Stereoselective synthesis of enamides by pd-catalyzed hydroamidation of electron deficient terminal alkynes

Article abstract of DOI:10.1021/jo301772f

Hydroamidation of electron-deficient terminal alkynes by amides in presence of Pd-catalyst has been exploited for the stereoselective synthesis of Z-enamides. The possible intramolecular hydrogen bonding between the amido proton and carbonyl oxygen of est

Full text of DOI:10.1021/jo301772f

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Note
Stereoselective synthesis of enamides by Pd-catalyzed
hydroamidation of electron deficient terminal alkynes
Niranjan Panda, and Mothkuri Raghavender
J. Org. Chem., Just Accepted Manuscript • Publication Date (Web): 17 Sep 2012
Downloaded from http://pubs.acs.org on September 18, 2012
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Stereoselective synthesis of enamides by Pd-catalyzed hydroamidation of
electron deficient terminal alkynes
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Niranjan Panda, * and M. Raghavender
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Department of Chemistry, National Institute of Technology, Rourkela-769008, Odisha, India
Email: npanda@nitrkl.ac.in; Tel: +91 661 2462653
O
O
1% Pd(OAc)2, NaOAc
+
R'
N
R'
NH2
H
CF3CO2H/ toluene
(r.t. - 700C)
CO2R
O
OR
Z-enamide
Abstract. Hydroamidation of electron-deficient terminal alkynes by amides in presence of Pd-
catalyst has been exploited for the stereoselective synthesis of Z-enamides. The possible
intramolecular hydrogen bonding between the amido proton and carbonyl oxygen of ester group
provides the extra stability to the Z-isomer of vinyl-palladium complex, which subsequently
undergo protodepalladation and lead to the Z-enamide selectively. This process is found to be
mild and operationally simple with broad substrate scope.
Keywords: Enamides; Hydroamidation; amides; terminal alkynes; palladium.
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Enamides constitute the core structure of many functional materials1 and natural products of
biological significance.2 Furthermore, enamides are proved to be a versatile intermediate for the
synthesis of heterocycles, amino acids and potential drug metabolites.3 Thus, a number of
methods have been developed for their synthesis.4 The classical methods include the
condensation of carbonyl derivatives with amides or acylation of imines leads to mixtures with
the E-enamide as major isomer.5-7 In contrast, stereoselective synthesis of thermodynamically
less favorable Z-enamide has been rarely explored. Indeed, several elegant methods such as
Curtius rearrangement of α, β-unsaturated acyl azides,8 and elimination of β-hydroxy-α-
silylamides (Peterson reaction),9 oxidative amidation of conjugated olefins,10 Pd- and/or Cu-
catalyzed cross-coupling of vinyl derivatives (viz, halides,11 triflates,12 tosylates,13 borates,14
ethers15) with amides have been reported for stereoselective synthesis of enamides. However,
requirement of rigorous reaction conditions and intricacy in starting material preparation often
limits their practical applications.16
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On the other hand, addition of amides to terminal alkynes, known as hydroamidation, has
been emerged as an appealing atom-economic approach to this substrate class. Evidently,
Watanabe and co-workers17 reported the ruthenium-complex mediated synthesis of E-enamides
at high temperature. Gooßen and co-workers18 developed ligand-mediated Ru-catalyzed
hydroamidation reactions that allow the anti-Markovnikov addition of various N-H nucleophiles
to terminal acetylenes for selective formation of either E- or Z-configured enamide derivatives.
Takai and co-workers19 used commercially available rhenium-catalyst (i.e. Re2(CO)6) for the
coupling of the cyclic amides with alkyl alkynes to access E-enamides. These Ru/Re-catalyzed
hydroamidation reactions so far reported are endowed with: the use of inactivated terminal
alkynes, the formation of doubly vinylated enamides and ligand-dependant stereoselectivity.20
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Evidently, the enamides synthesized by later methods often undergo double bond isomerization
to thermodynamically more stable E-enamides.18b Moreover, use of electron deficient terminal
alkynes as coupling partner in the hydroamidation process was not yet precedent. Therefore,
development of mild and efficient methods for stereoselective synthesis of Z-enamides from such
alkynes is particularly interesting. Based on our present interest on stereoselective synthesis of
enamides,10d we herein report a mild and efficient Pd-catalyzed hydroamidation protocol for the
stereoselective synthesis of Z-enamides from the electron deficient terminal alkynes through N-C
cross-coupling reactions (Scheme 1). Moreover, this method is found to be very practical and
results in the thermodynamically less favored Z-enamides selectively from the primary amides.
To the best of our knowledge, this is the first report on Pd-catalyzed hydroamidation of alkynes
to enamide.
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Scheme 1
O
Pd (II)
+
CO2R
CO2R
BQ, p-TsOH, r.t.
Previous work 10b-d
R'
N
O
H
O
OR
Z-enamide
R'
NH2
+
Pd (II), base
CF3CO2H/ toluene
Recent work
Our strategy originated from the seminal work of Fujiwara21 and Kitamura.22 They have
described the Pd-catalyzed coupling of ethyl propiolate with electron rich arenes through C-H
activation. It occurred to us that the use of amide as nucleophile instead of electron rich arene
may leads to vinyl-palladium complex which on subsequent protodepalladation in the presence
of Brønsted acid would afford the enamide. Unlike the Fujiwara’s report21 the possible
intramolecular hydrogen bonding between the amido proton and carbonyl oxygen of electron
deficient alkyne in the vinyl-palladium complex would eventually attribute to the Z-selectivity of
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the resulting enamide. With this in mind, we began our study using benzamide and ethyl
propiolate as the model substrates. Unfortunately, under similar conditions as reported by
Fujiwara (i.e. Pd(OAc)2/CF3CO2H) no trace of enamide 1a was obtained even at higher
temperature (70°C) with recovery of starting material (Table 1, entry 1). However, addition of
two equivalents of base such as NaOMe furnished the Z-enamide (1a) as the major product in
appreciable yield (44 %) at 70°C (entry 2). The appearance of doublets at δ 11.5 (for N-H) and
5.27 (vinylic proton) with coupling constant 8.8 Hz, reveals the formation of Z-enamide.10b
Optimization studies were then performed that varied the nature of bases, solvents and added
acids. These investigations revealed that the utilization of two equiv. of sodium acetate (NaOAc)
gave 1a (82 % yield) over a period of 12 h at 70 °C in toluene. No trace of E-enamide was
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indentified from TLC as well as H NMR. Decreasing as well as increasing the temperature led
to poor yield of enamide. Furthermore, polar solvents such as DMF, THF, CH3CN and 1,4-
dioxane resulted no or poor yield of isomeric mixture (entries 18-21). A satisfactory result was
obtained when dichloroethane (DCE) was used: enamide was isolated in 72% yield (Z/E 2:1
1
t
from H NMR) (entry 17). The use of other bases such as BuOK, NaOH, Cs2CO3 resulted in
lower yield. Excess of trifluoroacetic acid (5 equiv.) was found to be essential for the completion
of the reaction. 1 mol % of Pd(OAc)2 was confirmed to be optimal. An increase in catalyst
concentration from 1 mol % to 5 mol% afforded the product in lower yield due to unwanted
polymerization/decomposition. The catalytic efficiencies of other Pd-catalysts were also
examined and it revealed that among the tested catalysts (i.e. PdCl2, Pd(PPh3)2Cl2,
Pd(PPh3)2(OAC)2, Pd(TFA)2, Pd(OAc)2, Pd2(dba)3, Pd(PPh3)4 and Pd/C) Pd(OAc)2 displayed
higher activity under the same experimental conditions (entries 3-10).
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A plausible pathway for the selective synthesis of Z-enamide (1a) is outlined in Scheme
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2, although numerous details remain to be elucidated. The reaction of benzamide with ethyl
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Table 1. Optimization of reaction conditions a
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O
O
[Pd] (1 mol%)
NH2
N
H
+
Base (2 equiv.)
H+ (5 equiv.)
Solvent, 70 0C
O
OEt
CO2Et
1a
Entry catalyst
acid
solvent
additive % yield (Z/E)
1
2
3
4
5
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7
8
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
PdCl2
Pd(PPh3)2Cl2
Pd(PPh3)2(OAC)2 CF3CO2H
Pd(CF3CO2)2
Pd(dba)2
Pd(PPh3)4
Pd/C
CF3CO2H toluene
CF3CO2H toluene
CF3CO2H toluene
nil
0
44
82
31
68
56
72
16
0
0
26
<5
0
<10
0
15
NaOMe
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
tBuOK
NaOH
Cs2CO3
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
CF3CO2H
CF3CO2H
toluene
toluene
toluene
CF3CO2H toluene
CF3CO2H toluene
CF3CO2H toluene
CF3CO2H toluene
CH3CO2H toluene
9
10
11
12
13
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15
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20
21
Pd(OAc)2
PivOH
toluene
toluene
toluene
toluene
toluene
DCE
dioxane
CH3CN
DMF
nil
CF3CO2H
CF3CO2H
CF3CO2H
CF3CO2H
CF3CO2H
CF3CO2H
CF3CO2H
CF3CO2H
72 (2:1)
39 (1.8:1)
15 (1: 1.2)
0
0
THF
aReaction conditions: A mixture of benzamide (100 mg, 0.82 mmol), ethyl propiolate (0.12 mL,
1.23 mmol), Pd-catalyst (1 mol %), Brønsted acid (5 equiv) and additive (2 equiv.) in the
indicated solvent were heated at 70 °C for 12 h under N2 atmosphere.
propiolate in absence of trifloroacetic acid did not result any enamide (entry 13). Furthermore,
this cross-coupling in presence of acetic acid resulted only 26% of the enamide (entry 11) where
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as the cross-coupling in presence of Pd(CF3COO)2 afforded 72% yield of enamide (entry 7). It
indicates that at optimum reaction conditions like earlier observation of Fujiwara21 and
Kitamura,22 Pd(OAc)2 reacts with CF3CO2H and leads to the more reactive Pd(CF3COO)2.
Addition of the latter to the activated alkyne leads to the alkyne-palladium complex (I).
Nucleophilic attack of amide nitrogen to I results in vinyl-palladium complex (II and/or III). As
expected, like Chang10b and our’s10d report the possible hydrogen bonding between the
carbonyloxygen of alkyne and the N-H of amide (C=O…H-N) provides the additional stability to
the complex and thus drives the equilibrium towards II. This intramolecular H-bonding attributes
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to the excellent Z-selectivity of the hydroamidation reaction. Furthermore, in presence of excess
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of Brønsted acid, II undergoes protodepalladation23,
readily and affords the Z-enamide
selectively.
Scheme 2: The plausible mechanism
Pd(OAc)2
OEt
OEt
O
CF3CO2H
Ph
NH
O
Pd(CF3CO2)2
1a
O
OEt
CF3CO2H
Pd(OCOCF3)
OEt
O
Pd (OCOCF3)
OEt
F3COCO Pd
H
N
Ph
OCOCF3
Ph
O
N
I
O
O
H
III
O
II
O
+
Ph
AcO
H2N
AcOH
Having the optimal conditions, the scope of alkyne component was explored with different
substitutions. It revealed that electron-withdrawing substitutions like -COOH, COAr to the
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alkyne, resulted Z-enamides selectively in modest yield (Scheme 3). Unactivated alkynes such as
phenylacetylene and 1-octyne are inactive to afford the enamide, albeit the homocoupling of
alkynes were resulted.
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Scheme 3
O
O
1% Pd(OAc)2, NaOAc
+
Ph
N
H
Ph
NH2
TFA / toluene
70 0C
R
R
1a, R = CO2Et, 82%
2, R = CO2H, 60 %
3a, R = COC6H5, 43%
3b; R= COC6H4-p-OCH3, 45%
Next, we investigated the scope and limitation of the catalytic process with various amides
and the results are summarized in Table 2. Pleasingly, this catalytic protocol was found to be
tolerant to both electron-donating and -withdrawing aryl ring substitutions, and in most cases
moderate to good yields of enamides was obtained. As such, electron withdrawing substituents
(i.e. –NO2, Cl) to the aromatic ring, that decrease the nucleophilicity of amide still participated in
cross-coupling with ethyl propiolate and led to the Z-enamides in good yield without affecting
the selectivity. Heteroaryl amides also afforded the corresponding enamides in good yield with
retention of Z-selectivity (entries 8, 9). Amides with alkyl group, carbamate and urea are found
to be reactive to ethyl propiolate and resulted Z-enamides selectively (entries 13, 14). However,
when secondary amides were used, tertiary enamides with E-selectivity (J = 14.4 Hz) were
resulted in modest yield (entries 15-18). Cyclic amides such as pyrrolidinone, ethylene urea were
also underwent hydroamidation reaction and furnished the E-enamides in appreciable yield.
Selective formation of E-enamide is due to the lack of intramolecular hydrogen bonding in the
vinyl-palladium complex that drives the equilibrium towards the thermodynamically more stable
intermediate (e.g. III).
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Table 2: Enamide synthesisa
3
4
5
6
7
8
9
O
O
1 % Pd(OAc)2, NaOAc
+
H
R
N
R
N
TFA / toluene
70 0C, 12 h,
N2 atm.
CO2Et
R'
R'
CO2Et
Z- or E-enamide
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Entry
Substrate
O
Product % Yield Entry
O
Substrate
Product
% Yield
O
O
NH2
X
N
H
N
H
NH2
14
52
O
OEt
X
Ph
O
OEt
Ph
8
1
X= H
1a
82
68
62
56
72
50
56
75
56
O
O
OEt
2
3
4
5
6
7
8b
9
X = 4-OMe 1b
15b
H
N
46
54
H2N
NH2
H2N
X= 4-Cl
1c
1d
1e
1f
O
X = 2-Cl
9
O
OEt
O
X = 4-NO2
X = 2-NO2
X = 3-NO2
H
N
nBuO
16b
17b
nBuO
MeO
NH2
O
10
1g
O
O
X = 2-OMe 1h
Me
H
MeO
N
O
N
X = 2-OH
1i
56
41
Me
O
O
11
OEt
N
H
NH2
O
10
67
60
O
O
O
O
OEt
OEt
18b
Me
4
H
H
N
O
O
H
N
Me
N
NH2
11
12
H
S
S
12
O
O
OEt
5
O
O
O
O
O
O
H3C
NH2
N
H
6
H3C
72
54
H
52
55
N
19
20
N
OEt
O
O
OEt
OEt
O
13
O
O
O
N
H
NH2
13
H
HN
N
HN
N
OEt
7
14
aReaction conditions: 100 mg of amide, ethyl propiolate (1.5 equiv.), TFA (5 equiv.), Pd(OAc)2
(1 mol %), NaOAc (2 equiv.) heated at 70 °C for 12 h under N2 atmosphere. Reactions were
b
carried out at room temperature over a period of 36 h.
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In summary, the first Pd-catalyzed hydroamidation of activated terminal alkynes is
presented. The conditions can be applied to a number of amides as well as electron deficient
alkynes with good functional group tolerance. The reaction is stereoselective: primary amides
give Z-enamides whereas secondary amides give E-enamides selectively. The high
stereoselectivity is possibly due to the favorable intramolecular hydrogen bonding between the
carbonyl oxygen of alkyne and the N-H of amide in the vinyl palladium complex. This
methodology is simple and allows to access varieties of enamides with high stereoselectivity.
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Experimental Section
General procedure for enamide synthesis from alkyne
Method A: An oven dried round bottom flask was charged with amide (100 mg), Pd(OAc)2 (1
mol%), trifluoroacetic acid (5 equiv.), NaOAc (2 equiv.), and toluene (4 mL). The reaction
mixture was stirred for 5 minutes under nitrogen atmosphere at room temperature and then ethyl
propiolate (1.5 equiv.) was added dropwise. The reaction mixture was then stirred for 5 min. and
then temperature was raised to 70 °C. After 12 h, the reaction mixture was diluted with ethyl
acetate followed by water. The organic layer was separated and the aqueous layer was extracted
with ethyl acetate. The combined organic layer was dried over brine, anhydrous Na2SO4, and
then evaporated under reduced pressure. The crude residue was purified by column
chromatography over silica gel using mixture of petroleum ether and ethyl acetate as eluent to
give the pure enamide.
Method B: An oven dried round bottom flask was charged with amide (100 mg), Pd(OAc)2 (1
mol%), trifluoroacetic acid (5 equiv.), NaOAc (2 equiv.), and toluene (4 mL). The reaction
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mixture was stirred for 5 minutes under nitrogen atmosphere at room temperature and then ethyl
propiolate (1.5 equiv.) was added dropwise. The reaction mixture was stirred for 12 h at room
temperature (r. t.) and then diluted with ethyl acetate followed by water. The organic layer was
separated and the aqueous layer was extracted with ethyl acetate. The combined organic layer
was dried over brine, anhydrous Na2SO4, and then evaporated under reduced pressure. The crude
residue was purified by column chromatography over silica gel using mixture of petroleum ether
and ethyl acetate as eluent to give the pure enamide.
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(Z)-Ethyl 3-(benzamido)acrylate (1a)10b
1a was obtained following general procedure (Method A) as a white crystalline solid (179 mg,
82 % yield), mp: 76-77 oC. IR (KBr): 3324, 2955, 1684, 1638, 1581, 1508, 1480 cm-1. 1H NMR
(400 MHz, CDCl3): δ 11.54 (d, 1H, J = 9.6 Hz), 7.98-7.95 (m, 2H), 7.76 (dd, 1H, J1 = 11.2 Hz,
J2 = 8.8 Hz), 7.64-7.58 (m, 2H), 7.55-7.49 (m, 2H), 5.28 (d, 1H, J = 8.8 Hz), 4.25 (q, 2H, J = 7.2
13
Hz), 1.34 (t, 3H, J = 7.2 Hz). C NMR (100 MHz, CDCl3): δ 169.6 (s), 164.5 (s), 138.7 (d),
132.9 (d), 132.1 (s), 128.9 (d), 127.7 (d), 97.1 (d), 60.3 (t), 14.2 (q). MS (ESI,-Ve) m/z (relative
intensity) 217.90 [M-H]+, 100%). Anal. Calcd for C12H13NO3: C, 65.74; H, 5.98; N, 6.39. Found:
C, 65.40; H, 5.68; N, 6.09.
(Z)-Ethyl 3-(4-methoxybenzamido)acrylate (1b)
1b was obtained following general procedure (Method A) as a white crystalline solid (169 mg,
68 % yield), mp: 100-102oC. IR (KBr): 3433, 2998, 2967, 2924, 1670, 1622, 1479, 1369 cm.-1
1H NMR (400 MHz, CDCl3): δ 11.45 (d, 1H, J = 10.8 Hz), 7.94 (d, 2H, J = 8.8 Hz), 7.75 (dd,
1H, J1 = 11.2 Hz, J2 = 8.8 Hz), 6.99 (t, 2H, J1 = 6.8 Hz, J2 = 2 Hz), 5.24 (d, 1H, J = 9.2 Hz), 4.25
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(q, 2H, J = 6.8 Hz, J = 14.4 Hz) 3.89 (s, 3H), 1.35 (t, 3H, J = 7.2 Hz). C NMR (100 MHz,
CDCl3): δ 169.7 (s), 163.9 (s), 163.3 (s), 139.0 (d), 129.7 (d), 124.5 (s), 114.1 (d), 96.4 (d), 60.1
(t), 55.4 (t), 14.2(q). MS (ESI,-Ve) m/z (relative intensity) 248.13 ([M-H]+, 100%). Anal. Calcd
for C13H15NO4: C 62.64; H 6.07; N 5.62. Found: C 62.69; H 6.00; N 5.53.
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(Z)-Ethyl 3-(4-chlorobenzamido)acrylate (1c)
1c was obtained following general procedure (Method A) as yellow solid (157 mg, 62 % yield),
mp: 52-54oC. IR (KBr): 3290, 2932, 1702, 1678, 1639, 1590, 1509, 1486 cm-1. H NMR (400
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MHz, CDCl3): δ 11.54 (d, 1H, J = 10 Hz), 7.93-7.88 (m, 2H), 7.73 (dd, 1H, J1 = 11.2 Hz, J2 = 8.8
Hz), 7.50-7.46 (m, 2H), 5.29 (d, 1H, J = 8.8 Hz), 4.25 (q, 2H, J = 7.2 Hz ), 1.35 (t, 3H, J = 7.2
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Hz). C NMR (100 MHz, CDCl3): δ 169.7 (s), 163.4 (s), 139.3 (s), 138.6 (d), 130.6 (s), 129.2
(d), 129.1 (d), 97.5 (d), 60.4 (t), 14.2 (q). MS (ESI, -ve) m/z (relative intensity) 252.14 ([M-H]+,
100%). Anal. Calcd for C12H12ClNO3: C, 56.81; H, 4.77; N, 5.52. Found: C, 56.78; H, 4.68; N,
5.72.
(Z)-Ethyl 3-(2-chlorobenzamide)acrylate (1d)
1d was obtained following general procedure (Method A) as a white crystalline solid (141 mg,
56 % yield), mp: 85-87oC. IR (KBr): 3313, 3071, 2981, 2940, 2901, 1723, 1685, 1628, 1592,
1481, 1434, 1379, 1256, 1201, 1139, 1094, 1029 cm-1. 1H NMR (400 MHz, CDCl3): δ 11.18 (d,
1H, J = 9.6 Hz), 7.75-7.66 (m, 2H), 7.52-7.41 (m, 2H), 7.40-7.34 (m, 1H), 5.28 (d, 1H, J = 8.8
13
Hz), 4.20 (q, 2H, J = 7.2 Hz), 1.32 (t, 3H, J = 7.2 Hz). C NMR (100 MHz, CDCl3): δ 168.8,
164.4, 137.5, 133.2, 132.4, 131.5, 130.7, 130.5, 127.2, 98.1, 60.3, 14.2. MS (ESI, -ve) m/z
(relative intensity) 252.16 ([M-H]+, 100%). Anal. Calcd for C12H12ClNO3: C 56.81; H 4.77; N 5.52.
Found: C 57.02; H 5.00; N 5.92.
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(Z)-Ethyl 3-(4-nitrobenzamido)acrylate (1e)
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1e was obtained following general procedure (Method A) as yellow solid (190 mg, 72 % yield),
mp: 127-129oC. IR (KBr): 3437, 2990, 2912, 1687, 1670, 1628, 1527, 1477, 1346 cm.-1 1
H
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NMR (400 MHz, CDCl3): δ 11.69 (d, 1H, J = 10 Hz), 8.37-8.33 (m, 2H), 8.14-8.10 (m, 2H), 7.72
(dd, 1H, J1= 10.8 Hz, J2= 8.8 Hz), 5.36 (d, 1H, J = 8.8 Hz), 4.25 (q, 2H, J = 7.2 Hz), 1.34 (t, 3H,
J = 7.2 Hz). 13C NMR (100 MHz, CDCl3): δ 169.6 (s), 162.5 (s), 150.3 (s), 138.0 (d), 137.6 (s),
128.8 (d), 124.0 (d), 98.8 (d), 60.6 (t), 14.2 (q). MS (ES-APCI, +ve) m/z (relative intensity) 265
([M+H]+, 100%). Anal. Calcd for C12H12N2O5: C 54.55; H 4.58; N 10.60. Found: C 54.32; H
4.70; N 10.44.
(Z)-Ethyl 3-(2-nitrobenzamido)acrylate (1f)
1f was obtained following general procedure (Method A) as a white crystalline solid (132 mg, 50
% yield), mp: 108-109oC. IR (KBr): 3464, 3319, 3071, 2986, 2955, 1687, 1627, 1532, 1353,
1221, 1024 cm.-1 1H NMR (400 MHz, CDCl3): δ 11.71 (d, 1H, J = 10.0 Hz), 8.85-8.82 (m, 1H),
8.48-8.44 (m, 1H), 8.27-8.23 (m, 1H), 7.78-7.71 (m, 2H), 5.36 (d, 1H, J = 8.8 Hz), 4.30-4.23 (q,
2H), 1.38-1.33 (t, 3H). 13C NMR (100 MHz, CDCl3): δ 169.5 (s), 162.3 (s), 148.6 (s), 138.1 (d),
134.1 (s), 132.9 (d), 130.1 (d), 127.2 (d), 123.1 (d), 98.7 (d), 60.6 (t), 14.2 (q). MS (ESI, -ve) m/z
(relative intensity) 262.98 ([M-H]+, 100%). Anal. Calcd for C12H12N2O5: C 54.55; H 4.58; N
10.60. Found: C 54.82; H 4.78; N 10.89.
(Z)-Ethyl 3-(3-nitrobenzamido)acrylate (1g)
1g was obtained following general procedure (Method A) as yellow solid (147 mg, 56 % yield),
mp: 103-105oC. IR (KBr): 3693, 3292,3063, 2980, 2932, 1682, 1630, 1531,1379, 1349, 1202
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cm.-1 1H NMR (400 MHz, CDCl3): δ 10.92 (d, 1H, J = 9.6 Hz), 8.11 (m, 1H), 7.77-7.60 (m, 4H),
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5.33 (d, 1H, J = 8.8 Hz), 4.22-4.15 (q, 2H), 1.33-1.27 (t, 3H). C NMR (100 MHz, CDCl3): δ
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169.1 (s), 163.9 (s), 146.9 (s), 137.4 (d), 133.7 (d), 131.4 (d), 131.4 (s), 128.3 (d), 124.8 (d), 98.5
(d), 60.4 (t), 14.1 (q). MS (ESI, -ve) m/z (relative intensity) 263.02 ([M-H]+, 100%). Anal. Calcd
for C12H12N2O5: C 54.55; H 4.58; N 10.60. Found: C 54.74; H 4.67; N 11.00.
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(Z)-Ethyl 3-(2-methoxybenzamido)acrylate (1h)
1h was obtained following general procedure (Method B) as oil (186 mg, 75 % yield). IR (neat):
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3442, 3025, 2979, 2846, 1680, 1621, 1481, 1397cm-1. H NMR (400 MHz, CDCl3): δ 12.39 (d,
1H, J = 10.4 Hz), 8.27-8.22 (m, 1H), 7.78 (dd, 1H, J1 = 11.2 Hz, J2 = 8.8 Hz), 7.55-7.51 (m,
1H), 7.12-6.99 (m, 1H), 5.21 (d, 1H, J = 8.8 Hz), 4.25 (q, 2H, J= 7.2 Hz), 4.12 (s, 3H), 1.32 (t,
3H, J = 7.2 Hz). 13C NMR (100 MHz, CDCl3): δ 168.2 (s), 163.6 (s), 158.4 (s), 138.0 (d), 134.2
(d), 132.8 (d), 121.2 (d), 119.8 (s), 111.5 (d), 97.1 (d), 59.7 (t), 55.7 (q), 14.3 (q). MS (ESI, +ve)
m/z (relative intensity) 272.02 ([M+Na]+, 100%), 521.10 ([2M+Na]+, 90%). Anal. Calcd for
C13H15NO4: C 62.64; H 6.07; N 5.62. Found: C 62.48; H 5.90; N 5.38.
Ethyl 3-(2-hydroxybenzamido)acrylate (1i)
1i was obtained following general procedure (Method A) as a white crystalline solid (131 mg, 56
o
1
% yield), mp: 98-100 C. IR (KBr): 3311, 2956, 1686, 1661, 1636, 1602, 1517 cm-1. H NMR
(400 MHz, CDCl3): δ 11.84 (s, 1H), 11.75 (d, 1H, J = 9.6 Hz), 7.71 (dd, J1 = 10.8 Hz, J2 = 8.8
Hz), 7.63-7.59 (m, 1H), 7.52-7.39 (m, 1H), 7.09-7.03 (m, 1H), 7.02-6.92 (m, 1H), 5.33 (d, 1H, J
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= 8.8 Hz), 4.26 (q, 2H, J = 7.2 Hz ), 1.35 (t, 3H, J = 7.2 Hz). C NMR (100 MHz, CDCl3): δ
169.6 (s), 167.8 (s), 162.5 (s), 137.4 (d), 135.7 (d), 126.3 (d), 119.3 (d), 118.7 (d), 113.0 (s), 98.2
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(d), 60.5 (t), 14.2 (q). MS (ESI, -ve) m/z (relative intensity) 234.09 ([M-H]+, 100%). Anal. Calcd
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for C12H13NO4: C, 61.27; H, 5.57; N, 5.95. Found: C, 61.22; H, 5.74; N, 6.07.
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(Z)-3-(Benzamido)acrylic acid (2)
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2 was obtained following general procedure (Method A) as a white crystalline solid (114 mg, 60
% yield), mp: 163-165 °C. IR (KBr): 3327, 3036, 2997, 1697, 1671, 1594, 1402, 1239 cm.-1 1
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NMR (400 MHz, CDCl3): δ 11.29 (d, 1H), J = 10.8 Hz), 7.98-7.85 (m, 3H), 7.68-7.60 (m, 1H),
7.59-7.50 (m, 2H), 7.09-7.03 (m, 1H), 5.34 (d, 1H, J = 9.2 Hz). 13C NMR (100 MHz, CDCl3): δ
173.5 (s), 164.5 (s), 141.1 (d), 133.3 (d), 131.9 (s), 129.0 (d), 127.7 (d), 95.7 (d). MS (ESI, -ve)
m/z (relative intensity) 190.04 ([M-H]+, 100%). Anal. Calcd for C10H9NO3: C 62.82; H 4.74; N
7.33. Found: C 62.61; H 4.69; N 7.63.
N-((Z)-3-oxo-3-phenylprop-1-enyl)benzamide (3a) 26
3a was obtained following general procedure (Method A) as a white crystalline solid (89 mg, 43
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% yield), mp: IR (KBr):3338, 3063, 2912, 2858, 1692, 1638, 1585, 1384, 1234, 1012 cm-1. H
NMR (400 MHz, CDCl3): δ 12.95 (d, 1H, J = 9.2 Hz,), 8.07-8.10 (m, 2H), 7.90-8.02 (m, 3H),
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7.48-7.66 (m, 6H), 6.43 (d, 1H, J = 8.8 Hz). C NMR (100 MHz, CDCl3): δ 193.2(s), 165.3(s),
140.1(d), 138.1(s), 133.1(d), 132.9(d), 132.0(s), 128.9(d), 128.7(d), 128.0(d), 127.9(d), 100.8(d).
MS (ESI, -ve) m/z (relative intensity) 250.06 ([M-H]+, 100%).
N-((Z)-3-(4-methoxyphenyl)-3-oxoprop-1-enyl)benzamide (3b)
3b was obtained following general procedure (Method A) as a white crystalline solid (104 mg,
45 % yield), mp: 86-88 °C. IR (KBr): 3338, 3063, 2912, 2858, 1692, 1638, 1585, 1384, 1234,
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1012 cm-1. H NMR (400 MHz, CDCl3): δ 12.98 (d, 1H, J = 10 Hz), 8.05-8.13 (m, 2H), 7.96-
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2H), 6.98-7.02 (m, 2H), 6.40 (d, 1H, J = 8.8 Hz), 3.90 (s, 3H). C NMR (100 MHz, CDCl3): δ
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191.8 (s), 165.3 (s), 163.5 (s), 139.4 (d), 133.0 (d), 132.1 (s), 131.0 (s), 130.2 (d), 128.9 (d),
127.9 (d), 113.9 (d), 100.8 (d), 55.5 (q). MS (ESI, -ve) m/z (relative intensity) 280.09 ([M-H]+,
100%). Anal. Calcd for C17H15NO3: C, 72.58; H, 5.37; N, 4.98; O, 17.06. Found: C, 72.65; H,
5.33; N, 5.05.
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(Z)-Ethyl 3-(furan-2-carboxamido)acrylate (4)
4 was obtained following general procedure (Method A) as a white crystalline solid (140 mg, 67
% yield), mp: 83-85oC. IR (KBr): 3327, 3128, 2978, 2936, 2874, 1725, 1685, 1629, 1587, 1492,
1469 cm.-1 1H NMR (400 MHz, CDCl3): δ 11.38 (d, 1H, J = 8.8 Hz), 7.68-7.58 (m, 2H), 7.31 (m,
1H), 6.59-6.56 (m, 1H), 5.26 (d, 1H, J = 8.8 Hz), 4.25 (q, 2H, J = 7.2 Hz), 1.34 (t, 3H, J = 7.2
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Hz). C NMR (100 MHz, CDCl3): δ 169.1 (s), 155.6 (s), 146.5 (s), 145.6 (d), 137.3 (d), 117.0
(d), 112.6 (d), 97.4 (d), 60.3 (t), 14.2(q). MS (ESI, +ve) m/z (relative intensity) 210.12 ([M+H]+,
100%). Anal. Calcd for C10H11NO4: C 57.41; H 5.30; N 6.70. Found: C 57.59; H 5.18; N 6.58.
(Z)-Ethyl 3-(thiophene-2-carboxamido)acrylate (5)
5 was obtained following general procedure (Method A) as a white crystalline solid (135 mg, 60
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% yield), mp: 116-118oC. IR (KBr): 3335, 3070, 2952, 1674, 1627, 1525, 1470, 1425 cm-1. H
NMR (400 MHz, CDCl3): δ 11.40 (d, 1H, J = 9.6 Hz), 7.75-7.72 (m, 1H), 7.68 (dd, J1 = 8.8 Hz,
J2 = 5.6 Hz), 7.64-7.62 (m, 1H), 7.18-7. 15 (m, 1H), 5.25 (d, 1H, J = 8.8 Hz), 4.25 (q, 2H, J = 7.2
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Hz), 1.33 (t, 3H, J = 7.2 Hz). C NMR (100 MHz, CDCl3): δ 169.5 (s), 159.2 (s), 138.3 (d),
137.3 (s), 132.5 (d), 130.0 (d), 128.1 (d), 96.9 (d), 60.3 (t), 14.2 (q). MS (ESI, -ve) m/z (relative
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intensity) 224.06 ([M-H]+, 100%). Anal. Calcd for C10H11NO3S: C, 53.32; H, 4.92; N, 6.22; S,
14.23. Found: C, 53.48; H, 5.27; N, 6.32; S, 14.42.
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(Z)-Ethyl 3-acetamidoacrylate (6)10b
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6 was obtained following general procedure (Method A) as oil (81 mg, 52 % yield). IR (neat):
3325, 2950, 2925, 2850, 1719, 1686, 1630, 1502, 1398, 1386 cm.-1 1H NMR (300 MHz, CDCl3)
δ 10.42 (s, 1H), 7.49 (dd, 1H, J1 = 11.2 Hz, J2 = 8.8 Hz),5.12 (d, 1H, J = 9.2 Hz), 4.19 (q, 2H, J
= 7.2 Hz), 2.17 (s, 3H), 1.31 (t, 3H, J= 7.0 Hz). 13CNMR (100 MHz, CDCl3): δ 169.2 (s), 168.4
(s), 137.9 (d), 96.3 (d), 60.2 (t), 23.6 (q), 14.2 (q). MS (ESI, +ve) m/z (relative intensity) 158.06
([M+H]+, 100%).
(Z)-Ethyl 3-(acrylamido)acrylate (7)
7 was obtained following general procedure (Method A) as oil (93 mg, 55 % yield). IR (neat):
3335, 2981, 2940, 1682, 1630, 1480, 1409, 1376 cm.-1 1H NMR (400 MHz, CDCl3): δ 10.68 (bs,
1H), 7.58 (dd, 1H, J1 = 10.4 Hz, J2 = 9.2 Hz), 6.45 (d, 1H, J = 17.2 Hz), 6.28-6.18 (m, 1H), 5.86
(d, 1H, J = 10.4 Hz), 5.19 (d, 1H, J = 8.8 Hz), 4.20 (q, 2H, J = 6.8 Hz), 1.30 (t, 3H, J = 6.8 Hz).
13C NMR (100 MHz, CDCl3): δ 169.2 (s), 163.2 (s), 138.0 (d), 129.9 (d), 129.6 (d), 97.3 (d),
60.2 (t), 14.1 (q). MS (ESI, -ve) m/z (relative intensity) 168 ([M-H]+, 38%). Anal. Calcd for
C8H11NO3 : C, 56.80; H, 6.55; N, 8.28. Found: C, 56.91; H, 6.38; N, 8.21.
(2Z)-Ethyl 3-(cinnamamido)acrylate (8)10b
8 was obtained following general procedure (Method A) as a white crystalline solid (127 mg, 52
% yield), mp: 112-113oC. IR (KBr): 3435, 2986, 2936, 1679, 1627, 1479, 1380cm.-1 1H NMR
(400 MHz, CDCl3): δ 10.73 (d, 1H, J = 9.2 Hz), 7.79 (d, 1H, J = 15.6 Hz), 7.67 (dd, 1H, J1 = 8.8
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Hz, J2= 11.2 Hz), 7.60-7.55 (m, 2H), 7.44-7.39 (m, 3H), 6.54 (d, 1H, J = 15.6 Hz), 5.21 (dd, 1H,
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J = 8.8 Hz) 4.23 (q, 2H, J = 7.2 Hz), 1.34 (t, 3H, J = 7.2 Hz). C NMR (100 MHz, CDCl3): δ
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169.4 (s), 163.5 (s), 144.4 (d), 138.4 (d), 134.2 (s), 130.5 (d), 128.9 (d), 128.2 (d), 119.2 (d), 96.7
(d), 60.2 (t), 14.2 (q). MS (ESI, -ve) m/z (relative intensity) 243.88 ([M-H]+, 100%). Anal. Calcd
for C14H15NO3: C, 68.56; H, 6.16; N, 5.71. Found: C, 68.36; H, 6.42; N, 6.08.
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(Z)-Ethyl 3-ureidoacrylate (9)
9 was obtained following general procedure (Method B) as oil (72 mg, 46 % yield). IR (neat):
3431, 3384, 2970, 2924, 2851, 1710, 1656, 1632, 1510, 1463, 1366 cm.-1 1H NMR (400 MHz,
CDCl3): δ 9.98 (d, 1H, J = 10 Hz), 7.45 (dd, 1H, J1 = 11.4 Hz, J2 = 8.8 Hz), 5.03 (d, 1H, J = 8.8
Hz), 5.04 (s, 2H, -NH2), 4.18 (q, 2H, J = 7.2 Hz), 1.30 (t, 3H, J = 7.2 Hz). 13C NMR (100 MHz,
CDCl3): δ169.8 (s), 153.7 (s), 140.7 (d), 93.2 (d), 59.9 (t), 14.2 (q). MS (ESI, +ve) m/z (relative
intensity) 159 ([M+H]+, 100%), 316 ( [2M]+, 30%). Anal. Calcd for C6H10N2O3: C, 45.57; H,
6.37; N, 17.71. Found: C, 45.77; H, 6.29; N, 17.92.
Butyl (Z)-2-(ethoxycarbonyl)vinylcarbamate (10)
10 was obtained following general procedure (Method B) as oil (116 mg, 54 % yield). IR (neat):
3716, 3329, 2962, 2874, 1745, 1685, 1633, 1489, 1404, 1370, 1355 cm.-1 1H NMR (400 MHz,
CDCl3): δ 9.75 (bs, 1H), 7.27 (m, 1H), 5.03 (d, 1H, J = 8.8 Hz), 4.22-4.12 (m, 4H), 1.69-1.60 (m,
2H), 1.46-1.40 (m, 2H), 1.33 (t, 3H, J = 7.2 Hz), 0.96 (t, 3H, J = 6.6 Hz). 13C NMR (100 MHz,
CDCl3): δ 168.9 (s), 153.6 (s), 140.1 (d), 94.7 (d), 66.0 (t), 59.9 (t), 30.7 (t), 18.9 (t), 14.2 (q),
13.5 (q). MS (ESI, +ve) m/z (relative intensity) 238.14 ([M+Na]+, 100%). Anal. Calcd for
C10H17NO4: C, 55.80; H, 7.96; N, 6.51. Found: C, 55.85; H, 8.22; N, 6.72.
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11 was obtained following general procedure (Method B) as oil (104 mg, 56 % yield). IR (neat):
3098, 2974, 2958, 1733, 1705, 1629, 1446, 1376, 1360 cm.-1 1H NMR (400 MHz, CDCl3): δ 8.27
(bs, 1H), 5.20 (d, 1H, J = 14.4 Hz), 4.21 (q, 2H, J = 7.2 Hz), 3.86 (s, 3H), 3.13 (s, 3H), 1.28 (q,
3H, J = 7.2 Hz). 13C NMR (100 MHz, CDCl3): δ 167.4, 130.1, 128.0, 98.5, 60.0, 54.1, 31.3, 14.3.
MS (ESI, +ve) m/z (relative intensity) 187.07 ([M+H]+, 100%). Anal. Calcd for C8H13NO4: C,
51.33; H, 7.00; N, 7.48. Found: C, 51.42; H, 7.23; N, 7.42.
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(E)-Ethyl 3-(N-methylformamido)acrylate (12)
12 was obtained following general procedure (Method B) as oil (64 mg, 41 % yield). IR (neat):
2980, 2940, 2897, 1711, 1624, 1369 cm.-1 1H NMR (400 MHz, CDCl3): δ 8.48 (s), 7.82 (d, 1H, J
= 13.6 Hz), 5.44 (d, 1H, J = 14 Hz), 4.23 (q, 2H, J = 8 Hz), 3.09 (s, 3H), 1.31 (t, 3H, J = 8 Hz).
13C NMR (100 MHz, CDCl3): δ 166.8 (s), 163.1 (d), 143.4 (d), 100.0 (d), 60.4 (t), 27.7 (q), 14.3
(q). MS (ESI, +ve) m/z (relative intensity) 314.30 ([2M]+ 100%). Anal. Calcd for C7H11NO3: C,
C, 53.49; H, 7.05; N, 8.91. Found: C, 53.42; H, 7.22; N, 8.82.
(E)-Ethyl 3-(2-oxopyrrolidin-1-yl)acrylate (13)25
13 was obtained following general procedure (Method A) as a white crystalline solid (131 mg,
72 % yield), mp: 118-120 oC. IR (KBr): 3083, 2979, 2905, 1727, 1627, 1460, 1386, 1364, 1326
cm.-1 1H NMR (400 MHz, CDCl3): δ 8.12 (d, 1H, J = 14.4 Hz), 5.28 (d, 1H, J = 14.4 Hz), 4.25
(q, 2H, J = 7.2 Hz), 3.58 (t, 2H, J = 7.2 Hz), 2.58 (t, 2H, J = 7.2 Hz), 2.22-2.17 (m, 2H), 1.31 (t,
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3H, J = 7.2 Hz). C NMR (100 MHz, CDCl3): δ 174.1 (s), 167.1 (s), 137.2 (d), 100.8 (d), 60.2
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(t), 44.9 (t), 30.9 (t), 17.4 (t), 14.3 (q). MS (ESI, +ve) m/z (relative intensity) 206.21 ([M+Na]+,
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100%). Anal. Calcd for C9H13NO3: C, 59.00; H, 7.15; N, 7.65. Found: C, 59.19; H, 7.38; N, 7.72.
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(E)-Ethyl 3-(3-(4-hydroxyphenyl)-2-oxoimidazolidin-1-yl)acrylate (14)
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14 was obtained following general procedure (Method A) as a white crystalline solid (99 mg, 54
% yield), mp: 72-74oC. IR (KBr): 3402, 2979, 2932, 2901, 1728, 1628, 1480, 1431, 1391,
1368cm.-1 1H NMR (400 MHz, CDCl3): δ 8.05 (d, 1H, J = 13.6 Hz), 6.03 (bs, 1H), 4.98 (d, 1H, J
= 13.6 Hz), 4.19 (q, 2H, J = 7.2 Hz), 3.66 (m, 4H), 1.29 (t, 3H, J = 7.2 Hz). 13C NMR (100 MHz,
CDCl3): δ 167.5 (s), 157.4 (s), 138.8 (d), 96.3 (d), 59.9 (t), 42.0 (t), 37.4 (t), 14.3 (q). MS (ESI,
+ve) m/z (relative intensity) 207.10 ([M+Na]+, 100%). Anal. Calcd for C8H12N2O3: C, 52.17; H,
6.57; N, 15.21. Found: C, 52.38; H, 6.82; N, 15.49.
Acknowledgment. We thank DST, (Ref. No. SR-S1/OC-60/2011), New Delhi and BRNS (Ref.
No. 2012/37C/3/BRNS), DAE, Govt of India for financial support.
Supporting Information Available. Copies of NMR (1H and 13C) spectra. This material is
available free of charge via the Internet at http://pubs.acs.org.
References
(1) Yet, L. Chem. Rev. 2003, 103, 4283-4306.
(2) (a) Kohno, J.; Koguchi, Y.; Nishio, M.; Nakao, K.; Kuroda, M.; Shimizu, R.; Ohnuki, T.;
Komatsubara, S. J. Org. Chem. 2000, 65, 990-995. (b) Kunze, B.; Jansen, R.; Höfle, G.;
Reichenbach, H. J. Antibiot. 1994, 47, 881-886. (c) Ghosh, S.; Datta, D. B.; Sen, N. Synth.
Commun. 1987, 17, 299-307. (d) Maxwell, A.; Rampersad, D. J. Nat. Prod. 1989, 52, 411-
414. (e) Gooßen, L. J.; Blanchot, M.; Arndt, M.; Salih, K. S. M. Synlett. 2010, 1685-1687.
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5
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(3) (a) Carbery, D. R. Org. Biomol. Chem. 2008, 6, 3455-3460. (b) Matsubara, R.; Kobayashi,
S. Acc. Chem. Res. 2008, 41, 292-301.
7
8
9
(4) For an excellent review on the synthesis of enamides, see: Tracey, M. R.; Hsung, R. P.;
Antoline, J.; Kurtz, K. C. M.; Shen, L.; Slafer, B. W.; Zhang, Y. Sci. Synth. 2005, 5, 387-
475.
10
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50
51
52
53
54
55
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58
59
60
(5) (a) Couture, A.; Deniau, E.; Grandclaudon, P. Tetrahedron Lett. 1993, 34, 1479-1482. (b)
Dupau, P.; Le Gendre, P.; Brueau, C.; Dixneuf, P. H. Synlett 1999, 1832-1834.
(6) (a) Wang, X.; Porco, Jr. J. A. J. Org. Chem. 2001, 66, 8215-8221. (b) Bayer, A.; Maier, M.
E. Tetrahedron 2004, 60, 6665-6677.
(7) (a) Boeckman, R. K., Jr.; Goldstein, S. W.; Walters, M. A. J. Am. Chem. Soc. 1988, 110,
8250-8252. (b) Speckamp, W. N.; Moolenaar, M. J. Tetrahedron 2000, 56, 3817-3856. (c)
Kinderman, S. S.; van Maarseveen, J. H.; Schoemaker, H. E.; Hiemstra, H.; Rutjes, F. P. J. T.
Org. Lett. 2001, 3, 2045-2048.
(8) (a) Brettle, R.; Mosedale, A. J. J. Chem. Soc., Perkin Trans. 1 1988, 2185-2195. (b)
Kuramochi, K.; Watanabe, H.; Kitahara, T. Synlett 2000, 397-399. (c) Stefanuti, I.; Smith, S.
A.; Taylor, R. J. K. Tetrahedron Lett. 2000, 41, 3735-3738.
(9) (a) Ager, D. J. Synthesis 1984, 384-398. (b) Ager, D. J. Org. React. 1990, 38, 1-223. (c)
Fürstner, A.; Brehm, C.; Cancho-Grande, Y. Org. Lett. 2001, 3, 3955-3957.
(10) (a) Hosokawa, T.; Takano, M.; Kuroki, Y.; Murahashi, S-I. Tetrahedron Lett. 1992, 33,
6643-6646. (b) Lee, J. M.; Ahn, D.-S.; Jung, D.-Y.; Lee, J.; Do, Y.; Kim, S. K.; Chang, S.
J. Am. Chem. Soc. 2006, 128, 12954-12962. (c) Liu, X.; Hii K. K. Eur. J. Org. Chem. 2010,
5181-5189. (d) Panda, N.; Jena. A. K.; Raghavender, M. ACS Catal. 2012, 2, 539-543.
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(11) (a) Dehli, J. R.; Legros, J.; Bolm, C. Chem. Commun. 2005, 973-986. (b) Ogawa, T.; Kiji,
T.; Hayashi, K.; Suzuki, H. Chem. Lett. 1991, 1443-1446. (c) Shen, R.; Porco, J. A., Jr.
Org. Lett. 2000, 2, 1333-1336. (d) Jiang, L.; Job, G. E.; Klapars, A.; Buchwald, S. L. Org.
Lett. 2003, 5, 3667-3669. (e) Pan, X.; Cai, Q.; Ma, D. Org. Lett. 2004, 6, 1809-1812. (f)
Kozawa, Y.; Mori, M. J. Org. Chem. 2003, 68, 3064-3067.
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55
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(12) Wallace, D. J.; Klauber, D. J.; Chen, C.-Y.; Volante, R. P. Org. Lett. 2003, 5, 4749-4752.
(13) Klapars, A.; Campos, K. R.; Chen, C.-Y.; Volante, R. P. Org. Lett. 2005, 7, 1185-1188.
(14) Bolshan, Y.; Batey, R. A. Angew. Chem. Int. Ed. 2008, 47, 2109-2112.
(15) Brice, J. L.; Meerdinka, J. E.; Stahl, S. S. Org. Lett. 2004, 6, 1845-1848.
(16) (a) Lu, Z.; Kong, W.; Yuan, Z.; Zhao, X.; Zhu, G. J. Org. Chem. 2011, 76, 8524-8529. (b)
Arndt, M.; Salih, K. S. M.; Fromm, A.; Gooβen, L. J.; Menges, F.; Niedner-Schatteburg,
G. J. Am. Chem. Soc. 2011, 133, 7428-7449.
(17) Kondo, T.; Tanaka, A.; Kotachi, S.; Watanabe, Y. J. Chem. Soc., Chem. Commun. 1995,
413-414.
(18) (a) Gooβen, L. J.; Rauhaus, J. E.; Deng, G. Angew. Chem., Int. Ed. 2005, 44, 4042-4045.
(b) Gooβen, L. J.; Salih, K. S. M.; Blanchot, M. Angew. Chem., Int. Ed. 2008, 47, 8492-
8465.
(19) Yudha, S.; Kuninobu, Y.; Takai, K. Org. Lett. 2007, 9, 5609-5611.
(20) (a) Gooßen, L.J.; Arndt, M.; Blanchot, M.; Rudolphi, F.; Menges, F.; Niedner-
Schatteburg, G. Adv. Synth. Catal. 2008, 350, 2701-2707. (b) Buba, A. E.; Arndt, M.;
Gooßen, L. J. J. Organomet. Chem. 2011, 696, 170-178.
(21) Jia, C.; Lu, W.; Oyamada, J.; Kitamura, T.; Matsuda, K.; Irie, M.; Fujiwara, Y. J. Am.
Chem. Soc. 2000, 122, 7252-7263.
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(22) Oyamada, J.; Kitamura, T. Chem. Commun. 2008, 4992-4994.
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(23) Gabriele, B.; Mancuso, R.; Salerno, G. J. Org. Chem. Soc. 2008, 73, 7336-7341.
(24) Liégault, B.; Fagnou, K. Organometallics 2008, 27, 4841-4843.
(25) Muthusamy, S.; Gunanathan, C.; Babu, S. A. Synthesis 2002, 471-474.
(26) Khokhlov, P. S.; Savenkov, N. F.; Sokolova, G. D.; Strepikheev, Yu. A.; Kolesova, V. A.
Zhurnal Organicheskoi Khimii 1982, 18, 1010-1011.
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