Stereoselective total synthesis of the sesquiterpene (±)-β- isocomene

Article abstract of DOI:10.1055/s-2007-986634

Application of the Lewis acid mediated [3+2] cycloaddition of allyl-tert-butyldiphenylsilane combined with a modified Fleming-Tamao oxidation provides a stereoselective route to the triquinane sesquiterpene (±)-β-isocomene. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2007-986634

LETTER
2371
Stereoselective Total Synthesis of the Sesquiterpene (±)-b-Isocomene
S
A
tereoselective To
r
tal Synth
n
esis of the
S
d
esquiterpene
t
(
±
)
-Cameroo
W
nanol . Schmidt, Thomas Olpp, Elke Baum, Tina Stiffel, Hans-Joachim Knölker*
Department Chemie, Technische Universität Dresden, Bergstraße 66, 01069 Dresden, Germany
Fax +49(351)46337030; E-mail: hans-joachim.knoelker@tu-dresden.de
Received 20 June 2007
Abstract: Application of the Lewis acid mediated [3+2] cycloaddi-
tion of allyl-tert-butyldiphenylsilane combined with a modified
Fleming–Tamao oxidation provides a stereoselective route to the
triquinane sesquiterpene (±)-b-isocomene.
Key words: cycloadditions, Lewis acids, silicon, stereoselective
synthesis, terpenoids
1
(–)-β-isocomene
2 (–)-isocomene
Figure 1 Triquinane sesquiterpene natural products of the
isocomene type
The sesquiterpene (–)-b-isocomene (1) was isolated first
by Bohlmann and co-workers in 1979 during their inves-
tigation of various species of the South African genus
1
Berkheya (family: asteraceae, Figure 1). The natural
product was found along with other sesquiterpenes in the
roots of B. rhapontica (DC.) Hutch. & Burtt Davy, B.
setifera (DC.) and B. sp. novum aff. bipinnatifada. The
isomeric (–)-isocomene (2) was isolated first by Zalkow et
al. in 1977 from the hexane extract of Isocoma Wrightii, a
toxic plant, also known as Rayless Goldenrod or Jimmy-
weed, which is native to New Mexico and Texas
2
(
Figure 2). The relative configuration was established by
transformation of the natural product into the correspond-
ing diol and subsequent single-crystal X-ray analysis. In
the same year (–)-isocomene (2) was isolated by Bohl-
mann et al. from the roots of the South African Berkheya3
radula (Harv.) De Willd. and named berkheyaradulene.
However, the name (–)-isocomene prevailed. Since then, Figure 2 Isocoma wrightii (Courtesy of Texas Cooperative Exten-
both natural products have been found in various plants.4
,5
sion, Texas A&M University System)
The absolute configuration was assigned in 1993 by Fitjer
et al. based on rearrangement experiments of compounds
with known absolute configuration. For the biogenesis of
15
6
9
11
H
–
P2O72–
H
H
the isocomenes a cascade of rearrangement steps starting
1
7
from farnesyl pyrophosphate (3) has been proposed
4
5
5
–7
13
(
Scheme 1).
The intermediate presilphiperfolanyl
OP2O6–
12
cation (5) is considered as the crucial precursor for all
triquinanes and represents the parent compound for atom
numbering. Due to their unique skeleton, both natural
products have received considerable attention in organic
3
4
5
1
H
8
–10
synthesis.
An asymmetric synthesis of 2 was reported
9
by Rawal et al. in 1996. Due to the exocyclic methylene
group at C-6, b-isocomene is the more challenging target.
So far four total syntheses of (±)-b-isocomene [(±)-1]
have been described. The acid-catalyzed isomerization of
2
6
7
8
Scheme 1 Biogenetic pathway to the isomeric isocomenes 1 and 2
(
±)-b-isocomene [(±)-1] affords the thermodynamically
10
more stable isomer (±)-isocomene [(±)-2].
We described the formation of five-membered carbo-
cyclic rings by a formal [3+2] cycloaddition of sterically
1
1,12
hindered allylsilanes and a,b-unsaturated ketones.
This new methodology found diverse applications in
organic synthesis. Exploitation of the silylcyclopentanes
for natural product synthesis is feasible by the Fleming–
SYNLETT 2007, No. 15, pp 2371–2374
1
7
.0
9
.2
0
0
7
13
Advanced online publication: 28.08.2007
DOI: 10.1055/s-2007-986634; Art ID: G19207ST
©
Georg Thieme Verlag Stuttgart · New York

2
372
A. W. Schmid et al.
LETTER
Tamao oxidation.14 Even highly hindered silyl groups
e.g. triphenylsilyl, tert-butyldiphenylsilyl and di(isopro-
Sit-BuPh2
OH
[
pyl)phenylsilyl] can be converted into the corresponding
hydroxy groups by using our modified protocol for this re-
action. Herein, we report an application using our [3+2]
cycloaddition of allyl-tert-butyldiphenylsilane to the ste-
reoselective total synthesis of (±)-b-isocomene [(±)-1].
a)
b)
O
O
O
1
5
9
10
11
Our approach to (±)-b-isocomene [(±)-1] started from the
OSit-BuMe2
OSit-BuMe2
O
1
6
known enone 9, prepared by Yoshikoshi’s method via
Henry reaction and subsequent intramolecular aldol con-
c)
e)
d)
1
6b
densation. Since an enantioselective synthesis of enone
O
6d
9
has been reported,1 our approach would open up an
access to enantiopure 1 as well. The Lewis acid mediated
3+2] cycloaddition of 9 and allyl-tert-butyldiphenyl-
12
13
14
[
silane provided the tricyclic compound 10 as a single Scheme 2 Reagents and conditions: a) 1. TiCl , CH Cl , r.t., 10
4
2
2
1
7
diastereoisomer in high yield (85%; Scheme 2). The anti min; 2. allyl-tert-butyldiphenylsilane, reflux, 10 d (85%); b) 1.
BF ·2AcOH, 1,2-C H Cl , reflux, 46 h; 2. CsF, KHCO , H O , THF–
configuration of 10 was unequivocally proven by an X-
3
2
4
2
3
2
2
ray crystal-structure determination (Figure 3).18 This
MeOH (1:1), reflux, 12 h (86%, two steps); c) t-BuMe SiCl, imidazo-
le, CH Cl , r.t., 2 h (94%); d) 1. MePPh Br, n-BuLi, p-xylene, r.t.; 2.
2, p-xylene, reflux, 48 h (83%); e) 1. TBAF, H O, THF, reflux, 24 h,
2
2
2
3
assignment has been confirmed by comparison with the
1
(
2
1
2
stereochemical results of our previous studies. Remark-
ably, our cycloaddition establishes the decahydrocyclo-
penta[c]pentalene skeleton with three consecutive
quaternary carbon atoms in a single step. Protodesilyla-
tion of 10 using boron trifluoride–acetic acid complex fol-
lowed by oxidation of the resulting difluorosilane with
buffered hydrogen peroxide in the presence of cesium
97%); 2. TPAP, NMO, CH Cl , r.t., 16 h (95%).
2 2
1
5
fluoride (modified Fleming–Tamao oxidation) afforded
1
7
alcohol 11. Since methylenation in the presence of the
free hydroxy group was not possible, compound 11 was
transformed into the corresponding silyl ether 12. Wittig
olefination furnished compound 13, bearing the required
exocyclic double bond. Generation of the Wittig reagent
by addition of butyllithium to methyltriphenylphosphoni-
um bromide and subsequent slow addition of the ketone
while heating in p-xylene at reflux was required for this
transformation. The next task was the introduction of the
missing methyl group at C-9. Thus, the silyl ether was
cleaved followed by oxidation of the resulting alcohol to
the ketone 14 using catalytic amounts of tetrapropyl-
ammonium perruthenate (TPAP) and N-methylmor-
pholine N-oxide (NMO) as stoichiometric oxidant.19
A regio- and stereoselective alkylation was envisaged for
the introduction of the final methyl group. Due to the ster-
ic hindrance caused by the angular methyl group at C-7,
we expected a preferential deprotonation at C-9 leading to
the 9,10-enolate. Attack of the electrophile should occur
from the exo-face of the molecule, previously observed
Figure 3 Molecular structure of compound 10 in the crystal.
for various transformations at the 9,10-double bond of the HSQC, HMBC, and NOESY). Finally, the oxo group of
2
0
isocomene skeleton. Deprotonation with LiHMDS at 15 had to be removed. Wolff–Kishner reduction and
room temperature followed by treatment of the resulting thioketalization of the ketone failed. Thus, compound 15
enolate with iodomethane in the presence of N,N¢-dimeth- was reduced to the alcohol 16 using lithium aluminum hy-
yl-1,3-propyleneurea (DMPU) and catalytic amounts of dride. The relative configuration of 16 was assigned based
2
1
dimethylzinc led to compound 15 (Scheme 3). After re- on 2D NMR experiments (COSY, HSQC, HMBC, and
moval of starting material by flash chromatography, the NOESY). Transformation into the corresponding mesy-
desired product 15 was isolated along with two mono- late and subsequent nucleophilic displacement with lithi-
alkylated isomers and two double alkylation products.22 um aluminum hydride afforded (±)-b-isocomene [(±)-1].
The regio- and stereochemistry of the alkylation product The natural product was quantitatively isomerized to (±)-
10b
1
5 was assigned based on 2D NMR experiments (COSY, isocomene [(±)-2] using a literature procedure. The
Synlett 2007, No. 15, 2371–2374 © Thieme Stuttgart · New York

LETTER
Stereoselective Total Synthesis of the Sesquiterpene (±)-b-Isocomene
2373
O
O
HO
37, 4445. (f) Wenkert, E.; Arrhenius, T. S. J. Am. Chem.
Soc. 1983, 105, 2030. (g) Fitjer, L.; Kanschik, A.;
Majewski, M. Tetrahedron Lett. 1988, 29, 5525. (h) Rawal,
V. H.; Dufour, C.; Eschbach, A. J. Chem. Soc., Chem.
Commun. 1994, 1797. (i) Fitjer, L.; Majewski, M.; Monzó-
Oltra, H. Tetrahedron 1995, 51, 8835. (j) Review: Mehta,
G.; Srikrishna, A. Chem. Rev. 1997, 97, 671.
a)
b)
14
15
16
(
9) Total synthesis of (–)-isocomene (–)-2, see: Rawal, V. H.;
Eschbach, A.; Dufour, C.; Iwasa, S. Pure Appl. Chem. 1996,
6
8, 675.
(10) Total syntheses of (±)-b-isocomene [(±)-1], see:
a) Oppolzer, W.; Bättig, K.; Hudlicky, T. Helv. Chim. Acta
979, 62, 1493. (b) Oppolzer, W.; Bättig, K.; Hudlicky, T.
c)
d)
(
1
Tetrahedron 1981, 37, 4359. (c) Ranu, B. C.; Kavka, M.;
Higgs, L. A.; Hudlicky, T. Tetrahedron Lett. 1984, 25,
(±)-1
(±)-2
2
447. (d) Tobe, Y.; Yamashita, T.; Kakiuchi, K.; Odaira, Y.
Scheme 3 Reagents and conditions: a) 1. LiHMDS, THF, r.t., 2 h;
. MeI, ZnMe , DMPU, THF, –78 °C to 25 °C, 16 h (49%); b)
J. Chem. Soc., Chem. Commun. 1985, 898. (e)Willmore,N.
D.; Goodman, R.; Lee, H.-H.; Kennedy, R. M. J. Org. Chem.
1992, 57, 1216.
2
2
LiAlH , THF, –78 °C, 3 h (86%); c) 1. MsCl, EtN(i-Pr) , CH Cl ,
4
2
2
2
0
°C, 2 h; 2. LiAlH , Et O, reflux, 3 h (78%, two steps); d)
4 2
PTSA·H O, CH Cl , r.t., 3 h (100%).
(11) (a) Knölker, H.-J.; Jones, P. G.; Pannek, J.-B. Synlett 1990,
2
2
2
429. (b) Knölker, H.-J.; Foitzik, N.; Goesmann, H.; Graf, R.
Angew. Chem., Int. Ed. Engl. 1993, 32, 1081. (c) Knölker,
H.-J.; Jones, P. G.; Graf, R. Synlett 1996, 1155. (d)
spectroscopic data of our synthetic (±)-b-isocomene [(±)-
1
] and (±)-isocomene [(±)-2] are in full agreement with
Review: Knölker, H.-J. J. Prakt. Chem. 1997, 339, 304.
(e) Knölker, H.-J.; Baum, E.; Graf, R.; Jones, P. G.; Spieß,
O. Angew. Chem. Int. Ed. 1999, 38, 2583. (f) Knölker, H.-
J.; Foitzik, N.; Schmitt, O. Tetrahedron Lett. 1999, 40, 3557.
12) (a) Knölker, H.-J.; Foitzik, N.; Goesmann, H.; Graf, R.;
Jones, P. G.; Wanzl, G. Chem. Eur. J. 1997, 3, 538.
1
–3,17
those reported for the natural products.
In conclusion, our Lewis acid promoted [3+2] cycloaddi-
tion of allyl-tert-butyldiphenylsilane followed by the
modified Fleming–Tamao oxidation represents a power-
ful method for natural product synthesis. The efficiency of
this cyclopentannulation is emphasized by the fact that a
sterically hindered arrangement of three contiguous quar-
ternary carbon centers is constructed in high yield (85%).
We obtained (±)-b-isocomene [(±)-1] for the first time as
a solid (colorless crystals, mp 76–82 °C) in 9 steps and
(
(
(b) Knölker, H.-J.; Foitzik, N.; Gabler, C.; Graf, R. Synthesis
1999, 145. (c) Part 18 of Cycloadditions of Allylsilanes. For
part 17, see: Schmidt, A. W.; Olpp, T.; Schmid, S.; Goutal,
S.; Jäger, A.; Knölker, H.-J. Synlett 2007, 1549.
13) (a) Judd, W. R.; Ban, S.; Aubé, J. J. Am. Chem. Soc. 2006,
128, 13736. (b) Peng, Z.-H.; Woerpel, K. A. J. Am. Chem.
Soc. 2003, 125, 6018. (c) Nair, V.; Rajesh, C.; Dhanya, R.;
Rath, N. P. Org. Lett. 2002, 4, 953. (d) Roberson, C. W.;
Woerpel, K. A. J. Am. Chem. Soc. 2002, 124, 11342.
1
7% overall yield based on enone 9.
(
e) Akiyama, T.; Sugano, M.; Kagoshima, H. Tetrahedron
References and Notes
Lett. 2001, 42, 3889. (f) Micalizio, G. C.; Roush, W. R. Org.
Lett. 2001, 3, 1949. (g) Isaka, M.; Williard, P. G.;
Nakamura, E. Bull. Chem. Soc. Jpn. 1999, 72, 2115.
(1) Bohlmann, F.; Le Van, N.; Pham, T. V. C.; Jacupovic, J.;
Schuster, A.; Zabel, V.; Watson, W. H. Phytochemistry
(
h) Akiyama, T.; Hoshi, E.; Fujiyoshi, S. J. Chem. Soc.,
1979, 18, 1831.
Perkin Trans. 1 1998, 2121. (i) Akiyama, T.; Yamanaka, M.
Tetrahedron Lett. 1998, 39, 7885. (j) Groaning, M. D.;
Brengel, G. P.; Meyers, A. I. J. Org. Chem. 1998, 63, 5517.
(
(
(
2) Zalkow, L. H.; Harris, R. N. III; Van Derveer, D.; Bertrand,
J. A. J. Chem. Soc., Chem. Commun. 1977, 456.
3) Bohlmann, F.; Le Van, N.; Pickardt, J. Chem. Ber. 1977,
(
k) Brengel, G. P.; Meyers, A. I. J. Org. Chem. 1996, 61,
110, 3777.
3
1
2
230. (l) Masse, C. E.; Panek, J. S. Chem. Rev. 1995, 95,
293. (m) Panek, J. S.; Jain, N. F. J. Org. Chem. 1993, 58,
345. (n) Danheiser, R. L.; Takahashi, T.; Bertók, B.; Dixon,
4) (a) Bohlmann, F.; Zdero, C.; Bohlmann, R.; King, R. M.;
Robinson, H. Phytochemistry 1980, 19, 579. (b) Bohlmann,
F.; Ziesche, J. Phytochemistry 1980, 19, 2681.
B. R. Tetrahedron Lett. 1993, 34, 3845.
(c) Bohlmann, F.; Jakupovic, J.; Robinson, H.; King, R. M.
(
14) (a) Fleming, I. Chemtracts: Org. Chem. 1996, 9, 1.
Phytochemistry 1980, 19, 2769. (d) Bohlmann, F.; Misra, L.
N.; Jakupovic, J.; Robinson, H.; King, R. M. J. Nat. Prod.
(
b) Tamao, K. In Advances in Silicon Chemistry, Vol. 3; JAI
Press: Greenwich / CT, 1996, 1. (c) Jones, G. R.; Landais,
Y. Tetrahedron 1996, 52, 7599. (d) Mader, M. M.; Norrby,
P.-O. J. Am. Chem. Soc. 2001, 123, 1970.
1
984, 47, 658. (e) Jakupovic, J.; Kuhnke, J.; Schuster, A.;
Metwally, M. A.; Bohlmann, F. Phytochemistry 1986, 25,
133. (f) Weyerstahl, P.; Marschall, H.; Seelmann, I.;
1
(
(
15) (a) Knölker, H.-J.; Wanzl, G. Synlett 1995, 378.
Jakupovic, J. Eur. J. Org. Chem. 1998, 1205.
5) Bohlmann, F.; Jakupovic, J. Phytochemistry 1980, 19, 259.
6) Fitjer, L.; Monzó-Oltra, H. J. Org. Chem. 1993, 58, 6171.
7) Coates, R. M.; Ho, Z.; Klobus, M.; Wilson, S. R. J. Am.
Chem. Soc. 1996, 118, 9249.
(
b) Knölker, H.-J.; Jones, P. G.; Wanzl, G. Synlett 1998, 613.
(
(
(
16) (a) Miyashita, M.; Yanami, T.; Yoshikoshi, A. J. Am. Chem.
Soc. 1976, 98, 4679. (b) Miyashita, M.; Yanami, T.;
Kumazawa, T.; Yoshikoshi, A. J. Am. Chem. Soc. 1984, 106,
2
Chem., Int. Ed. Engl. 1984, 23, 798. (d) Urabe, H.; Hideura,
D.; Sato, F. Org. Lett. 2000, 2, 381. (e) Jung, M. E.;
Davidov, P. Org. Lett. 2001, 3, 3025.
149. (c) Dorsch, M.; Jäger, V.; Spönlein, W. Angew.
(
8) Total syntheses of (±)-isocomene [(±)-2], see: (a) Paquette,
L. A.; Han, Y.-K. J. Org. Chem. 1979, 44, 4014.
(
(
(
b) Pirrung, M. C. J. Am. Chem. Soc. 1979, 101, 7130.
c) Pirrung, M. C. J. Am. Chem. Soc. 1981, 103, 82.
d) Paquette, L. A.; Han, Y.-K. J. Am. Chem. Soc. 1981, 103,
(
17) Characteristic Spectroscopic Data of 10, 11, (±)-1, and (±)-2:
1
3
Compound 10: colorless crystals, mp 112 °C. C NMR and
1835. (e) Wender, P. A.; Dreyer, G. B. Tetrahedron 1981,
Synlett 2007, No. 15, 2371–2374 © Thieme Stuttgart · New York

2
374
A. W. Schmid et al.
LETTER
DEPT (125 MHz, CDCl ): d = 18.60 (C), 19.83 (CH ), 21.64
CDCl ): d = 13.00 (CH ), 17.27 (CH ), 23.16 (CH ), 23.71
3
3
3
3
3
3
(
CH), 23.23 (CH ), 23.72 (CH ), 28.47 (3 CH ), 35.46
(CH ), 24.01 (CH ), 31.91 (CH ), 33.62 (CH ), 37.22 (CH ),
2
3
3
3 2 2 2 2
(
5
CH ), 40.17 (CH ), 43.21 (CH ), 44.92 (CH ), 45.83 (C),
39.88 (CH), 42.60 (CH ), 56.61 (C), 59.86 (C), 63.75 (C),
132.66 (CH), 142.81 (C). MS (EI): m/z (%) = 204 (10) [M ],
2
2
2
2
2
+
3.14 (CH ), 59.61 (C), 62.43 (C), 127.48 (4 CH), 129.11 (2
2
CH), 133.76 (C), 134.12 (C), 136.47 (2 CH), 136.53 (2 CH),
189 (16), 175 (7), 162 (100), 161 (17), 147 (49), 134 (18),
133 (19), 119 (31), 105 (20), 91 (18). Anal. Calcd (%) for
C H O: C, 88.16; H, 11.84. Found: C, 88.20; H, 11.80.
2
23.74 (C=O). Anal. Calcd (%) for C H OSi: C, 80.87; H,
29 38
8
.89. Found: C, 80.64; H, 8.26.
1
5
24
1
3
Compound 11: colorless oil. C NMR and DEPT (125 MHz,
CDCl ): d = 21.12 (CH ), 22.96 (CH ), 23.00 (CH ), 35.58
(18) Crystal data for 10: C H OSi, crystal size:
29 38
3
–1
0.60 × 0.40 × 0.40 mm , M = 430.68 g mol , monoclinic,
3
3
2
3
r
(CH ), 41.29 (CH ), 45.48 (CH ), 46.23 (C), 49.07 (CH ),
space group P2 /c, l = 0.71073 Å, a = 13.4071(14),
2
2
2
2
1
5
0.19 (CH ), 57.46 (C), 61.44 (C), 71.76 (CH), 223.43
b = 12.1653(9), c = 16.2492(17) Å, b = 109.414(11)°,
2
3
–3
(
(
C=O).
±)-b-Isocomene [(±)-1]: colorless crystals, mp 76–82 °C.
V = 2499.6(4) Å , Z = 4, r
= 1.144 g cm , m = 0.112
calcd
–
1
mm , T = 200(2) K, q range = 2.14°–25.85°; reflections
IR (ATR): n = 3073, 2925, 2869, 2854, 1655, 1460, 1376,
1
collected: 18979, independent: 4787 (R = 0.0393). The
int
–
1 1
260, 1106, 1024, 878 cm . H NMR (500 MHz, CD Cl ):
structure was solved by direct methods and refined by full-
2
2
2
d = 0.92 (d, J = 7.0 Hz, 3 H), 0.99 (s, 3 H), 1.10 (s, 3 H),
.22–1.68 (m, 10 H), 2.00 (m, 1 H), 2.10 (d, J = 14.4 Hz, 1
H), 2.34 (dt, J = 14.4, 2.4 Hz, 1 H), 4.60 (m, 1 H), 4.63 (m,
matrix least-squares on F ; R = 0.0481, wR = 0.1275 [I >
1
2
–
3
1
2s(I)]; maximal residual electron density: 0.424 e Å .
CCDC 646230 contains the supplementary crystallographic
data for this structure. These data can be obtained free of
charge from The Cambridge Crystallographic Data Centre
via www.ccdc.cam.ac.uk/data_request/cif.
1
H). 13C NMR and DEPT (125 MHz, CD Cl ): d = 18.08
3 3 3 2 2
2 2
(CH ), 23.53 (CH ), 24.27 (CH ), 24.33 (CH ), 30.55 (CH ),
3
4.87 (CH ), 40.83 (CH), 41.95 (CH ), 43.15 (CH ), 48.23
2
2
2
(
(
1
1
CH ), 49.68 (C), 55.14 (C), 67.01 (C), 100.79 (CH ), 162.76
C). MS (EI): m/z (%) = 204 (21) [M ], 189 (68), 175 (12),
(19) (a) Griffith, W. P.; Ley, S. V. Aldrichimica Acta 1990, 23,
13. (b) Ley, S. V.; Norman, J.; Griffith, W. P.; Marsden, S.
P. Synthesis 1994, 639.
(20) (a) Kwart, L. D.; Tiedje, M. H.; Frazier, J. O.; Hudlicky, T.
Synth. Commun. 1986, 16, 393. (b) Hudlicky, T.; Kwart, L.
D.; Tiedje, M. H.; Ranu, B. C.; Short, R. P.; Frazier, J. O.;
Rigby, H. L. Synthesis 1986, 716.
(21) Morita, Y.; Suzuki, M.; Noyori, R. J. Org. Chem. 1989, 54,
1785.
(22) Ratio of compound 15/monoalkylated isomer 1/
monoalkylated isomer 2/dialkylated product 1/dialkylated
product 2 = 78.2:14.0:3.6:2.2:2.0.
2
2
+
62 (15), 161 (35), 149 (22), 148 (29), 147 (49), 134 (28),
33 (42), 122 (29), 121 (44), 120 (31), 119 (40), 109 (68),
08 (100), 107 (60). Anal. Calcd (%): for C H O: C, 88.16;
1
1
5
24
H, 11.84. Found: C, 88.27; H, 11.98.
(
2
±)-Isocomene [(±)-2]: colorless oil. IR (ATR): n = 3020,
927, 2866, 2853, 1672, 1458, 1443, 1375, 1002, 940, 845
–
1 1
cm . H NMR (500 MHz, CDCl ): d = 0.85 (d, J = 7.2 Hz,
3
3
1
1
H), 1.026 (s, 3 H), 1.030 (s, 3 H), 1.14–1.43 (m, 5 H), 1.48–
.58 (m, 4 H), 1.55 (d, J = 1.3 Hz, 3 H), 1.70–1.73 (m, 1 H),
1
3
.99 (m, 1 H), 4.85 (m, 1 H). C NMR and DEPT (125 MHz,
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