Regioselective total synthesis of edulane and its angular analogue

Article abstract of DOI:10.1039/a608227k

Herein we describe a 10-step total synthesis of edulane 3 and its angular analogue 18 from phloroglucinol. The key step involves ZnCl₂-catalysed condensation of the appropriately substituted 2H-chromenes 8, 9 and 10 with the 2-alkoxy-1,4-benzoquinones 11 and 12, respectively.

Full text of DOI:10.1039/a608227k

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Regioselective total synthesis of edulane and its angular analogue
Kandasamy Subburaj, Modachur G. Murugesh and Girish K. Trivedi*
Department of Chemistry, Indian Institute of Technology, Powai, Bombay-400 076, India
H erein we describe a 10-step total synthesis of edulane 3 and its angular analogue 18 from phloroglucinol.
The key step involves ZnCl2-catalysed condensation of the appropriately substituted 2H -chromenes 8, 9
and 10 with the 2-alkoxy-1,4-benzoquinones 11 and 12, respectively.
A large number of naturally occurring isoflavonoid phyto-
alexins possessing a furan ring system are biologically active,1
e.g. carbenegrin A-I 1 and carbenegrin A-II 2 isolated from the
O
OH
I
O
O
i
OMe
OMe
OMe
OMe
OMe OMe
5
6
7
OH
ii
iii
HO
HO
O
HO
O
9
10
8
1
O
O 7
O
O
O
O
O
O
O
2
O
+
3
6
O
O
4
OMe
OMe
OMe
1 Carbenegrin A-I
2 Carbenegrin A-II
10
9
8
Scheme 1 Reagents and conditions: i, K2CO3, acetone, reflux, 12 h;
ii, dry dioxane, p-TsOH, 68 ЊC, 2 h; iii, pyridine, 3-methylbut-2-enal,
140 ЊC, 48 h
O
O
O
O
O
the chromenes 8 and 9. In order to ascertain the linear and angu-
lar fusion of the chromenes formed, NOE studies on 8 and 9
were carried out. Irradiation of the methoxy proton signal of
chromene 8 at δ 3.76 led to an enhancement of the single aro-
matic proton singlet at δ 5.97. This indicated that the two aro-
matic carbons, i.e. the one bearing the methoxy and the other
unsubstituted, are adjacent. This is possible only in the angular
chromene 8. Likewise, irradiation of the methoxy signal of
chromene 9 at δ 3.74 gave enhancement of the olefinic proton at
δ 6.61 indicating it to be the linear compound. Base-catalysed
thermal cyclisation 12 of 7-hydroxy-5-methoxychroman 5 with
3-methylbut-2-enal in pyridine gave the chromene 10 (68%),
which was confirmed by the appearance of two one-proton
doublets with J 9.7 Hz at δ 5.37 and 6.59 for 9- and 10-H,
respectively. An irradiation study of this chromene clearly
confirmed it to be the angular compound.
The 2H-chromenes 8, 9 and 10 were subjected to ZnCl2-
catalysed condensation with 2-alkoxy-1,4-benzoquinones 11
and 12 to afford the corresponding pterocarpans 13, 14, 15 and
16 in good yields (Schemes 2 and 3). The appearance of an OH
absorption (ca. 3550 cmϪ1) in the IR spectra and a signal at δH
ca. 5.5 (1 H, d, J 6.5 Hz) in each case confirmed the formation
of pterocarpans. The pterocarpans 13 and 16 were conveniently
converted into their corresponding trifluoromethanesulfonates
(triflates) 17 and 19 by treatment with trifluoromethanesulfonic
anhydride in the presence of pyridine at Ϫ78 ЊC in 77 and 88%
yields respectively.3b The disappearance of the OH absorption
in the IR spectrum and the 1 H singlet at δ 5.21 (5.29 in the case
of 19) confirmed the formation of triflates. The triflates 19 and
17 when heated with a mixture of palladium() acetate, 1,1Ј-
bis(diphenylphosphino)ferrocene, triethylamine and formic
acid gave edulane 3 (84%) and its analogue 18 (78%) (Schemes 2
and 3).3b The formation of edulane 3 and its analogue 18 was
confirmed by the appearance of signals at δ 6.48 and 7.12 (both
OMe
OMe
O
O
O
OMe
3 Edulane
4 Neorautanin
roots of the plant ‘carbeeca de negra’, have been shown to have
potent anti snake venom activity.2 Because of the significant
biological activity associated with the pterocarpans, con-
siderable efforts have recently been directed towards the total
synthesis of such naturally occurring compounds.3,4 Thus, a
one-step, TiIV-catalysed synthesis of substituted pterocarpans
has been developed by Engler et al. through the reaction of
2-alkoxy-1,4-benzoquinones with appropriately substituted
2H-chromenes.3b,c,5 We have also reported an essentially quanti-
tative method for the synthesis of this class of compounds
using ZnCl2 as catalyst.6
In continuation of our work on the regioselective6,7 and
enantioselective8 synthesis of substituted pterocarpans, we have
attempted a total synthesis of edulane 3, a pterocarpan isolated
from the root bark of the Neorautania edulis by Brink et al.,9
and its angular analogue 18. Herein we describe this 10-step
synthesis from phloroglucinol.
Results and discussion
7-Hydroxy-5-methoxychroman 5 was prepared from phloro-
glucinol in a 5-step synthesis.10 3-Iodopropanal dimethyl acetal
611 on reaction with chroman 5 in K2CO3–acetone under reflux
gave the acetal 7 (74%; Scheme 1), acid-catalysed cyclisation 4
of which in dry dioxane gave the chromenes 8 and 9 (64%; 1:2
ratio). It was found that an increase in either the reaction time
or the temperature led to complete decomposition of the prod-
uct. Signals at δ 6.70 (1 H, d, J 9.81 Hz) and 5.5 (1 H, td, J 3.84
and 9.8 Hz) in the 1H NMR spectrum confirmed the identity of
J. Chem. Soc., Perkin Trans. 1, 1997
1875

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R1
R1
9
the solvent containing SiMe4 as an internal standard with
10
O
chemical shifts (δ) expressed as ppm downfield with respect
to SiMe4. J Values are given in Hz. Elemental analyses were
performed on a CEST 1106 elemental analyser. Mass spectra
were recorded on a Hewlett Packard MS Engine 5989-A mass
spectrometer.
8
1
O
OR2
O7
2
+
6
3
4
OMe
O
7-(3Ј,3Ј-Dimethoxypropoxy)-2,2-dimethyl-3,4-dihydro-5-
methoxybenzo[1,2-b]pyran 7
8 R1 = H
10 R1 = Me
11 R2 = Me
12 R2 = CH2Ph
A mixture of K2CO3 (200 mg, 1.45 mmol) and 7-hydroxy-5-
methoxy-2,2-dimethylchroman 5 (300 g, 1.4 mmol) in dry acet-
one (25 ml) was stirred for 10 min at 5–10 ЊC. 3-Iodopropanal
dimethyl acetal 6 (0.45 ml, 2.0 mmol) in dry acetone (10 ml) was
then gradually added to the mixture after which it was refluxed
overnight. The mixture was evaporated under reduced pressure
and extracted with dichloromethane (4 × 50 ml) and the com-
bined extracts were washed with water and brine, dried
(Na2SO4) and evaporated under reduced pressure. The product
was chromatographed over silica gel and eluted with LP–ethyl
acetate (98:2) to give the title compound 7 as a light yellow oil
(320 mg, 74%); νmax/cmϪ1 2947, 1624, 1591, 1499, 1453, 1393,
1123 and 814; δH (300 MHz, CDCl3) 1.30 [6 H, s, 2,2-(CH3)2],
1.74 (2 H, t, J 6.77, 3-H), 2.05 (2 H, q, J 6.04, 12.26, 2Ј-H), 2.55
(2 H, t, J 6.77, 4-H), 3.35 (6 H, s, 3Ј-OCH3), 3.78 (3 H, s, 5-
OCH3), 3.97 (2 H, t, J 6.28, 1Ј-H), 4.61 (1 H, t, J 5.86, 3Ј-H), 6.0
(1 H, d, J 2.4, Ar-H) and 6.03 (1 H, d, J 2.4, Ar-H); m/z 310
(Mϩ, 71%), 295 (100), 247 (29), 239 (71), 153 (47) and 75 (59).
iv
MeO
R
R2O
OH
10
11
12
9
R1
13
O
O
8
R1
1
O
O
O
O7
2
6
3
5
4
OMe
13 R = OH
17 R = OSO2CF3
18 R = H
OMe
13 R1 = H, R2 = Me
14 R1 = R2 = Me
15 R1 = Me, R2 = CH2Ph
v
vi
Scheme 2 Reagents and conditions: iv, ZnCl2 (1.5 equiv.), CH2Cl2, room
temp; v, (CF3SO2)2O, pyridine, Ϫ78 ЊC, 4 h; vi, Pd(OAc)2, 1,1Ј-
bis(DPP)ferrocene, Et3N, HCO2H, 75 ЊC, 1 h
3,4-Dihydro-2,2-dimethyl-5-methoxy-2H,8H-benzo[1,2-b:3,
4-bЈ]dipyran 8 and 6,7-dihydro-8,8-dimethyl-5-methoxy-2H,8H-
benzo[1,2-b:5,4-bЈ]dipyran 9
O
OR2
O
O
To a solution of toluene-p-sulfonic acid (catalytic amount) in
dry dioxane (25 ml) was added the alkylated chroman 7 (1 g, 3.2
mmol) in dry dioxane (15 ml). The mixture was heated at 68 ЊC
under a N2 atmosphere for 2 h and then allowed to cool to room
temperature. After 15 mins, it was diluted with water (25 ml) and
extracted with dichloromethane. The extract was washed with
water and brine, dried (Na2SO4) and concentrated. The result-
ant oil was subjected to silica gel column chromatography and
eluted with LP–ethyl acetate (99:1 and 98:2) to afford the
chromenes 8 and 9 as colourless oils. Chromene 8 (170 mg,
21.5%); νmax/cmϪ1 3019, 1979, 2940, 1621, 1453, 1216, 1117,
1025 and 755; δH (300 MHz, CDCl3) 1.31 [6 H, s, 2,2-(CH3)2],
1.74 (2 H, t, J 6.95, 3 H), 2.54 (2 H, t, J 6.96, 4-H), 3.76 (3 H, s,
OCH3), 4.69 (2 H, q, J 1.65, 8-H), 5.55 (1 H, td, J 3.84, 9.8,
9-H), 5.97 (1 H, s, 6-H) and 6.70 (1 H, d, J 9.81, 10-H); δC(125
MHz, CDCl3) 16.93, 26.93, 32.46, 55.62, 65.51, 74.5, 91.03,
102.85, 105.30, 116.15, 120.2, 150.38, 154.0 and 158.2; m/z 246
(Mϩ, 99%), 191 (80) and 161 (100). The chromene 9 (330 mg,
42%); νmax/cmϪ1 3026, 2979, 2940, 1617, 1479, 1216, 1143 and
762; δH (300 MHz, CDCl3) 1.31 [6 H, s, 8,8-(CH3)2], 1.75 (2 H, t,
J 6.77, 7-H), 2.65 (2 H, t, J 6.77, 6-H), 3.74 (3 H, s, OCH3), 4.69
(2 H, q, J 1.83, 2-H), 5.64 (1 H, td, J 9.88, 3.84, 3-H), 6.10 (1 H,
s, 10-H) and 6.61 (1 H, d, J 9.88, 4-H); δC(125 MHz, CDCl3)
17.08, 26.95, 32.61, 61.53, 65.38, 74.64, 100.8, 107.7, 108.8,
118.4, 119.9, 154.2, 154.69 and 155.43; m/z 246 (Mϩ, 86%), 191
(69) and 83 (100).
+
OMe
O
9
11 R2 = Me
iv
4
6
O
5
O
7
3
2
8
13
1
9
R1
O
OMe
12
10
11
OR2
16 R1 = OH, R2 = Me
19 R1 = OSO2CF3, R2 = Me
3 R1 = H, R2 = Me
v
vi
Scheme 3 Reagents and conditions: iv, ZnCl2 (1.5 equiv.), CH2Cl2, room
temp; v, (CF3SO2)2O, pyridine, Ϫ78 ЊC, 4 h; vi, Pd(OAc)2, 1,1Ј-
bis(DPP)ferrocene, Et3N, HCO2H, 75 ЊC, 1 h
1 H, d) and δ 6.43 (1 H, dd) in their 1H NMR spectra. This was
further confirmed by mass spectral evidence.
Experimental
Diphenyl diselenide, trifluoromethanesulfonic anhydride,
palladium() acetate and 1,1Ј-bis(diphenylphosphino)ferrocene
[bis(DPP)ferrocene] were purchased from the Aldrich Chemical
Co. 2-Methoxy-1,4-benzoquinones was prepared from vanillin
using aqueous H2O2.13 Melting points are uncorrected. TLC
analyses were carried out on glass plates coated with TLC
grade silica gel. Silica gel (100–200 mesh) were used for column
chromatography. Laboratory solvents were purified and pre-
dried before use according to standard procedures. Light pet-
roleum (LP; bp 60–80 ЊC) was used for column chromato-
graphy. IR spectra were recorded on a Perkin-Elmer 688 spectro-
meter. NMR spectra were recorded either on Bruker AM 500,
Varian VXR 300S or Bruker-200 instruments using CDCl3 as
3,4-Dihydro-2,2,8,8-tetramethyl-5-methoxy-2H,8H-benzo[1,2-b:
3,4-bЈ]dipyran 10
3-Methylbut-2-enal (0.87 ml, 9.0 mmol) was added to a mixture
of 7-hydroxy-5-methoxychroman 5 (1.8 g, 9.0 mmol) and dry
pyridine (2.9 ml, 36 mmol) at 140 ЊC (oil-bath temp.). After the
mixture had been heated under reflux for 12 h it was treated
with 3-methylbut-2-enal (0.87 ml, 9.0 mmol) and refluxing con-
tinued for 36 h. The mixture was then evaporated to dryness
under reduced pressure to remove the pyridine, after which it
was diluted with water (20 ml) and extracted with ethyl acetate.
The extract was washed with water and brine, dried (Na2SO4)
and evaporated to afford an oily residue. This was subjected to
1876
J. Chem. Soc., Perkin Trans. 1, 1997

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column chromatography and eluted with LP–ethyl acetate
(98:2) to give the chromene 10 as a colourless oil (1.67 g, 68%);
νmax/cmϪ1 3024, 2974, 2935, 1622, 1587, 1479, 1221 and 1149;
δH (300 MHz, CDCl3) 1.30 [6 H, s, 2,2-(CH3)2], 1.40 [6 H, s,
8,8-(CH3)2], 1.73 (2 H, t, J 6.8, 3-H), 2.54 (2 H, t, J 6.77, 4-H),
3.76 (3 H, s, OCH3), 5.37 (1 H, d, J 9.7, 9-H), 5.97 (1 H, s, 6-H)
and 6.59 (1 H, d, J 9.7, 10-H); δC(50 MHz, CDCl3) 16.75, 26.73,
27.78, 32.34, 55.35, 74.23, 75.87, 91.36, 102.05, 103.71, 117.17,
125.17, 150.11, 152.44 and 158.04; m/z 274 (Mϩ, 56%), 259
(100), 203 (85) and 181 (49).
H, d, J 7.0, 13a-H), 6.03 (1 H, s, 6-H), 6.61 (1 H, s, 12-H), 6.89
(1 H, s, 9-H) and 7.38 (5 H, m, ArH); δC(75 MHz, CDCl3)
16.81, 19.86, 24.92, 27.51, 28.45, 32.05, 48.70, 55.34, 71.34,
74.64, 76.21, 76.43, 91.39, 96.07, 100.92, 102.52, 111.07, 119.87,
127.89, 128.39, 128.70, 136.27, 139.57, 145.85, 153.02, 154.14,
154.39 and 159.01; m/z 488 (Mϩ, 53%), 473 (47), 397 (100) and
341 (78.4) (Found: C, 73.71; H, 6.59. C30H32O6 requires C,
73.75; H, 6.60%).
1,2,7a,12a-Tetrahydro-10,13-dimethoxy-9-hydroxy-3,3-
dimethyl-3H,7H-benzofuro[2Ј,3Ј:4,5]pyrano[3,2-g][1]-
benzopyran 16
Synthesis of the pterocarpans 13, 14, 15 and 16:
General procedure
The 2H-chromene 9 (120 mg, 0.49 mmol), 2-methoxy-1,4-
benzoquinone 11 (67 mg, 0.49 mmol) and ZnCl2 (99 mg, 0.74
mmol) gave compound 16 as a colourless solid (131 mg, 71%),
mp 165–168 ЊC; νmax/cmϪ1 3552, 3019, 2927, 2854, 1624, 1587,
1492, 1216, 1143 and 762; δH (300 MHz, CDCl3) 1.32 (3 H, s,
CH3), 1.34 (3 H, s, CH3), 1.77 (2 H, t, J 6.6, 2-H), 2.75 (2 H, dt,
J 2.4, 6.6, 1-H), 3.37 (1 H, m, 7a-H), 3.60 (1 H, t, J 11, 7ax-H),
3.84 (3 H, s, OCH3), 3.95 (3 H, s, OCH3), 4.16 (1 H, dd, J 4.95,
10.95, 7eq-H), 5.29 (1 H, s, OH), 5.60 (1 H, d, J 6.6, 12a-H),
6.22 (1 H, s, 5-H), 6.50 (1 H, s, 11-H) and 6.83 (1 H, s, 8-H);
δC(75 MHz, CDCl3) 17.17, 26.57, 27.06, 32.39, 39.89, 56.21,
61.52, 66.30, 74.57, 75.42, 94.94, 100.97, 106.28, 108.62, 110.32,
118.13, 139.73, 146.84, 153.11, 155.23, 156.33 and 159.27; m/z
384 (Mϩ, 15%), 179 (15), 149 (34), 97 (44) and 57 (100) (Found:
C, 68.74; H, 6.26. C22H24O6 requires C, 68.74; H, 6.29%).
To a well stirred solution of the 2-alkoxy-1,4-benzoquinone (11
or 12) (1 mol equiv.) in dichloromethane, ZnCl2 (1.5 mol equiv.)
was added, followed by a solution of the 2H-chromene (8, 9 or
10) (1 mol equiv.) in dichloromethane at room temperature
under nitrogen atmosphere. After completion of the reaction
(monitored by TLC), the mixture was diluted with water to
quench the reaction and then extracted with dichloromethane.
The extract was washed with water and brine, dried (Na2SO4)
and concentrated in vacuo. The products were chromato-
graphed over silica gel using LP–ethyl acetate (92:8) as eluent
to afford the title compounds.
3,4,8a,13a-Tetrahydro-10-hydroxy-5,11-dimethoxy-2,2-
dimethyl-2H,8H-benzofuro[2Ј,3Ј:4,5]pyrano[2,3-h][1]benzo-
pyran 13
The 2H-chromene 8 (200 mg, 0.81 mmol), 2-methoxy-1,4-
benzoquinone 11 (110 mg, 0.81 mmol) and ZnCl2 (160 mg, 1.21
mmol) gave compound 13 as a colourless solid (190 mg, 62%);
mp 85–88 ЊC; νmax/cmϪ1 3552, 3026, 1620, 1492, 1453, 1216 and
1130; δH (300 MHz, CDCl3) 1.28 (3 H, s, CH3), 1.45 (3 H, s,
CH3), 1.78 (2 H, m, 3-H), 2.58 (2 H, m, 4-H), 3.33 (1 H, m,
8a-H), 3.61 (1 H, t, J 11, 8ax-H), 3.78 (3 H, s, OCH3), 3.84 (3 H,
s, OCH3), 4.17 (1 H, q, J 4.9, 10.9, 8eq-H), 5.21 (1 H, s, OH),
5.56 (1 H, d, J 6.4, 13a-H), 6.02 (1 H, s, 6-H), 6.51 (1 H, s, 12-H)
and 6.82 (1 H, s, 9-H); m/z 384 (Mϩ, 100%), 328 (61) and 165
(15) (Found: C, 68.77; H, 6.28. C22H24O6 requires C, 68.74;
H, 6.29%).
3,4,8a,13a-Tetrahydro-5,11-dimethoxy-2,2-dimethyl-2H,8H-
benzofuro[2Ј,3Ј:4,5]pyrano[2,3-h][1]benzopyran-10-yl
trifluoromethanesulfonate 17
To a solution of the pterocarpan 13 (70 mg, 0.182 mmol) in
dichloromethane (10 ml) was added pyridine (0.061 ml, 0.75
mmol) at Ϫ78 ЊC, followed after 1 h, by trifluoromethane-
sulfonic anhydride (0.061 ml, 0.364 mmol). The mixture was
stirred at Ϫ78 ЊC for 4 h, after which it was warmed to room
temperature and poured into water (25 ml). The aqueous layer
was separated and extracted with dichloromethane (3 × 25 ml)
and the combined extracts were washed with water and brine,
dried (Na2SO4) and concentrated under reduced pressure to
give a colourless solid. This was chromatographed over silica
gel with LP–ethyl acetate (95:5) as eluent to give compound 17
as a colourless solid (72 mg, 77%), mp 125–127 ЊC; νmax/cmϪ1
3029, 2979, 2400, 1617, 1492, 1420, 1222 and 762; δH (300 MHz,
CDCl3) 1.44 [6 H, s, 2,2-(CH3)2], 1.81 (2 H, m, 3-H), 2.60 (2 H,
m, 4-H), 3.41 (1 H, m, 8a-H), 3.65 (1 H, t, J 10.9, 8ax-H), 3.78
(3 H, s, OCH3), 3.85 (3 H, s, OCH3), 4.17 (1 H, dd, J 4.9, 10.9,
8eq-H), 5.69 (1 H, d, J 6.6, 13a-H), 6.03 (1 H, s, 6-H), 6.58 (1 H,
s, 12-H) and 7.08 (1 H, s, 9-H); δC(125 MHz, CDCl3) 16.93,
26.02, 27.85, 32.27, 39.34, 55.65, 56.56, 66.27, 75.06, 76.84,
91.07, 96.52, 100.85, 103.4, 118.37, 118.97, 132.39, 152.65,
154.7, 155.56, 159.42 and 160.56; m/z 516 (Mϩ, 64%), 383 (97)
and 327 (100) (Found: C, 53.53; H, 4.47; S, 6.21. C23H23SO8F3
requires C, 53.49; H, 4.49; S, 6.24%).
3,4,8a,13a-Tetrahydro-10-hydroxy-5,11-dimethoxy-2,2,8,8-
tetramethyl-2H,8H-benzofuro[2Ј,3Ј:4,5]pyrano[2,3-h][1]-
benzopyran 14
The 2H-chromene 10 (160 mg, 0.58 mmol), 2-methoxy-1,4-
benzoquinone 11 (80 mg, 0.58 mmol) and ZnCl2 (120 mg, 0.87
mmol) gave compound 14 as a colourless solid (130 mg, 55%),
mp 94–96 ЊC; δH (300 MHz, CDCl3) 0.94 (3 H, s, CH3), 1.23 (3
H, s, CH3), 1.48 [6 H, s, 2-(CH3)2], 1.83 (2 H, m, 3-H), 2.58 (2 H,
m, 4-H), 3.12 (1 H, d, J 6.95, 8a-H), 3.78 (3 H, s, OCH3), 3.86 (3
H, s, OCH3), 5.25 (1 H, s, OH), 5.48 (1 H, d, J 6.95, 13a-H), 6.02
(1 H, s, 6-H), 6.51 (1 H, s, 12-H) and 6.86 (1 H, s, 9-H); δC(75
MHz, CDCl3) 16.82, 19.87, 25.0, 27.54, 28.42, 32.07, 48.73,
55.37, 56.13, 74.64, 76.28, 76.45, 91.40, 94.71, 100.98, 102.53,
110.89, 119.28, 139.31, 146.74, 153.0, 154.25, 154.41 and
159.03; m/z 412 (Mϩ, 91.2%), 397 (100), 341 (83.3) and 178
(29.4) (Found: C, 69.93; H, 6.89. C24H28O6 requires C, 69.87;
H, 6.85%).
1,2,7a,12a-Tetrahydro-10,13-dimethoxy-3,3-dimethyl-3H,7H-
benzofuro[2Ј,3Ј:4,5]pyrano[3,2-g][1]benzopyran-9-yl
trifluoromethanesulfonate 19
In a manner similar to that described for the preparation of the
triflate 17, the pterocarpan 16 (60 mg, 0.156 mmol) was con-
verted into 19 with pyridine (0.052 ml, 0.64 mmol) and trifluoro-
methanesulfonic anhydride (0.052 ml, 0.31 mmol). Silica gel
column chromatography of the crude product with 5% ethyl
acetate–LP as eluent, afforded the title compound as a colour-
less solid (70.8 mg, 88%), mp 176–179 ЊC; νmax/cmϪ1 3019, 2979,
2400, 1624, 1584, 1499, 1420, 1222, 1143 and 755; δH (300 MHz,
CDCl3) 1.33 (3 H, s, CH3), 1.35 (3 H, s, CH3), 1.78 (2 H, t, J
6.77, 2-H), 2.75 (2 H, dt, J 2.2, 6.77, 1-H), 3.47 (1 H, m, 7a-H),
3.64 (1 H, t, J 10.6, 7ax-H), 3.86 (3 H, s, OCH3), 3.95 (3 H, s,
OCH3), 4.16 (1 H, dd, J 4.9, 10.9, 7eq-H), 5.74 (1 H, d, J 6.7,
3,4,8a,13a-Tetrahydro-10-hydroxy-5-methoxy-11-benzyloxy-
2,2,8,8-tetramethyl-2H,8H-benzofuro[2Ј,3Ј:4,5]pyrano[2,3-h]-
[1]benzopyran 15
The 2H-chromene 10 (180 mg, 0.65 mmol), 2-benzyloxy-1,4-
benzoquinone 12 (140 mg, 0.65 mmol) and ZnCl2 (130 mg, 0.97
mmol) gave compound 15 as a colourless solid (190 mg, 61%),
mp 96–98 ЊC; νmax/cmϪ1 3539, 3427, 3019, 1617, 1596, 1492,
1341, 1216 and 762; δH (500 MHz, CDCl3) 0.95 (3 H, s, CH3),
1.24 (3 H, s, CH3), 1.48 (3 H, s, CH3), 1.50 (3 H, s, CH3), 1.84 (2
H, m, 3-H), 2.60 (2 H, m, 4-H), 3.13 (1 H, d, J 7.0, 8a-H), 3.79
(3 H, s, OCH3), 5.07 (2 H, s, OCH2), 5.33 (1 H, s, OH), 5.49 (1
J. Chem. Soc., Perkin Trans. 1, 1997
1877

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12a-H), 6.22 (1 H, s, 5-H), 6.58 (1 H, s, 11-H) and 7.09 (1 H, s,
8-H); δC(75 MHz, CDCl3) 17.2, 26.58, 27.11, 32.34, 39.43,
56.42, 61.57, 65.99, 74.75, 76.85, 96.22, 101.12, 105.48, 108.91,
118.38, 118.67, 132.44, 152.59, 155.24, 156.72, 159.29 and
160.07; m/z 516 (Mϩ, 34%), 383 (100), 368 (19), 313 (12) and 83
(53) (Found: C, 53.50; H, 4.49, S, 6.20. C23H23SO8F3 requires C,
53.49; H, 4.49; S, 6.21%).
H, s, 5-H), 6.42 (1 H, d, J 2.2, 11-H), 6.46 (1 H, dd, J 6.52, 2.2,
9-H) and 7.13 (1 H, d, J 8, 8-H); δC(75 MHz, CDCl3) 17.2,
26.54, 27.17, 32.41, 39.19, 55.56, 61.6, 66.38, 74.63, 75.97,
97.05, 100.98, 106.22, 108.70, 119.37, 124.66, 155.26, 156.42,
159.34, 160.99 and 161.12; m/z 368 (Mϩ, 3%), 86 (90), 83 (100)
and 47 (51) (Found: C, 71.69; H, 6.59. C22H24O5 requires C,
71.72; H, 6.57%).
3,4,8a,13a-Tetrahydro-5,11-dimethoxy-2,2-dimethyl-2H,8H-
benzofuro[2Ј,3Ј:4,5]pyrano[2,3-h][1]benzopyran 18
Acknowledgements
The authors are grateful to the Council of Scientific and Indus-
trial Research (CSIR) and BRNS (DAE) for the financial
assistance. One of us (K. S.) thanks the CSIR, New Delhi for
the award of a Senior Research Fellowship. We thank RSIC,
The triflate 17 (60 mg, 0.11 mmol) was dissolved in N,N-
dimethylformamide (3 ml) under an argon atmosphere at room
temperature. Palladium() acetate (15.9 mg, 0.070 mmol), 1,1Ј-
bis(diphenylphosphino)ferrocene (31 mg, 0.056 mmol), tri-
ethylamine (0.334 ml, 2.4 mmol) and aqueous formic acid (0.15
ml, 3.8 mmol) was added at 75 ЊC to the reaction mixture which
was then stirred for 1 h. After completion of the reaction
(monitored by TLC), the mixture was cooled to room temper-
ature, diluted with water (10 ml) and extracted with dichloro-
methane (2 × 25 ml). The combined extracts were washed with
water and brine, dried (Na2SO4) and concentrated in vacuo.
Column chromatography of the residue over silica gel using
LP–ethyl acetate (97:3) afforded compound 18 (32 mg, 78%),
mp 151–152 ЊC; νmax/cmϪ1 3019, 2979, 1617, 1597, 1505, 1466,
1446, 1216, 1117 and 760; δH (300 MHz, CDCl3) 1.23 (3 H, s,
CH3), 1.46 (3 H, s, CH3), 1.83 (2 H, m, 3-H), 2.59 (2 H, m, 4-H),
3.35 (1 H, m, 8a-H), 3.52 (1 H, t, J 10.9, 8ax-H), 3.77 (3 H, s,
OCH3), 3.78 (3 H, s, OCH3), 4.17 (1 H, q, J 5.2, 11.1, 8eq-H),
5.61 (1 H, d, J 6.8, 13a-H), 6.03 (1 H, s, 6-H), 6.43 (1 H, dd, J
2.8, 8.14, 10-H), 6.48 (1 H, d, J 2.3, 12-H) and 7.12 (1 H, d,
J 8.0, 9-H); δC(125 MHz, CDCl3) 16.96, 25.94, 27.96, 32.29,
39.15, 55.61, 55.69, 66.67, 74.93, 75.98, 91.0, 97.28, 101.5,
103.19, 106.2, 119.65, 124.65, 154.8, 155.54, 159.18, 161.23 and
161.47; m/z 368 (Mϩ, 100%), 312 (71), 221 (31) and 165 (32)
(Found: C, 71.72; H, 6.56. C22H24O5 requires C, 71.72; H,
6.57%).
1
I.I.T. Bombay (for H, 13C NMR and mass spectroscopy) and
T.I.F.R., Bombay (for 1H and 13C NMR spectroscopy) for spec-
tral analysis.
References
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1,2,7a,12a-Tetrahydro-10,13-dimethoxy-3,3-dimethyl-3H,7H-
benzofuro[2Ј,3Ј:4,5]pyrano[3,2-g][1]benzopyran 3
In a manner similar to that for the preparation of compound
18, the triflate 19 (40 mg, 0.077 mmol) was converted into edu-
lane 3 by heating a mixture of triflate 19 with palladium()
acetate (10.6 mg, 0.050 mmol), 1,1Ј-bis(diphenylphosphino)-
ferrocene (21 mg, 0.037 mmol), triethylamine (0.223 ml, 1.60
mmol) and formic acid (0.1 ml, 2.53 mmol) to 75 ЊC for 2 h.
Column chromatography of the resulting solid over silica gel
with LP–ethyl acetate (97:3) as eluent afforded the title com-
pound 3 (23.7 mg, 84% yield); mp 177–178 ЊC; νmax/cmϪ1 3019,
2979, 2400, 1624, 1584, 1499, 1479, 1347, 1216, 1143 and 767;
δH (300 MHz, CDCl3) 1.32 (3 H, s, CH3), 1.34 (3 H, s, CH3), 1.77
(2 H, t, J 6.5, 2-H), 2.76 (2 H, t, J 6.5, 1-H), 3.40 (1 H, m, 7a-H),
3.60 (1 H, t, J 10.98, 7ax-H), 3.77 (3 H, s, OCH3), 3.96 (3 H, s,
OCH3), 4.16 (1 H, m, 7eq-H), 5.66 (1 H, d, J 6.6, 12a-H), 6.22 (1
Paper 6/08227K
Received 5th December 1996
Accepted 20th February 1997
1878
J. Chem. Soc., Perkin Trans. 1, 1997