Stereoselective syntheses of (±)-komaroviquinone and (±)-faveline methyl ether through intramolecular Heck reaction

Article abstract of DOI:10.1021/jo051082i

An efficient, flexible, and stereoselective convergent route for constructing the trans-10-hydroxy-1,1-dimethyloctahydrodibenzo[a,d]cyclohepten- 7-ones (5a-c) was achieved via intramolecular Heck reaction. This strategy has been successfully implemented for the syntheses of (±)-komaroviquinone (3) through (±)-coulterone dimethyl ether (5c) and (±)-faveline methyl ether (1a).

Full text of DOI:10.1021/jo051082i

Stereoselective Syntheses of (()-Komaroviquinone and
(()-Faveline Methyl Ether through Intramolecular Heck Reaction
Sujaya Sengupta,† Michael G. B. Drew,‡ Ranjan Mukhopadhyay,† Basudeb Achari,† and
Asish Kr. Banerjee*,†
Medicinal Chemistry Division, Indian Institute of Chemical Biology, 4 Raja S. C. Mullick Road,
Kolkata-700 032, India, and School of Chemistry, University of Reading, Whiteknights,
Reading RG6 6AD, U.K.
ashisbanerjee@iicb.res.in
Received May 30, 2005
An efficient, flexible, and stereoselective convergent route for constructing the trans-10-hydroxy-
1,1-dimethyloctahydrodibenzo[a,d]cyclohepten-7-ones (5a-c) was achieved via intramolecular Heck
reaction. This strategy has been successfully implemented for the syntheses of (()-komaroviquinone
(3) through (()-coulterone dimethyl ether (5c) and (()-faveline methyl ether (1a).
Introduction
A number of total syntheses of the rearranged diter-
penoids 1d,5 1e,5b,6 and 1f5c,7 incorporating functionalized
6-7-6-fused tricycles have appeared in the literature.
The reported total syntheses5c,8 of (()-faveline methyl
ether (1a), (()-faveline (1b), and (()-deoxofaveline (1c)
involve generation of the basic tricyclic skeleton mainly
through acid-catalyzed cycliacylation8 or cyclialkylation5c
reactions. However, introduction of the 7-oxo group in
deoxofaveline (1c) was plagued with problems.5c,8b No
report exists so far for the synthesis of coulterone (2),
komaroviquinone (3), and cyclocoulterone (4). In continu-
ation of our studies on the palladium-mediated synthesis
of rearranged polycyclic diterpenoids,9,10 we report herein
the first total synthesis of (()-komaroviquinone (3)
through (()-coulterone dimethyl ether (5c) as well as a
simple route to (()-faveline methyl ether (1a).
A number of cytocidal compounds have been isolated
from the bark of the Brazilian plant favela (Cnidoscolus
phyllacanthus).1 Faveline methyl ether (1a), faveline
(1b), and deoxofaveline (1c) are typical members of
rearranged 9(10f20)-abeo-16,17-dinorabieta-8,11,13-
triene diterpenes (Figure 1). These molecules display
significant activity against P-388 murine leukemia cells.1
Several other rearranged abietane diterpenes, for ex-
ample, pisiferin (1d),2a,b isopisiferin (1e),2c and barbatusol
(1f),2d have also been described. Recently, isolation of
coulterone (2)3,4 and two new compounds in the icetexane
group of rearranged abietane diterpenes komaroviqui-
none (3)4 and cyclocoulterone (4)4 have been reported
from Dracocephalum komarovi. Komaroviquinone (3)
displays a strong trypanocidal activity against epimas-
tigotes of Trypanosoma cruzi, the causative agent of
American trypanosomiasis.4
(5) (a) Matsumoto, T.; Imai, S.; Yoshinari, T.; Matsuno, S. Bull.
Chem. Soc. Jpn. 1986, 59, 3103-3108. (b) Kametani, T.; Kondoh, H.;
Tsubuki, M.; Honda, T. J. Chem. Soc., Perkin Trans. 1 1990, 5-10. (c)
Majetich, G.; Hicks, R.; Zhang, Y.; Tian, X.; Feltman, T. L.; Fang, J.;
Duncan, S., Jr. J. Org. Chem. 1996, 61, 8169-8185.
(6) (a) Ghosh, A. K.; Ray, C.; Ghatak, U. R. Tetrahedron Lett. 1992,
33, 655-658. (b) Deb, S.; Bhattacharjee, G.; Ghatak, U. R. J. Chem.
Soc., Perkin Trans. 1 1990, 1453-1458.
† Indian Institute of Chemical Biology.
‡ University of Reading.
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3086.
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1151. (b) Hasegawa, S.; Hirose, Y.; Yatagai, M.; Takahashi, T. Chem.
Lett. 1984, 1837-1838. (c) Hasegawa, S.; Kojima, T.; Hirose, Y. Phyto-
chemistry 1985, 24, 1545-1551. (d) Kelecom, A. Tetrahedron 1983, 39,
3603-3609.
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34, 445-448.
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33, 655-658. (b) Ghosh, A. K.; Mukhopadhyay, C.; Ghatak, U. R. J.
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(9) Banerjee, M.; Mukhopadhyay, R.; Achari, B.; Banerjee, A. Kr.
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Tetrahedron Lett. 2005, 46, 1515-1519.
10.1021/jo051082i CCC: $30.25 © 2005 American Chemical Society
Published on Web 08/23/2005
7694
J. Org. Chem. 2005, 70, 7694-7700

Syntheses of (()-Komaroviquinone and (()-Faveline Methyl Ether
FIGURE 1. Rearranged 9(10f20)-abeo-abietane diterpenoids.
SCHEME 1. Retrosynthetic Analysis
with the allylcyclohexanone 9. The chlorides 10b and 10c
were prepared from p-toluic acid and 1,2,4-trimethoxy-
benzene via the modification of known sequences of
reactions13-17 involving intermediates 11-19 (schemes
given in the Supporting Information).
The gem-dimethylcyclohexanone
9 was prepared
(Scheme 2) by the conjugate addition of a methyl group18
to the allylcyclohexenone 21,19 obtained in turn from 20,
the methyl ester analogue of Hagemann’s ester.20 Barbier
reaction of 10a-c with 9 was initially carried out under
sonication according to the method of Abad et al.12a The
resulting crude mixture furnished the expected desired
products (8a-c) in low yield, along with a lot of undesired
byproducts including aromatic dimeric compounds. Switch-
ing on to reaction without sonication improved the yield
of the desired products, isolated in pure form as single
diastereoisomers as determined by spectral analysis. The
trans OH/H stereochemistry in the products, deduced by
analogy,10 received support from the X-ray structure
determination of 24b subsequently done.21 Thus, the
Barbier reaction of 10a-c with 9 appears to proceed
diastereoselectively, in line with the addition of Grignard
or alkyllithium reagents to 2-alkylcyclohexanones where
a steric approach control of the addition has been
suggested12b to determine the course of reaction.
Treatment of each of the benzylcyclohexanols 8a-c
with NBS in acetonitrile22 led to the corresponding
unstable bromomethylfurans 23a-c via formation of the
bromonium intermediate 22 followed by the intramo-
lecular participation of the hydroxy group as depicted in
Scheme 2. Further reaction of these intermediates 23a-c
with an excess of NBS gave the respective aromatic ring
brominated products 24a-c.
Results and Discussion
A short, flexible, and stereoselective convergent route
for the construction of the intermediate trans-10-hydroxy-
1,1-dimethyloctahydrodibenzo[a,d]cyclohepten-7-one core
structures (5a-c) was developed by employing the in-
tramolecular Heck reaction as the crucial carbon-carbon
bond-forming step, and the retrosynthetic analysis of the
tricyclic systems is shown in Scheme 1.
The key step involves the formation of the cycloheptene
ring (6a-c) by a palladium-catalyzed 7-exo cyclization11
of the allyl o-bromobenzylcyclohexanols (7a-c) with the
exo-methylene group in the correct position for oxidative
transformation to the hydroxycycloheptenones (5a-c).
The desired olefinic substrates 7a-c for the intramo-
lecular Heck reaction were prepared from the corre-
sponding benzylcyclohexanols 8a-c, which were obtained
by Barbier coupling12a,b of the benzyl chlorides 10a-c
(11) For examples of the intramolecular 7-exo Heck reaction, see
the following articles and reviews and the references therein: (a)
Gracias, V.; Moore, J. D.; Djuric, S. T. Tetrahedron Lett. 2004, 45, 417-
420. (b) Tietze, L. F.; Sommer, K. M.; Schneider, G.; Tapolcsa´nyi, P.;
Wo˜lfling, J.; Muˆller, P.; Noltemeyer, M.; Terlau, H. Synlett 2003, 1494-
1496. (c) Santose, L. S.; Pilli, R. A. Synthesis 2002, 87-93. (d) Caddick,
S.; Kofie, W. Tetrahedron Lett. 2002, 43, 9347-9350. (e) Link, J. T.
Org. React. 2002, 60, 157-534. (f) Tietze, L. F.; Ila, H.; Bell, H. P.
Chem. Rev. 2004, 104, 3453-3516. (g) Beletskaya, I. P.; Cheprakov,
A. V. Chem. Rev. 2000, 100, 3009-3066. (h) Dounay, A. B.; Overman,
L. E. Chem. Rev. 2003, 103, 2945-2963. (i) Link, J. T. In The Handbook
of Organopalladium Chemistry for Organic Synthesis; Negishi, E., Ed.;
Wiley, Sons: New York, 2002; Vol. 1, pp 1523-1560. (j) Link, J. T.;
Overman, L. E. In Metal Catalyzed Cross Coupling Reactions;
Diederich, F., Stang, P. J., Eds.; Wiley-VCH: Weinheim, 1998; pp 99-
154.
(13) Fleifel, A. M. J. Org. Chem. 1960, 25, 1024-1025.
(14) Chakraborti, A. K.; Basak, A.; Grover, V. J. Org. Chem. 1999,
64, 8014-8017.
(15) Sishido, K.; Goto, K.; Miyoshi, S.; Takaishi, Y.; Shibuya, M. J.
Org. Chem. 1994, 59, 406-414.
(16) Tori, M.; Hamaguchi, T.; Sagawa, K.; Sono, M.; Asakawa, Y. J.
Org. Chem. 1996, 61, 5362-5370.
(17) Burnell, R. H.; Caron, S. Can. J. Chem. 1992, 1446-1454 [for
an alternative method of preparation of 17].
(18) Pal, S.; Mukhopadhyay, J. K.; Ghatak, U. R. J. Org. Chem.
1994, 59, 2687-2694.
(19) Cairns, P. M.; Howes, C.; Jenkins, P. R. J. Chem. Soc., Perkin
Trans. 1 1990, 627-632.
(20) Begbie, A. L.; Golding, B. T. J. Chem. Soc., Perkin Trans. 1
1972, 602-605.
(21) The ORTEP diagrams of 5a and 24b are given in the Support-
ing Information.
(12) (a) Abad, A.; Agullo´, C.; Arno´, M.; Cun˜at, A. C.; Meseguer, B.;
Zaragoza´, R. J. J. Org. Chem. 1998, 63, 5100-5106. (b) Ashby, E. C.;
Laemmle, J. T. Chem. Rev. 1975, 75, 521-546.
(22) Carreno, M. C.; Ruano, J. L. G.; Sanz, G.; Toledo, M. A.; Urbano,
A. J. Org. Chem. 1995, 60, 5328-5331.
J. Org. Chem, Vol. 70, No. 19, 2005 7695

Sengupta et al.
SCHEME 2. Preparation of 24a-c
SCHEME 3. Preparation of 7a-c
SCHEME 4. Preparation of 6a-c
assignment of trans-stereochemistry to the allyl o-bro-
mobenzylcyclohexanols 7a-c and the corresponding pre-
cursors 8a-c was based on the established structure of
24b.
Regeneration of the allyl o-bromobenzylcyclohexanols
(7a-c) from the bromomethylfuran derivatives (24a-c)
was planned to be effected by using a zinc-mediated
debromination fragmentation reaction.23 Treatment of
24a and 24b with activated Zn dust and saturated NH4-
Cl solution indeed led to the allyl o-bromobenzyl cyclo-
hexanols 7a and 7b in excellent yields (Scheme 3). In
contrast, application of the same reaction to the highly
substituted bromoaryl analogue 24c proved troublesome
and resulted in the formation of the expected fragmenta-
tion product 7c along with the aromatic ring debromi-
nated compound 8c. This was probably due to the
buttressing effect24 caused by the fully substituted phenyl
ring in 24c, which makes the bromine atom relatively
labile in comparison to that in the analogues 24a-b. The
aromatic ring debromination could be suppressed by
reducing the reaction time to 6 h. Although the reaction
was incomplete, remarkably the formation of 8c was not
observed, and the desired 7c could be obtained in 65%
yield (Scheme 3). However, fragmentation of 24c with
acetic acid and activated zinc in methanol at room
temperature25 proved to be the method of choice, afford-
ing 7c in a substantially improved yield (84%). The
With the precursors 7a-c in hand, the synthetic
exercise was next directed toward the Heck reaction. To
our gratification, the intramolecular Heck cyclization of
7a and 7b with Pd(OAc)2, K2CO3, and PPh3 in acetonitrile
under reflux26 led to the seven-membered exo-cyclic
alkenes 6a and 6b in excellent yields (Scheme 4). Not
surprisingly, the highly crowded bromobenzyl cyclohex-
anol 7c produced under similar conditions only a small
amount of the cyclized product 6c with most of the
starting material remaining unchanged. However, the
7-exo product 6c could be obtained in 30% yield under
forcing conditions (120 h reflux, 61% based on recovered
starting material). Replacement of K2CO3 by triethyl-
amine in acetonitrile under reflux for 120 h resulted in
the formation of 6c in 58% yield (95% based on recovered
starting material). The yield of 6c could be further
improved (Scheme 4) by using diisopropylethylamine as
the base and heating the reaction mixture under reflux
for 96 h (68%, 93% based on recovered starting material).
Finally, oxidative cleavage27 of the exo-olefins 6a and
6b with OsO4 and NaIO4 gave the respective trans-
hydroxy ketones 5a and 5b in good yields (Scheme 5).
The structure of 5a was confirmed by X-ray diffraction
analysis.22
(23) Tanino, K.; Onuki, K.; Asano, K.; Miyashita, M.; Nakamura,
T.; Takahashi, Y.; Kuwajima, I. J. Am. Chem. Soc. 2003, 125, 1498-
1500.
(24) (a) Schlosser, M. Eur. J. Org. Chem. 2001, 3975-3984. (b)
Westheimer, F. H. In Steric Effects in Organic Chemistry; Newman,
M. S., Ed.; Wiley: New York, 1956; pp 523-555.
(25) (a) Clive, D. L. J.; Yu, M.; Sannigrahi, M. J. Org. Chem. 2004,
69, 4116-4125. (b) Iguchi, M.; Nishiyama, A.; Etoh, H.; Okamoto, K.;
Yamamura, S.; Kato, Y. Chem. Pharm. Bull. 1986, 34, 4910-4915.
(26) Ma, S.; Ni, B. J. Org. Chem. 2002, 67, 8280-8288.
(27) Clive, D. L. J.; Wang, J. J. Org. Chem. 2004, 69, 2773-2784.
7696 J. Org. Chem., Vol. 70, No. 19, 2005

Syntheses of (()-Komaroviquinone and (()-Faveline Methyl Ether
SCHEME 5. Preparation of 5a-c
SCHEME 7. Dehydration of 5b
SCHEME 6. Preparation of 3
Conclusion
The facile intramolecular Heck reaction of the olefinic
intermediates 7a-c provides a simple convergent route
to rearranged diterpenoids incorporating a tricyclic diben-
zo[a,d]cycloheptenone skeleton and led to the first total
synthesis of (()-komaroviquinone (3) through (()-coulter-
one dimethyl ether (5c). The methodology also constitutes
a convenient alternative route to (()-faveline methyl
ether (1a).
Similar oxidative cleavage27 of the highly crowded exo-
olefin 6c produced the corresponding hydroxy ketone 5c,
albeit only in moderate yield (Scheme 5). Although it
appeared that 5c exists in equilibrium with the hemi-
1
ketal form 25 in solution as revealed by the H and 13C
NMR spectra,28 direct oxidation29 of this mixture of 5c
and 25 with Ag(II)O in dilute HNO3 afforded (()-
komaroviquinone (3) as the only isolable product (Scheme
6).
Experimental Section
With an expedient synthesis of (()-komaroviquinone
(3) accomplished, the remaining task of converting the
key intermediate hydroxycycloheptenone 5b to (()-fave-
line methyl ether (1a) was undertaken. While reaction
of 5b with BF3‚Et2O in CH2Cl2 at 0 °C5c led (Scheme 7)
only to the olefin 26 (isofaveline methyl ether), the use
of SOCl2 in pyridine30 (at -10 °C for 5 h) produced a
mixture of the known tetrasubstituted olefinic ketone
2731 along with 26 in a ratio of 2:1 (as shown by 1H NMR).
2-Allyl-3,3-dimethylcyclohexanone (9). To a stirred sus-
pension of CuI18 (14 g, 73.5 mmol) in dry Et2O (86 mL) was
added MeLi (75 mL, 1.6 M solution in Et2O, 120 mmol)
dropwise during 30 min (-25 °C). The resulting yellow
suspension was cooled to -50 °C, and BF3‚OEt2 (10.2 mL, 80.5
mmol) was added. After 10 min, the temperature was raised
to -30 °C, a solution of 21 (3 g, 20 mmol) in Et2O (25 mL)
added dropwise during 1 h, and stirring was continued for 30
min at -30 °C. An additional aliquot of BF3‚OEt2 (10.2 mL,
80.5 mmol) was added to the mixture and stirring continued
for 2 h at -30 °C. The temperature of the bath was allowed to
warm to -10 °C, and thereafter the reaction was quenched
by dropwise addition of saturated NH4Cl solution. The reaction
mixture was filtered and the residue thoroughly washed with
Et2O. The combined organic extracts were washed with
saturated NH4Cl solution, saturated Na2S2O3 solution, and
brine and dried. After removal of the solvent, the crude product
was purified by column chromatography over silica gel (100-
200 mesh) using 2-4% EtOAc in hexane as eluent to afford 9
8b
Finally, dehydration of 5b with KHSO4 furnished an
easily separable mixture of (()-faveline methyl ether (1a)
1
and its isomer 26 (in 2:3 ratio as shown by H NMR).
The present strategy for the synthesis of faveline
methyl ether (1a) thus affords better overall yield of the
product (4.48%) compared to that (1.95%) of Majetich et
al.5c and is also more flexible in approach to permit
synthesis of many other related natural products.
1
(3 g, 90%) as a colorless oil: IR (neat) ν 1710 cm-1; H NMR
(28) The 1H NMR spectrum of the hydroxy ketone 5c in CDCl3
solution showed additional peaks (see the Experimental Section)
indicating the possible presence of two equilibrating forms. Recording
the spectrum of a freshly prepared solution of 5c in C5D5N, however,
suggested the presence of only one form (5c). The 13C NMR spectrum
was recorded later to establish if the keto (5c) or the hemiketal form
(25) was present. Unfortunately, conversion to the other form (25) had
taken place in the meantime and the solution showed peaks both for
a carbonyl carbon (δ 207.4) and a hemiketal carbon (δ 102.9), with
the former about four times more intense than the latter. The 1H NMR
spectrum of the same solution, recorded again, now showed additional
peaks supporting the presence of both the forms. The exchange appears
to occur at a faster rate in CDCl3 solution (where the presence of traces
of acid is not unexpected) and after a week’s time, the minor form
appeared to have become the major one.
(300 MHz, CDCl3) δ 0.79 (s, 3H), 1.07 (s, 3H), 1.57-1.66 (m,
2H), 1.71-1.92 (m, 2H), 2.03-2.11 (m, 1H), 2.21-2.36 (m, 3H),
2.40-2.47 (m, 1H), 4.90-4.98 (m, 1H), 5.02-5.03 (m, 1H),
5.70-5.83 (m, 1H); 13C NMR (75 MHz, CDCl3) δ 21.7, 22.8,
28.3, 29.2, 38.9, 39.4, 41.0, 60.6, 114.9, 137.6, 212.2; EI-MS
m/z 166 (M+, 66), 111 (61), 95 (84), 69 (100). Anal. Calcd for
C11H18O: C, 79.46; H, 10.91. Found: C, 79.32; H, 11.08.
(1S*,2S*)-2-Allyl-1-(3-methoxybenzyl)-3,3-dimethylcy-
clohexanol (8a). To a well-stirred suspension of small chips
of Li (590 mg, 85 mmol) in dry THF (160 mL) was added
dropwise a mixture of 9 (2.6 g, 15.7 mmol) and 10a (1.4 g, 8.9
mmol) in dry THF (50 mL) during 4 h at -10 °C. The reaction
mixture was then stirred at 0 °C for 24 h. It was filtered and
quenched with cold saturated solution of NH4Cl. The layers
were separated, and the organic part was evaporated under
reduced pressure; the residue was taken in EtOAc (50 mL).
The aqueous part was extracted with EtOAc (2 × 20 mL); the
(29) Snyder, C. D.; Rapoport, H. J. Am. Chem. Soc. 1972, 94, 227-
231.
(30) Allen, W. S.; Bernstein, S. J. Am. Chem. Soc. 1955, 77, 1028-
1032.
(31) Ho, T. L.; Chen, C. K. Tetrahedron 1995, 51, 5819-5824.
J. Org. Chem, Vol. 70, No. 19, 2005 7697

Sengupta et al.
combined organic extracts were washed with brine, dried, and
concentrated. Column chromatography of the residue over
silica gel (100-200 mesh) using 2-5% EtOAc in hexane
yielded 8a (1.7 g, 70%) as a colorless oil: IR (neat) ν 3573,
2934, 1597, 1488, 1460, 1367, 1262, 1155 cm-1; 1H NMR (300
MHz, CDCl3) δ 0.94 (s, 3H), 1.01 (s, 3H), 1.15-1.24 (m, 2H),
1.28-1.46 (m, 3H), 1.51-1.65 (m, 2H), 2.21-2.29 (m, 1H), 2.38
(d, J ) 13 Hz, 1H), 2.50-2.58 (m, 1H), 3.12 (d, J ) 13 Hz,
1H), 3.79 (s, 3H), 4.96 (ddd, J ) 2, 3, 10 Hz, 1H), 5.09 (ddd,
J ) 2, 3, 17 Hz, 1H), 5.89-6.02 (m, 1H), 6.72-6.80 (m, 3H),
7.21 (t, J ) 8 Hz, 1H); 13C NMR (75 MHz, CDCl3) δ 17.7, 21.5,
30.1, 32.2, 35.0, 38.0, 41.9, 48.1, 53.0, 54.9, 74.4, 111.5, 113.8,
116.3, 123.0, 128.9, 138.7, 142.0, 159.3; EI-MS m/z 288 (M+,
2), 273 (11), 167 (100). Anal. Calcd for C19H28O2: C, 79.12; H,
9.78. Found: C, 79.31; H, 9.65.
diluted with Et2O (100 mL) and filtered. The organic part was
washed with brine, dried, and concentrated. The crude product
was chromatographed over silica gel (100-200 mesh) using
2-5% EtOAc in hexane to provide 7a (720 mg, 88%) as white
solid: mp 62-63 °C; IR (KBr) ν 3523, 2936, 1587 cm-1 1H
;
NMR (300 MHz, CDCl3) δ 0.95 (s, 3H), 1.01 (s, 3H), 1.23-
1.62 (m, 9H), 2.24-2.31 (m, 1H), 2.48-2.58 (m, 1H), 2.65 (d,
J ) 13 Hz, 1H), 3.27 (d, J ) 13 Hz, 1H,), 3.77 (s, 3H), 4.98
(dd, J ) 1, 10 Hz, 1H), 5.12 (dd, J ) 1, 17 Hz, 1H), 5.90-6.04
(m, 1H), 6.65 (dd, J ) 3, 9 Hz, 1H), 6.84 (d, J ) 3 Hz, 1H),
7.42 (d, J ) 9 Hz, 1H); 13C NMR (75 MHz, CDCl3) δ 17.7, 21.7,
30.2, 32.2, 35.2, 37.4, 41.9, 46.9, 53.7, 55.4, 76.1, 113.8, 114.1,
116.8, 117.9, 133.4, 138.4, 141.8, 158.5; EI-MS m/z 368 (M+
for Br81, 19), 366 (M+ for Br79, 11), 353 (91), 351 (100). Anal.
Calcd for C19H27BrO2: C, 62.13; H, 7.41. Found: C, 62.29; H,
7.56.
(2S*,3aS*,7aS*)-7a-(2-Bromo-5-methoxybenzyl)-2-bro-
momethyl-4,4-dimethyloctahydrobenzofuran (24a). To a
well-stirred solution of 8a (1.17 g, 4.06 mmol) in dry CH3CN
(20 mL) was added NBS22 (0.795 g, 4.46 mmol) portionwise at
-20 °C. The reaction mixture was stirred for 2 h at the same
temperature. Then another lot of NBS (0.795 g, 4.46 mmol)
was added and the reaction mixture further stirred for 2 h at
-20 °C. Aqueous Na2S2O3 solution (10%) was then added, and
the layers were separated. The organic part was evaporated
under reduced pressure, and the crude product was extracted
with Et2O. The Et2O extract was washed with Na2S2O3
solution (5%, 50 mL) and brine, dried, and then evaporated to
leave an oil. The crude oil was chromatographed over silica
gel (100-200 mesh) using 1-2% EtOAc in hexane to yield 24a
(1.6 g, 88%) as an oil, which solidified after cooling: mp 70-
71 °C; IR (KBr) ν 2958, 1590, 1467 cm-1; 1H NMR (300 MHz,
CDCl3) δ 0.95 (s, 3H), 1.17 (s, 3H), 1.14-1.25 (m, 3H), 1.34-
1.45 (m, 1H), 1.47-1.62 (m, 1H), 1.67-1.82 (m, 1H), 1.85-
1.94 (m, 2H), 2.08-2.21 (m, 1H), 2.81 (d, J ) 14 Hz, 1H), 3.30
(dd, J ) 7, 10 Hz, 1H), 3.40 (dd, J ) 5, 10 Hz, 1H), 3.52 (d,
J ) 14 Hz, 1H), 3.78 (s, 3H), 4.15-4.22 (m, 1H), 6.64 (dd, J )
3, 9 Hz, 1H), 7.16 (d, J ) 3 Hz, 1H), 7.39 (d, J ) 9 Hz, 1H);
13C NMR (75 MHz, CDCl3) δ 19.9, 28.8, 30.5, 31.1, 32.6, 33.2,
33.7, 37.6, 44.5, 53.1, 55.3, 74.3, 85.0, 114.2, 116.6, 118.6, 132.8,
138.9, 158.1; EI-MS m/z 448 (M+ for 2 × Br81, 0.02), 446 (M+
for Br79 and Br81, 0.04), 444 (M+ for 2 × Br79, 0.02), 247 (66),
245 (62), 69 (100). Anal. Calcd for C19H26Br2O2: C, 51.14; H,
5.87. Found: C, 51.06; H, 5.99.
(1S*,2S*)-2-Allyl-1-(2-bromo-4-isopropyl-3,5,6-trimeth-
oxybenzyl)-3,3-dimethylcyclohexanol (7c). Method A. A
mixture of 24c (1 g, 1.82 mmol), activated zinc23 (4.47 g, 68.4
mmol), NH4Cl solution (40 mL, 50%), and ether (40 mL) was
vigorously stirred at room temperature for 6 h. The reaction
mixture was diluted with ether (100 mL) and filtered. After
usual workup, the crude residue was flash chromatographed
over silica gel (230-400 mesh); 0.5-1% EtOAc in hexane
eluted 7c (554 mg, 65%) as a colorless oil (which solidified on
cooling) while 2-4% EtOAc in hexane eluted the starting
material 24c (275 mg). 7c: mp 80-81 °C (crystallized from
MeOH); IR (KBr) ν 3484, 2935, 1452 cm-1; 1H NMR (300 MHz,
CDCl3) δ 0.83-1.00 (m, 1H), 0.94 (s, 3H), 1.00 (s, 3H), 1.12-
1.68 (m, 7H), 1.31 (d, J ) 7 Hz, 3H), 1.33 (d, J ) 7 Hz, 3H),
2.28-2.32 (m, 1H), 2.44-2.54 (m, 1H), 2.85 (d, J ) 14 Hz, 1H),
3.32 (d, J ) 14 Hz, 1H), 3.38-3.50 (m, 1H), 3.74 (s, 3H), 3.81
(s, 3H), 3.86 (s, 3H), 4.96 (d, J ) 10 Hz, 1H), 5.10 (d, J ) 17
Hz, 1H), 5.96-6.05 (m, 1H); 13C NMR (75 MHz, CDCl3) δ 18.1,
21.6, 21.9, 22.0, 26.8, 30.6, 32.2, 35.4, 37.5, 42.1, 43.0, 54.4,
59.8, 60.5, 61.4, 76.7, 113.6, 116.5, 130.8, 134.9, 142.5, 148.3,
151.7, 151.9; EI-MS m/z 470 (M+ for Br81, 2), 468 (M+ for Br79,
2), 304 (100). Anal. Calcd for C24H37BrO4: C, 61.40; H, 7.94.
Found: C, 61.29; H, 8.06.
Method B. To a solution of 24c (20 mg, 0.04 mmol) in
MeOH (0.4 mL) were added freshly activated zinc (20 mg, 0.31
mmol) and glacial acetic acid (0.3 mL), and the mixture was
stirred at room temperature.25 After 6 h, an additional lot of
freshly activated zinc (30 mg, 0.47 mmol) and MeOH (0.4 mL)
was added, and the stirring was continued for another 24 h.
The reaction mixture was filtered, diluted with H2O, and
extracted with EtOAc (2 × 10 mL). The combined organic
extracts were washed with saturated NaHCO3 solution and
brine, dried, and concentrated. The crude product was purified
by column chromatography over silica gel (100-200 mesh)
using 2-4% EtOAc in hexane to furnish 7c (14.5 mg, 84%).
(2S*,3aS*,7aS*)-7a-(2-Bromo-4-isopropyl-3,5,6-trimeth-
oxybenzyl)-2-bromomethyl-4,4-dimethyloctahydroben-
zofuran (24c). To a well-stirred solution of 8c (2 g, 5.13 mmol)
in dry CH3CN (170 mL) was added NBS22 (1.1 g, 6.18 mmol)
portionwise at -20 °C. The reaction mixture was stirred for 3
h at the same temperature. Then an additional lot of N-
bromosuccinimide (1.1 g, 6.18 mmol) was added and stirring
continued for another 48 h at room temperature. After usual
workup, the product was chromatographed over silica gel
(100-200 mesh) using 1-2% EtOAc in hexane to yield 24c
(2.39 g, 85%) as a white solid: mp 116-118 °C; IR (KBr) ν
(4aS*,11aS*)-7-Methoxy-1,1-dimethyl-10-methylene-
1,2,3,4,5,10,11,11a-octahydrodibenzo[a,d]cyclohepten-4a-
ol (6a). A mixture of 7a (500 mg, 1.36 mmol), K2CO3 (1.13 g,
8.2 mmol), and PPh3 (140 mg, 0.53 mmol) in dry CH3CN (50
mL) was degassed by sonication for 30 min. Pd(OAc)2 (60 mg,
0.267 mmol) was added to the reaction mixture. The mixture
was stirred for 1 h at room temperature and then heated to
reflux26 for 24 h under nitrogen atmosphere. The mixture was
cooled and filtered through Celite, and the residue washed
with dry ethyl acetate. The combined filtrate was evaporated
under reduced pressure to leave a residue. The crude product
was chromatographed over silica gel (100-200 mesh) using
2% EtOAc in hexane to afford 6a (325 mg, 83%) as a colorless
1
2955, 1581, 1450 cm-1; H NMR (300 MHz, CDCl3) δ 0.83-
0.92 (m, 1H), 0.97 (s, 3H), 1.18 (s, 3H), 1.26-1.46 (m, 1H), 1.31
(d, J ) 7 Hz, 6H), 1.51-1.74 (m, 3H), 1.75-1.83 (m, 1H), 1.93-
2.19 (m, 3H), 3.01 (d, J ) 13 Hz, 1H), 3.21 (t, J ) 9 Hz, 1H),
3.35-3.49 (m, 3H), 3.73 (s, 3H), 3.76 (s, 3H), 3.84 (s, 3H), 4.08-
4.15 (m, 1H); 13C NMR (75 MHz, CDCl3) δ 19.6, 20.9, 22.0,
26.8, 28.6, 31.2, 31.8, 32.5, 32.9, 33.6, 36.6, 39.6, 53.2, 59.4,
60.0, 61.3, 75.2, 85.5, 116.8, 131.1, 134.5, 149.3, 151.0, 151.7;
EI-MS m/z 550 (M+ for 2 × Br81, 1), 548 (M+ for Br79 and Br81,
3), 546 (M+ for 2 × Br79, 1), 533 (3), 505 (4), 245 (100). Anal.
Calcd for C24H36Br2O4: C, 52.57; H, 6.62. Found: C, 52.66; H,
6.57.
oil: IR (neat) ν 3473, 2932, 1606 cm-1 1H NMR (300 MHz,
;
CD3OD) δ 0.94 (s, 3H,), 0.96 (s, 3H,), 1.23-1.53 (m, 6H), 1.67-
1.73 (m, 1H), 1.90-1.94 (m, 1H), 2.36-2.45 (m, 1H), 2.53 (d,
J ) 13 Hz, 1H), 2.64 (d, J ) 14 Hz, 1H), 2.76 (d, J ) 14 Hz,
1H), 3.77 (s, 3H), 4.96 (d, J ) 2 Hz, 1H), 5.07 (s, 1H), 6.65 (d,
J 3 Hz, 1H), 6.73 (dd, J ) 3, 8 Hz, 1H), 7.10 (d, J 8 Hz, 1H);
13C NMR (75 MHz, CD3OD) δ 19.6, 22.0, 32.4, 32.8, 35.1, 42.1,
43.3, 52.7, 55.6, 56.9, 72.8, 112.3, 112.6, 117.6, 129.3, 137.9,
(1S*,2S*)-2-Allyl-1-(2-bromo-5-methoxybenzyl)-3,3-di-
methylcyclohexanol (7a). A mixture of 24a (1 g, 2.24 mmol),
zinc23 (2.5 g, 38.2 mmol), and NH4Cl solution (10 mL, 50%) in
Et2O (15 mL) was vigorously stirred at room temperature for
6 h. Then another lot of zinc (2.5 g, 38.2 mmol) was added,
and the reaction mixture was stirred for 6 h. The mixture was
7698 J. Org. Chem., Vol. 70, No. 19, 2005

Syntheses of (()-Komaroviquinone and (()-Faveline Methyl Ether
138.4, 153.9, 160.3; EI-MS m/z 286 (M+, 53), 202 (64), 167
(100). Anal. Calcd for C19H26O2: C, 79.68; H, 9.15. Found: C,
79.75; H, 9.21.
with brine and then dried. The solvent was evaporated under
reduced pressure to give a white solid. The crude solid was
chromatographed over silica gel (60-120 mesh) using 10-15%
ethyl acetate in hexane to afford 5a as a white solid (180 mg,
86%): mp 125-127 °C (crystallized from 5% EtOAc in hexane);
IR (KBr) ν 3470, 2937, 1657 cm-1; 1H NMR (300 MHz, CDCl3)
δ 0.82 (s, 3H), 0.99 (s, 3H), 1.09-1.18 (m, 1H), 1.39-1.73 (m,
5H), 1.82-1.95 (m, 2H), 2.62 (d, J ) 14 Hz, 1H), 2.67 (d, J )
9 Hz, 1H), 2.85 (2 × d, J ) 11, 18 Hz, 1H), 3.11 (d, J ) 14 Hz,
1H), 3.85 (s, 3H), 6.62 (d, J ) 2 Hz, 1H), 6.84 (brd, J ) 7 Hz,
1H), 7.70 (d, J ) 9 Hz,1H); 13C NMR (75 MHz, CDCl3) δ 18.5,
21.5, 32.1, 33.7, 38.5, 39.1, 40.7, 48.3, 49.9, 55.4, 73.4, 111.8,
115.9, 131.0, 131.3, 139.5, 162.5, 205.3; EI-MS m/z 288 (M+,
28), 149 (100). Anal. Calcd for C18H24O3: C, 74.97; H, 8.39.
Found: C, 75.09; H, 8.31.
(4aS*,11aS*)-4a-Hydroxy-8-isopropyl-6,7,9-trimethoxy-
1,1-dimethyl-1,2,3,4,4a,5,11,11a-octahydrodibenzo[a,d]-
cyclohepten-10-one (5c). To a solution of 6c (166 mg, 0.43
mmol) in a mixture of tBuOH (7 mL), acetone (7 mL), and H2O
(7 mL) was added N-methylmorpholine oxide (1 mL, 50%
aqueous solution). OsO4 27 (22 mg, 0.866 mmol, 20 mol %) was
then added at 0 °C. The mixture was stirred at 0 °C for 3 h
and then at room temperature for 96 h. A solution of Na2SO3
(40 mL, 45% aqueous solution) was added to the reaction
mixture, which was stirred for 1 h. After usual workup as
described for 5a, the crude product obtained was chromato-
graphed over silica gel (60-120 mesh). Elution with 2% EtOAc
in hexane furnished the starting olefin 6c (76 mg), while 30%
ethyl acetate in petroleum ether afforded the trihydroxy
compound (96 mg) (as revealed from 1H NMR and IR spectra),
which was directly used in the next step.
To the solution of above trihydroxy compound (95 mg) in
MeOH (7 mL) was added a solution of NaIO4 (prepared by
dissolving 175 mg in 2 mL of water) dropwise at 0 °C. The
reaction mixture was stirred at 0 °C for 2 h and then at room
temperature for 24 h and filtered. Usual workup furnished the
crude product which was chromatographed over silica gel (60-
120 mesh) using 10-15% EtOAc in hexane to afford 5c (70
mg, 42% in two steps; 77% based on recovered starting
material 6c) as a white solid: mp 138-140 °C (crystallized
from 2% ethyl acetate in petroleum ether); IR (KBr) ν 3484,
2944, 1673, 1574 cm-1; 1H NMR (300 MHz, pyridine-d5) δ 0.85
(s, 3H), 1.07 (brd t, J ) 12 Hz, 1H), 1.21 (s, 3H), 1.37 (d, J )
7 Hz, 3H), 1.39 (d, J ) 7 Hz, 3H), 1.35-1.48 (m, overlap, 2H),
1.61-1.71 (m, 1H), 1.80 (d, J ) 11 Hz, 1H), 2.02 (d, J ) 13
Hz, 1H), 2.14-2.23 (m, 1H), 2.86 (d, J ) 17 Hz, 1H), 3.06-
3.10 (m, 1H), 3.21 (m, 1H), 3.39 (dd, J 12, 16 Hz, 1H), 3.58
(sept, J 7 Hz, 1H), 3.77 (s, 3H), 3.88 (s, 6H), 5.80 (s, D2O
exchangeable, 1H); 13C NMR (75 MHz, pyridine-d5) [a mixture
of 5c (major) and the hemiketal 25 (minor); only the major
peaks shown] δ 19.2, 22.02, 22.06, 22.09, 32.1, 34.1, 40.4, 40.6,
41.6, 60.4, 63.4, 72.5, 128.1, 134.3, 147.6, 151.8, 154.4, 207.4
[additional peaks at δ 78.6 and 102.8 are assignable to 25];
EI-MS m/z 390 (M+, 73), 267 (29), 251 (100). Anal. Calcd for
C23H34O5: C, 70.74; H, 8.78. Found: C, 70.87; H, 8.83.
(4aS*,11aS*)-8-Isopropyl-6,7,9-trimethoxy-1,1-dimeth-
yl-10-methylene-1,2,3,4,5,10,11,11a-octahydrodibenzo-
[a,d]cyclohepten-4a-ol (6c). Method A. A mixture of 7c (40
mg, 0.09 mmol), K2CO3 (70.6 mg, 0.51 mmol), and PPh3 (8.9
mg, 0.03 mmol) in dry CH3CN (5 mL) was degassed by
sonication for 30 min. Pd(OAc)2 (3.8 mg, 0.02 mmol) was added
to the reaction mixture, and the mixture stirred for 1 h at room
temperature. It was then heated26 at 90 °C for 120 h. Usual
workup gave a crude product which was chromatographed over
silica gel (60-120 mesh). Eluting with 1-2% EtOAc in hexane
afforded starting material 7c (20 mg), while 2-4% EtOAc in
hexane furnished the cyclized product 6c (10 mg, 30%; 61%
based on recovered starting material) as a thick oil, which
solidified on cooling: mp 124-126 °C (crystallized from dry
1
methanol); IR (KBr) ν 3478, 2936, 1581 cm-1; H NMR (300
MHz, CDCl3) δ 0.92 (s, 3H), 1.01 (s, 3H), 1.22-1.35 (m,
overlapped, 2H), 1.32 (d, J ) 7 Hz, 3H), 1.34 (d, J ) 7 Hz,
3H,), 1.43-1.56 (m, 3H), 1.64 (s, 1H), 1.78-2.04 (m, 3H), 2.46
(d, J ) 14 Hz, 1H), 2.69 (brd, J ) 13 Hz, 1H), 3.14 (d, J ) 14
Hz, 1H), 3.45 (sep, J ) 7 Hz, 1H), 3.61 (s, 3H), 3.76 (s, 3H),
3.84 (s, 3H), 5.08 (s, 1H), 5.35 (s, 1H); 13C NMR (75 MHz,
CDCl3) δ 18.7, 21.4, 22.07, 22.10, 25.9, 32.1, 33.1, 34.3, 41.6,
42.0, 42.2, 59.7, 60.4, 60.5, 61.0, 70.7, 115.5, 126.8, 133.9, 145.8,
148.5, 150.5, 151.0 [one carbon signal could not be identified
due to overlap]; EI-MS m/z 388 (M+, 100), 247 (11), 224 (16).
Anal. Calcd for C24H36O4: C, 74.19; H, 9.34. Found: C, 74.06;
H, 9.27.
Method B. A mixture of 7c (280 mg, 0.60 mmol), triethyl-
amine (362.5 mg, 0.5 mL, 3.58 mmol), and PPh3 (62.6 mg, 0.24
mmol) in dry acetonitrile (25 mL) was sonicated for 30 min.
Palladium acetate (26.8 mg, 0.12 mmol) was added to the
reaction mixture and the mixture stirred for 1 h at room
temperature. It was then heated at 90 °C for 120 h. After usual
workup, the crude product was chromatographed over silica
gel (60-120 mesh) to afford the starting material 7c (110 mg)
and 6c (134 mg, 58%; 95% based on recovered starting
material).
Method C. A mixture of 7c (445 mg, 0.95 mmol), diisopro-
pylethylamine (1.23 g, 1.65 mL, 9.49 mmol), and PPh3 (99.5
mg, 0.38 mmol) in dry CH3CN (40 mL) was sonicated for 30
min. Pd(OAc)2 (42.6 mg, 0.19 mmol) was added, and the
mixture was stirred for 1 h at room temperature. It was then
heated at 90 °C for 96 h. After usual workup, the crude product
was chromatographed over silica gel (60-120 mesh) to afford
7c (120 mg) and 6c (250 mg, 68%; 93% based on recovered
starting material).
(4aS*,11aS*)-4a-Hydroxy-7-methoxy-1,1-dimethyl-1,2,-
3,4,4a,5,11,11a-octahydrodibenzo[a,d]cyclohepten-10-
one (5a). To a solution of 6a (200 mg, 0.7 mmol) in a mixture
of tBuOH (9 mL), acetone (9 mL), and H2O (9 mL) was added
N-methylmorpholine oxide (495 µL, 50% aqueous solution).
27
Three small crystals of OsO4 were then added at 0 °C. The
mixture was stirred for 5 h at 0 °C and for 2 h at room
temperature. A solution of Na2SO3 (14 mL, 45% aqueous
solution) was added, and the reaction mixture was stirred for
45 min. The solid was filtered and the filtrate evaporated to
leave a residue, which was taken up in EtOAc. The solid mass
was dissolved in H2O and extracted with EtOAc (50 mL). The
combined organic extracts were washed with brine and dried,
and solvent was removed in a rotary evaporator under reduced
pressure to leave the crude trihydroxy compound as a white
solid, which was directly used in the next step without
purification.
To the solution of the white solid in MeOH (10 mL) was
added a solution of NaIO4 (prepared by dissolving 222 mg in
3 mL of water) dropwise at 0 °C. The reaction mixture was
stirred at 0 °C for 2 h, then at room temperature for 3 h, and
filtered. The residue was dissolved in H2O and extracted with
EtOAc (100 mL). The combined organic extracts were washed
(()-Komaroviquinone (3). To a stirred solution containing
5c and 25 (28 mg, 0.07 mmol) in dioxane (1.4 mL, redistilled
over sodium) and silver(II) oxide29 (36 mg, 0.29 mmol) was
added HNO3 (717 µL, 6 N) at 5 °C. After the mixture was
stirred for 4 h at 5 °C, another portion of silver(II) oxide (36
mg) and HNO3 (717 µL, 6 N) was added and the stirring
continued for 4 h at the same temperature. The mixture was
diluted with water and extracted with EtOAc (50 mL). The
organic extract was washed with brine, dried, and evaporated
to give an orange oil. The product was purified over silica gel
(60-120 mesh) using 5% EtOAc in hexane to give 3 (18 mg,
69%) as a yellow-orange solid: mp 123-124 °C [natural (+)-3
was reported4 as an orange oil]; IR (KBr) ν 3404, 2944, 1651,
1
1606, 1455 cm-1; H NMR (300 MHz, CDCl3) δ 0.86 (s, 3H),
0.95 (s, 3H), 1.21 (d, J ) 7 Hz, 3H), 1.21 (d, J ) 7 Hz, 3H),
1.11-1.25 (m, overlapped, 1H), 1.56-1.66 (m, 2H), 1.68-1.75
(m, 2H), 1.78-1.90 (m, 1H), 1.99-2.08 (m, 2H), 2.25 (d, J )
J. Org. Chem, Vol. 70, No. 19, 2005 7699

Sengupta et al.
19 Hz, 1H), 2.30 (dd, J ) 13, 9 Hz, 1H), 2.55 (d, J ) 19 Hz,
1H), 3.23 (septet, J ) 7 Hz, 1H), 3.98 (s, 3H), 5.98 (brs, 1H);
13C NMR (75 MHz, CDCl3) δ 15.6, 20.38, 20.42, 24.3, 27.0, 29.8,
30.3, 31.3, 32.0, 39.0, 45.7, 51.5, 61.1, 79.3, 100.9, 137.1, 138.9,
142.2, 156.1, 183.6, 189.1 [1H NMR and 13C NMR of (()-3 are
identical with those of the natural (+)-34]; EI-MS m/z 360 (M+,
16), 316 (100), 301 (40). Anal. Calcd for C21H28O5: C, 69.98;
H, 7.83. Found: C, 69.83; H, 7.96.
of 26 and 27 as an oil. The crude oil was purified by
preparative TLC (multiple run in 2% EtOAc-hexane) to give
26 (5.6 mg, 30%) and 2731 (6 mg, 32%) as an oil.
Reaction of 5b with KHSO4: Formation of (()-Faveline
Methyl Ether (1a) and 26. The keto alcohol 5b (40 mg, 0.132
8
mmol) was fused with KHSO4 (40 mg, 0.294 mmol) at 190
°C under N2 atmosphere for 45 min, and the resulting mixture
was sublimed at 140-145 °C (0.1 mm of Hg) to give a solid.
The product was purified by preparative TLC (multiple run
in 2% EtOAc-hexane) to give 1a (10.8 mg, 28%) and 26 (15.8
mg, 42%) as white solids.
Reaction of 5b with BF3‚OEt2: Formation of (11aS*)-
7-Methoxy-1,1,8-trimethyl-1,2,3,5,11,11a-hexahydrodiben-
zo[a,d]cyclohepten-10-one (26). To a stirred solution of 5b
(20 mg, 0.066 mmol) in dry CH2Cl2 (2 mL) was added BF3‚
OEt2 (10 µL) at 0 °C.5c The reaction mixture was stirred at 0
°C for 3 h and then at room temperature for 6 h. The reaction
mixture was quenched with saturated NaHCO3 solution (5 mL)
and extracted with CH2Cl2 (20 mL). The organic part was
washed with brine and dried and the solvent evaporated to give
a yellow oil. The crude oil was purified by preparative TLC
(multiple run in 2% ethyl acetate-hexane) to give 26 (9.3 mg,
49%) as the only isolable product as a white solid: mp 135-
136 °C (crystallized from EtOAc in hexane); IR (KBr) ν 2916,
1a: mp 137-138 °C [lit.8b mp 138-140 °C]; IR (KBr) ν 2929,
1
1655, 1600 cm-1; H NMR (300 MHz, CDCl3) δ 0.75 (s, 3H),
1.12 (s, 3H), 1.42-1.62 (m, 2H), 1.64-1.76 (m, 2H), 2.18 (s,
3H), 2.30-2.38 (m, 3H), 3.01-3.03 (m, 2H), 3.87 (s, 3H), 6.29
(s, 1H), 6.59 (s, 1H) 7.62 (s, 1H); 13C NMR (75 MHz, CDCl3) δ
15.5, 20.7, 25.1, 28.9, 38.4, 40.2, 42.5, 43.0, 51.3, 55.4, 112.9,
124.7, 125.5, 129.7, 131.2, 136.3, 147.7, 160.9, 201.3; EI-MS
m/z 284 (M+, 100), 215 (81), 202 (94). Anal. Calcd for
C19H24O2: C, 80.24; H, 8.51. Found: C, 80.11; H, 8.65.
1
1654, 1601 cm-1; H NMR (300 MHz, CDCl3) δ 0.80 (s, 3H),
Acknowledgment. We are grateful to Prof. U. R.
Ghatak of this institute for his suggestions and criticism
and Dr. N. Uchiyama of Kyoto Pharmaceutical Univer-
sity for providing copies of spectra of natural (+)-
komaroviquinone for comparison. We also thank UGC
(New Delhi) and Dabur Research Foundation (India) for
the award of a Research Fellowship to S.S. and the
EPSRC and the University of Reading for funds of the
Image Plate system.
0.99 (s, 3H), 1.37-1.39 (m, 2H), 2.03-2.19 (m, 3H), 2.19 (s,
3H), 2.59 (dd, J ) 11, 17 Hz, 1H), 2.88 (d, J ) 17 Hz, 1H),
3.31 (d, J ) 15 Hz, 1H), 3.83 (d, J ) 15 Hz, 1H, overlapped by
3H singlet at 3.89), 3.89 (s, 3H), 5.67 (s, 1H), 6.60 (s, 1H), 7.73
(s, 1H); 13C NMR (75 MHz, CDCl3) δ 15.6, 19.2, 23.1, 29.4, 32.4,
37.2, 42.8, 43.1, 43.7, 55.5, 110.3, 121.9, 125.2, 128.8, 131.8,
135.6, 140.4, 161.6, 203.0; EI-MS m/z 284 (M+, 61), 256 (97),
200 (100). Anal. Calcd for C19H24O2: C, 80.24; H, 8.51. Found:
C, 80.39; H, 8.46.
Reaction of 5b with SOCl2 in Pyridine: Formation of
26 and 7-Methoxy-1,1,8-trimethyl-1,2,3,4,5,11-hexahy-
drodibenzo[a,d]cyclohepten-10-one (27). To a stirred solu-
tion of 5b (20 mg, 0.07 mmol) in pyridine (714 µL) was added
Supporting Information Available: Schemes 2 and 3
(containing compounds 11-19); experimental procedures for
1
5b, 6b, 7b, 8b,c, 10b,c, 12-19, 20a, 21, and 24b; H NMR
and 13C NMR spectral data of compounds 1a, 3, 5a-c, mixture
of 5c and 25, 6a-c, 7a-c, 8a-c, 24a-c, and 26; IR spectral
data of 3; and ORTEP diagrams of 5a and 24b. This material
is available free of charge via the Internet at http://pubs.acs.org.
30
SOCl2 (72 µL, 0.99 mmol) at -10 °C. The reaction mixture
was stirred for 5 h at the same temperature. The reaction
mixture was diluted with Et2O (25 mL), and the organic part
was washed successively with HCl (10 mL, 5%), water, and
brine, and dried. The solvent was evaporated to give a mixture
JO051082I
7700 J. Org. Chem., Vol. 70, No. 19, 2005