The Journal of Organic Chemistry
Note
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concentrated by rotary evaporation. The crude product was purified by
flash column chromatography with hexanes/EtOAc.
(103.1 mg, 68% yield, >98:2 E/Z): H NMR (500 MHz, CDCl3) δ
7.27 (d, J = 8.7, 2H), 6.83 (d, J = 7.2 Hz, 2H), 6.33 (d, J = 15.6 Hz,
1H), 6.02−5.87 (br s, 1H), 4.54−4.29 (br m, 1H), 3.79 (m, 3H),
3.50−3.31 (br s, 2H), 2.16−1.98 (br s, 1H), 1.98−1.66 (m, 3H), 1.42
(s, 9H); 13C{1H} NMR (126 MHz, CDCl3) δ 159.1, 154.8, 130.0,
129.0, 128.7, 127.5, 114.1, 79.2, 59.2, 55.4, 46.4, 32.8, 28.7, 23.2; IR
(neat) ν = 2972, 1686, 1607, 1510, 1477, 1455, 1389, 1363, 1300,
1244, 1161, 1105, 1033, 961, 917, 842, 806, 765, 731, 524 cm−1; MS
(ESI) m/z calcd for C18H25NO3Na ([M + Na]+) 326.1744, found
326.1732.
tert-Butyl (E)-2-Styrylpyrrolidine-1-carboxylate (3a). The general
procedure provided the titled compound as a white solid (99.6 mg,
73% yield, >98:2 E/Z): mp = 96−98 °C; 1H NMR (500 MHz,
CDCl3) δ 7.33 (m, 4H), 7.21 (t, J = 7.4 Hz, 1H), 6.40 (d, J = 15.6 Hz,
1H), 6.18−5.99 (br s, 1H), 4.60−4.32 (br m, 1H), 3.53−3.30 (br s,
2H), 2.15−1.99 (br s, 1H), 1.99−1.70 (m, 3H), 1.43 (s, 9H); 13C{1H}
NMR (126 MHz, CDCl3) δ 154.8, 137.2, 130.9, 129.6, 128.6, 127.4,
126.4, 79.3, 59.1, 46.4, 32.8, 28.7, 23.2; IR (neat) ν = 2973, 2875,
1687, 1493, 1477, 1388, 1363, 1253, 1160, 1107, 960, 917, 895, 877,
860, 771, 747, 692, 507 cm−1; MS (ESI) m/z calcd for C17H23NO2Na
([M + Na]+) 296.1626, found 296.1615.
tert-Butyl (E)-2-(2-(Benzo[d][1,3]dioxol-5-yl)vinyl)pyrrolidine-1-
carboxylate (3h). The general procedure provided the titled
compound as a colorless oil (88.8 mg, 56% yield, >98:2 E/Z): H
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tert-Butyl (E)-2-(4-Methyl)styrylpyrrolidine-1-carboxylate (3b).
NMR (500 MHz, CDCl3) δ 6.89 (s, 1H), 6.75 (m, 2H), 6.30 (d, J =
15.3 Hz, 1H), 6.00−5.83 (br m, 3H), 4.54−4.28 (br m, 1H), 3.51−
3.32 (br s, 2H), 2.14−2.00 (br s, 1H), 2.00−1.69 (m, 3H), 1.42 (s,
9H); 13C{1H} NMR (126 MHz, CDCl3) δ 148.1, 147.1, 131.7, 129.2,
120.9, 108.4, 105.8, 101.1, 79.3, 59.1, 46.4, 32.8, 28.7, 23.4; IR (neat) ν
= 2973, 2878, 1685, 1502, 1489, 1444, 1390, 1364, 1248, 1189, 1161,
1099, 1037, 959, 931, 886, 860, 799, 773, 732 cm−1; MS (ESI) m/z
calcd for C18H23NO4Na ([M + Na]+) 340.1525, found 340.1518.
tert-Butyl (E)-2-(4-Fluoro)styrylpyrrolidine-1-carboxylate (3i). The
general procedure provided the titled compound as a colorless oil
(91.7 mg, 63% yield, 96:4 E/Z): 1H NMR (500 MHz, CDCl3) δ 7.30
(dd, J = 8.4, 5.4 Hz, 2H), 6.99 (dd, J = 8.7, 6.9 Hz, 2H), 6.35 (d, J =
14.7 Hz, 1H), 6.07−5.93 (br s, 1H), 4.54−4.28 (br m, 1H), 3.51−3.35
(br s, 2H), 2.14−2.01 (br s, 1H), 2.01−1.75 (m, 3H), 1.42 (s, 9H);
The general procedure provided the titled compound as a colorless
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oil (94.8 mg, 66% yield, >98:2 E/Z): H NMR (500 MHz, CDCl3) δ
7.24 (d, J = 8.0 Hz, 2H), 7.11 (d, J = 7.6 Hz, 2H), 6.36 (d, J = 15.4 Hz,
1H), 6.11−5.95 (br s, 1H), 4.56−4.30 (br m, 1H), 3.53−3.32 (br s,
2H), 2.33 (s, 3H), 2.14−1.99 (br s, 1H), 1.99−1.67 (m, 3H), 1.42 (s,
9H); 13C{1H} NMR (126 MHz, CDCl3) δ 154.8, 137.1, 134.4, 129.9,
129.5, 129.3, 126.3, 79.3, 59.2, 46.4, 32.7, 28.7, 23.2, 21.3; IR (neat) ν
= 2972, 2927, 2874, 1688, 1513, 1477, 1454, 1388, 1363, 1253, 1161,
1107, 1040, 962, 917, 896, 859, 800, 770, 510 cm−1; MS (ESI) m/z
calcd for C18H25NO2 (M+) 287.1885, found 287.1882.
tert-Butyl (E)-2-(3-Trifluoromethyl)styrylpyrrolidine-1-carboxylate
(3c). The general procedure provided the titled compound as a
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colorless oil (127.9 mg, 75% yield, 98:2 E/Z): H NMR (500 MHz,
CDCl3) δ 7.61−7.34 (m, 4H), 6.42 (d, J = 14.5 Hz, 1H), 6.28−6.08
(br s, 1H), 4.63−4.28 (br m, 1H), 3.58−3.27 (br s, 2H), 2.19−1.98
(br s, 1H), 1.98−1.63 (m, 3H), 1.41 (s, 9H); 13C{1H} NMR (126
MHz, CDCl3) δ 154.7, 140.7, 138.0, 133.8, 129.1, 128.2, 126.5, 125.6,
13C{1H} NMR (126 MHz, CDCl3) δ 162.3 (d, JC−F = 246.1 Hz),
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154.7, 133.3, 130.8, 128.4, 127.8, 115.6, 79.3, 59.1, 46.4, 32.7, 28.6,
23.2; 19F NMR (470.8 MHz, CDCl3) δ −115.0, −115.3; IR (neat) ν =
2974, 2876, 1687, 1601, 1508, 1478, 1454, 1390, 1364, 1226, 1158,
1110, 1093, 963, 897, 852, 810, 790, 771, 517 cm−1; MS (ESI) m/z
calcd for C17H22FNO2Na ([M + Na]+) 314.1544, found 314.1540.
tert-Butyl (E)-2-(4-Bromo)styrylpyrrolidine-1-carboxylate (3j).
The general procedure provided the titled compound as a white
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124.4 (q, JC−F = 272.2 Hz), 123.9, 79.5, 59.0, 46.5, 32.6, 28.6, 23.2;
19F NMR (470.8 MHz, CDCl3) δ −62.5, −62. Characterization data
matched that reported in the literature.5
tert-Butyl (E)-2-(4-Cyano)styrylpyrrolidine-1-carboxylate (3d).
The general procedure provided the titled compound as a colorless
oil (114.8 mg, 77% yield, >98:2 E/Z): 1H NMR (500 MHz, CDCl3) δ
7.57 (d, J = 7.8 Hz, 2H), 7.41 (d, J = 8.0 Hz, 2H), 6.40 (d, J = 14.9 Hz,
1H), 6.31−6.14 (br s, 1H), 4.58−4.32 (br m, 1H), 3.53−3.30 (br s,
2H), 2.18−2.00 (br s, 1H), 1.97−1.62 (m, 3H), 1.40 (s, 9H); 13C{1H}
NMR (126 MHz, CDCl3) δ 154.7, 141.7, 135.2, 132.5, 128.0, 126.9,
119.1, 110.7, 100.1, 79.5, 59.0, 46.5, 32.6, 28.6, 23.2; IR (neat) ν =
2974, 2225, 1686, 1603, 1504, 1477, 1454, 1389, 1364, 1301, 1254,
1161, 1111, 968, 918, 896, 860, 811, 772, 547 cm−1; MS (ESI) m/z
calcd for C18H22N2O2Na ([M + Na]+) 321.1579, found 321.1579.
tert-Butyl (E)-2-(4-Acetyl)styrylpyrrolidine-1-carboxylate (3e). The
general procedure provided the titled compound as a colorless oil
(116.6 mg, 74% yield, 98:2 E/Z): 1H NMR (500 MHz, CDCl3) δ 7.87
(d, J = 8.0 Hz, 2H), 7.40 (d, J = 8.4, 2H), 6.42 (d, J = 14.8 Hz, 1H),
6.30−6.15 (br s, 1H), 4.58−4.32 (br m, 1H), 3.50−3.33 (br s, 2H),
2.56 (s, 3H), 2.17−2.02 (br s, 1H), 1.98−1.74 (m, 3H), 1.39 (s, 9H);
13C{1H} NMR (126 MHz, CDCl3) δ 197.6, 154.7, 141.9, 136.0, 134.0,
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semisolid (107.0 mg, 61% yield, >98:2 E/Z): H NMR (500 MHz,
CDCl3) δ 7.40 (d, J = 8.1 Hz, 2H), 7.20 (d, J = 8.2 Hz, 2H), 6.32 (d, J
= 15.2 Hz, 1H), 6.16−6.00 (br s, 1H), 4.57−4.28 (br m, 1H), 3.52−
3.32 (br s, 2H), 2.14−2.01 (br s, 1H), 1.97−1.65 (m, 3H), 1.40 (s,
9H); 13C{1H} NMR (126 MHz, CDCl3) δ 154.7, 136.2, 131.7, 129.1,
128.4, 127.9, 121.1, 79.4, 59.1, 46.5, 32.6, 28.6, 23.3; IR (neat) ν =
2973, 2875, 1687, 1487, 1454, 1389, 1364, 1253, 1161, 1109, 1072,
1008, 962, 917, 896, 854, 802, 773, 736, 504 cm−1; MS (ESI) m/z
calcd for C17H22BrNO2Na ([M + Na]+) 374.0732, found 374.0727.
tert-Butyl (E)-2-(3-Bromo)styrylpyrrolidine-1-carboxylate (3k).
The general procedure provided the titled compound as a white
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solid (101.8 mg, 58% yield, >98:2 E/Z): mp = 53−55 °C; H NMR
(500 MHz, CDCl3) δ 7.49 (s, 1H), 7.33 (d, J = 8.1 Hz, 1H), 7.24 (d, J
= 7.8 Hz, 1H), 7.17 (d, J = 7.9 Hz, 1H), 6.31 (d, J = 16.2 Hz, 1H),
6.17−6.02 (br s, 1H), 4.56−4.31 (br m, 1H), 3.51−3.28 (br s, 2H),
2.18−1.99 (br s, 1H), 1.99−1.64 (m, 3H), 1.41 (s, 9H); 13C{1H}
NMR (126 MHz, CDCl3) δ 154.7, 139.4, 132.6, 130.2, 129.6, 129.2,
128.2, 127.9, 125.1, 79.4, 59.0, 46.5, 32.7, 28.7, 23.1; IR (neat) ν =
2973, 2930, 1687, 1590, 1560, 1475, 1454, 1388, 1364, 1250, 1161,
1108, 1071, 994, 959, 906, 876, 860, 773, 684 cm−1; MS (ESI) m/z
calcd for C17H22BrNO2Na ([M + Na]+) 374.0732, found 374.0730.
tert-Butyl (E)-2-(2-(Pyridin-2-yl)vinyl)pyrrolidine-1-carboxylate
(3l). The general procedure provided the titled compound as a
128.9, 128.6, 126.4, 79.4, 59.1, 46.5, 28.6, 26.7, 23.2; IR (neat) ν =
2973, 2875, 1678, 1601, 1478, 1454, 1389, 1362, 1302, 1266, 1160,
1106, 956, 918, 896, 859, 810, 773, 730, 593 cm−1; MS (ESI) m/z
calcd for C19H25NO3 ([M + Na]+) 338.1732, found 338.1737.
tert-Butyl (E)-2-(4-Methoxycarbonyl)styrylpyrrolidine-1-carboxy-
late (3f). The general procedure provided the titled compound as an
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off-white semisolid (125.8 mg, 76% yield, 97:3 E/Z); H NMR (500
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colorless oil (97.3 mg, 71% yield, >98:2 E/Z): H NMR (500 MHz,
MHz, CDCl3) δ 7.96 (d, J = 7.4 Hz, 2H), 7.39 (d, J = 7.9 Hz, 2H),
6.42 (d, J = 13.0 Hz, 1H), 6.30−6.13 (br s, 1H), 4.58−4.33 (br m,
1H), 3.89 (s, 3H), 3.51−3.34 (br s, 2H), 2.16−2.01 (br s, 1H), 2.00−
1.69 (m, 3H), 1.40 (s, 9H); 13C{1H} NMR (126 MHz, CDCl3) δ
167.0, 154.7, 141.7, 137.2, 133.8, 130.0, 128.7, 126.3, 79.4, 59.1, 52.1,
46.5, 32.7, 28.6, 23.2; IR (neat) ν = 2974, 2877, 1719, 1690, 1606,
1568, 1478, 1434, 1391, 1365, 1278, 1164, 1108, 1017, 968, 918, 897,
867, 764, 698 cm−1; MS (ESI) m/z calcd for C19H25NO4Na ([M +
Na]+) 354.1681, found 354.1678.
CDCl3) δ 8.49 (d, J = 4.9 Hz, 1H), 7.56 (t, J = 7.7 Hz, 1H), 7.18 (d, J
= 8.2 Hz, 1H), 7.06 (t, J = 6.0 Hz, 1H), 6.58 (d, J = 15.6 Hz, 1H),
6.52−6.38 (br m, 1H), 4.58−4.35 (br m, 1H), 3.53−3.18 (br s, 2H),
2.12−1.97 (br s, 1H), 1.98−1.72 (m, 3H), 1.37 (s, 9H); 13C{1H}
NMR (126 MHz, CDCl3) δ 155.5, 154.7, 149.6, 136.6, 135.4, 129.3,
122.0, 121.7, 79.3, 58.8, 58.4, 46.7, 46.3, 32.4, 31.6, 28.6, 23.8, 23.1; IR
(neat) ν = 2973, 2875, 1686, 1585, 1564, 1470, 1430, 1388, 1363,
1254, 1150, 1109, 1089, 990, 968, 918, 900, 860, 766, 745 cm−1; MS
(ESI) m/z calcd for C16H23N2O2 ([M + H]+) 275.1760, found
275.1761.
tert-Butyl (E)-2-(4-Methoxy)styrylpyrrolidine-1-carboxylate (3g).
The general procedure provided the titled compound as a colorless oil
D
J. Org. Chem. XXXX, XXX, XXX−XXX