Jeong and Moloney
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(C4 AB), 192.9 (3-acyl AB), 192.7 (C4 CD), 189.2 (3-acyl CD), 176.5
(C2 CD), 170.2 (C2 AB), 104.6 (C3 AB), 101.2 (C3 CD), 51.8 (C5
CD), 48.5 (C5 AB), 33.9 (CH2), 33.56 (CH2), 32.7 (CH2), 31.9
(CH2), 29.4 (CH2), 29.3 (CH2), 25.97 (CH2), 25.59 (CH2), 24.9
(CH2), 22.7 (CH2), 14.1 (CH3). MS (ES-): 252.2 (M - H). HRMS
(M þ H): calcd for C14H24N1O3 254.1751, found 254.1751.
3H, C12). 13C NMR (125 MHz, CDCl3): 196.9 (C13 AB), 194.6
(C4 AB), 191.6 (C13 CD), 189.3 (C4 CD), 173.4 (C2 CD), 172.6
(C6 AB, CD), 165.5 (C2 AB), 105.9 (C3 AB), 103.3 (C3 CD),
53.7 (C5 CD), 49.9 (C5 AB), 41.5 (CH2), 41.1 (C17 AB*), 41.0
(C17 CD*), 39.6 (C15 AB*), 39.4 (CH2), 38.6 (C15 CD*), 37.7
(CH2), 37.6 (CH2), 37.5 (CH2), 37.2 (CH2), 36.7 (C20), 35.3
(CH2), 31.5 (CH2), 31.5 (CH2), 29.70 (CH2), 29.6 (CH2), 28.8
(CH2), 28.5 (CH2), 24.1 (CH2), 22.5 (CH2), 22.5 (CH2), 14.0
(C12). MS (ES-): 346.2 (M - H). HRMS (M - H): calcd for
C20H28N1O4 346.2024, found 346.2016.
3-(2-(Adamantan-1-yl)-1-hydroxyethylidene)-1-heptanoylpyr-
rolidine-2,4-dione (9c). Yield 48%, mp 82 °C; Form AB:CD =
50:50; 1H NMR (500 MHz, CDCl3): 4.27 (s, 2H, C5 AB), 4.10 (s,
2H, C5 CD), 3.01-2.97 (m, 2H, C7), 2.75 (s, 2H, C14),1.98 (br s,
3H, C17, C19 and C21), 1.72-1.63 (s, 14H, C8, C16, C18, C20
and C22-24), 1.39-1.30 (m, 6H, C9-11), 0.92-0.88 (m, 3H,
C12). 13C NMR (125 MHz, CDCl3): 196.1 (C4 AB), 195.2 (C13
AB), 190.7 (C13 CD), 189.3 (C4 CD), 173.5 (C2 CD), 173.4 (C6
ABa), 172.7 (C6 CDa), 165.6 (C2 AB), 106.9 (C3 AB), 104.5 (C3
CD), 53.8 (C5 CD), 50.4 (C5 AB), 46.9 (CH2), 46.3 (CH2), 42.7
(CH2), 42.6 (CH2), 37.7 (CH2), 37.4 (CH2), 36.7 (C15), 36.6
(CH2), 36.3 (C15), 31.6 (CH2), 31.5 (CH2), 28.8 (CH2), 28.8
(CH), 28.8 (CH), 24.16 (CH2), 24.1 (CH2), 22.5 (CH2), 14.0
(C12). MS (ES-): 386.3 (M - H). HRMS (M - H): calcd for
C23H32N1O4 386.2337, found 386.2343.
Ethyl 3-(1-Heptanoyl-2,4-dioxopyrrolidin-3-ylidene)-3-hydro-
xypropanoate (9d). Yield 33%, mp 33 °C; Form AB:CD =
70:30. 1H NMR (500 MHz, CDCl3): 4.38 (s, 2H, C5 AB), 4.23 (q,
2H, J = 7.0 Hz, C16), 4.15 (s, 2H, C5 CD), 3.98 (s, 2H, C14 CD),
3.95 (s, 2H, C14 AB), 3.00-2.94 (m, 2H, C7), 1.69-1.64 (m, 2H,
C8), 1.38-1.26 (m, 9H, C9-11 and C17), 0.91-0.88 (m, 3H,
C12). 13C NMR (125 MHz, CDCl3): 191.0 (C13 AB), 190.7 (C4
AB), 189.2 (C4 CD), 181.1 (C13 CD), 173.2 (C6 AB), 172.6 (C6
CD), 172.6 (C2 CD), 166.5 (C15 AB), 166.0 (C15 CD), 165.1 (C2
AB), 106.97 (C3 AB), 104.7 (C3 CD), 62.0 (C16 CD), 61.8 (C16
AB), 54.0 (C5 CD), 48.7 (C5 AB), 43.4 (CH2), 38.9 (CH2), 37.7
(CH2), 37.1 (CH2), 31.5 (CH2), 28.8 (CH2), 24.1 (CH2), 22.5
(CH2), 14.1 (C17), 14.00 (C12). MS (ES-): 324.2 (M - H). HRMS
(M - H): calcd for C16H22N1O6 324.1453, found 324.1454.
tert-Butyl (2-(1-Heptanoyl-2,4-dioxopyrrolidin-3-ylidene)-2-
hydroxyethyl)carbamate (9e). Yield 63%, mp 129 °C; Form
AB:CD = 75:25. 1H NMR (500 MHz, CDCl3): 5.23 (brs, 1H,
NH), 4.49 (s, 2H, C14), 4.41 (s, 2H, C5 AB), 4.11 (s, 2H, C5 CD),
2.94 (t, 2H, J = 7.5 Hz, C7), 1.69-1.63 (m, 2H, C8), 1.45 (s, 9H,
C17-19), 1.38-1.24 (m, 6H, C9-11), 0.88 (t, 3H, J = 6.5 Hz,
C12). 13C NMR (125 MHz, CDCl3): 196.3 (C13 AB), 195.2 (C13
CD), 189.2 (C4 CD), 187.9 (C4 AB), 173.2 (C2 CD), 173.1 (C6
AB), 168.7 (C6 CD), 165.0 (C2 AB), 157.0 (C15 CD), 155.7 (C15
AB), 106.01 (C3 AB), 103.3 (C3 CD), 83.6 (C16 CD), 80.1
(C16 AB), 53.4 (C5 CD), 51.6 (C14 CD), 48.1 (C5 AB), 47.4 (C14
AB), 37.0 (C7 CD), 36.9 (C7 AB), 31.6 (CH2 CD), 31.5 (CH2
AB), 28.9 (CH2 CD), 28.8 (CH2 AB), 28.2 (C17-19 AB), 27.9
(C17-19 CD), 24.2 (CH2 CD), 24.1 (CH2 AB), 22.5 (CH2 CD),
22.5 (CH2 AB), 14.1 (C12 CD), 14.0 (C12 AB). MS (ES-): 367.2
(M - H). HRMS (M - H): calcd for C18H27N2O6 367.1875,
found 367.1869.
Synthesis of 3-Acyl Tetramic Acids from Tetramic Acids
(Method E). 1-Heptanoyl-3-(1-hydroxyheptylidene)pyrrolidine-
2,4-dione (8k). Yield 94%, mp 50 °C; Form AB:CD = 55:45.
1H NMR (500 MHz, CDCl3): 4.29 (s, 2H, C5 AB), 4.10 (s, 2H,
C5 CD), 2.99-2.91 (m, 4H, C7 and C14), 1.72-1.65 (m, 4H, C8
and C15), 1.42-1.25 (m, 12H, C9-11 and C16-18), 0.90-0.87
1
(m, 6H, C12 and C19). H NMR (500 MHz, CD3OD): 4.19
(s, 2H, C5), 2.99-2.79 (m, 4H, C7 and C14), 1.69-1.63 (m, 4H,
C8 and C15), 1.42-1.29 (m, 12H, C9-11 and C16-18),
0.93-0.90 (m, 6H, C12 and C19). 13C NMR (125 MHz, CDCl3):
198.1 (C13 AB), 194.1 (C4 AB), 192.5 (C13 CD), 189.2 (C4 CD),
173.4 (C2 CD), 173.4 (C6 AB), 172.7 (C6 CD), 165.4 (C2 AB),
105.6 (C3 AB), 102.8 (C3 CD), 53.75 (C5 CD), 49.8 (C5 AB),
37.6 (CH2), 37.2 (CH2), 35.3 (CH2), 33.2 (CH2), 31.5 (CH2), 31.5
(CH2), 31.4 (CH2), 31.3 (CH2), 28.9 (CH2), 28.9 (CH2), 28.8
(CH2), 25.9 (CH2), 24.9 (CH2), 24.2 (CH2), 24.2 (CH2), 22.5
(CH2), 22.5 (CH2), 22.4 (CH2), 22.4 (CH2), 13.99 (CH3), 13.96
(CH3). 13C NMR (125 MHz, CD3OD): 196.1 (C13), 192.7 (C4,
triplet), 174.8 (C6), 170.6 (C2), 105.9 (C3), 52.4 (C5), 38.4 (CH2),
32.9 (CH2), 32.8 (CH2), 30.2 (CH2), 26.6 (CH2), 25.6 (CH2), 23.8
(CH2), 23.7 (CH2), 14.55 (CH3), 14.52 (CH3). MS (ES-): 322.2
(M - H). HRMS (M þ Na): calcd for C18H29N1Na1O4
346.1989, found 346.1983.
3-(1-Hydroxynonylidene)-1-(2-methylbenzoyl)pyrrolidine-2,4-
dione (8l). Yield 92% (oil); Form AB:CD = 55:45. H NMR
1
(500 MHz, CDCl3): 7.43-7.37 (m, 1H, C9), 7.32-7.26 (m, 3H,
C10-12), 4.52 (s, 2H, C5 AB), 4.33 (s, 2H, C5 CD), 2.93 (t, 2H,
J = 7.5 Hz, C15 CD), 2.85 (t, 2H, J = 7.5 Hz, C15 AB), 2.36 (s,
3H, C13 CD), 2.34 (s, 3H, C13 AB), 1.70-1.60 (m, 2H, C16),
1.42-1.24 (m, 10H, C17-21), 0.90-0.86 (m, 3H, C22). 13C
NMR (125 MHz, CDCl3): 198.3 (C14 AB), 194.4 (C4 AB), 193.1
(C14 CD), 188.9 (C4 CD), 172.6 (C2 CD), 169.3 (C6 AB), 168.5
(C6 CD), 164.2 (C2 AB), 135.9 (ArC), 135.6 (ArC), 134.9 (ArC),
134.6 (ArC), 130.4 (ArCH), 130.4 (ArCH), 130.2 (ArCH), 130.0
(ArCH), 126.6 (ArCH), 126.4 (ArCH), 125.5 (ArCH), 105.1 (C3
AB), 102.3 (C3 CD), 53.7 (C5 CD), 49.9 (C5 AB), 35.2 (C15 AB),
33.3 (C15 CD), 31.7 (CH2), 31.7 (CH2), 29.2 (CH2), 29.2 (CH2), 29.1
(CH2), 29.0 (CH2), 29.0 (CH2), 25.9 (CH2), 24.7 (CH2), 22.6 (CH2),
19.3 (C13), 19.3 (C13), 14.0 (C22). MS (ES-): 356.18 (M - H).
HRMS (M - H): calcd for C21H26N1O4 356.1867, found 356.1870.
3-(2-Cyclohexyl-1-hydroxyethylidene)-1-heptanoylpyrrolidine-
2,4-dione (9a). Yield 74% (oil); Form AB:CD = 55:45. 1H
NMR (400 MHz, CDCl3): 4.28 (s, 2H, C5 AB), 4.10 (s, 2H,
C5 CD), 3.01-2.96 (m, 2H, C7), 2.83 (d, 2H, J = 6.8 Hz, C14),
1.96-1.82 (m, 1H, C15), 1.76-1.05 (m, 18H, C8-11 and
C16-20), 0.91-0.88 (m, 3H, C12). 13C NMR (100 MHz,
CDCl3): 196.9 (C13 AB), 195.0 (C4 AB), 191.8 (C13 CD),
189.3 (C4 CD), 173.5 (C2 CD), 173.4 (C6 AB), 172.7 (C6 CD),
165.5 (C2 AB), 106.1 (C3 AB), 103.5 (C3 CD), 53.8 (C5 CD),
50.1 (C5 AB), 42.0 (C14), 40.5 (C14), 37.7 (C7), 37.3 (C7), 36.7
(C15), 35.8 (C15), 33.1 (CH2), 33.0 (CH2), 31.6 (CH2), 31.5
(CH2), 28.8 (CH2), 26.02 (CH2), 26.00 (CH2), 25.95 (CH2), 24.2
(CH2), 22.5 (CH2), 22.5 (CH2), 14.0 (C12). MS (ES-): 334.2
(M - H). HRMS (M - H): calcd for C19H28N1O4 334.2024,
found 334.2023.
1-Heptanoyl-3-(1-hydroxy-2-(2-(2-methoxyethoxy)ethoxy)-
ethylidene)pyrrolidine-2,4-dione (9f). Yield 38%, mp 37 °C;
Form AB:CD = 99:1. H NMR (500 MHz, CDCl3): 4.79 (s,
1
2H, C14), 4.42 (s, 2H, C5), 3.79-3.55 (m, 8H, C15-18), 3.38 (s,
3H, C19), 2.93 (t, 2H, J = 7.0 Hz, C7), 1.70-1.64 (m, 2H, C8),
1.39-1.29 (m, 6H, C9-11), 0.88 (t, 3H, J = 7.0 Hz, C12). 13C NMR
(125 MHz, CDCl3): 196.9 (C13), 188.3 (C4), 173.0 (C6), 165.2 (C2),
105.8 (C3), 73.0 (C14), 71.8 (CH2O), 71.1 (CH2O), 70.50 (CH2O),
70.47 (CH2O), 59.0 (C19), 48.4 (C5), 36.9 (C7), 31.5 (CH2), 28.8
(CH2), 24.1 (CH2), 22.5 (CH2), 14.0 (C12). MS (ES-): 370.2 (M -
H). MS (ESþ): 372.2 (M þ H), 394.2 (M þ Na). HRMS (M þ Na):
calcd for C18H29N1Na1O7; 394.1836, found 394.1830.
3-(2-((1S,2R,4R)-Bicyclo[2.2.1]heptan-2-yl)-1-hydroxyethylidene)-
1-heptanoylpyrrolidine-2,4-dione (9b). Yield 77% (oil); Form
AB:CD= 55: 45.1H NMR (500 MHz, CDCl3): 4.28 (s, 2H, C5
AB), 4.10 (s, 2H, C5 CD), 2.99-2.96 (m, 2H, C7), 2.93-2.87 (m,
1H, C14), 2.81-2.76 (m, 1H, C14), 2.24 (s, 1H, C17), 2.02 (s, 1H,
C20), 1.99-1.93 (m, 1H, C15), 1.72-1.64 (m, 2H, C8), 1.55-
1.11 (m, 14H, C9-11, C16, C18, C19 and C21), 0.90-0.87 (m,
J. Org. Chem. Vol. 76, No. 5, 2011 1353