Diels-Alder Reaction of 2-Amino-Substituted Furans
J . Org. Chem., Vol. 62, No. 12, 1997 4093
(1.3 mmol) of furan 9 and 5 mL of methyl acrylate in 10 mL of
benzene was heated at reflux for 48 h. The solvent was
removed under reduced pressure, and the resulting residue
was subjected to flash silica gel chromatography to give 0.28
g (92%) of 11 as a yellow solid: mp 102-103 °C; IR (KBr) 3445,
49.9, 50.9, 52.2, 53.1, 72.6, 84.7, 127.4, 133.3, 150.9, 169.3,
171.3, 172.8. Anal. Calcd for C12H15NO7‚H2O: C, 47.53; H,
5.65; N 4.62. Found: C, 47.70; H, 5.65; N, 4.62.
4-Am in o-1-h yd r oxy-2-m et h ylcycloh exa -3,5-d ien e-1,3-
d ica r boxylic Acid Dim eth yl Ester (16). A mixture con-
taining 0.20 g (1.4 mmol) of furan 9 and 4 mL of methyl
crotonate was heated in a sealed tube at 140-145 °C for 18 h.
The mixture was diluted with CH2Cl2 and filtered through a
pad of silica gel. After removal of the solvent under reduced
pressure, the resulting residue was subjected to flash silica
gel chromatography to give 0.20 g (57%) of 16 as a 3:2 mixture
of diastereomers. The minor diastereomer (0.08 g, 24%)
exhibited the following spectral properties: yellow solid; mp
155-156 °C; IR (KBr) 3321, 3218, 1732, 1660, 1614, 1533
1
3335, 1736, 1671 cm-1; H-NMR (CDCl3, 300 MHz) δ 2.87 (d,
1H, J ) 17.1 Hz), 2.93 (d, 1H, J ) 17.1 Hz), 3.20 (s, 1H), 3.71
(s, 3H), 3.82 (s, 3H), 6.02 (d, 1H, J ) 9.6 Hz), 5.60-6.40 (brs,
2H), 6.17 (d, 1H, J ) 9.6 Hz); 13C-NMR (CDCl3, 75 MHz) δ
32.8, 50.6, 53.1, 71.7, 85.6, 127.2, 133.7, 149.2, 169.7, 175.1.
Anal. Calcd for C10H13NO5: C, 52.86; H, 5.77; N, 6.16.
Found: C, 52.97; H, 5.80; N, 6.06.
4-Am in o-5-cyan o-1-h ydr oxycycloh exa-2,4-dien ecar box-
ylic Acid Meth yl Ester (12). A mixture containing 0.24 g
(1.7 mmol) of furan 9 and 4 mL of acrylonitrile in 10 mL of
benzene was heated at reflux for 18 h. The solvent was
removed under reduced pressure, and the residue was sub-
jected to flash silica gel chromatography to give 0.33 g (99%)
of 12 as a pale yellow solid: mp 93-94 °C; IR (KBr) 3241,
1
cm-1; H-NMR (CDCl3, 300 MHz) δ 1.10 (d, 3H, J ) 6.9 Hz),
3.06 (s, 1H), 3.07 (dq, 1H, J ) 6.9 and 1.1 Hz), 3.70 (s, 3H),
3.72 (s, 3H), 5.88 (dd, 1H, J ) 9.8 and 1.1 Hz), 5.93 (d, 1H, J
) 9.8 Hz); 13C-NMR (CDCl3, 75 MHz) δ 14.3, 36.3, 50.6, 53.2,
77.6, 93.3, 126.8, 136.3, 149.5, 169.8, 174.9. Anal. Calcd for
C11H15NO5: C, 54.77; H, 6.27; N 5.81. Found: C, 54.66; H,
6.26; N, 5.79.
1
2181, 1735, 1659 cm-1; H-NMR (CDCl3, 300 MHz) δ 2.61 (d,
1H, J ) 16.8 Hz), 2.90 (d, 1H, J ) 16.8 Hz), 3.71 (s, 1H), 3.83
(s, 3H), 4.72 (brs, 2H), 6.07 (d, 1H, J ) 9.8 Hz), 6.17 (d, 1H, J
) 9.8 Hz); 13C-NMR (CDCl3, 75 MHz) δ 33.3, 53.4, 67.7,
70.6, 120.0, 125.0, 133.4, 149.7, 174.3. Anal. Calcd for
C9H10N2O3: C, 55.67; H, 5.19; N,14.43. Found: C, 55.55; H,
5.18; N, 14.36.
The major diastereomer (0.12 g, 33%) exhibited the following
spectral properties: orange solid; mp 145-146 °C; IR (KBr)
3328, 1741, 1667, 1595, 1005 cm-1; 1H-NMR (CDCl3, 300 MHz)
δ 0.89 (d, 3H, J ) 6.8 Hz), 2.88 (s, 1H), 3.13 (dq, 1H, J ) 6.8,
0.9 Hz), 3.72 (s, 3H), 3.83 (s, 3H), 6.02 (d, 1H, J ) 9.8 Hz),
6.44 (dd, 1H, J ) 9.8, 0.9 Hz); 13C-NMR (CDCl3, 75 MHz) δ
16.6, 38.2, 50.7, 52.6, 75.4, 92.1, 126.7, 133.0, 148.7, 169.8,
173.6. Anal. Calcd for C11H15NO5: C, 54.77; H, 6.27; N, 5.81.
Found: C, 54.74; H, 6.26; N, 5.79.
4-Am in o-5-(ben zen esu lfon yl)-1-h yd r oxycycloh exa -2,4-
d ien eca r boxylic Acid Meth yl Ester (13). A mixture con-
taining 0.15 g (1.1 mmol) of furan 9 and 0.27 g (1.6 mmol) of
phenyl vinyl sulfone in 10 mL of benzene was heated at reflux
for 4 days. The solvent was removed under reduced pressure,
and the resulting residue was subjected to flash silica gel
chromatography to give 0.26 g (78%) of 13 as a pale yellow
solid: mp 124-125 °C; IR (KBr) 3511, 3237, 1728, 1659, 1566
cm-1; 1H-NMR (CDCl3, 300 MHz) δ 2.65 (d, 1H, J ) 16.5 Hz),
2.79 (d, 1H, J ) 16.5 Hz), 3.07 (s, 1H), 3.67 (s, 3H), 5.66 (brs,
2H), 5.94 (d, 1H, J ) 9.6 Hz), 6.09 (d, 1H, J ) 9.6 Hz), 7.48-
7.59 (m, 3H), 7.86-7.90 (m, 2H); 13C-NMR (CDCl3, 75 MHz) δ
33.3, 53.3, 71.7, 91.4, 126.4, 127.3, 128.9, 132.6, 134.3, 142.1,
145.0, 174.3. Anal. Calcd for C14H15NO5S: C, 54.36; H, 4.89;
N, 4.53. Found: C, 54.43; H, 4.92; N, 4.49.
7-Am in o-1,3-d ioxo-2-p h en yl-2,3-d ih yd r o-1H-isoin d ole-
4-ca r boxylic Acid Meth yl Ester (17). A mixture containing
0.2 g (1.5 mmol) of furan 9 and 0.3 g (1.6 mmol) of N-
phenylmaleimide in 15 mL of benzene was heated at reflux
for 12 h. The solvent was removed under reduced pressure.
The crude solid was recrystallized from a 1:1 mixture of CH2-
Cl2 and EtOAc to give 0.26 g (63%) of 17 as a yellow solid:
1
mp 215-216 °C; IR (KBr) 3180, 1761, 1700, 1633 cm-1; H-
NMR (CDCl3, 300 MHz) δ 3.95 (s, 3H), 5.72 (brs, 2H), 6.91 (d,
1H, J ) 8.7 Hz), 7.37-7.52 (m, 5H), 7.88 (d, 1H, J ) 8.7 Hz);
13C-NMR (DMSO-d6, 75 MHz) δ 52.0, 109.5, 116.1, 120.4,
127.5, 127.9, 128.7, 130.8, 131.9, 135.7, 148.7, 164.6, 165.6,
167.7. Anal. Calcd for C16H12N2O4: C, 64.86; H, 4.08.
Found: C, 64.80; H, 4.12.
5-Acet yl-4-a m in o-1-h yd r oxycycloh exa -2,4-d ien eca r -
boxylic Acid Meth yl Ester (14). A mixture containing 0.21
g (1.5 mmol) of furan 9 and 5 mL of methyl vinyl ketone in 10
mL of benzene was heated at reflux for 1 h. The solvent was
removed under reduced pressure, and the residue was sub-
jected to flash silica gel chromatography to give 0.24 g (74%)
of 14 as a yellow solid: mp 128-129 °C; IR (KBr) 3369, 1736,
1655 cm-1; 1H-NMR (CDCl3, 300 MHz) δ 2.16 (s, 3H), 2.86 (d,
1H, J ) 16.2 Hz), 3.01 (d, 1H, J ) 16.2 Hz), 3.25 (brs, 1H),
3.84 (s, 3H), 6.03 (d, 1H, J ) 9.6 Hz), 6.21 (d, 1H, J ) 9.6 Hz);
13C-NMR (CDCl3, 75 MHz) δ 27.5, 34.7, 53.1, 72.1, 95.2, 127.3,
135.4, 150.5, 174.7, 197.0. Anal. Calcd for C10H13NO4: C,
56.87; H, 6.20; N 6.63. Found: C, 56.84; H, 6.25; N, 6.55.
4-Am in o-1-h yd r oxy-cycloh exa -3,5-d ien e-1,2,3-t r ica r -
boxylic Acid Tr im eth yl Ester (15). A mixture containing
0.16 g (1.1 mmol) of furan 9 and 0.28 mL (2.2 mmol) of
dimethyl maleate in 4 mL of toluene was heated in a sealed
tube at 150 °C for 17 h. The mixture was taken up in CH2Cl2
and was filtered through a pad of silica gel. Removal of the
solvent under reduced pressure followed by subjection of the
residue to flash silica gel chromatography gave 0.26 g of a 1:3
mixture of two diastereomers of 15 in 80% yield. The minor
diastereomer (yellow solid, mp 167-168 °C) exhibited the
4-Am in oisop h th a lic Acid Dim eth yl Ester (20). To a
solution containing 0.25 g (1.1 mmol) of 4-amino-1-hydroxy-
cyclohexa-3,5-diene-1,3-dicarboxylic acid dimethyl ester (11)
in 10 mL of benzene was added 0.20 mL (1.6 mmol) of BF3‚
OEt2. The mixture was heated at reflux for 2 min, quenched
with a saturated NaHCO3 solution, and extracted with CH2-
Cl2. The combined organic extracts were dried over Na2SO4.
After removal of the solvent under reduced pressure, the
residue was subjected to flash silica gel chromatography to
give 0.22 g (96%) of 20 as a white solid: mp 127-128 °C; IR
(KBr) 3452, 3345, 1690, 1621 cm-1; 1H-NMR (CDCl3, 300 MHz)
δ 3.87 (s, 3H), 3.88 (s, 3H), 6.30 (brs, 2H), 6.65 (d, 1H, J ) 8.7
Hz), 7.89 (dd, 1H, J ) 8.7, 2.1 Hz), 8.57 (d, 1H, J ) 2.1 Hz);
13C-NMR (CDCl3, 75 MHz) δ 51.6, 109.6, 116.0, 117.6, 134.1,
134.8, 153.7, 166.5, 168.0. Anal. Calcd for C10H11NO4: C,
57.41; H, 5.30. Found: C, 57.34; H, 5.29.
4-Am in o-3-cya n oben zoic Acid Meth yl Ester (21). To a
solution containing 0.18 g (0.93 mmol) of 4-amino-5-cyano-1-
hydroxycyclohexa-2,4-dienecarboxylic acid methyl ester (12)
in 10 mL of benzene was added 0.20 mL (1.6 mmol) of BF3‚
OEt2. The mixture was heated at reflux for 10 min, quenched
with a saturated NaHCO3 solution, and extracted with CH2-
Cl2. The combined organic extracts were dried over Na2SO4.
After removal of the solvent, the residue was subjected to
flash silica gel chromatography to give 0.16 g (89%) of 21 as a
white solid: mp 156-157 °C; IR (KBr) 3463, 2222, 1726, 1645
cm-1; 1H-NMR (CDCl3, 300 MHz) δ 3.88 (s, 3H), 4.85 (brs, 2H),
6.75 (d, 1H, J ) 8.7 Hz), 7.98 (dd, 1H, J ) 8.7, 2.1 Hz), 8.12
(d, 1H, J ) 2.1 Hz); 13C-NMR (CDCl3, 75 MHz) δ 52.0, 95.4,
114.4, 116.6, 119.8, 134.9, 135.2, 152.6, 165.4. Anal. Calcd
for C9H8N2O2: C, 61.36; H, 4.58; N, 15.90. Found: C, 61.23;
H, 4.53; N, 15.92.
following spectral properties: IR (KBr) 3324, 1734, 1675 cm-1
;
1H-NMR (CDCl3, 300 MHz) δ 3.70 (s, 6H), 3.77 (s, 3H), 4.11
(s, 1H), 4.15 (s, 1H), 5.95 (d, 1H, J ) 9.9 Hz), 6.06 (d, 1H, J )
9.9 Hz); 13C-NMR (CDCl3, 75 MHz) δ 46.9, 50.9, 52.2, 53.5,
74.8, 76.3, 126.7, 136.6, 151.0, 169.1, 172.3, 172.4. Anal. Calcd
for C12H15NO7: C, 50.53; H, 5.30; N 4.91. Found: C, 50.66;
H, 5.41; N, 4.82.
The major diastereomer (yellow solid, mp 93-94 °C) exhib-
ited the following spectral properties: IR (KBr) 3438, 3331,
1
1738, 1674 cm-1; H-NMR (CDCl3, 300 MHz) δ 3.57 (s, 4H),
3.65 (s, 3H), 3.78 (s, 3H), 4.07 (s, 1H), 6.06 (d, 1H, J ) 9.9
Hz), 6.38 (d, 1H, J ) 9.9 Hz); 13C-NMR (CDCl3, 75 MHz) δ