A novel and efficient synthesis of bicyclo[2.2.2]octenones and sigmatropic shifts in ground and excited states: Stereoselective route to cis-decalins and diquinane frameworks

Article abstract of DOI:10.1021/jo048320e

(Chemical Equation Presented) A new and efficient synthesis of a variety of highly embellished bicyclooctenones having an endo-vinyl moiety and their sigmatropic shifts in ground and excited states leading to a stereoselective route to substituted cis-decalins and diquinane frameworks have been described. Functionalized bicyclo[2.2.2]octenones having an endo-vinyl group and a β,γ-enone chromophore were prepared by in situ generation of 6-chloromethyl-6-hydroxycyclohexadienones and cycloaddition with butadiene (also generated in situ) followed by manipulation of the adducts. The presence of contiguous carbonyl, hydroxyl, and chloromethyl groups in adducts led to the introduction of various alkyl groups α to the ketone in a stereoselective fashion. The 3,3-sigmatropic shift in the bridged bicyclic compounds gave the corresponding cis-decalins, whereas the triplet sensitized irradiation led to the formation of diquinanes as a result of a 1,2-acyl shift.

Full text of DOI:10.1021/jo048320e

A Novel and Efficient Synthesis of Bicyclo[2.2.2]octenones and
Sigmatropic Shifts in Ground and Excited States: Stereoselective
Route to cis-Decalins and Diquinane Frameworks
Vishwakarma Singh,*,† Sridhar R. Iyer,† and Shaikh M. Mobin‡
Department of Chemistry, National Single Crystal X-ray Diffraction Facility,
Indian Institute of Technology, Bombay, Mumbai 400 076, India
vks@chem.iitb.ac.in
Received September 22, 2004 (Revised Manuscript Received November 2, 2004)
A new and efficient synthesis of a variety of highly embellished bicyclooctenones having an endo-
vinyl moiety and their sigmatropic shifts in ground and excited states leading to a stereoselective
route to substituted cis-decalins and diquinane frameworks have been described. Functionalized
bicyclo[2.2.2]octenones having an endo-vinyl group and a â,γ-enone chromophore were prepared
by in situ generation of 6-chloromethyl-6-hydroxycyclohexadienones and cycloaddition with
butadiene (also generated in situ) followed by manipulation of the adducts. The presence of
contiguous carbonyl, hydroxyl, and chloromethyl groups in adducts led to the introduction of various
alkyl groups R to the ketone in a stereoselective fashion. The 3,3-sigmatropic shift in the bridged
bicyclic compounds gave the corresponding cis-decalins, whereas the triplet sensitized irradiation
led to the formation of diquinanes as a result of a 1,2-acyl shift.
Introduction
Recently, there has been an upsurge of interest in the
synthesis of cis-decalins.1,2 This is presumably due to the
occurrence and isolation of a number of terpenoids such
as agelasines3 (1, 2), kalihinene X4a (3) (Figure 1), and
thelepoganes4b,c that contain a highly substituted cis-
decalin core in their molecular architecture. Many of
these natural products exhibit wide-ranging and inter-
FIGURE 1. Agelasines, kalihinene terpenoids, and carbacy-
clin.
† Department of Chemistry.
‡ National Single Crystal X-ray Diffraction Facility.
esting biological activities. For example, agelasine A (1)
(Figure 1), a cis-clerodane diterpene, exhibits antimicro-
bial activity and strongly inhibits the activity of the
enzyme NaK-ATPase.3 The presence of a cis-decalin
framework in their structure with varying degrees of
substitution patterns and four or more contiguous stereo-
centers coupled with diverse biological activities has led
(1) (a) Reddy, D. A.; Kozmin, S. A. J. Org. Chem. 2004, 69, 4860-
4862. (b) Jung, M. E.; Piizzi, G. J. Org. Chem. 2003, 68, 2572-2582.
(c) Diaz, S.; Cuesta, J.; Gonzalez, A.; Bonjoch, J. J. Org. Chem. 2003,
68, 7400-7407. (d) Kim, K.; Maharoof, U. S. M.; Raushel, J.; Su-
likowski, G. A. Org. Lett. 2003, 5, 2777-2780. (e) Kundig, E. P.;
Cannas, R.; Laxmisha, M.; Ronggang, L.; Tchertchian, S. J. Am. Chem.
Soc. 2003, 125, 5642-5643.
(2) (a) Heckrodt, T. J.; Mulzer, J. J. Am. Chem. Soc. 2003, 125,
4680-4681. (b) Fleming, F. F.; Shook, B. C.; Jiang, T.; Steward, O. W.
Tetrahedron 2003, 59, 737-745. (c) Paquette, L. A.; Guevel, R.;
Sakamoto, S.; Kim, I. H.; Crawford, J. J. Org. Chem. 2003, 68, 6096-
6107. (d) Mehta, G.; Kumaran, R. S. Tetrahedron Lett. 2003, 44, 7055-
7059. (e) White, R. D.; Wood, J. L. Org. Lett. 2001, 3, 1825-1827.
(3) (a) Nakamura, H.; Wu, H.; Ohizumi, Y. Tetrahedron Lett. 1984,
25, 2989-2992. (b) Wu, H.; Nakamura, H.; Kobayashi, J.; Ohizumi,
Y.; Hirata, Y. Bull. Chem. Soc. Jpn. 1986, 59, 2495-2504.
(4) (a) Okino, T.; Yoshimura, E.; Hirota, H.; Fusetani, N. Tetrahe-
dron Lett. 1995, 36, 8637-8640. (b) Shoji, N.; Umeyama, A.; Teranaka,
M.; Arihara, S. J. Nat. Prod. 1996, 59, 448-450. (c) Iwagawa, T.;
Kaneko, M.; Okamura, H.; Nakatani, M.; van Soest, R. W. M. J. Nat.
Prod. 1998, 61, 1310-1312.
10.1021/jo048320e CCC: $30.25 © 2005 American Chemical Society
Published on Web 12/30/2004
J. Org. Chem. 2005, 70, 973-981
973

Singh et al.
SCHEME 1
FIGURE 2. Potential intermediates for cycloaddition.
substituted bicyclo[2.2.2]octanes are prepared by addition
of a vinyl group to bicyclo[2.2.2]octenones that gives a
mixture of stereoisomers.12 Recently, some other methods
involving double Michael addition,13 Michael addition
followed by reductive amination,14 homoallyl-homoallyl
radical rearrangement,15 and cycloaddition of o-quinone
ketals and related species have been developed for the
synthesis of bicyclo[2.2.2]octenones.16 However, most of
these methods have several limitations with regard to
introduction of functional groups and substituents on the
bicyclo[2.2.2]octane framework and often give a mixture
of regioisomers.
Conceptually, the desired bicyclooctenones of type 5
should be available via inverse electron demand cyclo-
addition of cyclohexa-2,4-dienones of type 8 with acyclic
1,3-dienes (Figure 2). Although there are some methods
for preparation of 6,6-disubstituted cyclohexadienones
viz., the alkylation of ortho-substituted phenols and
rearrangement of epoxyfulvene,17 these methods are not
easily adaptable for our purpose. Therefore, we developed
an indirect route to bicyclooctenones of type 5 by in situ
generation and cycloaddition of 6-chloromethyl-6-hy-
droxycyclohexadienones of type 9 with the butadiene
equivalent sulfolene 10 followed by manipulation of the
adducts as presented below.
Thus, sulfolene 10 was slowly added to a preheated
solution of the readily available dimer 11a18 in o-
dichlorobenzene at 140 °C. Chromatography of the reac-
tion mixture gave the adduct 12a as the major product
along with a minor amount of the enone 13a (Scheme
2), whose structures were deduced from their spectral
data and chemical transformation. The endo stereo-
chemistry of the vinyl group was proved through Cope
rearrangement (vide infra), and the orientation of chloro-
methyl and hydroxyl groups was suggested on the basis
of general tendency of cyclohexadienones during cyclo-
addition.19,20
to significant interest in the development of new and
efficient methods for the synthesis of functionalized cis-
decalins.1,2
The diquinane or bicyclo[3.3.0]octane moiety is present
in many natural products5 and also constitutes an
important building block for the synthesis of biologically
active compounds such as carbacyclin 4 (Figure 1).6 While
there are a number of methods for the synthesis of
diquinanes and polyquinanes,7 the search for new and
efficient methods is continuing.8
In view of the interest in the synthesis of cis-decalins
and diquinanes and our interest in the chemistry of
cyclohexadienones that have proved to be versatile reac-
tive intermediates in synthesis,9,10 we considered devel-
oping a general route to functionalized cis-decalins such
as 6 and diquinane frameworks of the type 7 from a
common precursor. It was contemplated that a 3,3-
sigmatropic shift in the appropriately designed bicyclo-
[2.2.2]octenones of type 5 would lead to the cis-decalins
such as 6, while a photochemical 1,2-acyl shift in 5 would
give the diquinane framework of type 7 in a stereoselec-
tive fashion (Scheme 1).We report herein a new meth-
odology for the synthesis of bridged bicyclic systems of
type 5 and their sigmatropic shifts in ground and triplet
excited states leading to a general, flexible, and stereo-
selective route to cis-decalins and diquinanes.11
Results and Discussion
Synthesis of Bicyclo[2.2.2]octenones Having an
endo-Vinyl Moiety. To develop a route to the cis-
decalins of type 6 and the diquinanes 7, it was necessary
to devise an efficient method for the synthesis of bicyclo-
[2.2.2]octenones of type 5. While such types of bicyclic
systems are not known in the literature, simpler vinyl-
(5) (a) Northcote, P. T.; Andersen, R. J. Tetrahedron Lett. 1988, 29,
4357-4360. (b) Cheng, X.-C.; Varoglu, M.; Abrell, L.; Crews, P.;
Lobkovsky, E.; Clardy, J. J. Org. Chem. 1994, 59, 6344-6348.
(6) (a) Bund, J.; Gais, H.-J.; Schmitz, E.; Erdelmaier, I.; Raabe, G.
Eur. J. Org. Chem. 1998, 7, 1319-1335. (b) Okamoto, S.; Subburaj,
K.; Sato, F. J. Am. Chem. Soc. 2000, 122, 11244-11245.
(7) (a) Mehta, G.; Srikrishna, A. Chem. Rev. 1997, 97, 671-720. (b)
Paquette, L. A.; Doherty, A. M. In Polyquinane Chemistry; Hafner, L.,
Rees, C. W., Trost, B. M., Lehn, J. L., Scheyler, P. V. R., Zahardanik,
R., Eds; Springer-Verlag: New York, 1987; Vol. 26, pp 1-225. (c) Singh,
V.; Thomas, B. Tetrahedron 1998, 54, 3647-3692.
(8) (a) Koech, P. K.; Krische, M. J. Org. Lett. 2004, 6, 691-694. (b)
Williams, D. R.; Reeves, J. T. J. Am. Chem. Soc. 2004, 126, 3434-
3435. (c) Geng, F.; Liu, J.; Paquette, L. A. Org. Lett. 2002, 4, 71-73.
(d) Krafft, M. E.; Bonaga, L. V. R.; Wright, J. A.; Hirosawa, C. J. Org.
Chem. 2002, 67, 1233-1246.
(9) (a) Singh, V. Acc. Chem. Res. 1999, 32, 324-333. (b) Singh, V.;
Pal, S.; Mobin, S. M. J. Chem. Soc., Chem. Commun. 2002, 2050-
2051. (c) Singh, V.; Praveena, G. D.; Mobin, S. M. Tetrahedron, 2004,
60, 4177-4182. (d) Singh, V.; Tosh, D. K.; Mobin, S. M. Tetrahedron
Lett. 2004, 45, 1729-1732.
(10) (a) Magdziak, D.; Meek, S. J.; Pettus, T. R. R. Chem. Rev. 2004,
104, 1383-1429. (b) Liao, C.-C.; Peddinti, R. K. Acc. Chem. Res. 2002,
35, 856-866. (c) Bhamare, N. K.; Granger, T.; Macas, T. S.; Yates, P.
J. Chem. Soc., Chem. Commun. 1990, 739-740.
(11) Singh, V.; Iyer, S. J. Chem. Soc., Chem. Commun. 2001, 2578-
2579. Preliminary communication.
(12) (a) Evans, D. A.; Scott, W. L.; Truesdale, L. K. Tetrahedron Lett.
1972, 13, 121-124. (b) Evans, D. A.; Scott, W. L.; Truesdale, L. K.
Tetrahedron Lett. 1972, 13, 137-140. (c) Banwell, M. G.; Dupuche, J.
R. J. Chem. Soc., Chem. Commun. 1996, 869-870.
(13) (a) Hagiwara, H.; Yamada, Y.; Sakai, H.; Suzuki, T.; Ando, M.
Tetrahedron 1998, 54, 10999-11010. (b) White, L. B.; Reusch, W.
Tetrahedron 1978, 34, 2439-2444.
(14) Ley, S. V.; Mynett, D. M.; Koot, W. J. Synlett 1995, 10, 1017-
1020.
(15) Toyota, M.; Yokota, M.; Ihara, M. Tetrahedron Lett. 1999, 40,
1551-1554.
(16) (a) Yen, C.-F.; Peddiniti, R. K.; Liao, C.-C. Org. Lett. 2000, 2,
2909-2912. (b) Hsieh, M.-F.; Rao, P. D.; Liao, C.-C. J. Chem. Soc.,
Chem. Commun. 1999, 1441-1442. (c) Drutu, I.; Njardarson, J. T.;
Wood, J. L. Org. Lett. 2002, 4, 493-496.
(17) (a) Schultz, A. G.; Dittami, J. P.; Myong, S. O.; Sha, C. K. J.
Am. Chem. Soc. 1983, 105, 3273-3279. (b) Alder, K.; Flock, H. F.;
Lessenich, H. Chem. Ber. 1957, 90, 1709-1720.
(18) (a) Singh, V.; Bedekar, A. V. Synth. Commun. 1989, 19, 107-
117. (b) Adler, E.; Holmberg, K. Acta Chem. Scand. 1974, 28b, 465-
472.
(19) (a) Bartby, D. M.; Chadwick, J. C.; Fray, G. I.; Saxton, R. G.
Tetrahedron 1977, 33, 1527-1532. (b) Gesson, J. P.; Hervaud, L.;
Mondon, M. Tetrahedron Lett. 1993, 34, 2941-2944. (c) Singh, V.;
Sharma, U.; Prasanna, V.; Porinchu, M. Tetrahedron 1995, 51, 6015-
6032.
974 J. Org. Chem., Vol. 70, No. 3, 2005

Synthesis of Bicyclo[2.2.2]octenones
SCHEME 2
SCHEME 5a
a Reagents/conditions: i, Zn, NH4Cl, MeOH-H2O (6:1), 33 °C;
ii, Jones oxidation; iii, aq ThF, ∆.
SCHEME 6a
SCHEME 3a
a Reagents/conditions: i, o-dichlorobenzene, 115 °C.
SCHEME 4a
a Reagents/conditions: i, NaH, THF, allyl bromide, ∆; ii, NaH,
methyl iodide, THF, ∆; iii, NaH, propargyl bromide, THF, ∆; iv,
HgO, 4% H2SO4, MeOH, 60 °C.
via the ketoepoxide 20 (Scheme 4). Alternatively, the
epoxide 20 was manipulated to bicyclooctenone 24 as
shown in Scheme 5. The reduction of ketoepoxide 20 with
zinc-NH4Cl in an aqueous protic solvent (MeOH-H2O)
at ambient temperature selectively gave the â-keto
alcohol 23 as the major product [syn/anti mixture (1:3),
1H NMR spectrum] that upon oxidation and decarboxy-
lation furnished 24 (Scheme 5).
Further, the treatment of ketone 18 with allyl bromide
in the presence of NaH-THF yielded a mixture of syn/
anti (85:15) isomers (1H NMR) from which the major syn
isomer 25 was isolated by column chromatography on
AgNO3-impregnated silica gel in good yield (Scheme 6).
The syn stereochemistry of the allyl chain was indicated
from the chemical shift of the methyl group at C-3 that
appeared downfield (δ 1.09) compared to the anti isomer
(δ 1.06) in accordance with earlier observation in related
systems. Such types of stereoselective alkylations have
also been observed by us as well as others.23 Similarly,
the ketone 21 was also alkylated with allyl bromide to
give the syn isomer 26 as a major product. The ketone
18 was also alkylated with methyl iodide to furnish the
compound 27 in good yield.
a Reagents/conditions: i, KOH, H2O-CHCl3, CTAB, rt; ii, Zn,
NH4Cl, dioxane, ∆.
Further, the dimers 11b and 11c were also prepared21
and subjected to pyrolysis in the presence of sulfolene,
which furnished the corresponding adducts 12b and 12c,
respectively (Scheme 2). Similarly, pyrolysis of the dimer
1418b and sulfolene gave the adduct 15 in good yield along
with a very minor amount of the enone 16 (Scheme 3).
Although the yields in the aforementioned cycloadditions
are moderate, the generation of molecular complexity is
noteworthy.22
Manipulation of Chloromethyl and Hydroxyl
Groups in 12a and 12b into Alkyl Groups: Synthe-
sis of Bicyclo[2.2.2]octenones of Type 5. The presence
of contiguous functional groups in adducts 12a-c pro-
vided a unique opportunity for further manipulation.
Thus, the adduct 12a was readily converted into epoxy
ketone 17 in a quantitative fashion on treatment with
aqueous KOH in chloroform containing cetyltrimethyl-
ammonium bromide (CTAB) as a phase-transfer catalyst
(Scheme 4). The reduction of the epoxy-ketone 17 with
activated zinc in refluxing dry dioxane containing am-
monium chloride, following a methodology developed in
our group, furnished the ketone 18 [as a syn/anti mixture
In addition, alkylation of 18 with propargyl bromide
gave the propargyl analogue as a mixture of syn/anti
isomers 28 and 29 in a selective fashion, from which some
of the syn isomer 28 was separated after repeated
chromatography on silica gel (Scheme 6). Further, hydra-
tion of the syn/anti mixture of 28 and 29 with HgO in
aqueous H2SO4 gave a mixture of diones from which the
dione 30 was isolated as the major product (66%) by
chromatography on AgNO3-impregnated silica gel (Scheme
1
(1:2), H NMR (300 MHz) spectrum] as a major product
along with the alcohol 19 as a minor product. Similarly,
the adduct 12b was also transformed into the ketone 21
(20) Caira, M. R.; Bedekar, A. V.; Singh, V. J. Chem. Crystallogr.
1995, 25, 583-587.
(21) Sharma, U. Ph.D. Dissertation, I. I. T., Bombay, 1997.
(22) (a) Corey, E. J.; Cheng, X.-M. The Logic of Chemical Synthesis;
John Wiley & Sons: New York, 1989. (b) Chanon, M.; Barone, R.;
Baralotto, C.; Julliard, M.; Hendrickson, J. B. Synthesis 1998, 1559-
1583.
(23) (a) Stork, G.; Baine, N. H. Tetrahedron Lett. 1985, 26, 5927-
5930. (b) Paquette, L. A.; Ra, C. S.; Silvestri, T. W. Tetrahedron 1989,
45, 3099-3106.
J. Org. Chem, Vol. 70, No. 3, 2005 975

Singh et al.
SCHEME 7
SCHEME 9
works. The photochemical reactions of â,γ-enones have
evoked a great deal of interest in the past,26,27 which has
been further enhanced recently28 because of their syn-
thetic potential and versatility. In general, the direct
irradiation of constrained â,γ- enones causes a 1,3-shift
of the acyl group, and sensitized irradiation results in a
1,2-acyl shift or oxa-di-π-methane rearrangement. Oxa-
di-π-methane reaction of bicyclo[2.2.2]octenones is well
documented.26c,27a,28 Although the range of the oxa-di-π-
methane rearrangement appears to be wide, it is quite
sensitive to the nature of both functional groups and
substituents.28b,c The triplet-sensitized photoreaction of
15, 25-27, and 30 was examined.
SCHEME 8
Thus, a solution of 27 in acetone (both solvent and
sensitizer) was irradiated in a Pyrex immersion well for
1.25 h. Removal of solvent followed by chromatography
of the photolysate gave the tricyclic ketone 39 in moder-
ate yield (35%) in addition to the recovered starting
material (15%) (Scheme 9).
Similarly, irradiation of the bicyclo[2.2.2]octenones 25
and 26 having an allyl group in addition to the endo-
vinyl moiety and â,γ-enone group furnished the oxa-di-
π-methane products 37 and 38, respectively (Scheme 9).
Irradiation of the compound 30, having another photo-
chemically reactive carbonyl group in addition to the â,γ-
enone moiety, also underwent oxa-di-π-methane rear-
rangement to give the diquinane framework 40 (Scheme
9). Similar irradiation of the compound 15, having a
hydroxyl group at the R position to the carbonyl group,
also gave the tricyclic ketone 36 in moderate yield as a
result of the oxa-di-π-methane rearrangement (Scheme
9).
6). However, the minor isomer could not be separated.
The structure and stereochemistry of the compound 30
was deduced from its spectral data and further confirmed
through its chemical transformation to 35 (vide infra).
[3,3]-Sigmatropic Shift of Substituted Bicyclo-
[2.2.2]octenones: A Novel, General, and Stereo-
selective Route to Functionalized cis-Decalins. Cope
rearrangement or 3,3-sigmatropic shift is a general
process.24 While the oxy Cope and the oxy-anion Cope
have been widely used in synthesis,24b-d the Cope rear-
rangement is not often used due to its reversibility and
harsh reaction conditions. Toward the synthesis of cis-
decalins, 3,3-sigmatropic shift in bicyclooctenones 12a-
c, 15, 24-26, 28, and 30 was explored.
Thus, heating a solution of 12a in o-dichlorobenzene
at ∼170 °C led to a clean 3,3-sigmatropic shift and
furnished the cis-decalin 13a in quantitative yield (Scheme
7). Similarly, heating the bicyclic compounds 12b, 12c,
and 15 furnished the corresponding cis-decalins 13b, 13c,
and 16 in good yields (Scheme 7).
Conclusion
The bicyclooctenones 25, 26, 28, and 30 (Scheme 6)
required a little higher temperature for 3,3-shift and gave
the corresponding cis-decalins 32-35 respectively (Scheme
8). The structure of 35 was confirmed by its single X-ray
structure determination. Thus, the structures and stereo-
chemistry of the preceding intermediates leading to 35
were also established. The 3,3-sigmatropic shift in com-
pound 24 gave the enone 31, the cis-diastereoisomer of
the Woodward’s precursor for steroids25 (Scheme 8).
Photochemical 1,2-Acyl Shift in Bicyclo[2.2.2]-
octenones and Synthesis of Diquinane Frame-
In summary, we have described a new and efficient
synthesis of a variety of functionalized bicyclooctenones
of type 12a-c, 15, 17-28, 30 having an endo-vinyl
moiety and their sigmatropic shifts in ground and excited
states. A new method for the synthesis of bicyclo[2.2.2]-
octenones was developed via in situ generation of 6-chlo-
(26) (a) Houk, K. N. Chem. Rev. 1976, 76, 1-74. (b) Hixon, S. S.;
Mariano, P. S.; Zimmerman, H. E. Chem. Rev. 1973, 73, 531-551. (c)
Givens, R. S.; Oettle, W. F. J. Chem. Soc., Chem. Commun. 1969,
1164-1165.
(27) (a) Schuster, D. I. In Rearrangement in Ground and Excited
States; de Mayo, P., Ed.; Academic Press: New York, 1980, Vol. 3, pp
167-279. (b) Engel, P. S.; Schexnayder, M. A. J. Am. Chem. Soc. 1975,
97, 145-153. (c) Coffin, R. L.; Givens, R. S.; Carlson, R. G. J. Am.
Chem. Soc. 1974, 96, 7554-7556.
(28) (a) Zimmerman, H. E.; Armesto, D. Chem. Rev. 1996, 96, 3065-
3112. (b) Singh, V. In CRC Handbook of Organic Photochemistry and
Photobiology; Horspool, W., Lenci, F., Eds.; CRC Press, 2004; pp 78-
1-78-34. (c) Demuth, M. In Organic Photochemistry, Padwa, A., Ed.;
Marcell Dekker: New York, 1991; Vol. 11, pp 37-97.
(24) (a) Woodward, R. B.; Hoffman, R. Conservation of Orbital
Symmetry; Academic Press: New York, 1972. (b) Rhoads, S. J.; Raulins,
N. R. Org. React. 1975, 22, 1-252. (c) Hill, R. K. In Comprehensive
Organic Synthesis; Trost, B. M., Fleming, I., Eds.; Pergamon Press:
Oxford, 1991; Vol. 5, Chapter 7.1, pp 785-826. (d) Paquette, L. A.
Tetrahedron 1997, 53, 13971-14020.
(25) Woodward, R. B.; Sondheimer, F.; Taub, D.; Heusler, K.;
McLamore, W. M. J. Am. Chem. Soc. 1952, 74, 4223-4251.
976 J. Org. Chem., Vol. 70, No. 3, 2005

Synthesis of Bicyclo[2.2.2]octenones
3-Hydroxy-1,3-dimethyl-7-endo-vinyl-bicyclo[2.2.2]oct-
5-en-2-one (15). The dimer 14 (3 g, 10.86 mmol) and sulfolene
(12 g, excess) were heated in o-dichlorobenzene (12 mL) at 115
°C for 5 h as described above, and the reaction mixture was
chromatographed on silica gel. Elution with petroleum ether
first gave o-dichlorobenzene. Continued elution with petroleum
ether/ethyl acetate (98:2) gave the adduct 15 (2.50 g, 60%) as
a solid, which was recrystallized from petroleum ether. Further
elution with petroleum ether/ethyl acetate (97:3) then gave the
enone 16 (0.075 g, ∼2%) as a colorless liquid.
romethyl-6-hydroxycyclohexadienones and cycloaddition
with butadiene (also generated in situ) followed by
stereoselective manipulation of the adducts. While Cope
rearrangement provided a highly efficient and stereose-
lective route to highly functionalized cis-decalins, the
photochemical 1,2-acyl shift led to synthesis of a bicyclo-
[3.3.0]octane framework. The present work also demon-
strates the creation of structural diversity from a common
precursor via modulation of chemical reactivity. Applica-
tion of this methodology toward synthesis of agelasines
and other biologically active compounds is underway.
Data for 15: mp 52-54 °C; IR (film) νmax 3466, 1724 cm-1
;
1
UV (MeOH) λmax 305.6 (w), 216.6 (s) nm; H NMR (300 MHz,
CCl4 + CDCl3) δ 6.46 (superimposed dd, J1 ) J2 ) 7.4 Hz,
1H), 5.87 (d, J ) 8.4 Hz, 1H), 5.44-5.32 (m, 1H), 4.95 (m, 2H),
2.80 (s merged with m, 2H), 2.58 (m, 1H), 2.35 (m, 1H), 1.24
(s, 3H), 1.20-1.08 (s merged with m, 4H); 13C NMR (75 MHz,
CDCl3 + CCl4) δ 213.92, 139.46, 136.17, 131.57, 115.78, 72.17,
51.31, 46.21, 43.31, 28.82, 26.08, 15.84. HRMS (EI): found
192.1140 (M+); calcd for C12H16O2 192.1150 (M+).
Experimental Section
3-Chloromethyl-3-hydroxy-7-endo-vinyl-bicyclo[2.2.2]-
oct-5-en-2-one (12a). To a solution of dimer 11a (3 g, 9.46
mmol) in o-dichlorobenzene (12 mL) at 140 °C was added the
sulfolene 10 (12 g, excess) at regular intervals using a solid-
addition funnel over a period of 7 h. Reaction mixture was
brought to room temperature and chromatographed on silica
gel. Elution with petroleum ether first gave o-dichlorobenzene.
Continued elution with petroleum ether/ethyl acetate (98:2)
gave the adduct 12a (1.60 g, 40%) as a solid, which was
recrystallized from petroleum ether/ethyl acetate (96:4). Fur-
ther elution with petroleum ether/ethyl acetate (97:3) gave the
enone 13a (0.065 g, ∼2%) as a liquid.
3-Spiroepoxy-7-endo-vinyl-bicyclo[2.2.2]oct-5-en-2-
one (17). To a solution of the adduct 12a (0.5 g, 2.35 mmol)
in chloroform (50 mL) containing cetyltrimethylammonium
bromide (CTAB) (0.035 g) as a phase-transfer catalyst was
added an aqueous solution of potassium hydroxide (0.145 g,
2.58 mmol in H2O, 10 mL). The reaction mixture was stirred
at room temperature (∼30 °C) for 5 h, after which the organic
phase was separated and the aqueous layer extracted with
chloroform (2 × 15 mL). The combined organic extract was
washed with brine (20 mL) and dried over anhydrous sodium
sulfate. Removal of solvent followed by column chromatogra-
phy [petroleum ether/ethyl acetate, (98:2)] of the residue on
silica gel gave the epoxy ketone 17 as a colorless liquid: IR
1
Data for 12a: mp 83-84 °C; IR (film) νmax 1726 cm-1; H
NMR (300 MHz, CCl4 + CDCl3) δ 6.54 (superimposed dd, J1
) J2 ) 7 Hz, 1H), 6.16 (superimposed dd, J1 ) J2 ) 7 Hz, 1H),
5.61-5.50 (m, 1H), 5.01 (d, J ) 16.8 Hz, 1H), 4.97 (d, J ) 10.2
Hz, 1H), 3.60 (part of an AB system, JAB ) 11.7 Hz, 1H), 3.48
(part of an AB system, JAB ) 11.7 Hz, 1H), 3.19 (br m, 2H),
2.85-2.77 (m overlapped with s, 2H), 2.45 (superimposed dd,
J1 ) J2 ) 11.2 Hz, 1H), 1.20 (d, J ) 13.2 Hz, 1H); 13C NMR
(75 MHz, CDCl3 + CCl4) δ 208.4, 140.1, 136.0, 126.9, 114.9,
73.33, 53.3, 50.55, 40.21, 40.00, 26.20. Analysis found: C,
61.72; H, 5.93%. Calcd for C11H13O2Cl: C, 62.10; H, 6.11%.
Mass (m/z) 212 (M+).
1
(neat) νmax 1740 cm-1; H NMR (300 MHz, CDCl3 + CCl4) δ
6.57 (superimposed dd, J1 ) J2 ) 7.2 Hz, 1H), 6.20 (superim-
posed dd, J1 ) J2 ) 7.2 Hz, 1H), 5.68-5.56 (m, 1H), 5.06 (d, J
) 18 Hz, 1H), 4.98 (d, J ) 10.2 Hz, 1H), 3.27 (d, J ) 6.3 Hz,
1H), 3.11 (part of an AB system, JAB ) 6.3 Hz, 1H), 2.89 (m,
1H), 2.80 (part of an AB system, JAB ) 6.3 Hz, 1H), 2.54 (m,
1H), 2.42-2.33 (m, 1H), 1.42 (m, 1H); 13C NMR (75 MHz,
CDCl3 + CCl4) δ 204.10, 139.91, 135.06, 127.40, 114.95, 57.20,
53.72, 52.88, 39.45, 38.64, 28.49. HRMS (EI): found 176.0828
(M+); calcd for C11H12O2 176.0832 (M+).
3-Chloromethyl-3-hydroxy-5-methyl-7-endo-vinyl-
bicyclo[2.2.2]oct-5-en-2-one (12b). Pyrolysis of dimer 11b
(3 g, 8.69 mmol) and sulfolene (12 g, excess) in o-dichloro-
benzene (12 mL) at 140 °C for 7 h as described above followed
by chromatography [petroleum ether/ethyl acetate (98:2)] gave
the adduct 12b (1.37 g, 35%) as a solid, which was recrystal-
lized from petroleum ether/ethyl acetate (96:4): mp 91-92 °C;
IR (film) νmax 1727 cm-1; 1H NMR (300 MHz, CCl4 + CDCl3) δ
5.74 (s, 1H), 5.62-5.50 (m, 1H), 5.0 (d, J ) 17.4 Hz, 1H), 4.93
(d, J ) 9.9 Hz, 1H), 3.61 (part of an AB system, JAB ) 12 Hz,
1H), 3.44 (d of a part of an AB system, J1 ) 12 Hz, J2 ) 3.4
Hz, 1H), 3.03 (m, 2H), 2.81-2.66 (m, 2H), 2.44 (m, 1H), 1.96
(s, 3H), 1.16 (superimposed dd of a d, J1 ) 13 Hz, J2 ) J3 )
2.7 Hz, 1H); 13C NMR (75 MHz, CDCl3 + CCl4) δ 208.68,
145.84, 140.37, 118.80, 114.67, 73.31, 52.98, 49.83, 44.94,
40.63, 26.05, 20.93. Analysis found: C, 63.38; H, 6.66%. Calcd
for C12H15O2Cl: C, 63.57; H, 6.62%. Mass (m/z) 226 (M+).
3-Methyl-7-endo-vinyl-bicyclo[2.2.2]oct-5-en-2-one (18).
To a suspension of activated zinc (7 g, excess) and ammonium
chloride (1 g, excess) in dry dioxane (20 mL) was added a
solution of the compound 17 (1.5 g, 8.52 mmol) in dry dioxane
(15 mL) and refluxed for 12 h. The reaction mixture was
filtered on a Celite pad to remove zinc and washed with ethyl
acetate. The filtrate was concentrated in vacuo and diluted
with water (15 mL) and extracted with ethyl acetate (3 × 25
mL). The combined organic layer was washed with brine (25
mL) and dried over anhydrous sodium sulfate. The solvent was
removed under vacuum, and the residue was chromatographed
on silica gel. Elution with petroleum ether/ethyl acetate (99:
1) first gave the compound 18 (0.91 g, 66%) as a syn/anti
mixture. Further elution with petroleum ether/ethyl acetate
(94:6) furnished the alcohol 19 in minor amounts (0.16 g, 12%)
as a colorless liquid.
3-Chloromethyl-3-hydroxy-1,5-dimethyl-7-endo-vinyl-
bicyclo[2.2.2]oct-5-en-2-one (12c). Pyrolysis of dimer 11c
(3 g, 8.04 mmol) and sulfolene (12 g, excess) in o-dichloro-
benzene (12 mL) at 115 °C for 5 h as described above followed
by chromatography [petroleum ether/ethyl acetate (98:2)] gave
the adduct 12c as a colorless liquid (1.93 g, 50%): IR (neat)
νmax 3475, 1717 cm-1; 1H NMR (400 MHz, CDCl3) δ 5.48-5.36
(s merged with m, 2H), 4.96 (m, 2H), 3.55 (part of an AB
1
Data for 18: IR (neat) νmax 1724 cm-1; H NMR (400 MHz,
CDCl3) δ 6.6 (superimposed dd, J1 ) J2 ) 7.3 Hz, 1H), 6.08
(superimposed dd, J1 ) J2 ) 7.3 Hz, 1H), 5.64-5.52 (m, 1H),
4.99 (d, J ) 17 Hz, 1H), 4.92 (d, J ) 9.7 Hz, 1H), 3.1 (m, 1H),
2.66 (m, 1H), 2.60 (m, 1H), 2.18 (m, 1H), 2.04 (m, 1H), 1.20 (d
with structure, J ) 12 Hz, 1H), 1.12 (d, J ) 7.3 Hz, 3H) (data
for major isomer). HRMS (EI): found 162.1032 (M+); calcd for
C11H14O 162.1039 (M+).
system, JAB ) 11.8 Hz, 1H), 3.45 (part of an AB system, JAB
)
1
11.8 Hz, 1H), 2.98 (m, 1H), 2.56 (s, 1H), 2.51 (m, 1H), 2.40 (m,
1H), 1.95 (s, 3H), 1.22 (dd of a d, J1 ) 13 Hz, J2 ) 4.9 Hz, J3
) 2.8 Hz, 1H), 1.11 (s, 3H); 13C NMR (100 MHz, CDCl3) δ
211.04, 145.07, 139.10, 124.35, 116.02, 73.96, 51.39, 50.26,
46.94, 44.37, 28.06, 20.90, 15.78. HRMS (EI): found 240.0920
(M+); calcd for C13H17O2Cl 240.0917 (M+).
Data for 19: IR (neat) νmax 3456 cm-1; H NMR (300 MHz,
CDCl3 + CCl4) δ 6.28 (superimposed dd, J1 ) J2 ) 7 Hz, 1H),
6.09 (superimposed dd, J1 ) J2 ) 7 Hz, 1H), 5.62-5.51 (m,
1H), 4.97-4.91 (m, 3H), 4.84 (d, J ) 10.2 Hz, 1H), 3.99 (s,
1H), 3.04 (m, 1H), 2.85 (dd, J1 ) 15.7 Hz, J2 ) 7.6 Hz, 1H),
2.66 (m, 1H), 1.96-1.88 (m, 1H), 1.76 (br s with structure, 1H),
J. Org. Chem, Vol. 70, No. 3, 2005 977

Singh et al.
1.24 (dd of a d, J1 ) 12.3 Hz, J2 ) 5.8 Hz, J3 ) 2.6 Hz, 1H);
13C NMR (75 MHz, CDCl3 + CCl4) δ 152.29, 143.51, 134.22,
130.35, 113.23, 107.65, 71.45, 45.69, 40.96, 35.25, 33.58; mass
(m/z) 162 (M+). HRMS (ESI): found 163.1130 [M+ + H];. calcd
for C11H15O 163.1123 [M+ + H].
2%). Further elution with petroleum ether/ethyl acetate (90:
10) gave the â-keto alcohol 23 as a colorless liquid (syn/anti
mixture, 1.51 g, 75%).
1
Data for 23: IR (neat) νmax 3426, 1717 cm-1; H NMR (300
MHz, CDCl3) δ 5.68 (br s, 1H), 5.58-5.49 (m, 1H), 4.98 (d, J
) 17.1 Hz, 1H), 4.91 (d, J ) 9.9 Hz, 1H), 3.81-3.75 (m, 1H),
3.63-3.55 (m, 1H), 2.98 (d, J ) 6 Hz, 1H), 2.68-2.60 (s merged
with m, 3H), 2.21-2.07 (m, 2H), 1.91 (s, 3H), 1.18 (d with
structure, J ) 12.4 Hz, 1H) (data for the major isomer). HRMS
(ESI): found 193.1247 [M+ + H]; calcd for C12H17O2 193.1229
[M+ + H].
3-Spiroepoxy-5-methyl-7-endo-vinyl-bicyclo[2.2.2]oct-
5-en-2-one (20). To a solution of the adduct 12b (0.53 g, 2.35
mmol) in chloroform (50 mL) containing cetyltrimethylammo-
nium bromide (CTAB) (0.035 g) was added an aqueous solution
of KOH (0.145 g, 2.58 mmol in 10 mL H2O). The reaction
mixture was stirred at room temperature (∼30 °C) for 5 h,
after which the organic phase was separated and the aqueous
layer extracted with chloroform (2 × 15 mL). The combined
organic extract was washed with brine (20 mL) and dried over
anhydrous sodium sulfate. Removal of solvent followed by
column chromatography [petroleum ether/ethyl acetate, (98:
2)] of the residue on silica gel gave the epoxy ketone 20 (0.440
5-Methyl-7-endo-vinyl-bicyclo[2.2.2]oct-5-en-2-one (24).
To a solution of the â-keto-alcohol 23 (2 g, 10.4 mmol) in
acetone (60 mL) at ∼5 °C was added freshly prepared Jones’
reagent dropwise. After completion of the reaction (TLC, 0.45
h), acetone was removed under vacuum, and the residue was
diluted with water (8 mL). The aqueous layer was extracted
with ethyl acetate (6 × 10 mL). The extract was combined and
dried over anhydrous sodium sulfate, and the solvent was
removed under vacuum to give the crude acid, which was
subjected to decarboxylation as follows. The carboxylic acid
was dissolved in THF-H2O mixture (1:1, 60 mL) and refluxed
for 12 h. The aqueous layer was saturated with sodium
chloride, extracted with ether (7 × 10 mL), and dried. The
solvent was removed in vacuo, and the residue was chromato-
graphed. Elution with petroleum ether/ethyl acetate (97:3)
gave the title compound 24 as a colorless liquid (0.76 g, 45%):
1
g, ∼100%) as a colorless liquid: IR (neat) νmax 1738 cm-1; H
NMR (300 MHz, CDCl3) δ 5.78 (d with structure, J ) 6.2 Hz,
1H), 5.71-5.59 (m, 1H), 5.05 (d with structure, J ) 17 Hz,
1H), and 4.98 (d with structure, J ) 10.6 Hz, 1H), 3.2 (dd, J1
) 6.2 Hz, J2 ) 2.1 Hz, 1H), 3.13 (part of an AB system, JAB
)
6.2 Hz, 1H), 2.88 (part of an AB system merged with a
multiplet, JAB ) 6.2 Hz, 2H), 2.39-2.29 (m, 2H), 1.94 (d, J )
1.8 Hz, 3H), 1.4 (m, 1H); 13C NMR (75 MHz, CDCl3) δ 205.42,
145.05, 140.23, 119.23, 114.77, 57.43, 53.66, 52.33, 44.03,
40.21, 28.23, 20.64. HRMS (EI): found 190.0979 (M+); calcd
for C12H14O2 190.0988 (M+).
1
IR (neat) νmax 1726 cm-1; H NMR (300 MHz, CDCl3 + CCl4)
3,5-Dimethyl-7-endo-vinyl-bicyclo[2.2.2]oct-5-en-2-
one (21). A solution of the compound 20 (1.5 g, 7.89 mmol) in
dry dioxane (15 mL) was added to a suspension of activated
zinc (7 g, excess) and NH4Cl (1 g, excess) in dry dioxane (20
mL), and the reaction mixture was refluxed for 12 h. The
reaction mixture was filtered and washed with ethyl acetate.
The filtrate was concentrated in vacuo, diluted with water (15
mL), and extracted with ethyl acetate (3 × 25 mL). The
combined extract was washed with brine (1 × 25 mL) and
dried. The solvent was removed under vacuum, and the
residue was chromatographed on silica gel. Elution with
petroleum ether/ethyl acetate (99:1) first gave the compound
21 (1.08 g, 66%) [ syn/anti mixture] as a colorless liquid.
Further, elution with petroleum ether/ethyl acetate (94:6)
furnished the alcohol 22 in minor amounts (0.18 g, 12%) as a
colorless liquid.
δ 5.68 (d, J ) 5.7 Hz, 1H), 5.61-5.50 (m, 1H), 4.98 (d, J )
16.8 Hz, 1H), 4.91 (d, J ) 9.9 Hz, 1H), 2.96 (d, J ) 6.6 Hz,
1H), 2.69 (s merged with m, 2H), 1.97 (m, 3H), 1.88 (s, 3H),
and 1.29 (br d, J ) 12.3 Hz, 1H); 13C NMR (75 MHz, CDCl3 +
CCl4) δ 211.02, 146.73, 140.97, 118.26, 114.23, 54.43, 39.45,
38.84, 38.03, 31.83, 20.26. HRMS (EI): found 162.1039 (M+);
calcd for C11H14O 162.1046 (M+).
3-Allyl-3-methyl-7-endo-vinyl-bicyclo[2.2.2]oct-5-en-2-
one (25). Sodium hydride (0.5 g of 60% w/w suspension in oil,
excess) was placed in a dry two-necked flask and washed with
dry petroleum ether, and tetrahydrofuran (5 mL) was added.
A solution of ketone 18 (0.6 g, 3.70 mmol) in tetrahydrofuran
(10 mL) was added slowly to the reaction mixture, and it was
refluxed for 1 h. Allyl bromide (1 mL, excess) was then added
to the reaction mixture, and the reaction mixture was further
refluxed for 8 h. The reaction mixture was then cooled in an
ice bath and quenched by careful addition of water, and it was
filtered on a Celite pad. The filtrate was then concentrated
under vacuum. The residue was diluted with water and
extracted with ether (3 × 10 mL). The combined extract was
washed with water (10 mL) and brine (10 mL) and dried over
anhydrous sodium sulfate. Removal of solvent and column
chromatography [petroleum ether/ethyl acetate, (99:1)] of the
residue on silica gel gave an inseparable mixture of alkylated
products as a syn/anti mixture (0.59 g, 79%) that was further
chromatographed on silver nitrate-impregnated silica gel.
Elution with petroleum ether/ethyl acetate (99:1) first gave
the mixture of the syn/anti isomers followed by the pure syn
isomer 25 (0.486 g, 65%) as a colorless liquid: IR (neat) νmax
1718 cm-1; UV (MeOH) λmax 296.4 (w), 217.6 (s) nm; 1H NMR
(300 MHz, CDCl3) δ 6.55 (superimposed dd, J1 ) J2 ) 7.2 Hz,
1H), 6.02 (superimposed dd, J1 ) J2 ) 7.2 Hz, 1H), 5.85-5.70
(m, 1H), 5.64-5.50 (m, 1H), and 5.1-4.90 (m, 4H), 3.11 (d with
structure, J ) 6.2 Hz, 1H), 2.76-2.64 (m, 2H), 2.26-2.12 (m,
2H), 2.08-1.99 (m, 1H), 1.19 (ddd, J1 ) 13.4, J2 ) 6.1, J3 )
2.5 Hz, 1H), and 1.09 (s, 3H); 13C NMR (75 MHz, CDCl3) δ
214.88, 140.74, 138.12, 133.64, 124.05, 117.92, 114.09, 55.04,
46.10, 43.33, 41.04, 39.14, 28.34, 21.21. HRMS (EI): found
202.1357 (M+); calcd for C14H18O 202.1352 (M+).
1
Data for 21: IR (neat) νmax 1724 cm-1; H NMR (400 MHz,
CDCl3) δ 5.68-5.52 (s merged with multiplet, 2H), 4.98 (d, J
) 17.2 Hz, 1H), 4.92 (d, J ) 9.6 Hz, 1H), 2.98 (dd, J1 ) 6 Hz,
J2 ) 2.4 Hz, 1H), 2.62-2.52 (m, 1H), 2.48 (d, J ) 2.4 Hz, 1H),
2.18-2.10 (m, 1H), 2.02 (m, 1H), 1.88 (s, 3H), 1.10 (d merged
with m, J ) 7.2 Hz, total 4H) (data for major isomer). HRMS
(EI): found 176.1193 (M+); calcd for C12H16O 176.1196 (M+).
1
Data for 22: IR (neat) νmax 3371 cm-1; H NMR (300 MHz,
CDCl3 + CCl4) δ 5.68 (d, J ) 6.6 Hz, 1H), 5.63-5.51 (m, 1H),
4.93-4.81 (m, 4H), 3.96 (s, 1H), 2.83 (m, 2H), 2.55 (m, 1H),
1.94-1.86 (m, 2H), 1.79 (d, J ) 1.5 Hz, 3H), 1.20 (ddd, J1 )
12.3 Hz, J2 ) 5.8 Hz, J3 ) 2.4 Hz, 1H); 13C NMR (75 MHz,
CDCl3 + CCl4) δ 152.31, 143.77, 142.99, 122.68, 113.04, 107.60,
71.85, 46.58, 45.63, 34.79, 34.32, 19.91. HRMS (ESI): found
177.1286 [M+ + H]; calcd for C12H17O 177.1279 [M+ + H].
3-Hydroxymethyl-5-methyl-7-endo-vinyl-bicyclo[2.2.2]-
oct-5-en-2-one (23). To a solution of the epoxy ketone 20 (2
g, 10.5 mmol) in MeOH-H2O (6:1, 70 mL) was added zinc
(activated 12 g, excess) and NH4Cl (2.2 g, 40.7 mmol). The
reaction mixture was stirred at ambient temperature (∼33 °C)
for 10 h, filtered on a Celite bed, and washed with ethyl acetate
(4 × 5 mL). The filtrate was concentrated under vacuum,
diluted with water (10 mL), and extracted with ethyl acetate
(4 × 5 mL). The combined extract was washed with brine (10
mL) and dried on anhydrous sodium sulfate. The solvent was
removed under reduced pressure, and the residue was purified
by column chromatography. Elution with petroleum ether/
ethyl acetate (98:2) gave the ketone 21 as a liquid (0.037 g,
3-Allyl-3,5-dimethyl-7-endo-vinyl-bicyclo[2.2.2]oct-5-
en-2-one (26). Sodium hydride (0.250 g of 60% w/w suspension
in oil, excess) was placed in a dry two-necked flask and washed
with dry petroleum ether, and tetrahydrofuran (2 mL) was
added to it. A solution of ketone 21 (0.3 g, 1.70 mmol) in
978 J. Org. Chem., Vol. 70, No. 3, 2005

Synthesis of Bicyclo[2.2.2]octenones
tetrahydrofuran (5 mL) was added slowly to the reaction
mixture, and the reaction mixture was refluxed for 1 h. Allyl
bromide (0.5 mL, excess) was then added to the reaction
mixture, and the reaction mixture was further refluxed for 7
h. The reaction mixture was worked up as described above,
and the product obtained was chromatographed on silver
nitrate-impregnated silica gel. Elution with petroleum ether/
ethyl acetate, (99:1) first gave a mixture of syn/anti isomers.
Continued elution furnished the syn isomer 26 (0.228 g, 62%)
as a colorless liquid: IR (neat) νmax 1719 cm-1; UV (MeOH)
mixture was then poured into water (5 mL) and extracted with
ethyl acetate (3 × 10 mL). The organic layer was washed with
brine (10 mL) and dried. The solvent was removed under
reduced pressure, and the residue was chromatographed on
silica gel. Elution with petroleum ether/ethyl acetate (90:10)
gave a mixture of the syn/anti isomers (0.105 g, 81%) in the
ratio of 85:15. This mixture was further subjected to column
chromatography on silver nitrate-impregnated silica gel. Elu-
tion with petroleum ether/ethyl acetate (94:6) first gave a
mixture of the syn/anti isomers. Continued elution with the
same solvent furnished the desired syn isomer 30 (0.085 g,
66%) as a colorless liquid: IR (neat) νmax 1715 cm-1; UV
(MeOH) λmax 296.6 (w), 214.4 (s) nm; 1H NMR (300 MHz, CDCl3
+ CCl4) δ 6.50 (superimposed dd, J1 ) J2 ) 7.2 Hz, 1H), 6.04
(superimposed dd, J1 ) J2 ) 7.2 Hz, 1H), 5.58-5.46 (m, 1H),
4.98 (d, J ) 16.5 Hz, 1H), and 4.92 (d, J ) 10.8 Hz, 1H), 3.28
(m, 1H), 3.08 (d, J ) 6.6 Hz, 1H), 2.65 (part of AB system
merged with a multiplet, JAB ) 16.5 Hz, 2H), 2.38 (part of an
AB system, JAB ) 16.5, 1H), 2.25-2.22 (m, 1H), 2.06 (s, 3H),
1.25-1.20 (m merged to a singlet, 4H); 13C NMR (75 MHz,
CDCl3 + CCl4) δ 213.50, 206.23, 140.73, 138.93, 125.13, 114.49,
54.50, 50.29, 45.30, 40.02, 38.38, 31.89, 28.33, and 20.94.
HRMS (ESI): found 219.1372 [M+ + H]; calcd for C14H19O2
219.1380 [M+ + H].
1
λmax 299 (w), 226 (s) nm; H NMR (300 MHz, CDCl3) δ 5.90-
5.69 (m, 3H), 5.12-4.80 (m, 4H), 2.97 (dd, J1 ) 7 Hz, J2 ) 3
Hz, 1H), 2.54-2.44 (m, 2H), 2.24 (d of part of an AB system,
JAB ) 14 Hz, J ) 8 Hz, 1H), 2.07 (d of part of an AB system,
JAB ) 14 Hz, J ) 8 Hz, 1H), 1.90 (d, J ) 1.5 Hz, 3H), 1.82-
1.69 (m, 2H), 1.02 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 216.45,
147.12, 140.55, 134.03, 120.54, 118.17, 115.11, 54.32, 47.31,
46.46, 43.16, 42.05, 26.60, 21.33, 19.46. HRMS (ESI): found
216.1503 (M+); calcd for C15H20O 216.1508 (M+).
3,3-Dimethyl-7-endo-vinyl-bicyclo[2.2.2]oct-5-en-2-
one (27). Sodium hydride (0.3 g of 60% w/w suspension in oil,
excess) was placed in a dry two-necked flask and washed with
dry petroleum ether, and tetrahydrofuran (2 mL) was added.
A solution of ketone 18 (0.3 g, 1.85 mmol) in tetrahydrofuran
(6 mL) was added slowly to the reaction mixture, and it was
refluxed for 1 h. Methyl iodide (1.5 mL, excess) was then added
to the reaction mixture, and the reaction mixture was further
refluxed for 8 h. It was then worked up as described above,
and the product thus obtained was chromatographed on silica
gel. Elution with petroleum ether/ethyl acetate (99:1) furnished
the alkylated product 27 (0.257 g, 79%) as a colorless liquid:
IR (neat) νmax 1724 cm-1; UV (MeOH) λmax 296.2 (w), 217.8 (s)
1-Chloromethyl-1-hydroxy-4a,5,8,8a-tetrahydro-1H-
naphthalen-2-one (13a). The adduct 12a (0.5 g, 2.35 mmol)
was heated in o-dichlorobenzene (8 mL) at 170 °C for 12 h.
The reaction mixture was chromatographed on silica gel.
Elution with petroleum ether first gave o-dichlorobenzene.
Further elution with petroleum ether/ethyl acetate (97:3)
furnished the enone 13a (0.495 g, ∼100%) as a colorless
liquid: IR (neat) νmax 3480, 1682 cm-1 1H NMR (300 MHz,
;
1
nm; H NMR (400 MHz, CDCl3) δ 6.56 (superimposed dd, J1
CDCl3 + CCl4) δ 6.73 (m of d, J ) 10 Hz, 1H), 6.06 (dd, J1 )
10 Hz, J2 ) 3.7 Hz, 1H), 5.69 (m, 2H), 3.80 (part of an AB
system, JAB ) 11.7 Hz, 1H), 3.71 (s, 1H), 3.57 (part of an AB
system, JAB ) 11.7 Hz, 1H), 3.03 (br m, 1H), 2.74-2.73 (m,
1H), 2.52 (d with structure, J ) 17.7 Hz, 1H), 2.32-2.16 (m,
2H), 1.70-1.61 (m, 1H); 13C NMR (75 MHz, CDCl3 + CCl4) δ
198.4, 156.2, 126.9, 126.7, 124.3, 78.6, 48.7, 39.1, 33.5, 30.2,
21.7. HRMS (EI): found 212.0596 (M+); calcd for C11H13O2Cl
212.0599 (M+).
) J2 ) 7.2 Hz, 1H), 6.02 (superimposed dd, J1 ) J2 ) 7.2 Hz,
1H), 5.61-5.51 (m, 1H), 4.99 (d, J ) 17.2 Hz, 1H), 4.92 (d, J
) 10 Hz, 1H), 3.08 (d, J ) 6 Hz, 1H), 2.69 (m, 1H), 2.58 (br s,
1H), 2.26 (m, 1H), 1.19 (ddd, J1 ) 13 Hz, J2 ) 5.8 Hz, J3 ) 2
Hz, 1H), 1.11 (s, 3H), 1.05 (s, 3H); 13C NMR (100 MHz, CDCl3)
δ 216.38, 141.09, 139.21, 124.21, 114.22, 55.00, 44.40, 43.31,
38.47, 28.66, 27.60, 24.45; mass (m/z) 176 (M+). HRMS (ESI):
found 177.1281 [M+ + H]; calcd for C12H17O 177.1279 [M+
H].
+
1-Chloromethyl-1-hydroxy-4a-methyl-4a,5,8,8a-tetra-
hydro-1H-naphthalen-2-one (13b). A solution of the adduct
12b (0.532 g, 2.35 mmol) in o-dichlorobenzene (8 mL) was
heated at 180 °C for 25 h, after which the reaction mixture
was chromatographed on silica gel. Elution with petroleum
ether followed by petroleum ether/ethyl acetate (98:2) gave the
o-dichlorobenzene and unreacted starting material (0.106 g,
20%), respectively. Further elution with petroleum ether/ethyl
acetate (97:3) furnished the enone 13b (0.399 g, 75%) as a solid
which was recrystallized from petroleum ether/ethyl acetate
(97:3): mp 96-97 °C; IR (film) νmax 3478, 1680 cm-1; 1H NMR
(300 MHz, CDCl3 + CCl4) δ 6.87 (d, J ) 10 Hz, 1H), 6.02 (d, J
) 10 Hz, 1H), 5.75 (m, 1H), 5.70 (m, 1H), 3.89 (part of an AB
3-Methyl-3-prop-2-ynyl-7-endo-vinyl-bicyclo[2.2.2]oct-
5-en-2-one (28). A solution of ketone 18 (0.6 g, 3.70 mmol) in
tetrahydrofuran (10 mL) was added to a suspension of sodium
hydride (0.5 g of 60% w/w suspension in oil, excess, washed
with dry pentane) in THF (5 mL), and the reaction mixture
was refluxed for 1 h. Propargyl bromide (0.6 mL, excess) was
then added to the reaction mixture, and the reaction mixture
was further refluxed for 10 h. The reaction mixture was
worked up as described previously, and the resulting product
was chromatographed on silica gel. Elution with petroleum
ether/ethyl acetate, (98:2) gave propargylated products 28 and
29 as a mixture of syn/anti isomers (0.44 g, 60%). Repeated
chromatography of the mixture on silica gel (100-200 mesh)
furnished the major syn isomer 28 as a colorless liquid: IR
system, JAB ) 10.5 Hz, 1H), 3.48 (part of an AB system, JAB
)
10.5 Hz, 1H), 2.78 (br m, 1H), 2.47-2.37 (m, 2H), 2.22
(superimposed dd, J1 ) J2 ) 14.7 Hz, 2H), 1.97 (d with
structure, J ) 14.7 Hz, 1H), 1.25 (s, 3H); 13C NMR (75 MHz,
CDCl3 + CCl4) δ 196.21, 160.82, 125.61, 125.30, 124.03, 45.45,
38.84, 36.43, 34.48, 27.33, 22.43. Analysis found: C, 63.64; H,
6.95%. Calcd for C12H15O2Cl: C, 63.57; H, 6.62%. Mass (m/z)
226 (M+).
(neat) νmax 1724 cm-1 1H NMR (400 MHz, CDCl3) δ 6.59
;
(superimposed dd, J1 ) J2 ) 7 Hz, 1H), 6.03 (superimposed
dd, J1 ) J2 ) 7 Hz, 1H), 5.62-5.50 (m, 1H), 5.0 (d, J ) 15.8
Hz, 1H), 4.93 (d, J ) 9.7 Hz, 1H), 3.12 (d, J ) 6.1 Hz, 1H), 3.0
(s with structure, 1H), 2.72 (m, 1H), 2.39 (d of a part of an AB
system, J1 ) 17 Hz, J2 ) 2.4 Hz, 1H), 2.24 (m, 1H), 2.14 (part
of an AB system, JAB ) 17 Hz, 1H), 2.05 (d, J ) 2.4 Hz, 1H),
1.23 (s merged with m, 4H); 13C NMR (75 MHz, CDCl3) δ
213.96, 140.69, 138.72, 124.80, 114.398, 80.56, 71.33, 54.76,
45.24, 40.52, 38.51, 29.01, 28.26, 21.11. HRMS (EI): found
200.1201 (M+); calcd for C14H16O 200.1195 (M+).
1-Chloromethyl-1-hydroxy-3,4a-dimethyl-4a,5,8,8a-tet-
rahydro-1H-naphthalen-2-one (13c). Heating a solution of
the adduct 12c (0.565 g, 2.35 mmol) in o-dichlorobenzene (8
mL) at 165 °C for 8 h followed by chromatography [petroleum
ether/ethyl acetate (98:2)] furnished the enone 13c (0.559 g,
∼100%) as a solid that was recrystallized from petroleum
ether/ethyl acetate (98:2): mp 57-59 °C; IR (film) νmax 3468,
1669 cm-1; 1H NMR (300 MHz, CDCl3) δ 6.66 (s, 1H), 5.79 (m,
1H), 5.75 (m, 1H), 3.92 (part of an AB system, JAB ) 10.8 Hz,
1H), 3.53 (part of an AB system, JAB ) 10.8 Hz, 1H), 2.80 (m,
3-Methyl-3-(2-oxo-propyl)-7-endo-vinyl-bicyclo[2.2.2]-
oct-5-en-2-one (30). A solution of the syn/anti mixture 28 and
29 (0.120 g, 0.6 mmol) in methanol (6 mL) was added to a
suspension of HgO (0.024 g) in 4% H2SO4 (2 mL), and the
reaction mixture was heated at 60 °C for 12 h. The reaction
J. Org. Chem, Vol. 70, No. 3, 2005 979

Singh et al.
1H), 2.42 (s merged with m, 2H), 2.20 (m, 1H), 2.15 (s, 1H),
2.0 (m, 1H), 1.84 (s, 3H), 1.22 (s, 3H); 13C NMR (75 MHz,
CDCl3) δ 197.63, 156.75, 131.83, 125.67, 124.57, 46.29, 38.82,
36.68, 33.75, 27.50, 22.45, 15.84. HRMS (EI): found 240.0905
(M+); calcd for C13H17O2Cl 240.0917 (M+).
with petroleum ether first gave diphenyl ether. Further elution
with petroleum ether/ethyl acetate (97:3) furnished the rear-
ranged product 34 (0.038 g, 50%) as a colorless liquid: IR
(neat) νmax 1673 cm-1; 1H NMR (300 MHz, CDCl3) δ 6.57 (d, J
) 9.9 Hz, 1H), 5.87 (d with structure, J ) 9.9 Hz, 1H), 5.71
(m, 1H), 5.65 (m, 1H), 3.06 (s, 1H), 2.60 (part of an AB system,
JAB ) 17.4 Hz, 1H), 2.43 (m, 2H), 2.13 (part of an AB system
partly merged with a multiplet, JAB ) 17.4 Hz, 3H), 1.99 (s,
1H), 1.76 (m, 1H), 1.19 (s, 3H); 13C NMR (75 MHz, CDCl3 +
CCl4) δ 201.48, 153.00, 128.70, 127.09, 125.03, 80.13, 71.44,
48.61, 38.84, 31.43, 30.69, 26.27, 23.55, 18.72. HRMS (ESI):
found 223.1092 [M+ + Na]; calcd for C14H16ONa 223.1093 [M+
+ Na].
1-Methyl-1-(2-oxo-propyl)-4a,5,8,8a-tetrahydro-1H-naph-
thalen-2-one (35). A solution of the diketone 30 (0.16 g, 0.73
mmol) in o-dichlorobenzene (4 mL) was refluxed at 180 °C for
30 h. Chromatography of the reaction mixture on silica gel
and elution with petroleum ether first gave o-dichlorobenzene.
Further elution with petroleum ether/ethyl acetate (94:6) gave
some unreacted starting material (0.012 g, 8%). Continued
elution with petroleum ether/ethyl acetate (92:8) furnished the
rearranged product 35 (0.105 g, 66%) as a solid, which was
recrystallized from petroleum ether/ethyl acetate (94:6): mp
73-74 °C; IR (film) νmax 1713, 1675 cm-1; 1H NMR (300 MHz,
CDCl3) δ 6.65 (m of d, J ) 10.2 Hz, 1H), 5.95 (dd, J1 ) 10.2
Hz, J2 ) 2.5 Hz, 1H), 5.80-5.72 (m, 1H), 5.68-5.6 (m, 1H),
3.02 (br m, 1H), 2.74 (part of an AB system, JAB ) 15 Hz, 1H),
2.62-2.40 (m merged with a part of an AB system, JAB ) 15
Hz, total 3H), 2.22-2.04 (s merged with a m, total 5H), 1.78-
1.60 (m merged with the signal due to H2O present in CDCl3,
1H), 1.2 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 206.82, 202.41,
153.82, 128.60, 126.78, 125.10, 48.92, 47.68, 37.96, 32.37,
31.99, 30.47, 23.73, 18.72. Analysis found: C, 76.84; H, 8.33%.
Calcd for C14H18O2: C, 77.06; H, 8.25%. Mass (m/z) 218 (M+).
1-Hydroxy-1,3-dimethyl-4a,5,8,8a-tetrahydro-1H-naph-
thalen-2-one (16). A solution of the adduct 15 (0.450 g, 2.35
mmol) in o-dichlorobenzene (8 mL) was heated at 140 °C for 8
h, after which it was chromatographed on silica gel. Elution
with petroleum ether first gave o-dichlorobenzene. Further
elution with petroleum ether/ethyl acetate (98:2) furnished the
enone 16 (0.445 g, ∼100%) as a colorless liquid: IR (neat) νmax
3500, 1673 cm-1; 1H NMR(300 MHz, CDCl3) δ 6.41 (d, J ) 1.5
Hz, 1H), 5.74-5.63 (m, 2H), 3.63 (s, 1H), 2.99 (m, 1H), 2.42-
2.12 (clusters of m, 4H), 1.81 (s with structure, 3H), 1.63-
1.51 (m, 1H), 1.38 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 203.20,
150.54, 132.69, 126.86, 124.53, 76.58, 43.07, 32.90, 30.66,
24.32, 22.28, 15.59. HRMS (EI): found 192.1140 (M+); calcd
for C12H16O2 192.1150 (M+).
4a-Methyl-4a,5,8,8a-tetrahydro-1H-naphthalen-2-one
(31). A solution of the compound 24 (0.1 g, 0.61 mmol) in
diphenyl ether (5 mL) was heated at 195 °C in a sealed tube
for 10 h, after which it was chromatographed on silica gel.
Elution with petroleum ether first gave diphenyl ether.
Further elution with petroleum ether/ethyl acetate (98:2)
furnished the rearranged product 31 (0.045 g, 45%) as a
colorless liquid: IR (neat) νmax 1680 cm-1; 1H NMR (300 MHz,
CDCl3) δ 6.81 (d, J ) 10 Hz, 1H), 5.87 (d, J ) 10 Hz, 1H),
5.74-5.62 (m, 2H), 2.44-2.31 (m, 3H), 2.13-1.94 (m, 3H),
1.87-1.79 (m, 1H), 1.17 (s, 3H); 13C NMR (75 MHz, CDCl3) δ
200.61, 161.28, 127.54, 124.69, 124.38, 41.32, 37.45, 34.60,
34.43, 28.56, 25.66. HRMS (ESI): found 163.1130 [M+ + H];
calcd for C11H15O 163.1123 [M+ + H].
1-Allyl-1-methyl-4a,5,8,8a-tetrahydro-1H-naphthalen-
2-one (32). A solution of the compound 25 (0.200 g, 0.99 mmol)
in o-dichlorobenzene (5 mL) was refluxed at 180 °C for 30 h,
after which the reaction mixture was chromatographed on
silica gel. Elution with petroleum ether followed by petroleum
ether/ethyl acetate (98:2) gave o-dichlorobenzene and some
unreacted starting material 25 (0.02 g, 10%), respectively.
Further elution with petroleum ether/ethyl acetate (96:4)
furnished the rearranged product 32 (0.09 g, 45%) as a
colorless liquid: IR (neat) νmax 1674 cm-1; 1H NMR (300 MHz,
CDCl3 + CCl4) δ 6.51 (d with structure, J ) 9.9 Hz, 1H), 5.87
(dd, J1 ) 9.9 Hz, J2 ) 2.7 Hz, 1H), 5.82-5.71 (m, 2H), 5.71-
5.59 (m, 1H), 5.08 (m, 2H), 3.09 (s with structure, 1H), 2.45-
2.37 (m, 2H), 2.17-2.04 (clusters of m, 4H), 1.78 (m, 1H), 1.06
(s, 3H); 13C NMR (75 MHz, CDCl3 + CCl4) δ 202.26, 152.20,
133.75, 129.08, 127.32, 124.95, 118.32, 49.15, 40.30, 39.62,
31.20, 30.76, 23.88, 18.62. HRMS (EI): found 202.1349 (M+);
calcd for C14H18O 202.1352 (M+).
Crystal data: C14H18O2, M ) 218.28, Ph1 Triclinic, Z ) 2, λ
) 0.70930°, a ) 6.6080(11) Å, b ) 8.3730(5) Å, c ) 12.3070(8)
Å, U ) 603.00(11) Å3, T ) 293(2) K, Dc ) 1.198 Mg m-3, µ )
0.078 mm-1, F(000) ) 236, size ) 0.30 mm × 0.20 mm × 0.15
mm. Reflections collected/unique ) 1572/1572 [R(int) ) 0.0000].
Final R indices [I > 2σ(I)]: R1 ) 0.0523, wR2 ) 0.1167, R
indices (all data): R1 ) 0.0969, wR2 ) 0.1392.
2,6-Dimethyl-2-hydroxy-7-vinyl-tricyclo[3.3.0.04,6]octa-
3-one (36). A solution of 15 (0.085 g, 0.44 mmol) in degassed
acetone (110 mL, solvent as well as sensitizer) was irradiated
with a mercury vapor lamp (125 W) in a Pyrex immersion well
for 1 h under nitrogen. Acetone was removed under vacuum,
and the residue was chromatographed. Elution with petroleum
ether/ethyl acetate (97:3) gave some unreacted starting mate-
rial (0.010 g, 12%). Further elution with petroleum ether/ethyl
acetate (96:4) yielded the photoproduct 36 (0.029 g, 35%) as a
1
solid: mp 63-64 °C; IR (film) νmax 3470, 1722 cm-1; H NMR
1-Allyl-1,4a-dimethyl-4a,5,8,8a-tetrahydro-1H-naph-
thalen-2-one (33). A solution of the compound 26 (0.08 g, 0.37
mmol) in diphenyl ether (4 mL) was heated at 195 °C in a
sealed tube for 10 h, after which it was brought to room
temperature and chromatographed on silica gel. Elution with
petroleum ether first gave diphenyl ether. Further elution with
petroleum ether/ethyl acetate (98:2) furnished the rearranged
product 33 (0.036 g, 45%) as a colorless liquid: IR (neat) νmax
(400 MHz, CDCl3) δ 5.75 (m, 1H), 5.0 (m, 2H), 2.65 (superim-
posed dd, J1 ) J2 ) 5.8 Hz, 1H), 2.4 (m, 2H), 2.2 (dd, J1
)
12.6 Hz, J2 ) 6.2 Hz, 1H), 1.9 (d, J ) 4.8 Hz, 1H), 1.75 (m,
2H), 1.30 (s, 3H), 1.15 (s, 3H); 13C NMR (100 MHz, CDCl3) δ
215.75, 139.67, 115.90, 81.37, 47.96, 46.71, 43.37, 39.84, 39.01,
27.10, 19.65. HRMS (EI): found 192.1150 (M+); calcd for
C12H16O2 192.11502 (M+).
1
1670 cm-1; H NMR (400 MHz, CDCl3) δ 6.73 (d, J ) 10 Hz,
2-Allyl-2-methyl-7-vinyl-tricyclo[3.3.0.04,6]octa-3-one (37).
A solution of 25 (0.080 g, 0.39 mmol) in degassed acetone (110
mL, solvent as well as sensitizer) was irradiated as described
above for 1.5 h. Acetone was removed under vacuum, and the
residue was chromatographed. Elution with petroleum ether/
ethyl acetate (99:1) gave some unreacted starting material
(0.014 g, 18%). Further elution with petroleum ether/ethyl
acetate (98:2) afforded the product 37 (0.036 g, 45%) as a
colorless liquid: IR (neat) νmax 1724 cm-1; 1H NMR (300 MHz,
CDCl3 + CCl4) δ 5.84-5.64 (m, 2H), 5.10-4.93 (m, 4H), 2.63
(m, 1H), 2.57 (m, 1H), 2.33 (m, 1H), 2.11 (d, J ) 7.2 Hz, 2H),
2.03-1.98 (m, 1H), 1.88-1.75 (m, 3H), 0.81 (s, 3H); 13C NMR
(75 MHz, CDCl3 + CCl4) δ 216.72, 141.07, 133.41, 118.54,
1H), 5.89 (d, J ) 10 Hz, 1H), 5.80-5.74 (m, 1H), 5.70-5.63
(m, 1H), 5.60-5.48 (m, 1H), 5.20-5.00 (m, 2H), 2.80 (dd, J1 )
13 Hz, J2 ) 5.5 Hz, 1H), 2.30-2.20 (m, 1H), 2.20-2.02
(overlapped m, 4H), 1.99-1.90 (m, 1H), 1.15 (s, 3H), 1.01 (s,
3H); 13C NMR (100 MHz, CDCl3) δ 203.90, 159.16, 135.09,
126.03, 125.78, 123.25, 117.54, 48.88, 41.83, 38.71, 34.89,
34.27, 28.82, 22.20, 20.71. HRMS (ESI): found 217.1574 (M+
+ H); calcd for C15H21O 217.1589 (M+ + H).
1-Methyl-1-prop-2-ynyl-4a,5,8,8a-tetrahydro-1H-naph-
thalen-2-one (34). A solution of the compound 28 (0.075 g,
0.37 mmol) in diphenyl ether (3 mL) was heated at 195 °C for
10 h, after which it was chromatographed on silica gel. Elution
980 J. Org. Chem., Vol. 70, No. 3, 2005

Synthesis of Bicyclo[2.2.2]octenones
114.46, 54.76, 47.55, 44.94, 43.18, 42.64, 35.92, 34.36, 15.35.
HRMS (EI): found 202.1361 (M+); calcd for C14H18O 202.1352
(M+).
2-Acetonyl-2-methyl-7-vinyl-tricyclo[3.3.0.04,6]octa-3-
one (40). A solution of 30 (0.075 g, 0.34 mmol) in degassed
acetone (110 mL, solvent as well as sensitizer) was irradiated
as described above. Acetone was removed under vacuum, and
the residue was chromatographed. Elution with petroleum
ether/ethyl acetate (98:2) first gave some unreacted starting
material (0.011 g, 15%). Further elution with petroleum ether/
ethyl acetate (97:3) furnished the product 40 (0.03 g, 40%) as
a colorless liquid: IR (neat) νmax 1717 cm-1; 1H NMR (600 MHz,
CDCl3) δ 5.83-5.77 (m, 1H), 5.01 (d, J ) 16.8 Hz, 1H), 4.96
(d, J ) 10.8 Hz, 1H), 2.99 (m, 1H), 2.66 (m, 1H), 2.52 (part of
AB system, JAB ) 15.6 Hz, 1H), 2.39 (part of AB system, JAB
) 15.6 Hz, 1H), 2.33 (m, 1H), 2.12 (s, 3H), 2.05 (m, 1H), 1.88
(m, 1H), 1.85-1.78 (m, 2H), and 0.95 (s, 3H); 13C NMR (150
MHz, CDCl3) δ 217.35, 206.40, 140.97, 114.26, 54.15, 50.91,
46.44, 42.94, 42.46, 36.20, 35.89, 34.38, 32.04, 15.04. HRMS
(ESI): found 219.1371 (M+ + H); calcd for C14H19O2 219.1380
(M+ + H).
2-Allyl-2,5-dimethyl-7-vinyl-tricyclo[3.3.0.04,6]octa-3-
one (38). A solution of 26 (0.080 g, 0.37 mmol) in degassed
acetone (110 mL, solvent as well as sensitizer) was irradiated
as described above. Removal of solvent followed by chroma-
tography [petroleum ether/ethyl acetate (99:1)] first gave some
unreacted starting material (0.009 g, 12%). Further elution
with petroleum ether/ethyl acetate (98:2) afforded the product
38 (0.04 g, 50%) as a colorless liquid: IR (neat) νmax 1718 cm-1
;
1H NMR (400 MHz, CDCl3) δ 5.86-5.68 (m, 2H), 5.17-4.93
(m, 4H), 2.40-2.33 (m partially merged with d, 1H), 2.30 (d,
J ) 6.1 Hz, 1H), 2.16 (m merged with d, J ) 7.3 Hz, 2H), 1.96
(d, J ) 9.7 Hz, 1H), 1.90-1.76 (m, 2H), 1.50 (s merged with
m, total 4H), 0.82 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 218.90,
140.10, 133.47, 118.82, 115.60, 56.21, 52.94, 45.24, 44.98,
44.94, 43.08, 41.63, 38.68, 18.92, 16.73. HRMS (EI): found
216.1507 (M+); calcd for C15H20O 216.1509 (M+).
2,2-Dimethyl-7-vinyl-tricyclo[3.3.0.04,6]octa-3-one (39).
A solution of 27 (0.070 g, 0.39 mmol) in degassed acetone (110
mL, solvent as well as sensitizer) was irradiated as described
above (1.25 h). Removal of solvent followed by chromatography
[petroleum ether/ethyl acetate (99:1)] first gave some unre-
acted starting material (0.01 g, 15%). Further elution with
petroleum ether/ethyl acetate (98:2) gave the photoproduct 39
Acknowledgment. We are grateful to Department
of Science and Technology, New Delhi, for continuing
financial support. We also thank SAIF, IIT Bombay for
the spectral facility and Prof. A. Srikrishna for some of
the NMR spectra. One of us (S.R.I.) is thankful to CSIR,
New Delhi, for a senior research fellowship.
(0.024 g, 35%) as a colorless liquid: IR (neat) νmax 1724 cm-1
;
Supporting Information Available: General procedure
1H NMR (400 MHz, CDCl3) δ 5.8 (m, 1H), 5.0 (d, J ) 17.2 Hz,
1H), 4.9 (d, J ) 10 Hz, 1H), 2.7 (m, 1H), 2.44 (superimposed
dd, J1 ) J2 ) 5.6 Hz, 1H), 2.35 (m, 1H), 2.05 (m, 1H), 1.9 (m,
1H), 1.85-1.70 (m, 2H), 1.09 (s, 3H), 0.9 (s, 3H); 13C NMR (100
MHz, CDCl3) δ 219.33, 141.34, 114.33, 51.62, 50.46, 42.81,
35.90, 35.59, 34.32, 28.73, 17.38. HRMS (ESI): found 177.1281
[M+ + H]; calcd for C12H17O 177.1279 [M+ + H].
for the preparation of silver nitrate-impregnated silica gel, 13
C
NMR spectra of compounds 12a-c, 13a-c, 15-17, 19, 20, 22,
24-28, 30-40, 1H NMR spectra of compounds 18, 21, 23, and
crystallographic data for compound 35. This material is
available free of charge via the Internet at http://pubs.acs.org.
JO048320E
J. Org. Chem, Vol. 70, No. 3, 2005 981