Rearrangements of cyclobutenones. Electrocyclic ring closure and thermal ring expansions of 3-allenyl- and 3-alkynyl-2-dienyl-4,4-dimethoxycyclobutenones

Article abstract of DOI:10.1021/jo010919g

Thermal rearrangements of 2-allenyl- and 2-alkynyl-3-(2-ethenylphenyl)-4,4-dimethoxycyclobutenones were studied. At ambient temperature, the allenyl compounds undergo an electrocyclic cascade to give bicyclo[4.2.0]-octadienyl-fused cyclobutenones. These u

Full text of DOI:10.1021/jo010919g

1388
J . Org. Chem. 2002, 67, 1388-1391
Sch em e 1a
Rea r r a n gem en ts of Cyclobu ten on es.
Electr ocyclic Rin g Closu r e a n d Th er m a l
Rin g Exp a n sion s of 3-Allen yl- a n d
3-Alk yn yl-2-d ien yl-4,4-
d im eth oxycyclobu ten on es
Antonio R. Hergueta and Harold W. Moore*
Department of Chemistry, University of California,
Irvine, California 92697-2025
halmoore@uci.edu
Received September 11, 2001
Abstr act: Thermal rearrangements of 2-allenyl- and 2-alky-
nyl-3-(2-ethenylphenyl)-4,4-dimethoxycyclobutenones were
studied. At ambient temperature, the allenyl compounds
undergo an electrocyclic cascade to give bicyclo[4.2.0]-
octadienyl-fused cyclobutenones. These unusual tetracyclic
cyclobutenones were shown to be viable synthetic precursors
to benzo[a]anthracene-7,12-diones, compounds representing
the framework of the angucycline group of naturally occur-
ring antibiotics. In contrast, the 2-alkynylcyclobutenones are
stable at ambient temperature but undergo a facile rear-
rangement at 110 °C (toluene) to give the previously
unknown naphthalene derivatives, 1,2-dihydro-2,2-dimethoxy-
1-(3-alkenylidene)naphtho[2,1-b]furans.
a
Key: (a) 1-lithio-3-phenyl-1-propyne/THF, -78 °C; (b) TEA/
THF, rt.
Reported here are two unusual rearrangements of 2-(2-
ethenylphenyl)-4,4-dimethoxycyclobutenones. The first
involves the conversion of 3-allenyl derivatives to highly
substituted tetracyclic cyclobutenones.1 Here, the tet-
raene moiety comprising the unsaturated cyclobutenone
subtituents undergoes facile electrocyclic ring closure to
give bicyclo[4.2.0]octadienyl-fused cyclobutenones. The
second involves reorganization of 3-alkynyl derivatives
to 1,2-dihydro-2,2-dimethoxy-1-(3-alkenylidene)naphtho-
[2,1-b]furan derivatives.2
These studies were encouraged by an unusual trans-
formation observed during the synthesis of 4,4-dimethoxy-
3-(3-phenyl-1-propynyl)-2-(2-ethenylphenyl)-2-cyclobuten-
1-one (2a ) from 2-(ethenylphenyl)-3,4,4-trimethoxy-
cyclobutenone (1) as outlined in Scheme 1. Specifically,
when the starting cyclobutenone was treated with the
1-lithio-3-phenyl-1-propyne in THF at -78 °C followed
by triethylamine (TEA) at ambient temperature,
3-[(Z)-benzylidene]-2b,3,4,4a-tetrahydro-2,2-dimethoxy-
dicyclobuta[a,c]naphthalen-1(2H)-one (5) was realized in
44% isolated yield. The structure of the product is based
upon its characteristic spectral properties including a
single-crystal X-ray analysis.
ring closure to provide the product 5. This mechanism is
consistent with the observation that treatment of a THF
solution of purified 2a with TEA resulted in the formation
of a green intermediate, presumably 4, the color of which
rapidly faded within a few seconds, and 5, obtained in
32% yield.
These results suggest that 3-allenyl-2-(2-ethenylphe-
nyl)-4,4-cyclobutenones would spontaneously rearrange
at ambient temperature to the corresponding bicyclo-
[4.2.0]octadiene systems. This was observed to be the case
as the results outlined in Scheme 2 indicate. Treatment
(-78 °C) of a THF solution of 1 with, respectively,
1-lithio-1-methoxyallene, 1-lithio-1-tert-butoxyallene,
1-lithio-3,3-dimethylallene, and 1-lithio-1-methoxy-1,2,3-
butatriene followed by an ammonium chloride quench
gave the corresponding tetracyclic cyclobutenones, 6
(81%), 7 (71%), 8 (74%), and 9 (35%). For 6-8, after the
quench and while warming to ambient temperature, a
deep blue coloration developed that faded as the reaction
proceeded, (6, 30 s), (7, 5 min), (8, 1 min). No color change
was observed during the formation of 9. Assuming
intermediates analogous in structure to 4, the more
persistent color presumably corresponds to the more
sterically hindered examples.
In a comparison study, thermolyses (toluene, 110 °C)
of the 3-alkynyl derivatives (2a -f) were investigated
(Scheme 3). Unlike the 3-allenyl derivatives, electrocyclic
ring closure of the trienyne moiety was not observed, nor
was alkyne/allene isomerization. Rather, the cyclobuten-
one ring is the key reacting group. Specifically, it
undergoes electrocyclic ring opening to the vinylketene
intermediates 10a -f, which proceed to the naphthols
11a -f. These were not isolated but led to the previously
The reaction is envisaged to involve base-catalyzed
(TEA) isomerization of the alkynyl group in 2a to the
corresponding allenyl derivative 3. This then undergoes
two consecutive electrocyclic reactions, an 8π ring closure
to the intermediate cyclooctatetraene 4 followed by a 6π
(1) An analogous transformation involving 2-alkenyl derivatives has
recently been reported. See: Tiedemann, R.; Heileman, M. J .; Schau-
mann, E.; Moore, H. W J . Org. Chem. 1999, 64, 2170; Heileman, M.
J .; Tiedemann, R.;.; Moore, H. W. J . Am. Chem. Soc. 1998, 120, 3801.
(2) For a recent review on the ring expansion of cyclobutenones,
see: Moore, H. W.; Yerxa B. R. Adv. Strain Org. Chem. 1995, 4, 81-
162.
10.1021/jo010919g CCC: $22.00 © 2002 American Chemical Society
Published on Web 01/25/2002

Notes
J . Org. Chem., Vol. 67, No. 4, 2002 1389
Sch em e 2a
Sch em e 4a
a
Key: (a) 2-lithioanisole/THF, -78 °C; (b) HCl, rt; (c) benzene,
reflux; (d) Ag2O, K2CO3; (e) bromine/CHCl3, -10 °C; (f) visible
light/CHCl3, rt.
a
Key: (a) 1-lithio-1-methoxyallene/THF, -78 °C; (b) 1-lithio-
1-tert-butoxyallene/THF, -78 °C; (c) 1-lithio-3,3-dimethoxyallene/
THF, -78 °C; (d) 1-lithio-1-methoxy-1,2,3-butatriene/THF, -78 °C.
starting materials for the synthesis of benza[a]anthracene-
7,12-diones, compounds representing the framework of
the angucycline group of natural products.3 An example
is outlined in Scheme 4. Here, the tetracylic cyclobuten-
one 6 was converted to 13 upon treatment with 2-lithio-
anisole in THF at -78 °C followed by hydrolysis of the
acetal linkage (HCl, ambient temperature). The crude
product was dissolved in benzene and subjected directly
to thermolysis at refluxing temperature followed by an
oxidative workup (Ag2O) to provide the quinone 14 in
60% overall yield.2
Sch em e 3a
Quinone 14 was stable to further thermolysis or
photolysis. This is of note since previously reported
examples lacking the 3-alkylidene moiety readily cleave
to the corresponding benza[a]anthracene-7,12-dione when
subjected to irradiation with fluorescent laboratory light.1,4
Such a transformation could also be accomplished with
14 by first addition of bromine to the ethylidene group
followed by photolysis with visible light.4 This provided
6,11-dimethoxybenzo[a]anthracene-7,12-dione (15) in 77%
overall yield from 14. The structure of 15 is in strict
agreement with its observed spectral properties.
In an analogous fashion, 6,11-dimethoxy-5-methylben-
za[a]anthracene-7,12-dione (19) was prepared from dim-
ethyl squarate as outlined in Scheme 5. Initially, the
cyclobutenone 16 was obtained in 71% yield upon treat-
ment of dimethyl squarate with 1-lithio-2-(1-methylethe-
nyl)benzene followed by a methanol quench.5 This was
then converted to 17 (72%) upon treatment 1-lithio-1-
methoxyallene in THF at -78 °C. This was then con-
verted to 19 in 48% overall yield by the method outlined
above.
(3) For a recent review on these compounds, see: Rohr, J .; Thiericke,
R. Natural Prod. Rep. 1992, 103. Also see: (a) Krohn, K.; Ballwanz,
F.; Baltus, W. Liebigs Ann. Chem. 1993, 911. (b) Larsen, D. S.; O’Shea,
M. D. Tetrahedron Lett. 1993, 34, 1373. (c) Krohn, K.; Khanbabaee,
K. Angew. Chem., Int. Ed. Engl. 1994, 33, 99. (d) Larsen, D. S.; O’Shea,
M. D. J . Chem. Soc., Perkin Trans. 1 1995, 1019 e) Kim, K.; Sulikowski,
G. A. Angew. Chem., Int. Ed. Engl. 1995, 34, 2397. (f) Matsuo, G.; Miki,
Y.; Nakata, M.; Matsumura, S.; Toshima, K. Chem. Commun. 1996,
225. (g) Carreno, M. C.; Urbano, A.; Fischer, J . Angew. Chem., Int.
Ed. Engl. 1997, 36, 1621. (h) Larsen, D. S.; O’Shea, M. D.; Brooker, S.
Chem. Commun. 1996, 203.
(4) Photolysis was carried out by exposing a benzene solution of the
quinone to two 40 W fluorescent lights for a few hours.
(5) This method is particularly efficient for the synthesis of substi-
tuted cyclobutendione monoketals from squaric acid. See, for ex-
ample: Gayo, L.; Moore, H. W. J . Org. Chem. 1992, 57, 6896;. Santora,
V. J .; Moore, H. W. J . Am. Chem. Soc. 1995, 117, 8486.
a
Key: (a) R-CtC-Li, THF, -78 °C; (b) toluene, 110 °C.
unknown naphthalene derivative 12a -f (25-81%) upon
addition of the naphtholic hydroxy group to the proximal
enyne substituent.
The structures of 12a -f are in agreement with their
observed spectral properties. Of particular note are the
absence of carbonyl group absorptions in their IR spectra
and the presence of an allenyl group stretch in the range
of 1932-1955 cm-1
.
The 3-alkylidene-2b,3,4,4a-tetrahydro-2,2-dimethoxy-
dicyclobuta[a,c]naphthalen-1(2H)-one, 5-9, are useful

1390 J . Org. Chem., Vol. 67, No. 4, 2002
Notes
Sch em e 5a
7.4 Hz, 1H), 7.22-7.24 (m, 2H), 7.26 (dt, J ) 1.4, 7.5 Hz, 1H),
7.31 (dt, J ) 1.4, 7.5 Hz, 1H), 7.34-7.37 (m, 1H), 7.37-7.42 (m,
2H), 7.63 (dd, J ) 1.3, 7.5 Hz, 1H); 13C NMR (CDCl3, 125 MHz)
191.6, 177.1, 152.4, 139.3, 137.8, 135.8, 130.7, 128.4, 127.9, 127.5,
127.4, 127.0, 126.2, 123.9, 123.4, 119.0, 53.8, 53.0, 46.0, 43.9,
37.3; exact mass calcd for C23H20O3 344.1412, found 344.1423.
2b,3,4,4a -Tetr a h yd r o-2,2,2b-tr im eth oxy-3-m eth ylen ed i-
cyclobu ta [a ,c]n a p h th a len -1(2H)-on e (6). To a solution of
methoxyallene (0.50 g, 7.14 mmol) in THF (25 mL) at -40 °C
was added nBuLi (4.46 mL, 1.6 M in hexanes, 7.14 mmol).7 The
resulting reaction mixture was stirred for 30 min (-40 °C),
cooled to -78 °C, and then transferred via cannula to a solution
of 1 (0.41 g, 1.60 mmol) in THF (25 mL). The resulting solution
was stirred for 30 min at -78 °C, quenched with saturated
ammonium chloride (20 mL), and extracted with diethyl ether.
The combined organic portion was washed with brine, dried over
anhydrous magnesium sulfate, and concentrated in vacuo.
Chromatography (hexanes/EtOAc ) 12:1) gave 6 (0.38 g, 81%)
as a white solid: mp 92.5-94.0 °C; IR (KBr) 2943, 1765, 1449
cm-1;1H NMR (CDCl3, 500 MHz) 2.28 (ddt, J ) 2.8, 9.1, 15.5
Hz, 1H), 3.00 (dddd, J ) 1.8, 1.9, 10.1, 15.5 Hz, 1H), 3.23 (s,
3H), 3.53 (s, 3H), 3.60 (s, 3H), 3.81 (dd, J ) 9.1, 10.1 Hz, 1H),
5.13 (s, 1H), 5.36 (s, 1H), 7.26 (d, J ) 7.5 Hz, 1H), 7.30 (dt, J )
1.3, 7.5 Hz, 1H), 7.35 (dt, J ) 1.3, 7.5 Hz, 1H), 7.69 (d, J ) 7.5
Hz, 1H); 13C NMR (CDCl3, 125 MHz) 189.4, 171.5, 154.5, 147.9,
138.3, 130.8, 127.3, 126.4, 122.8, 118.4, 108.2, 79.7, 53.2, 52.8,
51.9, 43.0, 35.0; exact mass calcd for C18H18O4 298.1204, found
298.1197.
a
Key: (a) 1-lithio-1-methoxyallene/THF, -78 °C; (b) 2-lithio-
anisole/THF, -78 °C; (c) HCl, rt; (d) benzene, reflux; (e) Ag2O/
K2CO3; (f) bromine/Cl3CH, -10 °C; (g) visible light/CHCl3, rt.
The significant points to arise from this study include
the following: (1) thermal rearrangements of 2-allenyl-
3-(2-ethenylphenyl)-4,4-dimethoxycyclobutenones were
observed to take place at ambient temperature to give
3-a lk yliden e-2b,3,4,4a -t et r a h ydr o-2,2-dim et h oxy-
dicyclobuta[a,c]naphthalen-1(2H)-one, 5-9. Such com-
pounds were found to be useful synthetic precursors to
benza[a]anthracene-7,12-diones, e.g., 15 and 19; (2) in
comparison, 2-alkynyl-3-(ethenylphenyl)-4,4-dimethoxy-
cyclobutenones were observed to be stable at ambient
temperature but rearranged to the unusual 1-(1-alky-
lidene)-1,2-dihydro-2,2-dimethoxynaphtho[2,1-b]furan,
12a -f, at 110 °C (refluxing toluene).
3-(1-H e xyn yl)-4,4-d im e t h oxy-2-(2-vin ylp h e n yl)-2-cy-
clobu ten -1-on e (2e). To a solution of 1-hexyne (0.13 mL, 1.15
mmol) in THF (15 mL) at -78 °C was added nBuLi (0.72 mL,
1.6 M in hexanes, 1.15 mmol). The resulting reaction mixture
was stirred for 30 min (-78 °C) and then transferred via cannula
to a solution of 1 (0.25 g, 0.96 mmol) in THF (25 mL). The
resulting solution was stirred for 1 h at -78 °C, quenched with
saturated sodium bicarbonate (20 mL), and extracted with
diethyl ether. The combined organic portion was washed with
brine, dried over anhyd. magnesium sulfate, and concentrated
in vacuo. Chromatography (hexanes/EtOAc ) 15:1) gave 2e
(0.203 g, 68%) as a yellow oil: IR (film) 2959, 2212, 1765, 1341
cm-1 1H NMR (CDCl3, 500 MHz) 0.93 (t, J ) 7.5, 3H), 1.44
;
Exp er im en ta l Section
(sextet, J ) 7.5 Hz, 2H), 1.58-1.64 (m, 2H), 2.59 (t, J ) 7.0 Hz,
2H), 3.63 (s, 6H), 5.34 (d, J ) 11.1 Hz, 1H), 5.72 (d, J ) 17.1
Hz, 1H), 7.06 (dd, J ) 11.1, 17.1 Hz, 1H), 7.29-7.32 (m, 1H),
7.39 (dd, J ) 7.2, 8.0 Hz, 1H), 7.62 (d, J ) 8.0 Hz, 1H), 7.64 (dd,
J ) 1.0, 7.5 Hz, 1H); 13C NMR (CDCl3, 125 MHz)192.6, 157.3,
155.3, 136.9, 135.2, 130.2, 129.1, 127.5, 126.5, 125.9, 121.2, 116.0,
115.3, 72.8, 53.1, 29.9, 22.0, 20.5, 13.4; exact mass calcd for
C20H22O3 310.1569, found 310.1560.
Gen er a l Meth od s. All air- or water-sensitive reactions were
carried out in flame-dried glassware under nitrogen. Tetrahy-
drofuran (THF) was dried by passing it through two 4 × 36 in.
columns of anhydrous neutral A-2 alumina. Flash column
chromatography was performed using silica gel (230-400 mesh)
according to the procedure of Still, Kahn, and Mitra.6 Analytical
TLC was performed on E. Merck silica gel 60 F254 coated on
1-(1-Hexen ylid en e)-1,2-d ih yd r o-2,2-d im eth oxyn a p h th o-
[2,1-b]fu r a n (12e). A solution of 2e (0.10 g, 0.32 mmol) in
toluene (10 mL) was refluxed for 8 h. Concentration in vacuo
and chromatography in Florisil (hexanes/EtOAc 75:1) gave 3a
(0.038 g, 38%) as a pale yellow oil: IR (film) 2950, 1955, 1627,
1459 cm-1; 1H NMR (CDCl3, 500 MHz) 0.93 (t, J ) 9.3 Hz, 3H),
1.46 (sextet, J ) 7.4 Hz, 2H), 1.60 (tq, J ) 7.4, 9.3 Hz, 2H), 2.32
(dq, J ) 6.8, 7.4 Hz, 2H), 3.47 (s, 3H), 3.50 (s, 3H), 6.08 (t, J )
6.8 Hz, 1H), 7.14 (d, J ) 8.8 Hz, 1H), 7.35 (dt, J ) 1.0, 7.5 Hz,
1H), 7.48 (dt, J ) 1.0, 8.2 Hz, 1H), 7.72 (d, J ) 8.8 Hz, 1H), 7.80
(d, J ) 8.2 Hz, 1H), 8.20 (d, J ) 8.4 Hz, 1H); 13C NMR (CDCl3,
125 MHz) 200.9, 154.6, 130.6, 129.7, 129.1, 129.0, 127.2, 123.7,
122.2, 113.5, 111.6, 101.5, 99.9, 51.6, 51.5, 31.0, 29.2, 22.3, 13.9;
exact mass calcd for C20H22O3 310.1569, found 310.1580.
1,2,2a,12b-Tetr ah ydr o-8,12b-dim eth oxy-1-m eth ylen eben -
zo[a ]cyclobu ta [c]a n th r a cen e-7,12-d ion e (14). To a solution
of 2-bromoanisole (0.50 g, 2.64 mmol) in THF (20 mL) at -78
°C was added nBuLi (1.65 mL, 1.6 M in hexanes, 2.64 mmol).
The resulting reaction mixture was stirred for 1 h (-78 °C) and
then transferred via cannula to a solution of 6 (0.20 g, 0.67 mmol)
in THF (20 mL). The resulting solution was stirred for 1 h at
-78 °C, and HCl (2 mL, 12 N) was added. This mixture was
stirred for 1 h to room temperature, neutralized with saturated
aqueous sodium bicarbonate (20 mL), and extracted with diethyl
glass. Melting points are uncorrected. H and13C NMR spectra
1
were recorded at 500 and 125 MHz, respectively, on CDCl3
solutions. All NMR spectra were referenced to CHCl3 resonance
(7.26 and 77.0 ppm) and are reported in units of δ with coupling
constants in hertz (Hz).
3-[(Z)-Ben zylid en e]-2b,3,4,4a -tetr a h yd r o-2,2-d im eth oxy-
d icyclobu ta [a ,c]n a p h th a len -1(2H)-on e (5). To a solution of
3-phenyl-1-propyne (0.25 g, 2.15 mmol) in THF (25 mL) at -78
°C was added nBuLi (1.34 mL, 1.6 M in hexanes, 2.15 mmol).
The resulting reaction mixture was stirred for 30 min (-78 °C)
and then transferred via cannula to a solution of 2-(2-vinylphe-
nyl)-3,4,4-trimethoxy-2-cyclobutene-1-one (1)2 (0.26 g, 1.00 mmol)
in THF (25 mL). The resulting solution was stirred for 1 h at
-78 °C, quenched with saturated ammonium chloride (20 mL),
and extracted with diethyl ether. The combined organic portion
was washed with brine, dried over anhydrous magnesium
sulfate, and concentrated in vacuo. The crude product was
dissolved in THF (25 mL), and dry TEA was added (0.30 mL,
2.15 mmol). This solution was stirred for 1 h at room temper-
ature and concentrated in vacuo. Chromatography (hexanes/
EtOAc ) 15:1) gave 5 (0.15 g, 44% overall yield from 1) as a
white solid: mp 122-123 °C (from hexanes/EtOAc); IR (KBr)
2942, 1758, 1635 cm-1;1H NMR (CDCl3, 500 MHz) 3.17-3.21
(m, 2H), 3.33 (s, 3H), 3.58 (s, 3H), 3.97 (q, J ) 8.4 Hz, 1H), 4.59
(dd, J ) 2.0, 8.1 Hz, 1H), 6.35 (d, J ) 2.0 Hz, 1H), 7.15 (d, J )
(7) Hoff, S.; Brandsma, L.; Arens, J . F. Recl. Trav. Chim. 1968, 87,
916. Hoff, S.; Brandsma, L.; Arens, J . F. Recl. Trav. Chim. 1968, 87,
1179. For a review, see: Zimmer, R. Synthesis 1993, 165.
(6) Still, C. W.; Kahn, M.; Mitra, A. J . Org. Chem. 1978, 43, 2923.

Notes
J . Org. Chem., Vol. 67, No. 4, 2002 1391
ether. The combined organic portion was washed with brine,
dried over anhydrous magnesium sulfate, and concentrated in
vacuo. The crude product was immediately heated in refluxing
benzene (20 mL) for 1 h, the reaction mixture was cooled to room
temperature and potassium carbonate (0.27 g, 1.98 mmol), and
silver(I) oxide (4.58 g, 1.98 mmol) were added. The reaction
mixture was stirred for 1 h to room temperature, filtrated, and
concentrated in vacuo. Chromatography (hexanes/EtOAc ) 10:
1) gave product 14 (0.145 g, 60% overall yield from 6) as an
orange solid: mp 164-166 °C; IR (KBr) 2924, 1664, 1586, 1560
ogy to the synthesis of 6, compound 17 (0.41 g, 72%, chroma-
tography, hexanes/EtOAc 15:1) was obtained as a white solid
from 16 (0.50 g, 1.82 mmol) and methoxyallene (0.57 g, 8.19
mmol): mp 98-99 °C; IR (KBr) 2944, 1767, 1630 cm-1; 1H NMR
(CDCl3, 500 MHz) 1.73 (s, 3H), 2.35 (s, 2H), 3.16 (s, 3H), 3.52
(s, 3H), 3.61 (s, 3H), 5.13 (s, 1H), 5.39 (s, 1H), 7.31 (dd, J ) 1.2,
7.4 Hz, 1H), 7.39-7.44 (m, 2H), 7.72 (d, J ) 7.4 Hz, 1H); 13C
NMR (CDCl3, 125 MHz) 189.5, 172.2, 154.2, 148.9, 142.5, 130.9,
126.9, 126.6, 124.8, 122.8, 108.4, 80.4, 53.2, 53.1, 52.8, 45.5, 42.9,
17.8; exact mass calcd for C19H20O4 312.1361, found 312.1349.
6,11-Dim et h oxy-5-m et h ylb en za [a ]a n t h r a cen e-7,12-d i-
on e (19). To a solution of 2-bromoanisole (0.48 g, 2.56 mmol) in
THF (20 mL) at -78 °C was added nBuLi (1.60 mL, 1.6 M in
hexanes, 2.56 mmol). The resulting reaction mixture was stirred
for 1 h (-78 °C) and then transferred via cannula to a solution
of 17 (0.20 g, 0.64 mmol), in THF (20 mL). The resulting solution
was stirred for 1 h at -78 °C, and HCl (2 mL, 12 N) was added.
This mixture was stirred for 1 h to room temperature, neutral-
ized with saturated sodium bicarbonate (20 mL), and extracted
with diethyl ether. The combined organic portion was washed
with brine, dried over anhydrous magnesium sulfate, and
concentrated in vacuo. The crude product (protected from light
by aluminum foil) was immediately heated in refluxing benzene
(20 mL) for 1 h then, the reaction mixture was cooled to room
temperature, and potassium carbonate (0.26 g, 1.92 mmol), and
silver(I) oxide (4.44 g, 1.92 mmol) were added. The reaction
mixture was stirred for 1 h to room temperature, filtered, and
concentrated in vacuo to give a light-sensitive orange oil that
was dissolved in CHCl3 (20 mL) and cooled to -10 °C, and
bromine (0.032 mL, 0.64 mmol) in CHCl3 (6 mL) was added. The
resulting reaction mixture was stirred for 1 h (-10 °C), stirred
overnight to room temperature in an aluminum foil lined
cardboared box containing two (2 ft, 40 W) fluorescent light
bulbs, and concentrated in vacuo. Chromatography (hexanes/
EtOAc ) 9:1) gave product 19 (0.10 g, 48% overall yield from
17) as an orange solid: mp 210 °C dec (from diethyl ether/
hexanes); IR (KBr) 2935, 1670, 1576, 1275 cm-1;1H NMR (CDCl3,
500 MHz) 2.72 (s, 3H), 3.95 (s, 3H), 4.04 (s, 3H), 7.27-7.30 (m,
1H), 7.59-7.71 (m, 3H), 7.76 (d, J ) 7.4 Hz, 1H), 8.04 (dd, J )
1.3, 7.4 Hz, 1H), 9.15 (d, J ) 8.2 Hz, 1H); 13C NMR (CDCl3, 125
MHz) 186.6, 184.2, 158.3, 152.5, 136.8, 136.5, 134.4, 134.1, 134.0,
128.9, 128.9, 127.6, 126.9, 126.9, 124.1, 123.7, 118.6, 116.8, 62.2,
56.5, 11.8; exact mass calcd for C21H16O4 332.1048, found
332.1049.
cm-1 1H NMR (CDCl3, 500 MHz) 2.34 (ddt, J ) 2.5, 9.6, 14.8
;
Hz, 1H), 2.89 (ddd, J ) 2.2, 10.0, 14.8 Hz, 1H), 3.12 (s, 3H),
3.74 (dd, J ) 9.6, 10.0 Hz, 1H), 4.03 (s, 3H), 5.15 (s, 1H), 5.69
(dd, J ) 2.2, 2.5 Hz, 1H), 7.24-7.27 (m, 2H), 7.35 (dd, J ) 1.4,
7.0 Hz, 1H), 7.40 (dt, J ) 1.2, 7.4 Hz, 1H), 7.65 (t, J ) 8.0 Hz,
1H), 7.75 (d, J ) 7.6 Hz, 1H), 8.04 (d, J ) 8.0 Hz, 1H); 13C NMR
(CDCl3, 125 MHz) 185.2, 182.8, 158.6, 147.6, 145.2, 138.7, 134.9,
134.5, 131.4, 131.2, 131.2, 127.7, 127.1, 126.6, 122.2, 118.7, 116.9,
110.2, 79.1, 56.5, 51.4, 41.1, 33.9; exact mass calcd for C23H18O4
358.1204, found 358.1221.
6,11-Dim eth oxyben za [a ]a n th r a cen e-7,12-d ion e (15). To
a solution of 14 (0.10 g, 0.27 mmol) in CHCl3 (25 mL) at -10 °C
was added bromine (0.014 mL, 0.27 mmol) in CHCl3 (1 mL). The
resulting reaction mixture was stirred for 1 h (-10 °C), stirred
overnight to room temperature in an aluminum foil lined
cardboared box containing two (2 ft, 40 W) fluorescent light
bulbs, and concentrated in vacuo. Chromatography (hexanes/
EtOAc ) 8:1) gave 15 (0.068 g, 77%) as an orange-yellow solid:
mp 219-220 °C (from EtOAc/hexanes); IR (KBr) 2927, 1669,
1587, 1283 cm-1;1H NMR (CDCl3, 500 MHz) 4.04 (s, 3H), 4.09
(s, 3H), 7.25 (d, J ) 8.4 Hz, 1H), 7.48 (s, 1H), 7.53 (dt, J ) 1.6,
7.6 Hz, 2H), 7.57 (dt, J ) 1.2, 8.1 Hz, 1H), 7.64 (t, J ) 8.0 Hz,
1H), 7.75 (d, J ) 7.7 Hz, 1H), 9.04 (d, J ) 8.5 Hz, 1H); 13C NMR
(CDCl3, 125 MHz) 186.4, 184.1, 158.3, 154.9, 137.5, 136.7, 135.9,
134.2, 129.2, 128.4, 127.0, 126.7, 124.9, 124.3, 123.5, 118.7, 116.6,
112.9, 56.5, 56.4; exact mass calcd for C20H14O4 318.0892, found
318.0887.
4-(2-Isop r op en ylp h en yl)-2,2,3-t r im et h oxycyclob u t en -
on e (16). In analogy to the synthesis of 1, compound 16 (0.75 g,
71%, chromatography, hexanes/EtOAc 10:1) was obtained as a
yellow oil from 1-bromo-2-isopropenylbenzene8 (1.00 g, 5.07
mmol) and dimethyl squarate (0.55 g, 3.90 mmol): IR (film)
2946, 1763, 1635 cm-1;1H NMR (CDCl3, 500 MHz) 2.12 (d, J )
0.8 Hz, 3H), 3.57 (s, 6H), 4.10 (s, 3H), 4.84 (dd, J ) 0.8, 1.7 Hz,
1H), 5.39 (dd, J ) 1.5, 1.7 Hz, 1H), 7.24 (dd, J ) 1.9, 5.5 Hz,
1H), 7.27 (dd, J ) 5.5, 7.4 Hz, 1H), 7.30 (dt, J ) 1.4, 7.4 Hz,
1H), 7.45 (dd, J ) 1.4, 7.4 Hz, 1H); 13C NMR (CDCl3, 125 MHz)-
188.9, 181.0, 145.1, 143.5, 131.2, 129.4, 128.5, 128.0, 126.8, 125.0,
115.5, 113.7, 60.0, 53.7, 23.9; exact mass calcd for C16H18O4
274.1204, found 274.1209.
Ack n ow led gm en t. The authors thank the National
Institutes of Health (GM-36312) for financial support
of this work and SmithKline Beecham for a generous
gift of squaric acid. We also grateful to Xunta of Galicia
and the Ministry of Education of Spain for a fellowship
to A.R.H.
2b,3,4,4a -Tetr a h yd r o-2,2,2b-tr im eth oxy-4a -m eth yl-3-m e-
th ylen ed icyclobu t[a ,c]n a p h th a len -1(2H)-on e (17). In anal-
Su p p or tin g In for m a tion Ava ila ble: X-ray crystallo-
graphic data for compounds 5 as well as spectral data for
compounds 7, 8, 9, 2a -d ,f, and 12a -d ,f. This material is
available free of charge via the Internet at http://pubs.acs.org.
(8) Bergmann, E.; Weizmann, A. Trans. Faraday Soc. 1936, 32,
1327. Meisters, A.; Mole, T. Aust. J . Chem. 1974, 27, 1665. Fleming,
I.; Woolias, M. J . Chem. Soc., Perkin Trans. 1 1979, 829. Swenton, J .
S.; Carpenter, K.; Chen, Y.; Kerns, M. L.; Morrow, G. W. J . Org. Chem.
1993, 58, 3308.
J O010919G