J. R. Mays et al. / Bioorg. Med. Chem. 18 (2010) 249–266
263
(11.10 mL). After stirring at rt for 18 h, triethylamine (60
l
L)
2.37 (s, 3H); 13C NMR (CDCl3, 125 MHz) d 176.6, 160.5, 155.7,
152.8, 147.9, 147.8, 132.8, 126.1, 125.0, 124.5, 122.6, 118.6,
114.5, 110.1, 110.0, 108.6, 101.4, 69.6, 8.4; IR (film) mmax 3076,
3016, 2995, 2918, 1641, 1620, 1601, 1504, 1493, 1427, 1389,
1337, 1281, 1252, 1232, 1202, 1144, 1115, 1084, 1072, 1038,
997, 935, 922, 851, 800, 783 cmÀ1; HRMS (ESI+) m/z: [M+H]+ calcd
for C20H16O5, 337.1076; found, 337.1067.
was added and the solvent was concentrated. The residue was
partially purified via column chromatography (SiO2, 50:1 CH2Cl2/
MeOH) and the coupled carbonate was used without further
purification.
Carbonate was added to MeOH (4.0 mL), CH2Cl2 (1.0 mL), and
triethylamine (400 lL) and stirred for 18 h at rt. The solvent was
concentrated and the residue purified via PTLC (SiO2, 20:1
CH2Cl2/MeOH then 20:1:1 CH2Cl2/MeOH/acetone then 40:40:1:1
CH2Cl2/EtOAc/MeOH/acetone) to give 32c as a colorless amorphous
solid (7 mg, 4% over two steps): 1H NMR (CDCl3/MeOD, 500 MHz) d
7.85 (s, 1H), 6.99 (d, J = 1.6 Hz, 1H), 6.90 (dd, J = 8.0, 1.7 Hz, 1H),
6.84 (d, J = 8.0 Hz, 1H), 6.57 (d, J = 2.2 Hz, 1H), 6.44 (d, J = 2.2 Hz,
1H), 5.96 (s, 2H), 5.54 (d, J = 2.1 Hz, 1H), 4.09 (dd, J = 9.4, 3.4 Hz,
1H), 4.06 (m, 1H), 3.56 (s, 3H), 3.30 (d, J = 9.4 Hz, 1H), 1.32 (s,
3H), 1.10 (s, 3H); 13C NMR (CDCl3/MeOD, 125 MHz) d 180.9,
162.6, 162.2, 158.9, 153.3, 148.0, 147.9, 124.4, 124.0, 122.6,
109.7, 108.7, 106.8, 101.4, 100.2, 98.3, 94.6, 84.2, 78.9, 71.0, 68.3,
62.0, 28.9, 22.7; IR (film) mmax 3410, 2980, 2920, 2849, 1722,
1655, 1614, 1574, 1504, 1493, 1470, 1435, 1369, 1308, 1271,
1248, 1209, 1194, 1180, 1157, 1117, 1038, 995, 955, 922, 847,
4.49. 6-Allyl-3-(benzo[d][1,3]dioxol-5-yl)-7-hydroxy-4H-
chromen-4-one (34a)
N,N-Diethylaniline (460 lL) was added to 33a (392 mg,
1.22 mmol) in a sealed flask and the solution was then heated to
170 °C for 48 h. The reaction was diluted with 1 M aqueous HCl
solution (50 mL) and CH2Cl2 (50 mL). The organic layers were
washed with 1 M aqueous HCl solution (3 Â 50 mL), dried
(Na2SO4), filtered, and concentrated. The residue was purified via
column chromatography (SiO2, 8:1:1 hexanes/CH2Cl2/EtOAc to
4:1:1 hexanes/CH2Cl2/EtOAc) then PTLC (SiO2, 2:1:1 hexanes/
CH2Cl2/EtOAc) to give 6-allyl 34a as a near-colorless amorphous
solid (3 mg, 1%): 1H NMR (CDCl3, 500 MHz) d 8.06 (s, 1H), 7.90 (s,
1H), 7.09 (d, J = 1.7 Hz, 1H), 6.97 (dd, J = 6.3, 1.7 Hz, 1H), 6.89–
6.86 (m, 2H), 6.05 (m, 1H), 5.99 (s, 2H), 5.24 (m, 1H), 5.21 (dq,
J = 6.8, 1.4 Hz, 1H), 3.53 (d, J = 6.4 Hz, 2H); 13C NMR (CDCl3,
125 MHz) d 176.1, 159.6, 156.9, 152.5, 147.9, 147.8, 135.7, 128.1,
125.9, 125.2, 125.1, 122.6, 118.5, 117.7, 110.0, 108.6, 103.4,
101.4, 35.0; IR (film) mmax 3076, 2953, 2918, 2872, 2851, 1620,
1574, 1504, 1495, 1435, 1404, 1371, 1319, 1275, 1252, 1240,
1151, 1138, 1042, 912, 858, 768 cmÀ1; HRMS (ESI+) m/z: [M+Na]+
calcd for C19H14O5, 345.0739; found, 345.0744.
;
822, 783, 737 cmÀ1 HRMS (ESI+) m/z: [M+H]+ calcd for
C24H24O10, 473.1448; found, 473.1427.
4.47. 7-(Allyloxy)-3-(benzo[d][1,3]dioxol-5-yl)-4H-chromen-4-
one (33a)
N,N-Diisopropylethylamine (645
lL, 481 mg, 3.72 mmol) and
allyl bromide (644 L, 900 mg, 7.44 mmol) were sequentially
l
added to 30a (700 mg, 2.48 mmol) in anhydrous N,N-dimethyl-
formamide (3.5 mL) and anhydrous acetonitrile (12.40 mL) and
the resulting solution was then heated to reflux for 4 h. After cool-
ing to rt, the reaction was poured into water and the precipitate
was collected by filtration. The residue was purified via column
chromatography (SiO2, 4:1:1 hexanes/CH2Cl2/EtOAc) to give 33a
as a colorless amorphous solid (418 mg, 52%): 1H NMR (CDCl3,
4.50. 6-Allyl-3-(benzo[d][1,3]dioxol-5-yl)-7-hydroxy-8-methyl-
4H-chromen-4-one (34b)
N,N-Diethylaniline (210 lL) was added to 33b (180 mg,
0.53 mmol) in a sealed flask and the solution was then heated to
170 °C for 48 h. The reaction was diluted with 1 M aqueous HCl
solution (10 mL) and the precipitate was collected by filtration.
The residue was purified via column chromatography (SiO2, 8:1:1
hexanes/CH2Cl2/EtOAc to 4:1:1 hexanes/CH2Cl2/EtOAc) to give 6-
allyl 34b as a near-colorless amorphous solid (93 mg, 19%): 1H
NMR (DMSO-d6, 500 MHz) d 9.74 (br s, 1H), 8.43 (s, 1H), 7.71 (s,
1H), 7.15 (d, J = 1.7 Hz, 1H), 7.07 (dd, J = 8.1, 1.7 Hz, 1H), 6.98 (d,
J = 8.1 Hz, 1H), 6.06 (s, 2H), 6.01 (m, 1H), 5.12–5.07 (m, 2H), 3.46
(d, J = 6.5 Hz, 1H), 2.31 (s, 3H); 13C NMR (DMSO-d6, 125 MHz) d
174.8, 157.8, 154.0, 153.5, 147.0, 146.8, 136.4, 126.2, 1225.9,
122.9, 122.7, 122.4, 116.5, 116.2, 111.4, 109.4, 108.1, 101.0, 33.9,
8.8; IR (film) mmax 3205, 2920, 2851, 1634, 1622, 1589, 1574,
1495, 1464, 1435, 1383, 1271, 1240, 1180, 1097, 1070, 1041,
933, 914, 856, 800, 764, 748 cmÀ1; HRMS (ESI+) m/z: [M+H]+ calcd
for C20H16O5, 337.1076; found, 337.1061.
500 MHz)
d 8.22 (d, J = 8.9 Hz, 1H), 7.92 (s, 1H), 7.11 (d,
J = 1.7 Hz, 1H), 7.02 (dd, J = 8.9, 2.4 Hz, 1H), 6.98 (dd, J = 8.0,
1.7 Hz, 1H), 6.88 (d, J = 8.0 Hz, 1H), 6.87 (d, J = 2.4 Hz, 1H), 6.08
(ddt, J = 17.3, 10.5, 5.3 Hz, 1H), 6.00 (s, 3H), 5.47 (dq, J = 17.3,
1.5 Hz, 1H), 5.37 (dq, J = 10.5, 1.5 Hz, 1H), 4.66 (dt, J = 5.3, 1.5 Hz,
2H); 13C NMR (CDCl3, 125 MHz) d 175.9, 163.1, 158.0, 152.4,
147.9, 147.8, 132.3, 128.1, 125.9, 122.6, 118.8, 118.6, 115.2,
110.0, 108.6, 101.4, 101.3; IR (film) mmax 3080, 2885, 1628, 1597,
1566, 1502, 1487, 1443, 1423, 1387, 1371, 1333, 1286, 1269,
1250, 1202, 1097, 1036, 937, 924, 852, 818, 781 cmÀ1; HRMS
(ESI+) m/z: [M+H]+ calcd for C19H14O5, 323.0919; found, 323.0915.
4.48. 7-(Allyloxy)-3-(benzo[d][1,3]dioxol-5-yl)-8-methyl-4H-
chromen-4-one (33b)
N,N-Diisopropylethylamine (645
lL, 481 mg, 3.72 mmol) and
allyl bromide (644 L, 900 mg, 7.44 mmol) were sequentially
l
4.51. 8-Allyl-3-(benzo[d][1,3]dioxol-5-yl)-7-hydroxy-4H-
added to 30b (702 mg, 2.37 mmol) in anhydrous N,N-dimethyl-
formamide (6.5 mL) and anhydrous acetonitrile (12.40 mL) and
the resulting solution was then heated to reflux for 4 h. After cool-
ing to rt, the reaction was poured into water (150 mL) and was ex-
tracted with CH2Cl2 (3 Â 200 mL) and EtOAc (200 mL). The organic
layers were dried (Na2SO4), filtered, and concentrated. The residue
was purified via column chromatography (SiO2, 4:1:1 hexanes/
chromen-4-one (34c)
The acidic aqueous layers from the construction of 34a were
concentrated, water (50 mL) was added, the precipitate was col-
lected by filtration and washed with cold Et2O to give 8-allyl 34c
as a grey amorphous solid (213 mg, 54%): 1H NMR (DMSO-d6,
500 MHz) d 10.75 (br s, 1H0, 8.42 (s, 1H), 7.89 (d, J = 8.8 Hz, 1H),
7.15 (d, J = 1.6 Hz, 1H), 7.07 (dd, J = 8.0, 1.7 Hz, 1H), 7.03 (d,
J = 8.8 Hz, 1H), 6.98 (d, J = 8.0 Hz, 1H), 6.06 (s, 2H), 5.97 (ddt,
J = 17.0, 10.2, 6.0 Hz, 1H), 5.02–4.95 (m, 2H), 3.53 (dbr t, J = 6.0,
1.5 Hz, 2H); 13C NMR (DMSO-d6, 125 MHz) d 174.8, 160.0, 155.3,
153.5, 147.0, 135.3, 125.8, 124.7, 122.8, 116.6, 115.2, 114.3,
112.8, 109.4, 108.1, 101.0, 26.5; IR (film) mmax 3234, 2905, 1618,
CH2Cl2/EtOAc) to give 33b as
a colorless amorphous solid
(199 mg, 25%): 1H NMR (CDCl3, 500 MHz) d 8.14 (d, J = 8.9 Hz,
1H), 7.99 (s, 1H), 7.12 (d, J = 1.7 Hz, 1H), 7.00 (d, J = 8.9 Hz, 1H),
6.99 (dd, J = 8.0, 1.7 Hz, 1H), 6.88 (d, J = 8.0 Hz, 1H), 6.10 (ddt,
J = 17.2, 10.6, 5.1 Hz, 1H), 6.00 (s, 2H), 5.47 (dq, J = 17.2, 1.5 Hz,
1H), 5.34 (dq, J = 10.6, 1.5 Hz, 1H), 4.70 (dt, J = 5.1, 1.5 Hz, 2H),