Enantiospecific approaches to bicyclic vibsanes: a ring-closing metathesis reaction-based strategy to functionalized bicyclo[4.3.1]decanes

Article abstract of DOI:10.1016/j.tetasy.2008.08.012

An enantiospecific synthesis of functionalized bicyclo[4.3.1]decane, the bicyclic core system present in some bi- and tricyclic vibsane diterpenoids, for example, vibsanin E, via an RCM reaction of 2,6-diallylcarvone derivatives is described. It has been further extended to the synthesis of tricyclo[6.4.1.0^1,5]tridecanes starting from 2,6,6-triallylcarvones.

Full text of DOI:10.1016/j.tetasy.2008.08.012

Tetrahedron: Asymmetry 19 (2008) 1984–1991
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Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Enantiospecific approaches to bicyclic vibsanes: a ring-closing metathesis
reaction-based strategy to functionalized bicyclo[4.3.1]decanes
*
Adusumilli Srikrishna , Vijendra H. Pardeshi, Gedu Satyanarayana
Department of Organic Chemistry, Indian Institute of Science, Bangalore 560 012, India
a r t i c l e i n f o
a b s t r a c t
Article history:
An enantiospecific synthesis of functionalized bicyclo[4.3.1]decane, the bicyclic core system present in
some bi- and tricyclic vibsane diterpenoids, for example, vibsanin E, via an RCM reaction of 2,6-diallyl-
carvone derivatives is described. It has been further extended to the synthesis of tricyclo[6.4.1.01,5]tride-
canes starting from 2,6,6-triallylcarvones.
Received 12 July 2008
Accepted 8 August 2008
Available online 29 August 2008
Ó 2008 Elsevier Ltd. All rights reserved.
1. Introduction
anes are depicted in Figure 1. This family contains a wide variety of
interrelated structural types ranging from mono to tricyclic
Vibsane diterpenes are rare natural products and they occur
systems. For example, 11-membered monocyclic vibsanin B 1 is
exclusively in Viburnum species.1 Representative examples of vibs-
related to cycloheptanoid vibsanin C 2 by a [3,3]-sigmatropic shift2
O
OH
H
O
O
O
H
OH
H
O
HO
O
O
O
O
O
O
O
Vibsanin B 1
Vibsanin E 3
Vibsanin C 2
OMe
OH
O
O
H
H
O
H
CHO
O
O
H
O
OH
OHC
H
O
O
H
Cyclovibsanin A 4
Aldolvibsanin B 6
Furanovibsanin D 5
H
OH
O
O
O
O
MeO
O
O
O
O
O
O
O
O
O
H
O
OMe
OH
Spirovibsanin A
Vibsanin O
Neovibsanin A
Figure 1.
* Corresponding author. Tel.: +91 80 22932 215; fax: +91 80 23600529.
E-mail address: ask@orgchem.iisc.ernet.in (A. Srikrishna).
0957-4166/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2008.08.012

A. Srikrishna et al. / Tetrahedron: Asymmetry 19 (2008) 1984–1991
1985
(Cope rearrangement). Similarly, the tricyclic vibsanin E 3, cyclo-
vibsanins, for example, 4 and furanovibsanins, for example, 5 are
related to vibsanin C 2 by an intramolecular ene-reaction followed
by either intramolecular etherification,3 carbocyclization or furan
formation of the 1,4-dione moiety. Whereas the hydrolysis of vibs-
anin C 2, followed by intramolecular aldol reaction leads to the
generation of aldolvibsanin B 6, some of the vibsanins have shown
potential biological activities, such as plant growth inhibition,
cytotoxicity, and neurite outgrowth promoting activity.1–3 Vibs-
anes are interesting from a synthesis point of view because of
the structural diversity present among them coupled with the
presence of dense functionality and biological activity. Although
there has been no total synthesis reported so far, several efforts
have been reported for the construction of the bicyclic core of vibs-
anin E and its analogues.4 In continuation of our interest in the
enantiospecific construction of polycyclic bridged natural prod-
ucts5 starting from the readily and abundantly available monoter-
pene (R)-carvone, we have initiated an enantiospecific approach to
vibsane diterpenoids. Herein, we report our investigations on the
rapid and efficient enantiospecific construction of the bicyclo-
[4.3.1]decane framework present in some bi- and tricyclic vibsanes
employing an RCM-based approach.
(R)-carvone 8 as the chiral starting material (Scheme 1). It was
visualized that introduction of two allyl moeities at the C-2 and
C-6 carbons of carvone 8 followed by a ring-closing metathesis
(RCM) reaction6 would lead to bicyclo[4.3.1]undecane system.
In order to avoid stereochemical ambiguity, reactions were car-
ried out starting from the stereodefined 6-allyl-6-methylcarvones
9 and 10, which were obtained7 by kinetic alkylation of carvone
8 with LDA and methyl iodide, followed by LDA and allyl bromide,
or vice versa, respectively. For the allylation at the C-2 carbon of
trans-methylallylcarvone 9, two alternate approaches, a base-med-
iated thermodynamic a-alkylation and a reductive allylation, were
explored, which surprisingly produced different stereochemistry at
the C-2 position (Scheme 2). Thus, the reaction of enone 9 with
sodium hydride and allyl bromide in a mixture of THF and HMPA
furnished the a-allylated b-enone 11, whose structure was estab-
lished from its spectroscopic data and the stereochemistry was
tentatively assigned, and which was confirmed by the RCM reac-
tion. As the reaction was found to be inefficient with first genera-
tion catalyst [Cl2(PCy3)2Ru@CHPh], the RCM reaction was carried
out using Grubbs’ second generation (G-II) catalyst. Treatment of
the diallylated compound 11 with 5 mol % Grubbs’ second genera-
tion catalyst in methylene chloride led to a clean RCM reaction
resulting in the formation of the bicyclo[4.3.1]decanone 12 in
87% yield. The presence of the sodiated molecular ion at m/z
239.1407 in the high-resolution mass spectrum revealed the loss
of an ethylene group supporting the monomeric nature of com-
pound 12. The presence of four ring olefinic protons in addition
2. Results and discussion
We envisioned the synthesis of the bicyclo[4.3.1]decane ring
system 7 present in some bi- and tricyclic vibsanes employing
O
O
O
2
6
7
8
9
10
carbon framework
(
R
)-carvone
of vibsanin E
Scheme 1.
O
O
O
b
a
77%
87%
H
9
12
11
c
73%
O
O
b
N
N
89%
H
Cl
Ru
Cl
Ph
13
16
PCy
3
G-II
O
O
S
R
d
d
11
13
97%
96%
15
14
Scheme 2. Reagents and conditions: (a) NaH, THF, HMPA, BrCH2CH@CH2; (b) G-II catalyst (5 mol %), CH2Cl2; (c) Li, liq. NH3, THF, BrCH2CH@CH2; (d) H2 (1 atm), 10% Pd/C,
MeOH.

1986
A. Srikrishna et al. / Tetrahedron: Asymmetry 19 (2008) 1984–1991
to two olefinic protons of the isopropenyl group in the 1H NMR
spectrum and the presence of six olefinic carbons (one quaternary
at 144.6, four methines at 134.5, 130.5, 128.9 and 128.0, and a
methylene at 114.4) in the 13C NMR spectrum established the
structure of bicyclic ketone 12.
10 mol % Grubbs’ first generation catalyst in methylene chloride
furnished the bicyclo[4.3.0]nonanone 20. The structures of the
bicyclic ketones 19 and 20 were established from their spectro-
scopic data. Alkylation of cis-allylmethylcarvone 10 with sodium
hydride and allyl bromide in THF and HMPA exclusively furnished
the diallyl compound 21 in 79% yield, which upon RCM reaction
with 5 mol % Grubbs’ second generation catalyst in methylene
chloride furnished the bicyclo[4.3.0]nonanone 22 in 89% yield,
whose structure was established from its spectroscopic data.
It was conceived that the presence of two allyl groups at the
C-6 position of carvone would effectively lead to bicyclo-
[4.3.1]decanes, irrespective of the stereochemistry at the C-2
position, and also could lead to tricyclic compounds by two RCM
reactions. Accordingly, the sequence was investigated with the tri-
allyl compounds 23 and 24. Exhaustive alkylation of carvone 8
with sodium hydride and allyl bromide in THF and HMPA fur-
nished a 2:3 mixture of 6,6-bisallylcarvone 25 and 2,6,6-trisallyl-
carvone 23, which were separated by column chromatography
on silica gel (Scheme 4). RCM reaction of trisallylcarvone 23 with
Grubbs’ first generation catalyst in methylene chloride furnished
a 5:4 mixture of the spiro compound 26 via mono RCM and tri-
cyclic product 27 via two RCM reactions, in 93% yield, which were
separated by column chromatography on silver nitrate impreg-
nated silica gel. The structures of the spiro and tricyclic com-
pounds 26 and 27 were established from their spectroscopic
data. Although spectroscopic data clearly established the structure
of the tricyclic ketone 27, in order to completely rule out the pos-
sibility of dimeric and oligomeric structure for the product 27 (a
serious competing side reaction encountered during RCM medi-
ated construction of medium sized rings and bridged compounds)8
and to confirm the stereochemistry at the two bridgehead quater-
nary carbon atoms, single crystal X-ray diffraction analysis of a
crystalline derivative of 27 was carried out. Thus, reduction of tri-
cyclic ketone 27 with lithium aluminum hydride (LAH) furnished
the secondary alcohol 28 in a highly stereoselective manner. Cou-
pling of the alcohol 28 with 3,5-dinitrobenzoic acid in the presence
of dicyclohexylcarbodiimide (DCC) and 4-N,N-dimethylaminopyr-
idine (DMAP) furnished ester 29, mp 201–203 °C. Single crystal
X-ray diffraction analysis of ester 29 (an ORTEP diagram is
depicted in Fig. 2) unambiguously established the stereochemistry
in compounds 23, 26 and 27.
In another direction, reductive allylation of trans-allylmethyl-
carvone 9 with lithium in liquid ammonia and allyl bromide
furnished the diallyl compound 13. The stereochemistry at the
newly created quaternary carbon atom in 13 was found, on the
basis of the RCM reaction, to be opposite to that of the diallyl
compound 11. This was further confirmed by hydrogenation
experiments. Hydrogenation of the diallyl compound 13 with
10% palladium over carbon as the catalyst furnished the saturated
compound 14, which was found to be different from product 15
obtained by hydrogenation of the diallyl compound 11, thus con-
firming the epimeric relationship at the newly created quaternary
carbon atom of the diallyl compounds 11 and 13. Treatment of
diallylated compound 13 with 5 mol % Grubbs’ second generation
catalyst in methylene chloride led to a clean RCM reaction result-
ing in the formation of the bicyclo[4.3.0]nonanone 16. The struc-
ture of the bicyclic ketone 16 was established from its
spectroscopic data, in particular the presence of signals due to a
typical allyl and cyclopentene olefinic groups in the 1H and 13C
NMR spectra.
Next, the sequence was carried out with cis-6-allyl-6-methyl-
carvone 10, Scheme 3. Accordingly, reductive allylation of the cis-
allylmethylcarvone 10 with lithium in liquid ammonia and allyl
bromide furnished a 3:1 epimeric mixture of the diallyl com-
pounds 17 and 18, which were separated by column chromatogra-
phy on
a silver nitrate impregnated silica gel column. The
formation of two isomers in the reductive allylation reaction is
probably the consequence of the opposite influence of the two
bulky groups at the C-5 and C-6 carbons of the cyclohexenone.
The stereochemistry in the diallyl compounds 17 and 18 were as-
signed tentatively, and were confirmed on the basis of the RCM
reactions. The RCM reactions were found to be efficient with first
generation Grubbs’ catalyst Cl2(PCy3)2Ru@CHPh. Thus, treatment
of the minor diallylated compound 18 with 10 mol % Grubbs’ first
generation catalyst in methylene chloride resulted in RCM reaction
leading to the formation of the bicyclo[4.3.1]decanone 19. Simi-
larly, treatment of the major diallylated compound 17 with
O
O
b
86%
H
O
a
67%
20
17
(3 : 1)
O
b
10
91%
O
c
H
79%
19
18
O
O
d
89%
H
21
22
Scheme 3. Reagents and conditions: (a) Li, liq. NH3, THF, BrCH2CH@CH2, 17:18 3:1; (b) Cl2(PCy3)2Ru@CHPh (10 mol %), CH2Cl2; (c) NaH, THF, HMPA, BrCH2CH@CH2; (d) G-II
catalyst (5 mol %), CH2Cl2.

A. Srikrishna et al. / Tetrahedron: Asymmetry 19 (2008) 1984–1991
1987
reaction of the trisallylcarvone 24 with Grubbs’ first generation
catalyst furnished a 1:1 mixture of the spiro compound 30 and
the bicyclo[4.3.1]decanone 31, which were separated on a silver ni-
trate impregnated silica gel column, and the structures were estab-
lished from their spectroscopic data. The trans-disposition of the
allyl and isopropenyl groups in the bicyclic compound 31 and
the low reactivity of the first generation Grubbs’ catalyst might
be responsible for the reaction to stop after the first RCM reaction.
Treatment of the bicyclic compound 31 with Grubbs’ second gen-
eration catalyst yielded the tricyclic system 32 in 92% yield, whose
structure was established from its spectroscopic data.
O
O
O
a
+
92%
8
25
23
O
O
b
23
27
91%
+
3. Conclusion
H
27
26
DNBO
(4 : 5)
In conclusion, we have developed a rapid and efficient enantio-
specific synthesis of the bicyclo[4.3.1]decane ring system of vibsa-
nins, containing functionality in all the three bridges. It has been
further extended to the enantiospecific synthesis of tricyclo-
[6.4.1]tridecanes via two RCM reactions. A novel reversal of the
stereoselectivity in the C-2 alkylation of carvones under base-
HO
c
d
97%
91%
H
H
mediated
a-alkylation and reductive allylation was also discov-
28
29
DNB = 2,4-dinitrobenzoyl
ered, which should be quite useful in stereoselective synthesis.
Scheme 4. Reagents and conditions: (a) NaH, THF, HMPA, BrCH2CH@CH2; (b)
Cl2(PCy3)2Ru@CHPh (10 mol %), CH2Cl2; (c) LAH, Et2O; (d) DCC, DMAP, 3,5-dinitro-
benzoic acid, CH2Cl2.
4. Experimental
IR spectra were recorded on a Jasco FTIR 410 spectrophotome-
ter. 1H (300 and 400 MHz) and 13C (75 and 100 MHz) NMR spectra
were recorded on JEOL JNM k-300 and Brucker Avance 400 spec-
trometers. The chemical shifts (d ppm) and coupling constants
(Hz) are reported in the standard fashion with reference to either
internal tetramethylsilane (for 1H) or the central line (77.0 ppm)
of CDCl3 (for 13C). In the13C NMR, the nature of carbons (C, CH,
CH2 and CH3) was determined by recording the DEPT-135 spectra,
and is given in parentheses. High-resolution mass spectra were re-
corded using Micromass Q-TOF micro mass spectrometer using
electronspray ionization mode. Optical rotations were measured
using a Jasco DIP-370 digital polarimeter and [a]D values are given
in units of 10ꢀ1 deg cm2 gꢀ1. All small-scale dry reactions were car-
ried out using standard syringe-septum technique. Reactions were
monitored by TLC on silica gel using a combination of hexane and
ethyl acetate as eluents. Acme’s silica gel (100–200 mesh) was
used for column chromatography (approximately 20 g per one g
of crude material).
4.1. (2R,5S,6S)-2,6-Bisallyl-5-isopropenyl-2,6-
dimethylcyclohex- 3-enone 11
Figure 2. ORTEP diagram of 29.
To a magnetically stirred suspension of NaH (116 mg, 60% dis-
persion in oil, 2.9 mmol, washed with dry hexanes) in THF (1 mL)
and HMPA (1 mL) was added a solution of enone 9 (60 mg,
0.29 mmol) in THF (1 mL), followed by allyl bromide (0.25 mL,
Reductive alkylation of 6,6-diallylcarvone 25 with lithium in
liquid ammonia and allyl bromide furnished the second trisallyl-
carvone 24 in a highly stereoselective manner (Scheme 5). RCM
O
O
O
a
79%
b
85%
+
O
H
24
25
31
30
(1 : 1)
c
31
92%
O
H
32
Scheme 5. Reagents and conditions: (a) Li, liq. NH3, THF, BrCH2CH@CH2; (b) Cl2(PCy3)2Ru@CHPh (10 mol %), CH2Cl2; (c) G-II catalyst (5 mol %), CH2Cl2.

1988
A. Srikrishna et al. / Tetrahedron: Asymmetry 19 (2008) 1984–1991
2.9 mmol), and reaction mixture was stirred for 10 h at rt. It was
then quenched with water (3 mL) and extracted with ether
(3 mL ꢁ 3). The combined ether extract was washed with brine
and dried (Na2SO4). Evaporation of the solvent and purification of
the residue over a silica gel column using CH2Cl2–hexane (1:9) as
24.8 (CH3), 23.4 (CH3), 23.2 (CH3), 22.9 (CH2); HRMS: m/z calcd
for C17H26ONa (M+Na): 269.1881; found: 269.1878.
4.4. (2S,3S,6S)-3-Isopropyl-2,6-dimethyl-2,6-
dipropylcyclohexanone 14
eluent furnished the ketone 11 (55 mg, 77%). ½a D23
¼ ꢀ289 (c 2.4,
ꢂ
CHCl3); IR (neat):
m
max/cmꢀ1 3077, 3018, 2979, 2933, 1702, 1640,
To a solution of the ketone 13 (28 mg, 0.11 mmol) in methanol
(1 mL) was added activated 10% Pd–C (10 mg). The reaction mix-
ture was stirred for 1 h at rt in an atmosphere of hydrogen, created
by evacuative replacement of air (balloon), and then the catalyst
was filtered off. Evaporation of the solvent furnished saturated
1457, 1438, 1378, 1290, 995, 916, 760, 732; 1H NMR (400 MHz,
CDCl3): d 5.65–5.55 (4H, m), 5.03 (2H, d, J 10.5 Hz), 4.99 (2H, d, J
16.9 Hz), 4.78 (1H, s), 4.71 (1 H, s), 3.04 (1H, d, J 4.6 Hz), 2.40–
2.30 (2H, m), 2.26 (1H, dd, J 13.6 and 7.8 Hz), 2.18 (1H, dd, J 13.6
and 6.9 Hz), 1.51 (3H, s, olefinic-CH3) 1.12 (3H, s) and 0.91 (3H,
s) [2 ꢁ tert-CH3]; 13C NMR (100 MHz, CDCl3): d 215.9 (C, C@O),
144.0 (C, C@CH2), 133.7 (CH), 133.4 (CH), 133.1 (CH), 126.7 (CH),
118.6 (CH2), 118.5 (CH2), 115.3 (CH2), 54.8 (CH), 49.9 (C), 46.7
(C), 44.3 (CH2), 42.9 (CH2), 24.8 (CH3), 20.8 (CH3), 19.6 (CH3);
HRMS: m/z calcd for C17H24ONa (M+Na): 267.1725; found:
267.1712.
ketone 14 (29 mg, 97%) as an oil. ½a D24
¼ þ51:7 (c 3.0, CHCl3); IR
ꢂ
(neat):
m
max/cmꢀ1 2958, 2933, 2873, 1692 (C@O), 1467, 1374,
1104, 1065, 1039, 993, 978; 1H NMR (400 MHz, CDCl3): d 1.95–
1.75 (3H, m), 1.70–1.30 (6H, m), 1.30–1.10 (5H, m), 0.98 (3H, s)
and 0.95 (3H, s) [2 ꢁ tert-CH3], 0.90–0.80 (12H, m); 13C NMR
(100 MHz, CDCl3): d 218.2 (C, C@O), 53.6 (C), 47.5 (C), 46.0 (CH),
41.8 (CH2), 39.3 (CH2), 37.4 (CH2), 26.2 (CH), 25.1 (CH3), 24.7
(CH3), 22.8 (CH3), 19.2 (CH3), 18.6 (CH2), 17.4 (CH2), 17.2 (CH2),
14.9 (CH3), 14.7 (CH3). HRMS: m/z calcd for C17H32ONa (M+Na):
275.2351; found: 275.2351.
4.2. (1S,6R,9S)-9-Isopropenyl-1,6-dimethylbicyclo[4.3.1]deca-
3,7-dien-10-one 12
To a magnetically stirred solution of the diallylcarvone 11
(24 mg, 0.98 mmol) in anhydrous CH2Cl2 (10 mL, 0.01 M) was
added Grubbs’ second generation catalyst (5 mg, 5 mol %). The
reaction mixture was stirred magnetically for 8 h at rt and the cat-
alyst was filtered off through a short silica gel column. Evaporation
of the solvent, followed by purification on a silica gel column using
CH2Cl2–hexane (1:9) as eluent furnished bicyclic ketone 12 (18 mg,
4.5. (2S,3S,6R)-3-Isopropyl-2,6-dimethyl-2,6-
dipropylcyclohexanone 15
To a solution of ketone 11 (40 mg, 0.16 mmol) in methanol
(1 mL) was added activated 10% Pd–C (10 mg). The reaction mix-
ture was stirred for 1 h at rt in an atmosphere of hydrogen, created
by evacuative replacement of air (ballon), and then the catalyst
was filtered off. Evaporation of the solvent furnished the saturated
86%) as an oil. ½a D23
ꢂ
¼ ꢀ265 (c 1.1, CHCl3); IR (neat):
m
max/cmꢀ1
3073, 3019, 2970, 2869, 1702, 1641, 1456, 1374, 1213, 1164,
1014, 997, 894, 810, 760, 672. 1H NMR (400 MHz, CDCl3): d 5.85–
5.75 (1H, m), 5.65–5.55 (1H, m), 5.51 (1H, dd, J 9.8 and 4.9 Hz),
5.38 (1H, d, J 9.8 Hz), 4.70 (1H, s), 4.67 (1H, s), 2.98 (1H, d, J
4.9 Hz), 2.34 (1H, dd J 15.0 and 7.6 Hz), 2.12 (1H, dd, J 15.7 and
6.6 Hz), 2.09 (1H, dd, J 15.7 and 4.5 Hz), 1.90 (1H, dd, J 15.0 and
4.8 Hz), 1.39 (3H, s, olefinic–CH3), 1.23 (3H, s) and 0.97 (3H, s)
[2 ꢁ tert-CH3]; 13C NMR (100 MHz, CDCl3): d 214.5 (C, C@O),
144.6 (C, C@CH2), 134.5 (CH), 130.5 (CH), 128.9 (CH), 128.0 (CH),
114.4 (CH2), 60.3 (CH), 50.9 (C), 48.2 (C), 41.8 (CH2), 40.2 (CH2),
25.2 (CH3), 22.5 (CH3), 19.1 (CH3); HRMS: m/z calcd for C15H20ONa
(M+Na): 239.1412; found: 239.1407.
ketone 15 (39 mg, 97%) as an oil. ½a D24
¼ þ19:4 (c 3.7, CHCl3); IR
ꢂ
(neat):
m
max/cmꢀ1 2959, 2934, 2872, 1694, 1464, 1375, 1105,
1054, 1019, 994, 734; 1H NMR (400 MHz, CDCl3): d 2.00–1.88
(1H, m), 1.80 (1H, quintet, J 6.9 Hz), 1.68–1.50 (6H, m), 1.25–1.05
(5H, m), 1.02 (3H, s) and 0.98 (3H, s) [2 ꢁ tert-CH3], 0.93 (3 H, d J
7.0 Hz), 0.90–0.80 (10H, m); 13C NMR (100 MHz, CDCl3): d 219.9
(C, C@O), 53.6 (C), 47.4 (C), 45.5 (CH), 43.0 (CH2), 39.5 (CH2), 35.1
(CH2), 27.3 (CH3), 26.1 (CH), 24.7 (CH3), 24.1 (CH3), 19.1 (CH3),
18.4 (CH2), 17.5 (CH2), 17.4 (CH2), 14.9 (2 C, CH3); HRMS: m/z calcd
for C17H32ONa (M+Na): 275.2351; found: 275.2351.
4.6. (1S,3R,6S)-3-Allyl-1,3,7-trimethylbicyclo[4.3.0]non-7-
en-2-one 16
4.3. (2S,3S,6R)-2,6-Bisallyl-5-isopropenyl-2,6-
dimethylcyclohexanone 13
RCM reaction of ketone 13 (46 mg, 0.19 mmol) in anhydrous
CH2Cl2 (19 mL, 0.01 M) using Grubbs’ second generation catalyst
(8 mg, 5 mol %) for 8 h at rt, followed by purification on a silica
gel column using CH2Cl2–hexane (1:9) as eluent furnished the
To freshly distilled liquid ammonia (50 mL) was added Li metal
(14 mg, 2 mmol). To the resultant blue coloured solution was
added a solution of the enone 9 (50 mg, 0.24 mmol) in dry THF
(4 mL) for over a period of 10 min. After 15 min the reaction mix-
ture was quenched with a solution of allyl bromide (0.18 mL,
2 mmol) in dry THF (1 mL) and the reaction was slowly allowed
to attain rt. Water (5 mL) was added to the reaction mixture after
3 h and extracted with ether (3 mL ꢁ 3). The combined organic ex-
tract was washed with brine (5 mL) and dried over Na2SO4. Evap-
oration of the solvent and purification of the residue over a silica
gel column using CH2Cl2–hexane (1:9) as eluent furnished ketone
bicyclic ketone 16 (36 mg, 89%) as an oil. ½a D23
¼ þ101 (c 2.8,
ꢂ
CHCl3); IR (neat): m
max/cmꢀ1 3077, 3043, 2964, 2936, 2875, 1712,
1640, 1452, 1376, 1243, 1005, 915, 830, 795; 1H NMR (300 MHz,
CDCl3): d 5.61 (1H, ddt, J 14.7, 8.1 and 6.3 Hz), 5.31 (1H, br s),
5.10–4.95 (2H, m), 2.85–2.75 (1H, m), 2.50–2.30 (2H, m), 2.25–
1.85 (4H, m), 1.80–1.50 (2H, m), 1.67 (3H, s, olefinic-CH3), 1.18
(3H, s) and 1.04 (3H, s) [2 ꢁ tert-CH3]; 13C NMR (75 MHz, CDCl3):
d 217.9 (C, C@O), 138.8 (C, C@CH2), 134.6 (CH), 123.3 (CH), 118.2
(CH2), 56.8 (C), 48.8 (CH), 47.2 (C), 45.4 (CH2), 39.2 (CH2), 31.7
(CH2), 28.6 (CH3), 17.3 (CH2), 16.7 (CH3), 14.6 (CH3); HRMS: m/z
calcd for C15H22ONa (M+Na): 241.1568; found: 241.1557.
13 (44 mg, 73%) as an oil. ½a D23
¼ þ56:9 (c 11.3, CHCl3); IR (neat):
ꢂ
m
max/cmꢀ1 3077, 2978, 2932, 2871, 1694, 1638, 1457, 1434, 1376,
998, 914; 1H NMR (300 MHz, CDCl3): d 5.80–5.45 (2H, m), 5.15–
4.95 (4H, m), 4.91 (1H, br s), 4.70 (1H, br s), 2.70–2.55 (2H, m),
2.35–2.05 (3H, m), 2.00–1.80 (2H, m), 1.78 (3H, s, olefinic-CH3),
1.70–1.40 (2H, m), 1.04 (3H, s) and 1.02 (3H, s) [2 ꢁ tert-CH3];
13C NMR (75 MHz, CDCl3): d 217.7 (C, C@O), 145.2 (C, C@CH2),
135.6 (CH), 133.7 (CH), 118.3 (CH2), 118.1 (CH2), 114.7 (CH2),
52.4 (C), 48.7 (CH), 47.2 (C), 43.4 (CH2), 42.3 (CH2), 34.9 (CH2),
4.7. (2R,3S,6S)- and (2R,3S,6R)-2,6-Bisallyl-3-isopropenyl-2,6-
dimethylcyclohexanones 17 and 18
To freshly distilled liquid ammonia (50 mL) was added Li metal
(35 mg, 5 mmol). To the resultant blue coloured solution was
added a solution of enone 10 (102 mg, 0.5 mmol) in dry THF

A. Srikrishna et al. / Tetrahedron: Asymmetry 19 (2008) 1984–1991
1989
(4 mL) for over a period of 10 min. After 15 min the reaction mix-
ture was quenched with a solution of allyl bromide (0.43 mL,
5 mmol) in dry THF (1 mL). Workup as described for the compound
13, followed by purification over a AgNO3 impregnated silica gel
column using CH2Cl2–hexane (1:9) as eluent furnished the
2.40–2.30 (2H, m), 2.20–2.05 (2H, m), 1.92–1.85 (1H, m), 1.80–
1.25 (3H, m), 1.68 (3H, s, olefinic-CH3), 1.17 (3H, s) and 1.06 (3H,
s) [2 ꢁ tert-CH3]; 13C NMR (100 MHz, CDCl3): d 220.4 (C, C@O),
141.8 (C), 134.2 (CH), 122.1 (CH), 118.1 (CH2), 56.5 (CH), 53.3 (C),
46.9 (C), 45.3 (CH2), 43.7 (CH2), 32.4 (CH2), 27.2 (CH3), 25.5
(CH3), 22.9 (CH2), 14.8 (CH3); HRMS: m/z calcd for C15H22ONa
(M+Na): 241.1568; found: 241.1563.
(2R,3S,6S)-isomer 17 (61 mg, 50%) as an oil. ½a D22
¼ þ2:7 (c 1.7,
ꢂ
CHCl3); IR (neat):
m
max/cmꢀ1 3077, 2976, 2936, 2870, 1694
(C@O), 1639, 1461, 1376, 995, 914, 898; 1H NMR (400 MHz, CDCl3):
d 5.62 (1H, dddd, J 17.0, 10.4, 8.0, and 6.8 Hz), 5.50 (1H, ddt, J 17.3,
10.2 and 7.2 Hz), 5.10–4.85 (5H, m), 4.60 (1H, br s), 2.50 (1H, dd, J
14.2 and 7.0 Hz), 2.31 (1H, dd, J 13.7 and 6.6 Hz), 2.23–2.05 (3H,
m), 2.00–1.90 (1H, m), 1.77 (3H, s, olefinic-CH3), 1.80–1.60 (3H,
m), 1.09 (3H, s) and 1.08 (3H, s) [2 ꢁ tert-CH3]; 13C NMR
(100 MHz, CDCl3): d 215.9 (C, C@O), 144.8 (C, C@CH2), 134.7
(CH), 134.3 (CH), 117.9 (CH2), 117.7 (CH2), 114.5 (CH2), 53.7
(CH), 51.6 (C), 47.2 (C), 44.8 (CH2), 39.2 (CH2), 35.0 (CH2), 24.7
(CH3), 24.4 (CH3), 23.2 (CH3), 22.8 (CH2); HRMS: m/z calcd for
4.10. (2R,5S,6R)-2,6-Bisallyl-5-isopropenyl-2,6-
dimethylcyclohex-3-enone 21
To a magnetically stirred suspension of NaH (192 mg, 60% dis-
persion in oil, 5.0 mmol, washed with dry hexanes) in THF (1 mL)
and HMPA (1 mL) was added a solution of enone 10 (102 mg,
0.5 mmol) in THF (1 mL), followed by allyl bromide (0.43 mL,
5.0 mmol), and reaction mixture was stirred for 10 h at rt. It was
then quenched with water (3 mL) and extracted with ether
(3 mL ꢁ 3). The combined ether extract was washed with brine
and dried (Na2SO4). Evaporation of the solvent and purification of
the residue over a silica gel column using CH2Cl2–hexane (1:9) as
C17H26ONa (M+Na): 269.1881. Found: 269.1880.
Further elution of the column with CH2Cl2–hexane (1:4) gave
(2R,3S,6R)-isomer 18 (21 mg, 17%) as an oil. ½a D22
¼ þ25:8 (c 1.7,
ꢂ
CHCl3); IR (neat):
m
max/cmꢀ1 3077, 2975, 2935, 2872, 1694
eluent furnished ketone 21 (94 mg, 77%). ½a D23
¼ ꢀ254 (c 3.1,
ꢂ
(C@O), 1639, 1457, 1375, 995, 914, 894; 1H NMR (400 MHz, CDCl3):
d 5.69 (1H, ddt, J 17.4, 10.2 and 7.4 Hz), 5.54 (1H, ddt, J 17.3, 10.2
and 7.3 Hz), 5.10–4.90 (5H, m), 4.51 (1H, s), 2.46 (1H, dd, J 14.2
and 7.2 Hz), 2.35–2.15 (4H, m), 1.98 (1H, dt, J 14.2 and 6.2 Hz),
1.87–1.80 (2H, m), 1.77 (3H, s, olefinic-CH3), 1.43 (1H, dt, J 14.1
and 6.2 Hz), 1.14 (3H, s) and 1.08 (3H, s) [2 ꢁ tert-CH3]; 13C NMR
(100 MHz, CDCl3): d 217.3 (C, C@O), 144.5 (C, C@CH2), 134.3
(CH), 133.9 (CH), 118.4 (CH2), 117.9 (CH2), 114.3 (CH2), 52.8
(CH), 51.1 (C), 47.0 (C), 42.9 (CH2), 39.2 (CH2), 33.7 (CH2), 25.7
(CH3), 24.5 (CH3), 24.3 (CH3), 22.0 (CH2); HRMS: m/z calcd for
CHCl3); IR (neat): m
max/cmꢀ1 3076, 3018, 2978, 2934, 2876, 1703
(C@O), 1639, 1459, 1439, 1374, 993, 914; 1H NMR (400 MHz,
CDCl3): d 5.80–5.60 (2H, m), 5.61 (2H, br s), 5.10–4.90 (4H, m),
4.85 (1H, s), 4.75 (1H, s), 2.94 (1H, s), 2.45 (1H, dd, J 14.3 and
7.3 Hz), 2.35 (1H, dd, J 13.6 and 5.8 Hz), 2.19 (1H, dd, J 13.6 and
7.1 Hz), 1.99 (1H, dd, J 14.3 and 7.3 Hz), 1.56 (3H, s, olefinic-CH3),
1.14 (3H, s) and 1.13 (3H, s) [2 ꢁ tert-CH3]; 13C NMR (100 MHz,
CDCl3): d 215.9 (C, C@O), 143.8 (C, C@CH2), 134.9 (CH), 133.5
(CH), 133.3 (CH), 127.1 (CH), 118.3 (CH2), 117.9 (CH2), 115.5
(CH2), 56.2 (CH), 49.1 (C), 47.5 (C), 44.5 (CH2), 38.3 (CH2), 24.6
(CH3), 23.3 (CH3), 21.2 (CH3); HRMS: calcd for C17H24ONa
(M+Na): m/z 267.1725; found: 267.1726.
C17H26ONa (M+Na): 269.1881. Found: 269.1882.
4.8. (1R,6R,7S)-7-Isopropenyl-1,6-dimethylbicyclo[4.3.1]dec-3-
en-10-one 19
4.11. (1R,3R,6S)-3-Allyl-1,3,7-trimethylbicyclo[4.3.0]nona-4,7-
dien-2-one 22
RCM reaction of ketone 18 (16 mg, 0.07 mmol) in anhydrous
CH2Cl2 (7 mL, 0.01 M) using Grubbs’ first generation catalyst
(5 mg, 10 mol %) for 8 h at rt, followed by purification on a silica
gel column using CH2Cl2–hexane (1:19) as eluent furnished the
RCM reaction of ketone 21 (30 mg, 0.12 mmol) in anhydrous
CH2Cl2(19 mL, 0.01 M) using Grubbs’ second generation catalyst
(10 mg, 5 mol %) for 6 h at rt, followed by purification on a silica
gel column using CH2Cl2–hexane (1:9) as eluent furnished the
bicyclic ketone 19 (13 mg, 91%) as an oil. ½a D23
¼ þ13:3 (c 1.1,
ꢂ
CHCl3); IR (neat):
m
max/cmꢀ1 3076, 3034, 2970, 2930, 1698
bicyclic ketone 22 (25 mg, 94%) as an oil. ½a D22
¼ ꢀ187 (c 2.4,
ꢂ
(C@O), 1640, 1451, 1376, 1199, 1012, 995, 894, 855; 1H NMR
(400 MHz, CDCl3): d 5.85–5.75 (2H, m), 4.89 (1H, s), 4.73 (1H, s),
2.72 (1H, dd, J 15.5 and 6.0 Hz), 2.63 (1H, dt, J 13.7 and 4.6 Hz),
2.54 (1H, dd, J 15.8 and 5.2 Hz), 2.21 (1H, dd, J 13.4 and 4.0 Hz),
2.00–1.85 (2H, m), 1.79 (3H, s, olefinic-CH3), 1.80–1.70 (1H, m),
1.62 (1H, td, J 13.7 and 5.1 Hz), 1.45–1.35 (1H, m), 1.08 (3H, s)
and 1.06 (3H, s) [2 ꢁ tert-CH3]; 13C NMR (100 MHz, CDCl3): d
215.8 (C, C@O), 145.4 (C, C@CH2), 130.1 (2C, CH), 113.8 (CH2,
C@CH2), 56.0 (CH), 52.3 (C), 48.4 (C), 40.6 (CH2), 37.8 (CH2), 33.5
(CH2), 27.4 (CH3), 25.4 (CH2), 24.9 (CH3), 23.8 (CH3); HRMS: m/z
calcd for C15H22ONa (M+Na): 241.1568; found: 241.1570.
CHCl3); IR (neat): m
max/cmꢀ1 3077, 3020, 2967, 2930, 2869, 2853,
1700 (C@O), 1640, 1452, 1367, 1105, 1014, 996, 916; 1H NMR
(400 MHz, CDCl3): d 5.73 (1H, dd, J 10.2 and 3.4 Hz), 5.68–5.50
(1H, m), 5.50 (1H, dd, J 10.2 and 1.8 Hz), 5.20 (1H, br s), 4.98 (1H,
d, J 12.3 Hz), 4.97 (1H, d, J 15.7 Hz), 2.89 (1H, br s H-6), 2.64 (1H,
dd, J 16.2 and 2.0 Hz), 2.47 (1H, dd, J 13.4 and 7.8 Hz), 2.11 (1H,
d, J 16.2 Hz), 2.04 (1H, dd, J 13.4 and 6.9 Hz), 1.74 (3H, s, olefinic-
CH3), 1.18 (3H, s) and 1.11 (3H, s) [2 ꢁ tert-CH3]; 13C NMR
(100 MHz, CDCl3): d 217.9 (C, C@O), 141.1 (C, C-7), 134.0 (CH),
131.9 (CH), 125.0 (CH), 122.2 (CH), 118.0 (CH2), 56.7 (CH, C-6),
52.4 (C), 47.4 (C), 44.9 (CH2), 44.2 (CH2), 26.5 (CH3), 24.8 (CH3),
15.1 (CH3); HRMS: m/z calcd for C15H20ONa (M+Na): 239.1412;
found: 239.1400.
4.9. (1R,3S,6S)-3-Allyl-1,3,7-trimethylbicyclo[4.3.0]nona-4,7-
dien-2-one 20
4.12. (2R,5S)-2,6,6-Trisallyl-5-isopropenyl-2-methylcyclohex-3-
RCM reaction of ketone 17 (16 mg, 0.07 mmol) in anhydrous
CH2Cl2 (7 mL, 0.01 M) using Grubbs’ first generation catalyst
(5 mg, 10 mol %) for 8 h at rt, followed by purification on a silica
gel column using CH2Cl2–hexane (1:19) as eluent furnished the
enone 23
To a magnetically stirred suspension of NaH (400 mg, 60% dis-
persion in oil, 10 mmol, washed with dry hexanes) in THF (1 mL)
and HMPA (1 mL) was added a solution of carvone 8 (150 mg,
1 mmol) in THF (1 mL), followed by allyl bromide (0.52 mL,
6 mmol), and the reaction mixture was stirred for 10 h at rt. It
was then quenched with water (3 mL) and extracted with ether
(3 mL ꢁ 3). The combined ether extract was washed with brine
bicyclic ketone 20 (12 mg, 86%) as an oil. ½a D23
¼ ꢀ66:6 (c 1.0,
ꢂ
CHCl3); IR (neat): m
max/cmꢀ1 3076, 3041, 2962, 2930, 2864, 1694
(C@O), 1448, 1373, 1015, 996, 915; 1H NMR (400 MHz, CDCl3): d
5.65 (1 H, ddt, J 17.3, 10.3 and 7.6 Hz), 5.20 (1H, br s, H-8), 5.05
(1H, d, J 10.3 Hz), 5.02 (1H, d, J 17.3 Hz), 2.63 (1H, dm, J 16.5 Hz),

1990
A. Srikrishna et al. / Tetrahedron: Asymmetry 19 (2008) 1984–1991
and dried over Na2SO4. Evaporation of the solvent and purification
of the residue over a silica gel column using CH2Cl2–hexane (1:9)
as eluent first furnished trisallyl carvone 23 (148 mg, 55%).
4.14. (1R,5S,8R,13R)-1,4-Dimethyltricyclo[6.4.1.01,5]trideca-
3,6,10-trien-13-ol 28
½
a 2D6
ꢂ
¼ ꢀ221:9 (c 4.7, CHCl3); IR (neat):
m
max/cmꢀ1 3076, 3018,
To a cold (0 °C), magnetically stirred solution of the tricyclic
ketone 27 (45 mg, 0.22 mmol) in dry ether (2 mL) was added
LiAlH4 (25 mg, 0.66 mmol), and reaction mixture was stirred for
1 h at rt. The reaction mixture was then diluted with ether
(3 mL) and quenched with a few drops of water. The organic layer
was separated and the aqueous phase was extracted with ether
(3 ꢁ 3 mL). The combined organic layer was washed with brine
(5 mL) and dried over Na2SO4. Evaporation of the solvent and puri-
fication of the residue over a silica gel column using ethyl acetate–
hexane (1:9) as eluent furnished the alcohol 28 (44 mg, 97%) as an
2978, 2930, 1836, 1700 (C@O), 1639, 1441, 995, 915; 1H NMR
(300 MHz, CDCl3): d 5.85–5.60 (4H, m), 5.50 (1H, ddt, J 16.8, 13.5
and 6.9 Hz), 5.15–4.95 (6H, m), 4.87 (1H, br s), 4.80 (1H, br s),
3.15 (1H, br s), 2.65–2.45 (3H, m), 2.30 and 2.21 (2H, 2 ꢁ dd, J
13.5 and 8.1 Hz), 1.99 (1 H, dd, 14.4 and 6.9 Hz), 1.75–1.63 (1H,
m), 1.60 (3H, s), 1.16 (3H, s); 13C NMR (75 MHz, CDCl3): d 215.4
(C, C@O), 143.6 (C, C@CH2), 134.1 (CH), 133.5 (CH), 133.2 (CH),
133.1 (CH), 126.7 (CH), 118.7 (CH2), 118.6 (CH2), 118.5 (CH2),
115.9 (CH2), 53.7 (CH, C-5), 52.3 (C, C-6), 47.1 (C, C-2), 44.3
(CH2), 38.6 (CH2), 35.2 (CH2), 24.6 (CH3), 21.1 (CH3); HRMS: m/z
calcd for C19H26ONa (M+Na): 293.1881; found: 293.1884.
oil. ½a 2D4
ꢂ
¼ ꢀ62:2 (c 2.6, CHCl3); IR (neat):
m
max/cmꢀ1 3422, 3014,
2960, 2923, 2851, 1454, 1376, 1144, 1098, 1049, 1023, 858, 817,
790, 750, 709, 647; 1H NMR (400 MHz, CDCl3): d 5.77 (1H, dd, J
10.0 and 4.1 Hz), 5.57 and 5.40 (2H, 2 ꢁ ddt, J 11.6, 8.4 and
3.2 Hz), 5.27 (1H, dd, J 10.0 and 2.2 Hz), 5.14 (1H, br s), 3.45 (1H,
s), 2.91 (1H, br s), 2.79 (1H, dq, J 15.6 and 2.8 Hz), 2.65–2.50 (2H,
m), 2.00 (1H, dm, J 15.6 Hz), 1.87 (1H, dd, J, 15,8 and 8.6 Hz),
1.78–1.72 (2H, m), 1.66 (3H, s, olefinic-CH3) and 1.08 (3H, s, tert-
CH3); 13C NMR (75 MHz, CDCl3): d 141.6 (C), 133.8 (CH), 129.7
(CH), 128.5 (CH), 127.4 (CH), 121.1 (CH), 78.7 (CH), 56.2 (CH),
47.4 (C), 44.9 (CH2), 38.7 (C), 34.9 (CH2), 33.8 (CH2), 28.6 (CH3),
15.1 (CH3); HRMS: m/z calcd for C15H20ONa (M+Na): 239.1412;
found: 239.1401.
Further elution of the column with CH2Cl2–hexane (1:4)
gave (5S)-6,6-bisallyl-5-isopropenyl-2-methylcyclohex-2-enone 25
(86 mg, 37%). ½a 2D3
ꢂ
¼ ꢀ47:5 (c 10, CHCl3); IR (neat):
m
max/cmꢀ1
3076, 2978, 2949, 2920, 1668, 1639, 1439, 1376, 1189, 1074,
997, 912; 1H NMR (300 MHz, CDCl3): d 6.48 (1H, br s, H-3), 5.83–
5.53 (2H, m, 2 ꢁ CH@CH2), 5.10–4.93 (4H, m, 2 ꢁ CH@CH2), 4.78
(1H, s) and 4.70 (1H, s) [C@CH2], 2.80–2.00 (7H, m), 1.76 (3H, s)
and 1.64 (3H, s) [2 ꢁ olefinic-CH3]; 13C NMR (75 MHz, CDCl3): d
201.8 (C, C@O), 145.8 (C, C = CH2), 140.0 (CH, C-3), 134.7 (C, C-2),
134.4 (CH), 133.9 (CH), 118.2 (CH2), 118.0 (CH2), 114.6 (CH2),
50.3 (C, C-6), 48.9 (CH, C-5), 38.7 (CH2), 35.2 (CH2), 28.9 (CH2),
22.3 (CH3), 16.6 (CH3); HRMS: m/z calcd for C16H23O (M+H):
231.1749; found: 231.1749.
4.15. (1R,5S,8R,13R)-1,4-Dimethyltricyclo[6.4.1.01,5]trideca-
3,6,10-trienyl 3,5-dinitrobenzoate 29
4.13. (7R,10S)-7-Allyl-10-isopropenyl-7-methylspiro[4.5]deca-
2,8-dien-6-one 26 and (1R,5S,8R)-4,8-dimethyltricyclo-
[6.4.1.01,5]trideca-3,6,10-trien- 13-one 27
To
0.16 mmol) in CH2Cl2 (2 mL) were added 3,5-dinitrobenzoic acid
(170 mg, 0.8 mmol), DCC and catalytic amount of DMAP
a magnetically stirred solution of alcohol 28 (35 mg,
a
To a magnetically stirred solution of trisallylcarvone 23 (50 mg,
0.18 mmol) in anhydrous CH2Cl2 (18 mL, 0.01 M) was added Grub-
bs’ first generation catalyst (15 mg, 10 mol %). The reaction mix-
ture was stirred magnetically for 2 h at rt and the catalyst was
filtered off through a short silica gel column. Evaporation of the
solvent and purification of the residue on an AgNO3 impregnated
silica gel column using ethyl acetate–hexane (1:49) as eluent fur-
(10 mg), and reaction mixture was stirred at rt for 4 h. The reaction
mixture was then diluted with water (5 mL) and extracted with
CH2Cl2 (3 ꢁ 3 mL). The combined organic layer was washed with
brine (5 mL) and dried over Na2SO4. Evaporation of the solvent
and purification of the residue over a silica gel column using ethyl
acetate–hexane (1:99) as eluent furnished the ester (58 mg, 91%),
which was recrystallized from a 1:1 mixture of ethyl acetate and
nished the spiro ketone 26 (22 mg, 50%) as an oil. ½a D26
ꢂ
¼ ꢀ366 (c
hexane. Mp: 201–203 °C; ½a D26
¼ þ10:3 (c 4.3, CHCl3); IR (neat):
ꢂ
2.2, CHCl3); IR (neat):
m
max/ cmꢀ1 3074, 3018, 2976, 2931, 2854,
m
max/cmꢀ1 3113, 3032, 2968, 2920, 2854, 2800, 1724, 1548, 1450,
1703, 1639, 1456, 1439, 1373, 1338, 1151, 1134, 997, 916, 897,
760, 667; 1H NMR (300 MHz, CDCl3): d 5.85–5.60 (4H, m), 5.47–
5.40 (1H, m), 5.15–4.97 (2H, m), 4.76 (1H, s), 4.68 (1H, s), 3.30–
3.05 (2H, m), 2.64–2.10 (5H, m), 1.48 (3H, s, olefinic-CH3), 1.18
(3H, s, tert-CH3); 13C NMR (75 MHz, CDCl3): d 214.0 (C, C@O),
144.8 (C, C@CH2), 134.6 (CH), 133.2 (CH), 130.0 (CH), 126.7 (CH),
125.6 (CH), 118.4 (CH2), 114.6 (CH2), 57.3 (C), 56.4 (CH, C-10),
47.4 (C), 45.5 (CH2), 44.8 (CH2), 36.3 (CH2), 24.5 (CH3), 19.9
(CH3); HRMS: m/z calcd for C17H22ONa (M+Na): 265.1568; found:
265.1569.
1342, 1277, 1171, 1090, 1072, 918, 859, 749, 719; 1H NMR
(400 MHz, CDCl3): d 9.25 (1H, t, J 2.0 Hz), 9.20 (2H, d, J 2.0 Hz),
5.91 (1H, dd, J, 10.0 and 4.1 Hz), 5.76 and 5.58 (2H, 2 ꢁ ddt, J
11.3, 8.5 and 2.9 Hz), 5.40–5.30 (2H, m), 5.21 (1H, br s), 3.06 (1H,
br s), 2.92 (1H, dq, J, 15.9 and 2.9 Hz), 2.68 (1H, dd, J 15.9 and
2.9 Hz), 2.20–1.85 (4H, m), 1.74 (3H, s, olefinic-CH3), 1.03 (3H, s,
tert-CH3); 13C NMR (100 MHz, CDCl3): d 162.8 (C, C@O), 148.9
(2C, C), 141.6 (C), 134.2 (C), 132.6 (CH), 129.8 (CH), 129.3 (2C,
CH), 128.5 (CH), 127.9 (CH), 122.3 (CH), 120.9 (CH), 83.9 (CH, C-
13), 56.5 (CH, C-5), 47.1 (C), 44.4 (CH2), 38.8 (C), 36.0 (CH2), 35.0
(CH2), 28.3 (CH3), 15.0 (CH3); Anal. Calcd for C22H22N2O6: C,
64.38; H, 5.40; N, 6.82. Found: C, 64.31; H, 5.71; N, 6.72.
Further elution of the column with ethyl acetate–hexane (1:19)
gave (1R,5S,8R)-4,8-dimethyltricyclo[6.4.1.01,5]trideca-3,6,10-tri-
en-13-one 27 (18 mg, 41%) as an oil; ½a D26
ꢂ
¼ ꢀ101:8 (c 1.7, CHCl3);
Crystal data: X-ray data were collected at 296 K on a SMART
CCD-BRUKER diffractometer with graphite-monochromated Mo
IR (neat): m
max/cmꢀ1 3020, 2967, 2929, 2852, 1703 (C@O), 1448,
1370, 1348, 1212, 1161, 1151, 1083, 987, 886, 817, 797, 703, 673;
1H NMR (300 MHz, CDCl3): d 5.90 (1H, dd, J 10.2 and 3.9 Hz), 5.83
(1H, dt, J 8.7 and 3.0 Hz), 5.78–5.65 (1H, m), 5.33 (1H, dd, J 10.2
and 2.1 Hz), 5.21 (1H, br s), 3.46 (1H, dq, J 10.5 and 2 Hz), 3.25
(1H, br s), 2.37 (1H, dd, J 15.0 and 8.4 Hz), 2.15–1.90 (4H, m), 1.63
(3H, s, olefinic-CH3), 1.19 (3H, s, tert-CH3); 13C NMR (75 MHz,
CDCl3): d 215.1 (C, C@O), 139.8 (C), 131.9 (CH), 130.0 (CH), 128.7
(CH), 128.5 (CH), 123.2 (CH), 58.6 (C), 58.5 (CH), 47.6 (C), 40.8
(CH2), 39.7 (CH2), 39.6 (CH2), 24.8 (CH3), 15.1 (CH3); HRMS: m/z
calcd for C15H18ONa (M+Na): 237.1255; found: 237.1254.
Ka radiation (k = 0.71073 Å). The structure was solved by direct
methods (SIR 92). Refinement was by full-matrix least-squares
procedures on F2 using SHELXL-97. The non-hydrogen atoms were
refined anisotropically, whereas hydrogen atoms were refined iso-
tropically. Mol. For. C22H22N2O6; MW = 410.15; colourless; Crystal
system: monoclinic; Space group P1211; cell parameters,
a = 8.716(4) Å, b = 6.691(3) Å, c = 17.428(8) Å;
97.640(8),
= 90.00, V=1007.3(8) Å3, Z = 2, Dc=1.201 g cmꢀ3
F(000) = 384, Total number of l.s. parame-
=0.083 mmꢀ1
ters = 273, R1 = 0.0590 for 2582 F0 > 2 (F0) and 0.0915 for all
a = 90.00, b =
c
,
l
.
r

A. Srikrishna et al. / Tetrahedron: Asymmetry 19 (2008) 1984–1991
1991
3733 data. wR2 = 0.1170, GOF = 1.014, restrained GOF = 1.014 for
all data. An ORTEP diagram is depicted in Figure 2. Crystallographic
data have been deposited with Cambridge crystallographic data
centre (CCDC 693972).
3.00–2.80 (2H, m), 2.50–2.15 (5H, m), 2.05–1.90 (2H, m), 1.85–
1.70 (1H, m), 1.70 (3H, s, olefinic-CH3), 1.45–1.30 (1H, m), 1.14
(3H, s, tert-CH3); 13C NMR (100 MHz, CDCl3): d 215.9 (C, C@O),
145.3 (C, C@CH2), 134.3 (CH), 128.9 (CH), 126.7 (CH), 118.1
(CH2), 113.6 (CH2), 57.9 (C), 53.1 (CH), 46.9 (C), 44.7 (CH2), 43.9
(CH2), 39.9 (CH2), 32.6 (CH2), 26.2 (CH3), 23.3 (CH3), 21.9 (CH2);
4.16. (3S,6R)-2,2,6-Trisallyl-3-isopropenyl-6-
methylcyclohexanone 24
HRMS: m/z calcd for C17H24ONa (M+Na): 267.1725; found:
267.1713.
To freshly distilled liquid ammonia (50 mL) was added Li metal
(18 mg, 2.5 mmol). To the resultant blue coloured solution was
added a solution of the enone 25 (115 mg, 0.5 mmol) in dry THF
(4 mL) for over a period of 10 min. After 15 min, the reaction mix-
ture was quenched with a solution of allyl bromide (0.26 mL,
3 mmol) in dry THF (1 mL). Workup followed by purification over
a silica gel column using CH2Cl2–hexane (1:19) furnished ketone
4.18. (1S,5S,8R)-4,8-Dimethyltricyclo[6.4.1.01,5]trideca-3,10-
dien-13-one 32
RCM reaction of the bicyclic ketone 31 (10 mg, 0.04 mmol) in
anhydrous CH2Cl2(4 mL, 0.01 M) using Grubbs’ second generation
catalyst (1 mg, 5 mol %) for 5 h at rt, followed by purification on
a silica gel column using CH2Cl2–hexane (1:9) as eluent furnished
24 (108 mg, 79%) as an oil. ½a D23
¼ þ65:6 (c 1.6, CHCl3); IR (neat):
ꢂ
m
max/cmꢀ1 3078, 2979, 2934, 2873, 1690 (C@O), 1449, 1376,
the tricyclic ketone 32 (8 mg, 90%) as an oil. ½a D24
¼ þ82:6 (c 1.0,
ꢂ
1177, 1066, 995, 914; 1H NMR (400 MHz, CDCl3): d 5.66 (1H, ddt,
J 17.1, 10.1 and 7.4 Hz), 5.60–5.35 (2H, m), 5.10–4.80 (7H, m),
4.54 (1H, s), 2.59 (1H, dd, J 14.5 and 6.4 Hz), 2.55–2.45 (2H, m),
2.23 (1H, dd, J 13.7 and 7.4 Hz), 2.20–2.10 (3H, m), 1.95–1.75
(3H, m), 1.76 (3H, s, olefinic-CH3), 1.45–1.35 (1H, m), 1.03 (3H, s,
tert-CH3); 13C NMR (100 MHz, CDCl3): d 215.4 (C, C@O), 144.4 (C,
C@CH2), 134.9 (CH), 134.0 (CH), 133.7 (CH), 118.4 (CH2), 118.2
(CH2), 118.1 (CH2), 114.7 (CH2), 54.8 (C), 49.0 (CH), 46.9 (C), 42.8
(CH2), 39.2 (CH2), 37.6 (CH2), 33.3 (CH2), 24.8 (CH3), 24.2 (CH3),
21.8 (CH2); HRMS: m/z calcd for C19H28ONa (M+Na): 295.2038;
found: 295.2038.
CHCl3); IR (neat): m
max/cmꢀ1 3040, 3016, 2962, 2928, 2873, 2850,
1705 (C@O), 1666, 1446, 1378, 1220, 1005, 910, 817, 794, 665,
645; 1H NMR (400 MHz, CDCl3): d 5.80–5.60 (2H, m), 5.34 (1H, br
s), 2.76 (1H, dd, J 17.0 and 7.1 Hz), 2.65–2.50 (2H, m), 2.20–1.70
(8H, m), 1.66 (3H, s, olefinic-CH3), 1.13 (3H, s, tert-CH3); 13C NMR
(100 MHz, CDCl3): d 215.8 (C, C@O), 138.8 (C, C-4), 130.3 (CH),
127.4 (CH), 123.4 (CH), 61.3 (C), 56.4 (CH, C-5), 47.8 (C), 42.6
(CH2), 41.8 (CH2), 40.1 (CH2), 32.3 (CH2), 28.1 (CH3), 22.3 (CH2),
14.9 (CH3); HRMS: m/z calcd for C15H20ONa (M+Na): 239.1412;
found: 239.1407.
Acknowledgement
4.17. (1R,6R,7S)-6-Allyl-7-isopropenyl-1-
methylbicyclo[4.3.1]dec-3-en-10-one 31
We thank the Council of Scientific and Industrial Research, New
Delhi for the award of research fellowships to V.H.P. and G.S.
RCM reaction of the ketone 24 (50 mg, 0.22 mmol) in anhydrous
CH2Cl2 (22 mL, 0.01 M) using Grubbs’ first generation catalyst
(8 mg, 5 mol %) for 8 h at rt, followed by purification over a AgNO3
impregnated silica gel column using ethyl acetate–hexane (1:49)
as eluent first furnished bicyclic ketone 31 (16 mg, 36%) as an oil.
References
1. Kawazu, K. Agric. Biol. Chem. 1980, 44, 1367; Fukuyama, Y.; Kubo, M.; Fujii, T.;
Matsuo, A.; Minoshima, Y.; Minami, H.; Morisaki, M. Tetrahedron 2002, 58,
10033; Duh, C.-Y.; El-Gamal, A. A. H.; Wang, S.-K. Tetrahedron Lett. 2003, 44,
9321; Fukuyama, Y.; Kubo, M.; Minami, H.; Yuasa, H.; Matsuo, A.; Fujii, T.;
Morisaki, M.; Harada, K. . Chem. Pharm. Bull. 2005, 53, 72.
2. Fukuyama, Y.; Minami, H.; Takaoka, S.; Kodama, M.; Kawazu, K.; Nemoto, H.
Tetrahedron Lett. 1997, 38, 1435.
3. Fukuyama, Y.; Minami, H.; Kagawa, M.; Kodama, M.; Kawazu, K. J. Nat. Prod.
1999, 62, 337.
4. Heim, R.; Wiedemann, S.; Williams, C. M.; Bernhardt, P. V. Org. Lett. 2005, 7,
1327; Tilly, D. P.; Williams, C. M.; Bernhardt, P. V. Org. Lett. 2005, 7, 5155;
Schwartz, B. D.; Tilly, D. P.; Heim, R.; Wiedemann, S.; Williams, C. M.; Bernhardt,
P. V. Eur. J. Org. Chem. 2006, 3181; Nikolai, J.; Loe, O.; Dominiak, P. M.; Gerlitz, O.
O.; Autschbach, J.; Davies, H. M. L. J. Am. Chem. Soc. 2007, 129, 10763 and
references cited therein.
5. Srikrishna, A.; Ravi, G. Tetrahedron 2008, 64, 2565; Srikrishna, A.; Satyanarayana,
G. Tetrahedron Lett. 2006, 47, 367; Srikrishna, A.; Satyanarayana, G. Tetrahedron
2005, 61, 8855; Srikrishna, A.; Satyanarayana, G. Tetrahedron: Asymmetry 2005,
16, 3992.
6. Grubbs, R. H.; Chang, S. Tetrahedron 1998, 54, 4413; Fürstner, A. Angew. Chem.,
Int. Ed. 2000, 39, 3013; Trnka, T. M.; Grubbs, R. H. Acc. Chem. Res. 2001, 34, 18;
Grubbs, R. H. Tetrahedron 2004, 60, 7117; Grubbs, R. H. In Handbook of
Metathesis; Wiley-VCH, 2003; Vol. 2.
7. Gesson, J.-P.; Jaquesy, J.-C.; Renoux, B. Tetrahedron 1989, 45, 5853; Srikrishna, A.;
Dethe, D. H. Tetrahedron Lett. 2003, 44, 7817.
½
a 2D4
ꢂ
¼ ꢀ11:3 (c 1.0, CHCl3); IR (neat):
m
max/cmꢀ1 3074, 3039,
2961, 2928, 2871, 1707 (C@O), 1637, 1472, 1449, 1377, 1191,
1179, 1005, 908, 749, 700; 1H NMR (400 MHz, CDCl3): d 5.90–
5.60 (3H, m), 4.98 (1H, d, J 16.7 Hz), 4.97 (1H, d, J 10.6 Hz), 4.87
(1H, s), 4.77 (1H, s), 2.75 (1H, dd, J 14.9 and 6.4 Hz), 2.70–2.55
(2H, m), 2.37 (1H, dd, J 13.3 and 3.9 Hz), 2.30 (1H, dd, J 13.7 and
6.3 Hz), 2.15 (1H, dd, J 13.7 and 7.9 Hz), 1.98–1.75 (3H, m), 1.78
(3H, s, olefinic-CH3), 1.60 (1H, td, J 13.6 and 4.8 Hz), 1.50–1.40
(1H, m), 1.07 (3H, s, tert-CH3); 13C NMR (100 MHz, CDCl3): d
214.2 (C, C@O), 145.2 (C, C@CH2), 136.8 (CH), 131.0 (CH), 129.2
(CH), 116.9 (CH2), 114.5 (CH2), 56.4 (C), 54.3 (CH), 48.4 (C), 42.3
(CH2), 40.8 (CH2), 36.7 (CH2), 31.9 (CH2), 27.1 (CH3), 25.2 (CH2),
23.1 (CH3); HRMS: m/z calcd for C17H24ONa (M+Na): 267.1725;
found: 267.1720.
Further elution of the column with ethyl acetate–hexane (3:97)
gave (7R,10S)-7-allyl-10-isopropenyl-7-methylspiro[4.5]dec-2-en-
6-one 30 (18 mg, 41%) as an oil. ½a D24
¼ ꢀ52:5 (c 1.0, CHCl3); IR
ꢂ
(neat):
m
max/cmꢀ1 3076, 3058, 2931, 2870, 1694 (C@O), 1639,
8. Paquette, L. A.; Fabris, F.; Tae, J.; Gallucci, J. C.; Hofferberth, J. E. J. Am. Chem. Soc.
2000, 122, 3391; Lee, C. W.; Grubbs, R. H. J. Org. Chem. 2001, 66, 7155; Srikrishna,
A.; Dethe, D. H. Tetrahedron Lett. 2005, 46, 3381.
1458, 1375, 1120, 1004, 913, 894; 1H NMR (400 MHz, CDCl3): d
5.66 (1H, ddt, J 17.6, 10.5 and 7.4 Hz), 5.53–5.50 (1H, m), 5.45–
5.40 (1H, m), 5.10–4.95 (2H, m), 4.85 (1H, br s), 4.36 (1H, br s),