Synthesis of functionalized γ-lactams via copper-catalyzed intramolecular C-vinylation of activated methylene compounds

Article abstract of DOI:10.1002/cjoc.201090281

With the catalysis of CuI/3,4,7,8-tetramethyl-1,10-phenanthroline, a number of N-(2-iodoallyl)-2-(ethoxycarbonyl) alkanamides underwent efficient intramolecular C-vinylation in THF at 50 °C leading to the synthesis of functionalized γ-lactams in 61%-99% y

Full text of DOI:10.1002/cjoc.201090281

FULL PAPER
Synthesis of Functionalized γ-Lactams via Copper-Catalyzed
Intramolecular C-Vinylation of Activated Methylene
Compounds†
Chen, Liquna(陈立群)
Shi, Mina,b(施敏)
Li, Chaozhong*,b(李超忠)
a School of Chemistry & Molecular Engineering, East China University of Science and Technology,
Shanghai 200237, China
b Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, China
With the catalysis of CuI/3,4,7,8-tetramethyl-1,10-phenanthroline, a number of N-(2-iodoallyl)-2-(ethoxy-
carbonyl)alkanamides underwent efficient intramolecular C-vinylation in THF at 50 ℃ leading to the synthesis of
functionalized γ-lactams in 61%—99% yields.
Keywords lactams, copper, catalysis, vinylation
Introduction
ation of activated methylene compounds with vinyl hal-
ides leading to the facile synthesis of functionalized
alkylidenecyclobutanes.9 Driven by our interest in cop-
per-catalyzed intramolecular vinylation reactions,4,8-10
we envisioned that the intramolecular C-vinylation
might be utilized for the synthesis of functionalized lac-
tams starting from suitable N-(haloalkenyl)amides.
Herein we disclose the details of our investigation.
Lactams are important structural motifs in many
biologically active natural products and medicinal
agents. They are also versatile intermediates in a num-
ber of areas ranging from organic synthesis to polymer
chemistry. Preparations of lactams have long been an
important topic in organic chemistry and continue to be
actively pursued.1 Our group has been focusing on the
synthesis of lactams via C- or N-radical cyclization,2
electrophilic halocyclization3 or copper-catalyzed intra-
molecular N-vinylation.4 Herein we report that the
Cu(I)-catalyzed intramolecular vinylation of activated
methylene compounds with vinyl iodides provides an
simple and efficient entry to functionalized γ-lactams.
The past decade has witnessed a rapid progress in
the formation of aryl (or vinyl) C—X bonds (X＝N, O,
S, etc.) via copper-catalyzed Ullmann coupling between
aryl (or vinyl) halides and heteroatom-centered nucleo-
philes.5 The high stability and low costs of the copper
catalysts make these transformations attractive for in-
dustrial applications. By the appropriate choice of cop-
per source, ligand, base and solvent, these reactions
have been developed to include a wide range of sub-
strates under mild conditions. This method was then
successfully extended to the C—C bond formation via
copper-catalyzed C-arylation of active methylene com-
pounds (the Hurtley coupling6).5 As a comparison, the
analogous C-vinylation is far less explored.7-9 Qian and
Pei reported the intermolecular cross-coupling of acti-
vated methylene compounds with β-bromostyrenes.7 We
recently developed the efficient intramolecular C-vinyl-
Results and discussion
N-Benzyl-N-(2-iodoallyl)-2-(ethoxycarbonyl)propan-
amide (1a) was chosen as the model substrate for the
optimization of reaction conditions (Table 1). Com-
pound 1a was first subjected to the following conditions
previously developed by us in the synthesis of alkyl-
idenecyclobutanes: CuI (20 mol%), L-proline (L-1, 80
mol%), Cs2CO3 (3 equiv.) in refluxing THF.9 After 20 h,
the expected product lactam 2a was obtained in only
about 10% yield while most of the starting material was
recovered (Entry 1, Table 1). We then screened the
ligands (Entries 2—7, Table 1). N,N'-Dimethylethylene-
diamine (L-2) showed the similar result. With the use of
1,10-phenanthroline (L-3) as the ligand, the yield of 2a
was increased to 50%. Switching the ligand to
3,4,7,8-tetramethyl-1,10-phenanthroline (L-4) resulted
in a further improvement in the product yield (56%). A
higher yield of 2a was achieved when the temperature
was lowered to 50 ℃ (Entry 7, Table 1), presumably
because the product lactam was more stable at lower
temperature. However, the yield was decreased when
only 10 mol% of CuI was used (Entry 8, Table 1). The
*
E-mail: clig@mail.sioc.ac.cn
Received March 25, 2010; revised and accepted April 22, 2010.
Project supported by the National Natural Science Foundation of China (Nos. 20702060 and 20832006) and the Shanghai Municipal Committee of
Science and Technology (No. 07XD14038).
† Dedicated to the 60th Anniversary of Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences.
1660
© 2010 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2010, 28, 1660— 1664

Synthesis of Functionalized γ-Lactams
effect of bases was also examined and Cs2CO3 turned
out to be superior to K2CO3 or K3PO4 (Entries 9 and 10,
Table 1).
tuted pattern in 1, which makes the cyclization confor-
mationally more favorable. Further investigations on the
above different mechanisms and on the control of enan-
tioselectivity of C-vinylation are currently underway in
our laboratory.
Table 1 Intramolecular C-vinylation of amide 1a
Table 2 Synthesis of γ-lactams 2
Entrya
Substrate
Product
Yieldb/%
61
O
O
O
O
EtO
EtO
Entrya
Ligandb
L-1
Base
Yieldc/%
EtO
EtO
N
1
N Bn
Bn
I
1
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
K2CO3
K3PO4
10
1a
2a
2
L-2
10
O
O
O
3
L-3
50
O
4
L-4
56
N
N Ar
Ar
I
5
L-5
27
6
L-6
21
1b (Ar = Ph)
2b
2c
2d
2
3
4
99
86
80
7d
8d,e
9
L-4
80 (61)
1c (Ar = 4-Cl-C6H4)
1d (Ar = 2-Cl-C6H4)
L-4
55 (38)
L-4
5
0
O
O
O
O
O
10
L-4
EtO
EtO
a
EtO
EtO
N
Reaction conditions: 1a (0.30 mmol), CuI (0.06 mmol), ligand
5
6
7
8
70
84
66
99
N Bu-t
(0.24 mmol), base (0.90 mmol), THF (10 mL), reflux, 20 h. b L-1:
L-proline; L-2: N,N'-dimethylethylenediamine; L-3: 1,10-phen-
anthroline; L-4: 3,4,7,8-tetramethyl-1,10-phenanthroline; L-5:
2-isobutyrylcyclohexanone; L-6: N,N-dimethylglycine hydro-
Bu-t
I
I
1e
2e
O
O
O
chloride. 1H NMR yield with the isolated yield in parentheses.
c
N
Ph
N Ph
d
e
Ph Ph
The reaction temperature was 50 ℃. 10 mol% of CuI and 40
1f
mol% of L-4 were employed.
2f
O
O
With the optimized conditions in hand (Entry 7, Ta-
ble 1), we set out to explore the scope and limitation of
this method. The results are summarized in Table 2. The
N-aryl or N-tert-butyl-substituted analogs of 1a all un-
derwent smoothly the intramolecular C-vinylation to
give the corresponding lactams in high yields (Entries 2
— 5, Table 2). The cyclization was also successful when
the methyl group in 1a was replaced by a bulky phenyl
group (Entry 6, Table 2). When lactone 1g was used as
the substrate, the spiro-lactam 2g was achieved in good
yield (Entry 7, Table 2). Furthermore, the 2-cyanoamide
1h also afforded the cyclization product 2h in almost
quantitative yield (Entry 8, Table 2). These results
clearly demonstrate the efficiency of this C— C coupling
strategy in the synthesis of functionalized lactams.
O
O
O
O
N
Ph
N Ph
I
1g
2g
O
O
NC
NC
N
Ph
N Ph
I
2h
1h
a
Experimental conditions: 1 (0.30 mmol), CuI (0.06 mmol), L-4
(0.24 mmol), Cs2CO3 (0.90 mmol), THF (10 mL), 50 ℃, 20 h.
b Isolated yield based on 1.
Scheme 1 Copper-catalyzed reaction of iodoamide 3
To further extend the scope of application, we pre-
pared
N-phenyl-N-(2-iodoallyl)-2-(ethoxycarbonyl)-
acetamide (3) and subjected to the treatment with
CuI/L-4 under the above optimized conditions. We were
surprised to find that no expected lactam 4 or its isom-
erized product 5 could be isolated. Instead, only
N-(2-iodoallyl)aniline (6) was isolated in about 50%
yield (Scheme 1). Apparently the β-elimination (to give
6) rather than the C-vinylation (to give 4 or 5) occurred
for the carbanions of 3. The reversed behavior in the
reactions of 1 might be attributed to the gem-disubsti-
Chin. J. Chem. 2010, 28, 1660— 1664
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1661

Chen, Shi & Li
FULL PAPER
Conclusion
－1
1388, 1323, 1156, 1094, 1013, 905, 841 cm ; EIMS
m/z (%): 376 (M＋－C2H5O, 4), 294 (100), 266 (13), 193
(8), 164 (14), 140 (25), 130 (22), 111 (17); HRMS calcd
for C15H17ClINO3 (M) 420.9942, found 420.9940.
N-(2-Chlorophenyl)-2-(ethoxycarbonyl)-N-(2-iodo-
The chemistry detailed above has clearly demon-
strated that the Cu(I)-catalyzed intramolecular C-vinyl-
ation provides a simple and efficient entry to function-
alized γ-lactams, which should be of important applica-
tion in organic synthesis.
allyl)propanamide (1d)
Colorless oil; 1H NMR
(CDCl3, 300 MHz) δ: 1.18—1.28 (m, 3H), 1.34—1.40
(m, 3H), 3.14—3.25 (m, 1H), 3.71—3.78 (m, 1H), 4.01
—4.16 (m, 2H), 5.30—5.43 (m, 1H), 5.81/5.87 (2s, 1H),
6.11/6.32 (2s, 1H), 7.30—7.41 (m, 2H), 7.49—7.56 (m,
2H); 13C NMR (CDCl3, 100 MHz) δ: 14.0/14.2, 14.6,
44.0/44.2, 58.1/59.2, 61.2/61.4, 103.5/104.5, 127.8/
127.9, 128.1/129.2, 130.3, 130.7/131.1, 131.9/132.0,
133.0/133.4, 138.0/138.5, 169.7/169.8, 170.3; IR (film)
ν: 3070, 2984, 2940, 1738, 1679, 1478, 1385, 1304,
Experimental
Typical procedure for the copper-catalyzed intra-
molecular C-vinylation
The mixture of amide 1a (0.12 g, 0.30 mmol), CuI
(12 mg, 0.060 mmol), L-4 (57 mg, 0.24 mmol) and
Cs2CO3 (0.29 g, 0.90 mmol) in THF (10 mL) was stirred
at 50 ℃ for 20 h under nitrogen atmosphere. The re-
sulting mixture was cooled down to room temperature
and filtered. The filtrate was then concentrated in vacuo
and the crude product was purified by flash chromatog-
raphy on silica gel with hexane/EtOAc (V∶V＝10∶1)
as the eluent to give the pure product 2a as a colorless
oil. Yield: 50 mg (61%).
－1
1223, 1190, 1095, 910, 772 cm ; EIMS m/z (%): 376
(M＋－C2H5O, 4), 294 (100), 266 (16), 186 (7), 164 (12),
140 (16), 130 (20), 111 (11); HRMS calcd for
C15H17ClINO3 (M) 420.9942, found 420.9946.
N-(tert-Butyl)-2-(ethoxycarbonyl)-N-(2-iodoallyl)-
propanamide (1e) Colorless oil; H NMR (CDCl3,
1
300 MHz) δ: 1.25 (t, J＝7.2 Hz, 3H), 1.37 (d, J＝6.6 Hz,
3H), 1.47 (s, 9H), 3.43 (q, J＝6.9 Hz, 1H), 4.04—4.34
(m, 4H), 6.00 (br, 1H), 6.42 (br, 1H); 13C NMR (CDCl3,
75.4 MHz) δ: 14.1, 14.2, 43.3, 56.0, 58.2, 61.7,
103.8/104.6, 126.9/127.2, 170.1; IR (film) ν: 2980, 1746,
N-Benzyl-2-(ethoxycarbonyl)-N-(2-iodoallyl)pro-
panamide (1a) Colorless oil; H NMR (CDCl3, 300
1
MHz) δ: 1.24/1.26 (2q, J＝7.2 Hz, 3H), 1.42/1.47 (2d,
J＝6.9 Hz, 3H), 3.64—3.75 (1H, m), 3.82—5.14 (m,
6H), 5.90—5.97 (m. 1H), 6.24 (br, 1H), 7.16—7.37 (m,
5H); 13C NMR (CDCl3, 75.4 MHz) δ: 14.3/14.4,
14.5/14.7, 43.3/43.5, 48.4/50.7, 56.4/58.1, 61.8/62.0,
104.6/105.3, 126.6/126.8, 127.1/127.8, 128.2/128.3,
128.9/129.3, 136.0/136.8, 170.5/170.6, 170.7; IR (film)
ν: 3065,－2983, 2939, 1738, 1659, 1427, 1186, 1098, 908,
－1
1664, 1393, 1186, 1095, 1032, 979, 904 cm ; EIMS
m/z (%): 323 (M＋－C2H5O, 5), 267 (1), 242 (12), 193
(2), 164 (21), 143 (4), 114 (7), 57 (100); HRMS calcd
for C13H22INO3 (M) 367.0644, found 367.0641.
2,N-Diphenyl-2-(ethoxycarbonyl)-N-(2-iodoallyl)-
acetamide (1f) Colorless oil; H NMR (CDCl3, 300
1
＋
1
737 cm ; EIMS m/z (%): 356 (M －C2H5O, 1), 274
(26), 234 (6), 200 (3), 146 (5), 129 (9), 106 (34), 91
(100); HRMS calcd for C16H20INO3 (M) 401.0488,
found 401.0489.
MHz) δ: 1.25 (d, J＝7.5 Hz, 3H), 4.17 (q, J＝7.2 Hz,
2H), 4.47—4.64 (m, 3H), 5.79 (s, 1H), 6.12 (s, 1H),
7.12—7.41 (m, 10H); 13C NMR (CDCl3, 100 MHz) δ:
14.1, 56.1, 60.6, 61.9, 104.0, 127.7, 127.9, 128.3, 128.8,
129.7, 129.8, 133.2, 141.2, 167.8, 168.6; IR (film) ν:
3070, 3030, 2980, 1747, 1668, 1595, 1494, 1384, 1303,
2-(Ethoxycarbonyl)-N-phenyl-N-(2-iodoallyl)pro-
panamide (1b) Colorless oil; H NMR (CDCl3, 300
1
MHz) δ: 1.24 (t, J＝7.2 Hz, 3H), 1.34 (d, J＝7.2 Hz,
3H), 3.42 (q, J＝7.2 Hz, 1H), 4.11 (q, J＝6.9 Hz, 2H),
4.58 (AB, J＝15.6 Hz, 2H), 5.84 (s, 1H), 6.22 (s, 1H),
7.30—7.46 (m, 5H); 13C NMR (CDCl3, 75.4 MHz) δ:
14.3, 14.4, 44.1, 60.5, 61.5, 104.7, 128.0, 128.7, 128.9,
130.1, 141.6, 170.2, 170.7; IR (film) ν: 3065, 2982,
1743, 1667, 1595, 1494, 1389, 1222, 1191, 1095, 909,
－1
1219, 1182, 1019, 910, 701 cm ; EIMS m/z (%): 448
(M＋－1, 5), 322 (100), 249 (7), 220 (3), 159 (10), 130
(15), 119 (9), 91 (13); HRMS calcd for C20H20INO3 (M)
449.0488, found 449.0490.
N-(2-Iodoallyl)-2-oxo-N-phenyl-tetrahydrofuran-
3-carboxamide (1g) White solid; m.p. 124—126 ℃;
1H NMR (CDCl3, 300 MHz) δ: 2.20—2.38 (m, 1H),
2.72—2.85 (m, 1H), 3.56 (t, J＝8.4 Hz, 1H), 4.19 (q,
J＝7.8 Hz, 1H), 4.48—4.56 (m, 1H), 4.62 (s, 2H), 5.85
(s, 1H), 6.26 (s, 1H), 7.44 (br, 5H); 13C NMR (CDCl3,
100 MHz) δ: 27.3, 43.7, 60.6, 67.4, 103.6, 128.0, 128.5,
128.9, 130.0, 141.1, 167.8, 173.5; IR (film) ν: 3065,
－1
＋
701 cm ; EIMS m/z (%): 342 (M －C2H5O, 3), 260
(100), 232 (14), 160 (20), 130 (35), 119 (11), 106 (28),
77 (35); HRMS calcd for C15H18INO3 (M) 387.0331,
found 387.0331.
N-(4-Chlorophenyl)-2-(ethoxycarbonyl)-N-(2-iodo-
allyl)propanamide (1c)
Colorless oil; 1H NMR
2926, 1－766, 1661, 1594, 1494, 1396, 1159, 1019, 911,
＋
(CDCl3, 300 MHz) δ: 1.24 (t, J＝7.2 Hz, 3H), 1.35 (d,
J＝6.9 Hz, 3H), 3.39 (q, J＝6.9 Hz, 1H), 4.11 (q, J＝7.2
Hz, 2H), 4.56 (AB, J＝15.6 Hz, 2H), 5.84 (s, 1H), 6.19
(s, 1H), 7.27 (d, J＝8.7 Hz, 2H), 7.41 (d, J＝8.7 Hz,
2H); 13C NMR (CDCl3, 75.4 MHz) δ: 14.1, 14.2, 43.9,
60.2, 61.4, 104.1, 128.4, 130.0, 130.1, 134.7, 139.8,
169.8, 170.3; IR (film) ν: 3100, 2983, 1738, 1672, 1492,
1
700 cm ; EIMS m/z (%): 244 (M －I, 100), 200 (5),
167 (3), 158 (3), 130 (16), 119 (4), 106 (11), 77 (13);
HRMS calcd for C14H14NO3 (M－I) 244.0974, found
244.0980.
2-Cyano-N-(2-iodoallyl)-N-phenylpropanamide
1
(1h) Colorless oil; H NMR (CDCl3, 300 MHz) δ:
1.50 (d, J＝7.2 Hz, 3H), 3.46 (q, J＝7.2 Hz, 1H), 4.52
1662
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Chin. J. Chem. 2010, 28, 1660— 1664

Synthesis of Functionalized γ-Lactams
(d, J＝15.3 Hz, 1H), 4.66 (d, J＝15.3 Hz, 1H), 5.84 (s,
1H), 6.10 (s, 1H), 7.34—7.52 (m, 5H); 13C NMR
(CDCl3, 100 MHz) δ: 15.9, 29.9, 60.5, 103.8, 118.1,
128.4, 129.2, 129.5, 130.3, 139.9, 165.7; IR (film) ν:
3070, 2943, 2246, 1678, 1595, 1493, 1392, 1216, 1139,
1019, 912, 703 cm ; EIMS m/z (%): 339 (M －1, 1),
213 (100), 167 (6), 157 (5), 130 (16), 119 (7), 106 (6),
77 (14); HRMS calcd for C13H13IN2O (M) 340.0073,
found 340.0070.
112 (16); HRMS calcd for C15H16ClNO3 (M) 293.0819,
found 293.0823.
Ethyl 1-(tert-butyl)-3-methyl-4-methylene-2-oxo-
pyrrolidine-3-carboxylate (2e)
Colorless oil; 1H
NMR (CDCl3, 300 MHz) δ: 1.20 (t, J＝7.2 Hz, 3H),
1.43 (s, 9H), 1.45 (s, 3H), 3.99—4.17 (m, 4H), 5.09—
5.12 (m, 2H); 13C NMR (CDCl3, 75.4 MHz) δ: 14.1,
19.1, 27.9, 50.1, 54.6, 57.0, 61.7, 109.3, 143.6, 170.8,
172.8; IR (film) ν: 2979, 1743, 1697, 1663, 1223, 1119,
＋
－1
＋
－1
Ethyl 1-benzyl-3-methyl-4-methylene-2-oxopyr-
1023, 909 cm ; EIMS m/z (%): 239 (M , 14), 224 (22),
210 (7), 183 (14), 166 (21), 150 (48), 137 (22), 110
(100); HRMS calcd for C13H21NO3 (M) 239.1521,
found 239.1524.
1
rolidine-3-carboxylate (2a) Colorless oil; H NMR
(CDCl3, 300 MHz) δ: 1.13 (t, J＝7.2 Hz, 3H), 1.48 (s,
3H), 3.75 (d, J＝14.1 Hz, 1H), 3.95 (dt, J＝14.1, 2.4 Hz,
1H), 4.08 (q, J＝6.9 Hz, 2H), 4.26 (d, J＝15.0 Hz, 1H),
4.76 (d, J＝15.0 Hz, 1H), 5.02 (s, 1H), 5.12 (br, 1H),
71.9—7.27 (m, 5H); 13C NMR (CDCl3, 75.4 MHz) δ:
14.1, 19.8, 46.7, 50.7, 55.7, 62.0, 110.1, 128.0, 128.3,
128.9, 136.0, 143.4, 170.6, 172.7; IR (film) ν: 2984,
Ethyl 4-methylene-2-oxo-1,3-diphenylpyrrolidine-
1
3-carboxylate (2f) Colorless oil; H NMR (CDCl3,
300 MHz) δ: 1.28 (t, J＝7.2 Hz, 3H), 4.29 (q, J＝7.2 Hz,
2H), 4.59 (AB, J＝13.2 Hz, 2H), 5.43 (s, 1H), 5.62 (s,
1H), 7.18 (t, J＝7.5 Hz, 1H), 7.26—7.41 (m, 5H), 7.58
(d, J＝8.4 Hz, 2H), 7.79 (d, J＝8.1 Hz, 2H); 13C NMR
(CDCl3, 100 MHz) δ: 14.0, 52.3, 62.2, 66.4, 113.8,
120.2, 125.2, 128.1, 128.3, 128.4, 129.0, 13＋5.9, 138.7,
140.0, 169.6, 169.7; EIMS m/z (%): 321 (M , 74), 292
(100), 248 (63), 220 (28), 129 (35), 115 (52), 104 (35),
77 (32); HRMS calcd for C20H19NO3 (M) 321.1365,
found 321.1359.
－1
1741, 1703, 1664, 143＋1, 1247, 1119, 1022, 701 cm ;
EIMS m/z (%): 273 (M , 10), 244 (5), 216 (2), 200 (32),
168 (1), 154 (1), 112 (2), 91 (100); HRMS calcd for
C16H19NO3 (M) 273.1365, found 273.1366.
Ethyl 3-methyl-4-methylene-2-oxo-1-phenylpyr-
1
rolidine-3-carboxylate (2b) Colorless oil; H NMR
(CDCl3, 300 MHz) δ: 1.21 (t, J＝7.2 Hz, 3H), 1.62 (s,
3H), 4.13—4.22 (m, 2H), 4.44 (d, J＝15.0 Hz, 1H),
4.63 (dt, J＝15.0, 2.1 Hz, 1H), 5.28 (br, 2H), 7.20 (t,
J＝7.2 Hz, 1H), 7.41 (t, J＝7.5 Hz, 2H), 7.69 (d, J＝8.1
Hz, 2H); 13C NMR (CDCl3, 75.4 MHz) δ: 14.2, 19.8,
52.7, 57.2, 62.1, 110.3, 120.5, 125.4, 129.3, 138.9,
142.3, 170.3, 171.8; IR (film) ν: 2984, 2937, 1737, 1710,
1598, 1495, 1392, 1229, 1119, 1093, 1020, 906, 759
4-Methylene-2,2'-dioxo-1-phenyl-spiro(pyrrolid-
in-3,3'-tetrahydrofuran) (2g) White solid, m.p. 112
1
—114 ℃; H NMR (CDCl3, 300 MHz) δ: 2.47—2.57
(m, 1H), 2.94—3.04 (m, 1H), 4.39—4.53 (m, 2H), 4.65
—4.80 (m, 2H), 5.31 (s, 1H), 5.38 (s, 1H), 7.21 (t, J＝
7.2 Hz, 1H), 7.40 (t, J＝8.1 Hz, 2H), 7.65 (d, J＝7.8 Hz,
2H); 13C NMR (CDCl3, 100 MHz) δ: 32.2, 52.7, 57.8,
66.9, 110.5, 120.4, 125.6, 129.1, 138.3, 140.2, 169.3,
173.6; EIMS m/z (%): 243 (M＋, 39), 199 (100), 184
(67), 170 (57), 156 (34), 130 (11), 104 (40), 77 (68);
HRMS calcd for C14H13NO3 (M) 243.0895, found
243.0892.
＋
－1
cm ; EIMS m/z (%): 259 (M , 21), 230 (12), 186 (100),
160 (23), 130 (12), 106 (20), 91 (14), 77 (39); HRMS
calcd for C15H17NO3 (M) 259.1208, found 259.1206.
Ethyl 1-(4-chlorophenyl)-3-methyl-4-methylene-
2-oxopyrrolidine-3-carboxylate (2c) Colorless oil;
1H NMR (CDCl3, 300 MHz) δ: 1.13 (t, J＝7.2 Hz, 3H),
1.54 (s, 3H), 4.05—4.13 (m, 2H), 4.33 (d, J＝13.2 Hz,
1H), 4.52 (dt, J＝13.2, 2.4 Hz, 1H), 5.21 (s, 2H), 7.30
(d, J＝8.7 Hz, 2H), 7.57 (d, J＝8.7 Hz, 2H); 13C NMR
(CDCl3, 75.4 MHz) δ: 14.0, 19.5, 52.4, 57.0, 62.0, 110.5,
121.3, 129.1, 130.3, 137.3, 141.7, 169.8, 171.7; IR (film)
ν: 2984, 1744, 1708, 1668, 1494, 1388, 1295,＋1227,
3-Cyano-3-methyl-4-methylene-2-oxo-1-phenyl-
1
pyrrolidine (2h) White solid, m.p. 72—74 ℃; H
NMR (CDCl3, 300 MHz) δ: 1.78 (s, 3H), 4.53 (AB, J＝
14.1 Hz, 2H), 5.49 (d, J＝1.2 Hz, 1H), 5.60 (d, J＝1.2
Hz, 1H), 7.23 (t, J＝7.5 Hz, 1H), 7.41 (t, J＝8.1 Hz,
2H), 7.64 (d, J＝7.8 Hz, 2H); 13C NMR (CDCl3, 100
MHz) δ: 23.7, 45.4, 51.3, 113.2, 118.3, 120.3, 125.9,
129.2, 137.9, 138.6, 167.0; IR (film) ν: 2990, 2240,
1712, 1673, 1495, 1398, 1277, 1223, 1094, 916, 761
－1
1085, 1101, 829 cm ; EIMS m/z (%): 293 (M , 24),
264 (10), 220 (100), 190 (6), 156 (5), 138 (14), 111 (23),
81 (29); HRMS calcd for C15H16ClNO3 (M) 293.0819,
found 293.0820.
＋
－1
cm ; EIMS m/z (%): 212 (M , 100), 197 (41), 183 (27),
169 (26), 158 (8), 119 (47), 106 (19), 91 (26); HRMS
calcd for C13H12N2O (M) 212.0950, found 212.0948.
2-(Ethoxycarbonyl)-N-(2-iodoallyl)-N-phenylacet-
Ethyl 1-(2-chlorophenyl)-3-methyl-4-methylene-
2-oxopyrrolidine-3-carboxylate (2d) Colorless oil;
1H NMR (CDCl3, 300 MHz) δ: 1.26 (t, J＝7.2 Hz, 3H),
1.61 (s, 3H), 4.19 (q, J＝7.2 Hz, 2H), 4.35 (d, J＝13.2
Hz, 1H), 4.50 (dt, J＝13.2, 2.4 Hz, 1H), 5.22 (s, 1H),
5.27 (s, 1H), 7.25—7.33 (m, 3H), 7.45—7.47 (m, 1H);
13C NMR (CDCl3, 75.4 MHz) δ: 14.0, 19.5, 53.3, 55.3,
61.8, 110.1, 127.9, 129.4, 129.5, 130.5, 13＋2.2, 135.4,
143.1, 170.1, 172.3; EIMS m/z (%): 293 (M , 18), 272
(13), 264 (18), 258 (40), 220 (100), 184 (16), 138 (12),
1
amide (3) White solid, m.p. 44—46 ℃; H NMR
(CDCl3, 400 MHz) δ: 1.23 (t, J＝7.2 Hz, 3H), 3.25 (s,
2H), 4.12 (q, J＝7.2 Hz, 2H), 4.60 (s, 2H), 5.84 (s, 1H),
6.24 (d, J＝1.2 Hz, 1H), 7.29—7.42 (m, 5H); 13C NMR
(CDCl3, 100 MHz) δ: 14.1, 41.8, 60.3, 61.4, 104.0,
128.0, 128.3, 128.8, 129.9, 141.4, 166.0, 167.5; EIMS
m/z (%): 246 (M＋－I, 100), 218 (18), 200 (3), 172 (3),
159 (6), 130 (20), 106 (17), 77 (13); HRMS calcd for
Chin. J. Chem. 2010, 28, 1660— 1664
© 2010 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
1663

Chen, Shi & Li
(a) Shen, M.; Li, C. J. Org. Chem. 2004, 69, 7906.
(b) Tang, Y.; Li, C. Tetrahedron Lett. 2006, 47, 3823.
(c) Hu, T.; Liu, K.; Shen, M.; Yuan, X.; Tang, Y.; Li, C. J.
Org. Chem. 2007, 72, 8555.
(a) Hu, T.; Li, C. Org. Lett. 2005, 7, 2035.
(b) Lu, H.; Li, C. Org. Lett. 2006, 8, 5365.
(c) Zhao, Q.; Li, C. Org. Lett. 2008, 10, 4037.
(d) Lu, H.; Yuan, X.; Zhu, S.; Sun, C.; Li, C. J. Org. Chem.
2008, 73, 8665.
FULL PAPER
C14H16INO3 (M) 373.0175, found 373.0170.
3
4
1
N-(2-Iodoallyl)aniline (6) Yellow oil; H NMR
(CDCl3, 300 MHz) δ: 3.98 (s, 2H), 4.23 (br, 1H), 5.84 (d,
J＝1.5 Hz, 1H), 6.33 (d, J＝1.8 Hz, 1H), 6.60 (d, J＝
8.7 Hz, 2H), 6.74 (t, J＝7.5 Hz, 1H), 7.18 (t, J＝8.4 Hz,
2H); 13C NMR (CDCl3, 75.4 MHz) δ: 55.9, 109.8, 113.1,
118.3, 125.2, 129.4, 146.6; EIMS m/z (%): 259 (M＋, 55),
132 (40), 117 (16), 106 (100), 93 (6), 77 (22), 65 (20),
51 (10); HRMS calcd for C9H10IN (M) 258.9858, found
258.9855.
5
For reviews, see: (a) Kunz, K.; Scholz, U.; Ganzer, D.
Synlett 2003, 2428.
(b) Ley, S. V.; Thomas, A. W. Angew. Chem., Int. Ed. 2003,
42, 5400.
(c) Beletskaya, I. P.; Cheprakov, A. V. Coord. Chem. Rev.
2004, 248, 2337.
Acknowledgment
We thank Shana Zhu of Shanghai Institute of Or-
ganic Chemistry for recording some of the IR spectra.
(d) Deng, W.; Liu, L.; Guo, Q.-X. Chin. J. Org. Chem. 2004,
24, 150.
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© 2010 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2010, 28, 1660— 1664