Intramolecular [2 + 2] photocycloaddition/thermal fragmentation: Formally "allowed" and "forbidden" pathways toward 5-8-5 ring systems

Article abstract of DOI:10.1021/ja044542i

The thermal fragmentation of highly functionalized, linear polycyclobutanes with a cis,syn,cis-relative stereochemistry is shown to offer a rapid entry into the dicyclopenta[a,d]cyclooctenyl (5-8-5) ring system. The thermolysis of polyfused cyclobutanes w

Full text of DOI:10.1021/ja044542i

Published on Web 01/07/2005
Intramolecular [2 + 2] Photocycloaddition/Thermal
Fragmentation: Formally “Allowed” and “Forbidden”
Pathways toward 5-8-5 Ring Systems
Scott J. Bader and Marc L. Snapper*
Contribution from the Department of Chemistry, Merkert Chemistry Center, Boston College,
2609 Beacon Street, Chestnut Hill, Massachusetts 02467
Received September 9, 2004; E-mail: marc.snapper@bc.edu
Abstract: The thermal fragmentation of highly functionalized, linear polycyclobutanes with a cis,syn,cis-
relative stereochemistry is shown to offer a rapid entry into the dicyclopenta[a,d]cyclooctenyl (5-8-5) ring
system. The thermolysis of polyfused cyclobutanes with a cis,syn,cis- or a cis,anti,cis-relationship proceeds
in a formally “symmetry-allowed” manner through the intermediacy of a cis,trans-cyclooctadiene. When a
bridging tether used to establish the cis,syn,cis-stereochemistry in the intramolecular [2 + 2] photocyclization
is present in the thermolysis step, however, the result of a formally “symmetry-forbidden” fragmentation is
observed yielding cis,cis-cyclooctadiene-containing 5-8-5 products. In general, the stereochemical
observations noted in these fragmentations offer new opportunities for accessing a variety of stereochemical
relationships in these 5-8-5 ring systems.
Introduction
of the allylic substituents on the cis,trans-cyclooctadiene
becomes inverted in the resulting cis,cis-1,5-cyclooctadiene
Martin and others have shown that cis,cis-1,5-cyclooctadiene
is generated upon thermal fragmentation of cis,syn,cis- and
cis,anti,cis-tricyclo[4.2.0.02,5]octanes (eq 1).11 Independent of
whether this is a concerted, symmetry-allowed [σ2a + σ2s]
fragmentation2 or a stepwise, biradical process as shown, it is
likely that the reaction proceeds through the intermediacy of a
cis,trans-1,5-cyclooctadiene.3 The resulting strained cyclooc-
tadiene can then isomerize through several Cope rearrangements
to the observed cis,cis-1,5-cyclooctadiene.4 Due to the ste-
reospecificity of Cope rearrangements, the configuration of one
product.
(1) (a) Martin, H.-D.; Eisenmann, E. Thermolysis of syn- and anti-Tricyclo-
[4.2.0.02,5]octane. Tetrahedron Lett. 1975, 661-664 and references therein.
For related fragmentations, see: (b) Cobb, R. L.; Mahan, J. E.; Fahey, D.
R. Dimers of Cyclobutene-1,2-dicarbonitrile and 1,3-Butadiene-2,3-dicar-
bonitrile: Preparation and Chemistry. J. Org. Chem. 1977, 42, 2601-2610.
(c) Walsh, R.; Martin, H.-D.; Kunze, M.; Oftring, A.; Beckhaus, H.-D.
Small Rings. Part 32. The Gas-Phase Kinetics, Mechanism, and Energy
Hypersurface for the Thermolyses of syn- and anti-Tricyclo[4.2.0.02,5]-
octane. J. Chem. Soc., Perkin Trans. 2 1981, 1076-1083. (d) Martin, H.-
D.; Hekman, M.; Rist, G.; Sauter, H.; Bellus, D. cis,trans-1,5-Cycloocta-
dienes. Angew. Chem., Int. Ed. Engl. 1977, 16, 406-407. (e) Martin, H.-
Along these lines, we have applied this fragmentation in the
rapid preparation of dicyclopenta[a,d]cyclooctenyl (5-8-5) ring
systems,5 a framework related to several diterpene natural
products. As illustrated in Scheme 1, we have shown that the
thermolysis of substituted cis,anti,cis-polyfused cyclobutanes,
D.; Eisenmann, E.; Kunze, M.; Bonacic-Koutecky, V. Die C8H12
-
Energiehyperfla¨che Thermolyse van syn und anti-Tricyclo[4.2.0.02, 5]octan.
Experimentelle und Theoretische Untersuchungen. Chem. Ber. 1980, 113,
1153. (f) Dave, P. R.; Duddu, R.; Li, J.; Surapaneni, R.; Gilardi, R.
Tetrahedron Lett. 1998, 39, 5481. (g) Bakkern, F. J. A. D.; Schro¨er, F.;
Klunder, A. J. H.; Zwanenburg, B. Tetrahedron Lett. 1998, 39, 9531-
9534.
(4) (a) Berson, J. A.; Dervan, P. B. J. Am. Chem. Soc. 1972, 94, 7597-7598.
(b) Berson, J. A.; Dervan, P. B.; Jenkins, J. A. J. Am. Chem. Soc. 1972,
94, 7598-7599.
(5) (a) Randall, M. L.; Lo, P. C.-K.; Bonitatebus, P. J.; Snapper, M. L. J. Am.
Chem. Soc. 1999, 121, 4534-4535. (b) Lo, P. C.-K.; Snapper, M. L. Org.
Lett. 2001, 3, 2819-2821. For examples of related cycloaddition/
fragmentations, see: (c) Wender, P. A.; Hubbs, J. C. J. Org. Chem. 1980,
45, 365-367. (d) Winkler, J. D.; Bowen, C. M.; Liotta, F. Chem. ReV.
1995, 95, 2003-2020. (e) Crimmins, M. T. Chem. ReV. 1988, 88, 1453-
1473. (f) Oppolzer, W. Acc. Chem. Res. 1982, 15, 135-141. (g) Wender,
P. A.; Eck, S. L. Tetrahedron Lett. 1982, 23, 1871-1874. (h) Lange, G.
L.; Organ, M. G. J. Org. Chem. 1996, 61, 5358-5361. (i) Lange, G. L.;
Lee, M. J. Org. Chem. 1987, 52, 325-331. (j) Kammermeier, S.; Herges,
R. Angew. Chem., Int. Ed. Engl. 1996, 35, 417-419. (k) Prinzbach, H.;
Weber, K. Angew. Chem., Int. Ed. Engl. 1994, 33, 2239-2257. (l) Mehta,
G.; Reddy, A. V.; Srikrishna, A. J. Chem. Soc., Perkin Trans. 1 1986,
291-297. (m) White, J. D.; Kim, J.; Drapela N. E. J. Am. Chem. Soc.
2000, 122, 8665.
(2) Woodward, R. B.; Hoffmann, R. The ConserVation of Orbital Symmetry;
Verlag Chemie Academic Press: Weinheim, Germany, 1970.
(3) Conformation restrictions limit stereomutation and fragmentation pathways
of these systems relative to the thermolyses of free cyclobutane. For lead
references into fragmentations of cyclobutanes, see: (a) Schaumann, E.;
Ketcham, R. Angew. Chem., Int. Ed. Engl. 1982, 21, 225. (b) Lewis, D.
K.; Glenar, D. A.; Kalra, B. L.; Baldwin, J. W.; Cianciosi, S. J. J. Am.
Chem. Soc. 1987, 109, 7225-7227. (c) Chickos, J. S.; Annamalai, A.;
Keiderling, T. A. J. Am. Chem. Soc. 1986, 108, 4398-4402. (d) Doubleday,
C., Jr. J. Am. Chem. Soc. 1993, 115, 11968-11983. (e) Hrovat, D. A.;
Borden, W. T. J. Am. Chem. Soc. 2001, 123, 4069-4072. For studies of
related systems, see: (f) Khuong, K. S.; Houk, K. N. J. Am. Chem. Soc.
2003, 125, 14867-14883.
9
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J. AM. CHEM. SOC. 2005, 127, 1201-1205
1201

A R T I C L E S
Bader and Snapper
Scheme 1. Fragmentations to 5-8-5 Ring Systems
Scheme 2. Synthesis of the syn,cis,syn-Thermolysis Precursor 7a
a (a) LAH, Et2O, 0 °C (98%); (b) 1,2-cyclopentadione, Amberlyst 15,
CH2Cl2, reflux (87%); (c) hν (Pyrex), acetone, -78 °C (74%).
Results and Discussion
We envisioned using cyclobutene 5, available through an
intramolecular cycloaddition of a functionalized cyclobutadiene,6
as a convenient starting point for our studies (Scheme 2). The
reduced ester could serve as a handle to link a cyclopentenone
chromophore for the intramolecular [2 + 2] photocycloaddition.
Toward this goal, reduction of the methyl ester to the corre-
sponding alcohol using LAH and an acid-catalyzed coupling
to 1,2-cyclopentadione produced the desired photoprecursor 6.
Irradiation of enone 6 through a Pyrex filter in acetone at -78
°C furnished the cis,syn,cis-polyfused cyclobutane system 7 in
74% yield. An X-ray crystallographic analysis of the product
revealed the relative head-to-tail stereochemistry in this cy-
cloaddition. As has been observed previously, the capto-dative
stabilization of the R-oxygen in the photoexcited state of the
cyclopentenone7 overrides the usual “rule of five” regiochemical
preference observed typically in this type of photocycloaddition
(i.e., 6 f 7b).8
In a related sequence, methyl ester 5 could also be converted
in one step to Weinreb amide 8.9 Addition of cyclopentenyl
anions could then furnish an exocyclic R,â-unsaturated ketone
that should produce the head-to-head cis,syn,cis-products in the
photocycloaddition step. As illustrated in Scheme 3, the reaction
of cyclopentenyllithium10 with the Weinreb amide 8 provides
ketone 9 in 96% yield. Other lithiated cyclopentenes can also
be prepared via a Shapiro reaction.11 For example, 2,2-
dimethylcyclopentanone12 can be transformed to the 2,4,6-
triisopropyltosylhydrazone upon treatment with the correspond-
ing hydrazide. Treatment of this hydrazone with n-BuLi
followed by addition of Weinreb amide 8 furnished compound
11 in 82% yield. Irradiation of either enone 9 or 11 in CH2Cl2
at low temperature through a Pyrex filter provided the desired
cis,syn,cis-polycyclic systems 10 or 12 in 70 and 50%13 yields,
such as 1 and 3, yield the 5-8-5 ring systems 2 and 4,
respectively. Of particular importance, a unique stereochemical
outcome is observed in these thermolyses, an outcome depend-
ing primarily on the relative stereochemistry of the fused thermal
precursors. Substrate 1 rearranges to cyclooctadiene 2 with
inversion of C-11 (eq 2 in Scheme 1), whereas substrate 3 yields
cyclooctadiene 4 with inversion at C-3 (eq 3 in Scheme 1). The
stereochemical differences in the products are the result of the
stereospecific Cope rearrangements on the conformationally
biased cis,trans-cyclooctadiene intermediates A and A′. The
formation of either 5-8-5 product is consistent with both a
stepwise, biradical mechanism and a symmetry-allowed [σ2a
+ σ2s] fragmentation.
In the interest of expanding our understanding of these
thermal fragmentations, as well as to access stereochemically
different 5-8-5 ring systems, we sought to prepare and explore
the fragmentation of substituted cis,syn,cis-tricyclo[4.2.0.0]-
octanes, such as illustrated in eq 4. Of particular interest,
especially considering potential natural product targets, is the
relative stereochemistry of the cyclooctadiene products arising
from these fragmentations. To overcome the known stereo-
chemical preference in the [2 + 2] photocycloaddition for
generating the cis,anti,cis-polyfused product, we developed a
new intramolecular route for accessing the desired cis,syn,cis-
thermolysis precursors. Reported herein are our findings on the
intramolecular photocycloaddition of cyclopentenones tethered
to functionalized cyclobutenes and the subsequent thermal
fragmentation of the resulting cis,syn,cis-polyfused photoad-
ducts.
(6) (a) Deak, H. L.; Stokes, S. S.; Snapper, M. L. J. Am. Chem. Soc. 2001,
123, 5152-5153. For the preparation of related cycloadducts, see: (b)
Limanto, J.; Tallarico, J. A.; Porter, J. R.; Khuong, S. K.; Houk, K. N.;
Snapper, M. L. J. Am. Chem. Soc. 2002, 124, 14748-14758. (c) Tallarico,
J. A.; Randall, M. L.; Snapper, M. L. J. Am. Chem. Soc. 1996, 118, 9196-
9197.
(7) Viehe, H. G.; Merenyi, R.; Stella, L.; Janousek, Z. Angew. Chem., Int. Ed.
Engl. 1979, 18, 917-932.
(8) (a) Takahashi, M.; Uchino, T.; Ohno, K.; Tamura, Y.; Ikeda, M. J. Org.
Chem. 1983, 48, 4241-4247. (b) Pirrung, M.; Chang, V. K.; DeAmicis,
C. V. J. Am. Chem. Soc. 1989, 111, 5824-5831.
(9) Williams, J. M.; Jobson, R. B.; Yasuda, N.; Marchesini, G.; Dolling, U.
H.; Grabowski, E. J. Tetrahedron Lett. 1995, 36, 5461-5464.
(10) Prepared from 1-chlorocyclopentene and Li+ in Et2O at room temperature
under Ar atmosphere for 2 days.
(11) For a review, see: Shapiro, R. H. Org. React. 1976, 23, 405-423.
(12) Purchased from Aldrich Chemical Co.
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1202 J. AM. CHEM. SOC. VOL. 127, NO. 4, 2005

Fragmentation of syn,cis,syn-Polyfused Cyclobutane Systems
Scheme 3. Thermolysis Precursors 10 and 12a
A R T I C L E S
Table 1. Symmetry-Forbidden Thermal Fragmentations of Bridged
cis,syn,cis-Systems
a (a) i-PrMgCl, N,O-dimethylhydroxylamine hydrochloride, THF, -20
°C (99%); (b) cyclopentenyllithium, THF, -78 to 0 °C (96%); (c) 2,2-
dimethylcyclopentylhydrazone, n-BuLi, THF, -78 to 0 °C; 8, THF, -78
to 0 °C (82%); (d) hν (Pyrex), CH2Cl2, -78 °C (70%, 10; 50%,13
12).
Scheme 4. Synthesis of Photoadducts 15 and 16a
a X-ray crystal structure available in the Supporting Information.Ther-
molysis: benzene, BHT (2 equiv), heat.
a (a) 6-Bromo-1,4-dioxaspiro[4.4]non-6-ene, n-BuLi, THF, -78 °C; 5,
THF, -78 to 0 °C (94%); (b) NaBH4, CeCl3‚7H2O, MeOH, 0 °C; 1 N HCl
(100%); (c) hν (Pyrex), CH2Cl2 (57% 15/16 (1:10)) or acetone/H2O (72%
15/16 (7:1)).
Each substrate in Table 1 undergoes the thermal fragmentation
to provide cleanly the ring-expanded cyclooctadiene products.
The relative stereochemistry of the fragmented products is
particularly noteworthy. Whereas our previous thermal frag-
mentations of the cis,anti,cis-systems proceeded along a formal
symmetry-allowed16 pathway resulting in an inversion of
stereochemistry in the observed products (i.e., Scheme 1), the
cis,syn,cis-substrates illustrated in Table 1 fragmented without
additional stereochemical consequences.17 Each substrate reacted
through a mechanism that is consistent with a “symmetry-
forbidden” [σ2s + σ2s] fragmentation.
A possible explanation for the difference in fragmentations
between the two ring systems is that the bridging tether present
in the cis,syn,cis-ring system precludes the formation of the
expected cis,trans-cyclooctadiene intermediate by not allowing
the initially generated cyclohexyl diradical to rearrange through
a chair transition state.3d For example, eq 5 illustrates a stepwise
fragmentation of the cis,anti,cis-precursor 1. Presumably, the
initially formed boat cyclohexyl diradical can relax into a chair
conformation, which leads to cis,trans-cyclooctadiene interme-
diate A. In contrast, eq 6 shows the generation of cyclooctadiene
18 from the cis,syn,cis-ring system 10. Note that the substituents
and bridging carbonyl in 10 preclude the initially generated
cyclohexyl diradical(s) from adopting a chair conformation.
To separate the stereochemical influence of the bridging tether
from the cis,syn,cis-ring fusion stereochemistry in the thermoly-
respectively. An X-ray crystal structure confirmed the head-to-
head cycloaddition stereochemistry in photoadduct 10.
To introduce additional functionality in the five-membered
ring, the vinyllithium reagent derived from a protected cyclo-
pentenone made by Smith et al.14 was used (Scheme 4). The
acetal-protected cyclopentenyl bromide undergoes a lithium-
halogen exchange upon exposure to n-BuLi at -78 °C. Exposure
of the cyclopentenyl anion to Weinreb amide 8 yields compound
13 in 94% yield. Irradiation of 13 under a variety of reaction
conditions did not, however, lead to any desired photoadducts.
In comparison, reduction of the exo-R,â-unsaturated ketone,
followed by a mild acidic workup, produced compound 14 in
quantitative yield. Irradiation of enone 14 generates two
photoadducts in a ratio that is dependent on the solvent
employed. Photocycloaddition in a protic media, such as
acetone/water, leads to compounds 15/16 in a 7:1 ratio.15 In an
aprotic solvent, such as CH2Cl2, however, 15/16 are produced
in a 1:10 ratio. Our rationale for the regiochemical dependence
of this photocycloaddition on solvent is based on the presence
of an intramolecular hydrogen bond between the ketone and
the â-hydroxyl group in aprotic solvents that restrict the
accessible conformations, allowing the head-to-tail product 16
to prevail. Disruption of this hydrogen bond in protic solvents,
however, relaxes the conformational preference of the molecule
and favors formation of the head-to-head product 15.
(13) With 50% yield based on 50% conversion.
(14) Smith, A. B., III.; Branca, S. J.; Pilla, N. N.; Guaciaro, M. A. J. Org. Chem.
1982, 47, 1855-1869.
(15) Determined by 1H NMR on the crude reaction mixture.
(16) While the fragmentations are likely to proceed through biradical intermedi-
ates, the terms symmetry-allowed and symmetry-forbidden are used to
describe the stereochemical changes occurring between the fused cyclobu-
tane starting materials and the corresponding cyclooctadiene products.
(17) For related observations, see: Doering, W. v. E.; DeLuca, J. P. J. Am.
Chem. Soc. 2003, 125, 10608-10614.
With access to several highly substituted cis,syn,cis-polycy-
clobutane systems, we were well poised to examine their thermal
fragmentations. In general, compounds were heated in a heavy-
walled sealed tube in degassed benzene with BHT (2 equiv) to
a temperature at which the starting material began to convert.
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J. AM. CHEM. SOC. VOL. 127, NO. 4, 2005 1203

A R T I C L E S
Bader and Snapper
Scheme 6. Tether Influence on Thermolysisa
a (a) At 90 °C, benzene; (b) 1 atm O2, TBSCl, imid., Et3N (78%); (c)
160 °C, benzene, or 90 °C, DBU, benzene (98%); (d) MeMgBr, (2.2 equiv)
benzene, 110 °C (89%, based on 90% conv.).
sis, we chose to examine the fragmentation in the absence of
the bridging group. Baeyer-Villiger oxidation18 of ketone 10
using m-CPBA gave an inseparable mixture of the regiochemical
lactones 22 and 23 in a 9:1 ratio (Scheme 5). Reduction of the
lactones with LAH provided the two diols 24 and 25, respec-
tively, which now could be readily separated in overall 98%
yield for the two steps. The minor regioisomer provided a solid
that could be analyzed by X-ray crystallography; this indicated
that the removal of the tether does not change the cis,syn,cis-
relationship of the polyfused cyclobutane rings.
Figure 1. X-ray crystal structure of thermolysis product 26 reacted with
air and 3,5-dinitrobenzoyl chloride.
with 3,5-dinitrobenzoyl chloride generated a crystalline material
that confirmed our suspicion (Figure 1); the thermolysis product
possessed a strained trans-olefin that epoxidizes readily in air.
In an optimized procedure, the thermolysis is run at 90 °C in
benzene for 3 h and is subsequently exposed to O2 (1 atm),
followed by TBS protection of the primary alcohol to give
epoxide 27 in 78% yield (Scheme 6). Of particular importance,
this result shows that unlike the examples described in Table 1
and eqs 2 and 3, thermolysis of a polyfused ring system with
the cis,syn,cis-relative stereochemistry and no bridging tether
rearranges in a formally symmetry-allowed fashion, but stops
at the cis,trans-cyclooctadiene intermediate.
Scheme 5. Synthesis of Diols 24 and 25a
a (a) m-CPBA, p-TsOH, benzene (99%, 22/23 (9:1)); (b) LAH, Et2O, 0
°C (99%, 24/25 (9:1)).
A minor product isolated in the thermolysis of diol 24, which
contained only two olefinic protons and a carbonyl stretch by
IR, is ketone 28. It is expected that this compound arose through
a [3,3]-sigmatropic rearrangement of compound 26, much like
that which is occurring in eq 3 of Scheme 1. Whereas the
cyclononadiene is only a predicted intermediate in the previous
thermolyses, the oxygen substituent in this case facilitates the
oxy-Cope and stabilizes the nine-membered ketone-containing
product 28. The thermolysis of the diol 24 could be optimized
to give exclusively the cyclononenone 28 by heating substrate
24 to 160 °C or by warming to 90 °C in the presence of DBU.
To determine whether cis,trans-cyclooctadiene 26 is indeed an
intermediate in the formation of the nine-membered ring
compound 28, the starting diol 24 was first heated to 90 °C in
benzene for 3 h to provide 26, and was then subjected to DBU
As illustrated in Scheme 6, heating diol 24 to 90 °C in
benzene revealed, by 1H NMR, a new diol 26 with three olefinic
protons. A major difference from previous 5-8-5 thermolyses
products, however, was the large, 18 Hz vicinal coupling
between a pair of olefinic protons that was observed in this
structure, an indication that the 5-8-5 system possessed a
trans-olefin in its cyclooctadienoid framework. This is not
unprecedented since studies by Martin and Eisenmann revealed
that cis,trans-cyclooctadiene is formed, along with cis,cis-
cyclooctadiene, in the thermolysis of syn- and anti-tricyclo-
[4.2.0.02,5]-octane.1a
Upon exposure to air, the trans-olefinic protons of compound
26 apparently shift upfield. Treatment of this new compound
(18) For a review, see: Renz, M.; Meunier, B. Eur. J. Org. Chem. 1999, 737.
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Fragmentation of syn,cis,syn-Polyfused Cyclobutane Systems
A R T I C L E S
and heated to 90 °C for an additional 3 h. The nine-membered
ring ketone 28 was isolated in 98% after purification on silica.
These results indicate that the bridge used to prepare the
photoadducts in Table 1 is responsible for the symmetry-
forbidden fragmentation pathway observed in these thermolyses.
Remarkably, similar control over the stereochemical course of
the thermolysis is possible by even the introduction of a
temporary bridging element. Treatment of diol 24 with MeMgBr
(2.2 equiv) in benzene by heating it to 110 °C for 6 h yielded
cis,cis-cyclooctadiene 29 in 80% with a 10% recovery of starting
material (Scheme 6). Presumably, the bridging magnesium
chelate established between the two alkoxide groups is sufficient
to steer the fragmentation toward the symmetry-forbidden
pathway. The structural and stereochemical identity of com-
pound 29 was confirmed by correlating this product with thermal
adduct 18, a structure established unambiguously through X-ray
crystallography. Interestingly, our inability to effect a thermal
oxy-Cope rearrangement on compound 29 provides additional
support that its formation is through a unique and separate
pathway from the trans-isomer 26.
tadiene product, whereas when a conformationally restrictive
tether is present, a symmetry-forbidden process is followed to
yield a cis,cis-cyclooctadiene-containing 5-8-5 product.
Overall, these highly strained, polyfused cyclobutane systems
provide a unique and rapid entry into the 5-8-5 ring system,
a framework found in several diterpenoid natural products.
Given the variety of relative stereochemical relationships in the
ring fusions of the possible natural product targets, it is
particularly important to have a flexible and predictable method
for generating these materials in a concise and stereocontrolled
manner. Knowledge on how to manipulate the relative stereo-
chemistry in these thermal fragmentations provides a unique
opportunity for accessing a wider range of suitable targets.
Acknowledgment. We thank the National Institute of General
Medical Sciences (National Institutes of Health, GM62824) for
financial support. In addition, S.J.B. acknowledges the Depart-
ment of Education for a GAANN Fellowship. We are grateful
to Schering-Plough for X-ray facility support, and Jarred T.
Blank for substantial assistance with X-ray crystallographic
studies. We also thank Ms. Kelli S. Khuong and Professor K.N.
Houk for helpful discussions.
Summary
The above observations highlight the substantial influence a
bridging substituent can have in the thermal fragmentation of
polyfused cyclobutanes with the cis,syn,cis-relative stereochem-
istry. In the absence of the bridge, the reaction proceeds in a
formal symmetry-allowed manner through a cis,trans-cyclooc-
Supporting Information Available: Experimental procedures
and data on new compounds are provided (PDF). This material
is available free of charge via the Internet at http://pubs.acs.org.
JA044542I
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