A rapid and efficient enantiospecific synthesis of the functionalized ABC-ring system of tetranortriterpene dumsins and their analogues

Article abstract of DOI:10.1016/j.tetasy.2008.05.015

A rapid and enantiospecific synthesis of the ABC ring system of tetranortriterpene dumsin and its analogues, starting from the readily available monoterpene (R)-carvone employing two RCM reactions as key steps, is described.

Full text of DOI:10.1016/j.tetasy.2008.05.015

Tetrahedron: Asymmetry 19 (2008) 1392–1396
Contents lists available at ScienceDirect
Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
A rapid and efficient enantiospecific synthesis of the functionalized
ABC-ring system of tetranortriterpene dumsins and their analogues
*
Adusumilli Srikrishna , Vijendra H. Pardeshi, Pinnu Thriveni
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:
Received 9 May 2008
Accepted 16 May 2008
A rapid and enantiospecific synthesis of the ABC ring system of tetranortriterpene dumsin and its ana-
logues, starting from the readily available monoterpene (R)-carvone employing two RCM reactions as
key steps, is described.
Ó 2008 Elsevier Ltd. All rights reserved.
1. Introduction
thesis of the functionalised AA0B ring system (mentioned as the
ABC ring system) of dumsin is reported by employing a very long
Phytochemicals acting as deterrents to insect feeding are fre-
quently found in pest-resistant plants, which can provide lead
compounds to develop environmentally friendly pest control
agents. The roots of the widely distributed East African plant Msin-
duzi, Croton jatrophoides Pax. (Euphorbiaceae), has long been used
by the native population to alleviate stomachaches and to offset
the symptoms of the common cold. In the search for environmen-
tally friendly pest control agents, Kubo et al. have screened extracts
of the bitter root bark of C. jatrophoides, which led to the identifi-
cation of a tetranortriterpene limonoid dumsin 1 possessing
remarkably potent insect antifeedant activity.1a The structure
was secured on the basis of detailed spectroscopic analysis and
ultimately by single crystal X-ray diffraction analysis. Subse-
quently, a number of dumsin analogues (Fig. 1) were isolated from
various extracts of C. jatrophoides1 and also from the root bark of
Turraea wakefieldii,2a and Walsura robusta,2b all possessing excel-
lent antifeedant activity. Structurally, dumsin and its analogues
possess an interesting tetranortriterpene framework with an A-
ring rearranged to a spiro system. In many of them, a new A0 het-
erocyclic ring formed through either hemiacetal or ether or peroxy
acetal linkage. Limonoids are attractive biologically active sub-
stances because they possess anti-HIV activity, antimalarial activ-
ity, and cytotoxicity against cancer cell lines in addition to insect
antifeedant activity.1e However, not much synthetic efforts have
been reported in the literature on the synthesis of dumsin and its
analogues. So far there is no report in the literature on either the
total synthesis or the construction of the complete ring system of
any of the dumsins. In 1994, Paquette had reported the first syn-
thetic efforts to dumsin by constructing the AB ring system of
dumsin.3a Subsequently (in 2003 and 2007), enantioselective syn-
sequence.3b,c Herein, we report a very rapid, short and efficient
enantiospecific approach to the functionalized ABC ring system
of dumsin and its analogues.
2. Results and discussion
We have envisioned the synthesis of the ABC-ring system 2 by
employing (R)-carvone 3 as the chiral starting material, Scheme
1. It was readily visualized that carvone 3 can serve as the B-ring
of dumsins, and spirocyclopentannulation at the C-6 carbon and
cyclohexannulation at the C-1, C-2 bond of carvone would lead
to an ABC ring system 2 of dumsins.
The synthetic sequence is depicted in Scheme 2. First, the con-
struction of the AB-ring system of dumsins was addressed via a
spirocyclopentannulation at the C-6 carbon of carvone, employing
RCM reaction of 6,6-bis-allyl carvone 4 as the key step. Thus,
kinetic allylation of carvone 3 with lithium diisopropylamide and
allyl bromide4 generated a 1:5 cis-trans mixture of 6-allylcarvone
5 in 95% yield, which on second allylation using the same condi-
tions furnished 6,6-bis-allylcarvone 4 in 87% yield. The RCM reac-
tion5 of bis-allylcarvone 4 with Grubbs’ first generation catalyst
Cl2(PCy3)2Ru@CHPh in refluxing methylene chloride furnished
the spiroenone 6 in 99% yield, containing the AB ring system of
dumsins, whose structure was deduced from its spectral data.
For the annulation of the C-ring to the AB ring system, the intro-
duction of two allyl groups at the C-6 C-7 carbons of the spiro-
enone 6 was conceived. An allyl group was introduced at the C-6
carbon atom by employing a 1,3-enone transposition methodol-
ogy.6 Sonochemically accelerated Barbier reaction of the spiro-
enone 6 with zinc and allyl bromide generated the tert-alcohol 7,
in quantitative yield, which on oxidation with PCC and silica gel
furnished the enone 8. A reductive allylation was explored for
the stereoselective introduction of the second allyl group at the
* Corresponding author. Tel.: +91 80 22 932 215; fax: +91 80 23 600 529.
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.2008.05.015

A. Srikrishna et al. / Tetrahedron: Asymmetry 19 (2008) 1392–1396
1393
O
O
O
AcO
AcO
AcO
H
AcO
A
AcO
AcO
C
D
O
O
O
HO
HO
HO
H
B
O
O
H
A'
O
O
O
O
O
O
H
H
H
O
O
1 Dumsin
Dumnin
Dumsenin
O
O
O
AcO
AcO
AcO
AcO
O
AcO
O
AcO
O
H
O
H
O
HO
O
H
H
H
H
O
O
O
O
OH
H
H
H
Zumsin
Zumsenin
Musiduol
O
O
O
AcO
AcO
HO
OAc
AcO
HO
O
AcO
O
HO
H
O
H
O
O
H
H
H
O
OAc
OAc
O
H
H
H
Zumketol
Zumsenol
Walsuronoid A
Figure 1.
23
20
22
18
O
21
12
30
C
2
11
A
17
13
16
C
14
A 1
B
3
D
15
9
8
10B
19
4
7
5
29
6
3
28
2
(R)-carvone
Dumsins carbon framework
ABC ring system
Scheme 1.
C-7 position. Treatment of the spiroenone 8 with lithium in liquid
ammonia followed by alkylation with allyl bromide furnished a 3:2
mixture of O- and C-allylated products 9 and 10 in 73% yield, which
were separated by column chromatography on silica gel. The ste-
reochemistry at the C-6 centre was assigned on the basis of ther-
modynamic considerations in analogy to the reduction of carvone
derivatives.7 It was further supported by the single crystal X-ray
diffraction analysis of the ketone 10 (an ORTEP is depicted in
Fig. 2). The O-allyl compound 9 on thermal Claisen rearrangement
at 180 °C in a sealed tube, contrary to the expectation, furnished
the stereoisomer 11 in 79% yield.8 RCM reaction of the bisallyl
compound 11 with Grubbs’ catalyst Cl2(PCy3)2Ru@CHPh in methy-
lene chloride at room temperature, followed by purification on a
silver nitrate impregnated silica gel column furnished the spiroe-
none 12 in 83% yield, containing the ABC ring system of dumsins
(containing a BC-cis ring fusion). On the other hand, the RCM reac-
tion of the bisallyl compound 10 with Grubbs’ catalyst Cl2(PCy3)2
Ru@CHPh in methylene chloride at room temperature furnished
the spiroenone 13 in quantitative yield, containing the ABC ring
system of dumsins (containing also a BC-trans ring fusion as in
dumsins), whose structure was deduced from its spectral data.
3. Conclusion
In conclusion, we have developed a rapid and efficient enantio-
specific synthesis of the ABC ring system of dumsin and its ana-
logues, containing functionality in all the three rings. The
isopropenyl group in 12 and 13 serves as a latent A0 ring of the
dumsins. A spirocyclopentannulation at the C-6 carbon and a
cyclohexannulation at the C-1 to C-2 carbons of carvone employing
two efficient RCM reactions have been employed as the key steps.
Extension of the methodology for further elaboration to dumsins is
currently under investigation.
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

1394
A. Srikrishna et al. / Tetrahedron: Asymmetry 19 (2008) 1392–1396
O
O
H
O
a
a
92%
87%
3
5
4
99% b
O
OH
c
d
100%
78%
O
O
6
8
7
e
73%
+
O
O
( 3 : 2 )
8
9
10
f
79%
b 100%
b
H
H
83%
O
O
O
12
11
13
Scheme 2. Reagents and conditions: (a) LDA, THF, BrCH2CH@CH2; (b) Cl2(PCy3)2Ru@CHPh (5 mol %), CH2Cl2; (c) Zn, BrCH2CH@CH2, THF, ))); (d) PCC, silica gel, CH2Cl2; (e) Li,
liq. NH3, THF, tBuOH, BrCH2CH@CH2; (f) sealed tube, 180 °C.
hexane and ethyl acetate as eluents. Acme’s silica gel (100–200
mesh) was used for column chromatography (approximately 20 g
per one gram of crude material).
4.1. (5S)-6,6-Bis-allyl-5-isopropenyl-2-methylcyclohex-2-enone
4
To a cold (0 °C), magnetically stirred solution of diisopropyl-
amine (0.52 ml, 3.7 mmol) in anhydrous THF (3 ml) was slowly
added a solution of n-BuLi (2.5 M in hexane, 1.4 ml, 3.5 mmol) over
a period of 5 min and stirred for 10 min. To the LDA thus formed
was added dropwise a solution of 6-allylcarvone4 5 (500 mg,
2.63 mmol) in anhydrous THF (2 ml) over a period of 10 min and
stirred for 45 min at the same temperature. The enolate was then
treated with allyl bromide (0.32 ml, 3.7 mmol) and stirred for
Figure 2. ORTEP diagram of 10.
10 h at rt. The reaction mixture was then diluted with water and
extracted with ether (3 ꢁ 5 ml). The combined organic extract
was washed with brine and dried over Na2SO4. Evaporation of
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 the 13C NMR, the nature of the carbons (C,
CH, CH2, and CH3) was determined by recording the DEPT-135
spectra, and is given in parentheses. High-resolution mass spectra
were recorded using a Micromass Q-TOF micro mass spectrometer
using electron spray ionization mode. Optical rotations were mea-
the solvent and purification of the residue over a silica gel column
using CH2Cl2–hexane (1:10) as eluent furnished bis-allylcarvone 4
(526 mg, 87%) as an oil. ½a D23
ꢂ
¼ ꢀ47:5 (c 10, CHCl3); IR (neat): mmax
/
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),
sured 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 carried out using a standard syringe-septum technique. Reac-
tions were monitored by TLC on silica gel using a combination of
22.3 (CH3), 16.6 (CH3); HRMS: Calcd for C16H23
231.1749. Found: 231.1749.
O (M+H):

A. Srikrishna et al. / Tetrahedron: Asymmetry 19 (2008) 1392–1396
1395
4.2. (10S)-10-Isopropenyl-7-methylspiro[4.5]deca-2,7-dien-6-
one 6
1.75 (3H, s) and 1.67 (3H, s) [2 ꢁ olefinic–CH3]; 13C NMR
(75 MHz, CDCl3): d 197.6 (C, C@O), 159.4 (C, C-6), 146.0 (C, C@CH2),
134.3 (CH), 131.6 (C, C-7), 129.9 (CH), 129.7 (CH), 116.8 (CH2),
114.9 (CH2), 52.3 (CH, C-10), 49.7 (C, C-5), 45.0 (CH2), 40.0 (2C,
CH2), 35.2 (CH2), 22.4 (CH3), 11.7 (CH3); HRMS: Calcd for
To
a magnetically stirred solution of enone 4 (50 mg,
0.22 mmol) in anhydrous CH2Cl2 (11 ml, 0.02 M) was added Grub-
bs’ first generation catalyst (13 mg, 7 mol %). The reaction mixture
was refluxed for 4 h and the catalyst was filtered off through a
short silica gel column. Evaporation of the solvent and purification
of the residue on a silica gel column using CH2Cl2–hexane (1:4) as
eluent furnished the spiro enone 6 (43 mg, 99%) as an oil.
C17H22ONa (M+Na): 265.1568. Found: 265.1566.
4.5. (6R,10S)-6-Allyl-10-isopropenyl-7-methyl-8-(prop-2-
enyloxy)spiro[4.5]deca-2,7-diene 9 and (6R,7S,10S)-6,7-bis-
allyl-10-isopropenyl-7-methylspiro[4.5]dec-2-en-8-one 10
½
a 2D5
ꢂ
¼ ꢀ179:2 (c 1.3, CHCl3); IR (neat):
m
max/cmꢀ1 3055, 2920,
2846, 1670, 1434, 1377, 1361, 1188, 1072, 1058, 895; 1H NMR
(300 MHz, CDCl3): d 6.52 (1H, s, H-8), 5.60 and 5.49 (2H, 2 ꢁ dt, J
6.0 and 2.1 Hz, H-2 and H-3), 4.76 (1H, s) and 4.62 (1H, s) [C@CH2],
2.90–2.50 (5H, m), 2.45–2.25 (2H, m), 1.79 (3H, s) and 1.64 (3H, s)
[2 ꢁ olefinic–CH3]; 13C NMR (75 MHz, CDCl3): d 200.9 (C, C@O),
146.4 (C, C@CH2), 140.8 (CH, C-8), 134.0 (C, C-7), 129.4 (CH),
127.0 (CH), 114.0 (CH2, CH2@C), 54.5 (C, C-5), 51.8 (CH, C-10),
41.8 (CH2), 37.8 (CH2), 29.0 (CH2), 22.0 (CH3), 16.9 (CH3); HRMS:
Calcd for C14H18ONa (M+Na): 225.1255. Found: 225.1257.
To freshly distilled liquid ammonia (50 ml) was added Li metal
(17.2 mg, 2.46 mmol). To the resulting blue-coloured solution was
added a solution of the enone 8 (50 mg, 0.246 mmol) and tert-butyl
alcohol (0.23 ml, 2.46 mmol) in dry THF (4 ml) over a period of
10 min. The reaction mixture was stirred for 15 min and quenched
with a solution of allyl bromide (0.22 ml, 2.46 mmol) in dry THF
(1 ml). It was then slowly warmed up to rt and stirred for 3 h.
Water (5 ml) was added to the reaction mixture and extracted with
ether (3 ml ꢁ 3). The ether extract was washed with brine (5 ml)
and dried over Na2SO4. Evaporation of the solvent followed by
purification on a silica gel column using CH2Cl2–hexane (1:9) first
4.3. (6S,10S)-6-Allyl-10-isopropenyl-7-methylspiro[4.5]deca-
2,7-dien-6-ol 7
furnished O-allylated product 9 (26 mg, 44%). ½a D20
¼ ꢀ38:6 (c 5.4,
ꢂ
CHCl3); IR (neat): m
max/cmꢀ1 3072, 3052, 2977, 2914, 2855, 1688,
To a sonochemically activated suspension of Zn (196 mg,
3 mmol) in dry THF (2 ml) in a round-bottom flask was slowly
added a solution of spiroenone 6 (60 mg, 0.3 mmol) and allyl
1637, 1439, 1376, 1349, 1164, 994, 908, 894; 1H NMR (300 MHz,
CDCl3): d 6.05–5.80 (2H, m), 5.65–5.45 (2H, m), 5.30 (1H, dd, J
17.1 and 1.5 Hz), 5.17 (1H, dd, J 10.8 and 1.5 Hz), 5.00 (1H, d, J
17.7 Hz), 4.92 (1H, d, J 9.6 Hz), 4.75 (1H, s) and 4.69 (1H, s)
[C@CH2], 4.20 (2H, d, J 5.7 Hz, O–CH2), 2.65–2.55 (2H, m), 2.40–
2.30 (4H, m), 2.20–1.80 (4H, m), 1.69 (3H, s) and 1.65 (3H, s)
[2 ꢁ olefinic–CH3]; 13C NMR (75 MHz, CDCl3): d 147.0 (C), 146.1
(C), 139.7 (CH), 135.0 (CH), 129.9 (CH), 129.2 (CH), 119.0 (C, C-7),
116.5 (CH2), 114.7 (CH2), 113.9 (CH2), 69.3 (CH2, OCH2), 52.3
(CH), 48.2 (C, C-5), 45.6 (CH), 41.5 (CH2), 40.0 (CH2), 37.8 (CH2),
28.9 (CH2), 21.2 (CH3), 16.4 (CH3); HRMS: Calcd for C20H28ONa
(M+Na): 307.2038. Found: 307.2043.
bromide (363 mg, 3 mmol) in THF (1 ml) over
a period of
5 min and irradiated sonochemically for 45 min. The reaction
mixture was then quenched with aq NH4Cl and extracted with
ether (3 ꢁ 5 ml). The ether extract was washed with brine and
dried (Na2SO4). Evaporation of the solvent and purification of
the residue on a silica gel column using CH2Cl2–hexane (1:4)
as eluent furnished the tertiary alcohol
7 (72 mg, 100%).
½
a 2D4
ꢂ
¼ þ3:0 (c 2.7, CHCl3); IR (neat):
m
max/cmꢀ1 3573, 3070,
2920, 2845, 1633, 1436, 1375, 1060, 1003, 893, 814, 768,
662; 1H NMR (300 MHz, CDCl3): d 5.93 (1H, ddt, J 16.8, 9.0
and 7.2 Hz), 5.68–5.60 (1H, m), 5.60–5.50 (1H, m), 5.34 (1H,
br s), 5.17–5.10 (2H, m), 4.72 (1H, s), 4.70 (1H, s), 2.77 (1H,
dd, J 11.1 and 6.6 Hz), 2.60–2.20 (8H, m), 2.05–1.94 (1H, m),
1.71 (3H, s) and 1.69 (3H, s) [2 ꢁ olefinic–CH3]; 13C NMR
Further elution of the column with CH2Cl2-hexane (1:4) fur-
nished C-allylated product 10 (17 mg, 29%) as a gummy solid,
which was recrystallised from methanol. Mp 99–101 °C;
½
a 2D0
ꢂ
¼ þ13:2 (c 4.8, CHCl3); IR (neat):
m
max/cmꢀ1 3074, 3054,
2972, 2868, 1707, 1637, 1458, 1431, 1376, 1275, 1240, 998, 910,
715, 667; 1H NMR (300 MHz, CDCl3): d 5.92–5.60 (2H, m), 5.57
(2H, s), 5.15–4.85 (4H, m), 4.75 (1H, s), 4.73 (1H, s), 2.91 (1H, t, J
14.4 Hz), 2.80–2.00 (10H, m), 1.92 (1H, t, J 4.2 Hz), 1.69 (3H, s, ole-
finic–CH3), 1.09 (3H, s, tert-CH3); 13C NMR (75 MHz, CDCl3): d 213.2
(C, C@O), 145.3 (C, C@CH2), 140.2 (CH), 135.6 (CH), 130.5 (CH),
130.2 (CH), 118.1 (CH2), 115.0 (CH2), 114.7 (CH2), 54.6 (CH), 53.3
(C), 50.7 (CH), 49.2 (C), 44.6 (CH2), 40.8 (CH2), 40.3 (CH2), 35.8
(CH2), 31.2 (CH2), 21.9 (CH3), 20.8 (CH3); HRMS: Calcd for
C20H28ONa (M+Na): 307.2038. Found: 307.2032. Anal. Calcd for
(75 MHz, CDCl3):
d 147.2 (C, C@CH2), 139.8 (C, C-7), 135.7
(CH), 130.9 (CH), 129.9 (CH), 121.9 (CH), 117.9 (CH2), 114.3
(CH2), 78.0 (C, C-6), 52.6 (C, C-5), 47.3 (CH, C-10), 44.6 (CH2),
37.9 (CH2), 36.5 (CH2), 28.6 (CH2), 20.6 (CH3), 20.0 (CH3);
HRMS: Calcd for
267.1721.
C17H24ONa (M+Na): 267.1725. Found:
4.4. (10S)-6-Allyl-10-isopropenyl-7-methylspiro[4.5]deca-2,6-
dien-8-one 8
C20H28O, C, 84.45; H, 9.92. Found: C, 84.42; H, 9.72.
To a magnetically stirred solution of the tertiary alcohol 7
(100 mg, 0.41 mmol) in anhydrous CH2Cl2 (2 ml) was added a
homogeneous mixture of PCC (440 mg, 2.1 mmol) and silica gel
(440 mg) and stirred vigorously for 1 day at rt. The reaction mix-
ture was then filtered through a small silica gel column and the
column eluted with excess CH2Cl2. Evaporation of the solvent
and purification of the residue on a silica gel column using
CH2Cl2–hexane (1:4) as eluent furnished the enone 8 (79 mg,
4.6. X-ray analysis data of 10
X-ray data were collected at 296 K on a SMART CCD-BRUKER dif-
fractometer with graphite-monochromated MoK
(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 anisotropi-
cally whereas hydrogen atoms were refined isotropically. Mol. for
a radiation
78%) as an oil. ½a D25
ꢂ
¼ þ7:8 (c 1.8, CHCl3); IR (neat):
m
max/cmꢀ1
3055, 2926, 2856, 1670, 1637, 1612, 1438, 1377, 1344, 910; 1H
NMR (300 MHz, CDCl3): d 5.80 (1H, ddt, J 16.8, 10.5 and 5.7 Hz),
5.66 (2H, s, H-2 and H-3), 5.13–4.98 (2H, m), 4.80 (1H, s) and
4.72 (1H, s) [C@CH2], 2.97 (2H, d, J 5.7 Hz), 2.80–2.40 (7H, m),
C
20H28O; MW = 284.42; colourless; crystal system: trigonal; space
group R3; cell parameters, a = 25.309(5) Å, b = 25.309(5) Å,
c = 7.2440(15) Å; 90.00, b 90.00,
120.00, V = 4018.6(14) Å3,
Z = 9, Dc = 1.058 g cmꢀ3 = 0.063 mmꢀ1
F(000) = 1404, Total
a
c
,
l
.

1396
A. Srikrishna et al. / Tetrahedron: Asymmetry 19 (2008) 1392–1396
number of l.s. parameters = 192, R1 = 0.0644 for 2015 F0 > 2
r
(F0)
4.9. (1S,4S,6R)-4-Isopropenyl-1-methylbicyclo[4.4.0]-
and 0.1146 for all 3500 data. wR2 = 0.1673, GOF = 1.022, restrained
GOF = 1.022 for all data. An ORTEP diagram is depicted in Figure 2.
Crystallographic data have been deposited with Cambridge Crystal-
lographic Data Centre (CCDC 681247).
decanespiro[5.10]cyclopenta-8,30-dien-2-one 13
The RCM reaction of enone 10 (20 mg, 0.07 mmol) in anhydrous
CH2Cl2 (7 ml, 0.01 M) using Grubbs’ first generation catalyst (6 mg,
10 mol %) for 4 h at room temperature followed by purification on
a silica gel column using CH2Cl2–hexane (1:4) as eluent furnished
4.7. (6R,7R,10S)-6,7-Bis-allyl-10-isopropenyl-7-methylspiro-
[4.5]dec-2-en-8-one 11
the RCM product 13 (18 mg, 100%) as an oil. ½a D21
¼ þ25:7 (c 2.5,
ꢂ
CHCl3); IR (neat): m
max/cmꢀ1 3051, 3024, 2924, 2856, 1709, 1656,
Allyl enol ether 9 (42 mg, 0.15 mmol) was taken in a sealed tube
and heated to 180 °C for 6 h. It was cooled and purified on a silica
gel column using CH2Cl2–hexane (1:4) to give enone 11 (32 mg,
1635, 1460, 1433, 1373, 1346, 1270, 1230, 1080, 895, 676, 662;
1H NMR (300 MHz, CDCl3): d 5.61 (2H, br s), 5.60–5.50 (2H, m),
4.76 (1H, s), 4.72 (1H, s), 3.00 (1H, t, J 14.1 Hz), 2.70–2.45 (3H,
m), 2.40–2.20 (3H, m), 2.20–1.90 (4H, m), 1.80 (1H, dd, J 10.5
and 5.7 Hz), 1.72 (3H, s, olefinic–CH3), 1.12 (3H, s, tert-CH3); 13C
NMR (75 MHz, CDCl3): d 214.4 (C, C@O), 145.2 (C, C@CH2), 129.6
(2C, CH), 125.2 (CH), 124.8 (CH), 114.9 (CH2, C@CH2), 56.2 (CH),
49.9 (CH), 47.4 (2C, C), 44.1 (CH2), 40.2 (CH2), 36.2 (CH2), 34.1
(CH2), 24.3 (CH2), 21.2 (CH3), 19.0 (CH3); HRMS: Calcd for
C18H24ONa (M+Na): 279.1725. Found: 279.1725.
79%) as an oil. ½a D24
ꢂ
¼ þ3:7 (c 1.9, CHCl3); IR (neat):
m
max/cmꢀ1
3076, 2974, 2929, 2860, 1707, 1639, 1446, 1378, 1124, 994, 912,
676; 1H NMR (300 MHz, CDCl3): d 5.85–5.75 (2H, m), 5.65–5.55
(2H, m), 5.10–4.90 (4H, m), 4.81 (1H, s), 4.61 (1H, s), 2.80–2.55
(3H, m), 2.54–2.42 (3H, m), 2.40–2.20 (4H, m), 2.18–2.10 (2H,
m), 1.68 (3H, s, olefinic–CH3), 1.11 (3H, s, tert-CH3); 13C NMR
(75 MHz, CDCl3): d 214.4 (C, C@O), 147.0 (C, C@CH2), 140.3
(CH), 133.8 (CH), 129.7 (CH), 129.0 (CH), 117.6 (CH2), 114.7
(CH2), 114.4 (CH2), 53.2 (CH), 52.5 (CH), 48.9 (2C, C), 44.4 (CH2),
43.0 (CH2), 40.4 (CH2), 39.1 (CH2), 32.4 (CH2), 23.6 (CH3), 21.9
(CH3); HRMS: Calcd for C20H28ONa (M+Na): 307.2038. Found:
307.2035.
Acknowledgement
We thank the Council of Scientific and Industrial Research, New
Delhi for the award of a research fellowship to V.H.P.
4.8. (1R,4S,6R)-4-Isopropenyl-1-methylbicyclo[4.4.0]decane-
References
spiro[5.10]cyclopenta-8,30-dien-2-one 12
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The RCM reaction of enone 11 (20 mg, 0.07 mmol) in anhy-
drous CH2Cl2 (7 ml, 0.01 M) using Grubbs’ first generation catalyst
(6 mg, 10 mol %) for 6 h at room temperature and work up as de-
scribed for the enone 6, followed by purification on a silica gel
column impregnated with silver nitrate using ethyl acetate–hex-
ane (1:30) as eluent furnished the tricyclic enone 12 (15 mg,
83%) as an oil. ½a D27
ꢂ
¼ ꢀ3:3 (c 0.6, CHCl3); IR (neat):
m
max/cmꢀ1
3052, 3026, 2968, 2912, 1705, 1455, 1433, 1375, 1272, 1231,
953, 894, 666; 1H NMR (400 MHz, CDCl3): d 5.68 (2H, s), 5.59
(2H, s), 4.82 (1H, s), 4.59 (1H, s), 2.88–2.75 (2H, m), 2.70–2.60
(2H, m), 2.50–2.00 (8H, m), 1.68 (3H, s, olefinic–CH3), 1.21 (3H,
s, tert-CH3); 13C NMR (100 MHz, CDCl3): d 215.3 (C, C@O), 147.1
(C, C@CH2), 129.6 (CH), 128.9 (CH), 125.9 (CH), 123.9 (CH),
114.4 (CH2, C@CH2), 53.1 (CH), 48.2 (C), 47.6 (C), 45.0 (CH), 43.7
(CH2), 42.1 (CH2), 39.6 (CH2), 33.4 (CH2), 24.3 (CH2), 23.82 (CH3),
23.79 (CH3); HRMS: Calcd for C18H24ONa (M+Na): 279.1725.
Found: 279.1725.
6. (a) Buchi, G.; Egger, B. J. Org. Chem. 1971, 36, 2021; (b) Srikrishna, A.;
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8. Similar temperature-based changes of the stereochemistry in allylations were
also observed in a few other carvone derivatives. Srikrishna, A.; Pardeshi, V. H.;
Satyanarayana, G., unpublished results.