Synthesis of (+)-amberketal and its analog from l-abietic acid

Article abstract of DOI:10.1016/j.tet.2007.06.063

(+)-Amberketal (1) and its analog (2) have been synthesized from commercially available l-abietic acid (3) by a selective reduction of an unsaturated aldehyde in the presence of a ketone and simultaneous reduction of an iodide using an aqueous suspension of Raney Ni as the key step.

Full text of DOI:10.1016/j.tet.2007.06.063

Tetrahedron 63 (2007) 9896–9902
Synthesis of (D)-amberketal and its analog from L-abietic acid
*
J. S. Yadav, Gakul Baishya and Uttam Dash
Division of Organic Chemistry, Indian Institute of Chemical Technology, Hyderabad-500007, Andhra Pradesh, India
Received 5 March 2007; revised 1 June 2007; accepted 21 June 2007
Available online 27 June 2007
Abstract—(+)-Amberketal (1) and its analog (2) have been synthesized from commercially available L-abietic acid (3) by a selective reduc-
tion of an unsaturated aldehyde in the presence of a ketone and simultaneous reduction of an iodide using an aqueous suspension of Raney Ni
as the key step.
Ó 2007 Published by Elsevier Ltd.
16
1. Introduction
12
15
11
20
17
13
14
Ambergris, the most important animal perfume aside from
civet, musk, and castreum, has been particularly used in per-
fume industry since ancient times for its unique fragrance
and fixative properties.1 The concretion formed in the intes-
tinal tract of the blue sperm whale, after one to three years of
aging smells of amber odor, which is used in perfumery in
the form of an infusion in alcohol. The high price of amber-
gris and enforced whale protection has encouraged chemists
to search for commercially viable synthetic substitutes.2 (+)-
Amberketal 1 is one of the most important synthetic equiv-
alents to the scarce natural ambergris source, which possess
a strong and tenacious ambergris-type odor.1a The natural
chiral pool of precursors for the synthesis of amberketal in-
clude manool,3 sclareol,4 communic acid,5 and anticopalic
acid.6
1
4
2
9
6
O
O
O
8
O
10
5
3
7
H
COOH
19
H
H
18
3
1
2
Figure 1.
O
O
OH
2
1
H
H
11
15
Several ambergris-type odorants have been synthesized
from commercially available L-abietic acid by different
research groups.7–10 Herein we report the synthesis of (+)-
amberketal and its analog by using commercially available
L-abietic acid as a starting material(Fig. 1).
OH
OH
C
A
B
H
R
H
COOH
The retrosynthetic analysis (Fig. 2) describes the oxidative
degradation of the C-ring of either iodo abietane 5 or tosylate
8 of abietol, regioselective construction of a C-8 exocyclic
double bond, and subsequent conversion of isopropyl ketone
to methyl ketone leading to the exact chiral synthon 15 of
(+)-amberketal 1.
5 R = I
8 R = OTs
3
Figure 2. Retrosynthetic analysis.
2. Results and discussion
The synthesis began with the conversion of abietic acid to
abietol 4 using LiAlH4 in THF at room temperature in
85% yield. Treatment of 4 with triphenyl phosphine–iodine–
imidazole in toluene at room temperature11 gave iodo abie-
tane 5 in 6% yield. When the reaction was performed at
Keywords: L-Abietic acid; Regioselective dihydroxylation; d,3-Epoxy-
ketone cyclization; (+)-Amberketal.
* Corresponding author. Fax: +91 40 27160512; e-mail: yadavpub@iict.
res.in
0040–4020/$ - see front matter Ó 2007 Published by Elsevier Ltd.
doi:10.1016/j.tet.2007.06.063

J. S. Yadav et al. / Tetrahedron 63 (2007) 9896–9902
9897
70 ꢀC, the formation of two inseparable side products along
with the iodo abietane were observed in TLC. The crude ma-
terial obtained after filtration through a small pad of silica
gel column was directly subjected to regioselective dihy-
droxylation with a catalytic amount of osmic acid (OsO4,
Me3NO$2H2O, t-BuOH–py–H2O, reflux, 48 h).8 This reac-
tion furnished a diastereomeric mixture of the diol 6 in a ratio
of 7:3 (b/a) (determined from their isolated yield) in 25%
yield for the two steps. Different solvent systems such as
acetone/water (N-methyl morpholine N-oxide as co-oxidant)
and PEG 40012 (Me3NO$2H2O as co-oxidant) were also
studied for the OsO4 catalyzed regioselective dihydroxyl-
ation. However, the starting iodo abietane was recovered
without even a trace of the diol 6. The oxidative cleavage
of the mixture of diol 6 was performed using NaIO4 in
an ethanol–water mixture (4:1) at room temperature,
which resulted in the formation of the key intermediate
of our strategy, the conjugate aldehyde 7, in 70% yield
(Scheme 1).10
The structure of the alcohol 11 was established by 1H NMR
and 13C NMR. The disappearance of the olefinic proton, al-
dehydic proton, and CH2–I protons and the appearance of
characteristic peaks at 3.52 ppm (triplet), 3.61 ppm (dou-
blet) for –CH2OH protons and at 0.81 ppm for the new
1
–CH3 group in H NMR spectrum confirmed the structure
of 11. Our next aim was to construct the exo-olefin at C-8
position and transform the isopropyl ketone into a methyl
ketone. The alcohol 11 was converted to its tosylate (88%)
with p-toluenesulfonyl chloride in pyridine at 0 ꢀC for
12 h.14 The tosylate 12 was treated with m-CPBA in
CH2Cl2 at reflux temperature to afford the isopropyl ester
1
13 in 68% yield.15 The H NMR spectra of ester 13 shows
the characteristic peak at 4.92 ppm as septet for isopropyl
ester proton. The exo-olefin 14 was prepared in 80% yield
using a reported procedure by the reaction of primary tosyl-
ate with 4 equiv of DBU in refluxing toluene for 24 h. The
exo-olefin 14 was treated with Tebbe’s reagent to afford the
methyl ketone 15, the synthon for (+)-amberketal synthesis
in 82% yield. The synthon 15 was converted to (+)-amberke-
tal 1 in 60% yield by treatment with a catalytic amount of
OsO4 in refluxing t-BuOH–H2O–pyridine mixture with tri-
methylamine N-oxide as co-oxidant (Scheme 3).4 (+)-Am-
berketal 1 was also prepared in two steps, i.e., epoxidation
with m-CPBA/aq NaHCO3 followed by d,3-epoxyketone
cyclization with ZnCl2 at 18 ꢀC.6 All the physical and spec-
troscopic data of the compound 1 are comparable with the
data reported in the literature.4
To improve the overall yield of the aldehyde 7 from abietic
acid, abietol 4 was tosylated with p-TsCl in pyridine at 0 ꢀC
to afford the tosylate derivative 8 in 84% yield, which on
subjecting to regioselective dihydroxylation afforded diol
9 in 48% yield as a 9:1 (b/a) mixture. The mixture of the
diol 9 was then subjected to the oxidative cleavage with
NaIO4 in ethanol and water (4:1) to afford the aldehyde 10
as a single product in 85% yield. The displacement of the to-
syl group in 10 by iodide was achieved in 50% yield using
excess NaI in DMF at 90 ꢀC for 12 h along with 20% yield
of an unidentified product (Scheme 2). The aldehyde 7
was obtained in similar overall yield (14.87 and 14.73%)
from L-abietic acid in the both Schemes 1 and 2, respectively.
In order to get the amberketal analog 2 the alcohol 11 was
treated with Tf2O in CH2Cl2 using pyridine as a base to pro-
duce the triflate derivative, which on subsequent treatment
with 3 equiv of DBU at room temperature afforded the
keto-olefin 16. The keto-olefin 16 was also obtained from
the tosylate 12 by the treatment with 4 equiv of DBU in re-
fluxing toluene. The epoxidation of 16 with m-CPBA/aq
NaHCO3 gave only a-epoxide 17 (95% yield) diastereose-
lectively, which under d,3-epoxyketone cyclization with
ZnCl2 at 18 ꢀC resulted in the amberketal analog 2 (75%
yield).6 The keto-olefin 16 was also converted to the analog
The selective reduction of both the conjugated double bond
and the aldehyde group in the presence of ketone group as
described by Barrero et al.13 and simultaneous removal of
iodo group was successfully achieved in a single step using
aqueous suspension of Raney Ni in THF at room tempera-
ture to afford the saturated primary alcohol 11 in 86% yield.
O
OH
OH
CHO
d
a
b
c
H
I
H
I
H
H
H
COOH
3
OH
I
7
5
4
6
Scheme 1. Reagents and conditions: (a) LiAlH4, THF, 0 ꢀC–rt, 3 h, 85%; (b) I2, imidazole, Ph3P, toluene, 70 ꢀC; (c) cat OsO4, Me3NO$2H2O, t-BuOH–H2O–
pyridine, reflux, 48 h, 25% in two steps; (d) NaIO4, EtOH–H2O, rt, 1.5 h, 70%.
O
O
OH
OH
c
CHO
CHO
d
a
b
H
OTs
H
I
H
OTs
10
H
OTs
H
OH
9
7
8
4
Scheme 2. Reagents and conditions: (a) p-TsCl, pyridine, 0 ꢀC, 12 h, 84%; (b) cat OsO4, Me3NO$2H2O, t-BuOH–H2O–pyridine, reflux, 48 h, 48%; (c) NaIO4,
EtOH–H2O, rt, 1.5 h, 85%; (d) excess NaI, DMF, 90 ꢀC, 12 h, 50%.

9898
J. S. Yadav et al. / Tetrahedron 63 (2007) 9896–9902
O
O
O
O
O
CHO
a
OTs
OTs
OH
b
c
H
H
H
H
I
12
13
11
7
O
O
O
O
O
d
ref 4 or 6
e
H
H
H
1
15
14
Scheme 3. Reagents and conditions: (a) Raney Ni, THF, rt, 20 h, 86%; (b) p-TsCl, pyridine, 0 ꢀC, 12 h, 88%; (c) m-CPBA, CH2Cl2, reflux, 24 h, 68%; (d) DBU,
toluene, reflux, 24 h, 88%; (e) Tebbe’s reagent, ꢁ10 ꢀC, 2 h, 82%.
2 by treatment with a catalytic amount of OsO4 in refluxing
t-BuOH–H2O–pyridine mixture with trimethylamine
N-oxide as co-oxidant (Scheme 4).4
shifts being given in parts per million with respect to internal
TMS and J values quoted in hertz. Mass spectra were re-
corded on micromass Quatro LC triple quadrapole mass
spectrometer for ESI analysis. All reaction mixtures were
stirred magnetically and were monitored by TLC using
0.25 mm E-Merck silica gel 60 F254 pre-coated glass plates,
which were visualized with UV light and then developed by
using iodine mixed with silica gel 60–120 mesh. (N.B. Car-
bon numbers are not according to IUPAC rule and they are
maintained unchanged through out all compounds.)
O
O
O
OTs
OH
b
a
H
H
H
12
16
c
e
11
O
4.1.1. Abiet-7,13-dien-18-ol (4). To a stirred solution of
L-abietic acid (6 g, 19.83 mmol) in dry THF (200 mL) was
added LiAlH4 (1.5 g, 2 equiv, 39.67 mmol) portion wise at
0 ꢀC for 30 min. Then the reaction mixture was stirred at
room temperature under nitrogen for 2.5 h. After completion
of the reaction as monitored by TLC, the reaction mass was
slowly poured into a beaker containing 20 g wet Na2SO4
with continuous stirring until the formation of a white pre-
cipitate. Then the solution was filtered and the filtrate was
concentrated under reduced pressure and purified by a silica
gel column (20:80 EtOAc–hexane as eluant) to give pure
abietol 4 (4.85 g) in 85% yield as a white solid. Rf¼0.61
(SiO2, 30% EtOAc in hexane); mp 79–81 ꢀC, [a]D25 ꢁ131.8
(c 1.1, CHCl3); IR (KBr): n 3340, 2925, 1463, 1380, 1030,
884 cmꢁ1; dH (200 MHz, CDCl3) 0.82 (3 H, s, 10-Me),
0.86 (3H, s, 4-Me), 0.99 and 1.02 (6H, 2d, J 3.0 Hz, 15-
Me2), 1.19–1.45 (4H, m), 1.49–1.62 (3H, m), 1.75–1.88
(3H, m), 1.95–2.05 (4H, m), 2.20 (1H, septet, J 6.8 Hz,
15-H), 3.07 and 3.32 (2H, 2d, J 10.5, 18-H), 5.32 (1H, m,
7-H), 5.70 (1H, s, 14-H); Mass (ESI): m/z 289 [M+H]+,
305 [M+Na]+; HRMS (ESI): calcd for C20H33O 289.2531
[M+H]+ and found 289.2522
O
O
d
O
H
17
H
2
Scheme 4. Reagents and conditions: (a) i. Tf2O, pyridine, CH2Cl2, 0 ꢀC–rt,
2 h, ii. DBU, CH2Cl2, rt, 3 h, 84% in two steps; (b) DBU, toluene, reflux,
24 h, 80%; (c) m-CPBA, CH2Cl2, 3 h, rt, 95%; (d) ZnCl2, CH2Cl2, 18 ꢀC,
14 h, 75%; (e) cat OsO4, Me3NO$2H2O, t-BuOH–H2O–pyridine, reflux,
48 h, 73%.
3. Conclusion
In conclusion, we have used L-abietic acid for the first time to
synthesize (+)-amberketal 1 in 10 steps (overall yield
3.31%) and its analog 2 with less ambergris tincture in 8
steps (overall yield 7.95%).
4. Experimental
4.1. General
4.1.2. 18-Iodo abiet-7,13-diene (5). To a stirred solution of
abieta-7,13-dien-18-ol 4 (1 g) in dry toluene (20 mL) tri-
phenyl phosphine (2.7 g, 3 equiv, 10.4 mmol) and iodine
(2.8 g, 3.2 equiv, 11.1 mmol) were added successively at
room temperature and stirred for 10 min followed by the
addition of imidazole (1.4 g, 6 equiv, 20.8 mmol). The reac-
tion mixture was allowed to stir for 1 h at room temperature
and the solid obtained after the reaction was filtered off and
the filtrate was evaporated and purified by column chroma-
tography eluting with hexane to afford pure iodide 5
(85 mg, 6% yield) as a liquid. To increase the yield, the
All commercial chemicals were used without further purifi-
cation. All solvents were purified by standard techniques.
Melting points were recorded on a Buchi R-535 apparatus
and are uncorrected. IR spectra were recorded on a Perkin–
Elmer 683 spectrophotometer using KBr optics. Optical rota-
tions were obtained on Jasco Dip 360 digital polarimeter. 1H
NMR and 13C NMR spectra were recorded on Gemini 200,
Bruker Avance 300 MHz, and Unity 400 MHz spectrometers
in CDCl3 using TMS as internal standard, with chemical

J. S. Yadav et al. / Tetrahedron 63 (2007) 9896–9902
9899
reaction mixture with same ratio of reactants was stirred at
70 ꢀC for 20 min and the same purification method was
applied to get the iodo derivative 5 (800 mg) that was di-
rectly charged for the next reaction. Rf¼0.9 (SiO2, hexane);
[a]2D5 ꢁ37.4 (c 0.8, CHCl3); IR (KBr): n 2923, 2854, 1647,
1459, 1378, 1021, 761 cmꢁ1; dH (200 MHz, CDCl3) 0.80
(3H, s, 10-Me), 0.99 and 1.01 (6H, 2d, J 2.2 Hz, 15-Me2),
1.08 (3H, s, 4-Me), 1.21–1.39 (4H, m), 1.49–1.62 (3H, m),
1.74–2.07 (7H, m), 2.20 (1H, septet, J 6.8 Hz, 15-H), 3.17
(2H, s, 18-H), 5.32 (1H, m, 7-H), 5.71 (1H, s, 14-H); dC
(75 MHz, CDCl3) 13.5, 18.6, 18.9, 20.8, 21.4, 22.7, 23.5,
27.9, 28.5, 34.89, 34.98, 35.3, 38.7, 39.7, 47.0, 50.7, 120.4
122.4, 135.5, 145.3.
stirred for 1.5 h at room temperature. After removing the sol-
vent under vacuum, the crude product was dissolved in
EtOAc (15 mL), washed with water (10 mL), dried over an-
hydrous Na2SO4, filtered and concentrated. The concentrate
was purified by a silica gel column (20:80 EtOAc–hexane) to
afford the pure aldehyde 7 (246 mg, 70%) as colorless oil.
Rf¼0.39 (SiO2, 20% EtOAc in hexane); [a]2D5 +32.2 (c
0.75, CHCl3); IR (KBr): n 2965, 2927, 1712, 1687, 1632,
1461, 1382, 1186, 1010, 702 cmꢁ1; dH (200 MHz, CDCl3)
0.82 (3H, s, 10-Me), 1.09 (3H, s, 4-Me), 1.10 (6H, d,
J 3.0 Hz, 15-Me2), 1.37 (2H, s), 1.28–1.41 (2H, m), 1.42–
1.58 (3H, m) 1.79–2.10 (3H, m), 2.16–2.24 (2H, m), 2.28–
2.44 (1H, m), 2.60 (1H, septet, J 6.8 Hz, 15-H), 3.09 (3H,
m), 6.72 (1H, m, 7-H), 9.35 (1H, s, –CHO); dC (75 MHz,
CDCl3) d 13.6, 18.0, 18.1, 18.2, 18.8, 21.0, 24.5, 26.8,
35.2, 36.7, 38.0, 39.1, 40.6, 42.4, 46.0, 50.1, 144.3, 151.6,
194.6, 215.1; Mass (ESI): m/z 431 [M+H]+, 453 [M+Na]+;
HRMS (ESI): calcd for C20H31I NaO2 [M+Na]+ 453.1266
and found 453.1269.
4.1.3. 13,14-Dihydroxy 18-iodo abietane (6b and 6a). To
a stirred solution of the crude iodo derivative 5 (800 mg,
2.0 mmol) in a t-BuOH (8 mL) and water (2 mL) mixture
was added OsO4 (2.5 mL of 0.2 wt % in t-BuOH,
0.01 equiv), Me3NO$2H2O, (670 mg, 3 equiv, 6.0 mmol)
and pyridine (0.3 mL). The reaction mixture was then heated
at reflux for 48 h. After completion of the reaction (as mon-
itored by TLC), it was cooled to room temperature and
treated with a 20% aq solution of NaHSO3 (30 mL) and con-
centrated under vacuum to remove t-BuOH, saturated with
NaCl (3 g) and extracted with diethyl ether (4ꢂ100 mL).
The combined organic layer was dried over anhydrous
Na2SO4, concentrated and purified by column chromato-
graphy (20:80 EtOAc–hexane) to afford the mixture of
13,14-dihydroxy 18-iodo-abietanes 6b and 6a in 7:3 ratio
(377 mg, 25% yield in two steps starting from 4) as a yellow
semisolid. The two diols 6b and 6a were separated by
column chromatography eluting with 15% EtOAc–hexane
and their individual spectral data were given.
4.1.5. Abiet-7,13-dien-18-yl p-toluenesulfonate (8). To
a solution of the alcohol 4 (3 g, 10.41 mmol) in freshly dis-
tilled pyridine (30 mL) was added freshly recrystalized
p-TsCl (2.57 g, 13.54 mmol, 1.3 equiv) at 0 ꢀC and the reac-
tion was stirred for 12 h at 0 ꢀC under a nitrogen atmosphere.
After removing the pyridine under vacuum, the crude mate-
rial was diluted with water (10 mL) and Et2O (50 mL), and
washed with 4% HCl (aq) solution (2ꢂ20 mL). The ether
layer was dried over anhydrous Na2SO4, filtered and concen-
trated. The concentrate was purified by a silica gel column
(5:95 EtOAc–hexane as eluant) to give pure tosylate 8
(3.9 g) in 84% yield as a gummy liquid. Rf¼0.6 (SiO2,
20% EtOAc in hexane); [a]2D5 ꢁ47.6 (c 1.1, CHCl3); IR
(KBr): n 2940, 2923, 2852, 1603, 1484, 1479, 1180, 1101,
975, 821 cmꢁ1; dH (300 MHz, CDCl3) 0.80 (3H, s, 10-
Me), 0.91 (3H, s, 4-Me), 1.02 and 1.05 (6H, 2d, J 1.2 Hz,
15-Me2), 1.19–1.29 (3H, m), 1.37–1.55 (5H, m), 1.74–1.88
(4H, m), 2.05 (2H, d, J 5.9 Hz), 2.23 (1H, septet, J 6.8 Hz,
15-H), 2.49 (3H, s, –OSO2Ph-p-Me), 3.48 and 3.60 (2H,
2d, J 9.3 Hz, 18-H), 5.23 (1H, m, 7-H), 5.71 (1H, s, 14-H),
7.32 (2H, d, J 7.6 Hz, Ar-H), 7.74 (2H, d, J 8.0 Hz, Ar-H);
dC (100 MHz, CDCl3) 13.9, 17.2, 17.7, 20.7, 21.2, 21.5,
22.4, 23.5, 27.2, 34.5, 34.7, 35.5, 36.6, 38.2, 43.4, 50.4,
77.9, 120.0, 122.2, 127.7 (2C), 129.6 (2C), 132.7, 135.2,
144.4, 145.0; Mass (ESI): m/z 443 [M+H]+, 465 [M+Na]+;
HRMS (ESI): calcd for C27H38NaO3S [M+Na]+ 465.2439
and 465.2435.
4.1.3.1. 13b,14b-Dihydroxy 18-iodo abietane (6b).
Rf¼0.36 (SiO2, 20% EtOAc in hexane); [a]2D5 ꢁ25.2 (c
0.6, CHCl3); IR (KBr): n 3445, 2928, 2868, 1712, 1659,
1443, 1382, 1021, 762 cmꢁ1; dH (200 MHz, CDCl3) 0.86
(3H, s, 10-Me), 0.89 and 0.92 (6H, 2d, J 7.1 Hz, 15-Me2),
0.98 (1H, m), 1.09 (3H, s, 4-Me), 1.21–1.56 (7H, m),
1.64–1.92 (5H, m), 2.02–2.21 (2H, m), 3.19 (2H, s, 18-H),
3.94 (1H, m, 14-H), 5.87 (1H, m, 7-H); dC (75 MHz,
CDCl3) 15.2, 16.5, 18.0, 18.7, 19.6 (2C), 22.9, 26.5, 28.9,
33.2, 35.3, 35.8, 39.69, 39.75, 46.7, 51.1, 73.4, 76.5,
120.0, 138.0. Mass (ESI): m/z 455 [M+Na]+; HRMS (ESI):
calcd for C20H33I NaO2 [M+Na]+ 455.1423 and found
455.1424.
4.1.3.2. 13a,14a-Dihydroxy 18-iodo abietane (6a).
Rf¼0.25 (SiO2, 20% EtOAc in hexane); [a]2D5 ꢁ15.4 (c
0.7, CHCl3); dH (200 MHz, CDCl3) 0.82 (3H, s, 10-Me),
0.87 and 0.90 (6H, 2d, J 2.7 Hz, 15-Me2), 0.96 (1H, m),
1.05 (3H, s, 4-Me), 1.10–1.32 (3H, m), 1.40–1.60 (5H,
m), 1.62–1.81 (4H, m), 1.84–1.98 (2H, m), 2.10–2.20 (2H,
m), 3.15 and 3.23 (2H, 2d, J 6.8 Hz, 18-H), 4.02 (1H, s,
14-H), 5.71 (1H, m, 7-H); dC (75 MHz, CDCl3) 14.6, 15.8,
16.0, 18.4, 19.3, 20.2, 23.1, 28.5 (2C), 28.6, 29.6, 35.1,
39.1, 39.7, 46.4, 46.8, 75.0, 76.5, 127.1, 137.9.
4.1.6. 13,14-Dihydroxy abiet-7-en-18-yl p-toluenesulfon-
ate (9b and 9a). To a stirred solution of the tosylate
8 (3 g, 6.787 mmol) in t-BuOH (20 mL) and water
(8 mL) was added OsO4 (8.5 mL of 0.2 wt % in t-BuOH,
0.01 equiv), Me3NO$2H2O (2.26 g, 20.360 mmol, 3 equiv),
and pyridine (1 mL). The reaction mixture was stirred at re-
flux for 48 h. After completion of the reaction (as monitored
by TLC), it was cooled to room temperature and treated with
a 20% aq solution of NaHSO3 (25 mL) and concentrated un-
der vacuum to remove t-BuOH, saturated with NaCl (6 g)
and extracted with diethyl ether (4ꢂ100 mL). The combined
organic layer was dried over anhydrous Na2SO4, concen-
trated, and purified by column chromatography (20:80
EtOAc–hexane as eluant) to afford the mixture of 13,14-
dihydroxy abieta-7-en-18-yl p-toluenesulfonates 9b and
4.1.4. 18-Iodo abiet-7-en-13-one-8-carbaldehyde (7). A
solution of NaIO4 (257 mg, 1.5 equiv, 1.21 mmol) in water
(1 mL) was added to a solution of diol 6 (350 mg,
0.81 mmol) in EtOH (6 mL). The reaction mixture was

9900
J. S. Yadav et al. / Tetrahedron 63 (2007) 9896–9902
9a in a total yield of 48% (1.55 g, 9b:1a ratio) as a white
solid. The two diols 9b and 9a were separated by column
chromatography eluting first with 200 mL of 15% EtOAc–
hexane and then continuing 20% EtOAc–hexane (600 mL)
and their individual spectral data were given.
90 ꢀC, then cooled to room temperature, diluted with water
(50 mL), extracted with Et2O (4ꢂ50 mL). The combined or-
ganic layers were dried over anhydrous Na2SO4, filtered and
concentrated. The concentrate was purified by column chro-
matography (10:90 EtOAc–hexane as eluant) to afford the
pure aldehyde 7 (460 mg, 50%) as colorless oil (spectral
data are same with product obtained in the oxidative cleav-
age of the diol mixture 6).
4.1.6.1. 13b,14b-Dihydroxy abieta-7-en-18-yl p-tolue-
nesulfonate (9b). Rf¼0.2 (SiO2, 30% EtOAc in hexane);
mp 103–105 ꢀC; [a]D25 ꢁ7.8 (c 2.05, CHCl3); IR (KBr):
n 3445, 2925, 2854, 1628, 1459, 1359, 1176, 1097, 1017,
964, 845, 816, 665 cmꢁ1; dH (300 MHz, CDCl3) 0.79 (3H,
s, 10-Me), 0.88 (3H, s, 4-Me), 0.90 and 0.91 (6H, 2d,
J 1.2 Hz, 15-Me2), 1.27–1.39 (9H, m), 1.43–1.56 (2H, m),
1.61–1.74 (2H, m), 1.86 (1H, m), 2.14 (1H, septet, J 6.8 Hz,
15-H), 2.47 (3H, s, –OSO2Ph-p-Me), 3.47 and 3.62 (2H, 2d,
J 9.4 Hz, 18-H), 3.80 (1H, m, 14-H), 5.72 (1H, m, 7-H), 7.30
(2H, d, J 7.9 Hz, Ar-H), 7.71 (2H, d, J 7.9 Hz, Ar-H); dC
(75 MHz, CDCl3) 15.6, 16.2, 17.6, 17.7, 17.8, 19.2, 21.5,
22.8, 26.3, 32.9, 35.2, 35.6, 36.5, 39.0, 42.8, 50.8, 73.0,
76.1, 78.0, 119.5, 127.8 (2C), 129.7 (2C), 132.7, 137.7,
144.6. Mass (ESI): m/z 476 [M]+; HRMS (ESI): calcd for
C27H40NaO5S [M+Na]+ 499.2494 and found 499.2505.
4.1.9. Abiet-13-one-14-ol (11). An aqueous suspension of
Raney Ni (4.25 g) was added to a stirred solution of aldehyde
7 (225 mg, 0.523 mmol) in THF (4 mL) and the mixture was
stirred at room temperature for 20 h. After completion of the
reaction as monitored by TLC, the reaction mixture was di-
luted with Et2O (15 mL), filtered through silica gel, and the
residue was washed with Et2O (3ꢂ15 mL). The filtrate was
evaporated under vacuum and the residue was purified by
column chromatography (10:90/40:60 EtOAc–hexane as
eluant) to afford saturated alcohol 11 (120 mg, 86%) as col-
orless oil. Rf¼0.35 (SiO2, 30% EtOAc in hexane); [a]D25
+36.91 (c 0.5, CHCl3); IR (KBr): n 3443, 2929, 1707,
1630, 1463, 1384, 1273, 1023, 757 cmꢁ1; dH (300 MHz,
CDCl3) 0.71 (3H, s, 10-Me), 0.81 and 0.85 (6H, 2s, 4-
Me2), 1.07 (6H, d, J¼7.1 Hz, 15-Me2), 1.14–1.52 (11H, m)
1.57–1.78 (3H, m), 1.98 (1H, m), 2.29–2.41 (1H, m),
2.44–2.63 (2H, m), 3.52 (1H, t, J 9.8 Hz, 14-H), 3.61 (1H,
d, J 9.8 Hz, 14-H); dC (75 MHz, CDCl3) 15.6, 17.6, 18.2,
18.3, 18.5, 19.6, 21.5, 29.3, 33.2, 33.4, 38.1, 39.1 (2C)
39.7, 40.8, 41.9, 52.8, 56.5, 61.4, 215.3; Mass (ESI): m/z
309 [M+H]+, 331 [M+Na]+; HRMS (ESI): calcd for
C20H36Na O2 [M+Na]+ 331.2613 and found 331.2625.
4.1.6.2. 13a,14a-Dihydroxy abieta-7-en-18-yl p-tolue-
nesulfonate (9a). Rf¼0.12 (SiO2, 30% EtOAc in hexane);
[a]2D5 +1.1 (c 0.75, CHCl3); dH (300 MHz, CDCl3) 0.78
(3H, s, 10-Me), 0.87 (3H, s, 4-Me), 0.89 (6H, s, 15-Me2),
1.20–1.87 (14H, m), 2.10 (1H, m), 2.46 (3H, s, –OSO2Ph-
p-Me), 3.47 and 3.62 (2H, 2d, J 9.4 Hz, 18-H), 3.94 (1H,
s, 14-H), 5.58 (1H, m, 7-H), 7.32 (2H, d, J 7.9 Hz, Ar-H),
7.75 (2H, d, J 7.9 Hz, Ar-H).
4.1.7. 18-(p-Toluenesulfonato) abiet-7-en-13-one-8-carb-
aldehyde (10). A solution of NaIO4 (0.968 g, 4.56 mmol,
1.5 equiv) in water (4 mL) was added to a solution of the
mixture diol 9b and 9a (1.45 g, 3.04 mmol) in EtOH
(16 mL). The reaction mixture was stirred for 1.5 h at
room temperature. After removing the solvent under vac-
uum, the crude product was dissolved in EtOAc (20 mL),
washed with water (20 mL), dried over anhydrous
Na2SO4, filtered and concentrated. The concentrate was pu-
rified by column chromatography (15:85 EtOAc–hexane as
eluant) to afford the pure aldehyde 10 (1.23 g, 85%) as color-
less oil. Rf¼0.31 (SiO2, 30% EtOAc in hexane); [a]2D5 +30.34
(c 0.5, CHCl3); IR (KBr): n 2927, 1687, 1461, 1358, 1176,
1096, 1017, 964, 843, 816, 667 cmꢁ1; dH (200 MHz,
CDCl3) 0.79 (3H, s, 10-Me), 0.89 (3H, s, 4-Me), 1.08 (6H,
d, J 7.0 Hz, 15-Me2), 1.25–1.61 (9H, m), 1.81–1.98 (2H,
m), 2.08–2.18 (1H, m), 2.24–2.43 (1H, m), 2.46 (3H, s,
–OSO2Ph-p-Me), 2.60 (1H, septet, J 6.6 Hz, 15-H), 3.02–
3.20 (1H, m), 3.42 and 3.68 (2H, 2d, J 10.1 Hz, 18-H),
6.63 (1H, m, 7-H), 7.29 (2H, d, J 8.2 Hz, Ar-H), 7.71 (2H,
d, J 8.2 Hz, Ar-H), 9.32 (1H, s, –CHO); dC (75 MHz,
CDCl3) d 14.2, 17.3, 17.4, 18.2, 18.3, 20.8, 21.6, 24.8,
35.3, 36.5, 36.7, 37.8, 40.6, 42.4, 42.6, 49.5, 77.3, 127.8
(2C), 129.8 (2C), 132.8, 144.2, 144.8, 151.7, 194.6, 215.2;
Mass (ESI): m/z 475 [M+H]+; HRMS (ESI): calcd for
C27H38NaO5S [M+Na]+ 497.2337 and found 497.2333.
4.1.10. Abiet-13-one-14-yl p-toluenesulfonate (12). p-TsCl
(80 mg, 0.421 mmol, 1.3 equiv) was added, at 0 ꢀC under
nitrogen, to a solution of alcohol 11 (100 mg, 0.324 mmol)
in freshly distilled pyridine (4 mL), the reaction mixture
was stirred for 12 h at 0 ꢀC under nitrogen. After removing
pyridine under vacuum, the crude material was diluted
with water (10 mL) and Et2O (15 mL), and washed with
4% HCl (aq) solution (20 mL). The ether layer was dried
over anhydrous Na2SO4, filtered, and concentrated. The con-
centrate was purified by a silica gel column (10:90 EtOAc–
hexane as eluant) to give pure tosylate 12 (132 mg) in 88%
yield as a gummy liquid. Rf¼0.76 (SiO2, 30% EtOAc in hex-
ane); [a]2D5 +38.45 (c 0.5, CHCl3); IR (KBr): n 2927, 2856,
1709, 1599, 1461, 1368, 1262, 1175, 1104, 813 cmꢁ1; dH
(300 MHz, CDCl3) 0.65 (3H, s, 10-Me), 0.76 and 0.82
(6H, 2s, 4-Me2), 1.05 and 1.08 (6H, 2d, J 1.1 Hz, 15-Me2),
1.20–1.55 (11H, m), 1.67–1.82 (3H, m), 1.88–1.93 (1H,
m), 2.01–2.05 (1H, m), 2.18–2.28 (1H, m), 2.45–2.57 (2H,
m), 2.46 (3H, s, –OSO2Ph-p-Me), 3.92–4.04 (2H, m, 14-
H), 7.31 (2H, d, J 7.9 Hz, Ar-H), 7.74 (2H, d, J 8.3 Hz,
Ar-H); dC (75 MHz, CDCl3) 15.6, 17.2, 18.1, 18.2, 18.4,
19.2, 21.3, 21.5, 28.8, 33.1, 33.3, 35.6, 37.8, 38.2, 38.8,
40.8, 41.7, 52.0, 56.1, 69.9, 127.7 (2C), 129.7 (2C), 133.2,
144.6, 214.4; Mass (ESI): m/z 463 [M+1]+, 485 [M+Na]+;
HRMS (ESI): calcd for C27H42NaO4S [M+Na]+ 485.2701
and found 485.2700.
4.1.8. 18-Iodo abiet-7-en-13-one-8-carbaldehyde (7). To
a solution of the aldehyde 10 (1.0 g, 2.10 mmol) in dry
DMF (20 mL) was added excess NaI (1.89 g, 12.65 mmol,
6 equiv). The reaction mixture was stirred for 12 h at
4.1.11. Abiet-13-oate-14-yl p-toluenesulfonate (13). A so-
lution of 77% m-CPBA (137 mg, 0.779 mmol, 3 equiv) in
CH2Cl2 (3 mL) was added to a solution of tosylate 12
(120 mg, 0.259 mmol) in CH2Cl2 (7 mL) and the mixture

J. S. Yadav et al. / Tetrahedron 63 (2007) 9896–9902
9901
was stirred at reflux under nitrogen for 24 h. The reaction
mixture was diluted with CH2Cl2 (15 mL). A saturated solu-
tion of NaHSO3 (10 mL) was added to the same and it was
washed with saturated NaHCO3 (aq) solution (5ꢂ20 mL)
and brine solution (10 mL). The organic layer was dried
over anhydrous Na2SO4, filtered, and concentrated. The con-
centrate was purified by a silica gel column (10:90 EtOAc–
hexane as eluant) to give pure isopropyl ester 13 (85 mg) in
68% yield as colorless oil. Rf¼0.55 (SiO2, 20% EtOAc in
hexane); [a]2D5 +34.47 (c 0.5, CHCl3); IR (KBr): n 2927,
2858, 1728, 1599, 1459, 1364, 1261, 1178, 1106, 945, 814,
665 cmꢁ1; dH (200 MHz, CDCl3) 0.59 (3H, s, 10-Me), 0.69
and 0.76 (6H, 2s, 4-Me2), 0.99–1.06 (3H, m), 1.15 (6H, d,
J 6.2 Hz, 15-Me2), 1.18–1.49 (9H, m), 1.49–2.27 (5H, m),
2.40 (3H, s, –OSO2Ph-p-Me), 3.87–4.00 (2H, m, 14-H),
4.92 (1H, septet, J 6.2 Hz, 15-H), 7.25 (2H, d, J 8.2 Hz, Ar-
H), 7.69 (2H, d, J 8.2 Hz, Ar-H); dC (75 MHz, CDCl3)
15.7, 17.1, 18.4, 20.7, 21.3, 21.5, 21.8 (2C), 28.7, 32.7,
33.1, 33.2, 35.4, 37.8, 38.8, 41.7, 51.9, 56.1, 67.5, 69.7,
127.8 (2C), 129.7 (2C), 133.2, 144.6, 172.9; Mass (ESI):
m/z 479 [M+1]+, 501 [M+Na]+; HRMS (ESI): calcd for
C27H42NaO5S [M+Na]+ 501.2650 and found 501.2654.
(3H, s, –COMe), 2.14–2.41 (2H, m), 2.47–2.62 (1H, m),
4.41 (1H, s, 14-H), 4.79 (1H, s, 14-H); dC (75 MHz,
CDCl3) 14.2, 17.4, 19.3, 21.6, 24.4, 29.6, 30.0, 33.6, 38.2,
38.9, 39.7, 42.0, 42.8, 55.4, 56.1, 106.2, 148.3, 209.5; Mass
(ESI): m/z 285 [M+Na]+; HRMS (ESI): calcd for
C18H30NaO [M+Na]+ 285.2194 and found 285.2195.
4.1.14. Abiet-8(14)-en-13-one (16). Method A: A mixture of
tosylate 12 (30 mg, 0.064 mmol) and DBU (19 mg,
0.129 mmol, 2 equiv) in dry toluene (5 mL) was refluxed
for 12 h and then another 2 equiv of DBU was added to
the reaction mixture and stirred at reflux for another 12 h.
The solvent was removed under vacuum; the crude was di-
luted with EtOAc (15 mL), and washed with water (2ꢂ
10 mL) and brine solution (5 mL). The EtOAc layer was
dried over anhydrous Na2SO4, filtered and concentrated;
and the residue was purified by column chromatography
(5:95 EtOAc–hexane as eluant) to afford the pure keto-olefin
16 (15 mg, 80% yield) as a colorless liquid. Method B: To
a stirred solution of the alcohol 11 (20 mg, 0.064 mmol)
and pyridine (10 mg, 0.129 mmol, 2 equiv) in dry CH2Cl2
(4 mL) was added trifluoromethanesulfonic anhydride
(23 mg, 0.084 mmol, 1.3 equiv) at 0 ꢀC and the mixture
stirred at room temperature for 2 h under nitrogen. The reac-
tion mixture was diluted with CH2Cl2 (10 mL) and washed
with water (10 mL) and brine solution (5 mL). The
CH2Cl2 layer was dried over anhydrous Na2SO4, filtered
and concentrated; and the residue was dried under vacuum.
To a solution of the dry residue in dry CH2Cl2 (4 mL) was
added DBU (29 mg, 0.194 mmol, 3 equiv) and the mixture
was stirred at room temperature for 3 h. The reaction
mixture was diluted with CH2Cl2 (10 mL) and washed
with water (10 mL) and brine solution (5 mL). The
CH2Cl2 layer was dried over anhydrous Na2SO4, filtered
and concentrated; and the residue was purified by column
chromatography (5:95 EtOAc–hexane as eluant) to afford
the pure keto-olefin 16 (16 mg, 84%) as a colorless liquid.
Rf¼0.58 (SiO2, 10% EtOAc in hexane); [a]2D5 +38.11 (c
0.75, CHCl3); IR (KBr): n 2929, 2846, 1710, 1641, 1462,
1383, 1215, 1078, 1013, 888, 761 cmꢁ1; dH (400 MHz,
CDCl3) 0.68 (3H, s, 10-Me), 0.80 and 0.86 (6H, 2s, 4-
Me2), 1.04 and 1.07 (6H, 2d, J 1.8 Hz, 15-Me2), 1.08–1.09
(3 H, m), 1.15–1.41 (3H, m), 1.44–1.59 (3H, m), 1.61–
1.99 (4H, m), 2.22–2.38 (2H, m), 2.42–2.58 (2H, m), 4.42
(1H, s, 14-H), 4.79 (1H, s, 14-H); dC (75 MHz, CDCl3)
14.3, 17.5, 18.20, 18.24, 19.3, 21.6, 24.4, 33.56, 33.60,
38.3, 38.9, 39.3, 39.7, 40.9, 42.1, 55.5, 56.3, 106.2, 148.4,
215.3; Mass (ESI): m/z 313 [M+Na]+; HRMS (ESI): calcd
for C20H34NaO [M+Na]+ 313.2507 and found 313.2519.
4.1.12. Abiet-8(14)-en-13-oate (14). A mixture of isopropyl
ester 13 (80 mg, 0.167 mmol) and DBU (50 mg,
0.328 mmol, 2 equiv) in dry toluene (5 mL) was refluxed
for 12 h and then another 2 equiv DBU was added to the re-
action mixture and stirred again at reflux temperature for 12
more hours. The solvent was removed under vacuum; the
crude was diluted with EtOAc (15 mL), and washed with
water (2ꢂ10 mL) and brine solution (10 mL). The EtOAc
layer was dried over anhydrous Na2SO4, filtered, and con-
centrated; and the residue was purified by column chromato-
graphy (5:95 EtOAc–hexane as eluant) to afford the pure
exo-olefin 14 (45 mg, 88% yield) as colorless liquid.
Rf¼0.81 (SiO2, 20% EtOAc in hexane); [a]2D5 +27.49 (c
0.5, CHCl3); IR (KBr): n 2926, 2851, 1732, 1643, 1460,
1374, 1255, 1174, 1109, 890 cmꢁ1; dH (300 MHz, CDCl3)
0.68 (3H, s, 10-Me), 0.80 and 0.87 (6H, s, 4-Me2), 1.02–
1.18 (3H, m), 1.21 (6H, d, J 6.0 Hz, 15-Me2), 1.25 (1H, s),
1.29–1.44 (4H, m), 1.45–1.63 (3H, m), 1.64–2.15 (5H, m),
4.48 (1H, s, 14-H), 4.81 (1H, s, 14-H), 4.95 (1H, septet,
J 6.4 Hz, 15-H); dC (75 MHz, CDCl3) 14.3, 19.1, 19.3,
21.7, 21.84, 21.89, 24.4, 33.55, 33.58, 33.61, 38.2, 38.9,
39.6, 42.1, 55.5, 56.2, 67.2, 106.4, 148.0, 173.7; Mass
(ESI): m/z 307 [M+1]+, 329 [M+Na]+; HRMS (ESI): calcd
for C20H34NaO2 [M+Na]+ 329.2456 and found 329.2454.
4.1.13. 14,15-Dinorlabd-8(17)-en-13-one (15). To a stirred
solution of exo-olefin 14 (40 mg, 0.130 mmol) in dry THF
(3 mL) was added Tebbe’s reagent (0.4 mL of 0.5 M solution
in toluene, 0.196 mmol, 1.5 equiv) at ꢁ10 ꢀC and the mixture
was allowed towarm up to 0 ꢀC in 2 h. After 2 h water (3 mL)
was added slowly to the reaction mixture and the solid precip-
itated was filtered off and washed with Et2O (3ꢂ10 mL). The
filtrate was concentrated under vacuum and the residue was
purified by column chromatography (10:90 EtOAc–hexane
as eluant) to afford the keto-olefin 15 (28 mg, 82% yield)
as colorless oil. Rf¼0.52 (SiO2, 10% EtOAc in hexane);
[a]2D5 +36.6 (c 0.4, CHCl3); IR (KBr): n 2926, 2849, 1716,
1639, 1459, 1360, 1160, 1109, 889, 760 cmꢁ1; dH
(200 MHz, CDCl3) 0.69 (3H, s, 10-Me), 0.80 and 0.87 (6H,
2s, 4-Me2), 0.99–1.61 (10H, m), 1.66–2.01 (3H, m), 2.08
4.1.15. Abiet-8,14-epoxy-13-one (17). A solution of 77%
m-CPBA (23 mg, 0.134 mmol, 3 equiv) in CH2Cl2 (4 mL)
and 2 mL of 5% NaHCO3 (aq) was added to a solution of
keto-olefin 16 (13 mg, 0.044 mmol) in CH2CL2 (4 mL)
and the mixture was stirred at room temperature for 3 h. Af-
ter dilution with CH2Cl2 (10 mL), a saturated solution of
NaHSO3 (6 mL) was added to the reaction mixture and it
was washed with saturated NaHCO3 (aq) solution (3ꢂ
20 mL) and brine solution (10 mL). The organic layer was
dried over anhydrous Na2SO4, filtered and concentrated.
The concentrate was purified by a silica gel column (15:85
EtOAc–hexane as eluant) to give a-epoxide 17 (13 mg) in
95% yield as a colorless liquid. Rf¼0.47 (SiO2, 20% EtOAc

9902
J. S. Yadav et al. / Tetrahedron 63 (2007) 9896–9902
in hexane); [a]2D5 +7.32 (c 0.6, CHCl3); IR (KBr): n 2959,
2929, 2870, 1725, 1447, 1381, 1283, 1125, 1071, 742,
658 cmꢁ1; dH (400 MHz, CDCl3) 0.84 (6H, d, J 2.6 Hz,
4-Me2), 0.89 (3H, s, 10-Me), 0.97–1.04 (2H, m), 1.05 and
1.08 (6H, 2d, J 1.5 Hz, 15-Me2), 1.14–1.64 (9H, m), 1.77–
1.88 (3H, m), 2.31 (1H, m), 2.42 (1H, d, J 4.5 Hz, 14-H),
2.42–2.68 (2H, m), 2.78 (1H, dd, J 1.5, 4.1 Hz, 14-H); dC
(75 MHz, CDCl3) 13.1, 14.7, 16.7, 16.8, 17.2, 20.1, 20.4,
32.00, 32.08, 35.3, 37.5, 38.9, 39.3, 40.2, 40.5, 49.4, 51.8,
53.6, 58.0, 213.8. Mass (ESI): m/z 307 [M+1]+, 329
[M+Na]+; HRMS (ESI): calcd for C20H34 NaO2 [M+Na]+
329.2456 and found 329.2462.
References and notes
1. (a) Ohloff, G. The Fragrance of Ambergris. In Fragrance
Chemistry; Theimer, E. T., Ed.; Academic: New York, NY,
1982; pp 535–573; (b) Bajgrowicz, J. A.; Broger, C.
Proceedings of the 13th International Congress of Flavours,
Fragrances and Essential oil; Baser, K. H. C., Ed.; AREP
ꢀ
Publications: Istanbul, 1995; pp 1–15; (c) Frater, G.;
Bajgrowicz, J. A.; Kraft, P. Tetrahedron 1998, 54, 7633–
ꢀ
7703; (d) Kraft, P.; Bajgrowicz, J. A.; Denis, C.; Frater, G.
Angew. Chem., Int. Ed. 2000, 39, 2980–3010.
2. (a) Castro, J. M.; Salido, S.; Altarejos, J.; Nogueras, M.;
Sanchez, A. Tetrahedron 2002, 58, 5941–5949; (b) Bolster,
M. G.; Langel, B. M. F.; Jansen, B. J. M.; Morin, C.; Groot,
A. Tetrahedron 2001, 57, 8369–8379; (c) Barrero, A. B.;
Altarejos, J.; Alvarez-Manzaneda, E.; Ramos, J. M.; Salido,
S. Tetrahedron 1993, 49, 6251–6262; (d) Zahra, J.; Chauvet,
F.; Coste-Maniere, I.; Martres, P.; Perfetti, P.; Waegell, B.
Bull. Soc. Chim. Fr. 1997, 134, 1001–1024; (e) Fehr, C.;
Faris, I. Angew. Chem., Int Ed. 2006, 45, 6904–6907.
3. (a) Schenk, H. R.; Gutmann, H.; Jeger, O.; Ruzicka, L. Helv.
Chim. Acta 1954, 37, 543–546; (b) Scheidedegger, U.;
Schaffner, K.; Jegger, O.; Schenk, H. R.; Gutmann, H.; Jeger,
O.; Ruzicka, L. Helv. Chim. Acta 1962, 45, 400–435; (c)
Demole, E. Experimentia 1964, 20, 609–610.
4.1.16. (8R,13S)-8a,13:13,14-Diepoxyabietane (2).
Method A: To a stirred solution of a-epoxide 17 (12 mg,
0.039 mmol) in dry CH2Cl2 (5 mL) was added ZnCl2
(3 mg, 0.022 mmol, 0.6 equiv) and the reaction mixture
was stirred at 18 ꢀC for 14 h. After completion of the reac-
tion (as monitored by TLC), the mixture was diluted with
CH2Cl2 (10 mL) and washed with water (5 mL) and brine
solution (5 mL). The organic layer was dried over anhydrous
Na2SO4, filtered and concentrated. The concentrate was pu-
rified by a silica gel column (5:95 EtOAc–hexane as eluant)
to give amberketal analog 2 (9 mg) in 75% yield as a semi-
solid. Method B: A stirred mixture of keto-olefin 16 (13 mg,
0.044 mmol), Me3NO$2H2O (14 mg, 0.134 mmol, 3 equiv),
t-BuOH (4 mL), water (0.6 mL), pyridine (0.1 mL), and
OsO4 (0.1 mL of 0.2% wt/v in t-BuOH, 0.02 equiv) was
stirred at reflux temperature for 48 h. The reaction mixture
was cooled to room temperature, treated with 20% NaHSO3
(aq) solution (3 mL), concentrated under vacuum to remove
t-BuOH, saturated with NaCl (400 mg), and extracted with
Et2O (3ꢂ5 mL). The combined organic layer was dried
over anhydrous Na2SO4, filtered and concentrated; the resi-
due was purified by column chromatography (5:95 EtOAc–
hexane) to afford pure amberketal analog 2 (10 mg, 73%
yield) as a semisolid. Rf¼0.58 (SiO2, 10% EtOAc in hexane)
[a]2D5 +11.3 (c 0.5, CHCl3); IR (KBr): n 2928, 2869, 1460,
1382, 1257, 1175, 1061, 1025, 906, 759 cmꢁ1; dH
(300 MHz, CDCl3) 0.79 (3H, s, 10-Me), 0.88 (6H, d,
J 1.5 Hz, 15-Me2), 0.90 and 0.93 (6H, 2s, 4-Me2), 1.06–
1.24 (3H, m), 1.37–1.45 (4H, m), 1.53–1.81 (10H, m),
3.20 (1H, dd, J 1.1, 6.7 Hz, 14-H), 4.24 (1H, d, J 6.7 Hz,
14-H); dC (75 MHz, CDCl3) 15.5, 16.8, 17.24, 17.27,
18.24, 20.0, 21.6, 30.6, 33.0, 33.5, 34.7, 35.8, 37.2, 38.6,
41.7, 53.7, 55.6, 73.5, 83.3, 109.5; Mass (ESI): m/z 307
[M+H]+; HRMS (ESI): calcd for C20H35O2 [M+H]+
307.2637 and found 307.2640.
ꢁ
4. (a) Coste-Maniere, I. C.; Zahra, J. P.; Waegell, B. Tetrahedron
Lett. 1988, 29, 1017–1020; (b) Martres, P.; Perfetti, P.; Zahra,
J. P.; Waegell, B. Tetrahedron Lett. 1991, 32, 765–766; (c)
Martres, P.; Perfetti, P.; Zahra, J. P.; Waegell, B. Tetrahedron
Lett. 1994, 35, 97–98; (d) Martres, P.; Perfetti, P.; Zahra,
J. P.; Waegell, B.; Giraudi, E.; Petrzilka, M. Tetrahedron Lett.
1993, 34, 8081–8084.
5. Barrero, A. F.; Altarejos, J.; Alvarez-Manzaneda, E. J.; Ramos,
J. M.; Salido, S. Tetrahedron 1993, 49, 9525–9534.
6. Costa, M. D. C.; Tavares, R.; Motherwell, W. B.; Curto,
M. J. M. Tetrahedron Lett. 1994, 35, 8839–8842.
7. Buchbauer, G.; Heneis, V. M.; Krejci, V.; Talsky, C.; Wunderer,
H. Monatsh. Chem. 1985, 116, 1345–1358.
8. Koyama, H.; Kaku, Y.; Ohno, M. Tetrahedron Lett. 1987, 28,
2863–2867.
9. (a) Cambie, R. C.; Franich, R. A.; Larsen, D.; Rutledge, P. S.;
Ryan, G. R.; Woodgate, P. D. Aust. J. Chem. 1990, 43,
21–46; (b) Cambie, R. C.; Rutledge, P. S.; Ryan, G. R.;
Strange, G. A.; Woodgate, P. D. Aust. J. Chem. 1990, 43,
867–881.
10. Costa, M. C.; Alves, S. P.; Correia, M. E.; Curto, M. J. M.
Synthesis 2006, 1171–1175.
11. (a) Garegg, P. J.; Samuelson, B. J. Chem. Soc., Perkin Trans. 1
1980, 2866–2869; (b) Garegg, P. J.; Johansson, R.; Ortega, C.;
Samuelson, B. J. Chem. Soc., Perkin Trans. 1 1982, 681–686.
12. Chandrasekhar, S.; Narsihmulu, Ch.; Sultana, S. S.; Reddy,
N. R. Chem. Commun. 2003, 1716–1717.
Acknowledgements
G.B. and U.D. thank CSIR, New Delhi for the award of
fellowship.
13. (a) Barrero, A. F.; Alvarez-Manzaneda, E. J.; Chahboun, R.;
Meneses, R. Synlett 2000, 197–200; (b) Barrero, A. F.;
Alvarez-Manzaneda, E. J.; Chahboun, R.; Meneses, R.
Synlett 1999, 1663–1666.
Supplementary data
14. Fieser, L. F.; Fieser, M. Reagents for Organic Synthesis; Wiley:
New York, NY, 1967; Vol. 1, p 1179.
Supplementary data associated with this article can be found
in the online version, at doi:10.1016/j.tet.2007.06.063.
15. Smith, M. B. Oxidation. In Organic Synthesis, 2nd ed.;
McGraw-Hill: New York, NY, 2002; pp 258–263.