The Journal of Organic Chemistry
Article
MHz, CDCl3): δ 10.09 (1H, s, 5-CHO), 7.56 (2H, m, 2″,6″-H), 7.00
(2H, m, 3″,5″-H), 6.98 (1H, s, 3′-H), 6.80 (1H, s, 6′-H), 6.03 (2H, m,
2-HAHB), 4.75 (2H, s, OCH2OCH3), 3.91 (3H, s, OCH3), 3.86 (3H, s,
OCH3), 3.85 (3H, s, OCH3), 3.15 (3H, s, OCH2OCH3). 13C NMR
(75 MHz, CDCl3): δ 189.5 (CHO), 159.3 (4″-C), 154.5 (7a-C), 149.7
(6-C), 149.3 (4′-C), 147.6 (5′-C), 142.6 (3a-C), 131.3 (2″,6″-C),
131.1 (1′-C), 124.6 (2′-C), 123.8 (1″-C), 123.2, 122.3, 113.8 (3″,5″-
C), 113.6, 113.3 (3′-C), 112.3 (6′-C), 102.1 (2-C), 101.1
(OCH2OCH3), 57.7 (OCH2OCH3), 56.1 (OCH3), 56.0 (OCH3),
55.2 (OCH3). IR (neat): νmax 3034, 1687, 1598 cm−1. MS (ESI) m/z:
511 (40, [M + 2+Na]+), 509 (100, [M + Na]+). HRMS (ESI) m/z:
[M + H]+ calcd for C25H24O835Cl 487.1160; found 487.1155.
113.6 (3′,5′-C), 113.3 (4-C), 109.1 (10a-C), 103.6 (10-C), 101.8 (2-
C), 95.6 (7-C), 56.5 (OCH3), 56.3 (OCH3), 55.3 (OCH3). IR (neat):
νmax 3539, 3071, 1609 cm−1. MS (EI) m/z: 394 (100, [M]+•), 351
(30). HRMS (EI) m/z: [M]+• calcd for C22H18O7 394.1053; found m/
z 394.1056.
Benzyl (8,9-Dimethoxy-4-(4-methoxyphenyl)benzo[b][1,3]-
dioxolo[4,5-e]benzofuran-5-yl)carbonate (17). 16 (16 mg, 37.0
μmol) was dissolved in anhydrous pyridine (1 mL) and CH2Cl2 (0.5
mL) and cooled to 0 °C. Benzyl chloroformate (10 μL, 12 mg, 73.0
μmol) was added dropwise, and the solution was stirred for 30 min.
The reaction was then quenched by the addition of water, and the
solution was extracted with EtOAc. The organic layer was washed with
saturated aqueous NaHCO3, water, and brine, dried with MgSO4,
filtered, and concentrated to give a yellow amorphous solid.
Purification was performed using flash column chromatography on
silica using 30% EtOAc in petroleum ether as eluent (Rf = 0.2),
4-(2-Chloro-4,5-dimethoxyphenyl)-6-(methoxymethoxy)-7-
(4-methoxyphenyl)benzo[d][1,3]dioxol-5-yl Formate (5). 6
(78.0 mg, 0.160 mmol) was added to a solution of potassium fluoride
(46 mg, 0.800 mmol) and m-CPBA (50%, 55 mg, 0.160 mmol) in
CH2Cl2 (20 mL) at 0 °C. After it was stirred for 2 h the reaction
mixture was filtered and the solvent removed to give a yellow oil.
Purification was performed by flash column chromatography on silica
using 50% EtOAc in petroleum ether as eluent (Rf = 0.4), yielding the
title compound as a colorless amorphous solid (49%, 40.0 mg, 0.0796
1
yielding a colorless amorphous solid (87%, 17.0 mg, 32.2 μmol). H
NMR (300 MHz, CDCl3): δ 7.47 (2H, m, 2″,6″-C), 7.40−7.25 (5H,
m, 2−6-H), 7.33 (1H, s, 7′-H), 7.09 (1H, s, 10′-H), 6.91 (2H, m,
3″,5″-H), 6.14 (2H, s, 2′-H), 5.20 (2H, s, OCH2Ph), 3.99 (OCH3),
3.97 (OCH3), 3.84 (OCH3). 13C NMR (75 MHz, CDCl3): δ 159.3
(4″-C), 153.2 (CO3), 151.8 (8′-C), 150.0 (9′-C), 146.4, 144.3, 140.9
(3′a-C), 140.6 (10′c-C), 137.0, 134.8, 131.0 (2″,6″-C), 128.6, 128.5
(3,5-C), 128.2 (2,6-C), 127.7, 123.2, 115.1, 113.9 (3″,5″-C), 113.1,
109.1 (10′b-C), 103.5 (10′-C), 102.1 (2′-C), 95.8 (7′-C), 70.5
(OCH2Ph), 56.5 (OCH3), 56.3 (OCH3), 55.2 (OCH3). IR (neat):
νmax 3030, 1764, 1609 cm−1. MS (EI) m/z: 528 (20, [M]+•), 394 (90),
393 (100), 363 (50). HRMS (EI) m/z: [M]+• calcd for C30H24O9
528.1420; found 528.1417.
5-(((Benzyloxy)carbonyl)oxy)-8,9-dimethoxy-4-(4-
methoxyphenyl)benzo[b][1,3]dioxolo[4,5-e]benzofuran-2-yl
Acetate (18). A solution of 17 (12 mg, 22.7 μmol) and lead
tetraacetate (23 mg, 51.8 μmol) in toluene (3 mL) was heated to
reflux for 2 h until the consumption of starting material was observed
by TLC. After it was cooled, the reaction mixture was filtered through
Celite and concentrated in vacuo, yielding the title compound as a
colorless amorphous solid (78%, 10.4 mg, 17.7 μmol). The title
compound was found to be unstable and was used directly in the next
step without further purification. 1H NMR (300 MHz, CDCl3): δ 7.89
(1H, s, 2-H), 7.57 (2H, m, 2″,6″-H), 7.40−7.25 (6H, m, 2′-6′-H, 7-H),
7.10 (1H, s, 10-H), 6.92 (2H, m, 3″,5″-H), 5.20 (2H, s, OCH2Ph),
4.00 (3H, s, OCH3), 3.97 (3H, s, OCH3), 3.84 (3H, s, OCH3), 2.09
(3H, s, C(O)CH3). IR (neat): νmax 3042, 1769, 1610, 1520 cm−1. MS
(EI) m/z: 586 (40, [M]+•), 567 (100). HRMS (EI) m/z: [M]+• calcd
for C32H26O11 586.1475; found 586.1473.
1
mmol). H NMR (300 MHz, CDCl3): δ 8.08 (1H, s, OCHO), 7.56
(2H, m, 2″,6″-H), 6.98 (2H, m, 3″,5″-H), 6.95 (1H, s, 3′-C), 6.78
(1H, s, 6′-C), 5.95 (2H, s, 2-H), 4.62 (2H, s, OCH2OCH3), 3.87 (3H,
s, OCH3), 3.82 (6H, s, OCH3), 3.14 (3H, s, OCH2OCH3). 13C NMR
(75 MHz, CDCl3): δ 159.6 (OCHO), 159.3 (4″-C), 149.7 (4′-C),
147.6 (5′-C), 143.1 (6-C), 142.0 (7a-C), 140.7 (3a-C), 135.7, 131.2
(2″,6″-C), 131.2 (1′-C), 125.3 (2′-C), 123.6 (1″-C), 121.4, 118.2,
113.7 (3″,5″-C), 112.4, 109.9, 101.7 (2-C), 99.2 (OCH2OCH3), 57.3
(OCH2OCH3), 56.1 (OCH3), 56.0 (OCH3), 55.2 (OCH3). IR (neat):
νmax 3069, 1752, 1610 cm−1. MS (ESI) m/z: 527 (40, [M + 2 + Na]+),
525 (100, [M + Na]+), 483 (50). HRMS (ESI) m/z: [M + Na]+ calcd
for C25H23O935Cl23Na 525.0928; found 525.0915.
8,9-Dimethoxy-5-(methoxymethoxy)-4-(4-methoxyphenyl)-
benzo[b][1,3]dioxolo[4,5-e]benzofuran (4). A solution of 5 (75
mg, 0.149 mmol) and copper(I) oxide (108 mg, 0.750 mmol) in
anhydrous pyridine (5 mL) was degassed via a freeze/thaw process
three times. The reaction mixture was then heated to relux for 16 h
with stirring. After the mixture was cooled, EtOAc was added and the
solution was then washed five times with water and then brine. The
organic layer was dried with MgSO4, filtered, and concentrated to yield
the title compound as a brown amorphous solid (96%, 63.0 mg, 0.144
1
mmol). H NMR (300 MHz, CDCl3): δ 7.61 (2H, m, 2′,6′-H), 7.34
(1H, s, 7-H), 7.00 (2H, m, 3′,5′-H), 7.11 (1H, s, 10-H), 6.10 (2H, s, 2-
H), 5.04 (2H, s, OCH2OCH3), 3.99 (3H, s, OCH3), 3.98 (3H, s,
OCH3), 3.86 (3H, s, OCH3), 3.21 (3H, s, OCH2OCH3). 13C NMR
(75 MHz, CDCl3): δ 159.0 (4′-C), 151.5, 149.8, 146.2 (6a-C), 145.0
(3a-C), 140.7 (5a-C), 135.1 (5-C), 132.4 (10c-C), 131.5 (2′, 6′-C),
124.7 (1′-C), 115.5 (10b-C), 113.6 (3′, 5′-C), 113.3 (4-C), 109.0
(10a-C), 103.5 (10-C), 101.8 (2-C), 98.5 (OCH2OCH3), 95.6 (7-C),
57.0 (OCH2OCH3), 56.5 (OCH3), 56.2 (OCH3), 55.2 (OCH3). IR
(neat): νmax 3036, 1609 cm−1. MS (EI) m/z: 438 (10, [M]+•), 407
(25), 269 (75), 200 (100). HRMS (EI) m/z: [M]+• calcd for
C24H22O8 438.1315; found 438.1313.
B e n z y l ( 1 , 2 - D i h y d r o x y - 7 , 8 - d i m e t h o x y - 3 - ( 4 -
methoxyphenyl)dibenzo[b,d]furan-4-yl)carbonate (19). A sol-
ution of 18 (10 mg, 17.7 μmol) in acetic acid (2 mL) was stirred at
room temperature for 30 min, at which time the solvent was removed
in vacuo, yielding the title compound as an unstable brown amorphous
solid (99%, 9.0 mg, 18 μmol) that was used immediately in the
1
following step. H NMR (300 MHz, CDCl3): δ 7.48 (2H, m, 2″,6″-
H), 7.42 (1H, s, 6′-H), 7.40−7.25 (5H, m, 2−6-H), 7.14 (1H, s, 9′-H),
6.95 (2H, m, 3″,5″-H), 5.22 (2H, s, OCH2Ph), 4.03 (3H, s, OCH3),
4.00 (3H, s, OCH3), 3.86 (3H, s, OCH3), 2.82 (1H, s, OH), 2.80 (1H,
s, OH).
8,9-Dimethoxy-4-(4-methoxyphenyl)benzo[b][1,3]dioxolo-
[4,5-e]benzofuran-5-ol (16). To a solution of 4 (60 mg, 0.137
mmol) in THF (5 mL) was added HCl (4.0 M in dioxane, 0.82 mL,
0.205 mmol), and the solution was stirred at room temperature for 2
h. After addition of water the solution was extracted with EtOAc and
the organic layer was washed with water and brine, dried with MgSO4,
filtered, and concentrated to give a colorless amorphous solid.
Purification was achieved via flash column chromatography on silica
using 50% EtOAc in petroleum ether as eluent (Rf = 0.4), yielding the
title compound as a colorless amorphous solid (83%, 50.0 mg, 0.114
4-Hydroxy-7,8-dimethoxy-3-(4-methoxyphenyl)dibenzo-
[b,d]furan-1,2-diyl Diacetate (20). A solution of 19 (30 mg, 58.1
μmol) in THF (5 mL) was cooled to −78 °C. Lithium
hexamethyldisilazide (1.0 M, 128 μL, 128 μmol) was then added
dropwise with stirring. After 30 min acetyl chloride (10 μL, 11 mg, 145
μmol) was added dropwise and the solution was warmed to room
temperature. The solution was then concentrated in vacuo and the
residue dissolved in EtOAc (5 mL). Palladium hydroxide on carbon
(10 mg) was added and the solution was stirred vigorously under an
atmosphere of hydrogen for 16 h. The reaction was then filtered and
concentrated to give a brown solid. Purification was achieved via flash
column chromatography on silica using 50% EtOAc in petroleum
ether as eluent (Rf = 0.2), yielding the title compound as a stable
1
mmol). H NMR (300 MHz, CDCl3): δ 7.56 (2H, m, 2′,6′-H), 7.32
(1H, s, 7-H), 7.06 (2H, m, 3′,5′-H), 7.02 (1H, s, 10-H), 6.06 (2H, s, 2-
H), 5.26 (broad s, 1H, 5-OH), 3.98 (3H, s, OCH3), 3.95 (3H, s,
OCH3), 3.85 (3H, s, OCH3). 13C NMR (75 MHz, CDCl3): δ 159.0
(4′-C), 151.6, 149.8, 146.2 (6a-C), 145.0 (3a-C), 140.8 (5a-C), 135.1
(5-C), 132.5 (10c-C), 131.6 (2′,6′-C), 124.7 (1′-C), 115.5 (10b-C),
1
brown amorphous solid (71%, 19.2 mg, 41.3 μmol). H NMR (400
1022
dx.doi.org/10.1021/jo402492d | J. Org. Chem. 2014, 79, 1017−1024