Thermal isomerization of cis,anti,cis-tricyclo[6.3.0.02,7]undec- 3-ene to endo-tricyclo[5.2.2.02,6]undec-8-ene

Article abstract of DOI:10.1021/ol052004k

(Chemical Equation Presented) The gas-phase thermal isomerization of cis,anti,cis-tricyclo[6.3.0.0^2,7]undec-3-ene (1) to endo-tricyclo[5.2.2.0^2,6]undec-8-ene (2) at 315°C occurs cleanly through a symmetry-forbidden [1,3] suprafacial,retention (sr) pathway.

Full text of DOI:10.1021/ol052004k

ORGANIC
LETTERS
2
005
Vol. 7, No. 23
195-5197
Thermal Isomerization of
2,7
5
cis,anti,cis-Tricyclo[6.3.0.0 ]undec-3-ene
2,6
to endo-Tricyclo[5.2.2.0 ]undec-8-ene
John E. Baldwin, Andrew R. Bogdan, Phyllis A. Leber,* and David C. Powers‡
†
‡
,‡
Department of Chemistry, Syracuse UniVersity, Syracuse, New York 13244, and
Department of Chemistry, Franklin and Marshall College,
Lancaster, PennsylVania 17604
phyllis.leber@fandm.edu
Received August 18, 2005
ABSTRACT
The gas-phase thermal isomerization of cis,anti,cis-tricyclo[6.3.0.02,7]undec-3-ene (1) to endo-tricyclo[5.2.2.02,6]undec-8-ene (2) at 315
cleanly through a symmetry-forbidden [1,3] suprafacial,retention (sr) pathway.
°C occurs
Woodward and Hoffmann’s 1965 seminal communication
on sigmatropic rearrangements dealt primarily with hydrogen
Table 1. Stereochemistry of [1,3] Shifts for Bicyclic and
Tricyclic Vinylcyclobutanes
shifts; [1,3] carbon migrations were mentioned only tangen-
1
tially in a footnote. A more detailed consideration of
sigmatropic rearrangements including carbon shifts was
provided in 1969.2 Despite the fact that Frey had already
formulated a mechanistically attractive analysis of the
vinylcyclobutane-to-cyclohexene isomerization as a diradical-
,3
4
,5
mediated process, Woodward and Hoffmann’s paradigm,
2
,3
when applied to [1,3] carbon sigmatropic migrations,
proved appealing to many. Serious debate over the impor-
tance of orbital symmetry control in such thermal isomer-
izations has continued into the present century.
An isomerization of a bicyclic vinylcyclobutane, the
conversion of 5-exo-methylbicyclo[2.1.1]hex-2-ene to 6-exo-
6
methylbicyclo[3.1.0]hex-2-ene reported in 1969 (Table 1,
entry 1), contributed prominently to an almost universal
†
Syracuse University.
Franklin and Marshall College.
‡
(
1) Hoffmann, R.: Woodward, R. B. J. Am. Chem. Soc. 1965, 87, 4389-
acceptance of the Woodward-Hoffmann interpretation of
vinylcyclobutane-to-cyclohexene conversions as concerted
[1,3] sigmatropic rearrangements, for the strongly favored
product corresponded to the allowed suprafacial inversion
4
390.
(2) Woodward, R. B.; Hoffmann, R. Angew. Chem., Int. Ed. Engl. 1969,
8
, 781-853.
(
3) Woodward, R. B.; Hoffmann, R. The ConserVation of Orbital
Symmetry; Academic Press: New York, 1970.
4) Frey, H. M. AdV. Phys. Org. Chem. 1966, 4, 148-193.
(6) Roth, W. R.; Friedrich, A. Tetrahedron Lett. 1969, 31, 2607-2610.
1
0.1021/ol052004k CCC: $30.25
© 2005 American Chemical Society
Published on Web 10/19/2005

(
si) reaction stereochemistry. 6-endo-Acetoxybicyclo[3.2.0]-
7
8
hept-2-enes labeled with an exo-deuterium or an exo-methyl
substituent at the migrating carbon C7 similarly showed that
1,3] carbon shift products were formed with more inversion
Scheme 1
[
than retention: the reported si/sr values were >19 for the
exo-deuterium-labeled reactant and 9.3 for the exo-methyl
9
substrate. A recent investigation of 7-exo-methylbicyclo-
[
3.2.0]hept-2-ene found that it isomerized with an si/sr ratio
10
of 6.8 (Table 1, entry 2).
Only one prior investigation of the thermal chemistry of
a bicyclo[4.2.0]oct-2-ene has appeared in the literature. In
1
973, Berson and Holder reported that 7-endo-acetoxy-8-
clohexenone15,16 with a 450-W medium-pressure mercury
lamp (Scheme 1). The reaction was allowed to proceed to
at least 75% conversion. The photochemical cycloadduct
isolated had spectral data matching those reported for this
exo-methylbicyclo[4.2.0]oct-2-ene isomerized to substituted
bicyclo[2.2.2]octenes with only modest selectivity favoring
11
the symmetry-allowed si pathway (si/sr ) 2.2). We have
recently confirmed12 that 8-exo-methylbicyclo[4.2.0]oct-2-
17
known structure. Chromatographic purification of the cyclo-
adduct facilitated formation of the tosylhydrazone derivative;
its relatively narrow melting point range (130-134 °C)
signified a fairly high degree of purity. The Shapiro mod-
ene gives isomeric [1,3] carbon shift products reflecting a
similar si/sr ratio, 2.4 (Table 1, entry 3).
Thus, bicyclic vinylcyclobutane systems isomerize through
[1,3] carbon shifts to give two products reflecting si and sr
18
ification of the Bamford-Stevens reaction gave compound
reaction stereochemistry, with the si outcome strongly or at
least modestly favored (Table 1, entries 1-3), a preference
interpreted by Carpenter in terms of dynamic rotational
effects. In these systems, antarafacial pathways (ar or ai)
are geometrically inaccessible for they would lead to
thermochemically disadvantaged products.
The present work involved designing, making, and study-
ing the thermal chemistry of a tricyclic vinylcyclobutane 1
for which three of the four canonical [1,3] pathways would
be geometrically prohibited. According to AM1 calculations,
a si pathway from 1 to trans-5,6-trimethylenebicyclo[2.2.2]-
oct-2-ene14 would be endothermic by 12.2 kcal/mol while
an sr reaction leading to 2 would be exothermic by 10.2
kcal/mol. An sr shift would not be inevitables1 might prove
thermally stable, or it might decompose only through
fragmentation.
1
3
1
, and the structure was confirmed by a C NMR DEPT
pulse sequence: δ 131.3 (dCH), 126.8 (dCH), 46.0 (CH),
40.5 (CH), 35.8 (CH), 35.2 (CH), 32.9 (CH ), 32.6 (CH ),
5.6 (CH ), 25.0 (CH ), 21.4 (CH ). Further characterization
of compound 1 was achieved by catalytic reduction to cis,-
1
3
2
2
2
2
2
2
2,7
13
anti,cis-tricyclo[6.3.0.0 ]undecane (5), which yielded a C
NMR spectrum with only six peaks: δ 43.2, 35.2, 32.2, 26.6,
26.3, 20.7. While the C11H18 saturated tricyclic hydrocarbon
is not a known compound, the cis,anti,cis and cis,syn,cis
13
analogues with 10 and 12 carbons and their C NMR spectra
recorded for CCl solutions) have been reported in the
literature. A simple 13C NMR additivity model predicts δ
1.4, 33.8, 32.7, 26.6, 24.5, 22.6 for the cis,anti,cis-isomer
(
4
1
9
4
2,7
of tricyclo[6.3.0.0 ]undecane, in reasonable agreement with
the experimental values. In additional support of this
structural assignment of 1, the reaction sequence of Scheme
The cyclopentane substructure within 1 would restrict the
1
starting with the cycloaddition of cyclohexene with
[1,3] shift possibilities, and it would tend to make thermal
2,7
cyclohexenone led to the known cis,anti,cis-tricyclo[6.4.0.0 ]-
dodecane.
cleavage of the C1-C2 bond to afford an alkyl, allylic
diradical intermediate more difficult through restricting
rotation about the C1-C8 bond. Thus, reduction of the rate
constant for thermal decomposition of 1 might be expected,
compared with the fragmentation and [1,3] isomerizations
observed in some model systems, such as 8-exo-methylbicyclo-
1
9
The precursor of compound 2 was accessed by Diels-
Alder cycloaddition of 1,3-cyclohexadiene and 2-cyclopen-
19
tenone using aluminum trichloride as a catalyst. Subsequent
2
0
reduction of ketone 6 to compound 2 was accomplished
2
1
via the following three-step sequence: treatment with
LiAlH , conversion of the resultant alcohols to mesylate
derivatives, and further reduction with LiEt BH. Substitution
of LiEt BH for LiAlH was necessitated by the observation
-
4
-1
12
[
4.2.0]oct-2-ene (k
Entry to the tricyclic system in compound 1 was achieved
by photochemical cycloaddition of cyclopentene and 2-cy-
d
) 2.0 × 10
s
at 315 °C ).
4
3
3
4
4
of both substitution and elimination products with LiAlH .
(
7) Berson, J. A.; Nelson, G. L. J. Am. Chem. Soc. 1967, 89, 5503-
5
1
504.
(
8) Berson, J. A.; Nelson, G. L. J. Am. Chem. Soc. 1970, 92, 1096-
(15) Cantrell, T. S. J. Org. Chem. 1974, 39, 3063-3070.
(16) Eaton, P. E. J. Am. Chem. Soc. 1962, 84, 2454-2455.
097.
(
9) Berson, J. A. Acc. Chem. Res. 1972, 5, 406-414.
(17) Lange, G. L.; Gottardo, C. Magn. Reson. Chem. 1996, 34, 660-
(10) Bender, J. D.; Leber, P. A.; Lirio, R. R.; Smith, R. S. J. Org. Chem.
666.
2
000, 65, 5396-5402.
11) Berson, J. A.; Holder, R. W. J. Am. Chem. Soc. 1973, 95, 2037-
038.
12) Bogle, X. S.; Leber, P. A.; McCullough, L. A.; Powers, D. C. J.
Org. Chem. 2005, 70, in press.
(18) Lightner, D. A.; Gawronski, J. K.; Bouman, T. D. J. Am. Chem.
Soc. 1980, 102, 5749-5754.
(
2
(19) Salomon, R. G.; Folting, K.; Streib, W. E.; Kochi, J. K. J. Am.
Chem. Soc. 1974, 96, 1145-1152.
(
(20) Fringuelli, F.; Guo, M.; Minuti, L.; Pizzo, F.; Taticchi, A.; Wenkert,
E. J. Org. Chem. 1989, 54, 710-712.
(21) Masjedizadeh, M. R.; Dannecker-Doerig, I.; Little, R. D. J. Org.
Chem. 1990, 55, 2742-2752.
(
13) Carpenter, B. K. J. Am. Chem. Soc. 1995, 117, 6336-6344.
(
14) (a) Clemans, G. B. J. Org. Chem. 1973, 38, 3459-3461. (b)
Clemans, G. B.; Blaho, J. K. J. Org. Chem. 1987, 52, 1621-1622.
5196
Org. Lett., Vol. 7, No. 23, 2005

-
6
-1
loss of 1) ) (k
f
+ ksr) ) 4.4 × 10 s , ksr (for the
-6 -1 -6
f
isomerization 1f 2) ) 1.4 × 10 s , and k ) 3.0 × 10
Scheme 2
-
1
s
(Scheme 3). The k
f
/ksr ratio is 2.1.
Scheme 3
The simplest mechanistic explanation for the thermal
This sequence of reactions (Scheme 2) gave the endo isomer
behavior of 1 is homolytic cleavage of the C1-C2 bond to
generate an alkyl, allylic diradical intermediate that partitions
itself between potential reformation of 1, formation of the
1,3] sr isomerization product 2, and fragmentation. The [1,3]
shift in compound 1 is more competitive with fragmentation
than in 8-exo-methylbicyclo[4.2.0]oct-2-ene (Table 1, entry
22
of compound 2, a known compound. Catalytic hydrogena-
tion of 2 converted it to another known compound (7) with
six nonequivalent carbons: δ 41.1, 30.0, 28.1, 27.2, 26.6,
[
1
3
2
0.3. These C NMR chemical shifts match those reported
23,24
in the literature.
The thermal reactions of 1 were followed at 315 °C using
3
), which at 315 °C affords predominantly fragmentation
with lesser amounts of the [1,3] shift products and epimer-
ization in a ratio of 74:15:11, respectively; the k
2
5
pentane as a bath gas and a gas-phase static reactor.
Reaction time versus relative concentration data were secured
through capillary GC analyses; the internal standard cyclo-
decane, product 2, and reactant 1 were well resolved and
eluted in that order (Figure 1). Product mixtures were
f
/(ksr + ksi)
1
2
ratio is 4.9.
In summary, the tricyclic vinylcyclobutane 1 undergoes
thermal isomerization exclusively through an sr pathway;
the si/sr value is 0 (Table 1, entry 4). Notably, this is the
first such example of a vinylcyclobutane labeled with an exo-
alkyl substituent on the migrating carbon that proceeds
without any contribution from the si pathway. The geo-
metrical constraints in 1 force a symmetry-forbidden su-
prafacial, retention outcome without greater fragmentation
or lesser [1,3] carbon-shift contributions.
The conversion of 1 to 2 provides another example of a
vinylcyclobutane-to-cyclohexene isomerization taking place
through a short-lived diradical intermediate giving products
in proportions influenced by geometrical constraints and
dynamic factors, rather than by more or less control by orbital
2
6
symmetry influences.
Acknowledgment. We thank the NSF for support of this
work through CHE-0244103 and CHE-0211120 at Syracuse
University and CHE-0075097 at Franklin & Marshall College
and acknowledge the Donors of the American Chemical
Society Petroleum Research Fund for partial support of this
research at Franklin & Marshall College.
OL052004K
(
22) Takaishi, N.; Fujikura, Y.; Inamoto, Y. J. Org. Chem. 1975, 40,
767-3772.
23) Inamoto, Y.; Aigami, K.; Takaishi, N.; Fujikura, Y.; Tsuchihasahi,
K.; Ikeda, H. J. Org. Chem. 1977, 42, 3833-3839.
24) Murakhovskaya, A. S.; Stepanyants, A. U.; Zimina, K. I.; Aref’ev,
O. A.; Epishev, V. I. Bull. Acad. Sci. USSR, DiV. Chem. Sci. 1975, 24,
Figure 1. Capillary GC analysis of gas-phase thermal reaction
mixture from 1 after 19 h at 315 °C: from left to right, internal
standard cyclodecane, 2, and 1.
3
(
(
8
47-849.
exceptionally clean; minor side products were not seen. Data
(
25) Baldwin, J. E.; Burrell, R. C. J. Org. Chem. 1999, 64, 3567-3571.
from six kinetic runs gave rate constants k
d
(for first-order
(26) Leber, P. A.; Baldwin, J. E. Acc. Chem. Res. 2002, 35, 279-287.
Org. Lett., Vol. 7, No. 23, 2005
5197