Asymmetric Diels-Alder addition of cyclopentadiene to chiral naphthoquinones

Article abstract of DOI:10.1016/S0957-4166(98)00087-1

Diels-Alder reactions of 1,4-naphthoquinones bearing a chiral auxiliary at C-2, with cyclopentadiene under Lewis acid conditions afforded the corresponding Diels-Alder adducts. High levels of diastereomeric excess were obtained using (R)-pantolactone, (S)-N-methyl-2-hydroxysuccinimide and trans- 2-phenylcyclohexanol as auxiliaries. Moderate asymmetric induction was achieved using Oppolzer's camphorsultam and (R)-(+)-4-benzyl-2-oxazolidinone as auxiliaries. X-Ray crystallographic analysis of the pantolactone adduct enabled determination of the stereochemistry of all adducts obtained.

Full text of DOI:10.1016/S0957-4166(98)00087-1

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 9 (1998) 1239–1255
Asymmetric Diels–Alder addition of cyclopentadiene to chiral
naphthoquinones
Margaret A. Brimble,∗ John F. McEwan and Peter Turner †
School of Chemistry, University of Sydney, NSW 2006, Sydney, Australia
Received 9 February 1998; accepted 25 February 1998
Abstract
Diels–Alder reactions of 1,4-naphthoquinones bearing a chiral auxiliary at C-2, with cyclopentadiene under
Lewis acid conditions afforded the corresponding Diels–Alder adducts. High levels of diastereomeric excess
were obtained using (R)-pantolactone, (S)-N-methyl-2-hydroxysuccinimide and trans-2-phenylcyclohexanol as
auxiliaries. Moderate asymmetric induction was achieved using Oppolzer’s camphorsultam and (R)-(+)-4-benzyl-
2-oxazolidinone as auxiliaries. X-Ray crystallographic analysis of the pantolactone adduct enabled determination
of the stereochemistry of all adducts obtained. © 1998 Elsevier Science Ltd. All rights reserved.
1. Introduction
The Diels–Alder reaction is without doubt one of the cornerstones of organic chemistry. It is undis-
putedly one of the most attractive tools available to the synthetic chemist and tremendous effort has
been focused on the search for regio- and stereoselective variants.1 Methods for performing asymmetric
Diels–Alder reactions involve the use of either a chiral diene,2 a chiral dienophile2 or a chiral catalyst,2,3
although there are only a few cases in which these methods have been applied to 1,4-naphthoquinones.4–7
In an earlier paper we report only moderate stereoinduction in cycloadditions of naphthoquinones to
various dienes using a variety of chiral catalysts.8 A large number of ligand–Lewis acid catalyst systems
were screened without obtaining significant enantiomeric excesses for Diels–Alder adducts, hence we
turned our attention to the use of a chiral auxiliary on the naphthoquinone itself.
Our interest in developing an asymmetric Diels–Alder reaction between naphthoquinones bearing an
electron withdrawing group at C-2 (1–5) and cyclopentadiene, stems from the possibility of stereo-
selectively forming a cyclopentannulated product 16–25 via fragmentation of the C-4,4a bond9 of
∗
†
Corresponding author.
X-Ray Crystallographic Unit, The University of Sydney.
0957-4166/98/$19.00 © 1998 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(98)00087-1

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6–15 affording an electrophilic site that is then trapped by a hydroxyl group (Scheme 1). The cy-
clopentannulated compounds 16–25 can be further transformed into pyranonaphthoquinones 28 after
removal of the chiral auxiliary followed by oxidative rearrangement (Scheme 2). Cyclopentannulated
pyranonaphthoquinones 28 are closely related to the large family of pyranonaphthoquinone antibiotics
which include the antifungal agents kalafungin10,11 and frenolicin.12,13
Scheme 1.
Scheme 2.
2. Results and discussion
The work reported herein examined the addition of cyclopentadiene to several 1,4-naphthoquinones
bearing a chiral auxiliary at C-2. The various chiral auxiliaries were attached to the naphthoquinone
moiety through an ester or amide linkage at C-2. The chiral quinones 1–5 were prepared by oxidation
of the corresponding dimethoxynaphthalenes 29–33 (Scheme 3), which in turn were formed from 1,4-
dimethoxy-2-naphthoic acid and the chiral auxiliary R*H (a–e) in high yield.

M. A. Brimble et al. / Tetrahedron: Asymmetry 9 (1998) 1239–1255
1241
Scheme 3.
2.1. Use of a chiral oxazolidinone
Addition of cyclopentadiene to quinone 1 bearing oxazolidinone a as chiral auxiliary at −78°C in the
presence of a variety of Lewis acids afforded adducts 6 (major) and 7 in high yield, which were separable
by flash chromatography. The optimum diastereoselectivity was achieved using ZnCl2 wherein 6 and 7
were obtained in 96% yield and in a ratio of 2.57:1 (Table 1).
Table 1
Effect of Lewis acid on reaction of 1 with cyclopentadiene†
2.2. Use of a camphorsultam
The next chiral auxiliary to be examined was the camphorsultam b which has been used effectively
in asymmetric Diels–Alder reactions by Oppolzer.2 Addition of cyclopentadiene to quinone 2, at −78°C
in the presence of a variety of Lewis acids, afforded a mixture of adducts 8 (major) and 9 which were
separable by flash chromatography, together with an inseparable mixture of compounds 18 and 19 in
some cases (Scheme 1). The optimum Diels–Alder reaction was achieved using ZnCl2 wherein adducts 8
and 9 were obtained in 66% yield and in a ratio of 7.4:1 (Table 2). Adduct 8 could be readily fragmented
to 18 using 1 equivalent of tin(IV) chloride in dichloromethane in quantitative yield (Scheme 1).
2.3. Use of (S)-N-methyl-2-hydroxysuccinimide
The Helmchen ligands14 (c and d) were also examined for their ability to achieve asymmetric induction
in the Diels–Alder reaction. These auxiliaries, which were attached via an ester rather than an amide
linkage, could potentially be removed under milder conditions. Addition of cyclopentadiene to quinone
3, at −78°C in the presence of Cu(OTf)2, ZnCl2 and Sn(OTf)2, afforded inseparable mixtures of adducts
10 (major) and 11 in high yield. The optimum result was achieved using ZnCl2 as the Lewis acid wherein

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M. A. Brimble et al. / Tetrahedron: Asymmetry 9 (1998) 1239–1255
Table 2
Effect of Lewis acid on reaction of 2 with cyclopentadiene†
Table 3
Effect of Lewis acid on reaction of 3 with cyclopentadiene†
adducts 10 and 11 were obtained in 87% yield and in a ratio of 4.3:1 (Table 3). Use of BF3·Et2O resulted
in complete formation of the fragmented products 20 and 21.
2.4. Use of (R)-pantolactone
In a similar manner, (R)-pantolactone15 d was attached to the naphthoquinone moiety via an ester
linkage. Addition of cyclopentadiene to quinone 4 at −78°C in the presence of a variety of Lewis
acids afforded inseparable mixtures of adducts 12 and 13 (major) in high yield. The optimum result
was achieved with ZnCl2 wherein adducts 12 and 13 were obtained in 64% yield and in a ratio of 1:45
(96% d.e., Table 4). Adduct 13 was readily fragmented to 23 using 1 equivalent of tin(IV) chloride in
dichloromethane in 65% yield (Scheme 1).
In contrast to all the other Diels–Alder adducts and the corresponding fragmented products which
were oils, 13 was isolated as a solid. X-Ray crystallography was therefore employed to deduce the
stereochemistry of adduct 13. An ORTEP16 depiction of 13 is given in Fig. 1. The pantolactone auxiliary
shields the lower face of quinone 4 therefore cyclopentadiene adds to the less hindered top face in an
endo fashion.
2.5. (1R,2S)-2-Phenyl-1-cyclohexanol
The final auxiliary to be examined was (1R,2S)-(−)-trans-2-phenyl-1-cyclohexanol e.17–19 Addition
of cyclopentadiene to quinone 5, at −78°C in the presence of ZnCl2, afforded a 35:1 inseparable mixture
(94% d.e.) of adducts 15 (major) and 14 in 60% yield. Compound 15 was readily fragmented to 25

M. A. Brimble et al. / Tetrahedron: Asymmetry 9 (1998) 1239–1255
1243
Table 4
Effect of Lewis acid on reaction of 4 with cyclopentadiene†
Fig. 1. Major isomer 13
using 1 equivalent of tin(IV) chloride in dichloromethane in 98% yield (Scheme 1). As a comparison, the
uncatalysed reaction afforded a higher yield of adducts 14 and 15 (81%) but lower asymmetric induction
(13% d.e.).
2.6. Removal of chiral auxiliaries
In order to form analogues of naphthoquinone natural products it was necessary to examine the ease
of removal of the chiral auxiliary. In general it was found that treatment of the fragmented Diels–Alder
adducts with a reducing agent such as lithium borohydride effected removal of the auxiliary (Scheme 2).
4-Benzyl-2-oxazolidinone was removed to give enantiomerically pure aldehyde 27 in 63% yield over
two steps from Diels-Alder adduct 6. The camphorsultam was removed from 18 in 61% yield to again
give enantiomerically pure 27. The Helmchen ligands were also successfully removed with LiBH4 in 43%
and 63% yield for 2-hydroxy-N-methylsuccinimide and pantolactone respectively. In a single attempt,
trans-2-phenyl-1-cyclohexanol was removed using LiBH4 in 17% yield. Attempted saponification of
the pantolactone ester using lithium hydroxide15 afforded only a complex mixture. It was found that
any aldehyde (27) which was further reduced to alcohol 26 under the reaction conditions could be
conveniently oxidized back to aldehyde 27 using MnO2 in dichloromethane (Scheme 2).

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M. A. Brimble et al. / Tetrahedron: Asymmetry 9 (1998) 1239–1255
Table 5
Optical rotation of 27 used to determine stereochemistry of 6–15
2.7. Determination of stereochemistry
The absolute stereochemistry of adducts 6–15 was determined from the sign of the specific rotation
(Table 5) of the derived aldehyde 27 formed via fragmentation of 6–15 with tin(IV) chloride and removal
of the auxiliary using lithium borohydride. Enantiomeric purity was conserved in the fragmentation and
in the removal of the chiral auxiliary. Aldehyde 27 of known absolute configuration was prepared from
adduct 13, the absolute stereochemistry having been determined by X-ray crystallography (vide supra).
2.8. Formation of cyclopentannulated pyranonaphthoquinone
Having successfully removed the chiral auxiliary, enantiomerically pure aldehyde 27 could then be
used as a starting material for the preparation of optically active pyranonaphthoquinone ring systems
such as 28. Towards this end, silver(II) oxide/nitric acid oxidative rearrangement of aldehyde 27 afforded
lactol 28 in 23% yield, whereas the use of ceric ammonium nitrate was ineffective for this transformation.
3. Conclusions
The use of chiral auxiliaries such as pantolactone at C-2 of 1,4-naphthoquinones has enabled levels
of up to 96% stereoinduction in Diels–Alder cycloadditions with cyclopentadiene to be achieved. Use
of lithium borohydride allowed removal of the chiral auxiliaries from the fragmented products 16–25 in
acceptable yields such that oxidative rearrangement to a cyclopentannulated pyranonaphthoquinone ring
system, similar to that found in nature, could be effected.
4. Experimental
4.1. General details
Melting points were determined using a Reichert Kofler block and are uncorrected. Infrared absorption
spectra were recorded using a Perkin–Elmer 1600 Series FTIR spectrometer as Nujol mulls or thin films
1
between sodium chloride plates. H NMR and 13C NMR spectra were obtained using either a Bruker
AM 400 or Bruker AC 200 spectrometer. 13C NMR spectra were interpreted with the aid of DEPT 135
and DEPT 90 experiments. Low resolution mass spectra were recorded using a VG 70-SE spectrometer
operating at an accelerating voltage of 70 eV. High resolution mass spectra were recorded at a nominal
resolution of 5000 or 10000 as appropriate, using EI, CI with ammonia or LSIMS with mnba. High

M. A. Brimble et al. / Tetrahedron: Asymmetry 9 (1998) 1239–1255
1245
resolution CI mass spectra were recorded at University of Otago, Dunedin, New Zealand and LSIMS
mass spectra were recorded at Central Services Laboratory, Hobart, Australia. Flash chromatography
was performed using Merck Kieselgel 60 (230–400 mesh) using hexane/ethyl acetate as eluent.
4.2. 1,4-Dimethoxy-2-naphthoic acid
1,4-Dihydroxy-2-naphthoic acid (5 g, 25 mmol) was dissolved in dry acetone (200 mL) and treated
with potassium carbonate (25 g, 184 mmol) followed by iodomethane (8 mL). The mixture was heated
under reflux under nitrogen for 12 h. The solvent was then removed and the product partitioned between
dichloromethane and water. The organic layer was separated, dried (MgSO4) and the solvent removed in
vacuo. Purification by flash chromatography (hexane:ethyl acetate, 8:1) gave methyl 1,4-dimethoxy-2-
naphthoate as colourless needles (6.15 g, 100%). This solid was dissolved in 1 M sodium hydroxide
(200 mL) and acetonitrile (20 mL) and heated under reflux for 1 h. The mixture was washed with
dichloromethane (100 mL), acidified with concentrated HCl to pH 1 and extracted with dichloromethane
(3×100 mL). The organic extract was dried (MgSO4) and the solvent removed to give the title compound
as a pale pink solid (5.45 g, 96%) which was of sufficient purity for subsequent transformations: mp
162–163°C (lit.20 mp 167–168°C).
4.3. 1,4-Dimethoxy-2-naphthoyl chloride21
1,4-Dimethoxy-2-naphthoic acid (556 mg, 2.39 mmol) was dissolved in thionyl chloride (2 mL) and
stirred at room temperature for 15 h. Excess thionyl chloride was then removed in vacuo to afford the
acid chloride as a brown solid in quantitative yield. The crude product was used immediately in the next
step.
4.4. Representative procedure for formation of amides 29 and 30
4.4.1. (−)-(R)-3-(10,40-Dimethoxy-20-naphthoyl)-4-(phenylmethyl)-2-oxazolidinone 29
To a solution of n-butyllithium (1.47 mL of a 2.35 M solution in THF, 3.46 mmol, 1.2 equiv.) in THF
(30 mL) at −78°C, was added (R)-(+)-4-benzyl-2-oxazolidinone22 (613 mg, 3.46 mmol) in THF (5 mL)
over 5 min. After stirring for 15 min, a solution of 1,4-dimethoxy-2-naphthoyl chloride (720 mg, 2.89
mmol) in THF (5 mL) was added over a further 15 min. The reaction mixture was stirred at −78°C
for 15 min, then at room temperature for 20 min. The solvent was removed under reduced pressure
and the residue redissolved in dichloromethane (30 mL). The dichloromethane layer was washed with
0.5 M hydrochloric acid (20 mL) and dried over MgSO4. The solvent was removed in vacuo and the
crude product purified by flash chromatography (hexane:ethyl acetate, 4:1) to give the title compound
29 as an amorphous colourless solid (595 mg, 53% over two steps from 1,4-dimethoxynaphthoic acid):
[α]D=−18.7 (c=1.7, CHCl3); 1H NMR (200 MHz, CDCl3) δ 2.94 (dd, J=13.3, 9.9 Hz, 1H, CHACHBPh),
3.62 (dd, J=13.3, 3.4 Hz, 1H, CHACHBPh), 3.95 (s, 3H, 10-OMe or 40-OMe), 4.00 (s, 3H, 40-OMe or 10-
OMe), 4.24 (dd, J=8.9, 3.8 Hz, 1H, 5-HB), 4.28 (dd, J=8.9, 8.9 Hz, 1H, 5-HA), 4.83–4.97 (m, 1H, 4-H),
6.69 (s, 1H, 30-H), 7.28–7.43 (m, 5H, Ph), 7.52–7.66 (m, 2H, 60-H and 70-H), 8.07–8.33 (m, 2H, 50-H
and 80-H); 13C NMR (50 MHz, CDCl3) δ 38.0 (CH2, CH2Ph), 55.7 (CH, C-4), 55.8 (CH3, 10-OMe or
40-OMe), 63.5 (CH3, 40-OMe or 10-OMe), 66.2 (CH2, C-5), 101.1 (CH, C-30), 122.6 (quat, C-20), 127.0
(CH, C-50 or C-80), 127.1 (CH, C-80 or C-50), 127.4 (CH, Ph), 127.9 (CH, C-60 or C-70), 128.0 (CH,
C-70 or C-60), 128.7 (quat, C-4a0 or C-8a0), 129.0 (CH, Ph), 129.3 (quat, C-8a0 or C-4a0), 129.5 (CH,
Ph), 135.3 (quat, Ph), 147.8 (quat, C-10 or C-40), 151.9 (quat, C-40 or C-10), 152.3 (quat, C-2), 168.0

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M. A. Brimble et al. / Tetrahedron: Asymmetry 9 (1998) 1239–1255
(quat, amide); IR (film) 1791 (s, amide), 1686 (oxazolidinone), 1595 (C_C), 1460, 1373 (s), 1216 cm−1
;
m/z (EI, %) 391 (M+, 64), 215 (C13H11O3, 34), 144 (36), 129 (37), 91 (C7H7, 100); HRMS analysis (EI,
M+) (C23H21O5N=391.1420) found m/z 391.1409.
4.4.2. (−)-[3aS-(3aα,6α,7aβ)]-Hexahydro-8,8-dimethyl-1-(10 ,40-dimethoxy-20-naphthoyl)-3H-3a,6-
methano-2,1-benzisothiazole-2,2-dioxide 30
Compound 30 was prepared from 1,4-dimethoxy-2-naphthoyl chloride (1.1 g, 4.3 mmol) and [3aS-
(3aα,6α,7aβ)]-hexahydro-8,8-dimethyl-3H-3α,6-methano-2,1-benzisothiazole-2,2-dioxide (925 mg,
4.3 mmol) as a colourless solid (1.6 g, 95%): 1H NMR (200 MHz, CDCl3) δ 0.97 (s, 3H, 8-MeA), 1.30
(s, 3H, 8-MeB), 1.20–2.08 (m, 7H, 6-CH, 7-CH2, 4-CH2 and 5-CH2), 3.45–3.56 (m, 2H, 3-CH2), 3.97 (s,
3H, 10-OMe or 40-OMe), 3.97 (s, 3H, 40-OMe or 10-OMe), 4.06–4.28 (m, 1H, 7a-H), 6.75 (s, 1H, 30-H),
7.51–7.63 (m, 2H, 60-H and 70-H), 8.08–8.29 (m, 2H, 50-H and 80-H); 13C NMR (50 MHz, CDCl3) δ
19.8 (CH3, 8-MeA), 20.9 (CH3, 8-MeB), 26.2 (CH2, C-5), 32.9 (CH2, C-4), 38.3 (CH2, C-7), 44.9 (CH,
C-6), 47.7 (quat, C-8), 48.6 (quat, C-3a), 52.9 (CH2, C-3), 55.7 (CH3, 10-OMe or 40-OMe), 63.7 (CH3,
40-OMe or 10-OMe), 64.9 (CH, C-7a), 102.6 (CH, C-30), 122.4 (CH, C-50 or C-80), 122.7 (CH, C-80
or C-50), 122.9 (quat, C-20), 127.0 (CH, C-60 or C-70), 127.0 (CH, C-70 or C-60), 127.8 (quat, C-4a0
or C-8a0), 128.1 (quat, C-8a0 or C-4a0), 150.0 (quat, C-10 or C-40), 151.3 (quat, C-40 or C-10), 167.6
(quat, amide); IR (KBr) 1684 (amide), 1653, 1594 (C_C), 1457, 1373, 1340, 1285 cm−1; m/z (EI, %)
429 (M+, 40), 157 (7), 129 (12), 108 (16), 28 (100); HRMS analysis (EI, M+) (C23H27O5NS=429.1610)
found m/z 429.1598.
4.5. Representative procedure for formation of esters 31–33
4.5.1. (−)-(S)-1-Methyl-2,5-dioxo-3-pyrrolidinyl 1,4-dimethoxynaphthalene-2-carboxylate 31
(S)-(−)-2-Hydroxy-N-methylsuccinimide (650 mg, 5.0 mmol) and 4-dimethylaminopyridine (17 mg,
0.17 mmol) were added to a solution of 1,4-dimethoxy-2-naphthoic acid (445 mg, 1.9 mmol) in
dichloromethane (10 mL) under nitrogen at 0°C with stirring. Dicyclohexylcarbodiimide (450 mg, 2.16
mmol) in dichloromethane (5 mL) was then added dropwise over 5 min. The mixture was stirred for a
further 5 min at 0°C, then at room temperature for 2 h. The solution was filtered through Celite to remove
dicyclohexyl urea and washed with 0.5 M hydrochloric acid solution (15 mL) and 10% sodium hydrogen
carbonate solution (15 mL). The organic layer was dried over MgSO4 and the solvent removed in vacuo.
The crude mixture was purified by flash chromatography (hexane:ethyl acetate, 5:1 then 3:1) to give the
title compound (31) as a colourless solid (455 mg, 70%): mp 138–140°C; [α]D=−1.00 (c=0.4, CH2Cl2);
1H NMR (200 MHz, CDCl3) δ 2.89 (dd, J=18.4, 4.8 Hz, 1H, 40-HB), 3.12 (s, 3H, N–Me), 3.34 (dd,
J=18.4, 8.7 Hz, 1H, 40-HA), 3.90 (s, 3H, 1-OMe or 4-OMe), 4.08 (s, 3H, 4-OMe or 1-OMe), 5.72 (dd,
J=8.7, 4.8 Hz, 1H, 30-H), 7.15 (s, 1H, 3-H), 7.58–7.69 (m, 2H, 6-H and 7-H), 8.15–8.42 (m, 2H, 5-H
and 8-H); 13C NMR (50 MHz, CDCl3) δ 25.1 (CH3, N–Me), 36.0 (CH2, C-40), 55.8 (CH3, 1-OMe or
4-OMe), 63.7 (CH3, 4-OMe or 1-OMe), 68.2 (CH, C-30), 103.1 (CH, C-3), 116.8 (quat, C-2), 123.4 (CH,
C-5 or C-8), 123.6 (CH, C-8 or C-5), 127.3 (CH, C-6 or C-7), 128.4 (CH, C-7 or C-6), 129.1 (quat, C-4a
or C-8a), 129.3 (quat, C-8a or C-4a), 151.5 (quat, C-1 or C-4), 153.2 (quat, C-4 or C-1), 165.1 (quat,
ester), 173.4 (quat, C-20), 173.6 (quat, C-50); IR (KBr) 1712 (quat, C_O), 1595 (C_C), 1439, 1375,
1217 cm−1; m/z (EI, %) 343 (M+, 100), 328 (M−Me, 75), 215 (C13H11O3, 47), 157 (45), 129 (61), 101
(46); anal. found: C, 63.09; H, 5.01; N, 3.90; C18H17O6N requires C, 62.97; H, 4.99; N, 4.08%.

M. A. Brimble et al. / Tetrahedron: Asymmetry 9 (1998) 1239–1255
1247
4.5.2. (+)-(30R)-Dihydro-4,4-dimethyl-2-oxo-3-furanyl 1,4-dimethoxynaphthalene-2-carboxylate 32
Compound 32 was prepared from (R)-pantolactone (660 mg, 5.1 mmol) and 1,4-dimethoxy-2-
naphthoic acid (400 mg, 1.7 mmol) as a colourless solid (460 mg, 78%): mp 118–120°C; [α]D=+1.44
1
(c=3.2, acetone); H NMR (200 MHz, CDCl3) δ 1.28 (s, 3H, 40-Me), 1.32 (s, 3H, 40-Me), 4.01 (s, 3H,
1-OMe or 4-OMe), 4.01 (s, 3H, 4-OMe or 1-OMe), 4.10–4.18 (m, 2H, 50-HA and 50-HB), 5.72 (s, 1H,
30-H), 7.22 (s, 1H, 3-H), 7.56–7.67 (m, 2H, 6-H and 7-H), 8.17–8.29 (m, 2H, 5-H and 8-H); 13C NMR
(50 MHz, CDCl3) δ 20.1 (CH3, 40-Me), 23.1 (CH3, 40-Me), 40.5 (quat, C-40), 55.7 (CH3, 1-OMe or 4-
OMe), 63.6 (CH3, 4-OMe or 1-OMe), 75.6 (CH2, C-50), 76.2 (CH, C-30), 103.3 (CH, C-3), 117.2 (quat,
C-2), 122.3 (CH, C-5 or C-8), 123.6 (CH, C-8 or C-5), 127.2 (CH, C-6 or C-7), 128.2 (CH, C-7 or C-6),
129.1 (quat, C-4a or C-8a), 129.2 (quat, C-8a or C-4a), 151.1 (quat, C-1 or C-4), 153.0 (quat, C-4 or
C-1), 165.0 (quat, ester), 172.5 (quat, C-20); IR (KBr) 1797 (C_O), 1710 (C_O), 1596 (C_C), 1461,
1373, 1214 cm−1; m/z (EI, %) 344 (M+, 100), 329 (M−Me, 17), 215 (47), 185 (24), 157 (13), 129 (15),
91 (17); anal. found: C, 66.18; H, 6.07; C19H20O6 requires C, 66.27; H, 5.85%.
4.5.3. (−)-(10R,20S)-2-Phenyl-1-cyclohexyl 1,4-dimethoxynaphthalene-2-carboxylate 33
Compound 33 was prepared from 1,4-dimethoxy-2-naphthoic acid (660 mg, 2.8 mmol) and (1R,2S)-
(−)-trans-2-phenyl-1-cyclohexanol (1.0 g, 5.7 mmol) as a colourless oil (500 mg, 45%): [α]D=−74.6
1
(c=1.9, CH2Cl2); H NMR (200 MHz, CDCl3) δ 1.13–2.48 (m, 8H, 30-CH2, 40-CH2, 50-CH2 and 60-
CH2), 2.91 (ddd, J=3.4, 11.2, 11.2 Hz, 1H, 20-H), 3.77 (s, 3H, 1-OMe or 4-OMe), 3.83 (s, 3H, 4-OMe
or 1-OMe), 5.25–5.43 (m, 1H, 10-H), 6.59 (s, 1H, 3-H), 7.12–7.39 (m, 5H, Ph), 7.46–7.63 (m, 2H, 6-H
and 7-H), 8.07–8.27 (m, 2H, 5-H and 8-H); 13C NMR (50 MHz, CDCl3) δ 24.8 (CH2, C-40), 25.9 (CH2,
C-50), 32.3 (CH2, C-30), 34.4 (CH2, C-60), 50.0 (CH, C-20), 55.5 (CH3, 1-OMe or 4-OMe), 63.0 (CH3,
4-OMe or 1-OMe), 76.8 (CH, C-10), 103.2 (CH, C-3), 119.5 (quat, C-2), 122.1 (CH, C-5 or C-8), 123.2
(CH, C-8 or C-5), 126.4 (CH, C-400), 126.8 (CH, C-6 or C-7), 127.3 (CH, C-7 or C-6), 127.5 (CH, C-
300), 128.2 (quat, C-4a or C-8a), 128.4 (CH, C-200), 128.9 (quat, C-8a or C-4a), 143.5 (quat, C-100), 150.9
(quat, C-1 or C-4), 151.0 (quat, C-4 or C-1), 165.7 (quat, ester); IR (film) 1721 (s, ester), 1596 (C_C),
1461, 1371 (s), 1227 cm−1; m/z (EI, %) 390 (M+, 31), 260 (100), 245 (60), 215 (41), 91 (C7H7, 61);
HRMS analysis (EI, M+) (C25H26O4=390.1831) found m/z 390.1822.
4.6. Representative procedure for CAN oxidation to quinones 1–5
4.6.1. (ꢀ)-(R)-3-(10,40-Dioxo-20-naphthoyl)-4-(phenylmethyl)-2-oxazolidinone 1
A solution of ceric ammonium nitrate (1.96 g, 3.6 mmol) in water (3 mL) was added dropwise to a
solution of 29 (560 mg, 1.4 mmol) in acetonitrile (20 mL). After stirring for 5 min, the mixture was
diluted with dichloromethane (70 mL), washed with water (2×30 mL), dried over MgSO4 and filtered
through a short florisil column. The solvent was then removed to give the title compound 1 as a bright
yellow oil (507 mg, 98%): [α]D=−86.9 (c=3.1, CHCl3); 1H NMR (200 MHz, CDCl3) δ 2.97 (dd, J=13.6,
9.5 Hz, 1H, CHAHBPh), 3.50 (dd, J=13.6, 3.3 Hz, 1H, CHAHBPh), 4.27 (dd, J=9.1, 3.4 Hz, 1H, 5-HB),
4.36 (dd, J=9.1, 9.1 Hz, 1H, 5-HA), 4.77–4.92 (m, 1H, 4-H), 6.96 (s, 1H, 30-H), 7.21–7.43 (m, 5H, Ph),
7.74–7.82 (m, 2H, 60-H and 70-H), 8.05–8.12 (m, 2H, 50-H and 80-H); 13C NMR (50 MHz, CDCl3) δ
37.5 (CH2, CH2Ph), 54.8 (CH, C-4), 67.3 (CH2, C-5), 126.4 (CH, C-50 or C-80), 126.7 (CH, C-80 or
C-50), 127.5 (CH, Ph), 129.0 (CH, Ph), 129.4 (CH, Ph), 131.3 (quat, C-4a0 or C-8a0), 131.8 (quat, C-8a0
or C-4a0), 134.2 (CH, C-60 or C-70), 134.3 (CH, C-70 or C-60), 134.3 (CH, C-30), 134.6 (quat, Ph), 144.6
(quat, C-20), 153.1 (quat, C-2), 163.5 (quat, amide), 181.7 (quat, C-10 or C-40), 183.9 (quat, C-40 or
C-10); IR (film) 1785 (s, amide), 1692 (oxazolidinone), 1668 (quinone), 1595 (C_C), 1358, 1295, 1256

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M. A. Brimble et al. / Tetrahedron: Asymmetry 9 (1998) 1239–1255
cm−1; m/z (EI, %) 361 (M+, 5), 185 (C11H5O3, 18), 157 (12), 149 (15), 91 (C7H7, 100); HRMS analysis
(EI, M+) (C21H15O5N=361.0950) found m/z 361.0969.
4.6.2. (−)-[3aS-(3aα,6α,7aβ)]-Hexahydro-8,8-dimethyl-1-(10 ,40-dioxo-20-naphthoyl)-3H-3a,6-
methano-2,1-benzisothiazole-2,2-dioxide 2
Compound 2 was prepared by CAN oxidation of 30 (430 mg, 1.0 mmol) as a yellow oil (390 mg,
1
98%): [α]D=−59.3 (c=0.58, CH2Cl2); H NMR (200 MHz, CDCl3) δ 0.95 (s, 3H, 8-MeA), 1.22 (s,
3H, 8-MeB), 1.19–2.48 (m, 7H, 6-CH, 7-CH2, 4-CH2 and 5-CH2), 3.36–3.52 (m, 2H, 3-CH2), 3.99 (dd,
J=7.8, 4.9 Hz, 1H, 7a-H), 6.97 (s, 1H, 30-H), 7.69–7.81 (m, 2H, 60-H and 70-H), 7.99–8.11 (m, 2H, 50-H
and 80-H); 13C NMR (50 MHz, CDCl3) δ 19.8 (CH3, 8-MeA), 20.3 (CH3, 8-MeB), 26.3 (CH2, C-5),
32.5 (CH2, C-4), 37.5 (CH2, C-7), 44.5 (CH, C-6), 47.8 (quat, C-8), 49.0 (quat, C-3a), 52.5 (CH2, C-
3), 64.5 (CH, C-7a), 126.3 (CH, C-50 or C-80), 126.6 (CH, C-80 or C-50), 131.0 (quat, C-4a0 or C-8a0),
131.6 (quat, C-8a0 or C-4a0), 134.2 (CH, C-60 or C-70), 134.2 (CH, C-70 or C-60), 135.7 (CH, C-30),
141.9 (quat, C-20), 161.6 (quat, amide), 181.2 (quat, C-10 or C-40), 183.8 (quat, C-40 or C-10); IR (KBr)
1692 (amide), 1670 (quinone), 1595 (C_C), 1460, 1338, 1295, 1253 cm−1; m/z (LSIMS, %) 400 (M++1,
88), 216 (80), 186 (C11H5O3, 100), 135 (68); HRMS analysis (LSIMS, M++1) (C21H22O5NS=400.1219)
found m/z 400.1214.
4.6.3. (−)-(30S)-1-Methyl-2,5-dioxo-3-pyrrolidinyl 1,4-dioxonaphthalene-2-carboxylate 3
Compound 3 was prepared by CAN oxidation of 31 (430 mg, 1.3 mmol) as a yellow oil (380 mg,
98%): [α]D=−53.8 (c=1.36, CHCl3); 1H NMR (200 MHz, CDCl3) δ 2.85 (dd, J=18.4, 4.7 Hz, 1H, 40-
HA), 3.04 (s, 3H, N–Me), 3.29 (dd, J=18.4, 8.6 Hz, 1H, 40-HB), 5.70 (dd, J=4.7, 8.6 Hz, 1H, 30-H),
7.32 (s, 1H, 3-H), 7.72–7.85 (m, 2H, 6-H and 7-H), 8.01–8.17 (m, 2H, 5-H and 8-H); 13C NMR (50
MHz, CDCl3) δ 25.1 (CH3, N–Me), 35.5 (CH2, C-40), 68.7 (CH, C-10), 126.4 (CH, C-5 or C-8), 127.0
(CH, C-8 or C-5), 127.1 (quat, C-4a or C-8a), 131.5 (quat, C-8a or C-4a), 134.4 (CH, C-7 or C-6),
134.7 (CH, C-6 or C-7), 137.7 (quat, C-2), 139.3 (CH, C-3), 162.2 (quat, ester), 172.5 (quat, C-20 or
C-50), 172.8 (quat, C-50 or C-20), 180.5 (quat, C-1 or C-4), 184.0 (quat, C-4 or C-1); IR (film) 1713 (b,
amide and ester), 1672 (quinone), 1594 (C_C), 1440, 1285, 1222, 1122 cm−1; m/z (EI, %) 315 (M+2,
16), 201 (26), 186 (C11H6O3, 100), 157 (C10H5O2, 64), 129 (49), 101 (57); HRMS analysis (EI, M+)
(C16H11O6N=313.0586) found m/z 313.0573.
4.6.4. (+)-(30R)-Dihydro-4,4-dimethyl-2-oxo-3-furanyl 1,4-dioxonaphthalene-2-carboxylate 4
Compound 4 was prepared by CAN oxidation of 32 (310 mg, 0.9 mmol) as a yellow oil (230 mg,
1
80%): [α]D=+46.6 (c=1.25, CHCl3); H NMR (200 MHz, CDCl3) δ 1.25 (s, 3H, 40-Me), 1.34 (s, 3H,
40-Me), 4.10–4.16 (m, 2H, 50-HA and 50-HB), 5.62 (s, 1H, 30-H), 7.40 (s, 1H, 3-H), 7.78–7.88 (m, 2H,
6-H and 7-H), 8.04–8.19 (m, 2H, 5-H and 8-H); 13C NMR (50 MHz, CDCl3) δ 19.9 (CH3, 40-Me), 22.9
(CH3, 40-Me), 40.6 (quat, C-40), 76.2 (CH2, C-50), 76.5 (CH, C-30), 126.4 (CH, C-5 or C-8), 127.0 (CH,
C-8 or C-5), 131.5 (quat, C-4a), 131.5 (quat, C-8a), 134.4 (CH, C-7 or C-6), 134.7 (CH, C-6 or C-7),
138.3 (quat, C-2), 139.1 (CH, C-3), 162.3 (quat, ester), 171.5 (quat, C-20), 180.6 (quat, C-1 or C-4), 184.1
(quat, C-4 or C-1); IR (film) 1792 (lactone), 1752 (ester), 1672 (quinone), 1595 (C_C), 1299, 1249, 1124
cm−1; m/z (EI, %) 316 (M++2, 9), 226 (13), 185 (100), 157 (82), 129 (45), 101 (69); HRMS analysis (EI,
M++2) (C17H16O6=316.0947) found m/z 316.0945.
4.6.5. (−)-(10R,20S)-2-Phenyl-1-cyclohexyl 1,4-dioxonaphthalene-2-carboxylate 5
Compound 5 was prepared by CAN oxidation of 33 (410 mg, 1.1 mmol) as a yellow oil (300 mg,
79%): [α]D=−29.8 (c=1.6, CH2Cl2); 1H NMR (200 MHz, CDCl3) δ 1.23–2.41 (m, 8H, 30-CH2, 40-CH2,

M. A. Brimble et al. / Tetrahedron: Asymmetry 9 (1998) 1239–1255
1249
50-CH2 and 60-CH2), 2.76 (ddd, J=3.3, 11.4, 11.4 Hz, 1H, 20-H), 5.22 (ddd, J=4.5, 10.5, 10.5 Hz, 1H,
10-H), 6.52 (s, 1H, 3-H), 7.11–7.34 (m, 5H, Ph), 7.52–7.77 (m, 2H, 6-H and 7-H), 7.94–8.08 (m, 2H,
5-H and 8-H); 13C NMR (50 MHz, CDCl3) δ 24.6 (CH2, C-40), 25.5 (CH2, C-50), 32.0 (CH2, C-30), 35.6
(CH2, C-60), 49.8 (CH, C-20), 78.3 (CH, C-10), 126.0 (CH, C-5 or C-8), 126.7 (CH, C-400 and C-8 or
C-5), 127.4 (CH, C-300), 128.3 (CH, C-200), 131.3 (quat, C-4a or C-8a), 131.5 (quat, C-8a or C-4a), 133.9
(CH, C-6 or C-7), 134.2 (CH, C-7 or C-6), 136.9 (CH, C-3), 139.6 (quat, C-2), 142.3 (quat, C-100), 162.2
(quat, ester), 180.8 (quat, C-1 or C-4), 184.5 (quat, C-4 or C-1); IR (film) 1738 (s, ester), 1668 (quinone),
1595 (C_C), 1450, 1354, 1249 cm−1; m/z (EI, %) 362 (M++2, 5), 204 (32), 187 (65), 158 (100), 130
(54); HRMS analysis (EI, M++2) (C23H22O4=362.1518) found m/z 362.1518.
4.7. Representative procedure for formation of Diels–Alder adducts 6–15
4.7.1. (−)-(4R,10R,40S,4a0S,9a0S)- and (+)-(4R,10S,40R,4a0R,9a0R)-3-(10,40,4a0,9a0-Tetrahydro-10,40-
methano-90,100-dioxo-4a0-anthroyl)-4-(phenylmethyl)-2-oxazolidinone 6 and 7 (using ZnCl2)
To quinone 1 (23 mg, 0.06 mmol) in dichloromethane (5 mL) at −78°C, was added zinc chloride
(64 µL of 1 M solution in CH2Cl2, 0.06 mmol). The mixture was then treated with freshly distilled
cyclopentadiene (30 µL) and stirred for 2 h. The mixture was poured into 10% sodium hydrogen
carbonate solution (6 mL) and extracted with dichloromethane (3×5 mL). The organic layer was dried
(MgSO4) and the solvent removed under reduced pressure. The resultant oil was purified by flash
chromatography (hexane:ethyl acetate, 4:1) to afford the Diels–Alder adducts 6 and 7 in a 2.57:1 ratio
(44% d.e.).
1
Adduct 6 was isolated as a yellow oil (19 mg, 69%): [α]D=−76.0 (c=1.0, CH2Cl2); H NMR (200
MHz, CDCl3) δ 1.51–1.74 (m, 2H, 110-HA and 110-HB), 2.82 (dd, J=13.3, 9.6 Hz, 1H, CHACHBPh),
3.35 (dd, J=13.3, 3.8 Hz, 1H, CHACHBPh), 3.42–3.52 (m, 1H, 10-H), 3.54 (d, J=4.1 Hz, 1H, 9a0-H),
3.78–3.93 (m, 1H, 40-H), 4.17 (dd, J=9.2, 3.7 Hz, 1H, 5-HB), 4.53 (dd, J=9.2, 9.2 Hz, 1H, 5-HA),
4.55–4.82 (m, 1H, 4-H), 5.58 (dd, J=5.5, 3.0 Hz, 1H, 20-H or 30-H), 5.83 (dd, J=5.5, 2.7 Hz, 1H, 30-H
or 20-H), 7.15–7.40 (m, 5H, Ph), 7.57–7.69 (m, 2H, 60-H and 70-H), 7.78–7.98 (m, 2H, 50-H and 80-H);
13C NMR (50 MHz, CDCl3) δ 38.3 (CH2, CH2Ph), 50.4 (CH2, C-110), 51.0 (CH, C-10), 55.2 (CH, C-4),
55.3 (CH, C-40), 55.7 (CH, C-9a0), 66.3 (quat, C-4a0), 67.2 (CH2, C-5), 126.1 (CH, C-50 or C-80), 126.3
(CH, C-80 or C-50), 127.5 (CH, Ph), 129.0 (CH, Ph), 129.3 (CH, Ph), 133.2 (CH, C-60 or C-70), 133.7
(CH, C-70 or C-60), 134.5 (CH, C-20 or C-30), 134.8 (quat, Ph), 135.9 (quat, C-4b0 or C-8a0), 136.2 (quat,
C-8a0 or C-4b0), 138.8 (CH, C-30 or C-20), 153.1 (quat, C-2), 170.4 (quat, amide), 194.2 (quat, C-90 or
C-100), 195.8 (quat, C-100 or C-90); IR (film) 1777 (s, amide), 1692 (oxazolidinone), 1672 (quinone),
1593 (C_C), 1356, 1295, 1260 cm−1; m/z (CI, CH4, rel. abundance) 428 (M++1, 32), 362 (M−C5H6,
100), 251 (28), 178 (76), 67 (26); HRMS analysis (LSIMS, M++1) (C26H22O5N=428.1498) found m/z
428.1505.
1
Adduct 7 was isolated as a yellow oil (7 mg, 27%): [α]D=+25.3 (c=0.9, CH2Cl2); H NMR (200
MHz, CDCl3) δ 1.60–1.81 (m, 2H, 110-HA and 110-HB), 2.75 (dd, J=13.4, 10.1 Hz, 1H, CHACHBPh),
3.41–3.51 (m, 2H, 1-H and CHACHBPh), 3.55 (d, J=4.1 Hz, 1H, 9a0-H), 3.93–4.01 (m, 1H, 40-H),
4.13–4.22 (m, 2H, 5-HA and 5-HB), 4.63–4.80 (m, 1H, 4-H), 5.82 (dd, J=5.4, 3.0 Hz, 1H, 20-H or 30-
H), 5.93 (dd, J=5.4, 2.7 Hz, 1H, 30-H or 20-H), 7.12–7.42 (m, 5H, Ph), 7.58–7.72 (m, 2H, 60-H and
70-H), 7.84–7.99 (m, 2H, 50-H and 80-H); 13C NMR (50 MHz, CDCl3) δ 37.0 (CH2, CH2Ph), 50.6 (CH2,
C-110), 51.0 (CH, C-10), 55.1 (CH, C-4), 55.3 (CH, C-40), 56.4 (CH, C-9a0), 65.8 (quat, C-4a0), 66.7
(CH2, C-5), 126.0 (CH, C-50 or C-80), 126.3 (CH, C-80 or C-50), 127.3 (CH, Ph), 129.0 (CH, Ph), 129.5
(CH, Ph), 133.3 (CH, C-60 or C-70), 133.7 (CH, C-70 or C-60), 134.6 (CH, C-20 or C-30), 135.3 (quat,
Ph), 136.0 (quat, C-4b0 or C-8a0), 136.2 (quat, C-8a0 or C-4b0), 138.8 (CH, C-30 or C-20), 153.0 (quat,

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M. A. Brimble et al. / Tetrahedron: Asymmetry 9 (1998) 1239–1255
C-2), 170.4 (quat, amide), 194.4 (quat, C-90 or C-100), 195.9 (quat, C-100 or C-90); IR (film) 1776 (s,
amide), 1691 (oxazolidinone), 1679 (quinone), 1592 (C_C), 1355, 1294, 1262 cm−1; m/z (CI, CH4, rel.
abundance) 428 (M++1, 34), 362 (M−C5H6, 100), 251 (26), 178 (72), 67 (18); HRMS analysis (LSIMS,
M++1) (C26H22O5N=428.1498) found m/z 428.1484. For other Lewis acids see Table 1 in text.
4.7.2. (−)-[3aS-(3aα,6α,7aβ),10R,40S,4a0S,9a0S]- and (−)-[3aS-(3aα,6α,7aβ),10S,40R,4a0R,9a0R]-
Hexahydro-8,8-dimethyl-1-[10 ,40,4a0,9a0-tetrahydro-10,40-methano-90,100-dioxo-4a0-anthroyl]-3H-3a,
6-methano-2,1-benzisothiazole-2,2-dioxide 8 and 9
Compounds 8 and 9 were prepared from quinone 2 (39 mg, 0.1 mmol) and cyclopentadiene using
ZnCl2 (1 equiv.), according to the standard procedure outlined above.
Adduct 8 was isolated as a colourless oil (26 mg, 58%): [α]D=−104.6 (c=1.2, CH2Cl2); 1H NMR (200
MHz, CDCl3) δ 0.93 (s, 3H, 80-MeA), 1.16 (s, 3H, 8-MeB), 1.21–2.35 (m, 8H, 6-CH, 7-CH2, 4-CH2, 5-
CH2 and 110-HB), 1.59 (m, 1H, 110-HA), 3.23 (d, J=13.7 Hz, 1H, 3-HA), 3.31 (d, J=13.7 Hz, 1H, 3-HB),
3.53–3.62 (m, 1H, 10-H), 3.84 (d, J=4.2 Hz, 1H, 9a0-H), 4.04 (dd, J=7.7 Hz, 4.9, 1H, 7a-H), 4.21–4.27
(m, 1H, 40-H), 5.87 (dd, J=5.5, 2.9 Hz, 1H, 20-H or 30-H), 5.97 (dd, J=5.5, 2.8 Hz, 1H, 30-H or 20-H),
7.58–7.70 (m, 2H, 60-H and 70-H), 7.96–8.07 (m, 2H, 50-H and 80-H); 13C NMR (50 MHz, CDCl3) δ
19.7 (CH3, 8-MeA), 21.2 (CH3, 8-MeB), 26.3 (CH2, C-5), 32.8 (CH2, C-4), 38.7 (CH2, C-7), 44.5 (CH,
C-6), 47.8 (quat, C-8), 48.3 (CH2, C-110), 50.1 (quat, C-3a), 51.0 (CH, C-10), 53.0 (CH, C-40), 54.5
(CH2, C-3), 57.9 (CH, C-9a0), 66.9 (CH, C-7a), 67.4 (quat, C-4a0), 126.5 (CH, C-50 or C-80), 127.0 (CH,
C-80 or C-50), 133.6 (CH, C-60 or C-70), 134.0 (CH, C-70 or C-60), 134.5 (CH, C-20 or C-30), 135.3 (quat,
C-4b0 or C-8a0), 135.3 (quat, C-8a0 or C-4b0), 138.8 (CH, C-30 or C-20), 169.3 (quat, amide), 191.4 (quat,
C-90 or C-100), 195.3 (quat, C-100 or C-90); IR (film, NaCl) 1689 (C_O), 1592 (C_C), 1331, 1262, 1138
cm−1; m/z (LSIMS, %) 466 (M++1, 12), 400 (M−C5H6, 100), 251 (19), 216 (54), 185 (37), 135 (39);
HRMS analysis (LSIMS, M++1) (C26H29O5NS=466.1688) found m/z 466.1674.
Adduct 9 was isolated as a colourless oil (4 mg, 8%): [α]D=+42.5 (c=0.16, CH2Cl2); 1H NMR (200
MHz, CDCl3) δ 0.93 (s, 3H, 8-MeA), 1.13 (s, 3H, 8-MeB), 1.20–2.37 (m, 7H, 6-CH, 7-CH2, 4-CH2 and
5-CH2), 1.60 (m, 1H, 110-HA), 1.76 (d, J=9.1 Hz, 1H, 110-HB), 3.16 (d, J=13.7 Hz, 1H, 3-HA), 3.31
(d, J=13.7 Hz, 1H, 3-HB), 3.47–3.56 (m, 1H, 10-H), 3.82–3.89 (m, 1H, 40-H), 3.92 (dd, J=7.7, 5.1 Hz,
1H, 7a-H), 4.08 (d, J=4.2 Hz, 1H, 9a0-H), 5.80 (dd, J=5.6, 2.9 Hz, 1H, 20-H or 30-H), 5.91 (dd, J=5.6,
2.8 Hz, 1H, 30-H or 20-H), 7.53–7.70 (m, 2H, 60-H and 70-H), 7.86–8.00 (m, 2H, 50-H and 80-H); 13C
NMR (50 MHz, CDCl3) δ 19.4 (CH3, 8-MeA), 19.9 (CH3, 8-MeB), 26.6 (CH2, C-5), 32.4 (CH2, C-4),
37.7 (CH2, C-7), 43.9 (CH, C-6), 47.8 (quat, C-8), 48.7 (CH2, C-110), 50.3 (quat, C-3a), 51.5 (CH, C-10),
52.5 (CH, C-40), 52.9 (CH2, C-3), 57.5 (CH, C-9a0), 65.9 (quat, C-4a0), 66.1 (CH, C-7a), 126.1 (CH, C-50
or C-80), 126.3 (CH, C-80 or C-50), 133.4 (CH, C-60 or C-70), 133.8 (CH, C-70 or C-60), 134.8 (CH, C-20
or C-30), 135.9 (quat, C-4b0 or C-8a0), 135.9 (quat, C-8a0 or C-4b0), 139.0 (CH, C-30 or C-20), 169.2
(quat, amide), 194.0 (quat, C-90 or C-100), 195.7 (quat, C-100 or C-90); IR (film, NaCl) 1687 (C_O),
1591 (C_C), 1330, 1263, 1137 cm−1; m/z (LSIMS, %) 466 (M++1, 15), 400 (M−C5H6, 100), 251 (18),
216 (56), 185 (25); HRMS analysis (LSIMS, M++1) (C26H29O5NS=466.1688) found m/z 466.1679. For
other Lewis acids see Table 2 in text.
4.7.3. (3S0,1R,4S,4aS,9aS)- and (3S0,1S,4R,4aR,9aR)-1-Methyl-2,5-dioxo-3-pyrrolidinyl 1,4,4a,9a-
tetrahydro-1,4-methano-9,10-dioxo-4a-anthracenecarboxylate 10 and 11
Compounds 10 and 11 were prepared from quinone 3 (20 mg, 0.06 mmol) and cyclopentadiene using
ZnCl2 (0.06 mmol), according to the standard procedure outlined above, and were isolated as a colourless
oil (21 mg, 87%): [4.3:1 ratio (62% d.e.), the asterisk denotes resonances for the minor diastereomer 11]
1H NMR (200 MHz, CDCl3) δ 1.63–1.81 (m, 2H, 11-HA and 11-HB), 2.48 (dd, J=18.3, 4.9 Hz, 1H, 40-

M. A. Brimble et al. / Tetrahedron: Asymmetry 9 (1998) 1239–1255
1251
HA), 2.73* (dd, J=18.3, 5.0 Hz, 1H, 40-HA), 2.95 (s, 3H, N–Me), 2.99* (s, 3H, N–Me), 3.06 (dd, J=18.3,
8.8 Hz, 1H, 40-HB), 3.10* (dd, J=18.3, 8.8 Hz, 1H, 40-HB), 3.55–3.63 (m, 1H, 1-H), 3.64–3.72 (m, 1H,
9a-H), 3.84–3.94 (m, 1H, 4-H), 5.26* (dd, J=5.0, 8.8 Hz, 1H, 30-H), 5.58 (dd, J=4.9, 8.8 Hz, 1H, 30-H),
5.95–6.05 (m, 2H, 2-H and 3-H), 7.65–7.77 (m, 2H, 6-H and 7-H), 7.92–8.13 (m, 2H, 5-H and 8-H); 13
C
NMR (50 MHz, CDCl3) δ 25.0 (CH3, N–Me), 35.0 (CH2, C-40), 48.6* and 48.7 (CH2, C-11), 49.1* and
49.3 (CH, C-1), 52.9* and 53.1 (CH, C-4), 54.5 and 54.8* (CH, C-9a), 64.0* and 64.1 (quat, C-4a), 68.0
and 69.1* (CH, C-30), 127.1 (CH, C-5 or C-8), 127.3* and 127.4 (CH, C-8 or C-5), 134.4 (CH, C-6 or
C-7), 134.7 (CH, C-7 or C-6), 135.6 and 135.7* (CH, C-2 or C-3), 136.5 (quat, C-4b or C-8a), 137.7
(CH, C-3 or C-2), 139.6 (quat, C-8a or C-4b), 170.1 and 170.4* (quat, ester), 172.6 (quat, C-20 or C-40),
172.8 (quat, C-40 or C-20), 192.6* and 192.9 (quat, C-9 or C-10), 195.0 and 195.1* (quat, C-10 or C-9);
IR (film) 1753 (ester), 1716 (amide), 1680 (quinone), 1591 (C_C), 1438, 1269, 1211, 1121 cm−1; m/z
(EI, %) 379 (M+, 1), 314 (M−C5H5, 7), 250 (11), 186 (C11H6O3, 38), 157 (C10H5O2, 30), 105 (93), 44
(100); HRMS analysis (EI, M+) (C21H17O6N=379.1056) found m/z 379.1103. For other Lewis acids see
Table 3.
4.7.4. (3R0,1R,4S,4aS,9aS)- and (3R0,1S,4R,4aR,9aR)-Dihydro-4,4-dimethyl-2-oxo-3-furanyl 1,4,4a,
9a-tetrahydro-1,4-methano-9,10-dioxo-4a-anthracenecarboxylate 12 and 13
Compounds 12 and 13 were prepared from quinone 4 (30 mg, 0.12 mmol) and cyclopentadiene using
ZnCl2 (0.12 mmol), according to the standard procedure outlined above, and were isolated as a colourless
solid (31 mg, 64%): mp 165–170°C; [45.3:1 ratio of diastereomers 13:12 (96% d.e.), the asterisk denotes
resonances for the minor diastereomer 12] 1H NMR (200 MHz, CDCl3) δ 0.66 and 1.09* (s, 3H, 40-Me),
1.12 and 1.19* (s, 3H, 40-Me), 1.71 (m, J=9.3 Hz, 1H, 11-HA), 1.86 (d, J=9.3 Hz, 1H, 11-HB), 3.64–3.68
(m, 1H, 1-H), 3.77 (d, J=4 Hz, 1H, 9a-H), 3.90–3.99 (m, 3H, 50-CH2 and 4-H), 5.34* and 5.35 (s, 1H,
30-H), 6.01–6.10 (m, 2H, 2-H and 3-H), 7.72–7.76 (m, 2H, 6-H and 7-H), 8.02–8.09 (m, 2H, 5-H and
8-H); 13C NMR (50 MHz, CDCl3) δ 19.3 and 19.7* (CH3, 40-Me), 22.7 and 22.9* (CH3, 40-Me), 40.1
and 40.2* (quat, C-40), 48.4 (CH2, C-11), 48.7 (CH, C-1), 52.0 and 52.5* (CH, C-4), 55.0 and 55.4*
(CH, C-9a), 64.0 and 65.0* (quat, C-4a), 75.7 (CH, C-30), 76.0 (CH2, C-50), 126.9 (CH, C-5 or C-8),
127.2 and 127.3* (CH, C-8 or C-5), 134.2 and 134.4* (CH, C-6 or C-7), 134.6 and 134.7* (CH, C-7 or
C-6), 134.8 and 135.0* (quat, C-4b), 134.8 and 135.0* (quat, C-8a), 136.4 and 135.9* (CH, C-2 or C-3),
137.7 and 137.6* (CH, C-3 or C-2), 170.1 and 170.2* (quat, ester), 171.4 (quat, C-20), 193.4 (quat, C-9
or C-10), 194.9 and 195.4* (quat, C-10 or C-9); IR (film) 1789 (lactone), 1756 (ester), 1681 (quinone),
1592 (C_C), 1267, 1210, 1156 cm−1; m/z (EI, %) 380 (M+, 1), 315 (M−C5H5, 12), 250, 185 (C11H5O3,
59), 157 (C10H5O2, 100), 66 (64); anal. found: C, 69.16; H, 5.47; C22H20O6 requires C, 69.46; H, 5.30%.
For an ORTEP diagram of 13 see Fig. 1. For other Lewis acids see Table 4.
4.7.5. (1R0,2S0,1R,4S,4aS,9aS)- and (1R0,2S0,1S,4R,4aR,9aR)-2-Phenyl-1-cyclohexyl 1,4,4a,9a-
tetrahydro-1,4-methano-9,10-dioxo-4a-anthracenecarboxylate 14 and 15
Compounds 14 and 15 were prepared from quinone 5 (75 mg, 0.21 mmol) and cyclopentadiene using
ZnCl2 (0.21 mmol), according to the standard procedure outlined above, and were isolated as a colourless
oil (53 mg, 60%); [35:1 mixture of diastereomers (94% d.e.), the asterisk denotes resonances for the
1
minor diastereomer 14], H NMR (200 MHz, CDCl3) δ 1.03–2.09 (m, 10H, 30-CH2, 40-CH2, 50-CH2,
60-CH2, 11-HA and 11-HB), 2.37 (ddd, J=3.6, 11.5, 11.5 Hz, 1H, 20-H), 2.54 and 3.37* (d, J=3.9 Hz, 1H,
9a-H), 3.19–3.27 and 3.36–3.44* (m, 1H, 1-H), 3.63–3.71 (m, 1H, 4-H), 4.97 (ddd, J=4.3, 10.8, 10.8 Hz,
1H, 10-H), 5.84–5.97 (m, 2H, 2-H and 3-H), 6.87–7.29 (m, 5H, Ph), 7.61–7.75 (m, 2H, 6-H and 7-H),
7.87–8.04 (m, 2H, 5-H and 8-H); 13C NMR (50 MHz, CDCl3) δ 24.5 (CH2, C-40), 25.5 and 25.6* (CH2,
C-50), 31.6 and 31.8* (CH2, C-30), 33.3 and 34.0* (CH2, C-60), 47.8* and 48.0 (CH2, C-11), 48.0 and

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M. A. Brimble et al. / Tetrahedron: Asymmetry 9 (1998) 1239–1255
48.2* (CH, C-9a), 49.5* and 49.9 (CH, C-20), 51.9 (CH, C-1), 54.6 and 55.0* (CH, C-4), 63.9 and 64.9*
(quat, C-4a), 77.6 and 78.0* (CH, C-10), 126.6 and 127.1* (CH, C-400), 126.4* and 126.7 (CH, C-5 or
C-8), 127.0 (CH, C-8 or C-5), 127.3 (CH, C-300), 128.3* and 128.4 (CH, C-200), 134.0 (CH, C-6 or C-7),
134.0 (CH, C-7 or C-6), 134.6* and 134.8 (quat, C-4b or C-8a), 134.9* and 135.2 (quat, C-8a or C-4b),
136.2 and 136.4* (CH, C-2 or C-3), 137.0 (CH, C-3 or C-2), 142.4 (quat, C-100), 169.9* and 170.2 (quat,
ester), 192.6* and 193.7 (quat, C-9 or C-10), 195.5 and 196.1* (quat, C-10 or C-9); IR (film) 1739 (s,
ester), 1681 (quinone), 1592 (C_C), 1222 cm−1; m/z (CI, CH4, rel. abundance) 427 (M++1, 20), 361
(100), 269 (15), 203 (42), 159 (58); HRMS analysis (LSIMS, M++1) (C28H27O4=427.1909) found m/z
427.1893.
4.8. Representative procedure for fragmentation of 6–15 to 16–25
4.8.1. (−)-[3aS-(3aα,6α,7aβ),6b0R,9a0R]-Hexahydro-8,8-dimethyl-1-[50 -hydroxy-6b0,70,9a0-
trihydrocyclopenta[b]-naphtho[1,2-d]furan-60 -oyl]-3H-3a,6-methano-2,1-benzisothiazole-2,2-dioxide
18
A solution of Diels–Alder adduct 8 (11 mg, 0.02 mmol) in dichloromethane (3 mL) cooled to 0°C,
was treated with tin(IV) chloride (4 mg) and stirred for 10 min. The mixture was then diluted with
dichloromethane (5 mL) and washed with 10% sodium hydrogen carbonate solution (2×5 mL). The
organic layer was dried over MgSO4 and the solvent removed in vacuo. Purification of the resultant
residue by flash chromatography (hexane:ethyl acetate, 3:1) afforded the title compound 18 as a yellow
oil (10 mg, 98%): [α]D=−136.0 (c=0.4, CH2Cl2); 1H NMR (200 MHz, CDCl3) δ 0.93 (s, 3H, 8-MeA),
1.10 (s, 3H, 8-MeB), 1.20–2.33 (m, 7H, 6-CH, 7-CH2, 4-CH2 and 5-CH2), 2.39 (dd, J=17.4, 2.0 Hz, 1H,
70-HB), 2.96 (dd, J=17.4, 8.5 Hz, 1H, 70-HA), 3.39 (d, J=15.3 Hz, 1H, 3-HA), 3.47–3.64 (m, 1H, 7a-H),
4.08 (d, J=15.3 Hz, 1H, 3-HB), 4.43 (ddd, J=8.5, 8.5, 2.0 Hz, 1H, 6b0-H) 6.00–6.17 (m, 3H, 80-H, 90-H
and 9a0-H), 7.46–7.64 (m, 2H, 20-H and 30-H), 7.97 (d, J=7.7 Hz, 1H, 10-H), 8.10 (d, J=7.8 Hz, 1H,
40-H), 11.23 (s, 1H, OH); 13C NMR (50 MHz, CDCl3) δ 20.7 (CH3, 8-MeA), 20.8 (CH3, 8-MeB), 26.7
(CH2, C-5), 32.0 (CH2, C-4), 39.6 (CH2, C-7), 39.9 (CH, C-6), 43.0 (CH2, C-70), 44.5 (CH, C-6b0), 49.6
(quat, C-8), 50.4 (quat, C-3a), 53.7 (CH2, C-3), 59.8 (CH, C-7a), 94.3 (CH, C-9a0), 103.6 (quat, C-60),
120.6 (quat, C-6a0), 121.7 (quat, C-4a0 or C-10b0), 121.9 (CH, C-10 or C-40), 124.1 (CH, C-40 or C-10),
127.1 (CH, C-20 or C-30), 127.4 (CH, C-30 or C-20), 128.3 (quat, C-10b0 or C-4a0), 129.7 (CH, C-80),
135.3 (CH, C-90), 153.6 (quat, C-10a0), 158.8 (quat, C-50), 168.2 (quat, amide); IR (film, NaCl) 1657
(C_O), 1596 (C_C), 1372, 1261, 1172 cm−1; m/z (LSIMS, %) 466 (M++1, 13), 400 (C21H23O5NS,
39), 250 (69), 216 (26), 186 (100); HRMS analysis (LSIMS, M++1) (C26H29O5NS=466.1688) found m/z
466.1672.
4.8.2. (30S,6bR,9aR)-1-Methyl-2,5-dioxo-3-pyrrolidinyl 5-hydroxy-6b,7,9a-trihydrocyclopenta[b]-naph-
tho[1,2-d]furan-6-carboxylate 21
Compound 21 was prepared by fragmentation of 11 (24 mg) using SnCl4 (1 equiv.) and was isolated
as a colourless oil (23 mg, 95%): (2.7:1 ratio, the asterisk denotes resonances for the minor diastereomer
20), 1H NMR (200 MHz, CDCl3) δ 2.43–2.53 (m, 1H, 7-HB), 2.73–3.10 (m, 2H, 40-HA and 7-HA), 3.37
(dd, J=18.4, 8.6 Hz, 1H, 40-HB), 4.53 (ddd, J=8.5, 8.5, 3.0 Hz, 1H, 6b-H), 5.79 (dd, J=4.7, 8.6 Hz, 1H,
30-H), 5.87–6.12 (m, 3H, 8-H, 9-H and 9a-H), 7.43–7.53 (m, 1H, 2-H or 3-H), 7.55–7.65 (m, 1H, 3-H
or 2-H), 7.86 (d, J=7.3 Hz, 1H, 1-H), 8.33 (d, J=8.4 Hz, 1H, 4-H), 11.38 and 11.41* (s, 1H, OH); 13C
NMR (50 MHz, CDCl3) δ 25.2 (CH3, N–Me), 35.9* and 36.1 (CH2, C-40), 42.2 and 42.4* (CH2, C-7),
46.7 (CH, C-6b), 68.1 and 68.5* (quat, C-30), 92.1* and 92.3 (CH, C-9a), 101.5 (quat, C-6), 119.2* and
119.3* (quat, C-6a), 121.7 (CH, C-1 or C-4), 124.5 (CH, C-4 or C-1), 124.7 (quat, C-4a or C-10b), 125.2

M. A. Brimble et al. / Tetrahedron: Asymmetry 9 (1998) 1239–1255
1253
(quat, C-10b or C-4a), 126.0 (CH, C-2 or C-3), 129.0 (CH, C-3 or C-2), 129.5* and 129.8 (CH, C-8),
135.9* and 136.5 (CH, C-9), 146.4 (quat, C-10a), 157.4 (quat, C-5), 169.9 (quat, ester), 172.6 (quat, C-20
or C-40), 173.0 (quat, C-40 or C-20); IR (film) 1714 (s, amide and ester), 1666, 1595 (C_C), 1439, 1386,
1285, 1223 cm−1; m/z (EI, %) 379 (M+, 9), 250 (C16H10O3, 100), 221 (13), 165 (36); HRMS analysis
(EI, M+) (C21H17O6N=379.1056) found m/z 379.1009.
4.8.3. (30R,6bR,9aR)-Dihydro-4,4-dimethyl-2-oxo-3-furanyl 5-hydroxy-6b,7,9a-trihydrocyclopenta[b]-
naphtho[1,2-d]furan-6-carboxylate 23
Compound 23 was prepared by fragmentation of 13 (20 mg, 0.05 mmol) using SnCl4 (1 equiv.) and
was isolated as a yellow oil (13 mg, 65%): 1H NMR (200 MHz, CDCl3) δ 1.25 (s, 3H, 40-Me), 1.30 (s,
3H, 40-Me), 2.63 (dd, J=18.2, 2.7 Hz, 1H, 7-HB), 3.33 (dd, J=18.2, 8.5 Hz, 1H, 7-HA), 4.07–4.22 (m,
2H, 50-HA and 50-HB), 4.47 (ddd, J=8.5, 8.5, 2.7 Hz, 1H, 6b-H), 5.86 (s, 1H, 30-H), 5.92–6.13 (m, 3H,
8-H, 9-H and 9a-H), 7.45–7.55 (m, 1H, 2-H or 3-H), 7.56–7.67 (m, 1H, 3-H or 2-H), 7.88 (d, J=8.0 Hz,
1H, 1-H), 8.37 (d, J=7.9 Hz, 1H, 4-H), 11.63 (s, 1H, OH); 13C NMR (50 MHz, CDCl3) δ 20.5 (CH3,
40-Me), 23.2 (CH3, 40-Me), 40.5 (quat, C-40), 42.2 (CH2, C-7), 46.7 (CH, C-6b), 75.7 (CH, C-30), 76.3
(CH2, C-50), 92.3 (CH, C-9a), 101.6 (quat, C-6), 119.4 (quat, C-6a), 121.7 (CH, C-1 or C-4), 124.5 (CH,
C-4 or C-1), 124.8 (quat, C-4a or C-10b), 125.2 (quat, C-10b or C-4a), 126.0 (CH, C-2 or C-3), 128.7
(CH, C-3 or C-2), 129.7 (CH, C-8), 136.8 (CH, C-9), 146.4 (quat, C-10a), 157.5 (quat, C-5), 169.9 (quat,
ester), 171.6 (quat, C-20); IR (film) 1789 (lactone), 1744 (ester), 1665, 1596 (C_C), 1385, 1294, 1153
cm−1; m/z (EI, %) 380 (M+, 16), 250 (C16H10O3, 100), 221 (26), 165 (62), 71 (59); HRMS analysis (EI,
M+) (C22H20O6=380.1260) found m/z 380.1260.
4.8.4. (+)-(10R,20S,6bR,9aR)-2-Phenyl-1-cyclohexyl 5-hydroxy-6b,7,9a-trihydrocyclopenta[b]-naph-
tho[1,2-d]furan-6-carboxylate 25
Compound 25 was prepared by fragmentation of 15 (40 mg, 0.09 mmol) using SnCl4 (1 equiv.) and
was isolated as a yellow oil (39 mg, 98%, 94% d.e.): [α]D=+77.2 (c=0.58, CH2Cl2); 1H NMR (200 MHz,
CDCl3) δ 1.01–2.39 (m, 9H, 30-CH2, 40-CH2, 50-CH2, 60-CH20 and 7-HB), 2.56 (dd, J=17.9, 8.5 Hz, 1H,
7-HA), 2.94 (ddd, J=3.2, 11.1, 11.1 Hz, 1H, 20-H), 4.40 (ddd, J=8.6, 8.6, 3.0 Hz, 1H, 6b-H), 5.61–5.78
(m, 1H, 10-H), 5.79–6.01 (m, 3H, 8-H, 9-H and 9a-H), 7.10–7.35 (m, 5H, Ph), 7.38–7.60 (m, 2H, 2-H
and 3-H), 7. 82 (d, J=8.3 Hz, 1H, 1-H), 8.31 (d, J=8.2 Hz, 1H, 4-H), 12.02 (s, 1H, OH); 13C NMR (50
MHz, CDCl3) δ 24.8 (CH2, C-40), 25.8 (CH2, C-50), 32.8 (CH2, C-30), 36.0 (CH2, C-60), 42.4 (CH2, C-
7), 46.7 (CH, C-6b), 49.6 (CH, C-20), 75.9 (CH, C-10), 92.0 (CH, C-9a), 103.0 (quat, C-6), 119.8 (quat,
C-6a), 121.5 (CH, C-1 or C-4), 124.3 (CH, C-4 or C-1), 124.5 (quat, C-4a or C-10b), 124.8 (quat, C-10b
or C-4a), 125.5 (CH, C-9), 126.6 (CH, C-2 or C-3), 127.2 (CH, C-400), 128.5 (CH, C-300), 128.9 (CH,
C-200), 128.9 (CH, C-3 or C-2), 136.5 (CH, C-8), 142.9 (quat, C-100), 145.9 (quat, C-10a), 156.4 (quat,
C-5), 170.5 (quat, ester); IR (film) 1643 (ester), 1595 (C_C), 1389, 1232, 1169 cm−1; m/z (EI, %) 426
(M+, 28), 268 (58), 250 (87), 165 (32), 91 (C7H7, 100); HRMS analysis (EI, M+) (C28H26O4=426.1831)
found m/z 426.1813.
4.9. Representative procedure for removal of chiral auxiliaries
4.9.1. (6bR*,9aR*)-6-Formyl-6b,9a-dihydro-5-hydroxy-7H-cyclopenta[b]naphtho[1,2-d]furan 27
Camphorsultam 18 (12 mg, 0.026 mmol) was dissolved in THF (2 mL) and lithium borohydride (0.4
mg, 2 equiv.) in THF (0.5 mL) added dropwise. After stirring for 30 min, the solvent was removed
under reduced pressure and the residue redissolved in dichloromethane (5 mL). The solution was washed
with 10% sodium hydrogen carbonate solution (2×2 mL) and dried over MgSO4. The solvent was then

1254
M. A. Brimble et al. / Tetrahedron: Asymmetry 9 (1998) 1239–1255
removed in vacuo and the crude product purified by flash chromatography (hexane:ethyl acetate, 4:1)
to give the title compound (27A) as a yellow solid (4 mg, 61%): mp 127–130°C; [α]D=−90.0 (c=0.40,
CH2Cl2); 1H NMR (200 MHz, CDCl3) δ 2.64 (dd, J=17.2, 2.5 Hz, 1H, 7-HB), 3.07 (dd, J=17.2, 8.2 Hz,
1H, 7-HA), 4.52 (ddd, J=8.5, 8.5, 2.5 Hz, 1H, 6b-H), 5.96–6.12 (m, 3H, 8-H, 9-H and 9a-H), 7.43–7.53
(m, 1H, 2-H or 3-H), 7.58–7.68 (m, 1H, 3-H or 2-H), 7.86 (d, J=7.3 Hz, 1H, 1-H), 8.37 (d, J=8.2 Hz,
1H, 4-H), 10.07 (s, 1H, CHO), 12.59 (s, 1H, OH); 13C NMR (50 MHz, CDCl3) δ 41.3 (CH2, C-7), 43.1
(CH, C-6b), 93.4 (CH, C-9a), 110.6 (quat, C-6), 119.7 (quat, C-6a), 121.8 (CH, C-1 or C-4), 124.9 (CH,
C-4 or C-1), 124.9 (quat, C-4a or C-10b), 126.0 (quat, C-10b or C-4a), 126.0 (CH, C-2 or C-3), 129.5
(CH, C-3 or C-2), 130.4 (CH, C-8), 135.1 (CH, C-9), 149.5 (quat, C-10a), 157.8 (quat, C-5), 193.5 (CH,
CHO); IR (film) 1634 (CHO), 1570 (C_C), 1378, 1292 cm−1; m/z (EI, %) 252 (M+, 100), 237 (21), 221
(27), 165 (25), 147 (25); HRMS analysis (EI, M+) (C16H12O3=252.0786) found m/z 252.0788.
4.9.2. (3aR,5R,11bS)-3a,5,11b-Trihydro-5-hydroxy-1H-cyclopenta[b]naphtho[2,3-d]pyran-6,11-dione
28
Aldehyde 27 (90 mg, 0.36 mmol) and silver(II) oxide (180 mg, 1.45 mmol) were mixed in dioxane
(6.0 mL) and nitric acid (1.36 M, 1.60 mL) was added. After stirring the resultant mixture for 5 min,
further portions of silver(II) oxide (180 mg, 1.45 mmol) and nitric acid (1.36 M, 1.60 mL) were added.
Stirring was then continued for 10 min and water (12 mL) added. The aqueous layer was extracted
with dichloromethane (2×10 mL), washed with water (10 mL), dried (MgSO4) and the solvent removed
under reduced pressure. The residue was purified by flash chromatography (hexane:ethyl acetate, 4:1),
1
affording the title compound 28 as a pale yellow oil (22 mg, 23%): [α]D=+96.0 (c=0.3, CH2Cl2); H
NMR (200 MHz, CDCl3) δ 2.25–2.46 (m, 1H, 1-HA or 1-HB), 2.97–3.20 (m, 2H, 1-HB or 1-HA and
11b-H), 5.11–5.22 (m, 1H, 3a-H), 5.91–6.07 (m, 1H, 2-H or 3-H), 6.16 (s, 1H, 5-H), 6.22–6.29 (m, 1H,
3-H or 2-H), 7.69–7.81 (m, 2H, 8-H and 9-H), 8.05–8.19 (m, 2H, 7-H and 10-H); 13C NMR (50 MHz,
CDCl3) δ 34.8 (CH, C-11b), 37.4 (CH2, C-1), 73.5 (CH, C-3a), 97.5 (CH, C-5), 126.3 (CH, C-7), 126.3
(CH, C-10), 129.2 (CH, C-2 or C-3), 131.6 (quat, C-6a or C-10a), 131.9 (quat, C-10a or C-6a), 133.8
(CH, C-8 or C-9), 134.0 (CH, C-9 or C-8), 139.0 (CH, C-3 or C-2), 139.6 (quat, C-11a), 144.6 (quat,
C-5a), 183.0 (quat, C-6 or C-11), 184.8 (quat, C-11 or C-6); IR (film) 3438 (OH), 1726 (C_O), 1663
(C_O), 1594 (C_C), 1326, 1296, 1161 cm−1; m/z (EI, %) 268 (M+, 14), 252 (100), 209 (65), 152 (52),
105 (75), 76 (85); HRMS analysis (EI, M+) (C16H12O4=268.0736) found m/z 268.0731.
Acknowledgements
We thank the University of Sydney and the Australian Research Council for financial support.
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