10.1002/cssc.201900748
ChemSusChem
FULL PAPER
3.83 (2H, s, Furan-CH2), 3.42 (2H, dd J 1.4, 6.4 Hz, CH2-CH=CH), 1.67
(1H, s, NH-). 13C NMR (100.5 MHz, CDCl3): δ 153.8, 142.0, 137.2, 131.9,
128.7, 128.1, 127.5, 126.4, 110.3, 107.2, 51.0, 45.5. IR (neat, ATR)
vmax/cm-1 3025, 2917, 1667, 1494, 1448, 1146 HRMS (ESI) m/z: Calcd
for C14H16NO (M+Na)+ 214.1226, found 214.1230.
3-(3-Phenylpropyl)-4-oxo-10-oxa-3-azatricyclo[5.2.1.01,5]dec-8-ene-6-
carboxylic acid 12d. Obtained as white crystals (72%). Mp 131.2–
°
1
132.4 C. H NMR (400 MHz, CDCl3): δ 7.3–7.1 (5H, m), 6.42 (1H, dd J
1.6, 5.8 Hz), 6.39 (1H, d J 5.8 Hz), 5.25 (1H, d J 1.5 Hz), 3.91 (1H, d J
11.9 Hz), 3.71 (1H, d J 11.9 Hz), 3.48 (1H, dd J 7.1, 14.1 Hz), 3.29 (1H,
dd J 7.0, 13.9 Hz), 2.84 (1H, d J 9.2 Hz), 2.81 (1H, d J 9.1 Hz), 2.7-2.5
(2H, m), 1.9–1.7 (2H, m). 13C NMR (100.5 MHz, CDCl3): δ 173.2, 172.8,
141.3, 137.4, 134.9, 128.6, 128.5, 126.1, 89.0, 82.5, 50.8, 49.1, 46.0,
43.0, 33.0, 28.6. IR (neat, ATR) vmax/cm-1 3018, 2936, 1727, 1663, 1180.
HRMS (ESI) m/z: Calcd for C18H19NNaO4 (M+Na)+ 336.1206, found
336.1204.
N-3-Phenylpropyl(furan-2-ylmethyl)amine 10d.[34] Cinnamyl derivative
10c (1.0 g, 4.7 mmol) was dissolved in methanol (10 mL) and 10%
palladium on carbon (50 mg) was added. The mixture was thoroughly
degassed with argon, then hydrogen was bubbled through the reaction
mixture for 10 minutes. The mixture was left stirring under hydrogen for
24 hours before being thoroughly purged with argon. The reaction
mixture was the diluted with EtOAc (50 mL), filtered through silica and
the solvent removed in vacuo to give compound 10d as a yellow oil
(95%). 1H NMR (400 MHz, CDCl3): δ 7.36 (1H, dd J 0.7, 1.8 Hz, Furan-H),
7.3–7.2 (2H, m, Ar-H), 7.2–7.1 (3H, m, Ar-H), 6.31 (1H, dd J 1.9, 3.1 Hz,
Furan-H), 6.16 (1H, d J 3.2 Hz, Furan-H), 3.78 (2H, s, Furan-CH2-), 2.66
(4H, m, NHCH2CH2CH2Ph), 1.83 (2H, dt J 7.5, 9.3 Hz, CH2CH2Ph), 1.55
(1H, s, NH). 13C NMR (100.5 MHz, CDCl3): δ 154.1, 142.2, 141.9, 128.5,
128.4, 125.9, 110.2, 106.9, 48.7, 46.3, 33.7, 31.7. IR (neat, ATR)
vmax/cm-1 3025, 2925, 1602, 1495, 1453, 1146. HRMS (ESI) m/z: Calcd
for C14H18NO (M+Na)+ 216.1383, found 216.1385.
Synthesis of methyl esters 13a–d. Carboxylic acid 12a–d (6.7 mmol)
was dissolved in methanol (20 mL), one drop of sulfuric acid was added
and the reaction was heated at reflux for 16 hours. The reaction mixture
was diluted with deionized water (10 mL) and adjusted to pH 8 with 1M
aqueous NaHCO3, after which the methanol was removed in vacuo. In
the case of ester 13a, the product precipitated as white crystals. In all
other cases, the product was extracted with CH2Cl2 (3x15 mL), which
was then washed with brine (20 mL), dried (MgSO4) and concentrated in
vacuo to give esters 13b–d.
Methyl
3-benzyl-4-oxo-10-oxa-3-azatricyclo[5.2.1.01,5]dec-8-ene-6-
Synthesis of oxa-norbornene lactams 12a-d. Secondary amine 10a-d
(81.0 mmol) and maleic anhydride 7 (7.9 g, 81.0 mmol) were stirred
together in toluene (100 mL) for 16 hours. The reaction was concentrated
in vacuo and the resulting solid recrystallized from acetone to give the
products as white crystalline solids.
carboxylate 13a.[37] Obtained as colourless crystals (95%). Mp 110.5–
°
111.9 C. 1H NMR (400 MHz, CDCl3): δ 7.4–7.2 (5H, m), 6.47 (1H, d J
5.6 Hz), 6.43 (1H, dd J 1.6, 5.9 Hz), 5.17 (1H, d J 1.7 Hz), 4.67 (1H, d J
15.0 Hz), 4.34 (1H, d J 15.0 Hz) 3.9–3.8 (4H, m), 2.83 (1H, d J 9.1 Hz),
2.76 (1H, d J 9.1 Hz). 13C NMR (100.5 MHz, CDCl3): δ 172.4, 170.8,
137.0, 136.0, 135.4, 128.9, 128.0, 127.7, 88.6, 81.5, 52.3, 51.2, 48.2,
46.8, 44.9. IR (neat, ATR) vmax/cm-1 3002, 2949, 1727, 1686, 1175.
HRMS (ESI) m/z: Calcd for C17H17NNaO4 (M+Na)+ 322.1050, found
322.1058.
3-Benzyl-4-oxo-10-oxa-3-azatricyclo[5.2.1.01,5]dec-8-ene-6-carboxylic
acid 12a.[35] Obtained as colourless crystals (55%). Mp 171.5–172.3 °C
°
(lit.[35] 170–174 C). 1H NMR (400 MHz, CDCl3): δ 7.4–7.2 (5H, m), 6.44
(1H, dd J 1.6, 5.8 Hz), 6.41 (1H, d J 5.8 Hz), 5.30 (1H, d J 1.6 Hz), 4.66
(1H, d J 14.9 Hz), 4.43 (1H, d J 14.9 Hz), 3.85 (1H, d J 12.0 Hz), 3.67
(1H, d J 12.0 Hz), 2.94 (1H, d J 9.1 Hz), 2.86 (1H, d J 9.1 Hz). 13C NMR
(100.5 MHz, CDCl3): δ 173.2, 172.7, 137.4, 135.3, 134.9, 129.1, 128.1,
128.1, 89.0, 82.5, 50.8, 48.7, 47.2, 46.1. IR (neat, ATR) vmax/cm-1. 3013,
2919, 1736, 1651, 1202, 1174. HRMS (ESI) m/z: Calcd for C16H16NO4
(MH+) 286.1074, found 286.1072.
Methyl
3-(Furan-2-ylmethyl)-4-oxo-10-oxa-3-azatricyclo[5.2.1.01,5
]
dec-8-ene-6-carboxylate 13b. Obtained as colourless crystals (77%).
Mp 104.3–105.2 °C. 1H NMR (400 MHz, CDCl3): δ 7.35 (1H, dd J 0.7, 1.8
Hz), 6.48 (1H, d J 5.9 Hz), 6.43 (1H, dd J 1.7, 5.9 Hz), 6.32 (1H, dd J 1.8,
3.2 Hz), 6.27 (1H, dd J 0.7, 3.2 Hz), 5.16 (1H, d J 1.6 Hz), 4.78 (1H, d J
15.6 Hz), 4.19 (1H, d J 15.6 Hz), 3.92 (1H, d J 11.8 Hz), 3.8–3.7 (4H, m),
2.80 (1H, d J 9.1 Hz), 2.73 (1H, d J 9.1 Hz). 13C NMR (100.5 MHz,
CDCl3): δ 172.4, 170.5, 149.9, 142.6, 137.1, 135.4, 110.7, 108.5, 88.6,
81.5, 52.4, 51.1, 48.8, 44.9, 39.8. IR (neat, ATR) vmax/cm-1. 2951, 1732,
1684, 1505. HRMS (ESI) m/z: Calcd for C15H15NNaO5 (M+Na)+ 312.0842,
found 312.0842.
3-(Furan-2-ylmethyl)-4-oxo-10-oxa-3-azatricyclo[5.2.1.01,5]dec-8-ene-
6-carboxylic acid 12b.[36] Obtained as colourless crystals (95%). Mp
150.9–151.7 °C (lit.[36] 150–151 °C). 1H NMR (400 MHz, CDCl3): δ 7.37
(1H, dd J 0.7, 1.7 Hz), 6.46 (2H, d J 0.6 Hz), 6.33 (1H, dd J 1.9, 3.2 Hz),
6.30 (1H, d J 3.2 Hz), 5.29 (1H, s), 4.79 (1H, d J 15.6 Hz), 4.27 (1H, d J
15.6 Hz) 3.94 (1H, d J 12.0 Hz), 3.78 (1H, d J 12.0 Hz), 2.91 (1H, d J 9.1
Hz), 2.84 (1H, d J 9.1 Hz). 13C NMR (100.5 MHz, CDCl3): δ 173.6, 172.1,
149.2, 142.8, 137.3, 135.1, 110.7, 109.0, 88.9, 82.4, 50.8, 49.1, 45.7,
40.0. IR (neat, ATR) vmax/cm-1 3141, 2956, 1726, 1693, 1172. HRMS
(ESI) m/z: Calcd for C14H13NNaO5 (M+Na)+ 298.0686, found 298. 0683.
Methyl 3-Cinnamyl-4-oxo-10-oxa-3-azatricyclo[5.2.1.01,5]dec-8-ene-6-
carboxylate 13c. Obtained as colourless crystals (89%). Mp 122.1–
122.8 °C. 1H NMR (400 MHz, CDCl3); 7.4–7.2 (5H, m), 6.57 (1H, d J
16.0 Hz), 6.51 (1H, d J 6.0 Hz), 6.45 (1H, dd J 6.0, 2.0 Hz), 6.11 (1H, dt J
16.0, 6.4 Hz), 5.19 (1H, d J 1.6 Hz), 4.22 (1H, dd J 15.2, 10.0 Hz), 3.99
(1H, dd J 15.2, 10.0 Hz), 3.98 (1H, d J 12.0 Hz), 3.79 (3H, s), 3.77 (1H, d
J 13.2 Hz), 2.84 (1H, d J 9.0 Hz), 2.76 (1H, d J 9.0 Hz). 13C NMR (100.5
MHz, CDCl3): 172.4, 170.5, 137.0, 136.4, 135.5, 133.5, 128.7, 127.9,
126.6, 123.2, 88.7, 81.5, 52.3, 51.3, 48.4, 45.0, 44.9; IR (neat, ATR)
3-Cinnamyl-4-oxo-10-oxa-3-azatricyclo[5.2.1.01,5]dec-8-ene-6-
carboxylic acid 12c. Obtained as a white solid (73%). Mp 158.6-
158.9 °C. 1H NMR (400 MHz, CDCl3): 7.4–7.2 (5H, m), 6.59 (1H, d J
16.0 Hz), 6.49 (1H, dd J 5.6, 1.6 Hz), 6.44 (1H, d J 5.6 Hz), 6.10 (1H, dt J
16.0, 6.4 Hz), 5.36 (1H, d J 1.6 Hz), 4.22 (1H, dd J 15.2, 5.6 Hz), 4.06
(1H, dd J 15.2, 5.6 Hz), 4.01 (1H, d J 12.0 Hz), 3.80 (1H, d J 12.0 Hz),
2.92 (1H, d J 9.2 Hz), 2.88 (1H, d J 9.2 Hz). 13C NMR (100.5 MHz,
CDCl3): 172.9, 172.6, 137.5, 136.2, 134.9, 134.2, 128.8, 128.2, 126.7,
122.4, 89.1, 82.6, 50.7, 48.9, 46.2, 45.4. IR (neat, ATR) max/cm-1 2913,
1699, 1638. HRMS (ESI) m/z: Calcd. for C18H17NNaO4 (M+Na)+
334.1050, found 334.1043.
max/cm-1 3022, 2950, 2905, 1734, 1694, 1596, 1575. HRMS (ESI) m/z:
Calcd. for C19H19NNaO4 (M+Na)+ 348.1206, found 348.1194.
Methyl 3-(3-Phenylpropyl)-4-oxo-10-oxa-3-azatricyclo[5.2.1.01,5]dec-
8-ene-6-carboxylate 13d. Purified by column chromatography on silica
eluting with EtOAc and obtained as a waxy white solid (100%). Mp 84–
1
87 °C. H NMR (400 MHz, CDCl3) δ = 7.3–7.2 (2H, m), 7.2–7.1 (3H, m),
6.48 (1H, d J 5.8 Hz), 6.43 (2H, dd J 5.8, 1.7 Hz), 5.16 (1H, d, J 1.7 Hz),
3.88 (1H, d J 11.6 Hz), 3.77 (3H, s), 3.69 (1H, d J 11.6 Hz), 3.6–3.4 (1H,
m), 3.4–3.2 (1H, m), 2.8–2.5 (4H, m), 1.9–1.8 (2H, m). 13C NMR (101
This article is protected by copyright. All rights reserved.