Paper
Organic & Biomolecular Chemistry
The aldehyde (2.0 eq.) was then added and the reaction
(E)-1-(3-Mesitylacryloyl)-5,6-dihydropyridin-2(1H)-one (14).
warmed to room temperature and stirred overnight. Saturated Compound 14 (20.0 mg, 57%) was prepared via the general
NH4Cl(aq.) was added and the aqueous phase was extracted procedure as a pale yellow solid. M.p.: 104–105 °C [lit.
with EtOAc. The combined organic layers were dried over 104 °C];18c νmax/cm−1 3691, 3067, 3011, 2926, 2857, 1687, 1608;
MgSO4, filtered and concentrated in vacuo. The crude product δH (400 MHz, CDCl3) 2.28 (3H, s), 2.38 (6H, s), 2.48 (2H, tdd,
was purified by flash column chromatography.
J = 6.4, 4.2, 1.8 Hz), 4.05 (2H, t, J = 6.4 Hz), 6.02 (1H, dt, J = 9.7,
Piperlongumine (1). Piperlongumine 1 (14.0 mg, 51%) was 1.8 Hz), 6.89 (2H, s), 6.93 (1H, dt, J = 9.7, 4.2 Hz), 7.09 (1H, d,
prepared via the general procedure as a white solid. M.p.: J = 16.0 Hz), 7.91 (1H, d, J = 16.0 Hz); δC (100 MHz, CDCl3)
120–121 °C [lit. 122–123 °C];18a νmax/cm−1 3692, 3606, 1686, 21.2, 21.3, 24.9, 41.8, 126.0, 126.8, 129.3, 131.7, 138.3, 137.4,
1603, 1583; δH (400 MHz, CDCl3) 2.47 (2H, tdd, J = 6.4, 4.2, 142.0, 145.5, 165.8, 169.2; Found (ESI): 270.1494 [MH]+,
1.9 Hz), 3.86 (3H, s), 3.87 (6H, s), 4.02 (2H, t, J = 6.4 Hz), 6.04 (required C17H20NO2 270.1489); Found (ESI): 292.1314 [MNa]+,
(1H, dt, J = 9.7, 1.9 Hz), 6.79 (2H, s), 6.93 (1H, dt, J = 9.7, 4.2 (required C17H19NO2Na 292.1308). Spectroscopic data in
Hz), 7.41 (1H, d, J = 15.6 Hz), 7.87 (1H, d, J = 15.6 Hz); accord with the literature.18c
δC (100 MHz, CDCl3) 24.9, 41.8, 56.3, 61.0, 105.6, 121.2, 125.9,
128.3, 139.9, 130.7, 143.9, 145.7, 166.0, 169.0; Found (ESI): one (15). Compound 15 (10.0 mg, 45%) was prepared via the
318.1327 [MH]+, (required C17H20NO5 318.1336); Found (ESI): general procedure as
white solid. M.p.: 178–180 °C;
340.1153 [MNa]+, (required C17H19NO5Na 340.1155). Spectro- νmax/cm−1 3691, 3606, 1688, 1602, 1522; δH (400 MHz, CDCl3)
scopic data in accord with the literature.18c
2.51 (2H, tdd, J = 6.4, 4.2, 1.9 Hz), 4.05 (2H, t, J = 6.4 Hz), 6.06
(E)-1-(3-(4-Nitrophenyl)acryloyl)-5,6-dihydropyridin-2(1H)-
a
(E)-1-(3-(4 Methoxyphenyl)prop-2-enoyl)-5,6-dihydropyridin- (1H, dt, J = 9.7, 1.9 Hz), 6.98 (1H, dt, J = 9.7, 4.2 Hz), 7.58 (1H,
2(1H)-one (11). Compound 11 (23.0 mg, 52%) was prepared via d, J = 15.7 Hz), 7.70 (1H, d, J = 15.7 Hz), 7.69–7.72 (2H, m),
the general procedure as a white solid. M.p.: 76–77 °C; 8.21–8.24 (2H, m); δC (100 MHz, CDCl3) 24.9, 41.8, 124.2,
νmax/cm−1 3691, 3606, 3011, 2937, 2840, 1686, 1601, 1513; 128.9, 125.7, 126.3, 140.0, 141.5, 146.2, 148.4, 165.9, 168.3;
δH (400 MHz, CDCl3) 2.46 (2H, tdd, J = 6.4, 4.2, 1.9 Hz), 3.83 Found (ESI): 273.0877 [MH]+, (required C14H13N2O4 273.0870);
(3H, s), 4.03 (2H, t, J = 6.4 Hz), 6.03 (1H, dt, J = 9.7, 1.9 Hz), Found (ESI): 295.0690 [MNa]+, (required C14H12N2O4Na
6.87–6.90 (2H, m), 6.92 (1H, dt, J = 9.7, 4.2 Hz), 7.41 (1H, d, J = 295.0689).
15.6 Hz), 7.49–7.57 (2H, m), 7.73 (1H, d, J = 15.6 Hz);
(E)-1-(3-(4-Fluoro-3 methoxyphenyl)acryloyl)-5,6-dihydropyri-
δC (100 MHz, CDCl3) 24.8, 41.6, 55.4, 114.2, 119.4, 126.0, din-2(1H)-one (16). Compound 16 (13.0 mg, 52%) was pre-
127.9, 130.0, 143.6, 145.3, 161.3, 165.8, 169.2; Found (ESI): pared via the general procedure as a white solid. M.p.:
258.1124 [MH]+, (required C15H16NO3 258.1125); Found (ESI): 112–114 °C; νmax/cm−1 3692, 3607, 3012, 2928, 2855, 1687,
280.0943 [MNa]+, (required C15H15NO3Na 280.0944). Spectro- 1602, 1515; δH (400 MHz, CDCl3) 2.48 (2H, tdd, J = 6.4, 4.2, 1.9
scopic data in accord with the literature.13b
Hz), 3.92 (3H, s), 4.04 (2H, t, J = 6.4 Hz), 6.05 (1H, dt, J = 9.7,
(E)-1-(3-(4-Bromophenyl)acryloyl)-5,6-dihydropyridin-2(1H)- 1.9 Hz), 6.95 (1H, dt, J = 9.7, 4.2 Hz), 7.04–7.17 (3H, m), 7.43
one (12). Compound 12 (23.0 mg, 60%) was prepared via the (1H, dd, J = 15.6, 0.6 Hz), 7.68 (1H, d, J = 15.6 Hz);
general procedure as a white solid. M.p.: 93–94 °C [lit. δC (100 MHz, CDCl3) 24.9, 41.8, 56.4, 112.6 (d, J = 2.3 Hz),
93 °C];18c νmax/cm−1 3692, 3607, 1686, 1618, 1602; 116.5 (d, J = 18.5 Hz), 121.8 (d, J = 2.3 Hz), 122.1 (d, J = 7.5 Hz),
δH (400 MHz, CDCl3) 2.48 (2H, tdd, J = 6.5, 4.2, 1.9 Hz), 4.03 126.0, 131.9 (d, J = 3.9 Hz), 142.9, 145.7, 148.1 (d, J = 10.8 Hz),
(2H, t, J = 6.5 Hz), 6.04 (1H, dt, J = 9.7, 1.9 Hz), 6.95 (1H, dt, J = 153.8 (d, J = 251.5 Hz), 166.0, 168.9; δF (376 MHz, CDCl3)
9.7, 4.2 Hz), 7.42–7.46 and 7.48–7.52 (4H, m), 7.49 (1H, d, J = −131.6; Found (ESI): 276.1023 [MH]+, (required C15H15FNO3
15.6 Hz), 7.65 (1H, d, J = 15.6 Hz); δC (100 MHz, CDCl3) 24.9, 276.1030); Found (ESI): 298.0842 [MNa]+, (required
41.8, 122.7, 124.4, 125.9, 129.8–132.1, 134.2, 142.2, 145.8, C15H14FNO3Na 298.0850).
165.9, 169.0; Found (ESI): 306.0123 [MH]+, (required
(E)-1-Cinnamoyl-5,6-dihydropyridin-2(1H)-one (17). Com-
C14H13BrNO2 306.0124); Found (ESI): 327.9939 [MNa]+, pound 17 (15.0 mg, 49%) was prepared via the general pro-
(required C14H12BrNO2Na 327.9944). Spectroscopic data in cedure as a yellow oil. δH (400 MHz, CDCl3) 2.42 (2H, tdd, J =
accord with the literature.18c
6.4, 4.2, 1.8 Hz), 4.02 (2H, t, J = 6.4 Hz), 6.01 (1H, dt, J = 9.7,
(E)-1-(3-(2,6-Dichlorophenyl)acryloyl)-5,6-dihydropyridin-2(1H)- 1.8 Hz), 6.26–7.39 (2H, m), 6.93 (1H, dt, J = 9.7, 4.2 Hz), 7.09
one (13). Compound 13 (15.0 mg, 67%) was prepared via (1H, d, J = 16.0 Hz), 7.44–7.61 (3H, m), 7.91 (1H, d, J = 16.0
the general procedure as a white solid. M.p.: 126–127 °C; Hz); δC (100 MHz, CDCl3) 24.9, 41.8, 121.8, 126.0, 126.8, 128.3,
νmax/cm−1 3692, 3606, 3083, 1688, 1624, 1602; δH (400 MHz, 128.7, 130.0, 143.7, 145.0, 166.2, 168.5; Found (ESI): 250.0847
CDCl3) 2.49 (2H, tdd, J = 6.4, 4.2, 1.9 Hz), 4.06 (2H, t, J = 6.4 [MNa]+, (required C14H13NO2Na 250.0838). Spectroscopic data
Hz), 6.03 (1H, dt, J = 9.7, 1.9 Hz), 6.94 (1H, dt, J = 9.7, 4.2 Hz), in accord with the literature.18c
7.17 (1H, t, J = 8.1 Hz), 7.34 (2H, d, J = 8.1 Hz), 7.59 (1H, d, J = (E)-1-(3-(Pyridin-3-yl)acryloyl)-5,6-dihydropyridin-2(1H)-one
16.0 Hz), 7.82 (1H, d, J = 16.0 Hz); δC (100 MHz, CDCl3) 24.9, (18). Compound 18 (13.0 mg, 52%) was prepared via the
41.8, 125.8, 128.9, 129.7, 130.1, 132.8, 135.3, 136.7, 145.8, general procedure as
a white solid. M.p.: 113–114 °C;
165.7, 168.5; Found (ESI): 296.0240 [MH]+, (required νmax/cm−1 3691, 3606, 3091, 1686, 1623, 1602; δH (400 MHz,
C14H12Cl2NO2 296.0240); Found (ESI): 318.0057 [MNa]+, CDCl3) 2.49 (2H, tdd, J = 6.4, 4.2, 1.9 Hz), 4.04 (2H, t, J =
(required C14H11Cl2NO2Na 318.0059).
6.4 Hz), 6.04 (1H, dt, J = 9.7, 1.9 Hz), 6.96 (1H, dt, J = 9.7, 4.2
Org. Biomol. Chem.
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