Enantioselective synthesis and determination of the absolute configuration of natural (-)-elegansidiol

Article abstract of DOI:10.1002/1099-0690(200106)2001:12<2293::AID-EJOC2293>3.0.CO;2-E

The enantioselective synthesis and determination of the absolute configuration of the title compound (-)-1 has been carried out starting from karahana lactone (+)-2 as an enantiopure building block. The structure was confirmed by single crystal X-ray diff

Full text of DOI:10.1002/1099-0690(200106)2001:12<2293::AID-EJOC2293>3.0.CO;2-E

FULL PAPER
Enantioselective Synthesis and Determination of the Absolute Configuration of
Natural (؊)-Elegansidiol
[a]
[a]
[a]
´
´
Gerard Audran, Jean-Marie Galano, and Honore Monti*
Keywords: Asymmetric synthesis / Configuration determination / Domino reactions / Natural products
The enantioselective synthesis and determination of the ab- ure building block. The structure was confirmed by single
solute configuration of the title compound (−)-1 has been car-
ried out starting from karahana lactone (+)-2 as an enantiop-
crystal X-ray diffraction analysis and the optical purity of (−)-
(1S,3R)-elegansidiol (−)-1 verified by chiral HPLC.
In 1999, Barrero et al.[1] isolated a new sesquiterpene, ele-
gansidiol (Ϫ)-1 {cis-3-[(E)-5-hydroxy-3-methyl-3-pentenyl]-
2,2-dimethyl-4-methylenecyclohexanol} (Figure 1), from
the hexane extracts of the aerial parts of Santolina elegans.
They established its structure on the basis of its spectro-
scopic properties and confirmed the structural assignments
by a racemic chemical synthesis, although the absolute con-
figuration of (Ϫ)-elegansidiol {[α]D ϭ Ϫ4.0 (c ϭ 1,
CHCl3)}, still remained unknown.
Figure 1. Structure of (Ϫ)-elegansidiol, (Ϫ)-1
We describe herein the first straightforward enantioselec-
tive synthesis of (Ϫ)-1 based on an original approach and
starting from an enantiopure building block for the intro-
duction and determination of the absolute stereochemistry.
Our methodology is outlined in Scheme 1.
We recently reported the synthesis of the required start-
ing enantiopure building block, (1R,5S)-8,8-dimethyl-2-
methylene-6-oxabicyclo[3.2.1]octan-7-one, (ϩ)-2 (karahana
lactone).[2] Reduction of (ϩ)-2 with diisobutylaluminum hy-
dride in toluene formed a 4:1 mixture of diastereomeric lac-
tols 3 (1:1) and aldehyde 4 in 95% yield. Numerous ex-
amples where the HornerϪWadsworthϪEmmons (HWE)
reaction is used for the coupling of β-ketophosphonates
with aldehydes have been reported, and various modifica-
tions have been developed.[3] Among them, the barium-hy-
droxide-promoted HWE reaction is a mild and efficient
method for epimerizable, base-sensitive aldehydes.[3e] This
procedure, applied to the isomeric (3 ϩ 4) mixture, using
the barium derivative of diethyl 2-oxopropylphosphonate in
THF at room temperature, afforded 92% of a 4:1 mixture
Scheme 1. Reagents and conditions: (a) Dibal-H, toluene, Ϫ70 °C,
95%; (b) (EtO)2P(O)CH2COMe, Ba(OH)2, THF, room temp., 92%;
(c) Ac2O, PPTS, toluene, reflux, 81%; (d) HSnBu3, Pd(PPh3)4,
ZnCl2, THF, room temp., 88%; (e) (i) CH2ϭCHMgBr, THF, Ϫ20
°C; (ii) Ac2O, Et3N, DMAP, THF, reflux, 85%; (f) Cl2PdII(-
MeCN)2, THF, room temp., 95%; (g) (i) K2CO3, MeOH, room
temp., quant.; (ii) recrystallization from Et2O/petroleum ether
of (5 ϩ 5Ј) as the only products resulting from the intramo-
lecular domino[4] oxa-conjugate addition of the hydroxyl
group to the intermediate enone system generated by the
HWE reaction. As shown in Scheme 2, in the aa/ee con-
formations of the intermediate HWE products (not isol-
ated), once the hydroxyl group and enone system are juxta-
posed in the synaxial disposition, the rate of the Michael-
initiated ring closure is, for entropic reasons, very high and
the equilibrium very favorable to the highly stabilized bicyc-
[a]
´
´
´
Laboratoire de Reactivite Organique Selective, UMR CNRS
6516,
´
´ ˆ
Faculte des Sciences et Techniques de St-Jerome-13397
Marseille cedex 20 France
Fax: (internat.) ϩ 33-491/288-862
E-mail: honore.monti@ros.u-3mrs.fr
Eur. J. Org. Chem. 2001, 2293Ϫ2296
WILEY-VCH Verlag GmbH, 69451 Weinheim, 2001
1434Ϫ193X/01/0612Ϫ2293 $ 17.50ϩ.50/0
2293

G. Audran, J.-M. Galano, H. Monti
FULL PAPER
lic compounds 5 and 5Ј. When a lower temperature was ray diffraction analysis[11] and the high optical purity of
applied (0 °C for 24 h), no HWE reaction occurred.
(Ϫ)-(1S, 3R)-1 was verified by HPLC (Figure 2).
Scheme 2. Conformations of the intermediate HWE reaction prod-
ucts (not isolated) and cyclized (5 ϩ 5Ј)
The stereochemistry of 5 and 5Ј were assigned as depicted
in Scheme 2 by the magnitude of the vicinal coupling con-
1
stants based on the Karplus relationship in the H NMR
spectrum. The torsional angle (Dreiding models) is ca. 45°
between 1-H and 7-H in 5 [J(1-H/7-H) ϭ 3.5 Hz) and ca. 90°
in 5Ј [J(1-H/7-H) ϭ 1.8 Hz). In support of these assignments,
the NOESY plots were characterized by a strong cross-peak
between H7 and Meeq (δ ϭ 1.10) in 5.
Figure 2. ORTEP view of (Ϫ)-1 (the ellipsoids are drawn at the
30% probability level) and chiral HPLC diagrams of rac-1 and (Ϫ)-
1 (conditions of analyses in Exp. Section).
Acetylation of (5 ϩ 5Ј) by heating under reflux with
acetic anhydride and PPTS produced crystalline (ϩ)-6 (m.p.
76 °C) as a single E stereoisomer (3Jtrans ϭ 15.9 Hz) in 81%
yield by an irreversible retro-Michael addition process.[5]
The conjugate reduction of α,β-unsaturated carbonyl com-
pounds is an active area of organic synthesis and the ar-
senal of relevant synthetic tools has been strikingly en-
riched.[6] After several attempts, the best chemoselective
1,4-conjugate reduction of the α,β-enone system of (ϩ)-6
was achieved with Bu3SnH/palladium catalyst in the pres-
ence of anhydrous ZnCl2 as the reducing system[7] to afford
an 88% yield of solid (ϩ)-7 (m.p. 40 °C). Subsequent expo-
sure of (ϩ)-7 to vinylmagnesium bromide and treatment of
the crude alcohols with acetic anhydride/triethylamine in
the presence of DMAP (dimethylaminopyridine) yielded
85% of diastereomeric diacetates 8. Soluble palladium(II)
salts are effective catalysts in promoting the highly E-stereo-
selective rearrangement of tertiary allylic acetates.[8] Treat-
ment of acetates 8 with dichlorobis(acetonitrile)palladiu-
m(II),[9] afforded diacetate (ϩ)-9 (95% yield, a 94:6 E/Z
In conclusion, an asymmetric synthesis of (Ϫ)-elegansi-
diol has been achieved, and the absolute configuration de-
termined, using (ϩ)-karahana lactone as the source of chir-
ality. The merits of this synthesis are high-yielding reaction
steps and secured absolute stereochemistry. The nonnatural
enantiomer (ϩ)-1 can be synthesized from the available (Ϫ)-
karahana lactone[2] following the reaction sequence de-
tailed above.
Experimental Section
1
General: H and 13C NMR spectra were recorded in CDCl3 solu-
tion on a Bruker AM-400, Bruker AM-300 or Bruker AM-200
spectrometer. Infrared spectra were obtained as films or KBr pellets
using a PerkinϪElmer 1600 FTIR spectrophotometer. Routine
monitoring of reactions was performed using Merck Silica gel 60
mixture, by GLC analysis). Treatment of (ϩ)-9 with excess F254, aluminum-supported TLC plates. Column chromatography
was performed with silica gel 60 (230Ϫ400 mesh) and gradients of
pentane/ether as eluent, unless otherwise stated. GC analyses were
carried out on a Chrompack 9001 equipped with a WCOT fused-
silica column (25 m ϫ 0.32 mm i.d.; CP-Wax-52 CB stationary
phase; N2 carrier gas: 50 kPa). HPLC experiments were performed
at 29 °C with a Merck-Hitachi LiChrograph model L-6000 HPLC
pump and L-4000 UV detector operating at 221 nm, and a Merck
D-2500 recorder. The chiral separation was performed using a com-
mercial column from Daisel: CHIRALCEL OD-H (250 ϫ
4.6 mm; 10 µm) with hexane/iPrOH (98:2 v/v) and a flow rate of
K2CO3 in methanol at room temperature caused cleavage
of the acetates and produced elegansidiol (Ϫ)-1 quantitat-
ively as a white solid (a 94:6 E/Z mixture, by GLC analysis).
Two successive recrystallizations from Et2O/petroleum
ether furnished pure elegansidiol (Ϫ)-1 {m.p. 82 °C, [α]D25
ϭ
1
Ϫ14.8 (c ϭ 1.0, CHCl3)}. The IR, H and 13C NMR spec-
tra of our synthetic sample were in complete agreement
with those of the literature.[1] However, the crystalline na-
ture of (Ϫ)-elegansidiol has not been reported,[1,10] con-
sequently the structure was secured by a single crystal X- 1 mL/min. Optical rotations were measured on a PerkinϪElmer
2294 Eur. J. Org. Chem. 2001, 2293Ϫ2296

The Synthesis and Absolute Configuration of Natural (Ϫ)-Elegansidiol
FULL PAPER
341 polarimeter. Microanalyses were performed at our University. and Ac2O (956 mg, 9.36 mmol) in toluene (10 mL) was treated with
Melting points are uncorrected. Unless otherwise stated, solutions PPTS (235 mg, 0.94 mmol) and heated at 110 °C for 7 h. After
were dried over magnesium sulfate and the solvents evaporated in
a rotary evaporator under reduced pressure.
being cooled to 25 °C, the reaction mixture was diluted with Et2O,
washed with aqueous NaHCO3 and brine, and dried (MgSO4).
After concentration, flash chromatography gave (ϩ)-6 (633 mg,
81% yield) as colorless crystals, m.p. 76 °C, [α]2D5 ϭ ϩ22.9 (c ϭ 1.0,
8,8-dimethyl-2-methylene-6-oxabicyclo[3.2.1]octan-7-ol (3) and 3-hy-
droxy-2,2-dimethyl-6-methylenecyclohexanecarbaldehyde (4):
A
CHCl3). Ϫ IR (KBr): ν˜ ϭ 3087, 3018, 1734, 1665, 1237, 909 cmϪ1
.
600 mg portion (3.60 mmol) of (ϩ)-2 was dissolved in 40 mL of
anhydrous toluene, and a 1  toluene solution of diisobutylalumi-
num hydride (7.2 mL, 7.20 mmol) was added dropwise at Ϫ70 °C
under an argon atmosphere. The reaction mixture was stirred for
45 minutes at this temperature, quenched with Na2SO4·10H2O (4 g)
and celite (5 g), and allowed to rise to room temp. Filtration
through a pad of MgSO4, concentration, and purification by flash
chromatography gave, in the same spot, a 1:1:0.5 mixture (1H NMR
determination) of lactols 3 and aldehyde 4 as a clear oil (577 mg,
95% yield). Ϫ IR (neat): ν˜ ϭ 3400, 3068, 1715, 1652, 1023, 928
1
Ϫ H NMR (200 MHz, CDCl3): δ ϭ 0.90 (s, 6 H), 1.63Ϫ1.76 (m,
1 H), 1.78Ϫ1.91 (m, 1 H), 2.07 (s, 3 H), 2.10Ϫ2.25 (m, 1 H), 2.27
(s, 3 H), 2.34Ϫ2.47 (m, 1 H), 2.64 (d, J ϭ 9.6 Hz, 1 H), 4.60 (s, 3
H), 4.72 (dd, J ϭ 8.7, 3.6 Hz, 1 H), 4.87 (s, 3 H), 6.08 (d, J ϭ
15.9 Hz, 1 H), 6.97 (dd, J ϭ 15.9, 9.6 Hz, 1 H). Ϫ 13C NMR
(50 MHz, CDCl3): δ ϭ 197.8 (C), 170.3 (C), 145.9 (C), 145.4 (CH),
132.9 (CH), 111.0 (CH2), 77.7 (CH), 55.8 (CH), 38.9 (C), 31.1
(CH2), 27.5 (CH2), 27.2 (CH3), 26.2 (CH3), 21.1 (CH3), 17.8 (CH3).
Ϫ C15H22O3 (250.16): calcd. C 71.97, H 8.86; found C 71.69, H
8.89.
1
cmϪ1. Ϫ H NMR (200 MHz, CDCl3): δ ϭ 0.91 (s, 6 H, 3), 0.98
(s, 3 H, 4), 1.13 (s, 6 H, 3 and 4), 1.33 (s, 3 H, 3), 1.55Ϫ1.95 (m, 3
H, 3 and 4), 2.10Ϫ2.45 (m, 6 H, 3 and 4), 2.50Ϫ2.70 (m, 6 H, 3
and 4), 2.78 (d, J ϭ 3.3 Hz, 1 H, 4), 3.40Ϫ3.52 (m, 1 H, 4), 3.86
(d, J ϭ 3.2 Hz, 1 H, 3), 4.06 (broad s, 1 H, 3), 4.64 (s, 1 H, 3), 4.72
(s, 1 H, 3), 4.74 (s, 1 H, 3), 4.80 (s, 1 H, 4), 4.95 (s, 1 H, 3), 5.03
(s, 1 H, 4), 5.33 (d, J ϭ 4.8 Hz, 1 H, 3), 5.64 (dd, J ϭ 7.4, 3.8 Hz,
1 H, 3), 9.75 (d, J ϭ 3.3 Hz, 1 H, 4). Ϫ 13C NMR (50 MHz,
CDCl3): δ ϭ 202.5 (C, 4), 146.1 (C, 3), 144.8 (C, 3), 141.7 (C, 4),
113.8 (CH2, 4), 112.1 (CH2, 3), 109.0 (CH2, 3), 101.1 (CH, 3), 98.8
(CH, 3), 85.4 (CH, 3), 83.6 (CH, 3), 78.9 (CH, 4), 65.9 (CH, 4),
60.3 (CH, 3), 57.9 (CH, 3), 42.8 (C, 3), 41.0 (C, 3), 39.8 (C, 4), 29.9
(CH2, 4), 27.5 (CH2, 4), 27.2 (CH2, 3), 26.9 (CH2, 3), 26.8 (CH3,
3), 26.5 (CH3, 4), 26.2 (CH2, 3), 26.1 (CH2, 3), 25.8 (CH3, 3), 21.9
(CH3, 3), 21.6 (CH3, 3). This mixture was used for the next reaction
without further purification.
(1S,3R)-2,2-dimethyl-4-methylene-3-(3-oxobutyl)cyclohexyl Acetate
(؉)-7: Tributyltin hydride (1.05 g, 3.60 mmol) was added to a solu-
tion of (ϩ)-6 (600 mg, 2.40 mmol), ZnCl2 (490 mg, 3.60 mmol),
and Pd(PPh3)4 (56 mg, 0.05 mmol) in dry THF (10 mL) at 25 °C
under an argon atmosphere. After stirring for 15 min., the reaction
mixture was concentrated and the residue purified by flash chroma-
tography to give (ϩ)-7 (533 mg, 88% yield) as a whitish solid, m.p.
40 °C, [α]2D5 ϭ ϩ21.7 (c ϭ 1.0, CHCl3). Ϫ IR (KBr): ν˜ ϭ 3081,
1740, 1715, 1646, 1243, 1029, 897 cmϪ1. Ϫ 1H NMR (200 MHz,
CDCl3): δ ϭ 0.83 (s, 3 H), 0.96 (s, 3 H), 1.49Ϫ2.05 (m, 6 H), 2.05
(s, 3 H), 2.10 (s, 3 H), 2.15Ϫ2.35 (m, 2 H), 2.40Ϫ2.59 (m, 1 H),
4.55 (s, 3 H), 4.66 (dd, J ϭ 7.7, 3.9 Hz, 1 H), 4.87 (s, 3 H). Ϫ 13C
NMR (50 MHz, CDCl3): δ ϭ 208.8 (C), 170.4 (C), 146.5 (C), 109.6
(CH2), 77.9 (CH), 51.6 (CH), 42.5 (CH2), 38.9 (C), 30.3 (CH2),
29.9 (CH3), 28.3 (CH2), 26.2 (CH3), 21.1 (CH3), 19.7 (CH2), 18.5
(CH3). Ϫ C15H24O3 (252.17): calcd. C 71.39, H 9.52; found C
71.71, H 9.48.
1-(8,8-dimethyl-2-methylene-6-oxabicyclo[3.2.1]oct-7-yl)acetone (5)
and (5Ј): A mixture of diethyl 2-oxopropylphosphonate (1.32 g,
6.79 mmol) and Ba(OH)2·8H2O (855 mg, 2.71 mmol, heated at 140
°C for 2 h under a flux of argon before use) in THF (6 mL) was
stirred at room temp. for 30 min. under an argon atmosphere. A
solution of (3 ϩ 4; 570 mg, 3.39 mmol) in wet THF (6 mL, 40:1
THF/H2O) was then added at this temperature. After being stirred
for 24 h, the reaction mixture was diluted with CH2Cl2, and washed
with aqueous NaHCO3 and brine. The organic extract was dried
(MgSO4), filtered, and concentrated. Purification by flash chroma-
tography gave an inseparable mixture of diastereomers 5 and 5Ј
1-{2-[3-(acetyloxy)-2,2-methyl-6-methylenecyclohexyl]ethyl}-1-
methylprop-2-enyl Acetate 8: To a solution of (ϩ)-7 (500 mg,
1.98 mmol) in THF (5 mL) at Ϫ20 °C under an argon atmosphere,
was added dropwise vinylmagnesium bromide (1  in THF, 3 mL,
3.0 mmol). The mixture was stirred at Ϫ20 °C for 15 min., allowed
to warm to 0 °C and the resulting orange solution then quenched
with aqueous NH4Cl. After warming to 25 °C, the reaction mixture
was extracted with Et2O. The organic layer was dried (MgSO4),
and concentrated to give the crude allylic alcohols as a yellow oil,
which was utilized for the next step without further purification.
The solution of allylic alcohols in THF (5 mL) was treated with
Et3N (610 mg, 6.0 mmol), DMAP (50 mg, 0.4 mmol), Ac2O
(615 mg, 6.0 mmol), and heated under reflux for 24 h. After being
cooled to 25 °C, the reaction mixture was diluted with Et2O,
washed with aqueous NaHCO3 and brine, and dried (MgSO4).
Concentration and purification by flash chromatography gave an
inseparable mixture of diastereomers 8 as a colorless oil (543 mg,
85% yield from 7). Ϫ IR (neat): ν˜ ϭ 3087, 1740, 1652, 1250, 1023,
˜
(4:1) as a colorless oil (650 mg, 92% yield). Ϫ IR (neat): ν ϭ 3068,
1722, 1652, 1067, 1043, 925 cmϪ1. Ϫ 1H NMR (200 MHz, CDCl3):
δ ϭ 0.86 (s, 6 H, 5 and 5Ј), 1.10 (s, 3 H, 5), 1.12 (s, 3 H, 5Ј),
1.46Ϫ1.79 (m, 4 H, 5 and 5Ј), 2.11 (s, 3 H, 5), 2.13 (s, 3 H, 5Ј), 2.17
(d, J ϭ 1.8 Hz, 1 H, 5Ј), 2.21 (d, J ϭ 3.5 Hz, 1 H, 5), 1.95Ϫ2.40 (m,
4 H, 5 and 5Ј), 2.47 and 2.73 (ABX, J ϭ 17.0, 7.0, 6.3 Hz, 2 H, 5),
2.62 and 2.92 (ABX, J ϭ 16.0, 7.9, 6.3 Hz, 2 H, 5Ј), 3.74 (broad d,
J ϭ 2.7 Hz, 2 H, 5 and 5Ј), 4.38 (broad t, J ϭ 6.6 Hz, 1 H, 5Ј),
4.51Ϫ4.59 (m partially overlapped, 1 H, 5), 4.54 (m partially over-
lapped, 2 H, 5 and 5Ј), 4.74 (m, 2 H, 5 and 5Ј). Ϫ 13C NMR
(50 MHz, CDCl3): δ ϭ 207.2 (C, 5), 145.8 (C, 5), 111.6 (CH2, 5),
107.4 (CH2, 5Ј), 83.7 (CH, 5Ј), 82.7 (CH, 5), 78.1 (CH, 5Ј), 74.6
(CH, 5), 58.6 (CH, 5Ј), 56.8 (CH, 5), 50.3 (CH2, 5Ј), 45.2 (CH2, 5),
42.1 (C, 5), 30.7 (CH3, 5), 30.5 (CH3, 5Ј), 27.9 (CH2, 5Ј), 27.2 (CH3,
5Ј), 27.1 (CH2, 5), 25.6 (CH2, 5), 25.5 (CH3, 5), 25.5 (CH2, 5Ј),
22.1 (CH3, 5Ј), 21.9 (CH3, 5). Ϫ C13H20O2 (208.15, 5 ϩ 5Ј mixture):
calcd. C 74.96, H 9.68; found C 75.25, H 9.71.
1
889 cmϪ1. Ϫ H NMR (200 MHz, CDCl3): δ ϭ 0.80 (s, 3 H), 0.95
(s, 3 H), 1.53 (s, 3 H), 1.50Ϫ2.10 (m, 8 H), 2.01 (s, 3 H), 2.05 (s, 3
H), 2.15Ϫ2.35 (m, 1 H), 4.61 (s, 1 H), 4.67 (dd, J ϭ 8.3, 3.9 Hz, 1
H), 4.88 (s, 1 H), 5.12 (d, J ϭ 11.0 Hz, 1 H), 5.13 (d, J ϭ 17.1 Hz,
1 H), 5.95 (dd, J ϭ 17.1, 11.0 Hz, 1 H), 5.96 (dd, J ϭ 17.1, 11.0 Hz,
1 H, minor). Ϫ 13C NMR (50 MHz, CDCl3): δ ϭ 170.5 (C), 169.9
(C), 146.6 (C), 141.9 (CH), 113.1 (CH2), 113.0 (CH2, minor), 109.5
(CH2), 83.2 (C, minor), 83.1 (C, major), 78.4 (CH), 52.4 (CH, ma-
jor), 52.3 (CH, minor), 39.2 (C), 39.0 (CH2), 31.1 (CH2), 28.5
(CH2), 26.1 (vinylic CH3, major), 23.6 (CH3), 23.4 (vinylic CH3,
(1S,3R)-2,2-dimethyl-4-methylene-3-[(1E)-3-oxobut-1-enyl]cyclo-
hexyl Acetate (؉)-6: A solution of (5 ϩ 5Ј; 650 mg, 3.12 mmol)
Eur. J. Org. Chem. 2001, 2293Ϫ2296
2295

G. Audran, J.-M. Galano, H. Monti
minor), 22.1 (CH3), 21.2 (CH3), 19.5 (CH2), 18.0 (CH3). This mix- 1478.4(2) A , Z ϭ 4, 1666 independent reflections, 1148 with I Ն
FULL PAPER
3
˚
ture did not give correct analytical data.
3σ(I); R(on F) ϭ 0.081; Rw ϭ 0.064.
(1S,3R)3-[(3E)-4-(acetyloxy)-3-methylbut-3-enyl]-2,2-dimethyl-
4-methylenecyclohexyl Acetate 9: To a solution of (ϩ)-8 (500 mg,
1.55 mmol) in dry THF (5 mL) at 25 °C under an argon atmo-
sphere was added dichlorobis(acetonitrile)palladium(II) (10 mg,
0.04 mmol). The reaction was monitored by GLC and, upon con-
sumption of the starting material (2 h), the solution mixture was
filtered through a pad of silica gel, and concentrated to give a yel-
low oil. This oil was purified by flash chromatography to give (ϩ)-
9 as a colorless oil (475 mg, 95% yield, a 94:6 E/Z mixture, by GLC
analysis). Ϫ [α]2D5 ϭ ϩ12.0 (c ϭ 1.0, CHCl3). Ϫ IR (neat): ν˜ ϭ
3081, 1734, 1646, 1244, 1020, 890 cmϪ1. Ϫ 1H NMR (200 MHz,
CDCl3): δ ϭ 0.78 (s, 3 H), 0.93 (s, 3 H), 1.67 (s, 3 H), 2.03 (s, 3
H), 1.50Ϫ2.15 (m, 7 H), 2.24Ϫ2.35 (m, 1 H), 4.56 (d, J ϭ 6.9 Hz,
1 H), 4.65 (dd, J ϭ 8.6, 4.0 Hz, 1 H), 4.58 (s, 1 H), 4.87 (s, 1 H),
5.30 (t, J ϭ 6.9 Hz, 1 H). Ϫ 13C NMR (50 MHz, CDCl3): δ ϭ
171.1 (C), 170.6 (C), 146.5 (C), 142.4 (C), 119.4 (CH, minor), 118.3
(CH, major), 109.4 (CH2), 78.4 (CH), 61.3 (CH2), 51.4 (CH), 39.1
(C), 38.2 (CH2), 31.2 (CH2), 30.7 (CH2, minor), 29.6 (CH2, minor),
28.5 (CH2), 26.1 (vinylic CH3), 26.0 (vinylic CH3, minor), 23.8
(CH2, minor), 23.5 (CH2), 21.2 (CH3), 21.0 (CH3), 17.9 (CH3), 16.4
(CH3). Ϫ C19H30O4 (322.21; E/Z mixture): calcd. C 70.77, H 9.38;
found C 71.04, H 9.35.
Acknowledgments
We are thankful to Prof. C. Roussel (ENSSPICAM, Marseilles) for
chiral HPLC analysis performed in his laboratory.
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T.-L. Ho, Tandem Organic Reactions, Wiley, New-York,
1992. Reviews: [4b] L. F. Tietze, Chem. Rev. 1996, 96, 115Ϫ136.
Ϫ
[4c]
[4d]
R. A. Bunce, Tetrahedron 1995, 51, 13103Ϫ13159. Ϫ
J. Rodriguez, Synlett 1999, 505Ϫ518.
I. T. Harrison, R. Grayshan, T. Williams, A. Semenovski, J. H.
Fried, Tetrahedron Lett. 1972, 13, 5151Ϫ5154.
[5]
[6]
(1S,3S)-3-[(3E)-5-hydroxy-3-methylpent-3-enyl]-2,2-dimethyl-4-
methylenecyclohexanol, Elegansidiol (Ϫ)-1: A solution of (ϩ)-9
(400 mg, 1.24 mmol) in MeOH (2 mL) at 25 °C was treated with
K2CO3 (1.60 g, 12.40 mmol) and stirred for 24 h. The mixture was
concentrated to remove MeOH, diluted with Et2O, filtered and
concentrated. Purification by flash chromatography gave (Ϫ)-1 as
a white solid (296 mg, quantitative yield, a 94:6 E/Z mixture, by
GLC analysis). After two successive recrystallizations from Et2O/
petroleum ether, pure elegansidiol (Ϫ)-1 (GLC analysis) was ob-
tained as white crystals, m.p. 82 °C, [α]2D5 ϭ Ϫ14.8 (c ϭ 1.0, CHCl3).
R. C. Larock, Comprehensive Organic Transformations, Wiley-
VCH, New York, 1999, chapter 1, p. 15Ϫ19.
[7] [7a]
P. Four, F. Guibe, Tetrahedron Lett. 1982, 23, 1825Ϫ1828.
[7b]
Ϫ
Y. T. Xian, P. Four, F. Guibe, G. Balavoine, Nouv. J.
Chim. 1984, 8, 611Ϫ614.
[8] [8a]
J. Tsuji, Palladium Reagents and Catalysts, John Wiley &
[8b]
Sons, Chichester, 1999, p. 399Ϫ404. Reviews:
R. P. Lutz,
L. E. Overman, Angew.
Chem. Int. Ed. Engl. 1984, 23, 579Ϫ587.
[8c]
Chem. Rev. 1984, 84, 205Ϫ247. Ϫ
[9] [9a]
L. E. Overman, F. M. Knoll, Tetrahedron Lett. 1979, 20,
Ϫ IR (KBr): ν ϭ 3521, 3288, 3075, 1646, 1016, 890 cmϪ1. Ϫ 1H
˜
[9b]
321Ϫ324. Ϫ
L. E. Overman, F. M. Knoll, J. Am. Chem.
NMR (400 MHz, CDCl3): δ ϭ 0.71 (s, 3 H), 1.01 (s, 3 H),
1.44Ϫ1.56 (m, 2 H), 1.56Ϫ1.64 (m, 2 H partially overlapped), 1.66
(s, 3 H), 1.77Ϫ1.87 (m, 2 H), 1.94Ϫ2.01 (m, 1 H), 2.09Ϫ2.15 (m,
1 H), 2.29Ϫ2.35 (dt, J ϭ 13.1, 4.8 Hz, 1 H), 3.40 (dd, J ϭ 9.6,
4.0 Hz, 1 H), 4.11 (d, J ϭ 7.1 Hz, 1 H), 4.58 (broad s, 1 H), 4.86
(broad s, 1 H), 5.38 (broad t, J ϭ 6.8 Hz, 1 H). Ϫ 13C NMR
(75 MHz, CDCl3): δ ϭ 147.1 (C), 140.2 (C), 123.1 (CH), 108.5
(CH2), 77.2 (CH), 59.4 (CH2), 51.2 (CH), 40.5 (C), 38.5 (CH2),
32.8 (CH2), 32.1 (CH2,), 25.9 (CH3), 23.6 (CH2), 16.3 (CH3), 15.7
(CH3). Ϫ C15H26O2 (238.19): calcd. C 75.58, H 10.99; found C
75.33, H 11.02.
Soc. 1980, 102, 865Ϫ867.
[10]
[11]
Unfortunately, we were unable to obtain an authentic sample
of (Ϫ)-1. The difference observed in the numerical value of the
specific rotation (Ϫ14.0 versus Ϫ4.0) seems to imply that nat-
ural (Ϫ)-elegansidiol is partially racemic.
Crystallographic data (excluding structure factors) for (Ϫ)-ele-
gansidiol, (Ϫ)-1 have been deposited with the Cambridge Crys-
tallographic Data Centre as supplementary publication no.
CCDC-153743. Copies of the data can be obtained free of
charge on application to CCDC, 12 Union Road, Cambridge
CB2 1EZ, UK [Fax: (internat.) ϩ 44-1223/336-033; E-mail:
deposit@ccdc.cam.ac.uk].
Crystallographic Data for (؊)-1: Orthorhombic crystals, space
Received December 11, 2000
˚
group P21212, a ϭ 13.836(1), b ϭ 17.630(1), c ϭ 6.0609(3) A, V ϭ
[O00634]
2296
Eur. J. Org. Chem. 2001, 2293Ϫ2296