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D.B. Baker et al. / Tetrahedron 69 (2013) 3690e3697
4.8. (E)-N-Methoxy-N-methyl-3-(naphthalen-2-yl)acrylamide
(2e)
(CDCl3, 126 MHz):
d
¼167.8, 163.0 (d, JCeF¼249 Hz), 151.1, 139.0,
128.0 (d, JCeF¼8 Hz), 115.9, 115.3 (d, JCeF¼21 Hz), 61.6, 32.3,
18.1 ppm; 19F{1H} NMR (CDCl3, 471 MHz):
d¼ꢂ113.2 ppm; MS
General procedure A: Compound 1 (50 mg, 0.43 mmol) was
employed. The Heck reaction was carried out for 5 h. The crude
material was purified by FCC eluting with 40% EtOAcepetrol
affording 2e as a white solid (88 mg, 82%).
(ESIþ) calculated for C12H15FNO2 [MþH]þ: 224.1081; found:
224.1080; FTIR 1647, 1621, 1601, 1509, 1233, 1162, 913, 831, 748,
743 cmꢂ1; Rf 0.25 (25% EtOAcepetrol).
1H NMR (CDCl3, 400 MHz):
d
¼7.95 (s,1H), 7.90 (d, J¼15.5 Hz,1H),
4.13. (E)-N-Methoxy-3-(4-methoxyphenyl)-N-methylbut-2-
enamide (5d)
7.87e7.78 (m, 3H), 7.72 (dd, J¼8.5, 1.5 Hz, 1H), 7.55e7.42 (m, 2H),
7.15 (d, J¼15.5 Hz, 1H), 3.78 (s, 3H), 3.33 ppm (s, 3H); 13C NMR
(CDCl3, 126 MHz):
d
¼167.0, 143.5, 134.1, 133.4, 132.7, 129.7, 128.5,
General procedure B: Compound 3 (50 mg, 0.39 mmol) was
employed. The Heck reaction was carried out for 15 h. The crude
material was purified by FCC eluting with 25% EtOAcepetrol
affording 5d as a colorless oil (68 mg, 74%).
127.8, 127.0, 126.6, 123.8, 116.0, 62.0, 32.6 ppm; mp 85e87 ꢀC
(CH2Cl2epetrol); Spectroscopic data is consistent with those found
in the literature.25
1H NMR (CDCl3, 400 MHz):
d
¼7.45 (d, J¼8.5 Hz, 2H), 6.90 (d,
4.9. (E)-3-(1H-Indol-5-yl)-N-methoxy-N-methylacrylamide (2f)
J¼8.5 Hz, 2H), 6.55 (s, 1H), 3.81 (s, 3H), 3.72 (s, 3H), 3.26 (s, 3H),
2.52 ppm (s, 3H); 13C NMR (CDCl3, 126 MHz):
d
¼168.2, 160.1, 151.8,
General procedure A: Compound 1 (50 mg, 0.43 mmol) was
employed. The Heck reaction was carried out for 4 h. The crude
material was purified by FCC eluting with 50% EtOAcepetrol
affording 2f as a colorless oil (95 mg, 94%).
135.2, 127.6, 114.2, 113.8, 61.6, 55.3, 32.4, 17.8 ppm; MS (ESIþ) cal-
culated for C13H18NO3 [MþH]þ: 236.1281; found: 236.1276; FTIR
1644, 1602, 1513, 1290, 1247, 1181, 1031, 979, 829, 679 cmꢂ1; Rf 0.30
(25% EtOAcepetrol).
1H NMR (CDCl3, 400 MHz):
d
¼9.27 (s, 1H), 7.91 (d, J¼15.5 Hz,
1H), 7.81 (s, 1H), 7.42 (dd, J¼8.5, 1.5 Hz, 1H), 7.35 (d, J¼8.5 Hz, 1H),
4.14. (E)-3-(1H-Indol-5-yl)-N-methoxy-N-methylbut-2-enam-
ide (5e)
7.18 (t, J¼2.5 Hz, 1H), 7.02 (d, J¼15.5 Hz, 1H), 6.53 (s, 1H), 3.75 (s,
3H), 3.31 ppm (s, 3H); 13C NMR (CDCl3, 126 MHz):
d
¼168.0, 145.7,
137.2, 128.2, 126.8, 125.7, 122.1, 121.6, 112.4, 111.8, 103.0, 61.9,
32.7 ppm; MS (ESIþ) calculated for C13H15N2O2 [MþH]þ: 231.1128;
found: 231.1120; FTIR 1642, 1593, 1475, 1420, 1385, 1349, 1332,
General procedure B: Compound 3 (50 mg, 0.39 mmol) was
employed. The Heck reaction was carried out for 15 h. The crude
material was purified by FCC eluting with 40% EtOAcepetrol
affording 5e as a colorless oil (67 mg, 70%).
1295, 1095, 1002, 909, 769, 730 cmꢂ1
.
1H NMR (CDCl3, 400 MHz):
d¼8.53 (s, 1H), 7.79 (s, 1H), 7.41e7.31
4.10. (E)-N-Methoxy-N-methyl-3-phenylbut-2-enamide (5a)
(m, 2H), 7.24e7.20 (m, 1H), 6.64 (s, 1H), 6.60e6.55 (m, 1H), 3.73 (s,
3H), 3.29 (s, 3H), 2.63 ppm (s, 3H); 13C NMR (CDCl3, 126 MHz):
General procedure B: Compound 3 (50 mg, 0.39 mmol) was
employed. The Heck reaction was carried out for 16 h. The crude
material was purified by FCC eluting with 20%e30% EtOAcepetrol
affording 5a as a colorless oil (53 mg, 66%).
d
¼168.5, 154.0, 136.1, 134.9, 127.9, 125.2, 120.7, 118.9, 114.3, 111.0,
103.1, 61.6, 32.6, 18.5 ppm; MS (ESIþ) calculated for C14H17N2O2
[MþH]þ: 245.1285; found: 245.1285; FTIR 1640, 1573, 1475, 1389,
1380, 1319, 1302, 1111, 1076, 1019, 931, 749, 676 cmꢂ1; Rf 0.15 (30%
EtOAcepetrol).
1H NMR (CDCl3, 400 MHz):
d
¼7.51e7.45 (m, 2H), 7.41e7.33 (m,
3H), 6.57 (s, 1H), 3.71 (s, 3H), 3.27 (s, 3H), 2.51 ppm (d, J¼1 Hz, 3H);
13C NMR (CDCl3, 126 MHz):
d
¼168.0, 152.3, 143.0, 128.6, 128.5, 126.3,
4.15. (E)-N-Methoxy-N-methyl-3-(4-(trifluoromethyl)phenyl)
but-2-enamide (5f)
116.0, 61.6, 32.4, 18.0 ppm; MS (ESIþ) calculated for C12H15NNaO2
[MþNa]þ: 228.0995; found: 228.0995; FTIR 1647, 1620, 1446, 1368,
1178, 1151, 1107, 978, 913, 696 cmꢂ1; Rf 0.55 (50% EtOAcepetrol).
General procedure B: Compound 3 (50 mg, 0.39 mmol) was
employed. The Heck reaction was carried out for 15 h. The crude
material was purified by FCC eluting with 20%e30% EtOAcepetrol
affording 5f as a colorless oil (71 mg, 67%).
¼7.64 (d, J¼8.5 Hz, 2H), 7.57 (d,
J¼8.5 Hz, 2H), 6.59 (s, 1H), 3.72 (s, 3H), 3.28 (s, 3H), 2.53 ppm (s,
3H); 13C NMR (CDCl3, 126 MHz):
4.11. (E)-N-Methoxy-N-methyl-3-(p-tolyl)but-2-enamide (5b)
General procedure B: Compound 3 (50 mg, 0.39 mmol) was
employed. The Heck reaction was carried out for 16 h. The crude
material was purified by FCC eluting with 20%e30% EtOAcepetrol
affording 5b as a colorless oil (61 mg, 71%).
1H NMR (CDCl3, 500 MHz):
d
d¼167.5, 150.6, 146.5, 130.5 (q,
JCeF¼33 Hz), 126.7, 125.5 (q, JCeF¼4 Hz), 124.0 (q, JCeF¼272 Hz),
1H NMR (CDCl3, 500 MHz):
d
¼7.40 (d, J¼8.0 Hz, 2H), 7.18 (d,
117.9, 61.7, 32.3, 18.0 ppm; 19F{1H} NMR (CDCl3, 471 MHz):
J¼8.0 Hz, 2H), 6.56 (s, 1H), 3.70 (s, 3H), 3.26 (s, 3H), 2.52 (s, 3H),
d
¼ꢂ62.6 ppm; MS (ESIþ) calculated for C13H14F3NNaO2 [MþNa]þ:
2.37 ppm (s, 3H); 13C NMR (CDCl3, 126 MHz):
d
¼168.1, 152.2, 140.1,
296.0869; found: 296.0872; FTIR 1651, 1617, 1325, 1167, 1117, 1015,
138.7, 129.2, 126.2, 115.2, 61.6, 32.3, 21.2, 17.9 ppm; MS (ESIþ) cal-
culated for C13H17NNaO2 [MþNa]þ: 242.1152; found: 242.1152; FTIR
1647, 1618, 1367, 1177, 1102, 1017, 978, 913, 814, 732 cmꢂ1; Rf 0.35
(20% EtOAcepetrol).
852, 689 cmꢂ1; Rf 0.35 (30% EtOAcepetrol).
4.16. (E)-N-Methoxy-N-methyl-3,5-diphenylpent-2-enamide
(6a)
4.12. (E)-3-(4-Fluorophenyl)-N-methoxy-N-methylbut-2-
enamide (5c)
General procedure B: Compound 4 (50 mg, 0.23 mmol) was
employed. The Heck reaction was carried out for 15 h. The crude
material was purified by FCC eluting with 20%e30% EtOAcepetrol
affording 6a as a colorless oil (53 mg, 76%).
Oxidative Heck conditions: A flame dried microwave vial, fitted
with a magnetic follower, was charged with potassium fluoride
(107 mg, 1.84 mmol), 4-hydroxy TEMPO (159 mg, 0.92 mmol),
phenylboronic acid (224 mg, 1.84 mmol), and Pd(OAc)2 (5.2 mg,
0.023 mmol). The reaction was sealed using a crimped microwave
General procedure B: Compound 3 (50 mg, 0.39 mmol) was
employed. The Heck reaction was carried out for 15 h. The crude
material was purified by FCC eluting with 20%e30% EtOAcepetrol
affording 5c as a colorless oil (56 mg, 70%).
1H NMR (CDCl3, 500 MHz):
d
¼7.49e7.42 (m, 2H), 7.10e7.01 (m,
2H), 6.53 (s, 1H), 3.71 (s, 3H), 3.27 (s, 3H), 2.51 ppm (s, 3H); 13C NMR