Regiospecific substitution of the carbon-boron bond of tris(4-trimethylsilylfuran-3-yl)boroxine and tris(4-methylfuran-3-yl)boroxine. Model approaches towards sesquiterpenoid furanoeudesmanes

Article abstract of DOI:10.1016/S0040-4020(02)01519-3

Furan-containing compounds occur abundantly in nature. Among them, the sesquiterpenoid furanoeudesmanes are particularly interesting due to their allergenic, plant-growth inhibiting, antibacterial as well as antitumor properties. Recently an organoboron protocol has been developed in our laboratory for the preparation of regiospecific-substituted furans. By utilizing such methodology, two common intermediates 1 and 2 that may lead to the synthesis of naturally occurring tubipofuran (3) furanoeudesm-4-ene (4) and furanoeudesma-1,4-dien-6-one (5) were obtained.

Full text of DOI:10.1016/S0040-4020(02)01519-3

Tetrahedron 59 (2003) 325–333
Regiospecific substitution of the carbon–boron bond of
tris(4-trimethylsilylfuran-3-yl)boroxine and
tris(4-methylfuran-3-yl)boroxine. Model approaches towards
sesquiterpenoid furanoeudesmanesq
*
Chung-Yan Yick, Tsun-Keung Tsang and Henry N. C. Wong
Department of Chemistry, Institute of Chinese Medicine, and Central Laboratory of the Institute of Molecular Technology for Drug
Discovery and Synthesis, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, People’s Republic of China
Received 2 October 2002; revised 29 October 2002; accepted 21 November 2002
Dedicated to Professor Wei-Shan Zhou on the occasion of his 80th birthday
Abstract—Furan-containing compounds occur abundantly in nature. Among them, the sesquiterpenoid furanoeudesmanes are particularly
interesting due to their allergenic, plant-growth inhibiting, antibacterial as well as antitumor properties. Recently an organoboron protocol
has been developed in our laboratory for the preparation of regiospecific-substituted furans. By utilizing such methodology, two common
intermediates 1 and 2 that may lead to the synthesis of naturally occurring tubipofuran (3) furanoeudesm-4-ene (4) and furanoeudesma-1,4-
dien-6-one (5) were obtained. q 2003 Elsevier Science Ltd. All rights reserved.
1. Introduction
the instability of some of the products, synthesis of this
family of compounds is still a challenge to organic chemists.
It is not surprising that up to now, only very few papers
reported the total synthesis of this class of natural products.4
During the last few decades, a large number of
furanoeudesmanes were isolated from higher plants, and
more recently this group of compounds have also been
encountered in marine organisms.2 Because of their potent
biological activities,3 much effort has been devoted to the
synthesis and studies of these molecules. However, due to
the highly diversified structures of the eudesmane units and
Employing our experience in the preparation of regio-
specifically substituted furans,5 we targeted to extend our
protocol towards the synthesis of furanoeudesmanes
through an intermediate 1 (Scheme 1). In this connection,
Scheme 1.
q See Ref. 1.
Keywords: Friedel–Crafts reactions; furans; Suzuki reaction; terpenes and terpenoids.
*
Corresponding author. Tel.: þ852-2609-6329; fax: þ852-2603-5057; e-mail: hncwong@cuhk.edu.hk
0040–4020/03/$ - see front matter q 2003 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(02)01519-3

326
C.-Y. Yick et al. / Tetrahedron 59 (2003) 325–333
Scheme 2.
Scheme 3.
our latest achievement in synthesizing angular analogs of 1
is noteworthy.6 It was hoped that 1 could be easily
converted to 2,5 precursor for our eudesmane program of
which tubipofuran (3), furanoeudesm-4-ene (4) and fur-
anoeudesma-1,4-dien-6-one (5) are our targets (Scheme 1).
The preparation of ring A precursor is shown in Scheme 3.
Starting from the Hageman’s ester,7 bromination was
expected to take place in an endocyclic mode.9 Thus, the
enone was first protected as an acetal, which was allowed to
react with bromine. Disappointingly, the reaction resulted in
a messy mixture. On the other hand, a direct bromination of
the Hageman’s ester with pyridinium bromide perbromide
in acetic acid gave cleanly a 2:1 diastereomeric mixture of
2. Results and discussion
1
dibromide 9 whose structure is supported by its H NMR
spectrum. A direct coupling of 9 with boroxine 7 was not
successful due to the instability of 9 under the basic
condition normally employed for the Suzuki coupling.10
Therefore, ketone 9 was protected with ethylene glycol,
resulting in an cyclic acetal 10 in a quantitative yield
(Scheme 3).
The retrosynthetic pathway for the preparation of 1 is shown
in Scheme 2. The ring C building block, tris(4-trimethyl-
silylfuran-3-yl)boroxine (7), was easily accessible through
our silicon–boron protocol,5 whose preparation can be
easily carried out in a large scale manner. Disconnection of
6 in ring B leads to compound 8 that is a Hageman’s ester
derivative.7 Hence, the allyl bromide group of 8 would serve
as a handle for the palladium(0)-catalyzed coupling reaction
with boroxine 7, while the ester group of 8 would be
important for ring B closure through a Friedel–Crafts
acylation.8 Lastly, catalytic hydrogenation of the double
bond in 6 followed by the removal of the carbonyl group
next to the furan would furnish 1, whose trimethylsilyl
group would then be transformed to a methyl group, leading
to 2.
As illustrated in Scheme 4, reaction of 10 with boroxine 7
proceeded smoothly in 10 M equivalents of aqueous K3PO4
and 5 mol% Pd(PPh3)4 in refluxing THF, affording 11 in
70% yield. The remaining bromine substituent was
effectively removed in two steps. Thus, hydrolysis of acetal
11 in refluxing 80% acetic acid gave ketone 12 in 65% yield.
It is noteworthy that 12 is very unstable and decomposes
readily. Despite this, a debromination reaction was
Scheme 4.

C.-Y. Yick et al. / Tetrahedron 59 (2003) 325–333
327
Scheme 5.
performed by stirring 12 with activated zinc in glacial acetic
acid to complete the reaction in 94% yield. Attempted
reprotection of the carbonyl group with ethylene glycol only
resulted in an unstable acetal which hydrolyzed readily once
in contact with silica gel or alumina during the chromato-
graphic purification. The generation of thioketal that
requires the addition of boron trifluoride as catalyst is not
recommended due to the likely protodesilylation problem.
The resulting ketone 13 was then reduced with NaBH4 in the
presence of CeCl3 in ethanol to afford a diastereomeric
mixture of compound 14 in a diastereomeric ratio of 2:1.
The final hurdle of ring B construction was smoothly
completed through a Friedel–Crafts acylation.8 Thus,
saponification of 14 with NaOH was followed immediately
by the addition of trifluoroacetic anhydride. After usual
work-up, the triflate intermediate was hydrolyzed with
methanolic sodium hydrogen carbonate to provide alcohol
15 in an overall yield of 55%. The diastereomeric mixture of
15 was separable by chromatography on silica gel.
this reason, the D4,4a isomer was isolated along with
compound 6 in the ratio of 3:1 after purification. This
isomeric mixture was hydrogenated with Adams’ catalyst to
afford a cis-decalin skeleton 16. The carbonyl group of ring
A was selectively protected with ethylene glycol in
refluxing benzene, providing the corresponding acetal 17
in 83% yield. The remaining carbonyl group was
removed successfully by the Barton–McCombie radical
deoxygenation method.12 Thus, treatment of 17 with
LiAlH4 offered a diastereomeric mixture of the correspond-
ing alcohol. A diastereomeric mixture of xanthate was
obtained employing a standard procedure.12 Finally, treat-
ment with n-Bu3SnH and AIBN in refluxing toluene
completed the synthesis of 18 (a protected form of 1) in a
total yield of 22%.
The cis-stereochemistry at the AB ring junction of 17 was
further confirmed by an X-ray crystallographic study
(CCDC 196030).13 The ORTEP plot of 17 is showed in
Figure 1.
As can be seen in Scheme 5, when compound 15 was treated
with the Dess–Martin periodinane,11 the reaction proceeded
instantly and completed within 15 min. After usual work-
up, 1H NMR spectroscopic study of the crude product
showed a strong signal at d 5.95, indicating the formation of
the desired enone 6. However, due to the highly acidic
methylene protons on ring B, the C–C double bond shifted
easily during chromatographic purification on silica gel. For
After obtaining a sufficient amount of 18, efforts had been
made to convert the trimethylsilyl group to a methyl
group.14 Unfortunately, several experiments had been
attempted but no positive result was secured in the
conversion of 18 to 2 (Scheme 6). In order to obtain a
proper precursor for our synthetic program, we therefore
started another program whose aim was to realize 2.
Figure 1. X-Ray crystal structure of 17.

328
C.-Y. Yick et al. / Tetrahedron 59 (2003) 325–333
gel 60F254 (0.25 mm thickness) precoated on aluminum
plates, and they were visualized under short (254Nm) UV
light. Compounds on TLC plates were visualized with a
spray of 5% dodecamolybdophosphoric acid in ethanol and
with subsequent heating. Column chromatography was
performed using E. Merck silica gel (230–400 mesh).
Scheme 6.
Melting points were measured on a Reichert Microscope
apparatus and were uncorrected. NMR spectra were
recorded on a Bruker DPX-300 spectrometer (300.13 MHz
As can also be seen in Scheme 4, a palladium-catalyzed
reaction between 10 and 196 gave 20 that is a methyl version
of 11. Standard transformations of 20 via steps
(20!21!22!23!24) identical to those for 11 led
eventually to compound 24 (Scheme 4). In Scheme 5,
compound 24 was oxidized to afford diketone 25, whose
C–C double bond was hydrogenated to form 26. The cis-
stereochemistry 26 was established by a 2D 1H–1H NOESY
study whose results are illustrated in Figure 2. As can be
seen, the cis-configuration of 26 is suggested by the
correlation of the methyl group at C-5 (d 1.32) and the
proton at C-10 (d 1.51), and is in line with our own
observation of the configuration shown in 17. With 26 in
hand, protection and removal of the conjugated keto group
led to 28. Deprotection by treatment with 2N HCl in THF
finally converted 28 to one of our targets 2. The realization
of 3, 4 and 5 employing 2 as a pivotal precursor is in
progress.
1
for H and 75.47 MHz for 13C). All NMR measurements
were carried out at 300 K in deuterated chloroform solution
unless otherwise stated. Chemical shifts are reported as
parts per million (ppm) in d unit in the scale relative to the
resonance of CDCl3 (7.26 ppm in the 1H, 77.00 ppm for the
central line of the triplet in the 13C modes, respectively).
Coupling constants (J) are reported in Hz. Splitting patterns
are described by using the following abbreviations: s,
1
singlet; d, doublet; t, triplet; q, quartet; m, multiplet. H
NMR data are reported in this order: chemical shift;
multiplicity, coupling constant(s), number of proton. Mass
spectra (MS and HRMS) were obtained with a Thermo-
finnigan MAT 95XL spectrometer and determined at an
ionized voltage of 70 eV unless otherwise stated. Relevant
data were tabulated as m/z. Elemental analyses were
performed at Shanghai Institute of Organic Chemistry,
Chinese Academy of Sciences, China.
3. Experimental
3.1. General
3.1.1. Ethyl 5-bromo-2-bromomethyl-1-methyl-4-oxo-
cyclohex-2-ene-1-carboxylate (9). To a solution of the
Hageman’s ester7 (5.4 g, 27.5 mmol) in acetic acid (20 mL)
was added pyridinium bromide perbromide (26.4 g,
82.5 mmol). The mixture was stirred at rt for 3 h. After
pouring into saturated aqueous NaHCO3 solution (80 mL),
it was extracted with diethyl ether (3£100 mL). The
combined organic extract was washed with water (50 mL)
and brine (50 mL). Upon drying (MgSO4) and evaporation
All reagents and solvents were reagent grade. Further
purification and drying by standard methods were employed
when necessary. All organic solvents were evaporated under
reduced pressure with a rotary evaporator. The plates used
for thin-layer chromatography (TLC) were E. Merck silica
Figure 2. 2D NOESY of 26.

C.-Y. Yick et al. / Tetrahedron 59 (2003) 325–333
329
of solvent under reduced pressure, the residue was
chromatographed on silica gel (200 g, hexanes–ethyl
acetate, 15:1) to afford 9 (7.8 g, 80%) as a yellow oil,
which consisted of a pair of anti and syn diastereomers in a
ratio of 2:1. NMR data of the anti-isomer: 1H NMR (CDCl3)
d 1.28 (t, J¼7.2 Hz, 3H, ethyl ester’s methyl protons), 1.57
(s, 3H, C-1 methyl protons), 2.44 (t, J¼13.8 Hz, 1H, one of
C-6 protons), 2.92 (dd, J¼13.8, 5.1 Hz, 1H, one of the C-6
protons), 4.07 (d, J¼19.8 Hz, 1H, one of the bromomethyl
protons), d 4.17–4.25 (m, 3H, one of the bromomethyl
protons and ethyl ester’s methylene protons), 4.92 (dd,
J¼13.8, 5.1 Hz, 1H, C-5 proton), 6.35 (s, 1H, C-3 olefinic
proton); 13C NMR (CDCl3) d 14.0, 23.2, 29.9, 45.7, 48.2,
48.8, 62.4, 129.4, 157.5, 172.0, 190.7. NMR data of the syn
nitrogen atmosphere. After being cooled to rt, THF was
removed under reduced pressure. The aqueous residue was
extracted with ethyl acetate (3£20 mL). The combined
organic extract was washed with brine (10 mL). After
drying (MgSO4) and evaporation of solvent under reduced
pressure, the residue was chromatographed on silica gel
(100 g, hexanes–ethyl acetate, 20:1) to afford 11 (1.2 g,
70%) as a colorless oil, which consisted of a pair of
diastereomers in a ratio of 2:1. NMR data of the major
1
component: H NMR (CDCl3) d 0.20 (s, 9H, trimethylsilyl
protons), 1.27 (t, J¼7.2 Hz, 3H, ethyl ester’s methyl
protons), 1.37 (s, 3H, methyl protons), 2.34 (t, J¼13.5 Hz,
1H, one of the C-6 protons), 2.60 (dd, J¼13.5, 3.6 Hz, 1H,
one of the C-6 protons), 3.14 (d, J¼17.4 Hz, 1H, one of the
furanylmethylene protons), 3.24 (d, J¼17.4 Hz, 1H, one of
the furanylmethylene protons), 3.94–3.97 (m, 2H, ethyl
ester’s methylene protons), 4.10–4.21 (m, 4H, dioxolanyl
protons), 4.66 (dd, J¼13.8, 3.6 Hz, 1H, C-5 proton), 5.23 (t,
J¼1.5 Hz, 2H, C-3 olefinic protons), 7.25 (s, 1H, one of the
furan a protons), 7.27 (s, 1H, one of the furan a protons);
13C NMR (CDCl3) d 20.5, 14.1, 24.4, 27.8, 43.7, 48.9, 52.9,
61.4, 65.9, 66.3, 104.6, 119.5, 124.7, 126.5, 141.8, 142.1,
148.5, 174.0; NMR data of the minor component: 1H NMR
(CDCl3) d 0.20 (s, 9H, trimethylsilyl protons), 1.26 (t,
J¼7.2 Hz, 3H, ethyl ester’s methyl protons), 1.44 (s, 3H,
C-1 methyl protons), 2.23 (dd, J¼13.2, 3.6 Hz, 1H, one of
the C-6 protons), 2.92 (t, J¼13.5 Hz, 1H, one of the C-6
protons), 3.07 (s, 2H, furanylmethylene protons), 3.94–3.97
(m, 2H, ethyl ester’s methylene protons), 4.10–4.21 (m, 4H,
dioxolanyl protons), 4.41 (dd, J¼13.8, 3.6 Hz, 1H, C-5
proton), 5.17 (t, J¼1.5 Hz, 1H, C-3 olefinic proton), 7.25 (s,
1H, one of the furan a protons), 7.27 (s, 1H, one of the furan
a protons); 13C NMR (CDCl3) d 20.5, 14.1, 21.6, 27.6,
43.0, 49.7, 52.2, 61.4, 65.7, 66.4, 104.5, 119.5, 124.4, 125.3,
141.8, 143.0, 148.5, 174.0; MS (EI) m/z 456 (Mþ). HRMS
(EI) calcd for C20H29BrO5Si: 456.0968. Found: 456.0968.
1
isomer: H NMR (CDCl3) d 1.30 (t, J¼7.2 Hz, 3H, ethyl
ester’s methyl protons), 1.64 (s, 3H, C-1 methyl protons),
2.52 (dd, J¼14.4, 4.5 Hz, 1H, one of the C-6 protons), 2.98
(dd, J¼14.4, 8.4 Hz, 1H, one of the C-6 protons), 4.03 (d,
J¼19.8 Hz, 1H, one of the bromomethyl protons), d 4.17–
4.25 (m, 3H, one of the bromomethyl protons and ethyl
ester’s methylene protons), 4.59 (dd, J¼8.4, 4.5 Hz, 1H, C-5
proton), 6.38 (s, 1H, C-3 olefinic proton); 13C NMR (CDCl3) d
13.9, 23.2, 29.5, 43.4, 45.8, 47.6, 62.3, 128.9, 159.0, 172.7,
189.9;MS(FAB)m/z 354 (Mþ). Anal. calcd for C11H14Br2O3:
C, 37.32; H, 3.99. Found: C, 37.43; H, 4.02.
3.1.2. Ethyl 5-bromo-2-bromomethyl-4-(1,3-dioxolan-2-
A
yl)-1-methyl-cyclohex-2-ene-1-carboxylate
(10).
mixture of 9 (3.5 g, 10 mmol), ethylene glycol (1.7 mL,
30 mmol) and a trace amount of p-toluenesulfonic acid in
benzene (30 mL) was refluxed with a Dean-Stark trap for
48 h. After cooled to rt, the mixture was washed with
saturated NaHCO3 (5 mL), water (5 mL) and brine (5 mL).
Drying (MgSO4) and evaporation of solvent under reduced
pressure provided 10 (3.9 g, quantitative) as a viscous
colorless oil, which consisted of a pair of diastereomers
1
deriving from 9. NMR data of the major component: H
NMR (CDCl3) d 1.27 (t, J¼7.2 Hz, 3H, ethyl ester’s methyl
protons), 1.44 (s, 3H, C-1 methyl protons), 2.32 (t,
J¼13.8 Hz, 1H, one of the C-6 protons), 2.59 (dd,
J¼13.5, 3.6 Hz, 1H, one of the C-6 protons), 4.56 (dd,
J¼13.8 Hz, 3.6 Hz, 1H, C-5 proton), 5.90 (s, 1H, C-3
olefinic proton), the dioxolanyl protons, ethyl ester’s
methylene protons and bromomethyl protons appeared as
a multiplet in the region at d 3.78–4.29; 13C NMR (CDCl3)
d 14.0, 23.8, 31.0, 43.6, 48.4, 51.8, 61.7, 66.1, 104.2, 131.1,
138.9, 173.6. NMR data of the minor component: 1H NMR
(CDCl3) d 1.27 (t, J¼7.2 Hz, 3H, ethyl ester’s methyl
protons), 1.49 (s, 3H, C-1 methyl protons), 2.25 (dd,
J¼13.2, 3.3 Hz, 1H, one of C-6 protons), 2.82 (t,
J¼13.2 Hz, 1H, one of the C-6 protons), 4.36 (dd,
J¼12.9, 3.6 Hz, 1H, C-5 proton), 5.90 (s, 1H, C-3 olefinic
proton); 13C NMR (CDCl3) d 14.0, 22.2, 30.3, 42.7, 48.9,
51.0, 61.7, 65.9, 66.5, 104.1, 130.4, 140.1, 173.6; MS (EI)
m/z 398 (Mþ). Anal. calcd for C11H18Br2O4: C, 39.40; H,
4.58. Found: C, 39.54; H, 4.53.
3.1.4. Ethyl 5-bromo-4-(10,30-dioxolan-20-yl)-1-methyl-2-
(4-methylfuran-3-yl)methylcyclohex-2-ene-1-carboxy-
late (20). Similar to the preparation of 11, compound 20 was
prepared from 19 (13.3 g, 41.2 mmol) in THF (20 mL) and a
mixture of 10 (48.6 g, 123.7 mmol), Pd(PPh3)4 (2.4 g,
2.0 mmol), 2 M aqueous K3PO4 (500 mL) in THF
(260 mL). The mixture was refluxed for 21 h. Usual work-
up and column chromatography on silica gel (420 g,
hexanes–ethyl acetate, 9:1) afforded 20 (29.4 g, 60%) as a
pale yellow oil, which consisted of a pair of diastereomers in
1
a ratio of 7:3. Data of the major component: H NMR
(CDCl3) d 1.26 (t, J¼7.1 Hz, 3H), 1.38 (s, 3H), 1.86 (s, 3H),
2.33 (t, J¼13.7 Hz, 1H), 2.40 (s, 1H), 2.55 (dd, J¼13.6,
3.7 Hz, 1H), 3.00 (d, J¼17.1 Hz, 1H), 3.88–4.02 (m, 2H),
4.04–4.23 (m, 4H), 4.63 (dd, J¼13.7, 3.7 Hz, 1H), 5.22 (t,
J¼1.5 Hz, 1H), 7.16 (s, 2H); 13C NMR (CDCl3) d 7.8, 14.1,
23.9, 25.9, 43.6, 48.7, 52.6, 61.4, 65.9, 66.4, 104.5, 116.4,
120.9, 125.5, 139.7, 140.9, 141.3, 173.8; Data of the minor
1
component: H NMR (CDCl3) d 1.34 (t, J¼7.1 Hz, 3H),
1.44 (s, 3H), 1.86 (s, 3H), 2.13 (s, 1H), 2.22 (dd, J¼13.0,
3.5 Hz, 1H), 2.89 (t, J¼13.3 Hz, 1H), 3.15 (dd, J¼17.3,
1.7 Hz, 1H), 4.04–4.23 (m, 4H), 4.23–4.33 (m, 2H), 4.40
(dd, J¼13.6, 3.5 Hz, 1H), 5.16 (t, J¼1.5 Hz, 1H), 7.16 (s,
2H); 13C NMR (CDCl3) d 7.8, 13.9, 21.3, 25.6, 42.9, 49.4,
52.0, 61.4, 65.8, 66.5, 104.5, 116.4, 120.2, 124.4, 139.6,
140.8, 142.1, 173.8; MS (EI) m/z 398 (Mþ). HRMS (FAB)
3.1.3. Ethyl 5-bromo-4-(10,30-dioxolan-20-yl)-1-methyl-2-
(4-trimethylsilylfuran-3-yl)methylcyclohex-2-ene-1-car-
boxylate (11). A mixture of 10 (1.5 g, 3.8 mmol), tris(4-
trimethylsilylfuran-3-yl)boroxine (7) (650 mg, 1.3 mmol),
Pd(PPh3)4 (220 mg, 0.2 mmol) in THF (50 mL) and
aqueous K3PO4 (2 M, 20 mL) was refluxed for 3 h under a

330
C.-Y. Yick et al. / Tetrahedron 59 (2003) 325–333
(MHþ) calcd for C18H24O5Br: 399.0807, 401.0782. Found:
399.0800, 401.0787. Anal. calcd for C18H23O5Br: C, 54.15;
H, 5.81. Found: C, 54.17; H, 5.98.
the preparation of 13, compound 22 was prepared from 21
(10.9 g, 30.8 mmol) in glacial acetic acid (141 mL), zinc
dust (4.0 g, 61.7 mmol). The mixture was stirred for 3 h at
rt. Usual work-up and column chromatography on silica gel
(310 g, hexanes–ethyl acetate, 5:1) afforded 22 (5.4 g, 64%)
3.1.5. Ethyl 5-bromo-1-methyl-4-oxo-2-(4-trimethylsilyl-
furan-3-yl)methylcyclohex-2-ene-1-carboxylate (12). A
solution of 11 (500 mg, 1.1 mmol) in 80% acetic acid
(10 mL) was heated to 808C (oil bath) for 2 h. After cooling
to rt, the solvent was removed under vacuum. The residue
was then chromatographed on silica gel (40 g, hexanes–
ethyl acetate, 20:1) to afford 12 (295 mg, 65%) as a
colorless oil, which consisted of a pair of diastereomers in a
ratio of 9:1. Data of the major component: 1H NMR
(CDCl3) d 0.16 (s, 9H), 1.29 (t, J¼7.2 Hz, 3H), 1.52 (s, 3H),
2.41 (t, J¼13.5 Hz, 1H), 2.95 (dd, J¼13.5, 5.1 Hz, 1H), 3.26
(s, 2H), 4.22 (q, J¼7.2 Hz, 2H), 4.98 (dd, J¼14.5, 5.4 Hz,
1H), 5.78 (s, 1H), 7.24 (s, 1H), 7.28 (d, J¼0.9 Hz, 1H); 13C
NMR (CDCl3) d 20.6, 14.0, 24.1, 29.2, 45.7, 48.8, 49.4,
62.1, 119.4, 122.8, 126.7, 141.9, 148.8, 163.4, 172.4, 190.0;
MS (EI) m/z 412 (Mþ). HRMS (EI) calcd for C18H25BrO4Si:
412.0705. Found: 412.0700.
1
as a colorless oil; H NMR (CDCl3) d 1.27 (t, J¼7.2 Hz,
3H), 1.53 (s, 3H), 1.86 (s, 3H), 1.90–2.09 (m, 1H), 2.33–
2.64 (m, 3H), 3.32 (d, J¼6.9 Hz, 2H), 4.08–4.31 (m, 2H),
5.68 (d, J¼1.5 Hz, 1H), 7.19 (d, J¼8.1 Hz, 2H); 13C NMR
(CDCl3) d 7.8, 14.1, 22.6, 27.5, 34.2, 34.7, 47.2, 61.5, 119.9,
120.0, 127.2, 140.1, 141.1, 163.2, 174.0, 198.4. Anal. calcd
for C16H20O4: C, 69.55; H, 7.30. Found: C, 69.31; H, 7.41.
3.1.9. Ethyl 1-methyl-4-hydroxy-2-(4-trimethylsilyl-
furan-3-yl)methylcyclohex-2-ene-1-carboxylate (14). To
a stirred solution of 13 (500 mg, 1.5 mmol) in absolute
ethanol (5 mL) was added CeCl3 (740 mg, 3 mmol)
followed by NaBH4 (86 mg, 2.3 mmol). After 0.5 h, the
solution was poured into saturated aqueous NH4Cl (5 mL)
solution and extracted with diethyl ether (3£10 mL). The
combined organic extract was washed with brine (10 mL).
After drying (MgSO4) and evaporation of solvent under
reduced pressure, the crude product was chromatographed
on silica gel to afford 14 (460 mg, 92%) as a colorless oil,
which consisted of a pair of diastereomers in a ratio of 2:1.
3.1.6. Ethyl 5-bromo-1-methyl-4-oxo-2-(4-methylfuran-
3-yl)methylcyclohex-2-ene-1-carboxylate (21). Similar to
the preparation of 12, compound 21 was prepared from 20
(20.4 g, 51.2 mmol) in 80% acetic acid (255 mL) heated to
858C for 6 h. Usual work-up and column chromatography
on silica gel (600 g, hexanes–ethyl acetate, 9:1) gave 21
(14.3 g, 79%) as a pale yellow oil, which consisted of a pair
of diastereomers in a ratio of 4:1. Data of the major
1
Compound 14 showed very complicated H and 13C NMR
spectra due to the presence of a pair of diastereomers.
Compound 14 was used in the subsequent step without
further spectroscopic characterization. MS (EI) m/z 336
(Mþ). HRMS (EI) calcd for C18H28O4Si: 336.1757. Found:
336.1755.
1
component: H NMR (CDCl3) d 1.28 (t, J¼7.1 Hz, 3H),
1.54 (s, 3H), 1.83 (s, 3H), 2.42 (t, J¼13.6 Hz, 1H), 2.91 (dd,
J¼13.6, 5.3 Hz, 1H), 3.35 (s, 2H), 4.12–4.33 (m, 2H), 4.93
(dd, J¼13.6, 5.3 Hz, 1H), 5.79 (s, 1H), 7.18 (s, 2H); 13C
NMR (CDCl3) d 7.9, 14.1, 23.8, 27.6, 44.2, 45.7, 48.8, 62.1,
119.5, 124.8, 125.8, 140.3, 141.1, 162.9, 172.4, 190.8. Data
of the minor component: 1H NMR (CDCl3) d 1.28 (t,
J¼7.1 Hz, 3H), 1.57 (s, 3H), 1.85 (s, 3H), 2.51 (dd, J¼13.8,
4.9 Hz, 1H), 3.00 (dd, J¼13.7, 10.9 Hz, 1H), 3.00 (dd,
J¼13.6, 1.5 Hz, 2H), 4.12–4.33 (m, 2H), 4.66 (dd, J¼10.9,
4.9 Hz, 1H), 5.75 (s, 1H), 7.18 (s, 2H); 13C NMR (CDCl3) d
7.8, 14.0, 22.2, 27.2, 45.7, 47.1, 49.4, 62.0, 119.8, 124.8,
125.8, 140.3, 141.1, 164.3, 173.0, 190.0. Anal. calcd for
C16H19O4Br: C, 54.10; H, 5.39. Found: C, 54.10; H, 5.46.
3.1.10. Ethyl 1-methyl-4-hydroxy-2-(4-methylfuran-3-
yl)methylcyclohex-2-ene-1-carboxylate (23). Similar to
the preparation of 14, compound 23 was prepared from 22
(6.76 g, 24.5 mmol) in absolute ethanol (72 mL), CeCl3
(9.0 g, 36.7 mmol) and NaBH4 (1.85 g, 48.9 mmol) at 08C
for 4 h. Usual work-up and column chromatography on
silica gel (180 g, hexanes–ethyl acetate, 3:1) yielded 23
(4.1 g, 60%) as a colorless oil. Compound 23 showed very
complex 1H NMR and 13C NMR spectra due to the presence
of a pair of diastereomers. Data of the major component: 1H
NMR (CDCl3) d 1.19–1.27 (m, 3H), 1.31 (s, 3H), 1.45–
1.78 (m, 3H), 1.79–1.92 (m, 4H), 2.08–2.20 (m, 1H), 2.92–
3.10 (m, 2H), 3.98–4.22 (m, 3H), 5.30–5.39 (m, 1H), 7.13
(s, 2H); 13C NMR (CDCl3) d 8.0, 14.1, 23.1, 26.3, 28.5,
32.7, 46.4, 60.9, 65.7, 120.4, 121.8, 127.5, 139.6, 139.7,
140.8, 176.1. Data of the minor component: 1H NMR
(CDCl3) d 1.19–1.27 (m, 3H), 1.38 (s, 3H), 1.45–1.78 (m,
3H), 1.79–1.92 (m, 4H), 1.95–2.06 (m, 1H), 2.92–3.10 (m,
2H), 3.98–4.22 (m, 3H), 5.30–5.39 (m, 1H), 7.13 (s, 2H);
13C NMR (CDCl3) d 8.0, 14.1, 22.9, 26.3, 28.3, 32.2, 46.6,
60.8, 65.6, 120.4, 121.8, 127.1, 139.6, 139.7, 140.6, 176.1.
Anal. calcd for C16H22O4: C, 69.04; H, 7.97. Found: C,
69.04; H, 7.91.
3.1.7. Ethyl 1-methyl-4-oxo-2-(trimethylsilylfuran-3-
yl)methylcyclohex-2-ene-1-carboxylate (13). To a sol-
ution of 12 (300 mg, 0.7 mmol) in glacial acetic acid (4 mL)
was added zinc dust (150 mg, 2.1 mmol). The mixture was
stirred for 0.5 h. The zinc dust was filtered off and the filtrate
was concentrated under vacuum. Chromatography on silica
gel (10 g, hexanes–ethyl acetate 8:1) afforded 13 (220 mg,
1
94%) as a colorless oil; H NMR (CDCl3) d 0.16 (s, 9H),
1.27 (t, J¼7.2 Hz, 3H), 1.49 (s, 3H), 1.93–2.01 (m, 1H),
2.38–2.56 (m, 3H), 3.40 (s, 2H), 4.15–4.23 (m, 2H), 5.66
(s, 1H), 7.23 (s, 1H), 7.26 (d, J¼1.2 Hz, 1H); 13C NMR
(CDCl3) d 20.6, 14.1, 22.7, 29.2, 34.2, 34.6, 47.2, 61.5,
119.3, 123.1, 128.0, 141.8, 148.7, 163.8, 173.9, 198.1; MS
(EI) m/z 334 (Mþ). Anal. calcd for C18H26O4Si: C, 64.64; H,
7.83. Found: C, 64.25; H, 7.82.
3.1.11. 6,7,8,8a-Tetrahydro-6-hydroxy-8a-methyl-3-(tri-
methylsilyl)naphtho[2,3-b]furan-9(4H)-one (15). To a
solution of 14 (300 mg, 0.9 mmol) in methanol (10 mL)
was added slowly an aqueous solution of sodium hydroxide
(2 M, 2.5 mL). The mixture was then refluxed for 24 h.
After diluted with water (10 mL), the resulting mixture was
washed with dichloromethane (10 mL). The aqueous layer
3.1.8. Ethyl 1-methyl-4-oxo-2-(4-methylfuran-3-
yl)methylcyclohex-2-ene-1-carboxylate (22). Similar to

C.-Y. Yick et al. / Tetrahedron 59 (2003) 325–333
331
was acidified with 3N HCl until the pH reached 4. It was
then extracted with dichloromethane (5£10 mL). The
combined organic extract was dried (MgSO4). After
removal of solvent under reduced pressure, the crude
product was dried under vacuum for a further 3 h and was
then dissolved in anhydrous dichloromethane (5 mL).
Trifluoroacetic anhydride (0.4 mL, 2.8 mmol) was slowly
added. After stirring at rt for 8 h, the reaction was quenched
with NaHCO3 (5 mL). The organic layer was separated and
the aqueous layer was extracted with diethyl ether
(3£5 mL). The combined organic extract was concentrated
and redissolved in methanol (5 mL). A drop of saturated
aqueous NaHCO3 was added. After 10 min at rt, the mixture
was diluted with water (5 mL) and extracted with diethyl
ether (5£5 mL). The combined organic extracts were dried
(MgSO4). After removal of solvent under reduced pressure,
the residue was purified by chromatography on silica gel
(50 g, hexanes–ethyl acetate, 3:1) to afford a chromato-
graphically separable diastereomeric mixture of 15 (50 mg,
20% and 90 mg, 35%), both as viscous colorless oils. NMR
(FAB) (MHþ) calcd for C14H17O3: 233.1173. Found:
233.1184.
3.1.13. 7,8-Dihydro-8a-methyl-3-(trimethylsilyl)-
naphtho[2,3-b]furan-6(4H),9(8aH)-dione (6). A stirred
solution of 15 (140 mg, 0.5 mmol) and Dess–Martin
periodinane (210 mg, 0.5 mmol) in dichloromethane
(5 mL) were kept at 278C under nitrogen for 1 h. The
reaction mixture was then quenched with saturated NaHCO3
(5 mL). The aqueous layer was extracted with diethyl ether
(3£5 mL). The combined organic layer was dried over
MgSO4 and concentrated under reduced pressure to yield 6
(140 mg, 100%) as a colorless oil; 1H NMR (CDCl3) d 0.03
(s, 9H), 1.49 (s, 3H), 2.26–2.40 (m, 3H), 2.48–2.53 (m,
1H), 3.48 (d, J¼19.5 Hz, 1H), 3.90 (dd, J¼19.5, 2.1 Hz,
1H), 5.96 (d, J¼1.8 Hz, 1H), 7.52 (s, 1H); MS (FAB) m/z
289 (MHþ); HRMS (EI) (Mþ) calcd for C16H20O3Si:
288.1182. Found: 288.1154. After purification of the above
crude product by chromatography on silica gel (20 g,
hexanes–ethyl acetate, 3:1), the D4,4a isomer was isolated
along with compound 6 (total yield: 130 mg, 92%) in the
ratio of 3:1 (6: D4,4a isomer) as a viscous yellow oil.
1
data of the major compound: H NMR (CDCl3) d 0.27 (s,
9H), 1.33 (s, 3H), 1.55–1.60 (m, 1H), 1.94–1.20 (m, 3H),
2.04 (br s, 1H), 3.22 (d, J¼18.3 Hz, 1H), 3.63 (dt, J¼18.3,
2.1 Hz, 1H), 4.18–4.21 (m, 1H), 5.67 (s, 1H), 7.43 (s, 1H);
13C NMR (CDCl3) d 20.9, 24.0, 27.9, 29.1, 30.6, 47.5, 66.4,
119.8, 128.6, 139.6, 140.6, 146.9, 152.4, 189.8. NMR data
of minor compound: 1H NMR (CDCl3) d 0.28 (s, 9H), 1.27
(s, 3H), 1.49–1.67 (m, 3H), 1.87–1.94 (m, 1H), 2.36–2.44
(ddd, J¼13.5, 11.7, 2.4 Hz, 1H), 3.24 (d, J¼18.0 Hz, 1H),
3.68 (dt, J¼18.0, 2.1 Hz, 1H), 4.20–4.21 (m, 1H), 5.74 (t,
J¼2.4 Hz, 1H), 7.43 (s, 1H); 13C NMR (CDCl3) d 20.9,
24.1, 26.3, 29.3, 30.8, 47.7, 65.4, 119.9, 128.1, 140.4, 140.6,
147.1, 152.3, 189.1. MS (FAB) m/z 291 (MHþ) (for the
diastereomeric mixture). Anal. calcd for C16H22O3Si (for
the diastereomeric mixture): C, 64.25; H, 8.39. Found: C,
64.00; H, 8.17.
3.1.14. 7,8-Dihydro-3,8a-dimethylnaphtho[2,3-b]furan-
6(4H),9(8aH)-dione (25). Similar to the preparation of 6,
compound 25 was prepared from 24 (270 mg, 1.1 mmol),
Dess–Martin periodinane (730 mg, 1.7 mmol) in dichloro-
methane (90 mL) for 3 h. Usual work-up and column
chromatography on silica gel (7 g, hexanes–ethyl acetate,
2:1) gave 25 (190 mg, 73%) as a colorless oil, which
consisted of a D4,4a isomer in the ratio of 4:1. Data of the
1
major component: H NMR (CDCl3) d 1.48 (d, J¼1.6 Hz,
3H), 2.05 (d, J¼1.1 Hz, 3H), 2.15–2.46 (m, 3H), 2.47–2.54
(m, 2H), 3.43 (d, J¼19.6 Hz, 1H), 3.79 (dd, J¼19.6, 1.9 Hz,
1H), 5.97 (d, J¼1.8 Hz, 1H), 7.47 (d, J¼1.1 Hz, 1H).
Compound 25 showed a very complex 13C NMR spectrum
due to the presence of the D4,4a isomer. MS (EI) m/z 230
(Mþ); HRMS (FAB) (MHþ) calcd for C14H15O3: 231.1021.
Found: 231.1012.
3.1.12. 6,7,8,8a-Tetrahydro-6-hydroxy-3,8a-dimethyl-
naphtho[2,3-b]furan-9(4H)-one (24). Similar to the
preparation of 15, compound 24 was prepared from 23
(4.3 g, 15.5 mmol) in methanol (116 mL) and 2 M sodium
hydroxide (39 mL) for 24 h. Usual work-up gave a product
which was treated with trifluoroacetic anhydride (13.2 mL,
92.9 mmol) in dichloromethane (77 mL). After stirring for
10 h, the mixture was again worked up as usual to give a
product which was treated with saturated NaHCO3 in
methanol (400 mL). Work-up and column chromatography
on silica gel (130 g, hexanes–ethyl acetate, 3:1) produced a
diastereomeric mixture of 24 (500 mg, 14% and 270 mg,
8%) as colorless oils. Data of the major compound: 1H NMR
(CDCl3) d 1.25 (s, 3H), 1.43–1.66 (m, 2H), 1.75–1.96 (m,
2H), 2.00 (s, 3H), 2.38 (ddd, J¼13.9, 10.0, 2.2 Hz, 1H), 3.15
(d, J¼18.2 Hz, 1H), 3.55 (dt, J¼18.2, 2.2 Hz, 1H),
4.10–4.26 (m, 1H), 5.73 (t, J¼2.4 Hz, 1H), 7.36 (s, 1H);
13C NMR (CDCl3) d 7.7, 24.1, 26.3, 28.4, 29.2, 47.6, 65.4,
120.2, 128.1, 137.0, 140.1, 145.0, 146.1, 189.0. Data of the
minor compound: 1H NMR (CDCl3) d 1.29 (s, 3H),
1.44–1.71 (m, 1H), 1.86–1.95 (m, 3H), 1.98 (d,
J¼0.8 Hz, 3H), 2.12–2.40 (m, 1H), 3.13 (d, J¼18.5 Hz,
1H), 3.52 (dt, J¼18.5, 2.1 Hz, 1H), 4.09–4.27 (m, 1H),
5.66 (s, 1H), 7.35 (d, J¼0.8 Hz, 1H); 13C NMR (CDCl3) d
7.6, 22.6, 24.0, 28.1, 28.9, 47.3, 66.3, 120.1, 128.6, 137.0,
139.1, 145.1, 145.8, 189.6; MS (EI) m/z 232 (Mþ); HRMS
3.1.15. 4,5,7,8-Tetrahydro-8a-methyl-3-(trimethylsilyl)-
naphtho[2,3-b]furan-6(4H),10(8aH)-dione
(16).
A
solution of 6 (1.97 g, 6.82 mmol) in methanol (170 mL)
was hydrogenated from a hydrogen balloon over platinum
(IV) oxide (0.17 g, 0.68 mmol). After stirring for 4.5 h, the
reaction mixture was filtered, washed with ethyl acetate and
hexanes. Upon removal of solvent under reduced pressure,
the residue was purified by chromatography on silica gel
(37 g, hexanes–ethyl acetate, 3:1) to afford 16 (1.16 g,
1
59%) as a colorless oil; H NMR (CDCl3) d 0.22 (s, 9H),
1.31 (s, 3H), 1.50 (dt, J¼13.3, 5.2 Hz, 1H), 2.22–2.56 (m,
6H), 2.63 (dt, J¼13.5, 4.5 Hz, 1H), 3.13 (dd, J¼17.3,
4.5 Hz, 1H), 7.46 (s, 1H); 13C NMR (CDCl3) d 21.0, 23.4,
27.1, 32.8, 38.6, 43.8, 44.7, 46.7, 121.1, 139.5, 146.2, 152.8,
188.6, 210.3; MS (FAB) m/z 291 (MHþ); HRMS (FAB)
(MHþ) calcd for C16H23O3Si: 291.1411. Found: 291.1423.
Anal. calcd for C16H22O3Si: C, 66.17; H, 7.63. Found: C,
66.15; H, 7.68.
3.1.16. 4,5,7,8-Tetrahydro-3,8a-dimethylnaphtho[2,3-
b]furan-6(4H),10(8aH)-dione (26). Similar to the
preparation of 16, compound 26 was prepared from the
hydrogenation of 25 (55 mg, 0.24 mmol) over platinum (IV)

332
C.-Y. Yick et al. / Tetrahedron 59 (2003) 325–333
oxide (11 mg, 0.02 mmol) in methanol (8 mL) for 4 h. Usual
work-up and column chromatography on silica gel (5 g,
hexanes–ethyl acetate, 2:1) gave 26 (29 mg, 52%) as a
disulfide (0.74 mL, 12.2 mmol), iodomethane (0.75 mL,
12.0 mmol), and sodium hydride (60% dispersion in mineral
oil) (0.14 g, 3.4 mmol) were subsequently added. The
mixture was stirred under nitrogen for 4.5 h at 08C. The
reaction mixture was then quenched with water (20 mL).
The aqueous layer was extracted with diethyl ether
(3£50 mL). The combined organic extract was washed
with brine (50 mL) and dried over MgSO4. After removal of
the solvent under reduced pressure, the residue was
dissolved in anhydrous toluene (3 mL) and the solution
was added dropwise under nitrogen over 30 min into a hot
(1108C) solution of tri-n-butyltin hydride (6.21 mL,
23.1 mmol) and a catalytic amount of AIBN (3.8 mg,
0.02 mmol) in anhydrous toluene (4 mL). After refluxing for
72 h, the reaction mixture was concentrated under vacuum.
The residue was purified by chromatography on silica gel
(20 g, hexanes–ethyl acetate, 5:1) to provide 18 (0.16 g,
1
colorless oil; H NMR (CDCl3) d 1.32 (s, 3H), 1.51 (td,
J¼13.4, 5.1 Hz, 1H), 1.99 (s, 3H), 2.23–2.59 (m, 6H), 2.66
(dt, J¼13.6, 5.4 Hz, 1H), 3.04 (dd, J¼17.6, 5.0 Hz, 1H),
7.43 (s, 1H); 13C NMR (CDCl3) d 7.7, 23.6, 24.8, 33.0, 38.7,
44.0, 44.5, 46.8, 121.4, 135.7, 145.3, 145.6, 188.5, 210.5;
MS (EI) m/z 232 (Mþ); HRMS (FAB) (MHþ) calcd for
C14H17O3: 233.1178. Found: 233.1162.
3.1.17. 4,5,7,8-Tetrahydro-8a-methyl-6,6-(10,30-dioxolan-
20-yl)-3-(trimethylsilyl)naphtho[2,3-b]furan-9-one (17).
A solution of 16 (0.81 g, 2.79 mmol), anhydrous benzene
(159 mL), ethylene glycol (3.12 mL, 55 mmol), and
p-toluenesulfonic acid monohydrate (280 mg, 1.39 mmol)
was refluxed for 15 h with a Dean–Stark apparatus. After
cooling to rt, the reaction mixture was diluted with ethyl
acetate (350 mL), then washed consecutively with saturated
aqueous NaHCO3 (350 mL), water (350 mL), and brine
(350 mL). The organic solution was then dried over MgSO4.
After removal of solvent under reduced pressure, the residue
was purified by chromatography on silica gel (26 g,
hexanes–ethyl acetate, 5:1) to furnish 17 (0.77 g, 83%) as
colorless crystals (hexanes–ethyl acetate); mp 162–1648C;
1H NMR (CDCl3) d 0.18 (d, J¼2.3 Hz, 9H), 1.16 (d,
J¼2.5 Hz, 3H), 1.25–1.72 (m, 6H), 2.23 2.45 (m, 2H),
3.03–3.18 (m, 1H), 3.79–3.91 (m, 4H), 7.37 (d, J¼2.1 Hz,
1H); 13C NMR (CDCl3) d 21.0, 24.5, 26.9, 30.9, 32.0, 37.8,
42.1, 46.8, 64.1, 64.2, 108.8, 120.8, 139.7, 146.5, 152.1,
189.7. Anal. calcd for C18H26O4Si: C, 64.64; H, 7.83.
Found: C, 64.74; H, 7.99.
1
22%) as a colorless oil; H NMR (CDCl3) d 0.19 (s, 9H),
0.98 (s, 3H), 1.36–1.92 (m, 7H), 2.09 (t, J¼14.4 Hz, 2H),
2.70–2.89 (m, 2H), 3.87–4.01 (m, 4H), 7.14 (s, 1H); 13C
NMR (CDCl3) d 20.7, 26.8, 27.4, 28.2, 31.3, 33.4, 36.6,
37.7, 38.5, 64.2, 64.2, 109.5, 116.6, 118.7, 145.7, 149.1; MS
(EI) m/z 320 (Mþ); HRMS (EI) (Mþ) calcd for C18H28O3Si:
320.1808. Found: 320.1791.
3.1.20. 4,5,7,8-Tetrahydro-3,8a-dimethyl-6,6-(10,30-
dioxolan-20-yl)naphtho[2,3-b]furan (28). Similar to the
preparation of 18, compound 28 was prepared from 27
(30 mg, 0.1 mmol) in three consecutive steps with proper
work-ups as shown above, employing the following
reagents, solvents and conditions: (1) LiAlH4 (5 mg,
0.13 mmol) in anhydrous THF (17 mL), 1 h at 08C; (2)
carbon disulfide (0.05 mL, 0.83 mmol), iodomethane
(0.05 mL, 0.8 mmol) and sodium hydride (60% dispersion
in mineral oil) (40 mg, 1 mmol), 5 h at 08C; (3) tri-n-butyltin
hydride (0.28 mL, 1 mmol), AIBN (1 mg), anhydrous
toluene, refluxed for 72 h. Usual work-up and column
chromatography on silica gel (5 g, hexanes–ethyl acetate,
3.1.18. 4,5,7,8-Tetrahydro-3,8a-dimethyl-6,6-(10,30-
dioxolan-20-yl)naphtho[2,3-b]furan-9-one (27). Similar
to the preparation of 17, compound 27 was prepared from
26 (29 mg, 0.1 mmol), ethylene glycol (0.14 mL,
2.5 mmol), p-toluenesulfonic acid monohydrate (12 mg,
0.06 mmol) in anhydrous benzene (7 mL) for 24 h. Usual
work-up and column chromatography on silica gel (5 g,
hexanes–ethyl acetate, 2:1) afforded 27 (21 mg, 60%) as a
1
10:1) gave 28 (14 mg, 47%) as a colorless oil; H NMR
(CDCl3) d 0.97 (s, 3H), 1.37–1.92 (m, 10H), 2.01 (dd,
J¼16.2, 3.4 Hz, 2H), 2.55–2.70 (m, 1H), 2.78 (d,
J¼16.9 Hz, 1H), 3.84 (m, 4H), 7.04 (s, 1H); 13C NMR
(CDCl3) d 8.1, 24.3, 27.4, 28.3, 31.3, 33.5, 36.6, 37.7, 38.1,
64.2, 109.5, 113.9, 119.7, 137.2, 148.6; MS (EI) m/z 262
(Mþ); HRMS (EI) (Mþ) calcd for C16H22O3: 262.1569.
Found: 262.1552.
1
colorless oil; H NMR (CDCl3) d 1.20 (s, 3H), 1.32–1.77
(m, 6H), 1.96 (d, J¼1.0 Hz, 3H), 2.27–2.48 (m, 2H), 3.03
(dd, J¼17.6, 5.4 Hz, 1H), 3.85–3.96 (m, 4H), 7.36 (d,
J¼1.0 Hz, 1H); 13C NMR (CDCl3) d 7.7, 24.5, 24.7, 31.0,
32.0, 38.1, 41.9, 46.9, 64.2, 64.3, 108.9, 121.1, 127.9, 136.0,
145.0, 189.6. Anal. calcd for C16H20O4: C, 69.55; H, 7.30.
Found: C, 69.34; H, 7.01.
3.1.21. 4,5,7,8-Tetrahydro-3,8a-dimethylnaphtho[2,3-
b]furan-6(5H)-one (2). To a solution of 28 (7 mg,
0.03 mmol) in THF (1 mL), an aqueous solution of 2N
HCl (0.02 mL, 0.04 mmol) was added. The reaction mixture
was stirred under nitrogen at rt for 15 h. It was then diluted
with water (5 mL) and neutralized with saturated aqueous
NaHCO3 solution (4 mL) to pH 7. After removal of THF
under reduced pressure, the aqueous layer was extracted
with diethyl ether (3£15 mL). The combined organic extract
was washed with brine (30 mL) and dried over MgSO4.
After evaporation under reduced pressure, the residue was
purified on a silica gel column (5 g, hexanes–ethyl acetate,
10:1) to provide 2 (3 mg, 45%) as a colorless oil; 1H NMR
(CDCl3) d 1.14 (s, 3H), 1.64–1.78 (m, 1H), 1.85–2.04 (m,
5H), 2.14 (dd, J¼16.3, 3.5 Hz, 1H), 2.28 (d, J¼8.2 Hz, 2H),
2.36 (dd, J¼16.3, 6.7 Hz, 2H), 2.43–2.57 (m, 1H),
3.1.19. 4,5,7,8-Tetrahydro-8a-methyl-6,6-(10,30-dioxolan-
20-yl)-3-(trimethylsilyl)naphtho[2,3-b]furan (18).
A
solution of 17 (770 mg, 2.31 mmol) in anhydrous THF
(60 mL) was added dropwise to an ice cooled (08C) solution
of LiAlH4 (96 mg, 2.31 mmol) in anhydrous THF (200 mL)
under nitrogen. After stirring for 1 h at 08C, the reaction
mixture was quenched with saturated aqueous NH4Cl
solution (150 mL), filtered through a bed of Fuller’s earth,
and rinsed with ethyl acetate (50 mL). The aqueous layer
was extracted with ethyl acetate (3£200 mL). The combined
organic extract was then washed consecutively with water
(300 mL), brine (300 mL), and dried over MgSO4. Upon
removal of solvent under reduced pressure, the residue was
dissolved in anhydrous THF (19 mL) at 08C. Carbon

C.-Y. Yick et al. / Tetrahedron 59 (2003) 325–333
333
Phytochemistry 1992, 31, 1545–1548. (e) Fontana, A.;
´
Avila, C.; Martınez, E.; Ortea, J.; Trivellone, E.; Cimino, G.
2.67–2.79 (m, 1H), 2.88 (d, J¼16.8 Hz, 1H), 7.17 (s, 1H);
13C NMR (CDCl3) d 8.9, 26.6, 26.9, 30.2, 33.5, 36.7, 37.8,
41.2, 43.9, 114.7, 120.5, 138.0, 149.4, 211.7; HRMS (EI)
(Mþ) calcd for C14H18O2: 218.1307. Found: 218.1310.
J. Chem. Ecol. 1993, 19, 339–356.
4. For a review, see: Allen, A. J.; Vaillancourt, V.; Albizati, K. F.
Org. Prep. Proceed. Int. 1994, 26, 1–84.
5. For reviews, see: (a) Wong, H. N. C. Pure Appl. Chem. 1996,
68, 335. (b) Song, Z. Z.; Wong, H. N. C.; Yang, Y. Pure Appl.
Chem. 1996, 68, 723. (c) Ye, X.-S.; Yu, P.; Wong, H. N. C.
Liebigs Ann. Chem. 1997, 459.
Acknowledgements
We are grateful to Professor Thomas C. W. Mak for
performing all X-ray crystallographic analyses. The work
described in this article was substantially supported by a
grant from the Research Grants Council of Hong Kong
Special Administrative Region, China (Project CUHK
450/95P). H. N. C. W. wishes to thank the Croucher
Foundation (Hong Kong) for a Croucher Senior Research
Fellowship (1999–2000).
6. Yick, C-Y.; Wong, H. N. C. Tetrahedron 2001, 57,
6935–6940.
7. Plieninger, H.; Suehiro, T. Chem. Ber. 1956, 89, 2789–2794.
8. Dallemagne, P.; Rault, S.; Pilo, J. C.; Foloppe, M. P.; Robba,
M. Tetrahedron Lett. 1991, 32, 6327–6328.
9. House, H. O. Modern Synthetic Reactions, 2nd ed.; W.A.
Benjamin: Menlo Park, CA, 1972; pp 459–478.
10. (a) Miyaura, N.; Yanagi, T.; Suzuki, A. Synth. Commun. 1981,
11, 513–519. (b) Miyaura, N.; Suzuki, A. Chem. Rev. 1995,
95, 2457–2483.
References
11. Dess, D. B.; Martin, J. C. J. Am. Chem. Soc. 1991, 113,
7277–7287.
1. Taken in part from the Ph.D. M.Phil. Theses of C.-Y.Y., and
T.-K.T., The Chinese University of Hong Kong, 1999 and
2002, respectively.
12. Barton, D. H. R.; McCombie, S. W. J. Chem. Soc., Perkin
Trans. 1 1975, 1574–1585.
2. (a) Roberts, J. S.; Bryson, I. Nat. Prod. Rep. 1984, 1, 105–169.
(b) Fraga, B. M. Nat. Prod. Rep. 1985, 2, 147–161. (c) Fraga,
B. M. Nat. Prod. Rep. 1986, 3, 273–289. (d) Fraga, B. M. Nat.
Prod. Rep. 1987, 4, 473–489. (e) Fraga, B. M. Nat. Prod. Rep.
1988, 5, 497–521. (f) Fraga, B. M. Nat. Prod. Rep. 1990, 7,
515–537. (g) Fraga, B. M. Nat. Prod. Rep. 1992, 9, 217–241.
(h) Fraga, B. M. Nat. Prod. Rep. 1993, 10, 397–419. (i) Fraga,
B. M. Nat. Prod. Rep. 1994, 11, 533–554. (j) Fraga, B. M. Nat.
Prod. Rep. 1995, 12, 303–320.
13. Single-crystal X-ray diffraction data for 17 were collected at
293 K on a Siemens SMART CCD diffractometer using
˚
Mo Ka radiation (l¼0.71073 A). Crystal data for 17:
C
18H26O4Si, M¼334.48, triclinic, space group p1,
˚
a¼14.8187(8), b¼14.8415(9), c¼16.8569(10) A, Z¼8,
Dc¼1.211 g cm23, m(Mo Ka)¼0.145 mm21. Least-squares
refinement based on 11473 reflections with I.2s(I) and 830
parameters led to R1¼0.0468, vR2¼0.1151 and GOF¼1.035.
The crystal structure of 17 has been deposited at the
Cambridge Crystallography Data Centre (CCDC 196030).
14. (a) Song, Z. Z.; Ho, M. S.; Wong, H. N. C. J. Org. Chem. 1994,
59, 3917–3926. (b) Wong, M. K.; Leung, C. Y.; Wong, H. N.
C. Tetrahedron 1997, 53, 3497–3512.
3. (a) Thompson, J. E.; Walker, R. P.; Wratten, S. J.; Faulkner,
D. J. Tetrahedron 1982, 38, 1865–1873. (b) Maradufu, A.
Phytochemistry 1982, 21, 677–680. (c) Tanka, J.-I.; Miki, H.;
Higa, T. J. Nat. Prod. 1992, 55, 1522–1524. (d) Kubo, I.;
Ying, B. P.; Castillo, M.; Brinen, L. S.; Clardy, J.