1563e1572; (b) Hughes, C. C.; Fenical, W. J. Am. Chem. Soc. 2010, 132,
2528e2529; (c) Jia, Y. X.; Katayev, D.; Kundig, E. P. Chem. Commun. 2010,
130e132; (d) Jesuraj, J. L.; Sivaguru, J. Chem. Commun. 2010, 4791e4793; (e)
Tomaszewski, M. J.; Boisvert, L.; Jin, S. Tetrahedron Lett. 2009, 50, 1435e1437; (f)
Chen, Y. H.; Zhang, Y. H.; Zhang, H. J.; Liu, D. Z.; Gu, M.; Li, J. Y.; Wu, F.; Zhu, X. Z.;
Li, J.; Nan, F. J. J. Med. Chem. 2006, 49, 1613e1623; (g) Keawin, T.; Rajviroongit,
S.; Black, D. S. Tetrahedron 2005, 61, 853e861; (h) Bacchi, A.; Costa, M.; Ca, N.
D.; Gabriele, B.; Salerno, G.; Cassoni, S. J. Org. Chem. 2005, 70, 4971e4979; (i)
Bette, V.; Mortreux, A.; Savoia, D.; Carpentier, J. F. Adv. Synth. Catal. 2005, 347,
289e302; (j) Bette, V.; Mortreux, A.; Lehmann, C. W.; Carpentier, J. F. Chem.
Commun. 2003, 332e333; (k) Bergman, J.; Engqvist, R.; Stalhandske, C.; Wall-
berg, H. Tetrahedron 2003, 59, 1033e1048; (l) Pasquier, C.; Pelinski, L.; Brocard,
J.; Mortreux, A.; Agbossou-Niedercorn, F. Tetrahedron Lett. 2001, 42,
2809e2812; (m) Fukuzawa, S.; Miura, M.; Matsuzawa, H. Tetrahedron Lett. 2001,
42, 4167e4169; (n) Sdira, S. B.; Felix, C.; Giudicelli, M. B.; Vocanson, F.; Perrin,
M.; Lamartine, R. Tetrahedron Lett. 2001, 46, 5659e5663.
1448, 747 cmꢁ1. 1H NMR (500 MHz, CDCl3):
d
8.30 (dd, J¼8.0, 1.0 Hz,
2H), 7.61e7.58 (m, 1H), 7.45 (t, J¼8.0 Hz, 2H), 7.17 (br, 1H), 3.37 (q,
J¼7.0 Hz, 2H), 1.67 (quint, J¼7.5 Hz, 2H), 1.38 (sextet, J¼7.5 Hz, 2H),
0.93 (t, J¼7.5 Hz, 3H). 13C NMR (125 MHz, CDCl3):
d 188.08, 161.93,
134.41, 133.46, 131.25, 128.54, 39.24, 31.40, 20.14, 13.78. MS (EI): m/z
(%) 205 (17) [Mþ], 105 (100), 77 (30), 57 (27).
4.2.17. 2-(1-Methyl-1H-indol-3-yl)-2-oxo-N-phenylacetamide
(2q)30. Yellow solid, 59% yield, mp 151e152 ꢀC. IR (KBr): 3356,
3149, 1682, 1630, 1589, 1508, 1440, 1368, 1078 cmꢁ1 1H NMR
.
(500 MHz, CDCl3):
7.72 (d, J¼8.0 Hz, 2H), 7.42e7.38 (m, 5H), 7.19 (t, J¼7.5 Hz, 1H),
3.88 (s, 3H). 13C NMR (125 MHz, CDCl3):
179.60, 160.23, 142.35,
d 9.42 (s, 1H), 9.04 (s, 1H), 8.47e8.45 (m, 1H),
d
137.06, 137.00, 129.18, 127.74, 124.93, 124.07, 123.67, 122.67,
119.86, 111.66, 110.04, 33.85. MS (EI): m/z (%) 278 (15) [Mþ], 158
(100), 77 (14).
4.2.18. 2-Oxo-N-phenyl-2-(thiophen-2-yl)acetamide
solid, 44% yield, mp 129e130 ꢀC. IR (KBr): 3307, 1689, 1643, 1407,
1361, 1283, 1050, 744 cmꢁ1 1H NMR (500 MHz, CDCl3):
9.15 (s,
(2r). Yellow
.
d
1H), 8.47 (d, J¼4.0 Hz, 1H), 7.86 (dd, J¼5.0, 1.0 Hz, 1H), 7.71 (d,
J¼8.0 Hz, 2H), 7.39 (t, J¼8.0 Hz, 2H), 7.22e7.18 (m, 2H). 13C NMR
(125 MHz, CDCl3):
d 178.38, 158.32, 139.23, 138.58, 136.44, 136.27,
129.26, 128.39, 125.43, 120.00. m/z (%) 231 (29) [Mþ], 111 (100), 77
(11). Anal. Calcd for C12H9NO2S: C, 62.32; H, 3.92; N, 6.06. Found: C,
62.23; H, 3.96; N, 6.10.
Acknowledgements
We thank the National Natural Science Foundation of China (No.
20972093), Shanghai Municipal Education Commission (No.
10YZ06 and J50102), and Science and Technology Commission of
Shanghai Municipality (No. 09ZR1412700) for financial support.
Supplementary data
9. (a) Goncalves, B. T.; Esteves, P. M.; Pinto, A. C.; Kaiser, C. R.; Silva, F. L. D.; Mi-
guez, E. M.; Silva, J. F. M. D. Magn. Reson. Chem. 2008, 46, 418e426; (b) Takeuchi,
Y.; Itoh, N.; Note, H.; Koizumi, T.; Yamaguchi, K. J. Am. Chem. Soc. 1991, 113,
6318e6320.
1H NMR and 13C NMR spectra of all compounds. Supplementary
data of 1H NMR and 13C NMR spectra of all compounds are avail-
able. Supplementary data associated with this article can be found,
in the online version, at doi:10.1016/j.tet.2011.11.005.
10. Ugi, I.; Fetzer, U. Chem. Ber. 1961, 94, 1116e1121.
11. (a) Bou-Harndan, F. R.; Leighton, J. L. Angew. Chem., Int. Ed. 2009, 48,
2403e2406; (b) Yang, L.; Wang, D. X.; Huang, Z. T.; Wang, M. X. J. Am. Chem. Soc.
2009, 131, 10390e10391; (c) Azoulay, J. D.; Itigaki, K.; Wu, G.; Bazan, G. C. Or-
ganometallics 2008, 27, 2273e2280; (d) Bolm, C.; Schmidt, F.; Zani, L. Tetrahe-
dron: Asymmetry 2005, 16, 1367e1376; (e) Heaney, F.; Fenlon, J.; McArdle, P.;
Cunningham, D. Org. Biomol. Chem. 2003, 1, 1122e1132; (f) Friedman, O. M.;
Parameswaran, K. N.; Burstein, S. J. Med. Chem. 1963, 6, 227e229.
12. (a) Ling, K.-Q.; Ye, J.-H.; Chen, X.-Y.; Ma, D.-J.; Xu, J.-H. Tetrahedron 1999, 55,
9185e9204; (b) Ling, K.-Q.; Ji, G.; Cai, H.; Xu, J.-H. Tetrahedron Lett. 1998, 39,
2381e2384.
13. (a) Liu, J. M.; Zhang, R. Z.; Wang, S. F.; Sun, W.; Xia, C. Org. Lett. 2010, 11,
1321e1324; (b) Szilagyi, A.; Farkas, R.; Petz, A.; Kollar, L. Tetrahedron 2009, 65,
4484e4489; (c) Takacs, A.; Petz, A.; Kollar, L. Tetrahedron 2008, 64, 8726e8730;
(d) Fairlamb, I. J. S.; Grant, S.; McCormack, P.; Whittall, J. Dalton Trans. 2007,
859e865; (e) Acs, P.; Muller, E.; Rangits, G.; Lorand, T.; Kollar, L. Tetrahedron
2006, 62, 12051e12056; (f) Miller, P. W.; Long, N. J.; Mello, A. J. D.; Vilar, R.;
Passchier, J.; Gee, A. Chem. Commun. 2006, 546e548; (g) Iizuka, M.; Kondo, Y.
Chem. Commun. 2006, 1739e1741; (h) Muller, E.; Peczely, G.; Foldes, R. S.; Ta-
kacs, E.; Kokotos, G.; Bellis, E.; Kollar, L. Tetrahedron 2005, 61, 797e802.
14. Garcia-Gonzalez, M. C.; Gonzalez-Zamora, E.; Santillan, R.; Dominguez, O.;
Mendez-Stivalet, M.; Farfan, N. Tetrahedron 2009, 65, 5337e5342.
References and notes
1. (a) Wang, Z. H.; Bois-Choussy, M.; Jia, Y. X.; Zhu, J. P. Angew. Chem., Int. Ed. 2010,
497, 2018e2022; (b) Jia, Y. X.; Bois-Choussy, M.; Zhu, J. P. Angew. Chem., Int. Ed.
2008, 47, 4167e4172; (c) Jia, Y. X.; Bois-Choussy, M.; Zhu, J. P. Org. Lett. 2007, 9,
2401e2404; (d) Shinohara, T.; Deng, H. B.; Snapper, M. L.; Hoveyda, A. H. J. Am.
Chem. Soc. 2005, 127, 7334e7336; (e) Deng, H. B.; Jung, J. K.; Liu, T.; Kuntz, K. W.;
Snapper, M. L.; Hoveyda, A. H. J. Am. Chem. Soc. 2003, 125, 9032e9034.
2. Ocain, T. D.; Rich, D. H. J. Med. Chem. 1992, 35, 451e456.
3. (a) Barrett, D. G.; Boncek, V. M.; Catalano, J. G.; Deaton, D. N.; Hassell, A. M.;
Jurgensen, C. H.; Long, S. T.; McFadyen, R. B.; Miller, A. B.; Miller, L. R.; Payne, J.
A.; Ray, J. A.; Samano, V.; Shewchuk, L. M.; Tavares, F. X.; Wells-Knecht, K. J., Jr.;
Willard, D. H.; Wright, L. L.; Zhou, H. Q. Bioorg. Med. Chem. Lett. 2005, 15,
3540e3546; (b) Catalano, J. G.; Deaton, D. N.; Long, S. T.; McFadyen, R. B.; Miller,
L. R.; Payne, J. A.; Wells-Knecht, K. J.; Wright, L. L. Bioorg. Med. Chem. Lett. 2004,
14, 719e722.
4. (a) Feng, L. S.; Liu, M. L.; Chai, Y.; Wang, B.; Zhang, Y. B.; Lv, K.; Guan, Y.; Guo, H.
Y.; Xiao, C. L.; Zhang, S. Eur. J. Med. Chem. 2011, 46, 341e348; (b) Manley, K.;
Clarina, I.; Bergh, J. J.; Petzer, J. P. Bioorg. Med. Chem. 2011, 19, 261e274; (c)

J. Shao et al. / Tetrahedron 68 (2012) 573e579
579
15. (a) Xu, G. Y.; Etzkorn, F. A. Org. Lett. 2010, 12, 696e699; (b) Chen, C. T.; Bettigeri,
S.; Weng, S. S.; Pawar, V. D.; Lin, Y. H.; Liu, C. Y.; Lee, W. Z. J. Org. Chem. 2007, 72,
8175e8185; (c) Radosevich, A. T.; Musich, C.; Toste, F. D. J. Am. Chem. Soc. 2005,
127, 1090e1091.
22. Armarego, W. L. F.; Chai, C. L. L. Purification of Laboratory Chemicals, 5th ed.;
Elsevier: New York, 2003.
23. Boryczka, S.; Suwinska, K.; Guillanton, G. L.; Do, Q. T.; Elothmani, D. J. Chem.
Crystallogr. 1998, 28, 555e560.
16. Buu-Hoi, N. P.; Saint-Ruf, G.; Bourgeade, J. C. J. Heterocycl. Chem. 1968, 5,
545e546.
17. Zhang, C.; Jiao, N. J. Am. Chem. Soc. 2010, 132, 28e29.
18. Bouma, M.; Masson, G.; Zhu, J. P. J. Org. Chem. 2010, 75, 2748e2751.
19. Wang, S. Y.; Song, B. R.; Sun, C. Y.; Deng, H. M.; Xu, B. Tetrahedron Lett. 2007, 48,
8982e8986.
24. Petyunin, P. A. Zh. Obshch. Khim. 1960, 30, 4042e4044.
25. Petyunin, P. A.; Mashevskaya, M. S.; Zalesov, V. S.; Karavaeva, E. G. Khim.-Farm.
Zh. 1972, 6, 11e13.
26. Gotthardt, H. Chem. Ber. 1987, 120, 751e760.
27. Voznyi, I. V.; Novikov, M. S.; Khlebnikov, A. F.; Kopf, J.; Kostikov, R. R. Russ. J. Org.
Chem. 2004, 40, 199e205.
20. Zhang, Z.; Liu, Y.; Ling, L.; Li, Y.; Dong, Y.; Gong, M.; Zhao, X.; Zhang, Y.; Wang, J.
J. Am. Chem. Soc. 2011, 133, 4330e4341.
28. Sai, K. K. S.; Esteves, P. M.; Penha, E. T.; Klumpp, D. A. J. Org. Chem. 2008, 73,
6506e6512.
21. (a) Park, K. K.; Tsou, L. K.; Hamilton, A. D. Synthesis 2006, 3617e3620; (b)
Pattabiraman, V. R.; Padakanti, S.; Veeramaneni, V. R.; Pal, M.; Yeleswarapu, K.
R. Synlett 2002, 947e951; (c) Harvey, R. G.; Abu-shqara, E.; Yang, C. X. J. Org.
Chem. 1992, 57, 6313e6317.
29. Kambe, N.; Inoue, T.; Takeda, T.; Fujiwara, S.; Sonoda, N. J. Am. Chem. Soc. 2006,
128, 12650e12651.
30. Thompson, M. J.; Borsenberger, V.; Louth, J. C.; Judd, K. E.; Chen, B. J. Med. Chem.
2009, 52, 7503e7511.