Thermal chemistry of bicyclo[4.2.0]oct-2-enes

Article abstract of DOI:10.1021/jo061964x

At 300 °C, bicyclo[4.2.0]oct-2-ene (1) isomerizes to bicyclo[2.2.2]oct-2-ene (2) via a formal [1,3] sigmatropic carbon migration. Deuterium labels at C7 and C8 were employed to probe for two-centered stereomutation resulting from C1-C6 cleavage and for one-centered Stereomutation resulting from C1-C8 cleavage, respectively. In addition, deuterium labeling allowed for the elucidation of the stereochemical preference of the [1,3] migration of 1 to 2. The two possible [1,3] carbon shift outcomes reflect a slight preference for migration with inversion rather than retention of stereochemistry; the si/sr product ratio is ～1.4. One-centered stereomutation is the dominant process in the thermal manifold of 1, with lesser amounts of fragmentation and [1,3] carbon migration processes being observed. All of these observations are consistent with a long-lived, conformationally promiscuous diradical intermediate.

Full text of DOI:10.1021/jo061964x

Thermal Chemistry of Bicyclo[4.2.0]oct-2-enes
David C. Powers,† Phyllis A. Leber,*,† Sarah S. Gallagher,† Andrew T. Higgs,†
Lynne A. McCullough,† and John E. Baldwin‡
Department of Chemistry, Franklin & Marshall College, Lancaster, PennsylVania 17604-3003, and
Department of Chemistry, Syracuse UniVersity, Syracuse, New York 13244
phyllis.leber@fandm.edu
ReceiVed September 22, 2006
At 300 °C, bicyclo[4.2.0]oct-2-ene (1) isomerizes to bicyclo[2.2.2]oct-2-ene (2) via a formal [1,3]
sigmatropic carbon migration. Deuterium labels at C7 and C8 were employed to probe for two-centered
stereomutation resulting from C1-C6 cleavage and for one-centered stereomutation resulting from C1-
C8 cleavage, respectively. In addition, deuterium labeling allowed for the elucidation of the stereochemical
preference of the [1,3] migration of 1 to 2. The two possible [1,3] carbon shift outcomes reflect a slight
preference for migration with inversion rather than retention of stereochemistry; the si/sr product ratio is
∼1.4. One-centered stereomutation is the dominant process in the thermal manifold of 1, with lesser
amounts of fragmentation and [1,3] carbon migration processes being observed. All of these observations
are consistent with a long-lived, conformationally promiscuous diradical intermediate.
Introduction
by these vinylcyclobutane derivatives have met with various
interpretationsscompeting orbital symmetry allowed and for-
bidden reactions,2a competing concerted and stepwise mech-
anisms,2b,f,h or even partitioning of a short-lived diradical2es
recent experimental3,4 and theoretical5,6 investigations have
suggested that these reactions are almost certainly mediated by
short-lived, nonstatistical diradical intermediates that partition
to multiple products from a common shallow plateau on the
potential energy surface.
Vinylcyclopropanes and vinylcyclobutanes undergo ring
expansion reactions to cyclopentenes and cyclohexenes, respec-
tively, via formal [1,3] sigmatropic carbon migrations. With
appropriately labeled substrates, four stereochemically distinct
[1,3] products may be observed. They are conventionally
denoted as si, sr, ai, and ar, where s or a refers to suprafacial
or antarafacial topology of the π-system and r or i refers to
retention or inversion of configuration at the migrating carbon.
According to the Woodward-Hoffmann paradigm, si and ar
products may be privileged as orbital symmetry-allowed con-
certed reactions, whereas sr and ai may not.1 Because of
geometrical constraints present in various bicyclic vinylcy-
clobutanes, such as those under investigation herein, antarafacial
processes are geometrically prohibited. Thus, si/sr ratios have
been used as a measure of the degree of orbital symmetry control
in their [1,3] sigmatropic rearrangements.2a
A cross-system comparison of the thermal chemistry of
bicyclo[2.1.1]hex-2-enes, bicyclo[3.2.0]hept-2-enes, and sub-
(2) (a) Berson, J. A. Acc. Chem. Res. 1972, 5, 406-414. (b) Berson,
J. A.; Nelson, G. L. J. Am. Chem. Soc. 1970, 92, 1096-1097. (c) Berson,
J. A.; Salem, L. J. Am. Chem. Soc. 1972, 94, 8917-8918. (d) Cocks,
A. T.; Frey, H. M. J. Chem. Soc. A 1971, 2564-2566. (e) Baldwin, J. E.;
Belfield, K. D. J. Am. Chem. Soc. 1988, 110, 296-297. (f) Kla¨rner, G.-G.;
Drewes, R.; Hasselmann, D. J. Am. Chem. Soc. 1988, 110, 297-298. (g)
Baldwin, J. E.; Belfield, K. D. J. Phys. Org. Chem. 1989, 2, 455-466. (h)
Bender, J. D.; Leber, P. A.; Lirio, R. R.; Smith, R. S. J. Org. Chem. 2000,
65, 5396-5402.
(3) (a) Baldwin, J. E.; Burrell, R. C. J. Am. Chem. Soc. 2001, 123, 6718-
6719. (b) Baldwin, J. E.; Burrell, R. C. J. Am. Chem. Soc. 2003, 125,
15869-15877.
(4) (a) Doering, W. v. E.; Elkmanis, J. L.; Belfield, K. D.; Kla¨rner,
F.-G.; Krawczyk, B. J. Am. Chem. Soc. 2001, 123, 5532-5541. (b) Doering,
W. v. E.; Cheng, X.; Lee, W.; Lin, Z. J. Am. Chem. Soc. 2002, 124, 11642-
11652.
Many thermal studies of bicyclo[3.2.0]hept-2-enes have been
reported.2 While the mixed stereochemical results exhibited
† Franklin & Marshall College.
‡ Syracuse University.
(1) Woodward, R. B.; Hoffmann, R. The ConserVation of Orbital
Symmetry; Verlag Chemie: Weinheim, 1970; pp 119-120.
10.1021/jo061964x CCC: $37.00 © 2007 American Chemical Society
Published on Web 12/13/2006
J. Org. Chem. 2007, 72, 187-194
187

Powers et al.
SCHEME 1. Synthesis of 1
SCHEME 2. Synthesis of 7-d-1
stituted monocyclic vinylcyclobutanes in a recent review7
identified the bicyclo[4.2.0]oct-2-enes as a logical bridge
between the more geometrically constrained bicyclo[2.1.1] and
-[3.2.0] compounds and the more conformationally flexible
monocyclic vinylcyclobutanes. As a consequence of this
analysis, three hypotheses concerning the thermal behavior of
vinylcyclobutanes were articulated:8 (1) the si/sr ratio should
correlate inversely with the degree of conformational freedom
of the vinylcyclobutane, (2) an exo-methyl stereochemical
marker on the migrating carbon should slow the rate of rotation
about the bond between that carbon and its adjacent carbon in
a short-lived diradical intermediate, as compared to the rate of
rotation of that fragment having deuterium rather than exo-
methyl as the marker,9,10 and thus should form products having
a higher si/sr ratio, and (3) fragmentation and a one-centered
epimerization or stereomutation should increasingly compete
with [1,3] shifts in vinylcyclobutanes having greater confor-
mational flexibility.
Two of the aforementioned predictions have already been
subjected to experimental verification.8 Leber and co-workers
noted that both predictions (1) and (3) were valid for a series
of methyl-substituted bicyclic vinylcyclobutane derivatives;
comparison of the kinetic behavior of 8-exo-methylbicyclo-
[4.2.0]oct-2-ene with 7-exo-methylbicyclo[3.2.0]hept-2-ene and
5-exo-methylbicyclo[2.1.1]hex-2-ene showed that, indeed, the
increase in flexibility accompanying increased ring size led both
to a smaller si/sr ratio and to greater total participation of the
fragmentation and stereomutation processes in the thermal
manifold. This earlier work did not subject prediction (2) to an
experimental evaluation.
made, as well as comparisons between methyl-labeled and
deuterium-labeled vinylcyclobutanes.
Results
Syntheses. The synthesis of bicyclo[4.2.0]oct-2-ene (1), as
shown in Scheme 1, started with the precursor 8,8-dichlorobi-
cyclo[4.2.0]oct-2-en-7-one (3), which was prepared in moderate
yield from 1,3-cyclohexadiene and trichloroacetyl chloride
according to a previously published procedure.11 Dechlorination
with zinc in acetic acid11 afforded bicyclo[4.2.0]oct-2-en-7-one
(4) in 89% yield. Low-temperature Wolff-Kishner reduction12
of 4 via the intermediacy of its hydrazone derivative gave
bicyclo[4.2.0]oct-2-ene (1). Spectral data recorded for 3 and 4,
both known compounds, were in agreement with the litera-
ture.11,13 In contrast, compound 1, while known,14,15 has been
subjected to rigorous spectral analysis for the first time. Not
1
only are high-field H NMR chemical shifts consistent with
previously reported low-field values, but 13C NMR data includ-
ing a DEPT pulse sequence have provided a compelling structure
proof for 1.
The synthesis of both epimers of 7-d-1 (Scheme 2) com-
menced from compound 3. Using a methodology previously
documented for site-specific deuterium labeling of bicyclo[3.2.0]-
hepta-2,6-dienes,16 compound 3 was subjected to the following
reaction sequence: reduction with NaBD4 in methanol to alcohol
5, mesylation with methanesulfonyl chloride and triethylamine,
and treatment with Na in liquid ammonia to 7-d-bicyclo[4.2.0]-
octa-2,7-diene (6). d0-Analogues of 513 and 617 are known
compounds; full spectral characterization was secured for 6, the
direct precursor to 7-d-1. Compound 6 was converted to 7-d-1
by a novel selective reduction using diimide generated in situ
by treatment of hydrazine with hydrogen peroxide at -20 °C.18
The present report details thorough kinetic analyses of
bicyclo[4.2.0]oct-2-ene (1), 7-d-bicyclo[4.2.0]oct-2-enes (7-d-
1), and 8-d-bicyclo[4.2.0]oct-2-enes (8-d-1). This work repre-
sents a further validation of predictions (1) and (3) and an initial
test of prediction (2). Explicit comparisons to the thermal
chemistry of other deuterium-labeled vinylcyclobutanes will be
2
Based on H NMR, it was shown that this reduction occurred
(11) Koltun, E. S.; Kass, S. R. J. Org. Chem. 2000, 65, 3530-3537.
(12) Burkey, J. D.; Leber, P. A.; Silverman, L. S. Synth. Commun. 1986,
16, 1363-1370.
(13) Kertesz, D. J.; Kluge, A. F. J. Org. Chem. 1988, 53, 4962-4968.
(14) (a) Mirbach, M. F.; Mirbach, M. J.; Saus, A. Z. Naturforsch. 1976,
32b, 47-52. (b) Mirbach, M. J.; Mirbach, M. F.; Saus, A. Z. Naturforsch.
1977, 32b, 281-284.
(15) Sohn, M.; Blum, J.; Halpern, J. J. Am. Chem. Soc. 1979, 101, 2694-
2698.
(16) Baldwin, J. E.; Belfield, K. D. J. Org. Chem. 1987, 52, 4772-
4776.
(17) Chapman, O. L.; Borden, G. W.; King, R. W.; Winkler, B. J. Am.
Chem. Soc. 1964, 86, 2660-2663.
(18) (a) Baldwin, J. E.; Leber, P. A. Tetrahedron Lett. 2001, 42, 195-
197. (b) Baldwin, J. E.; Leber, P. A. J. Am. Chem. Soc. 2001, 123, 8396-
8397.
(5) (a) Carpenter, B. K. J. Org. Chem. 1992, 57, 4645-4648. (b)
Carpenter, B. K. J. Am. Chem. Soc. 1995, 117, 6336-6344. (c) Carpenter,
B. K. Angew. Chem., Int. Ed. 1998, 37, 3340-3350.
(6) (a) Beno, B. R.; Wilsey, S.; Houk, K. N. J. Am. Chem. Soc. 1999,
121, 4816-4826. (b) Wilsey, S.; Houk, K. N.; Zewail, A. H. J. Am. Chem.
Soc. 1999, 121, 5772-5786. (c) Northrop, B. H.; Houk, K. N. J. Org. Chem.
2006, 71, 3-13.
(7) Leber, P. A.; Baldwin, J. E. Acc. Chem. Res. 2002, 35, 279-287.
(8) Bogle, X. S.; Leber, P. A.; McCullough, L. A.; Powers, D. C. J.
Org. Chem. 2005, 70, 8913-8918.
(9) Berson, J. A.; Pedersen, L. D.; Carpenter, B. K. J. Am. Chem. Soc.
1976, 98, 122-143.
(10) Pedersen, S.; Herek, J. L.; Zewail, A. H. Science 1994, 266, 1359-
1364.
188 J. Org. Chem., Vol. 72, No. 1, 2007

Thermal Chemistry of Bicyclo[4.2.0]oct-2-enes
SCHEME 3. Synthesis of 8-d-1
SCHEME 4. Synthesis of 2
preferentially from the exo face of the C7-C8 π-bond: 7-n-
d-1 (δ 1.77):7-x-d-1 (δ 1.91) ) 4.8:1.18,19
Thermal Reactions. Thermal reactions of 1, 7-d-1, 8-d-1,
and 2 were carried out in a well-conditioned thermal bulb at
300.0 °C.2h Preparative GC provided 1 of greater than 99.5%
purity, and seven kinetic runs starting with this purified reactant
1 were followed. These runs spanned a time range of 3-45 h,
corresponding to between 19% and 89% conversion of 1 to
products and greater than 3 half-lives. Thermal reactions starting
with 1 were also carried out at 275.0 and 315.0 °C to define
activation parameters. The Arrhenius plot yielded the activation
parameters Ea ) 51.8 ( 0.3 kcal/mol and log A ) 14.9 ( 0.1.
Samples of 7-d-1 and 8-d-1 were heated for varying lengths
of time up to 30 h, and the resultant kinetic runs were analyzed
The synthesis of 8-d-1 epimers (Scheme 3) was accomplished
via a similar methodology. After selective reduction of 3 with
zinc in AcOD to afford 8-d-8-chlorobicyclo[4.2.0]oct-2-en-7-
one (7), a reaction sequence analogous to that employed in the
synthesis of 6 gave first an alcohol using NaBH4 in CH3OD
and ultimately 8-d-bicyclo[4.2.0]octa-2,7-diene (8), which differs
from 6 only in the position of the deuterium label. Using the
aforementioned kinetically controlled diimide reduction, 8 was
efficiently converted to 8-d-1. Hydrogen was preferentially
delivered from the exo face of the cyclobutene π-bond: 8-n-
d-1 (δ 1.63):8-x-d-1 (δ 2.23) ) 5.9:1.19
2
by H NMR. Whereas 7-d-1 was studied to detect a possible
two-centered stereomutation at the C1-C6 bond, 8-d-1 was
examined to probe for a possible one-centered stereomutation
at C8 and to derive explicit stereochemical data for the [1,3]
carbon migration of C8 from C1 to C3. The principal results of
the thermal study of 7-d-1 and 8-d-1 at 300 °C have already
been communicated.19
The potential for retro Diels-Alder fragmentation of 2 was
investigated by following four kinetic runs starting with 2. After
240 h at 300.0 °C, only 10% of 2 had reacted. There was no
appreciable thermal loss of 2 at 45 h, corresponding to the
duration of the longest kinetic runs of 1. Because of the
prohibitively slow rate of the retro Diels-Alder reaction of 2,
and the fact that activation parameters have previously been
reported for this reaction,25 further thermal study was not
pursued. The limited kinetic data secured for loss of 2 led to a
rate constant at 300 °C of 1.3 ((0.1) × 10-7 s-1, a value
reasonably close to the 1.8 × 10-7 s-1 calculated using the
Arrhenius parameters reported by Huybrechts based on a more
extensive thermal study of 2 over the temperature range of 275-
360 °C.25
The data obtained through kinetic runs starting with 1 at 300
°C led to the first-order rate constants for loss of starting material
(k0), formation of 2 (k13), and fragmentation to give ethylene
plus 1,3-cyclohexadiene (kf) tabulated in Table 1. The experi-
mental first-order rate constants for parallel first-order reactions
in Table 1 correspond to the thermal reactions depicted in
Scheme 5, and the relationship k0 ) k13 + kf. Compound 2 is
essentially thermally inert over the time period for which the
thermal chemistry of 1 was observed, as the value calculated
for the retro Diels-Alder reaction is slower than k0 by 2 orders
of magnitude.
The independent syntheses of 7-d-1 and 8-d-1 as well as
selected NOE experiments with unlabeled 1 were employed to
2
achieve partial assignment of the proton resonances in 1. H
NMR results for 7-d-1 and 8-d-1 confirmed the assignments of
the C7 and C8 proton signals. Differentiations between absorp-
tions for endo and exo hydrogens on C7 and C8 were suggested
by the synthetic method used to prepare these compounds, and
assignments were confirmed with NOE experiments. When the
proton signal at δ 2.64 assigned to the bridgehead hydrogen on
C1 was irradiated, enhancement of the absorption at δ 2.23
(exo-H at C8) was observed. Similarly, irradiation of a peak at
δ 2.59, due to the bridgehead hydrogen on C6, enhanced the
resonance at δ 1.91 (exo-H at C7). The endo proton resonances
at both of these positions exhibit the expected shielding effect
of the proximal double bond;20 comparatively, the endo-H at
C8 (δ 1.63) is more shielded than the endo-H at C7 (δ 1.77)
due to its closer proximity to the shielding cone of the π-bond.
The synthesis of 2 (Scheme 4) originated with the known
compound bicyclo[2.2.2]oct-5-en-2-one (9) prepared by Diels-
Alder reaction of 1,3-cyclohexadiene and 2-chloroacrylonitrile
followed by base-catalyzed hydrolysis.21 Hydrogenation of 9
over a Pd catalyst yielded bicyclo[2.2.2]octan-2-one (10),
another known compound22 that was converted to 2 by a two-
step Shapiro modification of the Bamford-Stevens reaction via
the intermediacy of its tosylhydrazone derivative.23 Compound
2 is well-known, and the spectral data obtained for a pure sample
of this material closely matched the reported literature val-
1
ues.22,24 Of particular interest are the H NMR chemical shifts
of the exo and endo hydrogens in 2 at δ 1.48 and 1.21,
respectively.
(19) Baldwin, J. E.; Leber, P. A.; Powers, D. C. J. Am. Chem. Soc. 2006,
128, 10020-10021.
(23) Ye, Q.; Jones, M.; Chen, T.; Shevlin, P. B. Tetrahedron Lett. 2001,
42, 6979-6981.
(20) Rey, M.; Roberts, S.; Dieffenbacher, A.; Dreiding, A. S. HelV. Chim.
Acta 1970, 53, 417-432.
(24) Weyerstahl, P.; Gansau, C.; Marschall, H. FlaVour Fragrance J.
1993, 8, 297-306.
(21) Carrupt, P.-A.; Vogel, P. HelV. Chim. Acta 1989, 72, 1008-1028.
(22) Stothers, J. B.; Swenson, J. R.; Tan, C. T. Can. J. Chem. 1975, 53,
581-588.
(25) Huybrechts, G.; Rigaux, D.; Vankeerberghen, J.; Van Mele, B. Int.
J. Chem. Kinet. 1980, 12, 253-259.
J. Org. Chem, Vol. 72, No. 1, 2007 189

Powers et al.
TABLE 1. Parallel First-Order Rate Constants (×106 s) for 1
For conversion of 1 to 2, Ea ) 52.6 ( 0.7 kcal/mol and log A
) 14.7 ( 0.3. Relative to the activation parameters for [1,3]
rearrangement, those for fragmentation of 1 are quite compa-
rable: Ea ) 52.0 ( 0.3 kcal/mol and log A ) 14.8 ( 0.1. This
remarkable similarity is consistent with the two products from
1 sharing the same rate-determining step to form a diradical
intermediate common to both thermal products.
a
b
temp (°C)
k0
k13
kfc
k13/kf
275
300
315
1.7 ( 0.2
13.9 ( 0.3
44.1 ( 0.6
0.5
4.26
13.2
1.2
9.60
30.9
0.42
0.44
0.43
a Rate constant for overall loss of 1, where k0 ) k13 + kf. b Rate constant
for [1,3] shift of 1 to 2. c Rate constant for fragmentation of 1 to
1,3-cyclohexadiene and ethylene.
Gajewski has previously explicated the two major criteria of
concert, one energetic and one stereochemical.26 The energetic
test implicates a nonconcerted reaction whenever the experi-
mental Ea value is about equal to or larger than the bond
dissociation energy of the C-C bond being broken. The
activation parameters determined for overall loss of 1 (Ea )
51.8 kcal/mol; log A ) 14.9) are comparable to those reported
for vinylcyclobutane (Ea ) 49.3 kcal/mol; log A ) 14.5).27,28
For the vinylcyclobutane to cyclohexene isomerization, the
experimental Ea value is 47.5 ( 0.5 kcal/mol, essentially
identical to the Ea ) 47.9 kcal/mol barrier estimated using a
thermochemical model for complete C1-C2 bond rupture to
form a strain-free diradical intermediate.28 Gajewski asserted
that the activation free energies for almost every [1,3] shift are
5-10 kcal/mol higher than required for a simple bond homoly-
sis, a generalization consistent with [1,3] carbon shifts being
stepwise nonconcerted processes.26 Fundamentally, the vinyl-
cyclobutane reaction fails the energetic criterion of concert.
What then of the stereochemical criterion of concert? Despite
Gajewski’s admonition that stereoselectivity is a necessary but
insufficient criterion for concert,26 the almost complete stereo-
selectivity of the [1,3] shift in 5-exo-methylbicyclo[2.1.1]hex-
2-ene (first entry in Table 2) has been oft-cited in support of a
concerted mechanism for the vinylcyclobutane-to-cyclohexene
rearrangement. Given the three hypotheses enumerated previ-
ously, an examination of the stereochemical data in Table 2
reveals that the contribution from the symmetry-allowed si
pathway decreases with an increase in conformational flexibility
of the bicyclic vinylcyclobutanes.8 The si/sr ratio decreases
going down Table 2 for both the methyl- and the deuterium-
substituted series, suggesting that the conformational agility of
the molecule contributes to the stereochemical outcome of the
[1,3] shift. Thus, the first hypothesis is further substantiated by
extension to the more conformationally flexible bicyclo[4.2.0]-
oct-2-enes.
SCHEME 5. Thermal Reactions of Unlabeled 1
A possible two-centered epimerization at C1-C6 might have
been detected with the aid of a specific deuterium label at C7,
as outlined in Scheme 6. The endo isomer of 7-d-1, 7-n-d-1,
served as a probe of this stereomutation, and overall “ring-flip”.
It was not detected.
The absence of appreciable two-centered stereomutation was,
however, advantageous in that thermal isomerization of 7-d-1
as a mixture of 7-x-d-1 and 7-n-d-1 allowed unambiguous
2
determination of the H NMR chemical shifts of 5-x-d-2 and
2
5-n-d-2 (Scheme 7). The H NMR chemical shifts of δ 1.51
and 1.24 for 5-x-d-2 and 5-n-d-2, respectively, correspond well
1
to the H NMR shifts observed for 2 (Vide supra).
Scheme 8 illustrates the thermal reactions that were observed
starting from the epimers of 8-d-1; 8-n-d-1 and 8-x-d-1
interconvert via one-centered stereomutations, or epimerizations,
at C8; the one-way rate constant k8e defined in Scheme 8 is
3.06 × 10-5 s-1. Both epimers of 8-d-1 undergo [1,3] carbon
migration to 5-d-2 epimers with a slight preference for migration
with inversion of stereochemistry: ksi ) 2.46 × 10-6 s-1, ksr )
1.80 × 10-6 s-1, and k13 ) ksi + ksr ) 4.26 × 10-6 s-1; ksi/ksr
≈ 1.4. In addition, 8-d-1 fragments directly to 1,3-cyclohexa-
diene and d-ethylene: kf ) 9.60 × 10-6 s-1. The progression
of decreasing importance of rate constants is in the following
order: k8e > kf > k13.19
The absence both of octatriene isomers in product mixtures
and a “ring-flip” two-center stereomutation has been cited as
evidence that 1 does not undergo kinetically competitive C1-
C6 bond cleavage.19 It is possible, however, to envision a
degenerate [1,3] rearrangement of 1 involving C1-C6 bond
cleavage; that is, C6 could migrate from C1 to C3. A careful
examination of the 2H NMR spectra for thermal runs performed
on 8-d-1 excludes this possibility as well. This hypothetical
rearrangement, should it occur, would transform 8-x-d-1 to 4-x-
d-1, which would exhibit a 2H NMR signal at ca. δ 2.0 due to
an exo-allylic deuterium. No such peak was observed throughout
the thermal study of 8-d-1.
The second hypothesis, which relates to the stereochemical
effect of the substituent on the migrating carbon, states that a
substituent such as an exo methyl group on the migrating carbon
can retard the rate of rotation about the C-CHCH3 bond in the
diradical intermediate and thus increase the si/sr ratio. Con-
versely, replacing methyl with deuterium, as was done in this
study, will decrease the si/sr ratio. That is, in fact, what is
observed. For the bicyclo[4.2.0]oct-2-enes, an exo-methyl label
affords si/sr ) 2.4;8 a deuterium label, si/sr ) 1.4.19 The
generality of this trend can be validated by comparing the entries
in Table 2. Moreover, the data in Table 2 provide compelling
Discussion and Conclusions
(26) Gajewski, J. J. Acc. Chem. Res. 1980, 13, 142-148.
(27) Frey, H. M.; Pottinger, R. J. Chem. Soc., Faraday Trans. 1 1978,
74, 1827-1833.
An examination of the first-order rate constants in Table 1
shows that at all temperatures kf is greater than k13. Not only is
the k13/kf ratio significantly less than 1, but it is also constant.
Although one might expect fragmentation to increase as
temperature increases, that is not observed at least over this
fairly narrow 40 °C temperature range. Activation parameters
have been determined for both the [1,3] isomerization and
fragmentation processes based on the rate constants in Table 1.
(28) Lewis, D. K.; Charney, D. J.; Kalra, B. L.; Plate, A.-M.; Woodard,
M. H.; Cianciosi, S. J.; Baldwin, J. E. J. Phys. Chem. A 1997, 101, 4097-
4102.
(29) Roth, W. R.; Friedrich, A. Tetrahedron Lett. 1969, 2607-2610.
(30) Carpenter, B. K.; Newman-Evans, R. H. J. Am. Chem. Soc. 1984,
106, 7994-7995.
(31) Baldwin, J. E.; Fede, J.-M. J. Am. Chem. Soc. 2006, 128, 5608-
5609.
190 J. Org. Chem., Vol. 72, No. 1, 2007

Thermal Chemistry of Bicyclo[4.2.0]oct-2-enes
SCHEME 6. Undetected C1-C6 Double Stereomutation of 7-d-1
TABLE 2. Stereochemistry for [1,3] Shifts Shown by Bicyclic
Vinylcyclobutanes
SCHEME 7. Thermal Conversion of 7-d-1 Epimers to 5-d-2
Epimers
SCHEME 8. Kinetic Scheme for 8-d-1
TABLE 3. Relative Percent Contribution of Three Major Exit
Channels: [1,3] Carbon Shifts, Epimerizations, and Fragmentations
evidence that the [1,3] shift of bicyclic vinylcyclobutanes fails
the stereochemical criterion of concert.
The third and final hypothesis states that the combined extent
of stereomutation and fragmentation should increase at the
expense of the [1,3] isomerization as the bicyclic vinylcyclobu-
tane becomes more conformationally supple. To examine the
validity of this hypothesis for a series of bicyclic and monocyclic
vinylcyclobutanes, the relative contributions of each of the three
major exit channels available to vinylcyclobutanes, the [1,3]
migration, one-centered stereomutation or epimerization, and
fragmentation, are compared in Table 3.
mode of reaction for monocyclic systems. The existence on the
vinylcyclobutane potential energy surface of a trans-diradical
intermediate, from which isomerization to cyclohexene is
geometrically prohibited, undoubtedly contributes to the domi-
nance of the fragmentation exit channel for monocyclic
vinylcyclobutanes.6c Not only do the data in Table 3 substantiate
the final hypothesis, but they illustrate that the balance between
the three dominant exit channels available to the diradical
intermediate is easily altered by the conformational flexibility
of the reactant vinylcyclobutanes and, by extension, of the
related diradicals themselves.
The relative order of importance of rate constants for the three
reaction manifolds for four vinylcyclobutanes is indicated in
the next to last column of Table 3. The essentially rigid bicyclo-
[2.1.1]hex-2-ene experiences [1,3] rearrangement exclusively.
As soon as the bicyclic framework permits even modest
The exit channel data in Table 3 strikingly complement the
stereochemical data in Table 2 by supporting the conclusion
that the bicyclo[2.1.1]hex-2-enes are anomalous. The total
amount of epimerization and fragmentation combined increases
dramatically as the conformational flexibility of a bicyclic
vinylcyclobutane increases going down Table 3. For the bicyclic
vinylcyclobutanes, the [1,3] isomerization process gradually
becomes less important relative to epimerization and to a lesser
extent fragmentation. The relative amount of fragmentation is
comparable for both bicyclo[3.2.0]hept-2-ene and bicyclo[4.2.0]-
oct-2-ene. Comparing the bicyclic and the monocyclic vinyl-
cyclobutanes shows that fragmentation becomes the dominant
J. Org. Chem, Vol. 72, No. 1, 2007 191

Powers et al.
SCHEME 9. Epimerization at C8 in 8-d-1
conformational mobility, fragmentation and epimerization be-
come significant. Still, the [1,3] product is the dominant exit
channel for bicyclo[3.2.0]hept-2-ene. In contrast, the isomer-
ization is far less important for bicyclo[4.2.0]oct-2-ene (1), for
which epimerization is favored. It appears that subtle differences
in the dynamic factors associated with bond rotation in closely
related diradicals allow the intermediate to partition among the
various exit channels in myriad ways. The greater is the distance
between the migrating carbon and the migration terminus,8 the
more time the diradical has to explore conformational space
before reformation of a C-C bond or cleavage of a second C-C
bond defines a product.
for a long-lived, conformationally promiscuous diradical inter-
mediate on the potential energy surface.
Experimental Section
The fate of the diradical experiencing an inward trajectory5,6
of the migrating carbon accompanying bond homolysis is largely
determined by dynamic factors.5 The existence of a long-lived
diradical residing in a deeper local energy minimum that is
protected from immediate isomerization to 2 or fragmentation
to 1,3-cyclohexadiene and ethylene is consistent with the low
si/sr ratio ≈ 1.4, suggesting there is sufficient time for C7-C8
bond rotation before C8 reaches C3 in the [1,3] migration
(Scheme 9). Although residual bonding has been postulated as
a basis for the preference for the si product,5b,6c internal rotation
destroys residual bonding.4b Perhaps there still remains a small
contribution from a rapid direct inward trajectory leading
exclusively to the si product or from a subset of the diradical
population with greater angular momentum.
8,8-Dichlorobicyclo[4.2.0]oct-2-en-7-one (3). To a mixture of
70 g of zinc-copper couple (0.75 mol) in 25.0 mL of 1,3-
cyclohexadiene (0.262 mol) and 200 mL of anhydrous diethyl ether
was added a solution of 100 g of trichloroacetyl chloride (0.550
mol) and 100 mL of dimethoxyethane (DME) over a period of 1
h. The reaction was stirred overnight at room temperature. The
resulting mixture was filtered through a sintered glass funnel, and
the solid was washed several times with hexane. The organic phase
was washed sequentially with 0.5 N HCl, 5% NaOH, water, and
brine; filtered through a plug of silica gel and charcoal; dried with
MgSO4; evaporated under reduced pressure; and subjected to bulb-
to-bulb distillation at 1-2 Torr (55-60 °C) to afford 20.9 g of 3
(42%). IR (cm-1): 3050 (w), 1800 (s), 1650 (w), 705 (s). MS (m/
z): 194 (1%), 192 (4%), 190 (M+, 6%), 155 (14%), 127 (15%), 91
(33%), 79 (27%), 55 (100%). 1H NMR (500 MHz, CDCl3): δ 1.61
(1H, m), 1.95 (1H, m), 2.00 (1H, m), 2.07 (1H, m), 3.41 (1H, m),
4.07 (1H, m), 5.84 (1H, m), 6.05 (1H, m). 13C NMR (125 MHz,
CDCl3): δ 18.6 (CH2), 20.7 (CH2), 44.1 (CH), 53.2 (CH), 86.6
(CCl2), 122.9 (dCH), 132.3 (dCH), 196.6 (CdO).
Bicyclo[4.2.0]oct-2-en-7-one (4). To a mixture of 12.13 g of
zinc dust (0.186 mol) in 60 mL of absolute ethanol and 25 mL of
TMEDA was added 11.8 mL of glacial acetic acid (0.206 mol)
over 10 min. After addition of a solution of 6.00 g (31.4 mmol) of
3 in 12.6 mL of glacial acetic acid (0.219 mol), the reaction was
heated to 40 °C and stirred overnight. The reaction mixture was
passed through a sintered glass funnel, exercising care to avoid
exposing the pyrophoric zinc to air until it had been quenched by
the addition of water. The solids were washed thoroughly with 50:
50 pentane:ether before the organic layer was washed successively
with 1 N HCl, saturated NaHCO3, water, and brine and then dried
with MgSO4. Solvent was evaporated under reduced pressure,
affording 3.43 g (28.1 mmol, 89%) of 4. IR (cm-1): 3050 (w),
1780 (s), 1650 (w), 690 (m). MS (m/z): 122 (<1%), 91 (4%), 80
(100%), 79 (79%). 1H NMR (300 MHz, CDCl3): δ 1.49 (1H, m),
1.94 (3H, m), 2.53 (1H, dt), 2.85 (1H, m), 3.20 (1H, ddd), 3.49
(1H, m), 5.78 (1H, m), 5.87 (1H, m). 13C NMR (75 MHz, CDCl3):
δ 19.3 (CH2), 21.1 (CH2), 22.8 (CH), 51.9 (CH2), 57.2 (CH), 128.2
(dCH), 128.8 (dCH), 211.8 (CdO).
While compound 8-n-d-1 exhibits little preference for 5-n-
d-2, the orbital-symmetry allowed si product (Scheme 8), the
diradical intermediate has a far greater tendency to reclose to
the less thermodynamically stable 1 (with corresponding
epimerization at C8) than to isomerize to the more thermody-
namically stable 2: k8e > kf > k13.19 This suggests that the
conspicuous difference in rate order (Table 3) reported for the
bicyclo[3.2.0]hept-2-enes (k13 > kf > k7e) as compared to the
bicyclo[4.2.0]oct-2-enes is a consequence of different diradical
lifetimes, not rotational rates or diradical stabilities, for 11 and
12. A sufficiently high-energy barrier protecting the diradical
intermediate formed by C1-C8 bond homolysis of 1 from either
isomerization to 2 or fragmentation can account for the
difference in lifetimes for 11 and 12. If a shallow minimum on
a potential energy surface has associated with it wider exit
channels,6c then a steeper minimum will produce narrower exit
channels, favoring reclosure to starting material. Using Car-
penter’s terminology, the inefficiency of the direct trajectory
favors a reflected trajectory due to the facility of internal bond
rotation in the diradical intermediate.5b
Bicyclo[4.2.0]oct-2-ene (1). To a solution of 3.77 g of hydrazine
sulfate (29.1 mmol) in 10.5 mL of hydrazine hydrate was added
3.43 g (28.1 mmol) of 4 over 15 min. The reaction mixture was
stirred overnight at 65 °C, extracted with ether, dried over MgSO4,
and evaporated under reduced pressure to yield 2.95 g (21.7 mmol,
77%) of bicyclo[4.2.0]oct-2-en-7-one hydrazone. IR (cm-1): 3460
(w), 3200 (w), 3020 (w), 2930 (m), 1590 (w), 1540 (w), 700 (s).
To a solution of 1.58 g (14.1 mmol) of freshly sublimed potassium
tert-butoxide in 25 mL of anhydrous DMSO was added 1.39 g (9.24
mmol) of hydrazone over 5 h. After being stirred overnight, the
reaction was quenched with ice cold water (5 mL) and the product
was extracted into pentane. The organic phase was washed several
times with water to remove all residual DMSO, dried with MgSO4,
and purified by short-path distillation to give 0.489 g (4.53 mmol,
49%) of 1 as a colorless liquid. IR (cm-1): 3010 (w), 1650 (w),
700 (s). MS (m/z): 108 (2%), 91 (6%), 80 (100%), 79 (51%), 77
Given the kinetic dominance of epimerization at C8 evident
in product mixtures (Scheme 8) and an si/sr ratio close to one
for the two [1,3] shifts, any rationale championing orbital
symmetry control of the thermal isomerizations observed
becomes untenable. The small si/sr rate ratio corresponds to a
paltry difference in activation energy of less than 0.4 kcal/mol.
Not only does the low si/sr ratio provide a compelling refutation
of orbital symmetry control of the [1,3] sigmatropic rearrange-
ment, but also the low si/sr ratio and the competition between
the three exit channels constitute rigorous experimental support
1
(51%). H NMR (500 MHz, CDCl3): δ 1.48 (2H, m), 1.61 (1H,
192 J. Org. Chem., Vol. 72, No. 1, 2007

Thermal Chemistry of Bicyclo[4.2.0]oct-2-enes
m), 1.73 (1H, dq), 1.87 (1H, m), 1.97 (1H, m), 2.08 (1H, m), 2.19
(1H, dq), 2.59 (1H, m), 2.64 (1H, br s), 5.73 (1H, m), 5.79 (1H,
m). 13C NMR (125 MHz, CDCl3): δ 21.5 (CH2), 22.4 (CH2), 24.0
(CH2), 27.8 (CH2), 32.7 (CH), 33.0 (CH), 126.8 (dCH), 130.9 (d
CH).
z): 157 (2%), 129 (6%), 79 (27%), 55 (100%). 1H NMR (500 MHz,
CDCl3): δ 1.57 (1H, m), 2.03 (2H, m), 2.09 (1H, m), 3.23 (1H, br
m), 3.61 (1H, br m), 5.77 (1H, m), 6.02 (1H, m). 13C NMR (125
MHz, CDCl3): δ 18.1 (CH2), 20.7 (CH2), 29.8 (CH), 53.0 (CH),
62.4 (CDCl), 123.0 (dCH), 131.2 (dCH), 202.8 (CdO). The 13
C
NMR data matched the literature values for 8-endo-chlorobicyclo-
7-d-8,8-Dichlorobicyclo[4.2.0]oct-2-en-7-ol (5). To a solution
of 4.738 g of 3 (24.9 mmol) and 30 mL of MeOH at 0 °C was
added 0.90 g of NaBD4 (27 mmol) over 2 h. The reaction was
warmed to rt and stirred overnight. The reaction was extracted with
ether, washed sequentially with 1 N HCl, H2O, saturated NaHCO3,
H2O, and brine, and then dried with MgSO4. Evaporation at reduced
pressure afforded 3.864 g (20.0 mmol, 80%) of 5. IR (cm-1): 3300
(br, m), 3050 (w), 1650 (w), 860 (s), 710 (s).
[4.2.0]oct-2-en-7-one.13
8-d-Bicyclo[4.2.0]octa-2,7-diene (8). Compound 8 was prepared
according to the procedure for the preparation of 6. Starting with
5.24 g (33.4 mmol) of 7, 40 mL of d-methanol, and 5.58 g (134
mmol) of NaBH4, 3.95 g (24.7 mmol, 74%) of alcohol was isolated.
IR (cm-1): 3400 (br, m), 2920 (m), 2220 (w), 1640 (w), 705 (s).
MS (m/z): 159 (1%), 103 (16%), 80 (100%), 57 (31%). From 3.95
g (24.7 mmol) of alcohol, 7 mL of triethylamine, and 7.74 mL of
methanesulfonyl chloride (0.1 mol) was isolated 5.24 g (22.2 mmol,
90%) of mesylate derivative. IR (cm-1): 2930 (w), 2300 (w), 1350
(s), 1180 (s). The diene was prepared from 5.24 g of mesylate (22.2
mmol) as per the procedure for 6. Short-path distillation afforded
1.16 g (10.9 mmol, 49%) of 8. IR (cm-1): 3020 (w), 1640 (w),
7-d-Bicyclo[4.2.0]octa-2,7-diene (6). To a solution of 3.864 g
(20.0 mmol) of 5, 4 mL of triethylamine, and 100 mL of CH2Cl2
at 0 °C was added 3.1 mL of methanesulfonyl chloride (40 mmol)
over 15 min. The reaction was warmed to rt, stirred overnight,
extracted into CH2Cl2, washed sequentially with 1 N HCl, water,
saturated NaHCO3, water, and brine, and then dried over MgSO4.
Evaporation at reduced pressure afforded 3.20 g (16.6 mmol, 83%)
of mesylate. IR (cm-1): 3020 (w), 1650 (w), 1360 (s), 1170 (s),
710 (s). After condensing ca. 500 mL of ammonia, 1.84 g of sodium
metal (80 mmol) was added to the liquid ammonia in small pieces
over 15 min at -78 °C to yield an intense blue reaction mixture.
A solution of 3.20 g (16.6 mol) of mesylate in 40 mL of anhydrous
THF was slowly added to the reaction, which was then allowed to
stir at -78 °C for 5 h before slowly warming to -35 °C. The
reaction was then cooled to -60 °C, and sufficient NH4Cl was
added until the blue color dissipated. The reaction was then allowed
to warm slowly; before all of the ammonia had evaporated, 100
mL of pentane and 100 mL of water were added. The reaction was
extracted with pentane, washed sequentially with 1 N HCl, water,
saturated NaHCO3, water, and brine, and then dried with MgSO4.
Short-path distillation afforded 0.923 g (8.63 mmol, 52%) of 6. IR
(cm-1): 3020 (m), 1630 (w), 710 (s). MS (m/z): 107 (27%), 92
1
700 (s), 670 (s). H NMR (500 MHz, CDCl3): δ 1.33 (1H, tt),
1.75 (1H, m), 1.85 (1H, m), 1.99 (1H, m), 3.11 (1H, br s), 3.24
(1H, m), 5.82 (2H, m), 6.08 (1H, s). 13C NMR (125 MHz, CDCl3):
δ 21.5 (CH2), 25.8 (CH2), 41.4 (CH), 42.1 (CH), 128.0 (dCH),
2
129.2 (dCH), 136.4 (dCD), 137.6 (dCH). H NMR (92 MHz,
CDCl3): δ 5.92.
8-d-Bicyclo[4.2.0]oct-2-ene (8-d-1). Compound 8-d-1 was pre-
pared according to the procedure for the preparation of 7-d-1.
Starting with 1.164 g (10.9 mmol) of 8, crude 8-d-1 (0.962 g, 8.83
mmol) was isolated in 81% yield. Purity greater than 99% was
achieved via preparative GC. IR (cm-1): 3010 (w), 1640 (w), 730
(s). MS (m/z): 109 (2%), 92 (3%), 80 (100%), 79 (51%). 1H NMR
(500 MHz, CDCl3): δ 1.49 (2H, m), 1.59 (0.15H, m), 1.72 (1H,
m), 1.87 (1H, m), 1.98 (1H, m), 2.08 (1H, m), 2.18 (0.85H, dq),
2.59 (1H, m), 2.65 (1H, br s), 5.74 (1H, m), 5.79 (1H, m). 13C
NMR (125 MHz, CDCl3): δ 21.5 (CH2), 22.3 (CH2), 24.1 (CH2),
27.5 (CHD), 32.7 (CH), 32.9 (CH), 126.8 (dCH), 130.9 (dCH).
2H NMR (92 MHz, CHCl3): δ 2.23 (15%), 1.63 (85%).
Bicyclo[2.2.2]oct-5-en-2-one (9). To a solution of 27 mg of
hydroquinone in 20 mL (0.18 mol) of 1,3-cyclohexadiene was added
10 mL (11 g, 0.12 mol) of 2-chloroacrylonitrile (pretreated with
potassium hydroxide pellets from which it was decanted before
addition). After refluxing overnight in the dark at 90-100 °C, an
additional 10 mL of 1,3-cyclohexadiene was added, and the reaction
mixture was again refluxed overnight. The brown reaction mixture
was diluted with 15 mL of CH2Cl2, and the resultant solution was
filtered through a short silica gel column and then concentrated
under reduced pressure to yield 6.9 g of a dark brown liquid. IR
(cm-1): 3040 (w), 2240 (w), 1650 (w), 710 (s). To a solution of
the viscous residue in 95 mL of DMSO was slowly added an
aqueous solution of 11.6 g of KOH in 20 mL of water over 4 h
with continuous stirring. Stirring was continued for an additional
20 h; the addition of 200 mL of water was followed by five
successive extractions with pentane. The organic extract was then
washed with brine, dried over MgSO4, and concentrated under
reduced pressure to afford 2.6 g (0.021 mol, 18% overall) of
compound 9 as a white crystalline solid (mp 85-88 °C). IR (cm-1):
3040 (w), 1725 (s), 1610 (w), 700 (s). MS (m/z): 122 (23%), 80
(100%), 79 (88%). 1H NMR (500 MHz, CDCl3): δ 1.48 (m, 1H),
1.55 (m, 1H), 1.67 (m, 2H), 1.83 (m, 1H), 2.00 (m, 1H), 2.96 (m,
1H), 3.10 (br m, 1H), 6.17 (t, 1H), 6.45 (t, 1H). 13C NMR (125
MHz, CDCl3): δ 22.5 (CH2), 24.2 (CH2), 32.3 (CH), 40.5 (CH2),
48.5 (CH), 128.4 (dCH), 137.0 (dCH), 213.2 (CdO).
1
(42%), 79 (100%). H NMR (500 MHz, CDCl3): δ 1.34 (1H, tt),
1.76 (1H, m), 1.86 (1H, br m), 2.00 (1H, br m), 3.12 (1H, m), 3.25
(1H, m), 5.83 (2H, m), 5.86 (1H, s). 13C NMR (125 MHz, CDCl3):
δ 21.5 (CH2), 25.8 (CH2), 41.4 (CH), 42.0 (CH), 128.0 (dCH),
2
129.2 (dCH), 136.2 (dCH), 137.7 (dCD). H NMR (92 MHz,
CHCl3): δ 6.08.
7-d-Bicyclo[4.2.0]oct-2-ene (7-d-1). To a solution of 0.923 g
(8.63 mmol) of 6 and 30 mL of absolute ethanol was added 0.27
mL (8.63 mmol) of anhydrous hydrazine. The reaction was cooled
to -20 °C, and then 1 mL aliquots of 30% hydrogen peroxide were
added to the reaction mixture every 2 h while reaction progress
was monitored by GC. After 6 h, an additional 0.27 mL of
anhydrous hydrazine was added. Water (20 mL) was added to the
reaction after >80% conversion was achieved. Short-path distillation
afforded 0.715 g (6.56 mmol, 76%) of crude 7-d-1, which was
obtained in >99% purity by preparative GC (8’ × 1/4” 20% DC-
710 on Chrom P, 70 °C). IR (cm-1): 3020 (m), 2190 (w), 1640
(w), 690 (s). MS (m/z): 109 (3%), 92 (4%), 80 (100%), 79 (53%).
1H NMR (500 MHz, CDCl3): δ 1.48 (2H, m), 1.61 (1H, m), 1.73
(0.18H, m), 1.87 (0.82H, m), 1.97 (1H, m), 2.08 (1H, m), 2.19
(1H, dq), 2.59 (1H, m), 2.64 (1H, br s), 5.73 (1H, m), 5.79 (1H,
m). 13C NMR (125 MHz, CDCl3): δ 21.5 (CH2), 22.0 (CHD), 24.0
(CH2), 27.7 (CH2), 32.6 (CH), 33.0 (CH), 126.8 (dCH), 130.9
2
(dCH). H NMR (92 MHz, CHCl3): δ 1.77 (82%), 1.91 (18%).
8-exo-d-8-endo-Chlorobicyclo[4.2.0]oct-2-en-7-one (7). To a
solution of 9.22 g (48.5 mmol) of 3 in 100 mL of d-acetic acid
was slowly added 3.2 g of zinc dust (49 mmol). The reaction was
stirred until the gray color of zinc was observed to disappear. When
the reaction was deemed complete by GC-MS, it was cooled to 0
°C before ice water was added to the reaction vessel. After three
successive extractions with ether, the organic phase was washed
sequentially with saturated sodium bicarbonate, water, 1 N HCl,
water, and brine, and then dried with MgSO4. Evaporation at
reduced pressure afforded 7.08 g (45.1 mmol, 93%) of 7. MS (m/
Bicyclo[2.2.2]octan-2-one (10). A solution of 0.68 g (5.6 mmol)
of 9 in 50 mL of absolute ethanol, to which ca. 0.2 g of 10% Pd/C
was added, was placed in a Parr apparatus and subjected to medium-
pressure hydrogenation for 2 h. After the reaction mixture was
filtered through a sintered glass funnel, it was diluted with water,
extracted with ether, washed with water, dried with MgSO4, and
concentrated under reduced pressure to yield 0.62 g (5.0 mmol,
J. Org. Chem, Vol. 72, No. 1, 2007 193

Powers et al.
89%) of 10 as a white solid (mp 169-172 °C). IR (cm-1): 1720
× 0.2 mm i.d. × 0.10 µm film thickness) operating at an initial
temperature of 60 °C held for 1 min followed by a temperature
ramp of 0.5 °C/min to a maximum temperature of 120 °C. Retention
times (min) were as follows: 2 (9.0), 1 (10.0), and the internal
standard cyclooctane (11.8). Concentrations of fragments 1,3-
cyclohexadiene and ethylene were determined by difference as
compared to a time zero sample for each kinetic run.
1
(s), 1670 (w). MS (m/z): 124 (54%), 81 (36%), 80 (100%). H
NMR (500 MHz, CDCl3): δ 1.58 (m, 2H), 1.69 (m, 2H), 1.79 (m,
4H), 2.13 (m, 1H), 2.22 (m, 3H). 13C NMR (125 MHz, CDCl3): δ
23.3 (CH2), 24.7 (CH2), 27.9 (CH), 42.3 (CH), 44.7 (CH2), 218.1
(CdO).
Bicyclo[2.2.2]oct-2-ene (2). To a solution of 1.86 g (10.0 mmol)
of p-toluenesulfonylhydrazide in 50 mL of methanol was added
0.62 g (5.0 mmol) of 10. After sitting overnight, the resultant white
crystals were filtered, washed with 1:1 pentane:ether, and dried in
a vacuum oven to yield 0.99 g (3.4 mmol, 68%) of tosylhydrazone
(mp 214-215 °C). IR (cm-1): 3210 (m), 1650 (w), 1320 (s), 1170
(s), 670 (s). Under nitrogen atmosphere, 3.4 mL of 1.6 M MeLi in
ether (5.4 mmol) was added via syringe to a solution of 0.76 g
(2.6 mmol) of tosylhydrazone in 25 mL of TMEDA in an ice bath.
After the reaction was allowed to warm and stir overnight, it was
cooled to -30 °C, quenched with water, and extracted successively
with pentane. The organic layer was washed with water, 3 M NaOH,
1 N HCl, water, and brine, dried over MgSO4, and concentrated
by short-path distillation to give a colorless waxy solid. To facilitate
transfer, the waxy solid was dissolved in ca. 5 mL of pentane; 99%
yield of 2 was based on GC analysis of this pentane solution. IR-
(cm-1): 1620 (w). MS (m/z): 108 (18%), 80 (100%), 79 (47%).
1H NMR (500 MHz, CDCl3): δ 1.21 (br d, 4H), 1.48 (br d, 4H),
2.46 (br m, 2H), 6.23 (dd, 2H). 13C NMR (125 MHz, CDCl3): δ
25.7 (CH2), 29.5 (CH), 134.3 (dCH).
Thermal runs of deuterium-labeled compounds were removed
using standard vacuum line transfer and dissolved in chloroform
that had been purified by washing with concd H2SO4 and water
and then distilling from calcium hydride. H NMR spectra were
acquired at 92.15 MHz.
2
Acknowledgment. We acknowledge the donors of The
American Chemical Society Petroleum Research Fund and the
Franklin & Marshall College Hackman Scholars Program for
support of this research. S.S.G., A.T.H., and D.C.P. also received
partial support through Schappell Research Scholarships.
2
Supporting Information Available: H NMR spectrum of 7-d-1
and its thermal reaction mixture; tables of mole fractions for thermal
runs of 1 at 275, 300, and 315 °C and the associated first-order
rate plots; copies of an Arrhenius plot and a sample GC chromato-
1
gram for the gas-phase thermal decomposition of 1. Copies of H
NMR and 13C NMR spectra of compounds 1, 7-d-1, 8-d-1, 2, 6,
and 8 can be found in the SI section of ref 17. This material is
available free of charge via the Internet at http://pubs.acs.org.
Gas-Phase Reactions. Thermal reactions were conducted in an
apparatus described previously.2h Thermolysis samples were ana-
lyzed by GC on an HP cross-linked methyl silicone column (50 m
JO061964X
194 J. Org. Chem., Vol. 72, No. 1, 2007