Ultrasound assisted reductive cleavage of eudesmane and guaiane γ-enonelactones. Synthesis of 1α,7α,10αH-guaian-4,11-dien-3-one and hydrocolorenone from santonin

Article abstract of DOI:10.1016/S0040-4020(01)00986-3

Ultrasound enhances the rate of reductive cleavage of the C₆-oxygen bond of sesquiterpene enonelactones. trans-Eudesmanolides 1c-1g, cis-eudesmanolides 2a-2c, and trans-guaianolides 4a-4d react with Zn in acetic acid-H₂O under sonoch

Full text of DOI:10.1016/S0040-4020(01)00986-3

TETRAHEDRON
Pergamon
Tetrahedron 57 82001) 9719±9725
Ultrasound assisted reductive cleavage of eudesmane and guaiane
g-enonelactones. Synthesis of 1a,7a,10aH-guaian-4,11-dien-3-one
and hydrocolorenone from santonin
p
 Â
Gonzalo Blay, Victoria Bargues, Luz Cardona, BegonÄa Garcõa and Jose R. Pedro
 Á  Á
Departament de Quõmica Organica, Facultat de Quõmica, Universitat de Valencia, E-46100 Burjassot, Valencia, Spain
Received 9 July 2001; revised 6 September 2001; accepted 11 October 2001
AbstractÐUltrasound enhances the rate of reductive cleavage of the C6±oxygen bond of sesquiterpene enonelactones. trans-Eudesmano-
lides 1c±1g, cis-eudesmanolides 2a±2c, and trans-guaianolides 4a±4d react with Zn in acetic acid±H2O under sonochemical conditions to
afford the corresponding sesquiterpene acids 3a±3g and 5a±5d, respectively in good yields. Starting from 5d two natural guaianes
1a,7a,10aH-guaian-4,11-dien-3-one 86) and hydrocolorenone 87) have been prepared in good yields through a straightforward sequence.
q 2001 Elsevier Science Ltd. All rights reserved.
1. Introduction
Usually, sesquiterpene acids like 3 are prepared from the
most commonly occurring trans-lactones in a two step
process involving C6-epimerization to the cis-lactone and
subsequent reduction with Zn dust in acetic acid±methanol
at re¯ux. This procedure has been applied to the transfor-
mation of the eudesmanolides santonin 81a), artemisin 81b)
and its derivatives 1d and 1e into the sesquiterpene acids
3a,5 3b,6 3d7 and 3e,8 respectively, which have been used as
Sesquiterpene lactones constitute a very interesting group of
natural compounds1,2 on account of their wide spectrum of
biological activities. The corresponding sesquiterpene acids
are also interesting natural products not only because of
their biological activity but also because of their utility as
synthetic intermediates.1±4
Keywords: sonochemistry; cleavage reaction; terpenes; lactones.
Corresponding author. Tel.: 134-09-638-64329; fax: 134-09-638-64328; e-mail: jose.r.pedro@uv.es
p
0040±4020/01/$ - see front matter q 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020801)00 986-3

9720
G. Blay et al. / Tetrahedron 57 /2001) 9719±9725
intermediates in the synthesis of several natural sesquiter-
penes3,5,8 and sesquiterpene lactones.3,6±8
bond is equatorial 8entries 4±8) overriding the stereo-
electronic requirements for the reductive elimination. The
method is compatible with hydroxyl or acetate groups in the
B ring, although in one case 8entry 7) the hydroxy acid 3f
obtained suffered partial lactonization to give the 8,12-
eudesmanolide 3h. Unfortunately, when a dienone system
was present 8compounds 1a and 1b), complex reaction
mixtures were obtained due to the decomposition of the
dienone system.
A different procedure has been used by Loewenthal et al. in
their synthesis of 1-epicyclocolerenone.9 These authors
carried out the hydrogenolysis of three guaianolides with
chromous chloride in acetic acid with variable yields.
From guaianolide 4d these authors obtained the correspond-
ing acid 5d in 50% yield. More recently Suarez et al. have
developed an organosulfur or organoselenium mediated
method for this transformation which has been applied to
eudesmanolides 1a, 1c and 2a, and to guaianolide 4a.10 This
method gives in most cases better results but requires
special experimental conditions.
Table 1 also displays the results for four guaiane trans-g-
enonelactones obtained from santonin 81a) 8Scheme 1).
Irradiation of 4a±4d in the same conditions 8entries 9±12)
gave in all cases good results of the corresponding guaiane
acids 5a±5d. The method is compatible with the presence of
tertiary acetate or hydroxyl groups in the B ring as well as
with an exomethylene double bond. Neither enone reduction
products nor epimerization at the C-1 position were
observed in any case.
As part of our current synthetic programme related to
natural sesquiterpenes with biological activity,4 we have
described in a previous communication an easy ultra-
sound assisted reductive cleavage of several sesquiterpene
g-enonelactones.11 In this paper we wish to report in full,
our investigation on the ultrasound assisted cleavage of
eudesmanolides 1a±1g and 2a±2c and specially the exten-
sion to guaianolides 4a±4d to prepare the corresponding
sesquiterpene acids 3a±3g and 5a±5d, respectively. We
also wish to report the synthesis of 1a,7a,10aH-guaian-
4,11-dien-3-one 86) and hydrocolorenone 87) from 5d as
an example of the utility of these sesquiterpene acids as
synthetic intermediates. Structure 6 has been assigned to a
compound isolated from Baccharis boliviensis12 and hydro-
colorenone 87) was ®rst isolated from Euryops pedunculatus
by Bohlmann's group13 and recently from the indonesian
soft coral Nephthea chabrolii.14 Compound 7 exhibits
insecticidal activity towards neonate larvae of the polypha-
gous pest insect Spodoptera littoralis.14
Compound 5d has one of the two epimeric structures
proposed for 11,13-dihydropechuloic acid, a natural guaiane
acid isolated from Decachaeta scabrella.20 However
comparison of the natural product reported data20 with
those of our synthetic compound showed signi®cant
1
differences in their H NMR data for H-6a, H-6b and H-7
8d 2.63, 2.47 and 2.56, respectively, for the natural
compound; d 2.70, 2.40 and 2.15, respectively, for 5d),
and in the 13C NMR data for C-2, C-6, C-8 and C-9 8d
41.0, 36.5, 27.9 and 36.3, respectively, for the natural
compound;d 40.7, 29.4, 27.6 and 38.4, respectively, for
5d). On the basis of these differences the structure of
compound 5d should be discarded for the natural product.
With compound 5d in our hands21,22 we undertook the
2. Results and discussion
Table 1. Ultrasound assisted reductive cleavage of sesquiteerpene g-enone-
lactones
The use of ultrasound to enhance the chemical reactivity of
metal powder in heterogeneous solid±liquid systems is well
established and it has been the subject of several reviews.15
In the present work various reductive systems that have
been used for the ultrasound assisted reduction of different
functional groups were tried in order to carry out the reduc-
tive cleavage of the lactone ring. The use of aluminium±
nickel chloride/THF16 and zinc±nickel chloride/2-methoxy-
ethanol±water17 resulted unsucessful. Thus no reaction was
observed and the starting material was recovered unaltered
with the ®rst system while complex reaction mixtures were
obtained with the second one. However, zinc/acetic acid±
water18 gave good yields of the hydrogenolysis product in
all the samples where a g-enonelactone moiety was present.
Entry
Substrate
Time 8min)
Producta
Yield 8%)b,c
1
2
3
4
5
6
7
8
2a
2b
2c
1c
1d
1e
1f
1g
4a
4b
4c
4d
2
2
2
60
120
120
120
120
60
120
120
120
3a
3b
3c
3c
3d
3e
3f
3g
5a
5b
5c
5d
75
73
86
80885)
71875)
68871)
66870)d
65870)
85
9
10
11
12
78
70
70
a
As methyl ester after methylation with excess of ethereal diazomethane.
Yields refer to isolated and chromatographically pure compounds. Yields
in brackets refer to consumed starting material.
In entries 4±8 some reduction product 83±5%) of the unsaturated ketone
was observed.
Part of the 8,12-lactonization product 3h appeared during hydrogenolysis.
This yield refers to the 8,12-lactone 3h isolated after treatment of the
crude mixture with p-TsOH acid in benzene at re¯ux.
b
c
d
Table 1 displays the results obtained with several eudes-
mane and guaiane g-enonelactones. As expected, the reac-
tion proceeded extremely quickly and with good yields with
eudesmane cis-lactones 2a±2c 8entries 1±3) as the axial
disposition of the C6±oxygen ful®ls the stereoelectronic
requirements for an effective electron transfer from the
carbonyl group to the leaving group, and allows a minimum
expenditure of energy for the elimination.19 More interest-
ingly, the reaction also took place with the most usually
occurring trans-lactones 1c±1g where the C6±oxygen

G. Blay et al. / Tetrahedron 57 /2001) 9719±9725
9721
Scheme 1.
modi®cation of the C7 side chain in order to obtain
compounds 6 and 7 8Scheme 1). In a ®rst approach we
decided to protect the oxo group as a thioketal, which was
carried out by reaction of the methyl ester 8 with ethane-
dithiol in acetic acid±boron tri¯uoride for 48 h at re¯ux.
Unexpectedly this treatment caused epimerization at C-1
yielding 876%) an epimeric mixture of thioketals 12
8H-1b/H-1a in a ratio 3:1). Since the major reaction product
was the undesired C1 epimer, we decided not to protect the
ketone group and to reduce both carbonyl groups with
excess LiAlH4 to obtain the corresponding diol 9 as a C3
epimeric mixture, which could be selectively reoxidized at
C3 with MnO2 in CHCl3 at room temperature to afford the
desired compound 10 880% yield for the two steps). It is
important to remark that oxidation of diol 9 must be
performed immediately after reduction of compound 8
since it was observed that diol 9 is unstable and rapidly
dehydrate to diene 13 [1H NMR 8200 MHz) d 5.62 and
5.36 8two br. s, 1H each, H-3 and H-6); 13C NMR
8200 MHz) d 150.7, 140.2 8C, C-4, C-5), 131.9, 121.2
8CH, C-3, C-6)].
The elimination of the C-12 hydroxyl group was achieved in
two steps following the procedure described by Grieco et
al.23 The sequence involves transformation of the hydroxyl
group into o-nitrophenyl selenide 11 by treatment with
o-nitrophenyl selenocyanate and tri-n-butylphosphine
892%), followed by spontaneous elimination of the
corresponding selenoxide upon treatment with hydrogen
peroxide to give compound 6 in 95% yield. The physical

9722
G. Blay et al. / Tetrahedron 57 /2001) 9719±9725
and spectral data of compound 6 were in complete
agreement with those reported for the natural 11a,7a,
10aH-guaia-4,11-dien-3-one isolated from Baccharis
boliviensis.12 Finally, hydromercuration±demercuration24
of compound 6 afforded hydrocolorenone 87) 891%)
which showed the same spectral features and optical
rotation sign than the natural compound isolated from
E. pedunculatus13 and N. chabrolii.14
cated for one additional hour. Then, the reaction mixture
was ®ltered through Celite, extracted with ethyl acetate
and the combined organic layers were washed with brine
and dried over Na2SO4. Solvent removal afforded the acid
which was esteri®ed with an excess of ethereal diazo-
methane to give the corresponding methyl ester for charac-
terization.
24
3.2.1. Compound 3a. 75%; yellow oil; [a]D ˆ278.7 8c
In summary, an ultrasound assisted procedure for the
reductive cleavage of g-enonelactones has been developed.
This method constitutes a simple alternative to the literature
procedures and it is very much simpler and safer from the
experimental point of view. With regard to the classical
method5±8 the yields are higher, reaction times shorter and
for the most usually occurring eudesmane trans-lactones
there is no need for epimerization at the C6 carbon of the
lactone moiety. The procedure can also be applied to trans-
guaianolides with good results and it compares favourably
with the chromous chloride method.9 It is also safer than the
organosulfur or organoselenium mediated method10 which
requires a heavy wall tube with a high vacuum valve,
heating at high temperatures, and the recommended use of
a protective shield. The synthesis of guaiane acid 5d
obtained by this method allows us to discard this structure
for the natural 11,13-dihydropechuloic acid isolated from D.
scabrella.20 We have also showed that compound 5d is a
good starting material for the synthesis of natural guaianes 6
and 7 which were obtained in 56 and 50% overall yield,
respectively. The structure and absolute stereochemistry of
both compounds have been con®rmed.
1.60) [lit.5 [a]D ˆ299 8c 0.8, MeOH)]; IR 8NaCl) nmax
23
1
1730, 1660, 1630, 1610 cm21; H NMR 8200 MHz) d 6.72
8d, Jˆ9.8 Hz, 1H, H-1), 6.208d, Jˆ9.8 Hz, 1H, H-2), 3.70
8s, 3H, ±OMe), 2.71 8dt, Jˆ2.8, 12.8 Hz, 1H, H-6a), 2.44
8quint, Jˆ6.9 Hz, 1H, H-11), 2.01 8t, Jˆ12.8 Hz, 1H,
H-6b), 1.86 8s, 3H, 3H-15), 1.81 8dd, Jˆ2.9, 12.4 Hz, 1H,
H-9b), 1.75±1.408m, 3H, H-7, H-8 a, H-9a), 1.32 8td,
Jˆ3.4, 12.4 Hz, 1H, H-8b), 1.19 8d, Jˆ7.2 Hz, 3H,
3H-13), 1.18 8s, 3H, 3H-14); 13C NMR 850.3 MHz) d
186.3, 175.9, 158.9 8C, C-3, C-12, C-5), 156.4 8CH, C-1),
129.3 8C, C-4), 126.1 8CH, C-2), 51.5 8CH3, ±OCH3), 44.8,
42.0 8CH, C-7, C-11), 40.1 8C, C-10), 37.5, 31.8, 24.0 8CH2,
C-8, C-9, C-6), 23.2, 14.2, 10.3 8CH3, C-14, C-13, C-15).
3.2.2. Compound 3b. 73%; mp 93±948C 8hexane±EtOAc);
24
25
[a]D ˆ224.4 8c 1.47) [lit.6 [a]D ˆ214 8c 0.120.3)]; IR
8KBr) nmax, 3450, 1725, 1660, 1630, 1610 cm21; H NMR
1
8200 MHz) d 6.65 8d, Jˆ9.8 Hz, 1H, H-1), 6.14 8d, Jˆ
9.8 Hz, 1H, H-2), 3.99 8td, Jˆ4.5, 10.8 Hz, 1H, H-8), 3.66
8s, 3H, ±OCH3), 2.92 8dq, Jˆ2.3, 7.0Hz, 1H, H-11), 2.76
8dd, Jˆ3.8, 14.0Hz, 1H, H-6 a), 2.13 8t, Jˆ14.0Hz, 1H,
H-6b), 2.04 8dd, Jˆ4.5, 12.5 Hz, 1H, H-9b), 1.85 8s, 3H,
3H-15), 1.80±1.60 8m, 1H, H-7), 1.21 8d, Jˆ7.0Hz, 3H,
3H-13), 1.17 8s, 3H, 3H-14); 13C NMR 850.3 MHz) d
186.1, 176.0, 157.5 8C, C-3, C-12, C-5), 155.4 8CH, C-1),
129.6 8C, C-4), 125.8 8CH, C-2), 66.4 8CH, C-8), 51.6 8CH3,
±OCH3), 48.4 8CH, C-7), 45.2 8CH2, C-9), 40.2 8C, C-10),
39.3 8CH, C-11), 28.2 8CH2, C-6), 24.4, 13.3, 10.4 8CH3,
C-14, C-13, C-15).
3. Experimental
3.1. General methods
All melting points are uncorrected. Column chroma-
tography was performed on silica gel 8SDS, silica gel 40±
60 mm). Commercial reagents and solvents were analytical
grade or were puri®ed by standard procedures prior to use.25
All reactions involving air or moisture sensitive materials
were carried out under argon atmosphere. Speci®c rotations
were measured in CHCl3. IR spectra were recorded as liquid
®lm in NaCl for oils and as KBr discs for solids. NMR
spectra were run in CDCl3 8except stated otherwise) at
3.2.3. Compound 3c. 80% from 1c, 86% from 2c; oil;
24
23
[a]D ˆ11208 c 1.60) [lit.5 [a]D ˆ1115 8c 0.2, MeOH)];
IR 8NaCl) nmax, 1735, 1665, 1610cm 21; H NMR 8200
1
MHz) d 3.68 8s, 3H, ±OCH3), 2.608dt, Jˆ2.2, 12.6 Hz,
1H, H-6a), 2.49±2.31 8m, 3H, 2H-2, H-11), 1.88 8td, Jˆ
1.3, 12.6 Hz, 1H, H-6b), 1.78±1.58 8m, 5H, 2H-1, H-7, H-8,
H-9), 1.72 8d, Jˆ1.2 Hz, 3H, 3H-15), 1.46±1.35 8m, 2H,
H-80, H-90), 1.17 8d, Jˆ6.6 Hz, 3H, 3H-13), 1.16 8s, 3H,
3H-14); 13C NMR 850.3 MHz) d 199.0, 176.1, 161.3,
128.8 8C, C-3, C-12, C-5, C-4), 51.5 8CH3, ±OCH3), 45.0,
41.3 8CH, C-7, C-11), 41.5, 33.7, 32.0, 37.3 8CH2, C-2, C-8,
C-9, C-1), 35.8 8C, C-10), 24.6 8CH2, C-6), 22.3, 13.9, 10.7
8CH3, C-14, C-13, C-15).
1
200.1, 299.95, or 399.95 MHz for H and at 50.3 or 75.4
MHz for 13C NMR, and referenced to the solvent as internal
standard 8dHˆ7.24 ppm). The carbon type was determined
by DEPT experiments. Mass spectra were run by electron
impact at 70eV or chemical ionisation using methane as
ionising gas. A J.P. Selecta S.A ultrasound bath 8100 W,
40 KHz, ref 03000683) was used for sonication.
3.2.4. Compound 3d. 71%; mp 119±1218C 8ether) [lit.6 mp
24
120±1218C 8ether)]; [a]D ˆ198.5 8c 0.97) [lit.6 [a]D
25
ˆ
3.2. General procedure for the ultrasound assisted
cleavage of g-enonelactones
158 8c 0.1±0.3)]; IR 8KBr) nmax, 3300, 1730, 1650,
;
1610cm 21
1H NMR 8200 MHz) d 3.92 8ddd, Jˆ4.2,
10.5, 11.5 Hz, 1H, H-8), 3.70 8s, 3H, ±OCH3), 2.88 8qd,
Jˆ2.7, 7.2 Hz, 1H, H-11), 2.69 8dd, Jˆ3.6, 14.5 Hz, 1H,
H-6a), 2.60±2.30 8m, 2H, 2H-2), 2.02 8br. t, Jˆ14.5 Hz,
1H, H-6b), 1.92 8dd, Jˆ4.2, 12.7 Hz, H-9b), 1.89±1.69
8m, 3H, 2H-1, H-7), 1.76 8d, Jˆ1.3 Hz, 3H, 3H-15), 1.36
8dd, Jˆ11.1, 12.7 Hz, 1H, H-9a), 1.24 8d, Jˆ7.2 Hz, 3H,
Starting material 80.2 mmol) was dissolved in a mixture of
acetic acid±water 81:1) 84 mL). Zinc dust 88 mmol) was
added and the reaction mixture irradiated with an ultrasound
bath at room temperature 8ice addition) for 2 min or 1 h 8see
Table 1). For longer reaction times one portion of Zn
81.6 mmol) was added and the reaction mixture was soni-

G. Blay et al. / Tetrahedron 57 /2001) 9719±9725
9723
3H-13), 1.19 8s, 3H, 3H-14); 13C NMR 850.3 MHz) d 198.6,
176.3, 159.4, 129.3 8C, C-3, C-12, C-5, C-4), 66.9 8CH,
C-8), 51.8 8CH3, ±OCH3), 50.1 8CH2, C-9), 47.8, 39.7
8CH, C-7, C-11), 37.2 8CH2, C-1), 37.08C, C-10), 33.2,
29.1 8CH2, C-2, C-6), 23.2, 12.9, 11.08CH , C-14, C-13,
3
C-15).
2.50±2,40 8m, 2H, H-9, H-11), 2.35 8d, Jˆ4.3 Hz, 2H,
2H-2), 2.32±2.25 8m, 1H, H-60), 2.21±2.08 8m, 2H, H-7,
H-8), 1.94 8s, 3H, CH3CO2±), 1.79 8ddd, Jˆ3.7, 4.5,
1H, H-80), 1.14 8d, Jˆ7.0Hz, 3H, 3H-13), 1.00 8s, 3H,
3H-14); 13C NMR 875.4 MHz) d 207.3, 175.6, 170.9,
170.3, 138.6, 86.2 8C, C-3, C-12, C-5, CH3CO±, C-4,
C-10), 51.7 8CH3, ±OCH3), 48.4, 45.3, 38.3 8CH, C-1,
C-7, C-11), 38.9, 37.2, 35.8, 28.6 8CH2, C-2, C-6, C-9, C-8),
22.4, 19.3, 12.8, 8.2 8CH3, CH3CO±, C-14, C-13, C-15).
0
15.0Hz, 1H, H-9 ), 1.63 8s, 3H, 3H-15), 1.25±1.15 8m,
22
3.2.5. Compound 3e. 68%; oil; [a]D ˆ196.08 c 1.80) [lit.8
23
[a]D ˆ198.08 c 1.90)]; IR 8NaCl) nmax, 3450, 1730, 1660,
1
1610cm 21; H NMR 8200 MHz) d 3.708s, 3H, ±OCH ),
3
3.44 8dt, Jˆ4.4, 11.2 Hz, 1H, H-9a), 2.59 8ddd, Jˆ2.0, 3.6,
14.0Hz, 1H, H-6 a), 2.43 8dd, Jˆ4.4, 9.6 Hz, 2H, 2H-2),
2.43 8dq, Jˆ6.8, 7.6 Hz, 1H, H-11), 2.11 8dt, Jˆ4.4,
13.6 Hz, 1H, H-1), 1.908br. dt, Jˆ1.6, 14.0Hz, 1H,
H-6b), 1.88 8dddd, Jˆ2.0, 3.6, 4.4, 12.0 Hz, H-8a), 1.78
8dt, Jˆ9.6, 13.6 Hz, 1H, H-10), 1.82±1.708m, 2H, H-7,
OH), 1.75 8d, Jˆ0.8 Hz, 3H, 3H-15), 1.47 8q, Jˆ12.0Hz,
1H, H-8b), 1.19 8d, Jˆ6.8 Hz, 3H, 3H-13), 1.14 8s, 3H,
3H-14); 13C NMR 850.3 MHz) d 198.9, 175.8, 159.1,
130.4 8C, C-3, C-12, C-5, C-4), 77.6 8CH, C-9), 51.6
8CH3, ±OCH3), 44.5, 37.2 8CH, C-7, C-11), 41.4 8C,
C-10), 33.3, 33.3, 33.0, 31.4 8CH2, C-1, C-2, C-6, C-8),
15.6, 13.9, 11.2 8CH3, C-14, C-13, C-15).
19
3.2.9. Compound 5b. 78%; oil; [a]D ˆ158.1 8c 1.48);
HRMS 8CI) m/z 309.2059 8M11C2H5, 76, C18H29O4
required 309.2065), 281 8M111, 100), 280 8M1, 88), 263
892), 249 842), 231 848), 209 863), 193 882); IR 8NaCl) nmax
3445, 1730, 1684, 1618 cm21; 1H NMR 8200 MHz) d 3.64
8s, 3H, ±OMe), 3.15±3.09 8m, 1H, H-1), 2.63 8br. d, Jˆ
18.6 Hz, 1H, H-6), 2.46±2.23 8m, 3H, H-60, H-9, H-11),
2.39 8d, Jˆ4.8 Hz, 2H, 2H-2, overlapped with H-60, H-9,
H-11), 2.15±2.05 8m, 1H, H-7), 1.93 8dt, Jˆ2.9, 8.9 Hz, 1H,
H-90), 1.58 8s, 3H, 3H-15), 1.12 8d, Jˆ7.1 Hz, 3H, 3H-13),
0.82 8s, 3H, 3H-14); 13C NMR 850.3 MHz) d 208.4, 175.7,
171.9, 138.1, 74.3 8C, C-3, C-12, C-5, C-4, C-10), 51.7 8CH,
C-1), 51.6 8CH3, ±OCH3), 45.2, 38.5 8CH, C-7, C-11), 46.0,
37.5, 36.0, 28.8 8CH2, C-2, C-6, C-9, C-8), 20.5, 12.7, 8.0
8CH3, C-14, C-13, C-15).
3.2.6. Compound 3h. 66%, after treatment of the reaction
mixture with a catalytic amount of p-TsOH in benzene
83.8 mL) at re¯ux for 1 h, mp 104±1058C 8hexane±
24
18
3.2.10. Compound 5c. 70%; oil; [a]D ˆ151.5 8c 1.78);
CH2Cl2) [lit.6 mp 103±1048C 8hexane±CH2Cl2)]; [a]D
ˆ
191.6 8c 0.83) [lit.6 [a]D ˆ192 8c 0.1±0.3, Cl3CH)]; IR
8KBr) nmax, 1764, 1660, 1620 cm21; 1H NMR 8200 MHz) d
4.51±4.45 8m, 1H, H-8), 2.88 8quint, Jˆ7.0Hz, 1H, H-11),
2.65 8dd, Jˆ5.8, 13.9 Hz, 1H, H-6a), 2.53±2.38 8m, 3H,
2H-2, H-7), 2.28 8dd, Jˆ2.5, 15.5 Hz, 1H, H-9b), 1.94
8br. t, Jˆ1.3, 13.9 Hz, 1H, H-6b), 1.90±1.60 8m, 2H,
2H-1), 1.808s, 3H, 3H-15), 1.708dd, Jˆ4.4, 15.5 Hz, 1H,
H-9a), 1.28 8s, 3H, 3H-14), 1.26 8d, Jˆ7.0Hz, 3H, 3H-13);
13C NMR 850.3 MHz) d 198.3, 178.6, 157.5, 130.3 8C, C-3,
C-12, C-5, C-4), 76.6 8CH, C-8), 41.9 8CH2, C-9), 41.7, 40.8
8CH, C-7, C-11), 37.3 8CH2, C-1), 34.9 8C, C-10), 33.3
8CH2, C-2), 24.8 8CH3, C-14), 24.4 8CH2, C-6), 11.2, 9.6
8CH3, C-15, C-13).
HRMS 8CI) m/z 263 8M111, 100), 262.1566 8M1, 45,
C16H22O3 required 262.1568), 261 87), 247 87), 231 89),
25
175 841); IR 8NaCl) nmax 1730, 1707, 1631 cm21 1H
;
NMR 8300 MHz) d 4,84 8s, 1H, H-14), 4.77 8s, 1H, H-
140), 3.66 8s, 3H, ±OMe), 3.57±3.53 8m, 1H, H-1), 2.65
8ddd, Jˆ0.6, 6.6, 18.6 Hz, 1H, H-9), 2.55 8br. d, Jˆ
18.6 Hz, 1H, H-6), 2.47 8br. dd, Jˆ3.3, 13.8 Hz, 1H, H-2),
2.42 8dq, Jˆ6.9, 7.2 Hz, 1H, H-11), 2.32±2.27 8m, 1H,
H-7), 2.29 8dd, Jˆ2.7, 18.6 Hz, 1H, H-60), 2.23±2.09 8m,
2H, H-20, H-90), 1.61 8s, 3H, 3H-15), 1.13 8d, Jˆ6.9 Hz, 3H,
3H-13); 13C NMR 875.4 MHz) 208.3, 175.9, 173.5, 149.7,
135.6 8C, C-3, C-12, C-4, C-5, C-10), 111.0 8CH2, C-14),
51.6 8CH3, ±OCH3), 46.7, 44.5 8CH, C-1, C-7), 42.08CH ,
2
C-2), 36.9 8CH, C-11), 35.1, 34.3, 32.5 8CH2, C-6, C-8,
C-9), 13.8, 8.08CH 3, C-13, C-15).
24
3.2.7. Compound 3g. 65%; oil; [a]D ˆ168.5 8c 1.25);
HRMS 8CI) m/z 322.17808M 1, 5, C18H26O5 required
322.1780), 262 8100), 249 820), 202 862); IR 8NaCl) nmax
,
3.2.11. 3-Oxo-1,7,10aH,6,11bH-guai-4-en-6,12-olide -4d).
A mixture of compound 4c 8600 mg, 2.43 mmol), EtOAc
821 mL) and 5% Pd/C 8167 mg) was vigorously stirred
under H2 81 atm) for 2 h. The catalyst was removed by
®ltration on silica gel 8EtOAc), the ®ltrate concentrated
under vacuum and the residue chromatographed with 6:4±
4:6 hexane±EtOAc mixtures to separate 30mg 85%) of 4c
1730, 1655, 1600, 1240 cm21; 1H NMR 8200 MHz) d 5.25±
5.15 8m, 1H, H-8), 3.708s, 3H, ±OCH 3), 2.54±2.36 8m, 4H,
2H-2, H-6a, H-11), 2.308t, Jˆ14.0Hz, 1H, H-6 b), 2.108s,
3H, CH3CO2±), 2.14±2.03 8m, 1H, H-9b), 1.95±1.85 8m,
1H, H-7), 1.73 8d, Jˆ1.1 Hz, 3H, 3H-15), 1.75±1.69 8m, 2H,
2H-1), 1.508dd, Jˆ2.9, 15.5 Hz, 1H, H-9a), 1.26 8s, 3H,
3H-14), 1.13 8d, Jˆ6.9 Hz, 3H, 3H-13); 13C NMR
850.3 MHz) d 198.5, 176.1, 170.3, 159.7, 129.4 8C, C-3,
C-12, CH3CO2±, C-5, C-4), 68.6 8CH, C-8), 51.8 8CH3,
±OCH3), 44.9 8CH2, C-9), 43.2, 41.8 8CH, C-7, C-11),
37.3 8CH2, C-1), 35.3 8C, C-10), 33.2, 27.7 8CH2, C-2,
C-6), 24.1, 21.2, 15.5, 10.7 8CH3, C-14, CH3CO2±, C-13,
C-15).
22
and 530mg 888%) of compound 4d: oil; [a]D ˆ1185.08 c
0.70) [lit.9 [a]Dˆ1200]; MS 8CI) m/z 249 8M111, 100),
248 8M1, 20), 220 86), 175 85); IR 8NaCl) nmax 1778, 1700,
1305 cm21; 1H NMR 8200 MHz) d 4.82 8br. d, Jˆ10.6 Hz,
1H, H-6), 3.20±3.10 8m, 1H, H-1), 2.65 8dd, Jˆ6.6,
19.1 Hz, 1H, H-2), 2.29 8dq, Jˆ6.9, 11.5 Hz, 1H, H-11),
2.25±1.92 8m, 3H, H-20, H-7, H-10), 1.86 8s, 3H, 3H-15),
1.24 8d, Jˆ6.9 Hz, 3H, 3H-13), 0.66 8d, Jˆ7.2 Hz, 3H, 3H-
14); 13C NMR 850.3 MHz) d 207.7, 177.5, 164.0, 142.2 8C,
C-3, C-12, C-5, C-4), 81.7, 48.8, 44.3, 41.3 8CH, C-6, C-7,
C-1, C-11), 40.7, 35.1 8CH2, C-2, C-9), 34.9 8CH, C-10),
3.2.8. Compound 5a. 85%; mp 50±518C 8hexane±EtOAc)
22
[lit.10 mp 50±528C]; [a]D ˆ0 8c 1.16); IR 8KBr) nmax 1730,
1700, 1630 cm21; 1H NMR 8200 MHz) d 4.06±4.02 8m, 1H,
H-1), 3.66 8s, 3H, ±OMe), 2.67 8br. d, Jˆ19 Hz, 1H, H-6),
24.8 8CH2, C-8), 12.2, 12.2, 9.08CH , C-13, C-14, C-15).
3

9724
G. Blay et al. / Tetrahedron 57 /2001) 9719±9725
3.2.12. -11S)-3-Oxo-1,7,10aH-guai-4-en-12-oic acid -5d).
By the same general procedure used in the synthesis of
3a±3g and 5a±5c, compound 4d 8380mg, 1.53 mmol)
gave 330mg 886%) of acid 5d: mp 124±1258C 8hexane±
EtOAc) [lit.9 mp 136±136.58C 8hexane±isopropyl ether)];
stirring continued for 18 h. The solid was ®ltered off through
silica gel 8EtOAc), the solvent removed under vacuum and
the residue chromatographed with 7:3±5:5 mixtures of
hexane±EtOAc to give 125 mg 880%) of compound 10:
19
oil; [a]D ˆ1142.08 c 1.0); HRMS 8CI) m/z 237 8M111,
[a]D ˆ1141.1 8c 1.80); HRMS 8CI) m/z 250.1567 8M1,
100), 236.1782 8M1, 56, C15H24O2 required 236.1776), 218
848), 176 820); IR 8NaCl) nmax 3500±3300, 1692, 1627,
17
44, C15H22O3 required 250.1570), 248 86), 177 8100), 176
813); IR 8KBr) nmax 3200±2600, 1736, 1689, 1616 cm21; 1H
NMR 8400 MHz) d 3.14±3.08 8m, 1H, H-1), 2.70 8br. d,
Jˆ19.2 Hz, 1H, H-6), 2.57 8dd, Jˆ6.4, 18.8 Hz, 1H, H-2),
2.52 8dq, Jˆ4.8, 7.2 Hz, 1H, H-11), 2.408dd, Jˆ12.0,
19.2 Hz, 1H, H-60), 2.15±2.08 8m, 2H, H-7, H-10), 2.04
8br. d, Jˆ18.8 Hz, 1H, H-20), 1.81 8br. ddd, Jˆ4.0, 6.8,
1043 cm21
;
1H NMR 8400 MHz) d 3.58 8dd, Jˆ7.6,
10.8 Hz, 1H, H-12), 3.52 8dd, Jˆ6.4, 10.8 Hz, 1H, H-120),
3.14±3.08 8m, 1H, H-1), 2.62 8br. d, Jˆ19.6 Hz, 1H, H-6),
2.54 8ddd, Jˆ1.2, 6.8, 18.8 Hz, 1H, H-2), 2.408dd, Jˆ12.4,
19.6 Hz, 1H, H-60), 2.11±2.06 8m, 1H, H-10), 2.01 8dd,
Jˆ2.0, 18.8 Hz, 1H, H-20), 1.91 8dddd, Jˆ2.8, 3.2, 10.8,
12.4 Hz, 1H, H-7), 1.84±1.78 8m, 1H, H-9), 1.76±1.60
8m, 3H, H-8, H-90, H-11), 1.64 8d, Jˆ1.2 Hz, 3H, 3H-15),
1.27 8dddd, Jˆ3.6, 10.8, 13.6, 14.0 Hz, 1H, H-80), 0.88 8d,
Jˆ6.8 Hz, 3H, 3H-13), 0.60 8d, Jˆ7.2 Hz, 3H, 3H-14); 13C
NMR 850.3 MHz) d 208.5, 176.1, 137.4 8C, C-3, C-5, C-4),
65.8 8CH2, C-12), 45.8, 42.1 8CH, C-1, C-11), 41.3, 37.3
8CH2, C-2, C-9), 37.1 8CH, C-7), 36.7 8CH2, C-6), 35.4 8CH,
C-10), 26.5 8CH2, C-8), 12.1, 11.9, 7.9 8CH3, C-13, C-14,
C-15).
0
14.0Hz, 1H, H-9), 1.72±1.66 8m, 2H, H-8, H-9 ), 1.64 8s,
3H, 3H-15), 1.39 8ddt, Jˆ3.2, 10.8, 14.0 Hz, 1H, H-80), 1.19
8d, Jˆ7.2 Hz, 3H, 3H-13), 0.60 8d, Jˆ6.8, 3H, 3H-14); 13C
NMR 850.3 MHz) d 208.8, 180.5, 175.4, 137.1 8C, C-3,
C-12, C-5, C-4), 45.8, 45.3 8CH, C-1, C-11), 41.08CH ,
2
C-2), 38.6 8CH, C-7), 36.5, 36.3 8CH2, C-6, C-9), 35.1
8CH, C-10), 27.9 8CH2, C-8), 12.2, 11.9, 7.9 8CH3, C-13,
C-14, C-15).
3.2.13. Methyl -11S)-3-oxo-1,7,10aH-guai-4-en-12-oate
-8). To a solution of compound 5d 8330mg, 1.32 mmol)
in CH2Cl2 was added ethereal diazomethane in excess and
the reaction mixture was stirred for 1 h. After solvent
removal, the residue was chromatographed 88:2 hexane±
EtOAc) to yield 279 mg 880%) of methyl ester 8 as a colour-
3.2.15. -11S)-12-o-Nitrophenylselenyl-1,7,10aH-guai-4-
en-3-one -11). To a suspension of compound 10 852 mg,
0.22 mmol) and o-nitrophenylselenocyanate 8122 mg,
0.53 mmol) in THF 82.7 mL) at rt and under argon, was
added via syringe n-Bu3P 8175 mL, 0.682 mmol). After
1 h, the resulting solution was separated from a yellow
precipitate which was washed with ether. The organic
solvents were removed under reduced pressure and the
residue was chromatographed on silica gel 87:3 hexane±
EtOAc) to give 85 mg 892%) of compound 11 as a yellow
oil, IR 8NaCl) nmax 1685, 1625, 1585, 1560, 1505,
18
less oil with the following features: [a]D ˆ1175.5 8c
0.77); HRMS 8CI) m/z 265 8M111, 27), 264.1725 8M1,
95, C16H24O3 required 264.1725), 232 836), 178 860), 176
1
8100); IR 8NaCl) nmax 1730, 1690, 1630 cm21; H NMR
8400 MHz) d 3.68 8s, 3H, ±OCH3), 3.12±3.06 8m, 1H,
H-1), 2.64 8br. d, Jˆ19.6 Hz, 1H, H-6), 2.54 8dd, Jˆ6.4,
19.2 Hz, 1H, H-2), 2.47 8dq, Jˆ5.2, 7.2 Hz, 1H, H-11), 2.34
8br. dd, Jˆ12.8, 19.6 Hz, 1H, H-60), 2.11±2.04 8m, 2H, H-7,
H-10), 2.01 8d, Jˆ19.2 Hz, 1H, H-20), 1.79 8ddd, Jˆ4.0, 7.6,
1
1330cm 21; H NMR 8200 MHz) d 8.25 8d, Jˆ8.4 Hz, 1H,
Ar-H), 7.50±7.48 8m, 2H, 2Ar-H), 7.32±7.28 8m,1 H,
Ar-H), 3.10±3.00 8m, 1H, H-1), 2.96 8dd, Jˆ6.6, 11.7 Hz,
1H, H-12), 2.81 8td, Jˆ7.3, 11.7 Hz, 1H, H-120), 2.61 8br. d,
Jˆ19.7 Hz, 1H, H-6), 2.51 8dd, Jˆ6.4, 18.3 Hz, 1H, H-2),
2.39 8dd, Jˆ11.7, 19.5 Hz, 1H, H-60), 1.62 8br. s, 3H,
3H-15), 1.00 8d, Jˆ6.6 Hz, 3H, 3H-13), 0.59 8d, Jˆ
6.6 Hz, 3H, 3H-14); 13C NMR 850.3 MHz) d 208.1,
174.8, 137.6, 146.9 8C, C-3, C-5, C-4, Ar), 133.5 8CH,
Ar), 133.2 8C, Ar), 129.0, 126.4, 125.3 8CH, Ar), 45.7
8CH, C-1), 41.2 8CH2, C-2), 40.6, 38.7 8CH, C-11, C-7),
37.0, 36.0 8CH2, C-6, C-9), 35.2 8CH, C-10), 31.6, 26.4
8CH2, C-12, C-8), 15.9, 12.0, 8.0 8CH3, C-13, C-14,
C-15).
0
14.0Hz, 1H, H-9), 1.71±1.65 8m, 2H, H-8, H-9 ), 1.63 8br.
s, 3H, 3H-15), 1.38±1.28 8m, 1H, H-80), 1.16 8d, Jˆ7.2 Hz,
3H, 3H-13), 0.59 8d, Jˆ7.2 Hz, 3H, 3H-14); 13C NMR
850.3 MHz) d 208.0, 175.7, 174.4, 137.6 8C, C-3, C-12,
C-5, C-4), 51.5 8CH3, ±OCH3), 45.6, 45.3 8CH, C-1,
C-11), 41.1 8CH2, C-2), 38.9 8CH, C-7), 36.3 8CH2, C-6,
C-9), 35.1 8CH, C-10), 28.0 8CH2, C-8), 12.6, 11.9, 7.8
8CH3, C-13, C-14, C-15).
3.2.14. -11S)-3-Oxo-1,7,10aH-guai-4-en-12-ol -10). To a
suspension of LiAlH4 8150mg, 3.97 mmol) in dry 35 mL of
THF cooled at 08C under argon was added via syringe a
solution of compound 8 8175 mg, 0.66 mmol) in 4 mL of
THF. The reaction mixture was stirred for 15 min and
quenched at 08C with saturated aqueous NH4Cl. The
mixture was extracted with ether and dried on anhydrous
Na2SO4 and the solvent removed under vacuum to afford
a mixture of epimeric diols 9 [1H NMR 8200 MHz) d
4.65±4.408two m, H-3), 3.70±3.35 8two m, 2H-12)] as
an oil which was used in the following step without
puri®cation.
3.2.16. 1,7,10aH-Guai-4,11-dien-3-one -6). A solution of
compound 11 839 mg, 0.09 mmol) in THF 82.4 mL) at 08C
was treated with 30% H2O2 8230 mL) and after removal of
the ice bath the temperature was allowed to rise to rt. The
reaction mixture was stirred for 4.5 h, diluted with EtOAc
and extracted in the usual way. Chromatography of the
residue with 8:2 hexane±EtOAc eluted 19 mg 895%) of
compound 6 as an oil which presented the following
23
24
features: [a]D ˆ1157.1 8c 0.84) [lit.12 [a]D ˆ163 8c
0.23)]; HRMS 8CI) m/z 219 8M111, 100), 218.1620 8M1,
15, C15H22O required 218.1670), 163 85), 161 83), 109 83);
To a solution of diols 9 in CHCl3 88.7 mL, ®ltered through
basic alumina) was added MnO2 8745 mg, 7.94 mmol) and
the mixture was stirred at rt. After 6 h an additional portion
of MnO2 8745 mg, 7.94 mmol) was added and vigorous
IR 8NaCl) nmax 1693, 1630cm 21; H NMR 8400 MHz) d
4.73 8br. s, 1H, H-12), 4.68 8br. s, 1H, H-120), 3.14±3.08 8m,
1H, H-1), 2.75 8br. d, Jˆ19.2 Hz, 1H, H-6), 2.57 8dd, Jˆ6.4,
1

G. Blay et al. / Tetrahedron 57 /2001) 9719±9725
9725
18.8 Hz, 1H, H-2), 2.47 8br. dd, Jˆ12.0, 19.2 Hz, 1H, H-60),
References
2.31 8br. dd, Jˆ10.8, 12.0 Hz, 1H, H-7), 2.12±2.07 8m, 1H,
H-10), 2.03 8d, Jˆ18.8 Hz, 1H, H-20), 1.85±1.808m, 1H,
H-9), 1.75 8br. s, 3H, 3H-15), 1.77±1.68 8m, 2H, H-8, H-90),
1. Fraga, B. M. Nat. Prod. Rep. 1999, 16, 21 and earlier reports in
the series.
0
1.64 8br. s, 3H, 3H-13), 1.64±1.508m, 1H, H-8 ), 0.63 8d,
2. Connolly, J. D.; Hill, R. A. Dictionary of Terpenoids; Mono-
and Sesquiterpenoids; Vol. 1; Chapman & Hall: London,
1991.
Jˆ7.2 Hz, 3H, 3H-14); 13C NMR 850.3 MHz) d 208.1,
175.2, 150.8, 137.5 8C, C-3, C-5, C-11, C-4), 108.8 8CH2,
C-12), 45.9, 44.4 8CH, C-1, C-7), 41.2, 37.9, 36.6 8CH2, C-2,
C-6, C-9), 35.3 8CH, C-10), 31.2 8CH2, C-8), 20.0, 12.0, 7.9
8CH3, C-13, C-14, C-15).
3. 8a) Heathcock, C. H. The Total Synthesis of Natural Products;
Apsimon, J., Ed.; Wiley Interscience: New York, 1973; Vol. 2,
pp. 197±558. 8b) Heathcock, C. H.; Graham, S. L.; Pirrung,
M. C.; Plavac, F.; White, C. T. The Total Synthesis of Natural
Products; Apsimon, J., Ed.; Wiley Interscience: New York,
1983; Vol. 5. 8c) Pirrung, M. C. The Total Synthesis of Natural
Products; Goldsmith, D., Ed.; Wiley Interscience: New York,
2000; Vol. 11.
3.2.17. 3-Oxo-1,7,10aH-guai-4-en-11-ol -hydrocolorenone)
-7). To a solution of compound 6 819 mg, 0.087 mmol) in
0.54 mL of 1:1 THF±H2O mixture were added 29 mg
80.09 mmol) of Hg8OAc)2 and the mixture was stirred at rt
for 30min. To quench the reaction it was ®rst diluted with
ether 80.27 mL), cooled to 08C and it was added dropwise
3 M NaOH 80.1 mL) and 0.5 M aqueous NaBH4 80.1 mg)
and 69 mg of NaCl. The resulting mixture was vigorously
stirred at 08C for 10min diluted with ether and water and
extracted in the usual way. Chromatography with 1:1
hexane±EtOAc as eluent afforded 19 mg 891%) of
compound 7 as an oil with the following features:
Â
4. Blay, G.; Cardona, L.; Garcõa, B.; Pedro, J. R. Studies in
Natural Products Chemistry; Atta-ur-Rahman, I. O., Ed.;
Elsevier Science: Amsterdam, 2000; Vol. 24, pp. 53±129.
5. Piers, E.; Cheng, K. F. Can. J. Chem. 1968, 46, 377±383.
Â
6. Marco, J. A.; Arno, M.; Carda, M. Can. J. Chem. 1987, 65,
630±635.
7. Blay, G.; Fernandez, I.; Garcõa, B.; Pedro, J. R. Tetrahedron
Â
Â
1989, 45, 5925±5934.
8. Bargues, V.; Blay, G.; Garcia, B.; Garcia, C. L.; Pedro, J. R.
Tetrahedron 1995, 51, 5609±5616.
9. BuÈchi, G.; Kauffman, J. M.; Loewenthal, H. J. E. J. Am. Chem
Soc. 1966, 88, 3403±3408.
 Â
10. Francisco, C. G.; Freire, R.; Rodrõguez, M. S.; Suarez, E.
21
[a]D ˆ1103.8 8c 0.79) [lit.13 [a]Dˆ158.6 8c 0.46); lit.14
24
[a]D ˆ118 8c 0.2)]; HRMS 8CI) m/z 237.1857 8M111, 88,
C15H25O2 required 237.1885), 219 8100), 218 835), 177 811),
1
163 823); IR 8KBr) nmax 3500±3300, 1681, 1625 cm21; H
NMR 8400 MHz, CDCl3) d 3.12±3.06 8m, 1H, H-1), 3.07
8br. d, Jˆ19.6 Hz, 1H, H-6), 2.54 8ddd, Jˆ1.2, 6.4, 18.4 Hz,
1H, H-2), 2.18 8br. dd, Jˆ12.4, 19.6 Hz, 1H, H-60), 2.12±
2.09 8m, 1H, H-10), 2.03 8br. d, Jˆ18.4 Hz, 1H, H-20),
1.93±1.87 8m, 1H, H-8), 1.86±1.81 8m, 1H, H-9), 1.71±
1.64 8m, 2H, H-7, H-90), 1.66 8d, Jˆ1.2 Hz, 3H, 3H-15),
1.28±1.23 8m, 1H, H-80), 1.26 8s, 3H, 3H-12), 1.21 8s, 3H,
3H-13), 0.61 8d, Jˆ7.2 Hz, 3H, 3H-14); 1H NMR
8400 MHz, CD3COCD3) d 3.16±3.12 8m, 1H, H-1), 3.14
8br. d, Jˆ19.5 Hz, 1H, H-6), 2.46 8ddd, Jˆ1.2, 6.6,
18.3 Hz, 1H, H-2), 2.24 8br. dd, Jˆ11.6, 19.5 Hz, 1H,
H-60), 2.15±2.07 8m, 1H, H-10), 1.96±1.89 8m, 1H, H-8),
1.92 8ddd, Jˆ1.2, 1.8, 18.6 Hz, 1H, H-20), 1.83 8dddd,
Jˆ3.0, 3.6, 4.5, 13.7 Hz, 1H, H-9), 1.73 8dddd, Jˆ3.0,
3.6, 10.2, 13.6 Hz, 1H, H-90), 1.72±1.64 8m, 1H, H-7),
1.508q, Jˆ1.5 Hz, 3H, 3H-15), 1.34±1.25 8m, 1H, H-80),
1.21 8s, 3H, 3H-12), 1.17 8s, 3H, 3H-13), 0.62 8d, Jˆ6.9 Hz,
3H, 3H-14); 13C NMR 850.3 MHz, CDCl3) d 208.4, 175.4,
137.8, 73.1 8C, C-3, C-5, C-4, C-11), 48.0, 45.7 8CH, C-7,
C-1), 41.3, 36.8 8CH2, C-2, C-9), 35.3 8CH, C-10), 33.7,
27.1 8CH2, C-6, C-8), 27.4, 26.0, 12.2, 8.0 8CH3, C-12,
C-13, C-14, C-15); 13C NMR 875.4 MHz, CD3COCD3) d
206.3, 175.0, 137.1, 71.8 8C, C-3, C-5, C-4, C-11), 48.3,
45.4 8CH, C-7, C-1), 41.1, 37.08CH 2, C-2, C-9), 35.8
8CH, C-10), 33.7, 27.1 8CH2, C-6, C-8), 26.8, 25.7, 11.8,
7.3 8CH3, C-12, C-13, C-14, C-15).
Tetrahedron Lett. 1991, 32, 3413±3416.
11. Bargues, V.; Blay, G.; Cardona, L.; Garcõa, B.; Pedro, J. R.
Â
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Financial support from Direccion General de Investigacion
Cientõ®ca y Tecnica 8PB-94-0985) is gratefully acknowl-
edged. One of us 8V.B.) is especially thankful to Conselleria
 Á
de Cultura, Eduacio i Ciencia 8Generalitat Valenciana) for a
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grant.