Barrelene, a New Convenient Synthesis

Full text of DOI:10.1021/jo962267f

4162
J . Org. Chem. 1997, 62, 4162-4163
Sch em e 1a
Ba r r elen e, a New Con ven ien t Syn th esis
Sergio Cossu, Simone Battaggia, and
Ottorino De Lucchi*
Dipartimento di Chimica, Universita` Ca’ Foscari di Venezia,
Dorsoduro 2137, I-30123 Venezia, Italy
Received December 4, 1996
Barrelene (bicyclo[2.2.2]octa-2,5,7-triene, 1) is the for-
mal Diels-Alder adduct of acetylene to benzene.1 Since
neither acetylene nor benzene is reactive in cycloaddition
reactions, the synthesis of 1 requires the definition of
both an efficient acetylene equivalent2 and of a reagent
able to temporarily suppress the aromatic character of
benzene, in such a way as to allow it to react as a diene.3
In other words, this equals the definition of a synthon of
cyclohexatriene in cycloaddition reactions.3 In addition
to the synthetic challenge, barrelene is interesting by
itself, theoretically (it can be considered as a unique
Mo¨bius-like molecule),1 and spectroscopically.1 Finally,
barrelene is the starting material for the preparation of
the equally interesting semibullvalene via the photo-
chemical di-π-methane rearrangement.4
In addition to the first preparation of 1 reported by
Zimmerman and co-workers, which employes a multistep
reaction sequence starting from R-pyrone,1 two other
preparations of 1 were later reported by Dauben5a and
de Meijere,5b employing the maleic anhydride adducts to
cyclooctatetraene and hydroquinone. All these proce-
dures produce barrelene by photolysis and/or thermolysis
so that it becomes contaminated with byproducts that
are difficult to eliminate.
a
Reaction conditions: (i) benzene, 48 h, 80 °C; (ii) WCl6/BuLi,
THF, 24 h, rt; (iii) Na/Hg, buffered MeOH.
wise to add oxepin (2) from time to time during this
period to avoid unwanted decomposition of the diene and
formation of side products. We found it best to add a
half equivalent of 2 at the beginning and to add the
remaining quantity of the reagent in aliquots each day.
A rise in the temperature is detrimental to the yields and
purity of the reaction. In addition to polymeric materials,
a number of products formed that were not identified.
Lewis acids or other methods known to activate the
Diels-Alder reaction10 have been tried, but most of them
are not compatible with the nature of the diene, leading
to decomposition of oxepin (2) and formation of phenol.
The reaction with other sulfonyl dienophiles has been
carried out. With either the (E)-isomer 3b or with the
1,4-benzodithiin 1,1′,4,4′-tetraoxide 3c11 an improvement
of the reactivity was observed. The reaction of oxepin
(2) with (E)-3b takes 20 h in refluxing benzene, while
with benzodithiin 3c 48 h at rt. Both afford adducts 4b
or 4c quantitatively. Such a trend in reactivity has
already been observed in other experiments and is
reported in the literature.6
Following our interest in the synthesis of unsaturated
polycyclic compounds, we report an inexpensive and
expeditious preparation of high quality 1, based on the
cycloaddition of 1,2-bis(phenylsulfonyl)alkenes6 to oxepin
(2)7 (Scheme 1).
The starting reagents are rapidly available in multi-
gram quantities and close-to-quantitative yields, oxepin
(2) from 1,4-cyclohexadiene via bromination, epoxidation,
and elimination8 and (Z)-1,2-bis(phenylsulfonyl)ethylene
(3a ) from (Z)-dichloroethylene and thiophenol followed
by oxidation.6,9 The latter can also be purchased from
standard chemical suppliers. The Diels-Alder reaction
between 2 and 3 takes 2 days to reach completion. It is
(1) Zimmerman, H. E.; Grunewald, G. L.; Paufler, R. M.; Sherwin,
M. A. J . Am. Chem. Soc. 1969, 91, 2330.
(2) De Lucchi, O.; Modena, G. Tetrahedron 1984, 40, 2585.
(3) A review article covering this topic is in preparation.
(4) Zimmerman, H. E.; Binkley, R. W.; Givens, R. S.; Grunewald,
G. L.; Sherwin, M. A. J . Am. Chem. Soc. 1969, 91, 3316. Zimmerman,
H. E.; Iwamura, H. Ibid. 1970, 92, 2015.
(5) (a) Dauben, W. G.; Rivers, G. T.; Twieg, R. J .; Zimmerman, W.
T. J . Org. Chem. 1976, 41, 889. (b) Weitemeyer, C.; de Meijere, A.
Angew. Chem., Int. Ed. Engl. 1976, 15, 686. See also: Taylor, Y. N. J .
Org. Chem. 1972, 37, 2904.
(6) Cossu, S.; De Lucchi, O.; Fabbri, D.; Licini, G.; Pasquato, L. Org.
Prep. Proc. Int. 1991, 23, 571.
(7) Oxepin appears to have been used only once as a synthetic
equivalent of cyclohexatriene: Nakazawa, T.; Kubo, K.; Murata, I.
Angew. Chem., Int. Ed. Engl. 1981, 20, 189.
Adducts 4a -c can be deepoxidized readly with WCl6
and n-buthyllithium in very high yields.12 Other methods
of deoxygenation13 were tested; however, none of these
were superior to WCl6/BuLi. The compatibility of the
reducing agent with the sulfonyl group as well as the
double bonds is responsible for the observed reactivity.
Reductive desulfonylation with sodium amalgam in
(8) Vogel, E.; Boll, W. A.; Gunther, H. Tetrahedron Lett. 1965, 609.
Rastetter, W. H. J . Am. Chem. Soc. 1976, 98, 6350. Gillard, J . R.;
Newlands, M. J .; Bridson, J . N.; Burnell, D. J . Can. J . Chem. 1991,
69, 1337. The oxidation of 4,5-dibromocyclohexene to the epoxide occurs
in 95% yield in refluxing benzene for 1.5 h using a 5% excess of
m-chloroperbenzoic acid.
(9) Pasquato, L.; De Lucchi, O. In Encyclopedia of Reagents for
Organic Synthesis; Paquette, L. A., Ed.; Wiley: New York, 1995; Vol.
1, p 547. De Lucchi, O.; Lucchini, V.; Pasquato, L.; Modena, G. J . Org.
Chem. 1984, 49, 596.
(10) Pindur, U.; Lutz, G.; Otto, C. Chem. Rev. 1993, 93, 741.
(11) Wenkert, E.; Broka, A. Finn. Chem. Lett. 1984, 126. Nakayama,
J .; Nakamura, Y.; Hoshino, M. Heterocycles 1985, 23, 1119.
(12) Sharpless, K. B.; Umbreit, M. A.; Nieh, M. T.; Flood, T. C. J .
Am. Chem. Soc. 1972, 94, 6538.
(13) See, for example: Vedejs, E.; Fuchs, P. L. J . Am. Chem. Soc.
1973, 95, 822. Kauffmann, T.; Bisking, M. Tetrahedron Lett. 1984, 25,
293. Barton, D. H. R.; Fekih, A.; Lusinchi, X. Tetrahedron Lett. 1985,
26, 6197.
S0022-3263(96)02267-0 CCC: $14.00 © 1997 American Chemical Society

Notes
J . Org. Chem., Vol. 62, No. 12, 1997 4163
0.54 g (96% yield) of colorless crystals: mp 276 °C dec (CH2-
Cl2-Et2O); H NMR (200 MHz, CDCl3) δ 8.13-8.02, 7.88-7.78
(4 H, series of m, Ar), 5.63-5.52 (2 H, m), 4.12 (2 H, s), 4.02-
3.92 (m, 2 H), 3.45-3.88 (2 H, m); 13C NMR (50 MHz, CDCl3) δ
138.22, 138.83, 126.28, 125.67, 64.28, 44.77, 36.29.
buffered methanol occurs uneventfully, leading to bar-
relene in high yields. It is worth mentioning that among
the several methods of desulfonylation,6 the sodium
amalgam reduction of bis(phenylsulfonyl) compounds,
when leading to hydrocarbons, allows the clean separa-
tion of the hydrocarbon from the other products by a
simple extraction with pentane. The overall yields of
barrelene from 2 and 3a -c is near 75%.
It should be noted that other conceivable procedures
for the synthesis of 1, especially considering cis-3,5-
cyclohexadiene-1,2-diol and derivatives, have also been
tested. These procedures were recently used to prepare
benzobarrelenes14 and when applied to 1 turned out to
be less practical and/or more expensive than the one
presented here.
1
Rea ction of 4a -c w ith WCl6/Bu Li. P r ep a r a tion of 5a -
c. Gen er a l P r oced u r e. A solution of n-BuLi (0.4 mL of a 2.5
M solution in hexanes) was added to a deep red solution of WCl6
(0.2 g, 0.5 mmol) and dry THF (10 mL) stirred at -78 °C, under
argon, in the dark. After 40 min, the resulting yellow solution
was left to reach rt (ca. 1 h), treated with 4a (or 4b or 4c) (0.25
mmol), and stirred at rt for an additional 24 h. During this
period, the color changed from yellow to green. The crude
reaction mixture was concentrated under reduced pressure,
diluted with dichloromethane (2 mL), and purified through a
short silica gel column, CH2Cl2 eluant.
7r,8r-Bis(ph en ylsu lfon yl)bicyclo[2.2.2]octa-2,5-dien e (5a):
90% yield; mp 122-4 °C (CH2Cl2-Et2O); 1H NMR (400 MHz,
CDCl3) δ 8.00 (4 H, d, J ) 8.0 Hz, Ar), 7.66 (2 H, t, J ) 8.0 Hz,
Ar), 7.57 (4 H, t, J ) 8.0 Hz, Ar), 6.75-6.71 (2 H, m), 6.38-6.34
(2 H, m), 4.03 (2 H, quint, J ) 4.0 Hz), 3.74 (2 H, bs); 13C NMR
(100 MHz, CDCl3) δ 140.89, 136.77, 133.85, 133.58, 128.95,
128.83, 69.08, 39.73.
Exp er im en ta l Section
8-en do,9-en do-Bis(ph en ylsu lfon yl)-3-oxatr icyclo[3.2.2.02,4]-
n on -6-en e (4a ). A mixture of freshly prepared oxepin (2)8 (0.5
g, 5.3 mmol), (Z)-1,2-bis(phenylsulfonyl)ethylene (3a ) (1.09 g, 3.5
mmol), and benzene (10 mL) was placed in a screw-capped Pyrex
test tube purged with argon, sealed, and stirred at 80 °C. After
20 h, an extra amount of 2 (0.5 g, 5.3 mmol) was added. After
48 h, the reaction reached completion (TLC). The solid was
separated, washed with cold benzene (20 mL), and dried to afford
1.34 g (96% yield) of colorless crystals: mp 157-8 °C (CH2Cl2-
Et2O); 1H NMR (400 MHz, CDCl3) δ 8.05-7.92 (4 H, m, Ar),
7.71-7.53 (6 H, m, Ar), 6.14-6.03 (2 H, m), 3.86 (2 H, s), 3.60
(2 H, bs), 3.20-3.07 (2 H, m); 13C NMR (100 MHz, CDCl3) δ
133.87, 129.06 (2 C), 128.9, 126.49, 66.96, 46.09, 36.90.
7r,8â-Bis(ph en ylsu lfon yl)bicyclo[2.2.2]octa-2,5-dien e (5b):
85% yield; mp 211-3 °C (CH2Cl2-Et2O); 1H NMR (200 MHz,
CDCl3) δ 8.02-7.48 (10 H, m, Ar), 6.62-6.40 (4 H, m), 4.11-
3.98 (2 H, t, J ) 5.0 Hz), 3.82 (2 H, s); 13C NMR (50 MHz, CDCl3)
δ 141.44, 135.88, 133.86, 133.79, 129.05, 128.38, 66.81, 38.36.
1,4,4a ,10a -Tetr a h yd r o-1,4-eth en oth ia n th r en e 5,5,10,10-
1
tetr a oxid e (5c): 90% yield; mp 220 °C dec (CH2Cl2-Et2O); H
NMR (400 MHz, CDCl3) δ 8.13-8.03 (2 H, m, Ar), 7.86-7.78 (2
H, m, Ar), 6.65-6.57 (2 H, m), 6.09-6.01 (2 H, m), 4.50-4.40 (2
H, m), 3.91 (2 H, bs); 13C NMR (100 MHz, CDCl3) δ 137.74,
136.06, 133.70, 132.85, 126.18, 66.00, 39.27; IR (KBr disk) 3025,
2954, 1329, 1290, 1267, 1150, 1104, 694, 595.
8-en do,9-exo-Bis(ph en ylsu lfon yl)-3-oxatr icyclo[3.2.2.02,4]-
n on -6-en e (4b). A mixture of freshly prepared oxepin (2)8 (1.0
g, 10.6 mmol), (E)-1,2-bis(phenylsulfonyl)ethylene (3b) (1.09 g,
3.5 mmol), and benzene (10 mL) was placed in a screw-capped
Pyrex test tube, purged with argon, sealed, and stirred at 80
°C. After 20 h, the reaction reached completion (TLC). The solid
was collected by suction, washed with cold benzene (20 mL), and
recrystallized from dichloromethane-diethyl ether, affording
1.34 g (96% yield) of colorless crystals: mp 222-4 °C (CH2Cl2-
Bicyclo[2.2.2]octa -2,5,7-tr ien e (1). A mixture of 5a (or 5b
or 5c) (6 mmol) and KH2PO4 (1 g, 8.4 mmol) in dry methanol
(20 mL) was purged with argon, and sodium amalgam (ca. 6%,
an 8/1 equivalent ratio of sodium to substrate) was added in
portions with efficient stirring. The reaction mixture was stirred
at room temperature and monitored by TLC, eluting with
n-hexane. After 2 h, the conversion was complete. Water was
added, and the reaction mixture was extracted with n-pentane
(3 × 50 mL). The combined extracts were washed with brine,
dried (Na2SO4), and carefully concentrated under reduced pres-
sure (water pump, barrelene is highly volatile!) to furnish 1 (0.55
g, 90% yield), which was recognized by comparison of the
spectroscopic data with those reported in literature.1,15
1
Et2O); H NMR (200 MHz, CDCl3) δ 8.00-7.56 (10 H, series of
m, Ar), 5.96-5.83 (2 H, m), 3.98 (1 H, dd, J ) 6.0, 2.6 Hz), 3.86
(1 H, dd, J ) 6.0, 2.6 Hz), 3.82 (1 H, t, J ) 3.9 Hz), 3.69-3.51
(2 H, m), 3.39 (1 H, t, J ) 3.9 Hz); 13C NMR (50 MHz, CDCl3) δ
138.39 (2 C), 134.14 (2 C), 129.16 (2 C), 128.37 (2 C), 127.36,
125.53, 65.07, 62.60, 45.59, 45.09, 35.66, 35.45.
Ack n ow led gm en t. This work was supported by
CNR (Rome). We thank the Regione Veneto, Depart-
ment for Industry and Energy, for financial support in
purchasing the Varian Unity 400 NMR spectrometer.
14-O x a -3,10-d it h ia p e n t a c y c lo [10.3.2.0.2,110.4,9013,15]-
h ep ta d eca -4(9),5,7,16-tetr a en e 3,3,10,10-Tetr a oxid e (4c). A
dichloromethane (4 mL) solution of 3c (0.4 g, 1.74 mmol) in a
Pyrex test tube, equipped with a rubber septum and magnetic
stirring band, was purged with argon and sealed. An ethereal
solution (8 mL) of freshly prepared oxepin (2)8 (0.057 g, 0.6
mmol) was added by syringe, and the resulting mixture was
stirred at rt. After 12 and 36 h, two additional amounts of 2
(0.057 g, 0.6 mmol each) were added. The solid was collected
by suction, washed with cold diethyl ether (2 × 20 mL), and
recrystallized from dichloromethane-diethyl ether, affording
Su p p or tin g In for m a tion Ava ila ble: Copies of NMR
spectra (14 pages). This material is contained in libraries on
microfiche, immediately follows this article in the microfilm
version of the journal, and can be ordered from the ACS; see
any current masthead page for ordering information.
J O962267F
(14) Pu, L.; Grubbs, R. H. J . Org. Chem. 1994, 59, 1351.
(15) Taylor, G. N. J . Org. Chem. 1972, 37, 2904.