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S. Kang et al. / Tetrahedron 66 (2010) 4326e4329
or 400 MHz and 13C NMR at 75, 100, or 125 MHz. Chemical shifts
were recorded in parts per million relative to CHCl3 ( 7.24) and H2O
4.70) for 1H NMR and relative to the central CDCl3
77.21)
4.5. Ethyl 2-(acetoxymethyl)acrylate (3d)
d
(d
(d
To a cooled solution of ethyl 2-(hydroxymethyl)acrylate (6)
(1.0 g, 7.68 mmol) in dichloromethane (30 mL) were added tri-
ethylamine (2.75 mL, 19.74 mmol) and acetyl chloride (1.4 mL,
19.74 mmol). After stirring for 20 min, the reaction mixture was
washed with brine (2ꢂ30 mL), dried over anhydrous Na2SO4, and
concentrated. The residue was purified by column chromatography
(hexanes/EtOAc¼20:1) to afford 3d (1.21 g, 51%) as a colorless oil.
resonance for 13C NMR. Melting points were not corrected. Enan-
tiomeric excess (ee) was determined by HPLC using
4.6 mmꢂ250 mm Daicel Chiralpak AD-H column. Optical rotations
were measured on a JASCO DIP-1000 digital polarimeter. High-
resolution mass spectra (HRMS) were measured on a JEOL JMS-AX
505wA, JEOL JMS-HX/HX 110A spectrometer. Flash column chro-
matography was carried out using silica gel (230e400 mesh). For
thin-layer chromatography (TLC) analysis, Merck precoated TLC
plates (silica gel 60 GF254, 0.25 mm) were used. All solvents and
commercially available chemicals were used without additional
purification. Ethyl 2-(hydroxymethyl)acrylate (6) was prepared
according to reported procedures.7
1H NMR (300 MHz, CDCl3)
d 6.32 (s, 1H), 5.79 (s, 1H), 4.76 (s, 2H),
4.20 (q, J¼7.14 Hz, 2H), 2.06 (s, 3H), 1.26 (t, J¼7.14 Hz, 3H) ppm; 13C
NMR (75 MHz, CDCl3)
d 170.2, 165.0, 135.3, 127.0, 62.3, 60.8, 20.7,
14.0 ppm; IR (KBr)
n 2984, 1748, 1725, 1643, 1370, 1305, 1231, 1178,
.
1050, 953, 816 cmꢀ1
4.6. (S)-1-tert-Butyl 5-ethyl 2-(diphenylmethylene-amino)-
4.2. Ethyl 2-(benzoyloxymethyl)acrylate (3a)
4-methylenepentanedioate (4)
To a cooled solution of ethyl 2-(hydroxymethyl)acrylate (6)
(1.0 g, 7.68 mmol) in dichloromethane (30 mL) were added tri-
ethylamine (1.61 mL, 11.52 mmol) and benzoyl chloride (1.34 mL,
11.52 mmol). After stirring for 1 h, the reaction mixture was washed
with brine (2ꢂ30 mL), dried over anhydrous Na2SO4, and concen-
trated. The residue was purified by column chromatography (hex-
anes/EtOAc¼10:1) to afford 3a (1.06 g, 59%) as a colorless oil. 1H
A suspension of N-(diphenylmethylene)glycine tert-butyl ester
(2) (30 mg, 0.102 mmol), ethyl 2-(4-methoxybenzoyloxymethyl)
acrylate (3b) (40.4 mg, 0.153 mmol), and chiral phase-transfer
catalyst 7d (6.2 mg, 0.010 mmol) in dichloromethane (0.5 mL) was
cooled at ꢀ78 ꢁC. Solid CsOH$H2O (171 mg, 1.02 mmol) was then
added to the reaction mixture. After stirring at ꢀ78 ꢁC for 14 h, the
reaction mixture was washed with brine (2ꢂ2 mL), dried over an-
hydrous Na2SO4, and concentrated. The residue was purified by
column chromatography (hexanes/EtOAc¼20:1) to afford 4 (38 mg,
NMR (300 MHz, CDCl3)
d 8.06e8.03 (m, 2H), 7.58e7.53 (m, 1H),
7.46e7.40 (m, 2H), 6.40 (s, 1H), 5.91 (s, 1H), 5.05 (s, 2H), 4.24
(q, J¼7.14 Hz, 2H), 1.29 (t, J¼7.14 Hz, 3H) ppm; 13C NMR (100 MHz,
90%) as a pale yellow oil. 1H NMR (300 MHz, CDCl3)
d 7.59e7.57 (m,
CDCl3)
d
165.8, 165.1, 135.5, 133.0, 130.4, 129.5, 128.3, 127.0, 62.7,
2H), 7.39e7.26 (m, 6H), 7.11e7.08 (m, 2H), 6.17 (s, 1H), 5.60 (s, 1H),
4.18 (q, J¼4.38 Hz, 1H), 4.03e3.91 (m, 2H), 3.00 (dd, J¼13.53, 4.2 Hz,
1H), 2.79 (dd, J¼13.35, 8.97 Hz, 1H), 1.43 (s, 9H), 1.11 (t, J¼7.14 Hz,
14.0 ppm; IR (KBr)
n
2983, 1789, 1725, 1602, 1452, 1416, 1315, 1274,
1213, 1175, 1111, 1070, 1027, 712 cmꢀ1; HRMS (FAB): calcd for
[C13H15O4]þ: 235.0970, found: 235.0964.
3H) ppm; 13C NMR (75 MHz, CDCl3)
d 170.6, 170.5, 166.4, 139.5,
136.8, 136.4, 130.1, 128.7, 128.4, 128.2, 128.0, 127.9, 81.1, 64.5, 60.4,
4.3. Ethyl 2-(4-methoxybenzoyloxymethyl)acrylate (3b)
36.0, 28.0, 27.9, 13.9 ppm; IR (KBr) n 2978, 1721, 1626, 1446, 1392,
1368, 1280, 1151, 1028, 950, 846, 781, 698 cmꢀ1; HRMS (FAB): calcd
for [C14H17O5]þ: 408.2175, found: 408.2165.
To a cooled solution of ethyl 2-(hydroxymethyl)acrylate (6)
(1.0 g, 7.68 mmol) in dichloromethane (30 mL) were added tri-
ethylamine (1.61 mL, 11.52 mmol) and 4-methoxybenzoyl chloride
(2.62 g, 15.36 mmol). After stirring for 3 h, the reaction mixture was
washed with brine (2ꢂ30 mL), dried over anhydrous Na2SO4, and
concentrated. The residue was purified by column chromatography
(hexanes/EtOAc¼20:1) to afford 3b (634 mg, 31%) as a white solid.
4.7. (S)-1-tert-Butyl 5-ethyl 2-benzamido-
4-methylenepentanedioate (8)
A mixture of 4 (37.4 mg, 0.092 mmol), 1.0 M citric acid (1.5 mL),
and tetrahydrofuran (1.5 mL) was stirred at room temperature for
2 h. Sodium bicarbonate was added to the mixture until the pH
reached 7e8, and then benzoyl chloride (0.036 mL, 0.306 mmol)
was added. The mixture was stirred for 5 h. The tetrahydrofuran
was then evaporated and the residue diluted with ethyl acetate
(3 mL). The mixture was washed with brine (2ꢂ3 mL), dried over
anhydrous Na2SO4, and concentrated. The residue was purified by
Mp 40 ꢁC; 1H NMR (300 MHz, CDCl3)
d 8.13e7.98 (m, 2H),
6.93e6.88 (m, 2H), 6.38 (s, 1H), 5.89 (s, 1H), 5.02 (s, 2H), 4.24
(q, J¼7.14 Hz, 2H), 3.85 (s, 3H), 1.28 (t, J¼7.14 Hz, 3H) ppm; 13C NMR
(75 MHz, CDCl3) d 165.6, 165.2, 135.7, 131.6, 126.8, 122.2, 113.6, 62.5,
60.9, 55.4, 14.1 ppm; IR (KBr)
n 2980, 1721, 1606, 1511, 1458, 1366,
1309, 1258, 1167, 1101, 1028, 848, 769, 696 cmꢀ1; HRMS (FAB): calcd
for [C14H17O5]þ: 265.1076, found: 265.1083.
column chromatography (hexanes/EtOAc¼10:1) to afford
8
(32 mg, 90%) as
a
colorless oil. 1H NMR (300 MHz, CDCl3)
4.4. Ethyl 2-(4-nitrobenzoyloxymethyl)acrylate (3c)
d
7.80e7.77 (m, 2H), 7.50e7.38 (m, 3H), 7.14 (d, J¼6.96, 1H), 6.26 (s,
1H), 5.70 (s, 1H), 4.81e4.74 (m, 1H), 4.25e4.15 (m, 2H), 2.93e2.78
(m, 2H), 1.45 (s, 9H), 1.27 (t, J¼7.14 3H) ppm; 13C NMR (75 MHz,
To a cooled solution of ethyl 2-(hydroxymethyl)acrylate (6)
(1.0 g, 7.68 mmol) in dichloromethane (30 mL) were added tri-
ethylamine (1.64 mL, 11.78 mmol) and 4-nitrobenzoyl chloride
(2.18 g, 11.78 mmol). After stirring for 10 min, the reaction mixture
was washed with brine (2ꢂ30 mL), dried over anhydrous Na2SO4,
and concentrated. The residue was purified by column chroma-
tography (hexanes/EtOAc¼20:1) to afford 3c (1.21 g, 55%) as a pale
CDCl3)
d 170.5, 167.2, 166.7, 136.1, 133.8, 131.4, 128.4, 126.9, 82.2,
61.1, 53.0, 34.4, 27.8, 25.2, 13.9 ppm; IR (KBr)
n 3347, 2979, 1719,
1645, 1580, 1533, 1488, 1368, 1309, 1228, 1154, 1026, 953, 846,
714 cmꢀ1; HRMS (FAB): calcd for [C19H26O5N]þ: 348.1811, found:
348.1803. Enantiopurity was determined by chiral HPLC analysis
(DIACEL Chiralcel AD-H, hexanes/2-propanol¼9:1), flow
yellow solid. Mp 78 ꢁC; 1H NMR (300 MHz, CDCl3)
d
8.29e8.18
rate¼1.0 mL/min, 23 ꢁC,
l¼254 nm, retention time, minor
(m, 4H), 6.44 (s,1H), 5.93 (s,1H), 5.08 (s, 2H), 4.25 (q, J¼7.14 Hz, 2H),
10.4 min, minor 20.7 min, 99% ee.
1.29 (t, J¼7.14 Hz, 3H) ppm; 13C NMR (100 MHz, CDCl3)
d 165.0,
164.1, 150.6, 135.2, 135.1, 130.7, 128.2, 123.5, 63.8, 61.1, 14.1 ppm; IR
4.8. (S)-4-Methyleneglutamic acid hydrochloride (1$HCl)
(KBr)
963, 878, 854, 819, 784, 719 cmꢀ1
[C13H14O6N]þ: 280.0821, found: 280.0813.
n
3114, 1725, 1648, 1517, 1460, 1406, 1348, 1272, 1117, 1009,
;
HRMS (FAB): calcd for
A mixture of 8 (109 mg, 0.314 mmol) and 6.0 M HCl (2 mL) was
refluxed for 24 h. Concentration of the reaction mixture in vacuo