Molecular complexity from aromatics: A novel, stereoselective route to tricyclo[5.2.2.01,5]undecenones, tricyclo[6.2.2.01,6] dodecenones, and [n.3.3]propellanes

Article abstract of DOI:10.1021/jo702168s

(Chemical Equation Presented) A general stereoselective route to functionalized and substituted tricyclo [5.2.2.0^1,5]undecenones, tricyclo-[6.2.2.0^1,6]dodecenones, and [3.3.3]- and [4.3.3]propellanes from simple aromatic precursors is reported. The methodology involves generation and cycloaddition of annulated cyclohexa-2,4-dienones with various acrylates followed by manipulation of the resulting tricyclic adducts, leading to functionalized tricyclo-[5.2.2.0^1,5]undecenones and tricyclo[6.2.2.0^1,6]dodecenones endowed with a β,γ-enone chromophore. Photochemical reaction of the tricyclic chromophoric systems followed by reductive cleavage provided an efficient entry into propellanes.

Full text of DOI:10.1021/jo702168s

Molecular Complexity from Aromatics: A Novel, Stereoselective
Route to Tricyclo[5.2.2.01,5]undecenones,
Tricyclo[6.2.2.01,6]Dodecenones, and [n.3.3]Propellanes
Vishwakarma Singh,*,† Pramod K. Sahu,† Raj Bahadur Singh,† and Shaikh M. Mobin‡
Department of Chemistry and National Single Crystal X-ray Diffraction Facility,
Indian Institute of Technology, Bombay, Mumbai 400 076, India
Vks@chem.iitb.ac.in
ReceiVed October 6, 2007
A general stereoselective route to functionalized and substituted tricyclo [5.2.2.01,5]undecenones, tricyclo-
[6.2.2.01,6]dodecenones, and [3.3.3]- and [4.3.3]propellanes from simple aromatic precursors is reported.
The methodology involves generation and cycloaddition of annulated cyclohexa-2,4-dienones with various
acrylates followed by manipulation of the resulting tricyclic adducts, leading to functionalized tricyclo-
[5.2.2.01,5]undecenones and tricyclo[6.2.2.01,6]dodecenones endowed with a â,γ-enone chromophore.
Photochemical reaction of the tricyclic chromophoric systems followed by reductive cleavage provided
an efficient entry into propellanes.
Introduction
Propellanes, a unique class of organic compounds having
three rings conjoined together across a common C-C bond,
have fascinated chemists for a long time presumably because
of their unusual molecular structure, reactivity, and properties.1
Among various types, [3.3.3]propellanes belonging to the
polyquinane family have attracted greater attention due to
isolation2 of the sesquiterpenoid natural product modhephene
1 (Figure 1) that contains a [3.3.3]propellane framework in its
molecular architecture. Recently, more functionalized derivatives
of modhephene such as 1b,c were isolated from Leontopodium
alpinum and Psiadia anchusifolia.3 Most recently, natural
products containing a [3.3.3]propellane in their framework have
also been isolated from Taxus canadensis.4 Polyquinanes, in
FIGURE 1. [3.3.3]- and [4.3.3]propellanes, tricyclic compound,
sesquiterpene containing tricyclo[5.2.2.01,6]dodecane system, and aro-
matic precursor.
* Corresponding author. Fax: 091-22-25723480.
† Department of Chemistry.
general, have elicited intense interest for a long time due to
their molecular architecture and biological properties.5-7 Several
elegant methods leading to various types of polyquinanes have
been developed.5-11 However, the methods leading to [3.3.3]-
propellanes are only a few as compared to other polyquinanes,
and the search for the development of a new and efficient
methodology is continuing.8,12-14
‡ National Single Crystal X-ray Diffraction Facility.
(1) (a) Levin, M. D.; Kaszynski, P.; Michl, J. Chem. ReV. 2000, 100,
169-234. (b) Ginsberg, D. Propellanes: Structure and Reactions; Verlag
Chemie: Weinheim, Germany, 1975 and references therein.
(2) (a) Zalkow, L. H.; Harris, R. N.; Van Derveer, D. J. Chem. Soc.,
Chem. Commun. 1978, 420-421 (b) Zalkow, L. H.; Harris, R. N.; Burke,
N. I. J. Nat. Prod. 1979, 42, 96-102. (c) Bohlmann, F.; Zdero, C.;
Bohlmann, R.; King, R. M.; Robinson, H. Phytochemistry 1980, 19, 579-
582.
(3) (a) Gauvin, A.; Susperregui, J.; Barth, P.; Louis, R.; Deleris, G.;
Smadja, J. Phytochemistry 2004, 65, 897-901. (b) Comey, N.; Grey, A.
I.; Hook, I. L.; James, P.; Sheridan, H. Phytochemistry 1999, 50, 1057-
1060.
(4) (a) Shi, Q. W.; Sauriol, F.; Mamer O.; Zamir, L. O. Chem. Commun.
2003, 68-69. (b) Shi, Q. W.; Sauriol, F.; Lesimple, A.; Zamir, L. O. Chem.
Commun. 2004, 544-545.
10.1021/jo702168s CCC: $37.00 © 2007 American Chemical Society
Published on Web 11/30/2007
J. Org. Chem. 2007, 72, 10155-10165
10155

Singh et al.
SCHEME 1
FIGURE 2. Cyclohexa-2,4-dienones and annulated cyclohexadiene.
[4.3.3]Propellanes have not elicited much attention presum-
ably because of a lack of natural products containing this
framework. Although, recently, [4.3.3]propellanes of type 2 have
generated interest by virtue of their olfactory properties.15 For
example, propellane 2 and its congeners have been found to
possess woody amber odors.15a Therefore, it is not surprising
that there are only a few methods for their synthesis and that
these involve carbenium ion rearrangements.15a-c Recently,
Mattay and co-workers developed a route to [4.3.3]propellane
employing a PET reaction.15d
undecane framework is present in complex natural products such
as eremolactones17a and antheridic acid.17b Similarly, the
compounds of type 3b having a tricyclo[5.2.2.01,6]dodecane
framework are also important precursors for sesquiter-
penoids,18 and this framework is present in diterpenoid secoa-
tisanes, which were recently isolated from Chinese mangrove
Excoecaria agallocha L.19a,b The sesquiterpene 4, isolated from
alga Caloglossa leprieuri, also contains this framework.19c There
are only a few methods for the synthesis of tricyclic compounds
of type 3a,b, and existing methods have limitations with regard
to the introduction of functionality and substituents in the
tricyclic framework.
In view of the above findings and our continuing interest in
the development of new methodology via cycloaddition of
cyclohexadienones,20 we considered developing a general route
to functionalized tricyclic compounds of type 3a,b, [3.3.3]- and
[4.3.3]propellanes. We contemplated that functionalized tricyclic
compounds 3 may be easily derived from the keto-epoxide 7
via manipulation of the oxirane ring. The key tricyclic precursor
7 was thought to be assembled from the aromatic precursor 5
via its transformation to cycohexa-2,4-dienone 6 and cycload-
dition with an appropriate 2π-partner (Scheme 1). Further, it
was thought that a photochemical 1,2-acyl shift in tricyclic
compound 3 would lead to the tetracyclic compound 8 that upon
reductive cleavage of the cyclopropane ring would give pro-
pellanes of type 9 (Scheme 1).
Tricycloundecenones of type 3a are versatile synthetic
intermediates,11b,16 and this type of unusual tricyclo[5.2.2.01,5]-
(5) (a) Mehta G.; Srikrishna, A. Chem. ReV. 1997, 97, 671-720 and
references therein. (b) Little, R. D. Chem. ReV. 1996, 96, 93-114. (c) Gupta,
A. K.; Fu, X.; Snyder, J. P.; Cook, J. M. Tetrahedron 1991, 47, 3665-
3710. (d) Paquette, L. A.; Doherty, A. M. Polyquinane Chemistry; Springer-
Verlag: Berlin, 1987 and references therein.
(6) (a) Austin, K. A. B.; Banwell, M. G.; Harfoot, G. J.; Willis, A. C.
Tetrahedron Lett. 2006, 47, 7381-84. (b) Wu, Y. T.; Vidovic, D.; Magull,
J.; De Meijere, A. Eur. J. Org. Chem. 2005, 8, 1625-1636. (c) Tripp, J.
C.; Schiesser, C. H.; Curran, D. P. J. Am. Chem. Soc. 2005, 127, 5518-
5527. (d) Banwell, M. G.; Edward, A. J.; Harfoot, G. J.; Jolliffe, K. A.
Tetrahedron 2004, 60, 535-547. (e) Maiti, A.; Gerken, J. B.; Masjedizadeh,
M. R.; Minieux, Y. S.; Little, R. D. J. Org. Chem. 2004, 69, 8574-8582.
(f) Davis, C. E.; Duffy, B. C.; Coates, R. M. J. Org. Chem. 2003, 68, 6935-
6943. (g) Dhimane, A.; Aissa, C.; Malacria, M. Angew. Chem., Int. Ed.
2003, 41, 3284-3287. (h) Srikrishna, A.; Dethe, D. H. Org. Lett. 2003, 5,
2295-2298. (i) Mehta, G.; Murthy, A. S. K. Tetrahedron Lett. 2003, 44,
5243-5246. (j) Wang, J.-C.; Krische, M. J. Angew. Chem., Int. Ed. 2003,
41, 5855-5857.
(7) (a) Banwell, M. G.; Edward, A. J.; Harfoot, G. J.; Jolliffe, K. A. J.
Chem. Soc., Perkin Trans. 1 2002, 2439-2441. (b) Paquette, L. A.; Geng,
F. J. Am. Chem. Soc. 2002, 124, 9199-9203. (c) Russu, W. A.; Villalon,
V. P.; Wang, V. R.; Miranda, J. A.; Little, R. D. Tetrahedron Lett. 2002,
43, 8459-8461. (d) Harrowven, D. C.; Lucas, M. C.; Howes, P. D.
Tetrahedron 2001, 57, 9157-9162. (e) Harrowven, D. C.; Lucas, M. C.;
Howes, P. D. Tetrahedron Lett. 2000, 41, 8985-8987. (f) Ader, T. A.;
Champey, C. A.; Kuznetsova, L. V.; Li, T.; Lim, Y. H.; Rucando, D.;
Sieburth, S. M. Org. Lett. 2001, 3, 2165-2167. (g) Varma, S. K.; Eleisher,
E. B.; Moore, H. W. J. Org. Chem. 2000, 65, 8564-8573. (h) Rawal, V.
H.; Reddy, J. Org. Lett. 2000, 2, 2711-2712.
(8) De Boeck, B.; Harrington-Frost, N. M.; Pattenden, G. Org. Biomol.
Chem. 2005, 3, 340-347.
(9) Curran, D. P.; Shen, W. Tetrahedron 1993, 49, 755-770 and
references therein.
(10) Wender, P. A.; Dore, T. M. In CRC Handbook of Organic
Photochemistry and Photobiology; Horspool, W. M., Song, P. S., Eds.; CRC
Press: Boca Raton, FL, 1995; pp 280-300.
(11) (a) Pattenden, G.; Teague, H. J. Tetrahedron 1987, 43, 5637-5652.
(b) Mehta, G. Subrahmanyam, D. J. Chem. Soc., Perkin Trans. 1 1991,
395-401. (c) Zhao, S.; Mehta, G.; Helquist, P. Tetrahedron Lett. 1991,
32, 5753-5756. (d) Lange, G. L.; Gottardo, C. J. Org. Chem. 1995, 60,
2183-2187.
(15) (a) Frater, G.; Helmlinger, D.; Kraft, P. HelV. Chim. Acta 2006, 86,
678-696. (b) Marcos, I. S.; Martinez, B.; Sexmero, M. J.; Diez, D.; Basabe,
P.; Urones, J. G. Synthesis 2006, 3865-3873. (c) Helmlinger, D.; Frater,
G. Tetrahedron Lett. 1992, 33, 6119-6122. (d) Tzvetkov, N. T.; Neumann,
B.; Stammler, H.-G.; Mattay, J. Eur. J. Org. Chem. 2006, 351-370.
(16) (a) John Biju, P.; Laxmisha, M. S.; Subbarao, G. S. R. J. Chem.
Soc., Perkin Trans. 1 2000, 4512-4519. (b) Janaki, S. N.; Subba Rao, G.
S. R. J. Chem. Soc., Perkin Trans. 1 1997, 195-200. (c) Hagiwara, H.;
Uda, H. J. Chem. Soc., Perkin Trans. 1 1986, 629-632. (d) Weber, W.;
Spitzner, D.; Kraus, W. J. Chem. Soc., Chem. Commun. 1980, 1212-1213.
(e) Yamada, Y.; Nagaoka, H.; Kimura, M. Synlett 1977, 581-582.
(17) (a) ApSimon, J. The Total Synthesis of Natural Products; John Wiley
and Sons: New York, 1992; Vol. 8, p 222. (b) King, G. R.; Mander, L. N.;
Monck, N. J. T.; Morris, J. C.; Zhang, H. J. Am. Chem. Soc. 1997, 119,
3828-3829. (c) Corey, E. J.; Myers, A. G.; Takahashi, N.; Yamane, H.;
Schraudolf, H. Tetrahedron Lett. 1986, 27, 5083-5086.
(12) (a) Dvorak, C. A.; Rawal, V. H. J. Chem. Soc., Chem. Commun.
1997, 2381-2382. (b) Dvorak, C. A.; Dufour, C.; Iwasa, S.; Rawal, V. H.
J. Org. Chem. 1998, 63, 5302-5303. (c) Lee, H.-Y.; Kim, D.; Kim, S.
Bull. Korean Chem. Soc. 1999, 20, 269-270.
(13) (a) Laxmisha, M. S.; Subba Rao, G. S. R. Tetrahedron Lett. 2000,
41, 3759-3761. (b) Bertolini, T. M.; Nguyen, Q. H.; Harvey, D. F. J. Org.
Chem. 2002, 67, 8675-8678. (c) Tzvetkov, N.; Schmidtmann, M.; Muller,
A.; Mattay, J. Tetrahedron Lett. 2003, 44, 5979-5982.
(14) (a) Uyehara, T.; Murayama, T.; Sakai, K.; Ueno, M.; Sato, T.
Tetrahedron Lett. 1996, 37, 7295-7298. (b) Fitjer, L.; Majewski, M.;
Monzo-Oltra, H. Tetrahedron 1995, 51, 8835-8852. (c) Fitjer, L.; Rissom,
B.; Kanschik, A.; Egert, E. Tetrahedron 1994, 50, 10879-10892. (d) Sha,
C.-K.; Jean, T.-S.; Wang, D.-C. Tetrahedron Lett. 1990, 31, 3745-3748.
(18) (a) Sathya Shankar, P.; Subba Rao, G. S. R. J. Chem. Soc., Perkin
Trans. 1 1998, 539-548. (b) Bartoletti, A.; Barettoni, M.; Catteruccia, F.;
De Chiara, G.; Marini Bettolo, R.; Mastrangeli, C.; Scarpelli, R.; Tozzi,
C.; Lamba, D. Gazz. Chim. Ital. 1996, 126, 223-226. (c) Hagiwara, H.;
Okamoto, T.; Harada, N.; Hisashi, U. Tetrahedron 1995, 51, 9891-9898.
(19) (a) Wang, J. D.; Li, Z. Y.; Xiang, W. S.; Guo, Y.-W. HelV. Chim.
Acta 2006, 89, 1367-1372. (b) Wang, J. D.; Li, Z. Y.; Guo, Y.-W. HelV.
Chim. Acta 2005, 88, 979-985. (c) Xu, X. H.; Chang, J.; Lu, J. H.; Yao,
G. M.; Li, Y. M. Chin. Chem. Lett. 2002, 13, 953-954.
(20) (a) Singh, V. Acc. Chem. Res. 1999, 32, 324-333. (b) Singh, V.;
Pal, S.; Mobin, S. M. J. Org. Chem. 2006, 71, 3014-3025.
10156 J. Org. Chem., Vol. 72, No. 26, 2007

Molecular Complexity from Aromatics
SCHEME 2
SCHEME 3
Thus, the IR spectrum of 14a showed a characteristic
1
absorption band at 1731 cm-1 for the carbonyl group. The H
NMR (300 MHz, CDCl3) spectrum displayed a diagnostic signal
at δ 5.84 (d with str, J ) 6 Hz, 1H) for one olefinic proton and
a highly characteristic AB pattern for the oxymethylene protons
of the oxirane ring at δ 3.12 (part of an AB system, JAB ) 6
Hz, 1H) and 2.87 (part of an AB system, JAB ) 6 Hz, 1H). In
addition, signals were observed at δ 4.15 (q with str, J ) 7.2
Hz, 2H, -OCH2 of the ester group), and the proton at the
bridgehead exhibited a signal at δ 3.65 (dd, J1 ) 6 Hz, J2 )
2.4 Hz, 1H). Further resonances were shown at δ 3.06 (dd of
d, J1 ) 9.9 Hz, J2 ) 4.8 Hz, J3 ) 2.4 Hz, 1H), 2.56-2.40 (m,
2H), 2.32 (dd, J1 ) 12.9 Hz, J2 ) 10.2 Hz, 1H), 2.0-1.86
(overlapped m, 2H), 1.80-1.50 (complex m, 3H), 1.26 (t, J )
7.2 Hz, CH3).
The structure of the adduct was also supported by the derived
13C NMR spectral data that exhibited characteristic signals at δ
204.9 and 172.5 for the carbonyl groups present in the ethano
bridge and ester group, respectively. It also displayed signals
at δ 156.3 and 114.1 for the olefinic carbons. It further exhibited
signals at δ 61.1, 58.4, 51.0, 50.0, 48.6, 41.3, 31.3, 30.1, 29.7,
26.5, and 14.0 for the other carbons, thus accounting for all the
carbons of the adduct. The stereochemistry of the oxirane ring
was suggested on the basis of a general tendency of cyclohexa-
dienones during their cycloaddition20 and comparison with other
adducts whose structure was determined by X-ray single-crystal
analysis (vide infra).
Similar oxidation of o-hydroxymethyl indanol 5a in the
presence of methyl methacrylate, however, gave the correspond-
ing adduct 15a in low yield (22%) after a long reaction time.
Therefore, we considered the possibility of isolation of the spiro-
epoxycyclohexa-2,4-dienone 6a and attempted its cycloaddition
with methyl methacrylate at higher temperatures, although we
were aware that cyclohexa-2,4-dienones are generally unstable,
readily dimerize, and disintegrate upon heating. Hence, 5a was
oxidized with NaIO4 in aqueous Acetonitrile, and the product
mixture was chromatographed to give the cyclohexadienone 6a
in good yield (63%) as a yellow solid. Subsequent heating of
6a with methyl methacrylate in o-dichlorobenzene in a sealed
tube furnished the adduct 15a in good yield (50%) (Scheme 3).
To extend the scope of methodology, we also explored the
oxidation of o-hydroxymethyl indanols 13, 17, and 19 and the
cycloaddition of the resulting cyclohexadienones with acrylates.
6-Hydroxymethyl-5-indanol (16) and bis-hydroxymethylated 17
were prepared by hydroxymethylation of 5-indanol 12a.24a
Reduction of 16 with a Ni-Al alloy gave the known compound
1824b that upon hydroxymethylation readily gave the precursor
19 (Scheme 4).
We wish to report herein a novel and efficient synthesis of
tricyclic compounds of type 3a,b, and 7a,b endowed with a
â,γ-enone chromophore from simple aromatic precursors of type
5a,b and their photochemical transformation leading to a
stereoselective route to [3.3.3]- and [4.3.3]propellanes.
Results and Discussion
Synthesis of Tricyclic Compounds of Type 3 and 7 and
Their Congeners. While the compounds of type 3a,b having
functional groups in both the ethano bridges are not known,
their simpler analogues are generally prepared by Diels-Alder
reaction of annulated dienes of type 10 with ketene equivalents.21
However, the preparation of the diene of type 10 via Birch
reduction followed by isomerization is cumbersome and often
gives a mixture of adducts. Moreover, this method does not
permit introduction of functionality in the other ethano bridge
of the bicyclo[2.2.2]octane framework. Conceptually, the tri-
cyclic compounds 3a,b may also be directly obtained through
Diels-Alder reaction of cyclohexadienone 11a,b (Figure 2).
However, cyclohexa-2,4-dienones of type 11 are keto-tautomers
of the corresponding phenols and not easily accessible.
Therefore, we considered to develop an indirect, general, and
stereoselective route to the tricyclic compounds of type 3a,b
via cycloaddition of annulated spiroepoxy cyclohexadienones
of type 6a,b, which were thought to be generated by the
oxidation of annulated o-hydroxymethyl phenols 5a,b.
Initially, we focused our attention toward the synthesis of
tricycloundecenones 7a, and hence, the hydroxymethyl indanol
5a was required. Thus, 5-indanol 12a was brominated, and the
resulting bromo compound was hydroxymethylated to give 13.22
The reduction of 13 with Raney Ni by a modification of the
earlier method22 gave the 4-hydroxymethyl-5-indanol 5a. Oxi-
dation of 5a with aqueous sodium metaperiodate23 in the
presence of ethyl acrylate according to a method developed in
our laboratory23c furnished adduct 14a in good yield, as a result
of a regio- and stereoselective cycloaddition of the in situ
generated spiroepoxycyclohexa-2,4-dienone 6a (Scheme 2). The
structure of adduct 14a was deduced from its 1H NMR and 13
C
NMR spectral data, COSY spectrum, and comparison.
(21) (a) Selvakumar, N.; Janaki, S. N.; Pramod, K. Subbarao, G. S. R.
J. Chem. Soc., Perkin Trans. 1 1995, 839-846 and references therein. (b)
Hariprakasha, H. K.; Subbarao, G. S. R. Tetrahedron Lett. 1997, 38, 5343-
5346. (c) Mehta, G.; Subrahmanyam, D. J. Chem. Soc., Chem. Commun.
1985, 768-769.
(22) Andreetti, G. D.; Bohmer, V.; Jordan, G. J.; Tabayabai, M.;
Ugozzoli, F.; Vogt, W.; Wolff, A. J. Org. Chem. 1993, 58, 4023-4032.
(23) (a) Adler, E.; Brasen, S.; Miyake, H. Acta Chem. Scand. 1971, 25,
2055-2069. (b) Becker, H. D.; Bremholt, T.; Adler, E. Tetrahedron Lett.
1972, 13, 4205-4208. (c) Singh, V.; Prathap, S. Synlett 1994, 542-545.
(24) (a) Singh, V.; Sahu, P. K.; Mobin, S. M. Tetrahedron 2004, 60,
9925-9930. (b) Dean, R. E.; Midgley, A.; White, E. N.; Mcneil, D. J.
Chem. Soc. 1961, 2773-2779.
J. Org. Chem, Vol. 72, No. 26, 2007 10157

Singh et al.
SCHEME 4
SCHEME 7
SCHEME 5
Synthesis of Tricyclododecenones of Types 3b and 7b. To
prepare the tricyclic compounds of type 3b and 7b, the
hydroxymethyltetrahydronaphthol 5b was required. This com-
pound was prepared earlier by hydroxymethylation of 5,6,7,8-
tetrahydro-2-naphthol 12b in low yield.22 Gesson and co-workers
reported the reaction of 12b with formaldehyde in the presence
of phenyl boronic acid and subsequent oxidation of the resulting
dioxaborin, which gave 5b and the regioisomer 5c, the former
being a major product.25 We employed a slightly modified
hydroxymethylation method. Thus, tetrahydronaphthol 12b was
treated with HCHO and aqueous NaOH, and the reaction was
quenched with ammonium chloride (instead of acetic acid).
Usual workup and chromatography of the product gave an
inseparable mixture of 5b and 5c (40%) having the desired
SCHEME 6
1
regioisomer 5b as a major component (5b/5c; 3:1, H NMR)
and bis-hydroxymethylated product 5d (15%) (Scheme 7). It is
interesting to note that hydroxymethylation of 12b gave the
desired regioisomer 5b (major product) as a result of the reaction
at the more hindered carbon, which is in contrast to the behavior
of indanol 12a (vide supra). Such a difference in the regiose-
lectivity has also been observed in other electrophilic reactions
of indanol and tetrahydronaphthol.26
To prepare the adduct 14b, we examined the cycloaddition
of isolated cyclohexadienone 6b. Hence, the mixture of 5b,c
was oxidized with NaIO4 following our earlier procedure, which
gave the known spiroepoxycyclohexa-2,4-dienone 6b25 in 66%
yield as a major product (Scheme 7). Heating a solution of
cyclohexadienone 6b and ethyl acrylate in o-dichlorobenzene
in a sealed tube followed by chromatography gave the adduct
14b in excellent yield (72%) (Scheme 7). Similarly, the reaction
of 6b with methyl methacrylate also furnished the adduct 15b
in good yield (Scheme 7).
The presence of a contiguous keto-epoxide functionality in
adducts provided the opportunity for further manipulation. Thus,
the adduct 14a was subjected to reduction with zinc-NH4Cl in
aqueous methanol at ambient temperature, which gave the
â-hydroxyketone 28 (as a mixture of syn/anti isomers, 1H NMR)
in excellent yield (90%). Subsequent oxidation of the keto-
alcohol 28 with Jones’ reagent followed by decarboxylation
furnished the desired tricyclic keto-ester 29 (Scheme 8).
Similarly, the adduct 23 was also transformed into the keto-
ester 31. Reduction of the adduct 15a under the aforementioned
Thus, 6-bromo-4-hydroxymethyl-5-indanol 13 was oxidized
with NaIO4 in aqueous acetonitrile containing ethyl acrylate,
which furnished the adduct 22 in excellent yield (80%) as a
result of in situ generation of cyclohexadienone 20 and
cycloaddition (Scheme 5). Similar oxidation of 19 with sodium
m-periodate in the presence of ethyl acrylate also gave the
tricyclic adduct 23 in excellent yield (73%). In situ generation
of 20 and 21 and their reaction with methyl methacrylate
also gave the corresponding adducts 24 and 25, respectively
(Scheme 5). The cycloaddition of 21 with methyl methacrylate
was relatively less efficient as compared to the cyclohexa-
2,4-dienone 20 containing an electron withdrawing group
at C2.
The oxidation of bis-hydroxymethyl indanol 17 provided an
interesting situation, as it generated two types of cyclohexadi-
enones (26a and 26b), which may undergo cycloaddition. Thus,
treatment of 17 with aqueous NaIO4 in the presence of ethyl
acrylate gave adducts 27a and 27b in almost equal amounts,
whose structures were deduced from their spectral data (Scheme
6). The structure of adduct 27a was also confirmed through
single-crystal structure determination (see Supporting Informa-
tion).
(25) Gesson, J.-P.; Mondon, M.; Pokrovska, N. Synlett 1997, 1395-
1396.
(26) (a) Nilsson, J. L. G.; Selander, H.; Sievertsson, H.; Scanberg, I.;
Svenssom, K. G. Acta Chem. Scand. 1971, 25, 94-100. (b) Touzeau, F.;
Arrault, A.; Guillaumet, G.; Scalbert, E.; Pfeiffer, B.; Rettori, M. C.; Renard,
P.; Merour, J. Y. J. Med. Chem. 2003, 46, 1962-1979.
10158 J. Org. Chem., Vol. 72, No. 26, 2007

Molecular Complexity from Aromatics
SCHEME 8
SCHEME 9
SCHEME 10
conditions gave the keto-alcohol 33 as a major product along
with the ketone 32 as a minor product arising as a result of
deoxygenation of the oxirane ring. Similarly, the keto-epoxides
14b and 15b were also transformed into the tricyclic keto-esters
37 and 40, respectively.
It may be mentioned that the tricyclic compounds of type
14, 15, 22-25, and 28-40 having a â,γ-enone chromophore
are not so readily accessible otherwise, and the present
methodology provides an efficient route to such types of systems
from simple and readily available aromatic precursors.
Photochemical Reaction of Chromophoric Systems 29, 31,
34, 37, and 40 and Cleavage of the Cyclopropane Ring:
Synthesis of [3.3.3]- and [4.3.3]Propellanes. After having
developed syntheses of the tricyclic compounds, we first
explored the photochemical reaction of 29, 31, and 34 upon
sensitized irradiation. Photochemical reactions of â,γ-enones
have generated interest for a long time,27 which has considerably
increased recently due to their synthetic potential.27-30 In
general, triplet sensitized irradiation leads to a 1,2-acyl shift or
oxa-di-π-methane rearrangement, whereas a 1,3-acyl shift is
observed upon direct excitation (1S). Demuth and co-workers
examined the oxa-di-π-methane reaction in several simple
bicyclo[2.2.2]octenones and demonstrated their synthetic ap-
plication.28 Subsequently, the photoreaction of more complex
â,γ-enone systems was reported.21c,28,29 Although these reactions
are quite characteristic of their excited states, the photochemical
reactions depend on the structure of the chromophoric system
and the functional groups in a subtle fashion.27,28b Keeping the
previous facts in mind, a solution of the tricyclic 29 (λmax: 222
and 296 nm) in acetone (solvent as well as sensitizer) was first
irradiated with a mercury vapor lamp (APP, 125 W) in a Pyrex
immersion well (λ > 290 nm). However, no significant reaction
was observed (Scheme 9).
The unreactivity of 29 under the aforementioned irradiation
conditions could be presumably due to the annulation of the
strained five-membered ring through the â-carbon of the â,γ-
ene moiety since other tricyclic systems in which the â,γ-ene
carbons are not part of such type of an annulation undergo a
photochemical 1,2-acyl shift in a facile manner under similar
experimental conditions.27,28b Therefore, a solution of 29 in
acetone was irradiated in a quartz immersion well (λ > 200
nm) for 1 h upon which a reasonably clean reaction was
observed (TLC). Removal of the solvent followed by chroma-
tography of the photolysate furnished the tetracyclic photoprod-
uct 41 having a [3.3.3]propellane framework, in good yield
(52%) as a result of a 1,2-acyl shift. The structure of the
photoproduct 41 was revealed through spectroscopic data and
comparison with spectral features of its precursor. Similar
irradiation of 31 and 34 also gave the corresponding 1,2-acyl
shift (or oxa-di-π-methane) products 42 and 43, respectively.
Interestingly, irradiation of 37 and 40 in a Pyrex immersion
well proceeded smoothly and gave the photoproducts 44 (77%)
and 45 (65%) having a [4.3.3]propellane framework, respec-
tively (Scheme 9). These observations further suggest that the
unusual behavior of tricyclic 29, 31, and 34 could be due to
the presence of a strained five-membered ring. Treatment of
the tetracyclic 41 and 43-45 with tributyltin hydride31 gave
propellanes 46 and 47-49, respectively, as a result of selective
cleavage of the peripheral cyclopropane bond (Scheme 10).
(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) Demuth, M.; Hisken, W. Angew. Chem., Int. Ed. Engl. 1985,
24, 973-975. (b) Demuth, M.; Schaffner, K. Angew. Chem., Int. Ed. Engl.
1982, 21, 820-836.
(29) Zimmerman, H. E.; Armesto, D. Chem. ReV. 1996, 96, 3065-3112
and references therein.
(30) (a) Armesto, D.; Ortiz, M. J.; Romano, S.; Agarrabeitia, A. R.;
Gallega, M. G.; Ramos, A. In CRC Handbook of Organic Photochemistry
and Photobiology; Horspool, W. M., Lenci, F., Eds.; CRC Press: Boca
Raton, FL, 2004; Ch. 95. (b) Singh, V. In CRC Handbook Organic
Photochemistry and Photobiology; Horspool, W. M., Lenci, F., Eds.; CRC
Press: Boca Raton, FL, 2004; Chs. 78 and 79.
(31) Enholm, E. J.; Jia, Z. J. J. Org. Chem. 1997, 62, 174-181.
J. Org. Chem, Vol. 72, No. 26, 2007 10159

Singh et al.
29.7, 26.5, 14.0. HRMS (m/z): found 263.1291 [M + H]+; calcd
for C15H19O4 263.1283 [M + H]+.
Conclusion
Methyl-11-oxo-8-methyl-10-spiroepoxytricyclo[5.2.2.01,5]undec-
5-en-8-carboxylate (15a). To a solution of 5a (1.0 g, 6.1 mmol)
and methyl methacrylate (5 mL, excess) in acetonitrile (30 mL)
was added an aqueous solution of sodium m-periodate (1.5 g, 7
mmol) dropwise at 0-5 °C. After stirring for ∼3 h at 0-5 °C, the
reaction mixture was stirred at ambient temperature for 72 h. The
organic layer was separated, and the aqueous layer was saturated
with sodium chloride and extracted with ethyl acetate (3 × 20 mL).
The combined organic layer was washed with brine and dried over
anhydrous sodium sulfate. The solvent was removed under reduced
pressure, and the residue was chromatographed on silica gel. Elution
with petroleum ether-ethyl acetate (90:10) gave the desired adduct
In summary, we have described a novel and stereoselective
route to functionalized tricycloundecenones, tricyclodode-
cenones, and their photochemical transformation to propellanes.
The methodology involves the synthesis of bicyclo[2.2.2]-
octenones annulated through one of the bridgeheads via cy-
cloaddition of annulated cyclohexa-2,4-dienones with various
acrylates and a photochemical 1,2-acyl shift as key features.
The methodology generates all the three rings of propellane in
a single stereoselective sequence. We have also presented an
efficient cycloaddition of annulated cyclohexa-2,4-dienones with
ethyl acrylate and its derivative to various tricyclic compounds
containing a â,γ-enone chromophore that are not readily
accessible otherwise. The present work also constitutes a nice
example of the generation of molecular complexity from simple
precursors, which is an important aspect of design and develop-
ment of new methodology.32,33
15a (0.352 g, 22%) as a colorless liquid. IR (neat) νmax: 1730 cm-1
.
1H NMR (400 MHz, CDCl3): δ 5.86 (m, 1H), 3.71(s, 3H), 3.46
(d, J ) 6.4 Hz, 1H), 3.16 (part of the AB system, JAB ) 6 Hz,
1H), 2.86 (part of the AB system, JAB ) 6 Hz, 1H), 2.40 (m, 2H),
2.32 (d, J ) 13.2 Hz, 1H), 1.93-1.90 (d merged with m, J ) 13.2
Hz, total 2H), 1.75-1.60 (m merged with signal due to H2O
present in CDCl3, 2H), 1.59-1.40 (m, 1H), 1.31 (s, 3H). 13C NMR
(100 MHz, CDCl3): δ 205.2, 176.0, 156.1, 115.9, 58.3, 56.1,
52.4, 50.9, 48.6, 48.0, 40.0, 29.9, 29.7, 26.5, 25.5. HRMS (m/z):
found 285.1033 [M + Na]+, calcd for C15H18O4Na 285.1020
[M + Na]+.
Experimental Section
4-Hydroxymethyl-5-indanol (5a). To a solution of 13 (22.0 g,
90 mmol) in methanol (100 mL) was added KOH (4.5 g, 80.3
mmol) and Raney nickel (20 g, excess), and the resulting mixture
was stirred under a hydrogen atmosphere. After completion of the
reaction (TLC, 14 h), the reaction mixture was filtered, and the
wet catalyst was washed with methanol (3 × 20 mL) cautiously.
Methanol was removed, and an aqueous solution of ammonium
chloride was added. It was extracted with ethyl acetate (4 × 50
mL). The combined organic extract was dried over anhydrous
sodium sulfate. Removal of solvent followed by chromatography
[petroleum ether-ethyl acetate (80:20)] furnished the known com-
2,3-Dihydrospiro[indene-4,2′-oxiran]-5(1H)-one (6a). To a
solution of 5a (1.0 g, 6.1 mmol) in acetonitrile (15 mL) was added
a saturated aqueous solution of sodium m-periodate (2.6 g, 12 mmol)
dropwise (20 min) at 0-5 °C. The reaction mixture was saturated
with sodium chloride, the organic layer was separated, and the
aqueous layer was extracted with ethyl acetate (3 × 20 mL). The
combined organic extract was dried over anhydrous sodium sulfate.
The solvent was removed under reduced pressure, and the residue
was chromatographed on silica gel. Elution with petroleum ether-
ethyl acetate (90:10) gave the desired cyclohexadienone 6a (0.623
1
pound 5a in good yield (8.4 g, 57%), mp 109-110 °C. H NMR
(400 MHz, CDCl3): δ 7.44 (br s, 1H), 7.03 (d, J ) 7.8 Hz, 1H),
6.67 (d, J ) 7.8 Hz, 1H), 4.89 (br s, 2H), 2.84-2.76 (m, 4H),
2.02-2.07 (m, 2H). These spectral features are in good agreement
with the reported values.22 13C NMR (100 MHz, CDCl3): δ 154.1,
142.6, 135.6, 124.1, 120.4, 114.2, 61.0, 32.0, 30.8, 25.3.
g, 63%) which solidified in a refrigerator, mp 66-68 °C. IR (KBr)
1
ν
max: 1667, 1630 cm-1. H NMR (300 MHz, CDCl3): δ 7.16 (d,
J ) 9.9 Hz, 1H), 6.05 (d, J ) 9.9 Hz, 1H), 3.27 (s, 2H), 2.68-
2.60 (m, 2H), 2.60-2.51 (m, 1H), 2.40-2.28 (m, 1H), 2.11-2.01
(m, 2H). 13C NMR (75 MHz, CDCl3): δ 197.1, 147.8, 141.2, 139.4,
124.4, 58.6, 57.2, 33.9, 30.9, 23.0. HRMS (m/z): found 163.0767
[M + H]+; calcd for C10H11O2 163.0759 [M + H]+.
Ethyl-11-oxo-10-spiroepoxytricyclo[5.2.2.01,5]undec-5-en-8-
carboxylate (14a). To a solution of 5a (3.0 g, 18.3 mmol) in
acetonitrile (90 mL) was added ethyl acrylate (15 mL, excess), and
the reaction mixture was cooled in an ice bath (0-5 °C). A saturated
aqueous solution of sodium m-periodate (7.7 g, 36 mmol) was added
dropwise to the reaction mixture and stirred for 3 h. The reaction
mixture was brought to ambient temperature and stirred overnight.
The organic layer was separated, and the aqueous layer was
saturated with sodium chloride and extracted with ethyl acetate (3
× 40 mL). The combined organic layer was washed with brine
and dried over anhydrous sodium sulfate. The solvent was removed
under reduced pressure, and the residue was chromatographed on
silica gel. Elution with petroleum ether-ethyl acetate (95:5) gave
Preaparation of 15a by Reaction of Isolated Cyclohexa-2,4-
dienone 6a and Methyl Methacrylate. A mixture of cyclohexa-
dienone 6a (0.5 g, 3 mmol) and methyl methacrylate (3 mL) in
o-dichlorobenzene (3 mL) was heated in a sealed tube at 80 °C for
8 h. The reaction mixture was charged on a column of silica gel
and chromatographed. Elution with petroleum ether-ethyl acetate
(90:10) gave the adduct 15a (0.400 g, 50%), which was found to
be identical to the sample obtained by the method described
previously.
6-Methyl-5-indanol (18). To a stirred solution of 6-hydroxym-
ethyl-5-indanol 16 (1.0 g, 6.1 mmol) in aqueous KOH (3.7 M, 20
mL), a Raney nickel alloy (1.2 g, 30 mmol) was added in portions
at 0-10 °C. The reaction mixture was stirred under hydrogen
atmosphere. After completion of the reaction (TLC, 24 h), the
reaction mixture was decanted into a beaker containing crushed
ice and concd hydrochloric acid (6.4 mL). The residual wet Raney
nickel was washed with aqueous KOH solution (5 M, 3 × 10 mL),
and the combined acidic aqueous layer was extracted with diethyl
ether (3 × 30 mL) and washed with brine (1 × 20 mL). The organic
layer was dried over anhydrous sodium sulfate. Removal of solvent
furnished 18, which was recrystallized from petroleum ether (0.9
g, quantitative), mp 83-84 °C (lit. mp 79-80.5 and 83-84 °C24b).
the desired adduct 14a (2.44 g, 51%) as a colorless liquid. IR (neat)
1
ν
max: 1731 cm-1 (br). H NMR (300 MHz, CDCl3): δ 5.84 (d
with str, J ) 6 Hz, 1H, olefinic H), 4.15 (q with str, J ) 7.2 Hz,
2H, -OCH2), 3.65 (dd, J1 ) 6 Hz, J2 ) 2.4 Hz, 1H), 3.12 (part of
an AB system, JAB ) 6 Hz, 1H), 3.06 (ddd, J1 ) 9.9 Hz, J2 ) 4.8
Hz, J3 ) 2.4 Hz, 1H), 2.87 (part of an AB system, JAB ) 6 Hz,
1H), 2.56-2.40 (m, 2H), 2.32 (dd, J1 ) 12.9 Hz, J2 ) 10.2 Hz,
1H), 2.0-1.86 (overlapped m, 2H), 1.80-1.50 (complex m, 3H),
1.26 (t, J ) 7.2 Hz, 3H). 13C NMR (75 MHz, CDCl3): δ 204.9,
172.5, 156.3, 114.1, 61.1, 58.4, 51.0, 50.0, 48.6, 41.3, 31.3, 30.1,
1
IR (KBr) νmax: 3431 cm-1. H NMR (400 MHz, CDCl3): δ 6.97
(32) (a) Trost, B. M. Angew. Chem., Int. Ed. Engl. 1995, 34, 259-281.
(b) Corey, E. J.; Cheng, X.-M. The Logic of Chemical Synthesis; John Wiley
and Sons: New York, 1989.
(33) Chanon, M.; Barone, R.; Baralotto, C.; Julliard, M.; Hendrickson,
J. B. Synthesis 1998, 1559-1583.
(s, 1H), 6.66 (s, 1H), 4.59 (br s, 1H, hydroxyl proton), 2.87-2.78
(m, 4H), 2.21 (s, 3H), 2.09-2.00 (m, 2H). 13C NMR (CDCl3, 100
MHz): δ 152.4, 143.4, 136.3, 126.5, 121.3, 111.1, 32.9, 32.2, 26.0,
15.9.
10160 J. Org. Chem., Vol. 72, No. 26, 2007

Molecular Complexity from Aromatics
4-Hydroxymethyl-6-methyl-5-indanol (19). To a stirred solution
of 18 (3.0 g, 20.27 mmol) in aqueous sodium hydroxide (2 M, 200
mL) was added formaldehyde (10 mL, excess) and stirred for 24 h
at ambient temperature. The reaction mixture was neutralized with
ammonium chloride and extracted with ethyl acetate (3 × 30 mL).
The organic layer was dried over anhydrous sodium sulfate.
Removal of the solvent followed by chromatography (petroleum
ether-ethyl acetate, 95:5) first gave some unreacted starting material
followed by the desired compound 19 as a colorless solid (3.1 g,
Methyl-7,8-dimethyl-11-oxo-10-spiroepoxytricyclo[5.2.2.01,5]-
undec-5-en-8-carboxylate (25). Oxidation of 6-methyl-4-hydroxym-
ethyl-5-indanol 19 (0.5 g, 2.80 mmol), with sodium m-periodate
(1.0 g, 4.6 mmol) in the presence of methyl methacrylate (5 mL,
excess) in acetonitrile as described earlier, followed by workup and
chromatography [petroleum ether-ethyl acetate (95:5)] of the crude
product furnished the adduct 25 (0.186 g, 24%). IR (neat) νmax
:
1736 cm-1. 1H NMR (300 MHz, CDCl3): δ 5.52 (s, 1H), 3.68 (s,
3H), 3.21 (part of an AB system, JAB ) 6 Hz, 1H), 2.86 (part of an
AB system, JAB ) 6 Hz, 1H), 2.6-2.45 (m, 2H), 2.17 (part of AB
system, JAB ) 12 Hz, 1H), 1.97 (part of an AB system, JAB ) 12
Hz, partly merged with another m, 1H), 1.95 (m, 1H), 1.8-1.5 (m,
2H), 1.5-1.4 (m, 1H), 1.25 (s, 3H), 1.21 (s, 3H). 13C NMR (75
MHz, CDCl3): δ 205.2, 175.5, 154.4, 121.4, 58.1, 55.5, 52.0, 51.0,
49.6, 48.3, 43.9, 30.0, 29.9, 26.5, 21.8, 13.6. HRMS (m/z): found
299.1266 [M + Na]+; calcd for C16H20O4Na 299.1259 [M + Na]+.
Ethyl-7-hydroxymethyl-11-oxo-10-spiroepoxytricyclo[5.2.2.01,5]-
undec-5-en-8-carboxylate (27a) and Ethyl-1-hydroxymethyl-10-
oxo-11-spiroepoxytricyclo[5.2.2.02,6]undec-2-en-9-carboxylate
(27b). Oxidation of 4,6-bis-hydroxymethyl-5-indanol 17 (2 g, 10.3
mmol) with sodium m-periodate (2.35 g, 11 mmol) in the presence
of ethyl acrylate (10 mL, excess) in acetonitrile-methanol (60 mL,
5:1) as described earlier followed by workup and chromatography
[petroleum ether-ethyl acetate (90:10)] first gave the adduct 27a
(0.73 g, 24%) as a solid, mp 98-100 °C. Continued elution
furnished the other adduct 27b in moderate yield (0.69 g, 23%) as
a liquid.
1
86%), mp 84-85 °C. IR (KBr) νmax: 3440 cm-1. H NMR (300
MHz, CDCl3): δ 7.50 (br s, 1H, hydroxyl proton), 6.94 (s, 1H),
4.86 (s, 2H), 2.83-2.72 (m, 4H), 2.20 (s, 3H), 2.16-1.98 (m, 2H).
13C NMR (CDCl3, 75 MHz): δ 152.8, 139.5, 134.9, 125.8, 123.2,
119.5, 61.9, 32.1, 30.9, 25.3, 15.8. HRMS (m/z): found 201.0896
[M + Na]+; calcd for C11H14O2Na 201.0891 [M + Na]+.
Ethyl-7-bromo-11-oxo-10-spiroepoxytricyclo[5.2.2.01,5]undec-
5-en-8-carboxylate (22). To a stirred solution of 6-bromo-4-
hydroxymethyl-5-indanol 13 (1.0 g, 4.1 mmol) and ethyl acrylate
(3 mL, excess) in acetonitrile (30 mL) was added an aqueous
solution of sodium metaperiodate (1.9 g, 8.8 mmol) dropwise at
∼0-5 °C. After stirring the reaction mixture for 12 h, sodium
chloride was added, and the stirring was continued for another 1
h. The organic layer was separated, and the aqueous layer was
extracted with ethyl acetate (3 × 50 mL). The combined organic
layer was washed with brine and dried over anhydrous sodium
sulfate. The solvent was removed under reduced pressure, and the
residue was chromatographed on silica gel. Elution with petroleum
ether-ethyl acetate (95:5) gave the desired adduct 22 as a colorless
Data for 27a. IR (KBr) νmax: 3481, 1732 cm-1. 1H NMR (300
MHz, CDCl3): δ 5.71 (s, 1H), 4.15 (q, J ) 6.9 Hz, 2H), 3.99 (ddd,
J1 ) 16.5 Hz, J2 ) 12.3, J3 ) 7.8 Hz, 2H), 3.16 (part of an AB
system, JAB ) 5.7 Hz, 1H), 3.03 (dd, J1 ) 10.2 Hz, J2 ) 4.8 Hz,
1H), 2.90 (part of an AB system, JAB ) 5.7 Hz, 1H), 2.62-2.41
(m, 4H), 2.05-1.88 (m, 1H), 1.80-1.60 (m, 3H), 1.60-1.45 (m,
1H), 1.27 (t, J ) 6.9 Hz, 3H). 13C NMR (CDCl3, 75 MHz): δ
206.9, 172.5, 155.3, 115.5, 61.6, 61.0, 58.8, 56.4, 51.2, 48.6, 41.9,
34.5, 30.2, 29.8, 26.5, 14.1. HRMS (m/z): found 315.1219 [M +
Na]+; calcd for C16H20O5Na 315.1208 [M + Na]+.
Crystal Data. C16H20O5, M ) 292.32, monoclinic, space group
P21/a, a ) 8.8668(7) Å, b ) 12.9797(15) Å, c ) 13.0907(10) Å,
R ) γ ) 90°, â ) 106.213(4)°, U 1446.7(6) Å3, Dc ) 1.342 mg/
m3, Z ) 4, F(0,0,0) ) 624, λ ) 71073 Å, µ ) 0.099 mm-1 total/
unique reflections ) 2723/2542 [R(int) ) 0.0146], T ) 293(2) K,
θ range ) 1.62-24.97ï, final R[I>2σ(I)], R1 ) 0.0489, wR2 )
0.1181, R (all data): R1 ) 0.1027, wR2 ) 0.1381.
1
liquid (1.12 g, 80%). IR (neat) νmax: 1736 cm-1. H NMR (300
MHz, CDCl3): δ 6.03 (s, 1H), 4.32-4.01 (m, 2H), 3.28-3.21 (part
of an AB system, JAB ) 5.5 Hz merged with a signal due to another
proton, total 2H), 2.94 (part of an AB system, JAB ) 5.5 Hz, 1H),
2.68-2.38 (m, 3H), 2.06-1.88 (m, 1H), 1.84-1.46 (m, 4H), 1.30
(t, J ) 7.2 Hz, 3H). 13C NMR (75 MHz, CDCl3): δ 195.7, 171.5,
154.1, 120.3, 66.5, 61.3, 57.4, 51.5, 49.2, 48.7, 35.8, 29.9, 29.6,
26.5, 14.1. HRMS (m/z): found 363.0205 [M + Na]+; calcd for
C15H17O4BrNa 363.0208 [M + Na]+.
Ethyl-7-methyl-10-spiroepoxytricyclo[5.2.2.01,5]undec-5-en-8-
carboxylate (23). Oxidation of 6-methyl-4-hydroxymethyl-5-in-
danol 19 (1.72 g, 9.6 mmol), with sodium m-periodate (4.3 g, 20
mmol) in the presence of ethyl acrylate (15 mL, excess) in
acetonitrile as described earlier followed by workup and chroma-
tography (petroleum ether-ethyl acetate 95:5) of the crude product
furnished the adduct 23 (2.0 g, 73%). IR (neat) νmax: 1734 cm-1
.
1H NMR (300 MHz, CDCl3): δ 5.53 (s, 1H), 4.17-4.11 (m, 2H),
3.14 (part of an AB system, JAB ) 5.7 Hz, 1H), 2.87 (part of an
AB system, JAB ) 5.7 Hz, 1H), 2.74 (dd, J1 ) 9.9 Hz, J2 ) 5.4
Hz, 1H), 2.55-2.35 (m, 3H), 1.91-1.80 (m, 1H), 1.74-1.50 (m
merged with signal due to H2O in CDCl3, 4H), 1.30-1.24 (s merged
with triplet, total 6H). 13C NMR (75 MHz, CDCl3): δ 205.1, 173.2,
154.6, 119.2, 60.7, 58.3, 51.2, 51.1, 48.5, 46.2, 34.8, 30.0, 29.8,
26.6, 15.8, 14.2. HRMS (m/z): found 277.1444 [M + H]+; calcd
for C16H21O4: 277.1440 [M + H]+.
Data for 27b. IR (neat) νmax: 3428, 1735 cm-1. 1H NMR (300
MHz, CDCl3): δ 4.20-3.95 (m, 4H), 3.17 (part of an AB system
partly merged with a m, JAB ) 6 Hz, 1H), 3.14 (m,1H), 2.90 (part
of an AB system, JAB ) 6 Hz, 1H), 2.66-2.64 (m, 1H), 2.54-
2.47 (m, 6H), 2.15-1.90 (m, 2H), 1.81 (ddd, J1 ) 7.5, J2 ) 5.1, J3
) 2.5 Hz, 1H), 1.27 (t, J ) 7.2 Hz, 3H). 13C NMR (75 MHz,
CDCl3): δ 205.2, 172.6, 144.4, 136.4, 60.9, 60.2, 58.2, 57.4, 52.7,
41.2, 38.3, 32.9, 31.1, 28.8, 23.4, 14.1. HRMS (m/z): found
315.1220 [M + Na]+; calcd for C16H20O5Na 315.1208 [M + Na]+.
1-Hydroxymethyl-5,6,7,8-tetrahydro-2-naphthol (5b), 3-Hy-
droxymethyl-5,6,7,8-tetrahydro-2-naphthol (5c), and 1,3-Dihy-
droxymethyl-5,6,7,8-tetrahydro-2-naphthol (5d). To 5,6,7,8-
tetrahydro-2-naphthol 12b (5.0 g, 33.8 mmol) was added aq NaOH
[1.4 g, 35 mmol dissolved in water (50 mL)] at ∼5 °C, and then
aq formaldehyde (36%, 2.8 mL, 34 mmol) was added. The reaction
mixture was stirred at ambient temperature for 12 h. It was quenched
with solid ammonium chloride and extracted with ethyl acetate (4
× 50 mL). The combined extract was dried on sodium sulfate. The
solvent was removed under vacuum, and the residue was chro-
matographed on silica gel. Elution with petroleum ether-ethyl
acetate (90:10) first gave some unreacted starting material. Further
elution with petroleum ether-ethyl acetate (80:20) furnished a
mixture of 5b and 5c (2.4 g, 40%), which solidified in the
refrigerator. Subsequent elution with ethyl acetate gave the dihy-
droxymethylated compound 5d as a solid (1.0 g, 14%).
Methyl-7-bromo-8-methyl-11-oxo-10-spiroepoxytricyclo-
[5.2.2.01,5]undec-5-en-8-carboxylate (24). Oxidation of 6-bromo-
4-hydroxymethyl-5-indanol 13 (0.5 g, 2.05 mmol), with sodium
m-periodate (0.860 g, 4 mmol) in the presence of methyl meth-
acrylate (5 mL, excess) in acetonitrile as described earlier followed
by workup and chromatography (petroleum ether-ethyl acetate 95:
5) of the crude product furnished the adduct 24 (0.423 g, 60%) as
a colorless liquid. IR (neat) νmax: 1734 cm-1. 1H NMR (300 MHz,
CDCl3): δ 6.07 (t, J ) 2 Hz, 1H), 3.74 (s, 3H), 3.32 (part of an
AB system, JAB ) 5.5 Hz, 1H), 2.93 (part of an AB system, JAB
)
5.5 Hz, 1H), 2.62-2.4 (m, 2H), 2.13 (q, J ) 12.4 Hz, 2H), 2.03-
1.89 (m, 1H), 1.79-1.58 (m, merged with signal due to H2O in
CDCl3, 2H), 1.54-1.4 (m, 1H), 1.36 (s, 3H). 13C NMR (75 MHz,
CDCl3): δ 195.7, 173.7, 153.7, 122.5, 73.9, 57.1, 52.5, 52.3, 51.4,
49.0, 43.8, 29.9, 29.7, 26.6, 22.8. HRMS (m/z): found 341.0387
[M + H]+; calcd for C15H18O4Br 341.0388 [M + H]+.
J. Org. Chem, Vol. 72, No. 26, 2007 10161

Singh et al.
Data for 5b,c. Mp 52-56 °C. IR (KBr) νmax: 3402, 1596 cm-1
,
ambient temperature (∼30 °C) for 8 h (TLC). It was filtered on a
Celite bed and washed with ethyl acetate. The filtrate was
concentrated under reduced pressure and diluted with water and
extracted with ethyl acetate (4 × 40 mL). The combined organic
layer was washed with brine and dried. The solvent was removed
under reduced pressure, and the residue was chromatographed.
Elution with petroleum ether-ethyl acetate (88:12) gave the alcohol
1H NMR (400 MHz, CDCl3): δ 6.87 (d, J ) 8.4 Hz), 6.72 (s),
6.62 (d, J ) 8.4 Hz), 6.54 (s), 4.82 (s), 4.70 (s), 2.68-2.56 (m),
1.78-1.68 (m) (signals due to major isomer). 13C NMR (100 MHz,
CDCl3) δ: 153.8, 153.1, 138.3, 134.7, 129.7, 128.9, 128.6, 128.5,
122.5, 122.1, 116.2, 114.0, 63.9, 59.9, 29.4, 29.2, 28.4, 26.1, 23.3,
23.1, 23.0, 22.7 (signals due to both isomers). HRMS (m/z): found
201.0893 [M+Na]+; calcd for C11H14O2Na 201.0891 [M+Na]+.
28 (syn/anti mixture) as a colorless liquid (1.81 g, 90%) [IR (neat)
1
ν
max: 3480, 1718 cm-1. H NMR (300 MHz, CDCl3): δ 5.77-
Data for 5d. Mp 120-122 °C. IR (KBr) νmax: 3460, 3228 cm-1
.
1H NMR (400 MHz, CD3OD): δ 6.83 (s, 1H), 4.76 (s, 2H), 4.63
(s, 2H), 2.73-2.66 (m, 4H), 1.79-1.71 (m, 4H). 13C NMR (100
MHz, CD3OD): δ 153.7, 136.2, 129.3, 129.2, 126.0, 124.9, 62.3,
58.3, 30.6, 27.0, 24.6, 24.3. HRMS (m/z): found 231.0988 [M +
Na]+; calcd for C12H16O3Na 231.0997 [M + Na]+.
5.71 (m, 1H), 4.17-4.05 (m, 2H), 3.85-3.62 (m, 2H), 3.51 (dd, J1
) 6 Hz, J2 ) 2.4 Hz, 1H), 3.0-2.65 (m, 2H), 2.6-2.42 (m, 1H),
2.4-2.22 (m, 1H), 2.00-1.64 (m, 7H), 1.64-1.58 (m, 1H), 1.25
(t, J ) 7.2 Hz, 3H). 13C NMR (75 MHz, CDCl3): δ 215.2, 172.8,
159.1, 112.1, 61.4, 61.0, 52.8, 51.4, 48.8, 40.4, 34.0, 30.1, 29.5,
25.9, 14.1].
5,6,7,8-Tetrahydro-2H-spiro[naphthalene-1,2′-oxiran]-2-
one (6b). To a mixture of 5b,c (2.3 g, 12.8 mmol) in acetonitrile
(50 mL) was added aqueous solution of sodium m-periodate (6 g,
28 mmol) dropwise (30 min) at 0-5 °C. The reaction mixture was
saturated with sodium chloride, the organic layer was separated,
and the aqueous layer was extracted with ethyl acetate (3 × 50
mL). The combined organic extract was dried over anhydrous
sodium sulfate. The solvent was removed under reduced pressure,
and the residue was chromatographed on silica gel. Elution with
petroleum ether-ethyl acetate (85:15) gave the desired cyclohexa-
dienone 6b (1.5 g, 66%) as a yellow liquid, which solidified after
being kept in a refrigerator, mp 80-82 °C. IR (KBr) νmax: 1669,
The keto-alcohol 28 thus obtained was subjected to oxidation
and decarboxylation as described next. Thus, a solution of the
â-keto-alcohol 28 (1.5 g, 5.64 mmol) in acetone (50 mL) was
oxidized with freshly prepared Jones’ reagent at 0 °C. After
completion of the reaction (TLC), acetone was removed under
vacuum at ambient temperature, and the residue was diluted with
water (10 mL) and extracted with diethyl ether (3 × 25 mL). The
combined organic layer was washed with brine and dried over
anhydrous sodium sulfate. The solvent was removed, and the
resulting â-keto acid was dissolved in a THF-water mixture (1:1,
30 mL) and refluxed for 10 h. It was brought to ambient
temperature, and sodium chloride was added. The organic layer
was separated, and the aqueous layer was extracted with diethyl
ether (3 × 30 mL). The combined organic layer was washed with
saturated sodium bicarbonate and brine and dried over anhydrous
sodium sulfate. The solvent was removed under reduced pressure,
and the residue was chromatographed on silica gel. Elution with
petroleum ether-ethyl acetate (98:2) gave 29 (0.780 g, 60%) as a
1
1636 cm-1. H NMR (300 MHz, CDCl3): δ 6.96 (d, J ) 9.9 Hz,
1H), 6.11 (d, J ) 9.9 Hz, 1H), 3.21 (part of an AB system, JAB
)
8 Hz, 1H), 3.13 (part of an AB system, JAB ) 8 Hz, 1H), 2.33-
2.20 (m, 3H), 1.94-1.55 (m, 5H). 13C NMR (75 MHz, CDCl3): δ
196.4, 147.0, 141.7, 132.0, 123.3, 58.6, 58.5, 28.9, 22.5, 22.2, 21.3.
HRMS (m/z): found 177.0907 [M + H]+; calcd for C11H13O2
177.0916 [M + H]+.
colorless liquid. IR (neat) νmax: 1732 cm-1 (br). UV (MeOH)
Ethyl-12-oxo-11-spiroepoxytricyclo[6.2.2.01,6]dodec-6-en-9-
carboxylate (14b). A mixture of cyclohexadienone 6b (1.15 g, 6.5
mmol), ethyl acrylate (5.3 mL, excess), and o-dichlorobenzene (5
mL) was taken in a sealed tube and heated to 110 °C for 10 h,
after which the reaction mixture was charged on a column of silica
gel and chromatographed. Elution with petroleum ether-ethyl acetate
(90:10) furnished the adduct 14b (1.3 g, 72%) as a solid, mp 60-
1
λ
max: 220, 290 nm. H NMR (300 MHz, CDCl3): δ 5.72 (d, J )
6.3 Hz, 1H), 4.12 (q with structure, J ) 7 Hz, 2H), 3.46 (dd, J1 )
6.3 Hz, J2 ) 2.1 Hz, 1H), 2.92 (m, 1H), 2.50-2.45 (m, 1H), 2.34-
2.32 (m, 1H), 2.11 (d, J ) 18 Hz, 1H), 1.99-1.70 (m, 7H), 1.24
(t, J ) 7 Hz, 3H). 13C NMR (75 MHz, CDCl3): δ 211.6, 173.2,
157.8, 112.5, 60.9, 51.5, 46.9, 44.7, 40.1, 35.5, 34.1, 30.2, 25.9,
14.1. HRMS (m/z): found 257.1143 [M + Na]+; calcd for
C14H18O3Na 257.1154 [M + Na]+.
1
62 °C. IR (KBr) νmax: 1731 cm-1. H NMR (400 MHz, CDCl3):
δ 5.81 (d, J ) 6.4 Hz, 1H), 4.19-4.13 (m, 2H), 3.64 (dd, J1 ) 6
Hz, J2 ) 2 Hz, 1H), 3.10 (part of an AB system, JAB ) 5.6 Hz,
1H), 3.04 (ddd, J1 ) 10 Hz, J2 ) 5.2 Hz, J3 ) 2.4 Hz, 1H), 3.00
(part of an AB system, JAB ) 5.6 Hz, 1H), 2.50-2.43 (m, 1H),
2.33-2.25 (m, 1H), 2.17-1.95 (m, 2H), 1.77-1.30 (m merged with
triplet, 6H), 1.27 (t, J ) 7.2 Hz, 3H). 13C NMR (75 MHz, CDCl3):
δ 204.1, 172.6, 149.3, 117.6, 61.1, 58.8, 50.0, 49.3, 40.3, 32.9,
27.9, 24.5, 21.6, 20.8, 14.1. HRMS (m/z): found 299.1269 [M +
Na]+; calcd for C16H20O4Na 299.1259 [M + Na]+.
Ethyl-7-methyl-11-oxo-tricyclo[5.2.2.01,5]undec-5-en-8-car-
boxylate (31). To a solution of the adduct 23 (1.5 g, 5.43 mmol)
in methanol-water (6:1, 70 mL) was added NH4Cl (1.3 g, 21.5
mmol) and activated zinc (12 g, excess). The reaction mixture was
stirred at ambient temperature for 6 h (TLC). It was filtered on a
Celite bed and washed with ethyl acetate. The filtrate was
concentrated under reduced pressure and diluted with water and
extracted with ethyl acetate (4 × 30 mL). The combined organic
layer was washed with brine and dried over anhydrous sodium
sulfate. The solvent was removed under reduced pressure, and the
residue was chromatographed. Elution with petroleum ether-ethyl
acetate (90:10) gave the alcohol 30 (syn/anti mixture) as a colorless
Methyl-9-methyl-12-oxo-11-spiroepoxytricyclo[6.2.2.01,6]dodec-
6-en-9-carboxylate (15b). Compound 6b (1.4 g, 7.95 mmol),
methyl methacrylate (4 mL, excess), and o-dichlorobenzene (5 mL)
were heated in a sealed tube at ∼110 °C for 8 h. Chromatography
of the reaction mixture [petroleum ether-ethyl acetate (90:10)] gave
1
liquid (1.30 g, 86%). [IR(neat) νmax: 3499, 1716 cm-1. H NMR
(300 MHz, CDCl3): δ 5.44 (s, 1H), 4.24-4.00 (m, 2H), 3.90-
3.60 (m, 2H), 2.8 (br s, 1H) 2.65-2.42 (m, 1H), 2.4-2.23 (m,
1H), 2.06-2.02 (m, 1H), 2.02-1.60 (m, 5H), 1.50 (ddd, J1 ) 8.4
Hz, J2 ) 6.6 Hz, J3 ) 1.8 Hz, 1H), 1.6-1.4 (m, 6H). 13C NMR
(75 MHz, CDCl3): δ 214.8, 173.2, 157.4, 117.2, 61.8, 60.6, 52.9,
51.9, 48.4, 45.3, 34.1, 33.1, 30.0, 25.7, 15.5, 14.1].
the adduct 15b (0.960 g, 44%) as a solid, mp 70-72 °C. IR (KBr)
1
ν
max: 1738, 1732 cm-1. H NMR (400 MHz, CDCl3): δ 5.84 (d
with str J ) 6.2 Hz, 1H), 3.71 (s, 3H), 3.46 (d, J ) 6.4 Hz, 1H),
3.14 (part of an AB system, JAB ) 5.6 Hz, 1H), 3.00 (part of an
AB system, JAB ) 5.6 Hz, 1H), 2.48-2.36 (m, 2H), 2.28-2.21
(m, 1H), 1.75-1.61 (m, 3H), 1.60-1.50 (m, 1H), 1.49-1.35 (m,
2H), 1.31-1.24 (m merged with s, total 4H). 13C NMR (100 MHz,
CDCl3): δ 204.5, 176.3, 149.1, 119.7, 58.9, 55.4, 52.6, 50.1, 46.9,
41.7, 40.1, 28.0, 25.8, 24.8, 21.8, 21.1. HRMS (m/z): found
277.1446 [M + H]+; calcd for C16H21O4 277.1440 [M + H]+.
Ethyl-11-oxo-tricyclo[5.2.2.01,5]undec-5-en-8-carboxylate (29).
To a solution of the adduct 14a (2.0 g, 7.6 mmol) in methanol-
water (6:1, 70 mL) was added zinc (activated 18 g, excess) and
NH4Cl (3.3 g, 59 mmol). The reaction mixture was stirred at
The keto-alcohol 30 thus obtained was subjected to oxidation
and decarboxylation to give 31 as follows. A solution of the â-keto-
alcohol 30 (1.0 g, 3.59 mmol) in acetone (40 mL) was oxidized
with freshly prepared Jones’ reagent at 0 °C. After completion of
reaction (TLC), isopropyl alcohol was added to destroy excess
oxidant. Acetone was removed in vacuum at ambient temperature,
and the residue was diluted with water (10 mL) and extracted with
diethyl ether (3 × 25 mL). The combined organic layer was washed
10162 J. Org. Chem., Vol. 72, No. 26, 2007

Molecular Complexity from Aromatics
with brine and dried over anhydrous sodium sulfate. The solvent
was removed, and the resulting â-keto acid was dissolved in a THF-
water mixture (1:1, 45 mL) and refluxed for 10 h. Workup as
described earlier followed by chromatography [petroleum ether-
ethyl acetate (98:2)] gave the titled compound 31 (0.545 g, 61%)
extract was washed with brine and dried over anhydrous sodium
sulfate. The solvent was removed under reduced pressure, and the
residue was purified by column chromatography. Elution with
petroleum ether-ethyl acetate (92:8) first gave 35 (0.189 g, 8%) as
a colorless liquid. Further elution with petroleum ether-ethyl acetate
(80:20) gave the keto-alcohol 36 (1.882 g, 75%, mixture of syn/
anti isomers) as a thick colorless liquid.
1
as a colorless liquid. IR (neat) νmax: 1729 cm-1. H NMR (300
MHz, CDCl3): δ 5.40 (s, 1H), 4.15-4.07 (m, 2H), 2.63-2.51 (m,
2H), 2.35-2.25 (m, 1H), 2.25-1.76 (m, 7H), 1.68-1.61 (m, 1H),
1.35-1.20 (triplet merged with a singlet, total 6H). 13C NMR
(CDCl3, 75 MHz): δ 211.2, 173.7, 156.3, 117.4, 60.5, 51.7, 46.5,
44.9, 44.4, 37.7, 35.5, 30.1, 25.8, 15.7, 14.2. HRMS (m/z): found
249.1479 [M + H]+; calcd for C15H21O3 249.1491 [M + H]+.
Methyl-8,10-dimethyl-11-oxo-tricyclo[5.2.2.01,5]undec-5-en-8-
carboxylate (32) and Methyl-10-hydroxymethyl-8-methyl-11-
oxo-tricyclo[5.2.2.01,5]undec-5-en-8-carboxylate (33). To a solu-
tion of the adduct 15a (0.75 g, 2.9 mmol) in methanol-water (6:1,
84 mL) was added NH4Cl (0.75 g, excess) and activated zinc (5 g,
excess). The reaction mixture was stirred at ambient temperature
for 8 h (TLC). It was filtered on a Celite bed and washed with
ethyl acetate. The filtrate was concentrated under reduced pressure
and diluted with water and extracted with ethyl acetate (4 × 20
mL). The combined organic layer was washed with brine and dried
over anhydrous sodium sulfate. The solvent was removed under
reduced pressure, and the residue was chromatographed. Elution
with petroleum ether-ethyl acetate (90:10) first gave the minor
ketone 32 (0.080 g, 11%) as a colorless liquid. IR (neat) νmax: 1722
1
Data for 35. IR (neat) νmax: 1727 cm-1, H NMR (300 MHz,
CDCl3): δ 5.69 (d with str, J ) 6.3 Hz, 1H), 4.17-4.07 (m, 2H),
3.42 (dd, J1 ) 2.1 Hz, J2 ) 6.6 Hz, 1H), 2.81 (ddd, J1 ) 9.9 Hz,
J2 ) 6.0 Hz, J3 ) 2.1 Hz, 1H), 2.36-2.30 (m, 2H), 1.92-1.83 (m,
2H), 1.75-1.51 (m, 7H), 1.25 (t, J ) 7.2 Hz, 3H), 1.02 (d, J) 7.2
Hz, 3H). 13C NMR (100 MHz, CDCl3): δ 213.8, 173.3, 153.2,
115.9, 61.0, 50.6, 45.4, 42.7, 40.3, 28.9, 28.2, 26.5, 20.5, 18.1, 14.2,
11.3. HRMS (m/z): found 263.1660 [M + H]+; calcd for C16H23O3
263.1647 [M + H]+.
1
Data for 36. IR (neat) νmax: 3479, 1731 cm-1, H NMR (300
MHz, CDCl3): δ 5.71 and 5.65 (two d, J ) 6.3 Hz, total 1H),
4.20-4.05 (m, 2H), 3.95-3.80 (m, 1H), 3.74-3.64 (m, 1H), 3.53-
3.47 (m, 1H), 2.98-2.89 (m, 1H), 2.41-2.23 (m, 2H), 2.08-1.84
(m, 3H), 1.80-1.62 (m, 7H), 1.25 (t, J ) 7 Hz, 3H). 13C NMR
(100 MHz, CDCl3): δ 214.0, 173.2, 153.3, 115.6, 61.0, 60.0, 52.0,
50.9, 42.1, 40.4, 30.7, 28.1, 26.3, 20.3, 18.0, 14.1 (signals due to
one isomer). HRMS (m/z): found 279.1602 [M + H]+; calcd for
C16H23O4 279.1596 [M + H]+.
Ethyl-12-oxo-tricyclo[6.2.2.01,6]dodec-6-en-9-carboxylate (37).
To a solution of â-keto-alcohol 36 (1.882 g, 6.77 mmol) in acetone
(30 mL) was added freshly prepared Jones’ reagent at 5 °C. After
completion of the reaction (TLC), acetone was removed under
vacuum. The residue was diluted with water (20 mL) and extracted
with ethyl acetate (4 × 20 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 dissolved in the
THF-H2O mixture (1:1, 40 mL) and refluxed for 12 h. The reaction
mixture was saturated with NaCl, and the organic layer was
separated. The aqueous layer was extracted with diethyl ether (3
× 20 mL). The combined organic extract was dried over sodium
sulfate. The solvent was removed under reduced pressure, and the
residue was chromatographed on silica gel. Elution with petroleum
ether-ethyl acetate (90:10) gave 37 (1.110 g, 66%) as a colorless
liquid. IR (neat) νmax: 1728 cm-1. UV (MeOH) λmax: 215, 294
1
cm-1. H NMR (400 MHz, CDCl3): δ 5.77-5.74 (m, 1H), 3.67
(s, 3H), 3.27 (d, J ) 6 Hz, 1H), 2.46-2.40 (m, 1H), 2.32-2.22
(m, 1H), 2.15 (dd, J1 ) 13.6 Hz, J2 ) 2 Hz, 1H), 1.88-1.72 (m,
3H), 1.70-1.65 (m merged with signal due to H2O present in
CDCl3, 5H), 1.22 (s, 3H), 1.07 (d, J ) 7.6 Hz, 3H). 13C NMR
(100 MHz, CDCl3): δ 215.8, 178.7, 158.9, 114.8, 57.5, 52.4, 50.3,
48.0., 47.1, 35.7, 34.1, 30.3, 25.9, 25.5, 11.0. HRMS (m/z): found
271.1323 [M + Na]+; calcd for C15H20O3Na 271.1310 [M + Na]+.
Continued elution with petroleum ether-ethyl acetate (80:20)
furnished the â-keto-alcohol 33 as a colorless liquid (0.600 g, 80%).
IR (neat) νmax: 3512, 1720 cm-1. 1H NMR (400 MHz, CDCl3): δ
5.78-5.76 (m, 1H), 3.87-3.72 (m, 1H), 3.70-3.66 (m merged with
s, total 4H), 3.32 (d, J ) 6 Hz, 1H), 2.46-2.41 (m, 1H), 2.31-
2.27 (m, 1H), 2.20 (dd, J1 ) 13.6 Hz, J2 ) 2 Hz, 1H), 2.09-2.00
(m, 1H), 2.00-1.82 (m, 1H), 1.82-1.73 (m, 3H), 1.56 (d, J ) 14
Hz, 1H), 1.28 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 217.2,
176.3, 158.9, 114.7, 61.0, 57.7, 54.0, 52.6, 48.9, 48.4, 37.0, 34.0,
30.1, 26.2, 25.2. HRMS (m/z): found 265.1451 [M + H]+; calcd
for C15H21O4 265.1440 [M + H]+.
1
nm. H NMR (300 MHz, CDCl3): δ 5.68 (d, J ) 6.2 Hz, 1H),
4.16-4.09 (m, 2H), 3.45 (dd, J1 ) 6.2 Hz, J2 ) 2.1 Hz, 1H), 2.95
(ddd, J1 ) 10.2 Hz, J2 ) 5.7 Hz, J3 ) 2.4 Hz, 1H), 2.38-2.24 (m,
2H), 2.06-1.76 (m, 3H), 1.73-1.58 (m, 7H), 1.25 (t, J ) 7.2 Hz,
3H). 13C NMR (100 MHz, CDCl3): δ 210.2, 173.0, 151.1, 116.1,
60.7, 51.1, 44.9, 40.0, 39.9, 35.0, 30.9, 26.3, 20.9, 18.6, 14.0. HRMS
(m/z): found 249.1487 [M + H]+; calcd for C15H21O3 249.1491
[M + H]+.
Methyl-8-methyl-11-oxo-tricyclo[5.2.2.01,5]undec-5-en-8-car-
boxylate (34). The keto-alcohol 33 (0.540 g, 2 mmol) thus obtained
was oxidized with Jones’ reagent as described earlier, and the
resulting â-keto acid was decarboxylated in refluxing aq THF. Usual
workup and chromatography [petroleum ether-ethyl acetate (90:
10)] gave 34 as a colorless liquid (0.300 g, 63%). IR νmax: 1732
Methyl-9,11-dimethyl-12-oxo-tricyclo[6.2.2.01,6]dodec-6-en-9-
carboxylate (38) and Methyl-9-methyl-11-hydroxymethyl-12-
oxo-tricyclo[6.2.2.01,6]dodec-6-en-9-carboxylate (39). To a solu-
tion of epoxy ketone 15b (0.900 g, 3.2 mmol) in methanol-water
(6:1, 84 mL) was added zinc (activated, 5 g, excess) and ammonium
chloride (0.900 g, excess). The reaction mixture was stirred at
ambient temperature for 8 h. Workup as described earlier and
chromatography [petroleum ether-ethyl acetate (92:8)] of the
product mixture first gave 38 (0.150 g, 17%). Further elution (80:
20) gave the keto-alcohol 39 (0.670 g, 74%) as a colorless liquid.
1
cm-1. H NMR (400 MHz, CDCl3): δ 5.76 (d, J ) 6 Hz, 1H),
3.67 (s, 3H), 3.30 (d, J ) 6 Hz, 1H), 2.46-2.26 (m, 3H), 2.08
(part of an AB system JAB ) 18.3 Hz, 1H), 1.94 (d of part of an
AB system, JAB ) 18.3 Hz, J2 ) 3.3 Hz, 1H), 1.87-1.70 (m, 4H),
1.52 (d, J ) 12.8 Hz, 1H), 1.28 (s, 3H). 13C NMR (100 MHz,
CDCl3): δ 212.0, 176.3, 157.5, 114.6, 57.6, 52.3, 47.17, 47.15,
45.0, 42.7, 35.4, 30.1, 26.9, 25.9. HRMS (m/z): found 235.1329
[M + H]+; calcd for C14H19O3 235.1334 [M + H]+.
1
Data for 38. IR (neat) νmax: 1722 (br) cm-1. H NMR (400
Ethyl-11-methyl-12-oxo-tricyclo[6.2.2.01,6]dodec-6-en-9-car-
boxylate (35) and Ethyl-11-hydroxymethyl-12-oxo-tricyclo-
[6.2.2.01,6]dodec-6-en-9-carboxylate (36). To a solution of epoxy
ketone 14b (2.5 g, 9.06 mmol) in methanol-water (6:1, 35 mL)
was added zinc (activated, 18 g, excess) and ammonium chloride
(1.8 g, excess). The reaction mixture was stirred at ambient
temperature for 8 h. The reaction mixture was then filtered through
a Celite bed and washed with ethyl acetate (2 × 5 mL). The filtrate
was concentrated under vacuum, and the residue was diluted with
water and extracted with ethyl acetate (3 × 50 mL). The combined
MHz, CDCl3): δ 5.61 (d with str, J ) 5.8 Hz, 1H), 3.54 (s, 3H),
3.12 (d, J ) 5.8 Hz, 1H), 2.17-2.11 (m, 3H), 1.82-1.74 (m, 1H),
1.58-1.40 (m, 6H), 1.34 (d, J ) 13.6 Hz, 1H), 1.09 (s, 3H), 0.90
(d, J ) 7.2 Hz, 3H). 13C NMR (100 MHz, CDCl3): δ 214.7, 176.4,
152.8, 118.1, 56.5, 52.2, 47.7, 46.3, 42.3, 35.9, 27.9, 26.3, 25.4,
20.3, 17.8, 10.0. HRMS (m/z): found 263.1636 [M + H]+; calcd
for C16H23O3 263.1647 [M + H]+.
1
Data for 39. IR (neat) νmax: 3504, 1719 cm-1. H NMR (400
MHz, CDCl3): δ 5.74 (d, J ) 5.6 Hz, 1H), 3.80-3.72 (m, 2H),
J. Org. Chem, Vol. 72, No. 26, 2007 10163

Singh et al.
ν
max: 1731 cm-1. H NMR (400 MHz, CDCl3): δ 3.70 (s, 3H),
2.54-2.32 (m, 4H), 2.09-1.84 (m, 6H), 1.72-1.60 (m merged with
signal due to H2O in CDCl3, 2H), 1.26 (s, 3H). 13C NMR (100
MHz, CDCl3): δ 216.0, 177.7, 60.8, 57.7, 55.6, 55.3, 53.9, 52.5,
46.4, 43.3, 39.6, 28.8, 28.4, 23.3. HRMS (m/z): found 235.1334
[M + H]+; calcd for C14H19O3 235.1334 [M + H]+.
1
3.68 (s, 3H), 3.30 (d, J ) 6.4 Hz, 1H), 3.26 (dd, J1 ) 8.5 Hz, J2
) 4 Hz, 1H), 2.35 (dd, J1 ) 14.0 Hz, J2 ) 2.4 Hz, 1H), 2.27-2.24
(m, 2H), 2.09-2.05 (m, 1H), 1.74-1.57 (m, 6H), 1.39 (d, J ) 14
Hz, 1H), 1.28 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 216.6,
176.3, 152.9, 118.1, 60.0, 56.9, 53.1, 52.5, 48.3, 41.9, 37.5, 27.9,
26.3, 25.2, 20.2, 17.9. HRMS (m/z): found 279.1604 [M + H]+;
calcd for C16H23O4 279.1596 [M + H]+.
Ethyl-11-oxo-tetracyclo[5.3.2.02,701,10]dodecan-9-carboxy-
late (44). A solution of ketone 37 (0.095 g, 0.4 mmol) in degassed
acetone (100 mL, solvent as well as sensitizer) was irradiated with
mercury vapor lamp (125 W) in a Pyrex immersion well for 2 h
under nitrogen. Acetone was removed under vacuum, and the
residue was chromatographed. Elution with petroleum ether-ethyl
acetate (85:15) furnished tetracyclic compound 44 (0.074 g, 77%).
IR (neat) νmax: 1728 cm-1. 1H NMR (400 MHz, CDCl3): δ 4.20-
4.14 (m, 2H), 2.80 (ddd, J1 ) 10.5 Hz, J2 ) 6.5 Hz, J3 ) 1.2 Hz,
1H), 2.42-2.16 (m, 3H), 2.00-1.60 (m, 11H), 1.27 (t, J ) 7.2
Hz, 3H). 13C NMR (75 MHz, CDCl3): δ 213.8, 174.2, 60.8, 52.9,
49.8, 47.7, 46.9, 45.4, 43.2, 38.6, 31.2, 24.4, 20.3, 18.2, 14.2. HRMS
(m/z): found 249.1498 [M + H]+; calcd for C15H21O3 249.1491
[M + H]+.
Methyl-9-methyl-12-oxo-tricyclo[6.2.2.01,6]dodec-6-en-9-car-
boxylate (40). A solution of â-keto-alcohol 39 (0.650 g, 2.33 mmol)
in acetone (30 mL) was oxidized with Jones’ reagent as described
previously. After completion of the reaction (TLC), acetone was
removed under vacuum. The residue was diluted with water (20
mL) and extracted with ethyl acetate (4 × 20 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 dissolved in a THF-H2O mixture (1:1, 40 mL) and refluxed
for 12 h. The reaction mixture was saturated with NaCl, and the
organic layer was separated. The aqueous layer was extracted with
ether (3 × 20 mL). Combined organic extract was dried over sodium
sulfate. The solvent was removed under reduced pressure, and the
crude product was purified by column chromatography. Elution with
petroleum ether-ethyl acetate (90:10) gave 40 (0.413 g, 71%) as
Methyl-9-methyl-11-oxo-tetracyclo[5.3.2.02,701,10]dodecan-9-
carboxylate (45). A solution of the ketone 40 (0.100 g, 0.4 mmol)
in degassed acetone (100 mL, solvent as well as sensitizer) was
irradiated with a mercury vapor lamp (125 W) in a Pyrex immersion
well for 1 h and 10 min under nitrogen. Acetone was removed
under vacuum, and the residue was chromatographed. Elution with
petroleum ether-ethyl acetate (90:10) furnished the product 45 as
1
colorless liquid. IR (neat) νmax: 1732 cm-1. H NMR (400 MHz,
CDCl3): δ 5.71 (d, J ) 6.2 Hz, 1H), 3.67 (s, 3H), 3.30 (d, J ) 6.2
Hz, 1H), 2.41 (dd, J1 ) 13.2 Hz, J2 ) 3.3 Hz, 1H), 2.26-2.24 (br
m, 2H), 2.04 (d of part of an AB system, JAB ) 18.3 Hz, J2 ) 3.3
Hz, 1H), 1.83 (part of AB system, J ) 18 Hz, 1H), 1.71-1.56 (m,
6H, overlapped with signal due water in CDCl3), 1.31-1.28 (s
merged with a m, 4H). 13C NMR (100 MHz, CDCl3): δ 210.9,
176.3, 150.9, 118.2, 57.1, 52.3, 46.8, 45.3, 43.5, 39.8, 30.9, 26.9,
26.3, 20.9, 18.6. HRMS (m/z): found 249.1497 [M + H]+; calcd
for C15H21O3 249.1491 [M + H]+.
1
a colorless liquid (0.065 g, 65%). IR (neat) νmax: 1732 cm-1, H
NMR (400 MHz, CDCl3): δ 3.72 (s, 3H), 2.65 (dd, J1 ) 13.6 Hz,
J2 ) 2.2 Hz, 1H), 2.48 (m of d, J ) 18 Hz, 1H), 2.33 (dd, J1 )
10.0 Hz, J2 ) 1.3 Hz, 1H), 2.15 (d, J ) 18 Hz, 1H), 1.85 (d, J )
10 Hz, 1H), 1.78-1.60 (m, 8H), 1.57 (d with str, J ) 13.3 Hz,
1H), 1.33 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 214.9, 177.6,
55.6, 54.8, 52.3, 50.9, 50.6, 48.1, 47.9, 44.7, 31.8, 24.5, 23.3, 19.9,
17.7. HRMS (m/z): found 249.1498 [M + H]+; calcd for C15H21O3
249.1491 [M + H]+.
Ethyl-10-oxo-tetracyclo[4.3.2.02,601,9]undec-8-carboxylate (41).
A solution of 29 (0.070 g, 0.3 mmol) in acetone (100 mL) was
irradiated with a medium-pressure mercury vapor lamp (125 W, λ
max: 254 nm) in a quartz immersion well for 3 h under nitrogen.
The solvent was removed, and the residue was chromatographed.
Elution with petroleum ether-ethyl acetate (95:5) first gave some
unreacted starting material. Continued elution gave the photoproduct
41 as a colorless liquid (0.036 g, 51%). IR (neat) νmax: 1731 cm-1
Ethyl-7-oxo-tricyclo[3.3.3.01,5]undec-3-carboxylate (46). To a
stirred solution of 41 (0.100 g, 0.43 mmol) in dry benzene (30 mL),
AIBN (0.07 g, 0.42 mmol) and tributyltin hydride (0.5 mL, 1.7
mmol) were added, and the reaction mixture was refluxed for 6 h
under an atmosphere of nitrogen. Benzene was removed, and the
residue was chromatographed on silica gel. The column was eluted
with petroleum ether to remove the tin impurity. Further elution
with petroleum ether-ethyl acetate (98:2) furnished propellane 46
(0.053 g, 51%) as a colorless liquid. IR (neat) νmax: 1738, 1732
1
(br). H NMR (300 MHz, CDCl3): δ 4.16 (q, J ) 7.2 Hz, 2H),
2.85 (ddd, J1 ) 11.4, J2) 6.6, and J3 ) 1.5 Hz, 1H), 2.42 - 2.24
(m, 2H), 2.22-1.82 (m, 9H), 1.62 (dt, J1 ) 8.4, J2 ) 7.8 Hz, 1H),
1.26 (t, J ) 7.5 Hz, 3H). 13C NMR (75 MHz, CDCl3): δ 215.1,
174.1, 60.9, 58.0, 56.8, 53.2, 49.0, 46.2, 43.1, 37.9, 37.7, 28.4, 27.6,
14.2. HRMS (m/z): found 235.1338 [M + H]+; calcd for C14H19O3
235.1334 [M + H]+.
1
cm-1. H NMR (300 MHz, CDCl3): δ 4.13 (q, J ) 7.5 Hz, 2H),
2.77 (m, 1H), 2.36 (q of AB type, J1 ) 13.1 Hz, J2 ) 6 Hz, 4H),
2.15-2.00 (m, 2H), 2.00-1.90 (m, 2H), 1.83-1.60 (m, 4H), 1.45-
1.30 (m, 2H), 1.26 (t, J ) 7.5 Hz, 3H). 13C NMR (75 MHz,
CDCl3): δ 218.2, 174.3, 60.4, 55.9, 52.7, 44.7, 43.6, 41.4, 24.6,
14.1. HRMS (m/z): found 237.1498 [M + H]+; calcd for C14H21O3
237.1491 [M + H]+.
Ethyl-1-methyl-10-oxo-tetracyclo[4.3.2.02,601,9]undec-8-car-
boxylate (42). A solution of 31 (0.074 g, 0.3 mmol) in acetone
(100 mL) was irradiated with a medium-pressure mercury vapor
lamp (125 W, λ max: 254 nm) in a quartz immersion well for 3 h
under nitrogen. The solvent was removed, and the residue was
chromatographed (petroleum ether-ethyl acetate 95:5) to give some
unreacted starting material. Continued elution gave the photoproduct
Methyl-3-methyl-7-oxo-tricyclo[3.3.3.01,5]undec-3-carboxy-
late (47). To a stirred solution of 43 (0.07 g, 0.3 mmol) in dry
benzene (10 mL), AIBN (0.04 g, 2.4 mmol) and tributyltin hydride
(0.5 mL, 1.7 mmol) were added, and the reaction mixture was
refluxed for 12 h under an atmosphere of nitrogen. Benzene was
removed, and the residue was chromatographed on silica gel.
Elution with petroleum ether-ethyl acetate (95:5) furnished the
42 as a colorless liquid (0.036 g, 48%). IR (neat) νmax: 1733 cm-1
.
1H NMR (300 MHz, CDCl3): δ 4.24-4.03 (m, 2H), 2.94 (dd, J1
) 11.5 Hz, J2 ) 6 Hz, 1H), 2.41-2.23 (m, 2H), 2.23-1.92 (m,
4H), 1.91-1.56 (m, 5H), 1.28 (t, J ) 7 Hz, 3H), 1.14 (s, 3H). 13
C
NMR (75 MHz, CDCl3): δ 214.5, 172.9, 62.6, 60.8, 56.2, 53.7,
50.3, 50.1, 47.0, 44.2, 38.2, 28.5, 24.9, 16.9, 14.5. HRMS (m/z):
found 249.1482 [M + H]+; calcd for C15H21O3 249.1491 [M +
H]+.
Methyl-8-methyl-10-oxo-tetracyclo[4.3.2.02,601,9]undec-8-car-
boxylate (43). A solution of 34 (0.170 g, 0.72 mmol) in acetone
(300 mL) was irradiated with a medium-pressure mercury vapor
lamp (125 W, APP) in a quartz immersion well for 2 h under
nitrogen. The solvent was removed, and the residue was chromato-
graphed. Elution with petroleum ether-ethyl acetate (85:15) gave
the photoproduct 43 as a colorless liquid (0.052 g, 30%). IR (neat)
propellane 47 (0.035 g, 50%) as a colorless liquid. IR (neat) νmax
:
1732 cm-1. 1H NMR (400 MHz, CDCl3): δ 3.68 (s, 3H), 2.56 (d,
J ) 13.6 Hz, 2H), 2.40 (AB system, JAB ) 18.3 Hz, 4H), 1.80-
1.50 (cluster of m, 8H), 1.28 (s, 3H). 13C NMR (100 MHz,
CDCl3): δ 219.6, 178.4, 57.4, 54.4, 52.2, 51.3, 42.0, 26.8, 25.3,
23.6. HRMS (m/z): found 237.1485 [M + H]+; calcd for C14H21O3
237.1491 [M + H]+.
Ethyl-11-oxo-tricyclo[4.3.3.01,6]dodecan-8-carboxylate (48). A
solution of 44 (0.164 g, 0.66 mmol), tributyltin hydride (0.3 mL,
0.3 g, 0.99 mmol), and AIBN (0.108 g) in dry benzene (65 mL)
10164 J. Org. Chem., Vol. 72, No. 26, 2007

Molecular Complexity from Aromatics
was refluxed for 12 h under nitrogen atmosphere. Solvent was
removed under vacuum, and the residue was chromatographed. Tin
impurities were removed by elution with petroleum ether. Elution
with petroleum ether-ethyl acetate (95:5) furnished the product 48
Hz, 2H), 1.42-1.18 (m merged with s, 11H). 13C NMR (100 MHz,
CDCl3) δ: 219.0, 179.5, 52.3, 49.9, 48.6, 47.8, 47.4, 31.4, 30.1,
21.3. HRMS (m/z): found 251.1657 [M + H]+; calcd for C15H23O3
251.1647 [M + H]+.
1
(0.105 g, 64%). IR (neat) νmax: 1738 (br) cm-1. H NMR (400
MHz, CDCl3): δ 4.16 (q, J ) 7.6 Hz, 2H), 3.10-3.03 (m, 1H),
2.30-2.14 (m, 6H), 1.94-1.88 (m, 2H), 1.67-1.36 (m, 8H), 1.27
(t, J ) 7.2 Hz, 3H). 13C NMR (100 MHz, CDCl3): δ 218.5, 176.5,
60.6, 49.2, 48.3, 40.2, 39.8, 31.5, 21.5, 14.2. HRMS (m/z): found
251.1658 [M + H]+; calcd for C15H23O3 251.1647 [M + H]+.
Methyl-8-methyl-11-oxo-tricyclo[4.3.3.01,6]dodecan-8-carbox-
ylate (49). A solution of 45 (0.100 g, 0.4 mmol), tributyltin hydride
(0.5 mL, 0.50 g, 1.7 mmol,), and AIBN (0.045 g) in dry benzene
(10 mL) was refluxed for 6 h under nitrogen atmosphere. Removal
of solvent followed by chromatography [petroleum ether-ethyl
Acknowledgment. We are grateful to the Department of
Science and Technology for continuing financial support. P.K.S.
and R.B.S. thank CSIR, New Delhi for a fellowship. Thanks
are due to DST for creating a national single-crystal X-ray
facility.
Supporting Information Available: 1H NMR and 13C NMR
spectra of 14a,b, 15a,b, 5a-d, 6a,b, 19, 22-25, 27a,b, and 49
and CIF data and ORTEP diagram of 27a. This material is available
free of charge via the Internet at http://pubs.acs.org.
acetate (95:5)] gave the product 49 (0.090 g, 89%). IR (neat) νmax
:
1
1738, 1732 cm-1, H NMR (400 MHz, CDCl3): δ 3.65 (s, 3H),
2.60 (d, J ) 14 Hz, 2H), 2.18 (d, J ) 4 Hz, 4H), 1.55 (d, J ) 14
JO702168S
J. Org. Chem, Vol. 72, No. 26, 2007 10165