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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f) A.FoceUa.　 S.　Teltel.　and　 A.　 Brossi,J.Org,　 Chem.,42,3456(1977);g) A.　 A.　Jaxa-Chamiec,　 P.　G.　 Sammes.

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G. W. Kirby, Springer-Verlag, Wien-New York, 1983, pp. 1-266. 3) Preliminary communication: Y. Ozaki and S. Kim, Synth. Commun., 15, 1171 (1985). 4) a) H. Suginome and T. Iwadare, Bull. Chem. Soc. Jpn., 39, 1535 (1966); b) S. H. Harper, A. D. Kemp, W. G. E.

Underwood, and R. V. M. Campbell, J. Chem. Soc. (C), 1969, 1109. 5) a) T. B. H. McMurry, E. Martin, D. M. X. Donnelly, and J. C. Thompson, Phytochemistry, 11, 3283 (1972); b)

N. W. Preston, ibid., 16, 2044 (1977); J. L. Ingham and K. R. Markham, ibid., 19, 1203 (1980). 6) K. Iwai, H. Kosugi, H. Uda, and M. Kawai, Bull. Chem. Soc. Jpn., 50, 242 (1977). 7) J. D. Loudon and R. K. Razdan, J. Chem. Soc., 1954, 4299; E. M. Padfield and M. L. Tomlinson, ibid., 1950,

2272. 8) a) W. D. Cotterill, J. Cottam, and R. Livingstone, J. Chem. Soc. (C), 1970, 1006; b) J. Colonge and A. Guyot,

Bull. Soc. Chim. Fr., 1958, 329. 9) J. N. Chatterjea, S. C. Shaw, and J. N. Singh, J. Indian Chem. Soc., 51, 281 (1974).

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