10.1002/ejoc.201900078
European Journal of Organic Chemistry
FULL PAPER
3-(3,4-dimethoxyphenyl)-4-oxo-4H-furo[2,3-h]chromene-2-carboxylic
acid (19).To a solution of 9.0 mg (0.023 mmol) of compound 18 in 0.5 mL
of DMF was added 0.2 mL of a 20% aqueous NaOH solution, and the
reaction mixture was stirred at r.t. for 10 min. The resulting mixture was
then partitioned between H2O and EtOAc. The aqueous layer was acidified
with a 1N HCl solution to pH3 and extracted with EtOAc. The organic
phase was dried with Na2SO4 (s), and concentrated under reduced
pressure to give 7.1 mg (84% yield) of the acid 19 as a yellow solid; mp
146-148 ºC; IR (neat) 2926, 2853, 1703, 1618, 1516, 1463, 1258, 1141,
and 1027 cm-1;1 H-NMR (400 MHz, DMSO-d6) 훿 3.73 (s, 3H), 3.79 (s, 3H),
6.85 (dd, 1H, J = 8.3 and 1.6 Hz), 6.93 (d, 1H, J = 1.6 Hz), 6.98 (d, 1H, J
= 8.3 Hz), 7.39 (d, 1H, J = 1.7 Hz), 7.80 (d, 1H, J = 8.8 Hz), 8.01 (d, 1H, J
= 8.8 H), and 8.27 (brs, 1H); 13C-NMR (100 MHz, DMSO-d6) 훿 176.2,
162.6, 157.9, 152.4, 149.4, 148.8, 148.1, 147.8, 123.7, 123.4, 122.5, 121.6
118.7, 116.8, 113.9, 111.2, 111.0, 104.3, 55.53, and 55.50; HRMS Calcd
for [(C20H15O7)+H]+: 367.0812. Found: 367.0819.
(3, 6H), 3.85 (s, 3H), 3.87 (s, 3H), 4.11 (q, 2H, J = 7.1 Hz), 5.23 (d, 1H, J
= 10.9 Hz), 5.27 (d, 1H, J = 17.7 Hz), 6.12 (dd, 1H, J = 17.7 and 10.9 Hz),
6.76-6.90 (m, 3H), 6.99 (dd, 1H, J = 8.9 and 2.2 Hz), 7.05 (d, 1H, J = 8.9
and 2.2 Hz), 8.05 (d, 1H, J = 8.9 Hz); 13C-NMR (100 MHz, CDCl3) 176.7,
162.0, 161.8, 156.5, 150.7, 149.0, 148.5, 142.9, 126.9, 125.0, 123.7, 122.2,
119.2, 117.5, 114.7, 112.9, 110.7, 105.8, 81.1, 62.2, 55.75, 55.74, 27.0(x2),
and 13.5; HRMS Calcd for [(C25H26O7)+Na]+: 4611.1571. Found: 461.1572.
Ethyl 3-(3,4-dimethoxyphenyl)-7-hydroxy-8-(2-methylprop-1-en-1-yl)-
4-oxo-4H-chromene-2-carboxylate (23). The solution of 20 mg (0.049
mmol) of the alkene 22 in 0.5 mL of DMF was heated using microwave
reactor at 200 °C for 30 min. After that, the solvent was removed under
reduced pressure and the crude residue was purified by flash silica gel
column chromatography eluted with 20% acetone/hexane solution to give
18 mg (90% yield) of the alkene 23 as the pale yellow solid; IR (neat) 3221,
2934, 1739, 1619, 1560, 1515, 1438, 1267, 1212, 1171, and 1025 cm-1;
1H-NMR (400 MHz, CDCl3) δ 1.01 (t, 3H, J = 7.1 Hz), 1.71 (s, 3H), 1.82 (s,
3H), 3.59 (d, 2H, J = 7.3 Hz), 3.85 (s, 3H), 3.87 (s, 3H), 4.18 (q, 2H, J =
7.1 Hz), 5.31 (brt, 1H, J = 7.3 Hz), 6.82 (dd, 1H, J = 8.1 and 1.9 Hz), 6.86-
6.92 (m, 3H), and 7.93 (brd, 1H, J = 8.8 Hz; 13C-NMR (100 MHz, CDCl3)
178.0, 161.8, 160.5, 155.0, 150.9, 149.1, 148.6, 134.1, 133.9, 124.8, 124.7,
123.6, 122.3, 120.7, 117.0, 115.5, 115.2, 113.0, 110.7, 62.4, 55.8(x2), 25.8,
22.1, 17.8, and 13.7; HRMS Calcd for [(C25H26O7)+Na]+: 461.1571. Found:
461.1568.
6-oxo-dehydroelliptone (20).To solution containing 8.5 mg (0.023 mmol)
of the acid 19 in 0.2 mL of 1:1 MeCN/H2O solution, were added 18 mg
(0.070 mmol) of K2S2O8 and 0.7 mg (0.002 mmol) of AgNO3. The solution
mixture was heated at 60 oC for 15 h, cooled to r.t., and quenched with a
saturated aqueous NaHCO3 solution. After stirring additional 15 min, the
mixture was extracted with aa 1:3 i-PrOH:CH2Cl2 solution (4x). The
combined organic layer was then washed with a saturated aqueous NaCl
solution, dried with Na2SO4 (s), and concentrated under reduced pressure
to give 6.2 mg (75% yield) of the title compound 20 as a bright yellow solid;
bright yellow solid, mp decomp. 321-323 ºC; IR (neat) 3146, 1741, 1648,
1625, 1513, 1449, 1292, 1271, 1223, 1165, and 1051 cm-1; 1 H-NMR (400
MHz, CDCl3) 훿 3.99 (s, 3H), 4.06 (s, 3H), 6.94 (s, 1H), 7.38 (dd, 1H, J =
2.2 and 0.8 Hz), 7.66 (dd, 1H, J = 8.9 and 0.8 Hz), 7.82 (d, 1H, J = 2.2 Hz),
8.26 (d, 1H, J = 8.9 Hz), and 9.04 (s, 1H); 13C-NMR (100 MHz, CDCl3) 훿
177.1, 159.0, 156.0, 151.4, 150.1, 146.9, 146.4, 145.4, 142.1, 122.1, 122.0,
119.6, 117.5, 111.4, 108.1, 107.9, 104.9, 99.6, 56.34, 56.27; HRMS Calcd
for [(C20H12O7)+H]+: 365.0656. Found: 365.0663.
Ethyl 3-(3,4-dimethoxyphenyl)-4-oxo-8-(prop-1-en-2-yl)-8,9-dihydro-
4H-furo[2,3-h]chromene-2-carboxylate (24). To a solution containing 25
mg (0.057 mmol) of the alkyne 23 in 0.6 mL of toluene under Ar
atmosphere at rt was added 7 mg (125 mg/mmol by wt) of 4Aº molecular
sieve powder, 12 mg (0.11 mmol) of Na2CO3, 1 µL (0.012 mmol) of pyridine,
and 7.4 mg (0.023 mmol) of Pd(TFA)2. The solution flask was then flushed
with O2 and kept under O2 balloon. The reaction mixture was stirred at
100 °C for 15 h, then filtered to a pad of celite and washed thoroughly with
CH2Cl2. The filtrated was evaporated under reduced pressure and the
crude residue was purified by preparative TLC eluted with 30%
acetone/hexane solution to give 10.8 mg (44% yield) of the title compound
24 as a pale yellow solid, along with 4.8 mg (19% yield) of compound 27
as a pale yellow solid; Compound 24; IR (neat) 2959, 2935, 2835, 1734,
1647, 1627, 1606, 1515, 1452, 1404, 1263, 1244, 1192, 1170, 1142, and
1024 cm-1; 1H-NMR (400 MHz, CDCl3) δ 1.02 (t, 3H, J = 7.1 Hz), 1.79 (s,
3H), 3.23 (dd, 1H, J = 16.8 and 7.8 Hz) , 3.57 (dd, 1H, J = 16.0 and 9.9
Hz), 3.86 (s, 3H), 3.89 (s, 3H), 4.13 (q, 2H, J = 7.1 Hz), 4.96 (s, 1H), 5.11
(s, 1H), 5.42 (brt, 1H, J = 9.0 Hz), 6.81 (dd, 1H, J = 8.3 and 1.9 Hz), 6.86
(d, 1H, J = 1.9 Hz), 6.88 (d, 1H, J = 8.3 Hz), 6.91 (d, 1H, J = 8.6 Hz), and
8.07 (d, 1H, J = 8.6 Hz); 13C-NMR (100 MHz, CDCl3) 176.5, 165.5, 162.0,
152.8, 150.2, 149.1, 148.5, 142.7, 128.0, 124.9, 123.7, 122.3, 117.9, 113.1,
113.0, 112.9, 110.7, 109.1, 87.9, 62.3, 55.80, 55.79, 31.3, 17.0, and 13.5;
HRMS Calcd for [(C25H24O7)+Na]+: 459.1414. Found: 459.1412.
Ethyl 3-(3,4-dimethoxyphenyl)-7-((2-methylbut-3-yn-2-yl)oxy)-4-oxo-
4H-chromene-2-carboxylate (21). To a solution containing 200 mg (0.54
mmol) of the alcohol 15 in 5.4 mL of acetone at r.t. under Ar atmosphere
was added 82 µL (0.81 mmol) of 3-chloro-3-methylbut-1-yne, 373 mg (2.7
mmol) of K2CO3, 21 mg (0.108 mmol), and 99 mg (0.59 mmol) of KI. The
mixture was then stirred at 60 °C for 1.5 h. After that, the resulting solution
was cooled to r.t., filtered through a pad of celite and washed thoroughly
with EtOAc. The filtrate was evaporated under reduced pressure and the
crude residue was purified by flash silica gel column chromatography
eluted with 15% and 40% acetone/hexane solution to give 145 mg (62%
yield) of the alkyne 21 as the pale yellow solid; IR (neat) 3245, 2990, 2837,
1736, 1648, 1620, 1515, 1440, 1263, 1248, 1195, 1137, and 1025 cm-1;
1H-NMR (400 MHz, CDCl3) δ 1.03 (t, 3H, J = 7.1 Hz), 1.75 (3, 6H), 2.71 (s,
1H), 3.87 (s, 3H), 3.89 (s, 3H), 4.14 (q, 2H, J = 7.1 Hz), 6.81 (dd, 1H, J =
8.2 and 2.0 Hz), 6.86 (d, 1H, J = 2.2 Hz), 6.89 (d, 1H, J = 8.2 Hz), 7.15 (dd,
1H, J = 8.9 and 2.3 Hz), 7.43 (d, 1H, J = 2.3 Hz), and 8.12 (d, 1H, J = 8.9
Hz); 13C-NMR (100 MHz, CDCl3) 176.7, 162.1, 160.9, 156.5, 150.8, 149.1,
148.6, 127.1, 125.1, 123.7, 122.3, 118.9, 118.1, 113.0, 110.7, 106.0, 84.3,
75.5, 72.8, 62.3, 55.83, 55.82, 29.4(x2), and 13.6; HRMS Calcd for
[(C25H24O7)+Na]+: 459.1414. Found: 459.1414.
3-(3,4-dimethoxyphenyl)-4-oxo-8-(prop-1-en-2-yl)-8,9-dihydro-4H-
furo[2,3-h]chromene-2-carboxylic acid (25). To a solution containing 18
mg (0.04 mmol) of the ester 24 in 0.5 mL of a 3:2:1 of THF/MeOH/H2O
solution at r.t. was added 4 mg (0.08 mmol) of LiOH.H2O. The resulting
mixture was stirred for 4 h and organic solvent was removed under
reduced pressure. The crude residue was then diluted with H2O and
partitioned with EtOAc. The aqueous layer was acidified with a 1N HCl
solution to pH3 and extracted with EtOAc (4x). The combined organic layer
was then washed with a saturated aqueous NaCl solution, dried with
Na2SO4(s), and concentrated under reduced pressure to give 16 mg (95%)
of the title compound 25 as a pale yellow solid; IR (neat) 2926, 2858, 1737,
1619, 1575, 1516, 1453, 1295, 1263, 1241, 1212, 1198, 1171, and 1028
cm-1; 1H-NMR (300 MHz, DMSO-d6) δ 1.77 (s, 3H), 3.19 (dd, 1H, J = 15.9
and 7.8 Hz), 3.62 (dd, 1H, J = 15.9 and 9.9 Hz), 3.72 (s, 3H), 3.79 (s, 3H),
4.97 (s, 1H), 5.12 (s, 1H), 5.54 (brt, 1H, J = 8.1 Hz), 6.80 (dd, 1H, J = 8.3
and 1.9 Hz), 6.88 (d, 1H, J = 1.9 Hz), 6.97 (d, 1H, J = 8.3 Hz), 7.06 (d, 1H,
J = 8.6 Hz), and 7.92 (d, 1H, J = 8.6 Hz); 13C-NMR (75 MHz, CDCl3) δ
175.4, 164.9 162.5, 152.1, 151.8, 148.7, 148.0, 143.0, 127.2, 123.7, 122.7,
Ethyl 3-(3,4-dimethoxyphenyl)-7-((2-methylbut-3-en-2-yl)oxy)-4-oxo-
4H-chromene-2-carboxylate (22). The solution of 400 mg (0.92 mmol) of
the alkyne 21 and 194 mg (0.092 mmol of Pd) of Lindlar catalyst (5% Pd)
in 9.2 mL of CH2Cl2 was stirred under 175 psi of H2 atmosphere for 8 h.
After the reaction completed, the solution was filtered to a pad of celite and
washed thoroughly with CH2Cl2. The filtrated was evaporated under
reduced pressure and the crude residue was purified by flash silica gel
column chromatography eluted with 20% acetone/hexane solution to give
402 mg (100% yield) of the alkene 22 as a pale yellow solid; IR (neat) 2979,
2936, 1837, 1736, 1647, 1619, 1607, 1515, 1439, 1261, 1205, 1171, 1139,
and 1025 cm-1; 1H-NMR (400 MHz, CDCl3) δ 1.01 (t, 3H, J = 7.1 Hz), 1.55
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