A stereoselective total synthesis of (-)-seychellene

Article abstract of DOI:10.1016/j.tet.2008.01.035

A stereoselective total synthesis of the tricyclic sesquiterpene (-)-seychellene, starting from (R)-carvone via (R)-3-methylcarvone has been accomplished, employing a combination of intermolecular Michael addition-intramolecular Michael addition sequence,

Full text of DOI:10.1016/j.tet.2008.01.035

Available online at www.sciencedirect.com
Tetrahedron 64 (2008) 2565e2571
www.elsevier.com/locate/tet
A stereoselective total synthesis of (ꢀ)-seychellene
*
A. Srikrishna , G. Ravi
Department of Organic Chemistry, Indian Institute of Science, Bangalore 560012, India
Received 26 November 2007; received in revised form 22 December 2007; accepted 9 January 2008
Available online 13 January 2008
Abstract
A stereoselective total synthesis of the tricyclic sesquiterpene (ꢀ)-seychellene, starting from (R)-carvone via (R)-3-methylcarvone has been
accomplished, employing a combination of intermolecular Michael additioneintramolecular Michael addition sequence, a stereoselective
hydrogenation, and an intramolecular alkylation reaction.
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords: Seychellene; Sesquiterpene synthesis; Intramolecular alkylation; Carvone; Double Michael reaction
1. Introduction
synthetic chemists and a number of reports appeared on the
synthesis of seychellene 1 in its racemic form.2 As a part of
our interest in the enantiospecific synthesis of tricyclic sesqui-
terpenes starting from the readily available monoterpene
(R)-carvone, such as neopupukeananes, pupukeananes, valeri-
ananoids, patchouli alcohol, etc.,3 we have recently reported4
the first enantiospecific synthesis of ent-seychellene 1 and epi-
seychellene 6 via intramolecular alkylation of ketomesylate 7
(Scheme 1) followed by the degradation of the isopropylidene
group. A one step reduction of the olefin as well as the ester
group in the a,b-unsaturated ester 8 using lithium in liquid
ammonia conditions was employed for the creation of the sec-
ondary methyl group. Since the stereoselectivity in the lith-
iumeliquid ammonia reaction was not good, an alternative
strategy via the catalytic hydrogenation of the olefin in 8 was
explored and herein, we describe a stereoselective synthesis of
(ꢀ)-seychellene 1.
The structurally novel tricyclic sesquiterpene (ꢀ)-seychel-
lene 1 was first isolated from the patchouli oil (from the leaves
of Pogostemon cablin Benth obtained from the Seychelles
Islands) as one of the minor components along with a- and
b-patchoulene 2 and 3 and patchouli alcohol 4.1 It was subse-
quently isolated from a variety of species belonging to
Pogostemon and Nardostachys jatamansi. The relative structure
as well as the absolute configuration of seychellene 1 was estab-
lished by Ourisson and Wolff based on the degradation studies.1
Structurally and biogenetically, seychellene 1 is closely related
to the tricyclic alcohol patchouli alcohol 4.
10
1
11
7
2
8
5
3
OH
5
4
1
2
3
The tricyclic structure containing a carbon framework tricy-
clo[5.3.1.03,8]undecane (homoisotwistane 5) incorporating two
vicinal quaternary carbon atoms attracted the attention of
O
O
O
O
MsO
1 α-Me
6 β-Me
EtOOC
(S)-9
7
8
* Corresponding author. Fax: þ91 80 23600529.
E-mail address: ask@orgchem.iisc.ernet.in (A. Srikrishna).
Scheme 1. Earlier route to (þ)-seychellene.
0040-4020/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.01.035

2566
A. Srikrishna, G. Ravi / Tetrahedron 64 (2008) 2565e2571
2. Results and discussion
place from the b-face of the molecule as the a-face is blocked
by the bicyclic system, leading to the required isomer in a
stereoselective manner.
It was contemplated that among the two rotamers A and B
(considering that the methyl group of the crotonyl side chain
prefers to occupy outside the bicyclo[2.2.2]octane framework
and hydrogen adds from the less hindered face of the molecule),
although molecular mechanics calculations indicated that both
rotamers are energetically very similar, in rotamer B hydroge-
nation takes place preferably from the a-face of the molecule
due to the steric crowding of the bridgehead methyl (located
on the b-face of the molecule), whereas in rotamer A it takes
Since the selective hydrogenation of the trisubstituted double
bond in the presence of tetrasubstituted double bond in the
a,b-unsaturated ester 8 was found to be unsuccessful, it was de-
cided to degrade the isopropylidene group prior to the elabora-
tion of the side chain. As (S)-3-methylcarvone (S)-9 resulted in
ent-seychellene (þ)-1, for generating (ꢀ)-seychellene 1, the se-
quence was started with (R)-3-methylcarvone (R)-9, which was
prepared using an earlier developed method5 via a 1,3-dipolar
cycloaddition of diazomethane to (R)-carvone 10 followed by
thermolysis of the resultant pyrazoline derivative, Scheme 2.
Generation of the kinetic lithium dienolate of 3-methylcarvone
(R)-9 with 1.1 equivalents of lithium hexamethyldisilazide in
hexane followed by treatment with 1 equiv of methyl acrylate
generated the bicyclic keto ester 11 via tandem intermolecular
Michael additioneintramolecular Michael addition sequence.6
EtOOC
COOEt
A
B
O
O
O
O
a
b
c
66%
70%
100%
MeOOC
MeOOC
12
10
11
9
d
94%
O
S
S
O
O
O
O
g
f
e
O
90%
MeOOC
99%
98%
MeOOC
13
MeOOC
99%
MeOOC
16
15
14
h
O
O
O
O
j
k
i
O
O
O
O
94%
88%
85%
OH
17
O
OH
19
O
H
20
18
l
93%
O
O
O
O
o
m
n
98%
O
O
O
90%
100%
OH
OH
COOEt
22
COOEt
21
24
23
91%
p
O
O
r
q
86%
76%
OMs
26
1
25
Scheme 2. Reagents: (a) (i) CH2N2, Et2O; (ii) 190 ꢁC, (CH2OH)2; (b) LiHMDS, hexane, CH2]CHCOOMe; (c) PTSA, C6H6; (d) (i) O3eO2, MeOHeCH2Cl2; (ii)
Me2S; (e) (CH2SH)2, BF3$Et2O, CH2Cl2; (f) Raney Ni, EtOH; (g) (CH2OH)2, PTSA, C6H6; (h) LAH, Et2O; (i) PDC, CH2Cl2; (j) MeMgI, Et2O; (k) PCC, NaOAc,
CH2Cl2; (l) (EtO)2P(O)CH2COOEt, NaH, THF; (m) 10% PdeC, H2 (1 atm), hexane; (n) LAH, Et2O; (o) H2OeAcOH (1:1); (p) MsCl, Py, CH2Cl2; (q) NaH, THF;
(r) Mg, TiCl4, CH2Cl2, THF.

A. Srikrishna, G. Ravi / Tetrahedron 64 (2008) 2565e2571
2567
Isomerization of the olefinic bond of the isopropenyl group in
4. Experimental section
the keto ester 11 with a catalytic amount of p-toluenesulfonic
acid (PTSA) in refluxing benzene furnished the ester 12 in
100% yield. Ozonolysis followed by reductive work-up with di-
methyl sulfide transformed keto olefin 12 into dione 13 in 94%
yield. In diketone 13, the C-5 ketone is sterically more crowded
than the C-8 ketone, which has been exploited for the selective
reductive removal of the C-8 ketone. Thus, reaction of the dike-
tone 13 with 1,2-ethanedithiol and a catalytic amount of boron
trifluoride diethyl etherate in methylene chloride furnished the
thioketal 14 in 98% yield, which on desulfurization with Raney
nickel in refluxing ethanol quantitatively furnished the keto es-
ter 15. To avoid regiochemical problems, the ketone group in the
keto ester 15 was protected as its ketal by reacting with 1,2-etha-
nediol and p-toluenesulfonic acid in refluxing benzene using
a DeaneStark apparatus to furnish the ketal ester 16. The ester
in 16 was then modified into a methyl ketone. Accordingly, re-
duction of the ester 16 with lithium aluminum hydride (LAH) in
diethyl ether furnished the primary alcohol 17, which on oxida-
tion with pyridinium dichromate (PDC) in methylene chloride
generated the aldehyde 18. Grignard reaction of the aldehyde
18 with methylmagnesium iodide followed by oxidation of
the resultant secondary alcohol 19 with pyridinium chlorochro-
mate (PCC) and sodium acetate in methylene chloride furnished
the methyl ketone 20. HornereWadswortheEmmons reaction
of the ketone 20 with triethyl phosphonoacetate and sodium hy-
dride in refluxing THF furnished the unsaturated ester 21. As an-
ticipated, hydrogenation of the a,b-unsaturated ester 21 with
10% palladium over carbon as the catalyst in hexane furnished
the saturated ester 22 in a highly stereoselective manner
(>95%). Reduction of the ester 22 with LAH furnished the
hydroxy ketal 23, which was transformed into (ꢀ)-seychellene
employing an intramolecular alkylation strategy. Thus, hydroly-
sis of the ketal moiety in the hydroxy ketal 23 with aqueous ace-
tic acid followed by mesylation of the resultant hydroxy ketone
24 with methanesulfonyl chloride and pyridine in methylene
chloride generated the ketomesylate 25 in 91% yield.
4.1. General
Melting points were recorded using a Mettler FP1 melting
point apparatus in capillary tubes and are uncorrected. IR spec-
tra were recorded on PerkineElmer 781 and Jasco FTIR 410
spectrophotometers. H (300 MHz) and 13C (75 MHz) NMR
1
spectra were recorded on JNM l-300 spectrometer. The chem-
ical shifts (d, parts per million) and coupling constants (hertz)
are reported in the standard fashion with reference to either in-
ternal tetramethylsilane (for 1H) or the central line (77.0 ppm)
of CDCl3 (for 13C). In the 13C NMR, the nature of carbons (C,
CH, CH2, CH3) was determined by recording the DEPT-135
spectra and is given in parentheses. High-resolution mass spec-
tra were recorded using Micromass Q-TOF micro mass spec-
trometer using electron spray ionization mode. Optical
rotations were measured using a Jasco DIP-370 digital polarim-
eter and [a]D values are givenin units of 10ꢀ1 deg cm2 gꢀ1. Ozo-
nolysis experiment was carried out using Fischer 502 ozone
generator. Hydrogenation reaction at 1 atm pressure was carried
out using a balloon filled with hydrogen. Thin-layer chromatog-
raphies (TLC) were performed on glass plates (7.5ꢂ2.5 and
7.5ꢂ5.0 cm) coated with Acme’s silica gel G containing 13%
calcium sulfate as binder and various combinations of ethyl
acetate, methylene chloride, and hexane were used as eluent.
Visualization of spots was accomplished by exposure to iodine
vapor or anisaldehydeeH2SO4 or MeOHeH2SO4 spray fol-
lowed by heating. Acme’s silica gel (100e200 mesh) was used
for column chromatography (approximately 15e20 g per 1 g
of the crude product).
4.2. Methyl (1R,2R,4S,6S,8R)-8-(1-methylethenyl)-1,6-
dimethyl-5-oxobicyclo[2.2.2]octane-2-carboxylate (11)
To a cold (ꢀ70 ꢁC) magnetically stirred solution of hexame-
thyldisilazane (3.3 mL, 15.8 mmol) in dry hexane (40 mL) was
slowly added a solution of n-BuLi (2.5 M in hexane, 5.8 mL,
14.6 mmol) and the reaction mixture was stirred for 15 min at
the same temperature. To LiHMDS thus formed was added
drop wise a solution of (R)-3-methylcarvone 95 (2.0 g,
12.2 mmol) in dry hexane (16 mL) and the reaction mixture
was stirred for 45 min at the same temperature. Methyl acrylate
(1.21 mL, 13.4 mmol) was added to the reaction mixture and
stirred for 3 h at rt. It was then filtered through a small silica
gel column using ethyl acetateehexane (1:3) as eluent. Evapo-
ration of the solvent and purification of the residue on a silica gel
column using ethyl acetateehexane (1:19) as eluent furnished
the bicyclic adduct 11 (2.0 g, 66%) as oil. [a]2D1 ꢀ76.8 (c 7.3,
CHCl3); IR (neat): nmax/cmꢀ1 3087, 2949, 1740, 1720, 1647,
Intramolecular alkylation reaction of the ketomesylate 25
with sodium hydride in refluxing THF furnished norseychelle-
none 26, whose structure was established by comparing the
spectral data with that of the racemic compound reported in
the literature. Finally, methylenation of the ketone 26 with
methylene chlorideemagnesiumetitanium chloride7 in THF
furnished (ꢀ)-seychellene 1, which exhibited 1H and 13C
NMR spectral data identical to that reported in the literature2e
for the racemic compound.
3. Conclusions
In summary, we have developed an efficient enantiospecific
methodology for the stereoselective synthesis of (ꢀ)-seychel-
lene 1 starting from (R)-carvone 10 via (R)-3-methylcarvone
9. A combination of intermolecular Michael additioneintramo-
lecular Michael addition sequence, a stereoselective hydrogena-
tion, and an intramolecular alkylation reaction was strategically
employed for the generation of the tricyclic system containing
two vicinal quaternary carbon atoms.
1
1458, 1437, 1369, 1217, 1163, 1043, 1024, 897, 848, 760; H
NMR (300 MHz, CDCl3): d 4.72 (2H, s), 3.69 (3H, s), 2.77
(1H, qd, J 7.5 and 1.8 Hz), 2.67 (1H, t, J 9.0 Hz), 2.60e2.40
(2H, m), 2.07 (2H, dd, J 9.0 and 3.0 Hz), 1.82e1.45 (2H, m),
1.68 (3H, s), 0.99 (3H, d, J 7.2 Hz), 0.94 (3H, s); 13C NMR
(75 MHz, CDCl3): d 216.3 (C), 175.1 (C), 146.6 (C), 110.5
(CH2), 51.5 (CH3), 46.1 (CH), 45.6 (CH), 45.1 (CH), 43.7

2568
A. Srikrishna, G. Ravi / Tetrahedron 64 (2008) 2565e2571
(CH), 37.9 (C), 35.3 (CH2), 27.9 (CH2), 22.2 (CH3), 21.7 (CH3),
8.5 (CH3). HRMS, m/z calcd for C15H22O3Na (MþNa):
273.1467; found: 273.1455.
4.5. Methyl (1R,2R,4R,6S)-1,6-dimethyl-5-oxobicyclo-
[2.2.2]octane-spiro[8.20]-1,3-dithiolane-2-carboxylate (14)
To a cold (0 ꢁC) magnetically stirred solution of the diketone
13 (750 mg, 3.3 mmol) and 1,2-ethanedithiol (0.56 mL,
6.7 mmol) in dry CH2Cl2 (5 mL) was added a catalytic amount
of BF3$Et2O and stirred for 2 h at rt. Aqueous NaOH solution
(5%, 2 mL) was added to the reaction mixture and extracted
with CH2Cl2 (3ꢂ6 mL). The combined organic layer was
washed with brine (8 mL) and dried (Na2SO4). Evaporation of
the solvent and purification of the residue over a silica gel col-
umn using ethyl acetateehexane (1:19) as eluent furnished the
thioketal 14 (920 mg, 98%) as colorless oil. [a]2D1 ꢀ75.3
(c 9.5, CHCl3); IR (neat): nmax/cmꢀ1 2932, 1724, 1452, 1435,
1368, 1270, 1222, 1200, 1166, 1030, 1012, 906, 846; 1H NMR
(300 MHz, CDCl3): d 3.68 (3H, s), 3.50e3.20 (4H, m), 2.70e
2.35 (5H, m), 2.20e2.00 (2H, m), 1.05 (3H, d, J 7.5 Hz), 0.93
(3H, s); 13C NMR (75 MHz, CDCl3): d 211.9 (C), 174.3 (C),
64.7 (C), 55.4 (CH), 51.4 (CH3), 47.3 (CH2), 45.6 (CH), 43.8
(CH), 39.6 (2C, CH2), 38.6 (C), 25.7 (CH2), 21.7 (CH3), 10.1
(CH3). HRMS, m/z calcd for C14H20O3S2Na (MþNa):
323.0752; found: 323.0760.
4.3. Methyl (1R,2R,4S,6S)-8-(1-methylethylidene)-1,6-
dimethyl-5-oxobicyclo[2.2.2]octane-2-carboxylate (12)
To a magnetically stirred solution of the keto ester 11 (1.0 g,
4.0 mmol) in benzene (10 mL) was added PTSA (153 mg,
0.8 mmol) and the reaction mixture was refluxed for 1 h. It
was then filtered through a short silica gel column using
CH2Cl2 as eluent. Evaporation of the solvent and purification
of the residue over a silica gel column using ethyl acetateehex-
ane (1:19) as eluent furnished the keto ester 12 (1.0 g, 100%) as
colorless oil. [a]D21 ꢀ40.0 (c 0.6, CHCl3); IR (neat): nmax/cmꢀ1
2954, 2936, 2878, 1727, 1453, 1435, 1366, 1302, 1263, 1195,
1163, 1023, 907; 1H NMR (300 MHz, CDCl3): d 3.68 (3H, s),
3.26 (1H, t, J 2.7 Hz), 2.69 (1H, qd, J 7.5 and 1.8 Hz), 2.52
(1H, dd, J 10.5 and 6.9 Hz), 2.29 (1H, d, J 16.8 Hz), 2.12 (1H,
ddd, J 13.5, 7.2, and 2.1 Hz), 2.05e1.85 (2H, m), 1.68 (3H, s),
1.61 (3H, s), 1.01 (3H, s), 0.99 (3H, d, J 7.5 Hz); 13C NMR
(75 MHz, CDCl3): d 212.9 (C), 174.9 (C), 127.1 (C), 125.2
(C), 51.4 (CH3), 47.6 (CH), 47.5 (CH), 44.7 (CH), 38.5 (C),
37.5 (CH2), 27.2 (CH2), 22.5 (CH3), 20.3 (CH3), 19.8 (CH3),
9.9 (CH3). HRMS, m/z calcd for C15H22O3Na (MþNa):
273.1467; found: 273.1462.
4.6. Methyl (1R,2R,4R,6S)-1,6-dimethyl-5-oxobicyclo-
[2.2.2]octane-2-carboxylate (15)
To a magnetically stirred solution of the thioketal 14
(750 mg, 2.5 mmol) in dry ethanol (5 mL) was added excess
of Raneynickel (500 mg) and refluxed for 2 h. The reaction mix-
ture was cooled and filtered through a short silica gel column to
remove the catalyst. Evaporation of the solvent and purification
of the residue over a silica gel column using ethyl acetateehex-
ane (1:19) as eluent furnished the keto ester 15 (520 mg, 99%) as
colorless oil. [a]D22 ꢀ51.1 (c 20.0, CHCl3); IR (neat): nmax/cmꢀ1
2951, 2873, 1724, 1452, 1367, 1212, 1190, 1166, 1044, 1017,
4.4. Methyl (1R,2R,4S,6S)-1,6-dimethyl-5,8-dioxobicyclo-
[2.2.2]octane-2-carboxylate (13)
A pre-cooled (ꢀ70 ꢁC) mixture of ozone in oxygen was
passed through a cold (ꢀ70 ꢁC) solution of the keto olefin 12
(1.0 g, 4.0 mmol) and a catalytic amount of NaHCO3 in metha-
nol (3 mL) and CH2Cl2 (12 mL) until it turns blue (ca. 16 min).
The reaction mixturewas flushed off with oxygen. Dimethyl sul-
fide (0.44 mL, 6 mmol) was added to the reaction mixture, then
slowly warmed up to rt and magnetically stirred for 5 h. The re-
action mixture was diluted with water (8 mL) and extracted with
CH2Cl2 (3ꢂ7 mL). The combined organic layer was washed
with brine (8 mL) and dried (Na2SO4). Evaporation of the
solvent and purification of the residue on a silica gel column us-
ing ethyl acetateehexane (1:9) as eluent furnished the diketone
13 (850 mg, 94%) as a colorless solid, which was recrystallized
from a 1:1 mixture of CH2Cl2 and hexane. Mp: 86e88 ꢁC; [a]D20
ꢀ30.8 (c 5.2, CHCl3); IR (thin film): nmax/cmꢀ1 2971, 2883,
1731, 1455, 1406, 1372, 1304, 1016, 908, 854; 1H NMR
(300 MHz, CDCl3): d 3.73 (3H, s), 3.11 (1H, t, J 3.3 Hz), 2.87
(1H, qd, J 7.5 and 2.4 Hz), 2.77 (1H, dd, J 10.5 and 7.2 Hz),
2.42 (1H, d, J 19.2 Hz), 2.40e2.20 (2H, m), 2.12 (1H, dd, J
19.2 and 2.7 Hz), 1.17 (3H, s), 1.07 (3H, d, J 7.5 Hz); 13C
NMR (75 MHz, CDCl3): d 206.9 (C), 204.3 (C), 173.5 (C),
62.3 (CH), 51.6 (CH3), 46.4 (2C, CH and CH2), 44.9 (CH),
38.7 (C), 25.5 (CH2), 21.4 (CH3), 10.1 (CH3). HRMS, m/z calcd
for C12H16O4Na (MþNa): 247.0946; found: 247.0935. Anal.
Calcd for C12H16O4: C, 64.27; H, 7.19. Found: C, 64.31; H,
7.23%.
1
925; H NMR (300 MHz, CDCl3): d 3.68 (3H, s), 2.71 (1H,
qd, J 7.5 and 1.8 Hz), 2.63 (1H, dd, J 10.5 and 7.5 Hz), 2.35e
2.25 (1H, m), 2.15e1.90 (2H, m), 1.88e1.60 (3H, m), 1.40e
1.25 (1H, m), 1.02 (3H, d, J 7.5 Hz), 0.93 (3H, s); 13C NMR
(75 MHz, CDCl3): d 217.2 (C), 175.1 (C), 51.4 (CH3), 46.9
(CH), 45.3 (CH), 41.3 (CH), 38.1 (C), 28.7 (CH2), 26.7 (CH2),
24.1 (CH2), 22.5 (CH3), 9.1 (CH3). HRMS, m/z calcd for
C12H18O3Na (MþNa): 233.1149; found: 233.1154.
4.7. Methyl (1R,2R,4R,6S)-1,6-dimethylbicyclo[2.2.2]octane-
spiro[5.20]-1,3-dioxolane-2-carboxylate (16)
To a magnetically stirred solution of the keto ester 15
(680 mg, 3.6 mmol) in benzene (10 mL) were added 1,2-ethane-
diol (0.4 mL, 7.3 mmol) and PTSA (50 mg, 0.26 mmol) and the
reaction mixture was refluxed for 7 h by using DeaneStark wa-
ter trap. Satd aq NaHCO3 solution (4 mL) was added to the re-
action mixture and extracted with ether (3ꢂ8 mL). The ether
extract was washed with brine (8 mL) and dried (Na2SO4).
Evaporation of the solvent and purification of the residue over
a silica gel column using ethyl acetateehexane (1:19) as eluent
furnished the ketal ester 16 (740 mg, 90%) as colorless oil.

A. Srikrishna, G. Ravi / Tetrahedron 64 (2008) 2565e2571
2569
[a]D24 ꢀ56.7 (c 15.8, CHCl3); IR (neat): nmax/cmꢀ1 2940, 2875,
1
951, 927; H NMR (300 MHz, CDCl3): d 4.00e3.73 (4H, m),
4.10. (1S,2R,4R,6S)-2-(1-Hydroxyethyl)-1,6-dimethylbicyclo-
[2.2.2]octane-spiro[5.20]-1,3-dioxolane (19)
1732, 1462, 1434, 1381, 1364, 1220, 1194, 1161, 1143, 1052,
3.64 (3H, s), 2.48 (1H, qd, J 7.2 and 2.7 Hz), 2.34 (1H, t, J
9.3 Hz), 2.15e1.50 (5H, m), 1.40e1.25 (1H, m), 1.05e0.92
(1H, m), 0.75 (3H, s), 0.74 (3H, d, J 7.2 Hz); 13C NMR
(75 MHz, CDCl3): d 175.4 (C), 112.2 (C), 65.3 (CH2), 63.2
(CH2), 50.9 (CH3), 47.1 (CH), 38.8 (CH), 35.5 (C), 33.0 (CH),
28.0 (CH2), 26.0 (CH2), 22.2 (CH3), 21.7 (CH2), 7.3 (CH3).
HRMS, m/z calcd for C14H22O4Na (MþNa): 277.1416; found:
277.1416.
To an ice cold magnetically stirred solution of the aldehyde
18 (520 mg, 2.32 mmol) in anhydrous ether (2 mL) was added
a solution of methylmagnesium iodide [freshly prepared from
magnesium (111 mg, 4.64 mmol) and methyl iodide (0.4 mL,
6.96 mmol)] in dry ether (5 mL) and stirred for 45 min at the
same temperature. The reaction was then quenched with satd
aq NH4Cl solution (2 mL) and extracted with ether (3ꢂ7 mL).
The combined ether layer was washed with brine (8 mL) and
dried (Na2SO4). Evaporation of the solvent and purification of
the residue over a silica gel column using ethyl acetateehexane
(1:9) as eluent furnished the secondary alcohol 19 (525 mg,
94%) as oil. [a]D21 ꢀ43.8 (c 1.5, CHCl3); IR (neat): nmax/cmꢀ1
3460, 2958, 2931, 2872, 1465, 1378, 1360, 1265, 1148, 1103,
4.8. (1S,2R,4R,6S)-1,6-Dimethylbicyclo[2.2.2]octane-spiro-
[5.20]-1,3-dioxolane-2-methanol (17)
To a cold (0 ꢁC) magnetically stirred solution of the ester 16
(510 mg, 2.01 mmol) in dry ether (3 mL) was added LAH
(153 mg, 2.0 mmol) and stirred for 30 min at rt. Ethyl acetate
(0.5 mL) was added to the reaction mixture to consume the ex-
cess LAH. The reaction mixture was then quenched with water
(10 mL) and extracted with ether (3ꢂ5 mL). The ether extract
was washed with brine (3 mL) and dried (Na2SO4). Evaporation
of the solvent and purification of the residue on a silica gel
column using ethyl acetateehexane (1:9) as eluent furnished
the alcohol 17 (450 mg, 99%) as colorless oil. [a]2D2 ꢀ45.8 (c
15.4, CHCl3); IR (neat): nmax/cmꢀ1 3412, 2934, 2872, 1463,
1
1049, 1062, 946, 742; H NMR (300 MHz, CDCl3): d 4.16e
4.12 (1H, m), 4.00e3.70 (4H, m), 2.55e2.50 (1H, m), 2.23
(1H, br s), 1.90e1.16 (8H, m), 1.12 (3H, d, J 6.6 Hz), 0.85
(3H, s), 0.77 (3H, d, J 6.9 Hz); 13C NMR (75 MHz, CDCl3):
d 112.8 (C), 66.7 (CH), 65.0 (CH2), 63.0 (CH2), 46.5 (CH),
40.3 (CH), 35.0 (C), 33.9 (CH), 29.5 (CH2), 22.8 (CH3), 22.3
(CH3), 21.9 (CH2), 21.3 (CH2), 8.2 (CH3). HRMS, m/z calcd
for C14H24O3Na (MþNa): 263.1623; found: 263.1624.
4.11. 1-[(1S,2R,4R,6S)-1,6-Dimethylbicyclo[2.2.2]octane-
spiro[5.20]-1,3-dioxolan-2-yl]ethanone (20)
1
1380, 1356, 1168, 1148, 1097, 1058, 1039, 949; H NMR
(300 MHz, CDCl3): d 4.00e3.65 (5H, m), 3.52 (1H, dd, J 10.2
and 7.2 Hz), 1.93 (1H, qd, J 7.5 and 1.8 Hz), 1.80e1.30 (8H,
m), 1.10e0.95 (1H, m), 0.78 (3H, s), 0.77 (3H, d, J 7.5 Hz);
13C NMR (75 MHz, CDCl3): d 112.6 (C), 64.9 (CH2), 63.6
(CH2), 62.9 (CH2), 43.1 (CH), 40.2 (CH), 34.0 (C), 33.2 (CH),
28.8 (CH2), 26.7 (CH2), 22.4 (CH3), 21.7 (CH2), 7.8 (CH3).
HRMS, m/z calcd for C13H22O3Na (MþNa): 249.1467; found:
249.1465.
To a magnetically stirred suspension of PCC (715 mg,
3.32 mmol) and NaOAc (430 mg, 4.99 mmol) in anhydrous
CH2Cl2 (3 mL) was added a solution of the secondary alcohol
19 (400 mg, 1.66 mmol) in anhydrous CH2Cl2 (2 mL) and
stirred vigorously for 3 h at rt. The reaction mixture was then
filtered through a small silica gel column and the column was
eluted with more CH2Cl2. Evaporation of the solvent and
purification of the residue on a silica gel column using ethyl
acetateehexane (1:9) as eluent furnished the ketone 20
(337 mg, 85%) as oil. [a]D20 ꢀ84.0 (c 9.0, CHCl3); IR (neat):
nmax/cmꢀ1 2935, 2873, 1706, 1460, 1358, 1143, 1103, 1064,
947; 1H NMR (300 MHz, CDCl3): d 4.08e3.70 (4H, m), 2.55
(1H, t, J 9.3 Hz), 2.46 (1H, q, J 7.5 Hz), 2.15 (3H, s), 2.00e
1.46 (4H, m), 1.40e1.26 (1H, m), 1.10e0.80 (2H, m), 0.82
(3H, s), 0.73 (3H, d, J 7.2 Hz); 13C NMR (75 MHz, CDCl3):
d 211.1 (C), 112.2 (C), 65.3 (CH2), 63.2 (CH2), 53.3 (CH),
38.6 (CH), 35.7 (C), 33.3 (CH), 32.4 (CH3), 28.5 (CH2), 26.1
(CH2), 22.4 (CH3), 21.9 (CH2), 7.4 (CH3). HRMS, m/z calcd
for C14H22O3Na (MþNa): 261.1467; found: 261.1468.
4.9. (1S,2R,4R,6S)-1,6-Dimethylbicyclo[2.2.2]octane-spiro-
[5.20]-1,3-dioxolane-2-carboxaldehyde (18)
To a magnetically stirred solution of the primary alcohol 17
(454 mg, 2.0 mmol) in dry CH2Cl2 (2 mL) was added PDC
(1.5 g, 4.0 mmol) and stirred for 6 h at rt. The reaction mixture
was then filtered through a short silica gel column and eluted
with excess CH2Cl2. Evaporation of the solvent and purification
of the residue on a silica gel column using ethyl acetateehexane
(1:9) as eluent furnished the aldehyde 18 (395 mg, 88%) as col-
orless oil. [a]D23 ꢀ54.7 (c 2.9, CHCl3); IR (neat): nmax/cmꢀ1
2940, 2874, 2726, 1717, 1461, 1382, 1355, 1167, 1148, 1101,
1
1056, 946; H NMR (300 MHz, CDCl3): d 9.49 (1H, d, J
4.12. Ethyl E-3-[(1S,2S,4R,6S)-1,6-dimethylbicyclo[2.2.2]-
octane-spiro[5.20]-1,3-dioxolane-2-yl]but-2-enoate (21)
3.3 Hz), 3.70e3.45 (4H, m), 2.00e1.80 (2H, m), 1.71 (1H, qd,
J 7.5 and 1.8 Hz), 1.60e1.40 (2H, m), 1.35e1.20 (2H, m),
1.20e1.06 (1H, m), 0.85e0.74 (1H, m), 0.66 (3H, s), 0.54
(3H, d, J 6.9 Hz); 13C NMR (75 MHz, CDCl3): d 204.5 (CH),
111.8 (C), 65.3 (CH2), 63.4 (CH2), 54.2 (CH), 42.2 (CH), 36.1
(C), 32.8 (CH), 28.2 (CH2), 23.0 (CH3), 22.0 (CH2), 21.7
(CH2), 8.1 (CH3). HRMS, m/z calcd for C13H21O3 (MþH):
225.1485; found: 225.1495.
A suspension of sodium hydride (460 mg, 60% dispersion in
oil, 11.5 mmol) in hexanes under nitrogen atmospherewas mag-
netically stirred for 10 min and the solvent was syringed out.
The oil free NaH was then suspended in dry THF (2 mL) and
cooled in an ice bath. Triethyl phosphonoacetate (2.4 mL,
12.0 mmol) was added drop wise and the reaction mixture was

2570
A. Srikrishna, G. Ravi / Tetrahedron 64 (2008) 2565e2571
stirred for 30 min at rt. A solution of ketone 20 (550 mg,
2.31 mmol) in dry THF (2 mL) was added drop wise to the reac-
tion mixture and refluxed for 48 h. The reaction was then
quenched by careful addition of satd aq NH4Cl solution
(3 mL) and extracted with ether (3ꢂ6 mL). The ether extract
was washed with brine (6 mL) and dried (Na2SO4). Evaporation
of the solvent and purification of the residue over a silica gel col-
umn using ethyl acetateehexane (1:19) as eluent furnished the
a,b-unsaturated ester 21 (660 mg, 93%) as oil. [a]2D3 ꢀ40.2 (c
5.0, CHCl3); IR (neat): nmax/cmꢀ1 2958, 2938, 2874, 1713,
1634, 1461, 1227, 1210, 1143, 1102, 1049, 949, 865; 1H NMR
(300 MHz, CDCl3): d 5.75 (1H, s), 4.13 (2H, q, J 6.9 Hz),
4.00e3.70 (4H, m), 2.23 (3H, s), 2.30e2.10 (1H, m), 2.00e
1.50 (5H, m), 1.44e1.26 (2H, m), 1.29 (3H, t, J 6.9 Hz),
1.00e0.90 (1H, m), 0.76 (3H, d, J 7.5 Hz), 0.69 (3H, s); 13C
NMR (75 MHz, CDCl3): d 166.5 (C), 162.1 (C), 118.4 (CH),
112.4 (C), 65.4 (CH2), 63.3 (CH2), 59.3 (CH2), 52.7 (CH),
39.9 (CH), 36.5 (C), 33.8 (CH), 29.6 (CH2), 27.9 (CH2), 22.5
(CH3), 21.9 (CH2), 19.7 (CH3), 14.5 (CH3), 7.9 (CH3).
HRMS, m/z calcd for C18H28O4Na (MþNa): 331.1885; found:
331.1881.
washed with brine (3 mL) and dried (Na2SO4). Evaporation of
the solvent and purification of the residue on a silica gel column
using ethyl acetateehexane (1:3) as eluent furnished the alcohol
23 (38 mg, 98%) as oil. [a]D22 ꢀ69.8 (c 4.1, CHCl3); IR (neat):
nmax/cmꢀ1 3397, 2929, 2871, 1462, 1265, 1151, 1102, 1056,
947; 1H NMR (300 MHz, CDCl3): d 4.00e3.50 (6H, m),
2.05e1.20 (13H, m), 0.89 (3H, d, J 7.2 Hz), 0.81 (3H, s), 0.74
(3H, d, J 7.2 Hz); 13C NMR (75 MHz, CDCl3): d 113.1 (C),
65.3 (CH2), 63.1 (CH2), 61.6 (CH2), 46.1 (CH), 40.6 (CH),
35.4 (C), 34.3 (CH2), 34.0 (CH), 30.8 (CH2), 29.9 (CH), 23.4
(CH2), 21.8 (CH2), 21.7 (CH3), 18.8 (CH3), 7.6 (CH3).
HRMS, m/z calcd for C16H28O3Na (MþNa): 333.2042; found:
333.2042.
4.15. (1R,3S,4S,5S)-5-[(1S)-3-Hydroxy-1-methylpropyl]-3,4-
dimethylbicyclo[2.2.2]octan-2-one (24)
A solution of the ketal 23 (22 mg, 0.08 mmol) in acetic acid
(0.5 mL) and water (0.5 mL) was heated at 60 ꢁC for 1 h. It was
then cooled, diluted with 3 N HCl (2 mL), and extracted with
CH2Cl2 (3ꢂ3 mL). The combined organic phase was washed
with aq NaHCO3 (3 mL) and brine (6 mL), and dried
(Na2SO4). Evaporation of the solvent and purification of the res-
idue on a silica gel column using ethyl acetateehexane (1:3) as
eluent furnished the keto alcohol 24 (16 mg, 90%) as oil. [a]D21
ꢀ27.5 (c 0.4, CHCl3); IR (neat): nmax/cmꢀ1 3408, 2931, 2871,
1716, 1513, 1462, 1387, 1216, 1053, 829; 1H NMR
(300 MHz, CDCl3): d 3.75e3.50 (2H, m), 2.44 (1H, qd, J 7.2
and 1.8 Hz), 2.29 (1H, br s), 2.18e2.00 (1H, m), 2.00e1.50
(7H, m), 1.40e1.05 (3H, m), 1.01 (3H, d, J 7.2 Hz), 0.97 (3H,
s), 0.93 (3H, d, J 6.9 Hz); 13C NMR (75 MHz, CDCl3):
d 219.3 (C), 60.9 (CH2), 46.6 (CH), 46.4 (CH), 42.6 (CH),
37.9 (C), 34.4 (CH2), 31.5 (CH2), 29.7 (CH), 24.7 (CH2), 23.9
(CH2), 21.9 (CH3), 19.2 (CH3), 9.5 (CH3). HRMS, m/z calcd
for C14H24O2Na (MþNa): 247.1674; found: 247.1672.
4.13. Ethyl (3S)-3-[(1S,2S,4R,6S)-1,6-dimethylbicyclo[2.2.2]-
octane-spiro[5.20]-1,3-dioxolan-2-yl]butanoate (22)
To a solution of the unsaturated ester 21 (46 mg, 0.14 mmol)
in hexane (1 mL) was added activated 10% PdeC (25 mg) and
the reaction mixture was stirred at 1 atm pressure hydrogen at-
mosphere, created by evacuative displacement of air (balloon),
for 4 h. The reaction mixture was passed through a short silica
gel column to remove the catalyst. Evaporation of the solvent
and purification of the residue over a silica gel column using
ethyl acetateehexane (1:19) as eluent furnished the saturated es-
ter 22 (46 mg, 100%) as oil. [a]2D3 ꢀ57.9 (c 9.4, CHCl3); IR
(neat): nmax/cmꢀ1 2959, 2937, 2873, 1734, 1462, 1381, 1271,
1
1173, 1151, 1064, 1034, 948; H NMR (300 MHz, CDCl3):
d 4.11 (2H, q, J 7.2 Hz), 4.00e3.70 (4H, m), 2.49 (1H, dd, J
13.5 and 3.6 Hz), 2.45e2.25 (1H, m), 2.16 (1H, dd, J 13.5 and
11.4 Hz), 2.00 (1H, qd, J 7.2 and 1.5 Hz), 1.80e1.30 (7H, m),
1.26 (3H, t, J 7.2 Hz), 1.05e0.94 (1H, m), 0.92 (3H, d, J
6.6 Hz), 0.84 (3H, s), 0.75 (3H, d, J 6.9 Hz); 13C NMR
(75 MHz, CDCl3): d 173.3 (C), 112.8 (C), 65.4 (CH2), 63.1
(CH2), 59.9 (CH2), 45.4 (CH), 40.5 (CH), 37.2 (CH2), 35.3
(C), 33.9 (CH), 30.7 (2C, CH and CH2), 23.6 (CH2), 21.8
(CH3), 21.7 (CH2), 19.4 (CH3), 14.4 (CH3), 7.6 (CH3).
HRMS, m/z calcd for C18H30O4Na (MþNa): 291.1936; found:
291.1927.
4.16. (3S)-3-[(1S,2S,4R,6S)-1,6-Dimethyl-5-oxobicyclo-
[2.2.2]octan-2-yl]but-1-yl methanesulfonate (25)
To an ice cold (0 ꢁC) magnetically stirred solution of the keto
alcohol 24 (9 mg, 0.04 mmol) in pyridine (1 mL) and CH2Cl2
(0.5 mL) was added methanesulfonyl chloride (0.03 mL,
0.4 mmol) and the reaction mixture was stirred for 45 min at
rt. It was then diluted with 2 mL of water and extracted with
CH2Cl2 (3ꢂ2 mL). The organic layer was washed with 3 N
HCl (2 mL), satd aq NaHCO3 solution (2 mL), and brine
(5 mL), and dried (Na2SO4). Evaporation of the solvent and
purification of the residue on a silica gel column using ethyl
acetateehexane (1:3) as eluent furnished the ketomesylate 25
(11 mg, 91%) as oil. [a]D21 ꢀ42.4 (c 2.0, CHCl3); IR (neat):
nmax/cmꢀ1 2956, 2941, 2874, 1716, 1471, 1354, 1174, 976,
4.14. (3S)-3-[(1S,2S,4R,6S)-1,6-Dimethylbicyclo[2.2.2]-
octane-spiro[5.20]-1,3-dioxolane-2-yl]butanol (23)
1
To a cold (0 ꢁC) magnetically stirred solution of the saturated
ester 22 (46 mg, 0.14 mmol)in dry ether (1 mL) was added LAH
(32 mg, 0.87 mmol) and stirred for 1 h at rt. Ethyl acetate
(0.5 mL) was added to the reaction mixture to consume the ex-
cess LAH. The reaction was then quenched with water (1 mL)
and extracted with ether (3ꢂ5 mL). The ether extract was
949, 892; H NMR (300 MHz, CDCl3): d 4.30e4.10 (2H, m),
2.94 (3H, s), 2.31 (1H, qd, J 7.2 and 1.8 Hz), 2.27 (1H, br s),
2.20e2.00 (1H, m), 2.00e1.35 (8H, m), 1.30e1.10 (1H, m),
0.99 (3H, d, J 7.5 Hz), 0.95 (3H, d, J 7.2 Hz), 0.94 (3H, s);
13C NMR (75 MHz, CDCl3): d 218.2 (C), 67.8 (CH2), 46.7
(CH), 46.3 (CH), 42.6 (CH), 38.0 (C), 37.5 (CH), 31.7 (CH2),

A. Srikrishna, G. Ravi / Tetrahedron 64 (2008) 2565e2571
2571
31.1 (CH2), 29.8 (CH3), 24.8 (CH2), 23.9 (CH2), 21.9 (CH3),
18.8 (CH3), 9.6 (CH3). HRMS, m/z calcd for C15H26O4SNa
(MþNa): 325.1450; found: 325.1437.
4.17. (1R,3R,6S,7S,8S)-3,6,8-Trimethyltricyclo[5.3.1.03.8]-
undecan-2-one (norseychellenone 26)
2860, 1642, 1462, 1379, 1366, 883; 1H NMR (300 MHz,
CDCl3): d 4.79 (1H, d, J 1.5 Hz), 4.58 (1H, d, J 1.5 Hz), 2.20
(1H, s), 1.95e1.75 (1H, m), 1.70e1.10 (11H, m), 0.96 (3H, s),
0.83 (3H, s), 0.75 (3H, d, J 6.6 Hz); 13C NMR (75 MHz,
CDCl3): d 162.4 (C), 103.4 (CH2), 44.7 (CH), 39.8 (C), 37.6
(CH), 37.2 (CH2), 35.1 (C), 31.6 (CH2), 29.9 (CH), 27.7 (CH2),
26.5 (CH2), 26.4 (CH2), 24.9 (CH3), 20.7 (CH3), 18.7 (CH3).
A suspension of sodium hydride (20 mg, 60% dispersion in
oil, 0.5 mmol) in hexanes under nitrogen atmosphere was mag-
netically stirred for 10 min and the solvent was syringed out.
The oil free NaH was then suspended in dry THF (0.5 mL)
and cooled in an ice bath. A solution of ketomesylate 25
(15 mg, 0.05 mmol) in THF (1 mL) was added drop wise to
the reaction mixture and then it was refluxed for 7 h. The reac-
tion was then quenched by careful addition of satd aq NH4Cl so-
lution (3 mL) and extracted with ether (3ꢂ2 mL). The combined
ether layer was washed with brine (5 mL) and dried (Na2SO4).
Evaporation of the solvent and purification of the residue over
a silica gel column using ethyl acetateehexane (1:19) as eluent
furnished norseychellenone 26 (8 mg, 76%) as oil. [a]2D3 ꢀ57.3
(c 1.1, CHCl3); IR (neat): nmax/cmꢀ1 2952, 2929, 2870, 1718,
1465, 1381, 1366, 1270, 1244, 1152, 1029, 997, 828; 1H NMR
(300 MHz, CDCl3): d 2.21 (1H, br s), 2.05e1.85 (1H, m),
1.85e1.51 (8H, m), 1.45e1.23 (3H, m), 0.96 (3H, s), 0.94
(3H, s), 0.80 (3H, d, J 6.9 Hz); 13C NMR (75 MHz, CDCl3):
d 222.7 (C), 49.1 (C), 43.9 (CH), 42.9 (CH), 37.4 (C), 33.4
(CH2), 30.6 (CH2), 29.9 (CH), 26.7 (CH2), 24.0 (CH2), 22.8
(CH2), 20.2 (CH3), 19.4 (CH3), 18.6 (CH3). HRMS, m/z calcd
for C14H22ONa (MþNa): 229.1568; found: 229.1563.
Acknowledgements
We thank the Council of Scientific and Industrial Research,
New Delhi for the award of a research fellowship to G.R. and
Dr. G. Satyanarayana for helpful discussions.
References and notes
1. (a) Wolff, G.; Ourisson, G. Tetrahedron Lett. 1968, 3849; (b) Wolff, G.;
Ourisson, G. Tetrahedron 1969, 25, 4903; (c) Maheshwari, M. L.; Saxena,
D. B. Indian J. Chem. 1974, 12B, 1221.
2. (a) Rao, G. S. R. S.; Bhaskar, K. V. J. Chem. Soc., Perkin Trans. 1 1993,
2813; (b) Hagiwara, H.; Okano, A.; Uda, H. J. Chem. Soc., Perkin Trans.
1 1990, 2109; (c) Stork, G.; Baine, N. H. Tetrahedron Lett. 1985, 26,
5927; (d) Welch, S. C.; Chou, C.-Y.; Gruber, J. M.; Assercq, J.-M.
J. Org. Chem. 1985, 50, 2668; (e) Welch, S. C.; Gruber, J. M.; Morrison,
P. A. J. Org. Chem. 1985, 50, 2676; (f) Jung, M. E.; McCombs, C. A.;
Takeda, Y.; Pan, Y.-G. J. Am. Chem. Soc. 1981, 103, 6677; (g) Yamada,
K.; Kyotani, Y.; Manabe, S.; Suzuki, M. Tetrahedron 1979, 35, 293; (h)
Frater, G. Helv. Chim. Acta 1974, 57, 172; (i) Fukamiya, N.; Kato, M.;
Yoshikoshi, A. J. Chem. Soc., Perkin Trans. 1 1973, 1843; (j) Mirrington,
R. N.; Schmalzl, K. J. J. Org. Chem. 1972, 37, 2877; (k) Piers, E.; de Wall,
W.; Britton, R. W. J. Am. Chem. Soc. 1971, 93, 5113; For an attempted
synthesis, see: Cory, R. M.; Bailey, M. D.; Tse, D. W. C. Tetrahedron
Lett. 1990, 31, 6839.
4.18. (1R,3S,6S,7S,8S)-3,6,8-Trimethyl-2-methylenetricyclo-
[5.3.1.03.8]undecane (seychellene 1)
3. (a) Srikrishna, A.; Kumar, P. R.; Gharpure, S. J. Indian J. Chem. 2006, 45B,
1909; (b) Srikrishna, A.; Satyanarayana, G. Tetrahedron Lett. 2006, 47,
367; (c) Srikrishna, A.; Satyanarayana, G. Tetrahedron: Asymmetry 2005,
16, 3992; (d) Srikrishna, A.; Satyanarayana, G. Tetrahedron 2005, 61,
8855; (e) Srikrishna, A.; Satyanarayana, G. Org. Lett. 2004, 6, 2337; (f)
Srikrishna, A.; Gharpure, S. J. J. Org. Chem. 2001, 66, 4379; (g) Srikrishna,
A.; Gharpure, S. J. J. Chem. Soc., Perkin Trans. 1 2000, 3191; (h)
Srikrishna, A.; Gharpure, S. J. Tetrahedron Lett. 1999, 40, 1035.
4. Srikrishna, A.; Ravi, G.; Satyanarayana, G. Tetrahedron Lett. 2007, 48, 73.
5. Srikrishna, A.; Hemamalini, P. Indian J. Chem. 1990, 29B, 152.
6. (a) Zhao, R.-B.; Zhao, Y.-F.; Song, G.-Q.; Wu, Y.-L. Tetrahedron Lett.
1990, 31, 3559; (b) Ihara, M.; Fukumoto, K. Angew. Chem., Int. Ed.
Engl. 1993, 32, 1010; (c) Miyaoka, H.; Yamada, Y. Bull. Chem. Soc. Jpn.
2002, 75, 203.
To an ice cold suspension of Mg (97 mg, 4.03 mmol) and
TiCl4 (0.11 mL, 1.01 mmol) in CH2Cl2 (2 mL) was added
drop wise a solution of the ketone 26 (28 mg, 0.13 mmol) in
CH2Cl2 (1.5 mL) and THF (1 mL), and stirred for 30 min at
0 ꢁC and for 20 min at rt. The reaction mixture was recooled
to 0 ꢁC, satd aq potassium carbonate solution (4 mL) was added,
and extracted with ether (3ꢂ4 mL). The ether extract was
washed with brine (5 mL) and dried (Na2SO4). Evaporation of
the solvent and purification of the residue over a silica gel col-
umn using hexane as eluent furnished (ꢀ)-seychellene 1
(21 mg, 86%) as oil. [a]2D2 ꢀ70.0 (c 0.3, CHCl3) {lit.1 [a]D
ꢀ72 (c 0.4, CHCl3)}; IR (neat): nmax/cmꢀ1 3067, 2954, 2925,
7. Yan, T.-H.; Tsai, C.-C.; Chien, C.-T.; Cho, C.-C.; Huang, P.-C. Org. Lett.
2004, 6, 4961.