1790 Vol. 35 (1987)
Chem. Pharm. Bull.
35( 5 )1790-1795(1987) _
Aromatic Annelation with ƒ¿-Phenylsulfinyl-ƒÁ-butyrolactones.
A Novel Route to 4-(2-Hydroxyalkyl)-1,3-benzenediols
YUTAKA OZAKI, KEIKO MOCHIDA, and SANG-WON KIM*
Faculty of Pharmaceutical Sciences, Josai University,
Keyakidai, Sakado, Saitama 350-02, Japan
(Received September 22, 1986)
A number of 4-(2-hydroxyalkyl)-1,3-benzenediols (4) were synthesized by thermolysis of 1,3-
cyclohexadiones (3), which were obtained by the reaction of ƒ¿-phenylsulfiny1-ƒÁ-butyrolactones (I)
with ƒ¿,ƒÀ-unsaturated ketones (2), providing a new aromatic annelation. One of the compounds thus
obtained, 4-(3,4-dihydro-4-hydroxy-7-methoxy-2H-1-benzopyran-3-yl)-1,3-benzenediol (4n), was
converted to isomedicarpin (5b) and homopterocarpin (5c).
Keywords-annelation; aromatic synthesis; 1,3-benzenediol; ƒ¿-phenylsulfinyl-ƒÁ-butyro-
lactone; ƒ¿,ƒÀ-unsaturated ketone; pterocarpan; homopterocarpin; isomedicarpin
The annelation of aliphatic compounds by means of Michael-type reactions has been
utilized for the synthesis of aromatic systems such as phenols,1a-e) hydroquinones,1a,e)
resorcinols,1 a,f -h) naphthalenes,1a,i-m) etc.,1n) including natural products. The advantage of
forming aromatic rings from aliphatic compounds lies in the ability to control the position of
substituents on the aromatic rings according to the starting materials employed. It is effective
not only for the regiospecific preparation of aromatic compounds but also for the preparation
of synthetic analogues or closely related natural products by means of simple modification of
the starting materials.
As part of our research to develop methods to construct various aromatic compounds
from aliphatic compounds, we have developed a new route to 1,3-benzenediols possessing a 2-
hydroxyalkyl side chain at the C-4 position of the aromatic ring. This arrangement of the
substituents on the aromatic ring is found in naturally occurring isoflavonoids such as the
pterocarpans,2) some of which are well-known as phytoalexins. Here, we describe in detail a
new preparation of highly substituted 1,3-benzenediols by annelation with ƒ¿-phenylsulfinyl-ƒÁ-
butyrolactones.3)
Chart 1
No. 5 1791
Treatment of the ƒ¿-phenylsulfinyl-ƒÁ-butyrolactones (la-f) with the ƒ¿,ƒÀ-unsaturated
ketones (2a-c) at room temperature in absolute methanol in the presence of magnesium
methoxide afforded unstable intermediates 3. From their infrared (IR) spectra (1720 cm-1)
and the results of the following reactions, it can be presumed that the 1,3-cyclohexadione
systems are formed by the Michael-induced ring closure sequence. Thermolysis of these
intermediates 3 in refluxing benzene gave the 1,3-benzenediols (4a-n) with the alcoholic side
chain at the 4 position of the aromatic rings in moderate yields. The moiety [-O-C5(R1)-
C,(R2)-] of the lactones turned into the side chain unit of the produced aromatic rings, which
carried the substituents R3 and R4 from the ƒ¿,ƒÀ-unsaturated ketones. Their structures were
confirmed by the spectral data and by chemical transformation. Compound 4n was
transformed to homopterocarpin4) (5c) via isomedicarpin5) (5b) in the reported manner4a) to
confirm the alcoholic structure. The pterocarpan framework 5a was similarly obtained from
compound 4m.
Chart 2
Chart 3
1792 Vol. 35 (1987)
The starting lactones employed were obtained as follows. The simple lactones (la-d)
were obtained according to the reported method6) and the three-ring-system lactone, cis-
3a,9b-dihydro-3-(phenylsulfinyl)-4H-furo[3,2-c] [1]benzopyran-2(3H)-one (le), was synthe-
sized from 2,3-dihydro-4H-1-benzopyran-4-one (6a). Bromination of 6a followed by treat-
ment with sodium diethyl malonate gave diethyl (3,4-dihydro-4-oxo-2H-1-benzopyran-3-y1)-
malonate (6c), which was hydrolyzed under acidic conditions to give 3,4-dihydro-4-oxo-2H-1-
benzopyran-3-acetic acid (6d). Reduction of 6d with aluminum sec-butoxide gave the lactone
(7a). The a-phenylthio-y-butyrolactone (7b) was obtained from 7a on treatment with lithium
diisopropylamide (LDA) followed by the addition of diphenyldisulfide. Oxidation of 7b with
m-chloroperbenzoic acid (MCPBA) gave le. Another lactone If was formed from 2,3-
dihydro-7-methoxy-4H-1-benzopyran-4-one7) (6e) in the same way.
In conclusion, various 4-(2-hydroxyalkyl)-1,3-benzenediols (4a-n) were obtained by the
annelation reaction of substituted ƒ¿-phenylsulfinyl-ƒÁ-butyrolactones with 7,ƒÀ-unsaturated
ketones, and this method was successfully applied to construct the pterocarpan framework by
using three-ring-system lactones such as le and 1f
Experimental
Melting points were determined on a Yanaco model MP micro melting point apparatus and are uncorrected. IR
spectra were obtained on a Hitachi 285 IR spectrophotometer. Proton nuclear magnetic resonance (1H-NMR) spectra
were recorded on a JEOL JNM-PMX 60si spectrometer or a JEOL JNM-GX270 FT spectrometer using tetramethyl-
silane (TMS) as an internal standard, and a carbon-13 nuclear magnetic resonance (13C-N MR) spectrum on a JNM-
GX270 FT spectrometer at 67.8 MHz with TMS as an internal standard. High-resolution mass spectra (MS) were
obtained on a JEOL JMS-01SG spectrometer. An ultraviolet (UV) spectrum was recorded on a Hitachi model 200-10
spectrophotometer. All extracts were dried over anhydrous MgSO4. Column chromatography was performed with
Kieselgel 60 (70-230 mesh) and Kiselgel 60 PF254 (Merck), respectively.
Diethyl (3,4-Dihydro-4-oxo-2H-1-benzopyran-3-yl)malonate (6c) A mixture of 2,3-dihydro-4H-l-benzo-
pyran-4-one (6a)7) (14.8 g) and CuBr2 (22.3 g) in AcOEt (150 ml) was stirred under reflux for 2 h. The mixture was
filtered and the filtrate was washed with sat.aq. NaHCO3, water and brine, and then dried. Evaporation of the
solvent in vacuo gave 3-bromo-2,3-dihydro-4H-1-benzopyran-4-one (6b). A solution of diethyl malonate (17 g) in
tetrahydrofuran (THF) (50 ml) was added to a suspension of NaH (60%, 4.0 g) in THF (150 ml) at 5•Ž, and the
mixture was stirred at room temperature for 15 min. Next, a solution of 6b in THF (80 ml) was added at room
temperature and the stirring was continued for 10 h. The reaction mixture was poured into water and acidified with
10% HCl. The product was extracted with Et2O and the extract was washed with sat.aq. NaHCO3, water, and brine,
and then dried. After evaporation of the solvent, the crude product was chromatographed on silica gel with CHCl3 to
give pure 6c (12.5 g, 40:8%) as a pale yellow oil. High-resolution MS: Calcd for C16H18O6 (306.1102). Found:
306.1075 (M +). IR (CHCl3):1730, 1685, 1605 cm-1. 1H-NMR (CDCl3) ƒÂ: 1.30 (3H, t), 1.35 (3H, t), 3.45 (1H, m), 4.05
(1H, m), 4.20 (2H, q), 4.25 (2H, q), 4.60 (2H, m), 6.8-7.5 (3H, m), 7.80 (1H, dd, J=3, 8 Hz).
3,4-Dihydro-4-oxo-2H-1-benzopyran-3-acetic Acid (6d) A mixture of 6c (20 g), AcOH (10 ml), 90% HCOOH
(40 ml), and conc. H2SO4 (3 drops) was refluxed for 10 h. After evaporation of the solvent in vacuo, the residue was
dissolved in Et2O and the acid was extracted with sat.aq. NaHCO3. The aqueous solution was washed with Et2O and
acidified with 10% HCl. The product was extracted with Et2O and the extract was washed with brine and dried. After
evaporation of the solvent, the residue was recrystallized from benzene to give colorless crystals (9.9 g, 73.5%). mp
109-110 •Ž. Anal. Calcd for C111-110O4: C, 64.07; H, 4.89. Found: C, 63.77; H, 4.84. IR (KBr): 1720, 1690,
1605 cm-1. 1H-NMR (CDCl3) ƒÂ: 2.70 (1H, dd, J= 8, 17 Hz), 3.05 (1H, dd, J= 5, 17 Hz), 3.30 (1H, m), 4.20 (1H, d,
J= 10 Hz), 4.60 (1H, dd, J=6, 10 Hz), 6.8-7.7 (3H, m), 7.90 (1H, dd, J= 3, 8 Hz).
cis-3a,9b-Dihydro-4H-furo[3,2-c][1]benzopyran-2(3H)-one (7a)-A mixture of Al (1.35 g) and HgCl2 (trace) in
sec-BuOH (100 ml) was refluxed until the solid was dissolved. A suspension of 6d (5.0 g) in sec-BuOH (15 ml) was
added to this mixture and the solution was refluxed for 14 h. After evaporation of the solvent in vacuo, 10% HCl was
added to the residue at 0•Ž and the mixture was stirred for 8 h. The resulting precipitates were collected and dried.
Recrystallization from EtOH gave colorless needles (4.0 g, 86.7%), mp 102-104 •Ž. Anal. Calcd for C11 H10O3: C,
69.46; H, 5.30. Found: C, 69.31; H, 5.21. IR (CHC13): 1775 cm-1. 1H-NMR (CDCl3) 6: 2.3-3.2 (3H, m, C3-112, C3a-
H), 3.85 (1H, dd, J=8, 10 Hz, C4-Hax), 4.25 (1H, dd, J =4, 10 Hz, C4-Heq), 5.50 (1H, d, J = 5.5 Hz, C9b-H), 6.8-7.6
(4H, m, aromatic H).
cis-3a,9b-Dihydro-3-(phenylthio)-4H-furo[3,2-c][1]benzopyran-2(3H)-one (7b) Butyllithium (28 ml of 1.5
solution in hexane) was added to a solution of diisopropylamine (6.8 ml) in dry THF (40 ml) at - 78 •Ž and the
No. 5 1793
mixture was stirred at - 78 C for 15 min. Next, a solution of 7a (3.6 g) in dry THF (25 ml) was added, and the stirring
was continued for 1 h at -78 C. A solution of diphenyldisulfide (4.5 g) and hexamethylphosphoric triamide (3.6 ml)
in dry THF (25 ml) was added to the reaction mixture at - 78•Ž. The stirring was continued for 1 h at - 70•Ž, for 1 h
at - 30•Ž, and for 1 h at 0•Ž. The reaction was quenched by addition of sat.aq. NH4Cl and the product was
extracted with Et2O. The extract was washed with 10% HCl, sat.aq. NaHCO3, water, and brine, and then dried. After
evaporation of the solvent, the residue was chromatographed on silica gel with benzene to give colorless crystals
(3.4g, 60.2%), mp 94-95 •Ž (from EtOH). Anal. Calcd for C17H14O3S: C, 68.43; H, 4.73. round: C, 68.25; H, 4.76.
IR (CHCl3): 1770 cm-1. 1H-NMR (CDCl3) ƒÂ: 2.90 (1H, m, C3a-H), 3.81 (1H, d, J = 7 Hz, C3-H), 4.15 (2H, m, C4-H2),
5.40 (1H, d, J =7 Hz, C9b-H), 6.8-7.7 (9H, m, aromatic H).
Diethyl (3,4-Dihydro-7-methoxy-4-oxo-2H-1-benzopyran-3-yl)malonate (6g)-This compound (6g) was ob-
tained from 6e via 3-bromo-2,3-dihydro-7-methoxy-4H-1-benzopyran-4-one (6g)8b) in 45.5°/a yield as colorless
crystals, mp 64-66 C (from cyclohexane). Anal. Calcd for C17H20O7: C, 60.71; H, 5.99. Found: C, 60.47; H, 5.89. IR
(CHCl3): 1735, 1680, 1615, 1575cm-1.
3,4-Dihydro-7-methoxy-4-oxo-2H-1-benzopyran-3-acetic Acid (6h)-This compound (6h) was obtained from
6g in 58.7% yield as colorless crystals, mp 131-133 •Ž (from benzene). Anal. Calcd for C12H12O5: C, 61.01; H, 5.12.
Found: C, 60.74; H, 4.84. IR (KBr): 1715, 1675, 1610, 1580 cm-1. (lit.9) mp 137-138 •Ž).
cis,3a,9b-Dihydro-7-methoxy-4H-furo[3,2-c][1]benzopyran-2(3H)-one (7c)-This compound (7c) was ob-
tained from 6h in 72.9% yield as colorless crystals, mp 88-90•Ž (from EtOH). Anal. Calcd for C12H12O4: C, 65.44;
H, 5.49. Found: C, 65.13; H, 5.30. IR (CHCl3): 1780, 1620, 1580 cm-1. 1H-I-NMR (CDCl3) 6: 2.42 (1H, dd, J =3.7 ,
17.6 Hz, C3-H), 2.86 (1H, dd, J = 8.3, 17.6 Hz, C3-H), 3.00 (1H, m, C3a-H), 3.79 (3H, s, OMe), 3.78 (1H, m, C441..),
4.19 (1H, m, C4-Heq), 5.44 (1H, d, J= 5.9 Hz, C9,-H), 6.43 (1H, d, J= 3 Hz, C6-H), 6.61 (1H, dd, J= 3, 8 Hz, C8-H),
7.29 (1H, d, J =8 Hz, C9-H). mp 88-88.5 •Ž).
cis-3a,9b-Dihydro-7-methoxy-3-(phenylthio)-4H-furo[3,2-c][1]benzopyran-2(311)-one (7d)-This compound
(7d) was obtained from 7c in 78.8% yield as colorless crystals, mp 95-97•Ž (from Et2O). Anal. Calcd for C18F116O4S:
C, 65.83; H, 4.91. Found: C, 65.83; H, 4.79. IR (KBr): 1770, 1625, 1585 cm-1.
Preparation of 1,3-Benzenediols (4a-n)-All of these compounds were prepared by the following general
method which is exemplified by the preparation of 4a.
General Method: 4-(2-Hydroxyethyl)-1,3-benzenediol (4a)-3-Buten-2-one (2a) (194 mg, 2.3 mmol) was added
to a mixture of dihydro-3-(phenylsulfinyl)-2(3H)-furanone (1a)6) (315 mg, 1.5 mmol) and magnesium methoxide
(from Mg, 255 mg) in absolute MeOH (5 ml) at room temperature. The resulting solution was stirred for 16 h. After
evaporation of the solvent in vacuo, 10% HCl was added to the residue at 0•Ž and the product was extracted with
CH2Cl2. The extract was washed with water and dried. Evaporation of the solvent in vacuo gave colorless crystals 3
(R1 = R2 = R3 = R4 = H). IR (Nujol): 1720 cm-1. A suspension of these crystals in benzene (3 ml) was refluxed for 3 h.
After removal of the solvent, the residue was chromatographed on silica gel with 3% MeOH/CHCl3 (v/v) to give pure
4a as an oil (130 mg, 56.3%). IR (film): 3300, 1620 cm-1. 1H-NMR (CDCl3-CD3OD, 5: 1) 6: 2.76 (2H, t, J= 6 Hz),
3.80 (2H, t, J=6 Hz), 6.25 (1H, dd, J= 3, 8 Hz), 6.36 (1H, br s), 6.88 (1H, d, J=8 Hz). Methylation of this compound
with Me2SO4/K2CO3 in acetone gave 2,4-dimethoxybenzeneethanol, mp 66-67 °C. mp 67 •Ž).
4-(2-Hydroxyethyl)-6-methyl-1,3-benzenediol (4b) This compound (4b) was obtained from la and 3-methyl-
3-buten-2-one (2b)12 in 45% yield as colorless crystals, mp 101-102•Ž (from CHCl3). Anal. Calcd for C9H12O3: C,
64.27; H, 7.19. Found: C, 63.96; H, 6.98. IR (KBr): 3400, 1625 cm-1. 1H-N MR (CDCl3) 6: 2.12 (3H, s), 2.76 (2H, t),
3.81 (2H, t), 6.32 (1H, s), 6.76 (1H, s). High-resolution MS: Calcd for C9H12O3 (168.0785). Found: 168.0779 (M ).
4-(2-Hydroxyethyl)-2,6-dimethyl-1,3-benzenediol (4c)-This compound (4c) was obtained from la and 2-
methyl- 1 -penten-3-one (2c)13) in 30.4% yield as an oil. High-resolution MS: Calcd for C10F11403 (182.0942). Found:
182.0902 (M+). IR (film): 3400, 1620 cm-1. 1H-NMR (CDCl3) ƒÂ: 2.17 (6H, s), 2.78 (2H, t), 3.89 (2H, t), 6.69 (1H, s).
Anal. Calcd for C31 H20N6O18 (tris-3,5-dinitrobenzoate, mp 128-131•Ž from EtOH): C, 48.70; H, 2.64; N, 10.99.
Found: C, 48.79; H, 2.70; N, 10.78.
4-(2-Hydroxypropyl)-1,3-benzenediol (4d)-This compound (4d) was obtained from dihydro-5-methyl-3-
(phenylsulfinyl)-2(3H)-furanone (1b)6) and 2a in 40.7% yield as an oil. High-resolution MS: Calcd for C9H12O3
(168.0785). Found: 168.0789 (M t). IR (film): 3300, 1620 cm-1. 1H-NMR (CDC13-CD3OD, 4: 1) 6: 1.19 (3H, d,
J=6.5 Hz), 2.68 (2H, m), 4.08 (1H, m), 6.30 (1H, dd, J= 3, 8 Hz), 6.36 (1H, br s), 6.84 (1H, d, J= 8 Hz). Anal. Calcd for
C11H16O3 (dimethylether, by 150 •Ž/1 mmHg, mp 49-50•Ž): C, 67.32; H, 8.22. Found: C, 67.05; H, 8.23.
4-(2-Hydroxypropyl)-6-methyl-1,3-benzenediol (4e)-This compound (4e) was obtained from lb and 2b in
42.0% yield as an oil. High-resolution MS: Calcd for C10H14O3 (182.0942). Found: 182.0926. IR (film): 3350,
1630cm-1. 1H-NMR (CDCl3-CD3OD, 5 : 1) ƒÂ: 1.19 (3H, d, J= 6Hz), 2.11 (3H, s), 2.65 (2H, m), 4.06 (1H, m), 6.34
(1H, s), 6.72 (1H, s). Anal. Calcd for C31 H20N6O18 (tris-3,5-dinitrobenzoate, mp 117-120 •Ž from EtOH): C, 48.70;
H, 2.64; N, 10.99. Found: C, 48.72; H, 2.61; N, 10.90.
4-(2-Hydroxypropyl)-2,6-dimethyl-1,3-benzenediol (4f)-This compound (4f) was obtained from lb and 2c in
19.9% yield as colorless crystals, mp 103-105 •Ž (from CHCl3). High-resolution MS: Calcd for C11H16O3
(196.1099). Found: 196.1098 (M t). IR (KBr): 3400, 1615cm-1. 1H-NMR (CDCl3-CD3OD, 5 : 1) 6: 1.20 (3H, d,
J=6 Hz), 2.12 (6H, s), 2.72 (2H, m), 4.10 (1H, m), 6.64 (1H, s). Anal. Calcd for C32H22N6O18 (tris-3,5-
1794 Vol. 35 (1987)
dinitrobenzoate, mp 239-241 °C from AcOEt-EtOH): C, 49.36; H, 2.84., N, 10.80. Found: C, 49.65; H, 2.82; N, 10.59.
4-(2-Hydroxy-2-phenylethyl)-1,3-benzenediol (4g) This compound (4g) was obtained from dihydro-5-phenyl-
3-(phenylsulfinyl)-2(3H)-furanone (lc)6) and 2a in 42.6% yield as colorless crystals, mp 136-138•Ž (from benzene).
High-resolution MS: Calcd for C14H4O3 (230.0942). Found: 230.0956 (M+). Anal. Calcd for C14H14O3: C, 73.02; H,
6.13. Found: C, 73.22; H, 6.10. IR (KBr): 3400, 1635, 1605 cm-1. 1H-NMR (CDC13-CD3OD, 5: 1) 6 : 2.87 (1H, dd,
J=4,16 Hz), 3.02 (1H,dd,J=8, 16 Hz), 4.90 (1H,dd,J=4, 8 Hz), 6.29 (1H,dd,J=4, 8 Hz), 6.41 (1H,d,J=4 Hz), 6.75
(1H, d, J =8 Hz), 7.35 (5H, br s).
4-(2-Hydroxy-2-phenylethyl)-6-methyl-1,3-benzenediol (4h)-This compound (4h) was obtained from lc and 2b
in 44.4% yield as an oil. High-resolution MS: Calcd for C1 5 H16O3 (244.1098). Found: 244.1062 (M+). IR (film): 3400,
1620cm-1. 1H-NMR (CDCl3)ƒÂ : 2.00 (3H, s), 2.70 (1H, dd, J=3.5, 11 Hz), 2.99 (1H, dd, J=9, 11 Hz), 4.79 (1H, dd,
J=3.5, 9 Hz), 6.35 (1H, s), 6.61 (1H, s), 7.24 (5H, s-like). Anal. Calcd for C361-128O6, (tribenzoate, mp 161-163•Ž
from AcOEt): C, 77.68; H, 5.07. Found: C, 77.50; H, 5.04.
4-(2-Hydroxy-2-phenylethyl)-2,6-dimethyl-1,3-benzenediol (4i)-This compound (4i) was obtained from lc and
2c in 27.7% yield as an oil. High-resolution MS: Calcd for C16H18O3 (258.1255). Found: 258. 1236 (Mt). IR (film):
3400, l620 cm-1. 1H-NMR (CDCl3) ƒÂ: 2.05 (3H, s), 2.08 (3H, s), 2.70 (1H, dd, J= 2.5, 14.5 Hz), 3.04 (1H, dd, J=9,
14.5 Hz), 4.86 (1H, dd, J = 2.5, 9 Hz), 6.52 (1H, s), 7.34 (5H, s-like). Anal. Calcd for C22H24O6 (triacetate, mp 131-
132•Ž from EtOH): C, 68.73; H, 6.29. Found: C, 68.49; H, 6.36.
4-(trans-2-Hydroxycyclohexyl)-1,3-benzenediol (4j)-This compound (4j) was obtained from hexahydro-3-
(phenylsulfinyl)-2(3H)-benzofuranone (1d)6) and 2a in 21.3% yield as colorless crystals, mp 153-155•Ž (from
benzene). High-resolution MS: Calcd for C12H16O3 (208.1099). Found: 208.1085 (M+). Anal. Calcd for C12H16O3: C,
69.21; H, 7.74. Found: C, 68.95; H, 7.46. IR (KBr): 3450, 1620 H-NMR (CDCl3) ƒÂ : 1.2-2.2 (9H, m), 2.6-2.9
(1H, t-like), 3.4-3.8 (1H, br), 6.29 (1H, d, J= 3 Hz), 6.39 (1H, dd, J= 3, 8 Hz), 6.96 (1H, d, J=8 Hz).
4-(trans-2-Hydroxycyclohexyl)-6-methyl-1,3-benzenediol (4k)-This compound (4k) was obtained from id and
2b in 16.4% yield as colorless crystals, mp 164-165 •Ž (from benzene). High-resolution MS: Calcd for C13H18O3
(222.1255). Found: 222.1249 (M t). Anal. Calcd for C13H18O3: C, 70.24; H, 8.16. Found: C, 70.49; H, 8.35. IR
(CHC13): 3300, 1605 cm-1.1H-NMR (CDC13-CD3OD, 5: 1) ƒÂ: 1.2-2.1 (9H, m), 2.12 (3H, s), 2.55-2.90 (1H, t-
like), 3.30-3.75 (1H, br), 6.33 (1H, s), 6.86 (1H, s).
4-(trans-2-Hydroxycyclohexyl)-2,6-dimethyl-1,3-benzenediol (41)-This compound (41) was obtained from Id
and 2c in 10.7% yield as an oil. High-resolution MS: Calcd for C14H20O3 (236.1411). Found: 236.1436 (Mt). IR
(film): 3450, 1615 cm -1. 1H-NMR (CDCl3) 6: 1.2-2.1 (914, m), 2.15 (3H, s), 2.17 (3H, s), 2.40-2.90 (1H, t-like),
3.20-3.75 (1H, br), 6.73 (1H, s). Anal. Calcd for C2O-12606 (triacetate, mp 121-123 C from EtOH): C, 66.28; H,
7.23. Found: C, 66.07; H, 7.44.
4-(3,4-Dihydro-cis-4-hydroxy-2H-1-benzopyran-3-y1)-1,3-benzenediol (4m) A solution of MCPBA (70%,
2.7g) in CH2Cl2 (50 ml) was added to a solution of 7b (3.0 g) in CH2Cl2 (30 ml) with stirring at 0•Ž, and the stirring
was continued for 2 h. The solution was washed with sat.aq. NaHCO3 and water, and then dried. After evaporation
of the solvent in vacuo at 20•Ž, the residue was chromatographed on silica gel with CHCl3 to give le as colorless
crystals (2.6 g, 82.3%), mp 140-145•Ž. IR (CHC13): 1770cm1. Compound 4m was obtained from le and 2a in
29.4% yield as colorless crystals, mp 182-185 •Ž. High-resolution MS: Calcd for C15H1404 (258.0891). Found:
258.0906 (M IR (KBr): 3410, 1620 cm-1. Anal. Calcd for C21H20O7 (triacetate, mp 1 19-124•Ž from EtOH): C,
65.61; H, 5.24. Found: C, 65.49; H, 5.37.
4-(3,4-Dihydro-cis-44‘ydroxy-7-methoxy-2H-1-benzopyran-3-y1)-1,3-benzenediol (4n)-Oxidation of 7d gave if
in 78.5% yield as colorless crystals (mp 147-150 •Ž) in the same manner as noted for le. IR (Nujol): 1760, 1620,
1580 cm -1. Compound 4n was obtained from if and 2a in 15.5% yield as colorless crystals, mp 184-187•Ž (from
EtOH-H2O). High-resolution MS: Calcd for C16H16O5 (288.0997). Found: 2880986 (M IR (KBr): 1620, 1580,
1500 cm-1.1H-NMR (CDCl3-CD3OD, 20 : 1) ƒÂ: 3.49 (1H, m, C3,-H), 3.79 (3H, s, OMe), 4.20 (1H m, C2,-H„„), 4.64
(1H, dd, J= 10.5, 12.5 Hz, C2,-He,), 4.84 (1H, br s, width, 5.5 Hz, C4,-H), 6.35 (2H, m, C2-H, C(,-H), 6.42 (1H, d,
J =2.2 Hz, C8,-H), 6.51 (1H, dd, J=2.2, 8.1 Hz, C6,-H), 6.90 (1H, d, J=8.1 Hz, C5,-H), 7.18 (1H, d, J=8.8 Hz, C5-H).
Anal. Calcd for C22H2208 (triacetate, mp 152-155 •Ž from EtOH): C, 63.76; H, 5.35. Found: C, 63.47; H, 5.34.
cis-6a,11a-Dihydro-6H-benzofuro[3,2-c][1]benzopyran-9-ol (5a)-A mixture of 4m (100 mg) and AcOH (3 ml)
was refluxed for 1 h and the solvent was evaporated off in vacua. The residue was chromatographed on silica gel with
CHCl3 to afford 5a as an oil (41 mg, 44.1%). IR (CHCl3): 3400, 1630 cm-1. 1 H-NMR (CDC13) ƒÂ: 3.59 (1H, m, C6a-
H), 3.63 (1H, m, C6-Hax), 4.27 (1H, m, C6-Heq), 5.54 (1H, d, J6.6 Hz, C11a-H), 6.37 (2H, m, C8-H, C10-H), 6.95 (I H,
d, J=8.1 Hz, C4-H), 7.03-7.30 (3H, m, C2-H, C3-H, C7-H), 7.53 (1H, d, J = 8.0 Hz, C1-H). Anal. Calcd for C22H,604
(tribenzoate, mp 131-134•Ž from EtOH): C, 76.73; H, 4.68. Found: C, 76.68; H, 4.87.
cis-6a,11a-Dihydro-3-methoxy-6H-benzofuro[3,2-c][1]benzopyran-9-ol (d/-Isomedicarpin)5) (5b)-This com-
pound (5b) was obtained in 61.3% yield from 4n in the same way as noted for 5a; colorless crystals, mp 92-95•Ž
(from benzene). High-resolution MS: Calcd for C16H14O4 (270.0891). Found: 270.0910 (M+). Anal. Calcd for
C16H14O4: C, 71.10; H, 5.22. Found: C, 71.00; H, 5.06. IR (KBr): 3380, 3270, 1620, 1600, 1580cm-1. 1H-NMR
(CDCl3) ƒÂ: 3.52 (1H, m, C6a-H), 3.63 (1H, m, C6-Hax), 3.79 (3H, s, OMe), 4.24 (11-1, dd-like, J=5, 11 Hz, C6-Heq),
4.97 (1H, s, OH), 5.51 (1H, d, J=6.6 Hz, C11a-H), 6.32-6.36 (2H, m, C8-H, C10-H), 6.47 (1H, d, J=2.7 Hz, C4-H),
No. 5 1795
6.64 (1H, dd, J=2.7, 8.1 Hz, C2-H), 7.08 (1H, d, J=8.8 Hz, C7-H), 7.42 (1H, d, J=8.1 Hz, C1-H).14)(lit,5a mp 63-
64•Ž).
cis-6a,11a-Dihydro-3,9-dimethoxy-6H-benzofuro[3,2-c][1]benzopyran (dl-Homopterocarpin)4)(5c)-A mixture
of 5b (30 mg), K2CO3 (40 mg), and Me2SO4 (30 mg) in acetone (4 ml) was refluxed for 2 h. The mixture was filtered
and the filtrate was evaporated in vacuo. The residue was subjected to preparative thin-layer chromatography
(AcOEt-hexane, 4 : 6) to afford 5c as colorless crystals (27 mg, 85.7%), mp 129-130 •Ž (from EtOH). Anal. Calcd for
C17H16O4: C, 71.82; H, 5.67. Found: C, 71.70; H, 5.69. IR (CHCl3): 1620, 1595sh, 1495cm-1. H-NMR (CDCl3) ƒÂ:
3.52 (1H, m, C6oa-H), 3.63 (1H, m, C6-Hax), 3.76 (3H, s, OMe), 3.78 (3H, s, OMe), 4.24 (1H, dd-like, J=5, 11 Hz, C6-
Heq), 5.50 (1H. d, J=6.7 Hz, C11a-H), 6.42-6.49 (3H, m, C4-H, C8-H, C10-H), 6.64 (1H, dd, J=2.5, 8.5 Hz, C2-H),
7.12 (1H, d, J=8.9 Hz, C7-H), 7.42 (1H, d, J=8.5 Hz, C1-H).14) 13C-NMR (CDC13) ƒÂ: 39.5 (d, C6a), 55.4 (q, OMe),
55.5 (q, OMe), 66.6 (t,C6) 78.6 (d, C11a), 96.9 (d), 101.6 (d), 106.4 (d), 109.2 (d), 112.4 (s), 119.1 (s), 124.7 (d), 131.9
(d), 156.7 (s), 160.8 (s), 161.0 (s), 161.2 (s). UV ƒÉEtOHmaxnm (log ƒÃ): 281sh (3.83), 286 (3.88). (lit.4a) mp 123-125•Ž).
Acknowledgement We are grateful to Mr. Takaichi Katoh and Mr. Fumihiko Takagi for their technical
assistance.
References and Notes
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