Thermal reactions of anti- and syn-dispiro[5.0.5.2]tetradeca-1,8-dienes: Stereomutation and fragmentation to 3-methylenecyclohexenes. Entropy-dictated product ratios from diradical intermediates?

Article abstract of DOI:10.1021/ja004128s

A series of cyclobutanes substituted 1,2- by polyenes of increasing radical-stabilizing power has been investigated to test the proposition that stabilization energies obtained independently from apposite, cis,-trans geometric isomerizations can be succes

Full text of DOI:10.1021/ja004128s

5532
J. Am. Chem. Soc. 2001, 123, 5532-5541
Thermal Reactions of anti- and
syn-Dispiro[5.0.5.2]tetradeca-1,8-dienes: Stereomutation and
Fragmentation to 3-Methylenecyclohexenes. Entropy-Dictated Product
Ratios from Diradical Intermediates?
W. von E. Doering,*,† Juris L. Ekmanis,† Kevin D. Belfield,† F.-G. Kla1rner,*,‡ and
Bernd Krawczyk‡
Contribution from the Department of Chemistry and Chemical Biology, HarVard UniVersity,
Cambridge, Massachusetts 02138-2902, and the Institut fu¨r Organische Chemie, UniVersita¨t GH Essen,
D-45117 Germany
ReceiVed NoVember 30, 2000
Abstract: A series of cyclobutanes substituted 1,2- by polyenes of increasing radical-stabilizing power has
been investigated to test the proposition that stabilization energies obtained independently from apposite, cis,-
trans geometric isomerizations can be successfully transferred to another system, in this paper, cyclobutanes.
The first member of the series, 3-methylenecyclohexene (1), is photodimerized to anti- and syn-dispiro[5.0.5.2]-
tetradeca-1,8-dienes (anti-2 and syn-2), which undergo stereomutation (stereochemical interconversion) and
cycloreversion (fragmentation) to 1 when heated in the range 72.1-118.2 °C: anti-2 f syn-2, ∆Hq ) 30.3
kcal mol-1, ∆Sq ) 0.2 cal mol-1 K-1; anti-2 f 1, ∆Hq ) 32.8 kcal mol-1, ∆Sq ) +8.0 cal mol-1 K-1
.
Agreement with an enthalpy of activation predicted by assuming full allylic stabilization in a hypothetical
diradical intermediate is good. An example of further activation by a radical-stabilizing group is manifested
by the ∼20 000-fold acceleration in rate shown by the system 1-phenyl-3-methylenecyclohexene (3) and anti-
and syn-2,9-diphenyldispiro[5.0.5.2]tetradeca-1,8-dienes (anti-4 and syn-4), measured, however, only at 43.6
°C. In both systems 2 and 4, volumes of activation for stereochemical interconversion and cycloreversion
have been determined and found to be essentially identical within experimental uncertainties, ∆Vq ) +10.2
( 1.0 and +12.6 ( 1.4 cm3 mol-1, respectively (weighted means). These strongly positive values are consistent
with the rate-determining step being the first bond-breaking, while the near identity of the volumes of activation
argues against the indispensable second bond-breaking being a determining factor in fragmentation. These
results are consistent with the theoretically based construct of Charles Doubleday for the paradigm, cyclobutane,
in which the ratio between two channels of exit from a “generalized common biradical” is not controlled by
enthalpy and entropy, as in the transition state model, but by entropy alone.
Introduction
have been extensive.1-4 At the experimental level, intrepid
purists have explored these questions with deuterium as a
minimal perturbation,5-8 while soldiering pragmatists have
introduced more drastic perturbations in the hope of achieving
answers.
Dealing mechanistically with not-obviously-concerted thermal
rearrangements that involve competitive formation of two or
more products has a long and frustrating history. The pressing
question in mechanistic thinking about such “no-mechanism”
systems has centered about the nature and role of hypothetical
diradical intermediates. Expressed specifically in terms of the
archetypal system, cyclobutane and two molecules of ethylene,
two questions may be asked. Should bond-breaking (or bond-
making in the reverse direction) lead to barrier-protected,
diradical-like tetramethylenes in gauche and antiperiplanar
conformations, each capable of further internal rotation prior
to cleavage to two molecules of ethylene, or to closure to
cyclobutane? Or should the elements of bond-breaking, bond-
making, and internal rotations be combined into competing
“concerted” processes, some “allowed”, some “forbidden”?
Theoretical efforts to elucidate the thermal behavior of the
pristinely unsubstituted archetypal cyclobutane in the gas phase
(1) (a) Doubleday, C., Jr.; Camp, R. N.; King, H. F.; Page, M.; McIver,
J. W., Jr.; Mullally, D. J. Am. Chem. Soc. 1984, 106, 447-448. (b)
Doubleday, C., Jr.; Page, M.; McIver, J. W., Jr. J. Mol. Struct. (THEOCHEM)
1988, 163, 331-341. (c) Doubleday, C., Jr. J. Am. Chem. Soc. 1993, 115,
11968-11983. (d) Doubleday, C., Jr. Chem. Phys. Lett. 1995, 233, 509-
513. (e) Doubleday, C., Jr. J. Phys. Chem. 1996, 100, 15083-15086.
(2) Bernardi, F.; Bottoni, A.; Robb, M. A.; Schlegel, H. B.; Tonachini,
G. J. Am. Chem. Soc. 1985, 107, 2260-2264. Bernardi, F.; De, S.; Olivucci,
M.; Robb, M. A. J. Am. Chem. Soc. 1990, 112, 1737-1744.
(3) Marcus, R. A. J. Am. Chem. Soc. 1995, 117, 4683-4690.
(4) Moriarty, N. W.; Lindh, R.; Karlstro¨m, G. Chem. Phys. Lett. 1998,
289, 442-450.
(5) Dervan, P.; Santilli, D. J. Am. Chem. Soc. 1980, 102, 3863-3870.
(6) (a) Goldstein, M. J.; Cannarsa, M. J.; Kinoshita, T.; Koniz, R. F.
Stud. Org. Chem. (Amsterdam) 1987, 31, 121-133. (b) Cannarsa, M. J.
The Synthesis and Thermolysis of Stereospecifically Labeled 1,2,3,4-
Cyclobutanes-D4. Ph.D. Dissertation, Cornell University, Ithaca, NY, 1984;
Diss. Abstr. Int. B 1984, 45, 1468B (Order No. 84-15,310).
(7) Lewis, D. K.; Glenar, D. A.; Kalra, B. L.; Baldwin, J. E.; Cianciosi,
S. J. J. Am. Chem. Soc. 1987, 109, 7225-7227.
* To whom correspondence may be addressed. E-mail: doering@chemistry.
harvard.edu; klaerner@oc1.orgchem.uni-essen.de.
† Harvard University.
(8) Chickos, J.; Annamalia, A.; Keiderling, T. J. Am. Chem. Soc. 1986,
108, 4398-4402.
‡ Universita¨t GH Essen.
10.1021/ja004128s CCC: $20.00 © 2001 American Chemical Society
Published on Web 05/16/2001

Entropy-Dictated Product Ratios from Diradical Intermediates?
J. Am. Chem. Soc., Vol. 123, No. 23, 2001 5533
Figure 1. Activation parameters for stereomutation and fragmentation
in the system 1/2 are given as ∆Hq in kilocalories per mole and ∆Sq in
calories per mole per kelvin. Conformations of the diradical intermedi-
ates are depicted at the top.
Among well-studied examples are the systems 1,3-butadiene/
1,2-divinylcyclobutane and piperylene/1,2-dipropenylcyclobu-
tane.9 Both are representative of dienes free to assume cisoid
or transoid conformations ad libitum, and both encompass
several reaction channels in the forward direction, including
dimerization to cyclobutanes, cyclooctadienes, and vinylcyclo-
hexenes, as well as stereomutation and cycloreversion of the
resulting cyclobutanes. Mechanistic studies understandably have
been complicated.
In the present study, a larger but chemically simpler diene is
examined: 3-methylenecyclohexene (1) and two derived [2 +
2] photodimers, anti- and syn-dispiro[5.0.5.2]tetradeca-1,8-diene
(anti-2 and syn-2). A close relative included in this study
involves further substitution by the strongly radical-stabilizing
phenyl group: system 3/4 consisting of 1-phenyl-3-methyl-
enecyclohexene (3) and anti- and syn-2,9-diphenyldispiro-
[5.0.5.2]tetradeca-1,8-diene (anti-4 and syn-4). The butadiene
group in these semicyclic dienes being strictly confined to a
transoid conformation, dimers of the vinylcyclohexene and 1,5-
cyclooctadiene types are precluded on thermodynamic grounds
owing to the energetic cost of having trans double bonds in
small rings. Permitted reactions are limited to stereochemical
interconversion (stereomutation) and cycloreversion (fragmenta-
tion) (Figure 1), just as they are in the archetype.
Figure 2. Polyenes and their corresponding anti-cyclobutane dimers
(but not syn-) are shown, along with heats of formation and derived
heats of dimerization (kcal mol-1) as calculated by using Roth’s
molecular mechanical program, MM2EVBH.
though yields are low in all procedures, the product of the flow
pyrolysis can be purified by distillation (99%), whereas that
from the other two methods requires laborious enrichment by
preparative GLC to achieve no better than 90% purity.13,14
Thermal dimerization of 1 has been attempted in vain at
atmospheric pressure and temperatures where the related dimeric
cyclobutanes 2 (vide infra) undergo cycloreversion.15 The
unfavorably large entropy of a bimolecular reaction appears to
have overwhelmed a favorable difference in enthalpy of forma-
tion,16 which, however, has been made less so than in the arche-
type by a substantial enthalpy of conjugation in the monomer
(∼7.5 kcal mol-1), and what appears to be repulsive strain
energy in the tetrasubstituted dimer (∼6 kcal mol-1), as calcu-
lated by the force field program MM2EVBH (see Figure 2).17b,18
(12) Smithson, L.; Ibrahim, N.; Wieser, H. Can. J. Chem. 1983, 61, 442-
453; McIntosh, J. M.; Steevensz, R. S. Can. J. Chem. 1977, 55, 2442.
(13) A formal preparation of 1 exists in the base-catalyzed equilibration
of any of its double-bond isomers: 1 (13%); 1-methyl- (44%), 2-methyl-
(44%), and 5-methyl- (1%) cyclo-1,3-hexadienes, and 1-methylcyclohexa-
1,4-diene (44%).14
Results
(14) Staley, S. W. Thermodynamics of Cyclic Dienes, Ph.D. Dissertation,
Yale University, New Haven, CT, 1964.
(15) Ekmanis, J. L. Diradicals in Thermal Rearrangements: A) cis- and
trans-Dispiro[5.0.5.2]tetradeca-1,8-dienes; B) Methylenecyclobutane. Ph.D.
Dissertation, Harvard University, Cambridge, MA, 1976; Diss. Abstr. Intern.
B 1976, 37, 224B (Order No. 76-14,401).
(16) There are many examples where thermodynamics for dimerization
is favorable, among them the spectacular protoanemonin-anemonin
system: Moriarty, R. M.; Romain, C. R.; Karle, I. L.; Karle, J. J. Am. Chem.
Soc. 1965, 87, 3251-3252.
(17) (a) Roth, W. R.; Adamczak, O.; Breuckmann, R.; Lennartz, H.-W.;
Boese, R. Chem. Ber. 1991, 124, 2499-2526. (b) Roth, W. R.; Staemmler,
V.; Neumann, M.; Schmuck, C. Liebigs Ann. 1995, 1061-1118.
(18) Neumann, M. Das MMEVBH-Kraftfeld. Ph.D. Dissertation (Pro-
fessor W. R. Roth, research director), Ruhr-Universita¨t Bochum, 1994; pp
111, 112, 133-142.
For the preparation of 1 in quantity, the method of Blomquist
et al.10 involving the Prins reaction of cyclohexene and
formaldehyde followed by flow pyrolysis of the resulting
3-acetoxymethylcyclohexene11 is preferred to the reaction of
the Wittig reagent from methyl bromide with cyclohex-2-enone,
or that from 3-bromocyclohexene with formaldehyde.12 Al-
(9) Gajewski, J. J. Hydrocarbon Thermal Isomerizations; Academic
Press: New York, 1981; pp 61-67 and further sections for references.
(10) Blomquist, A. T.; Verdol, J.; Adami, C. L.; Wolinski, J.; Phillips,
D. D. J. Am. Chem. Soc. 1957, 79, 4976-4980.
(11) (a) Blomquist, A. T.; Meinwald, Y. C. J. Am. Chem. Soc. 1959, 81,
667-672. (b) Williamson, K. L.; Keller, R. T.; Fonken, G. S.; Szmuszk-
ovicz, J.; Johnson, W. S. J. Org. Chem. 1962, 27, 1612-1615.

5534 J. Am. Chem. Soc., Vol. 123, No. 23, 2001
Doering et al.
could be accomplished satisfactorily by using the reagent of
Dess and Martin.24 In the ultimate decarbonmonoxylation by
means of chlorotris(triphenylphosphine)rhodium,25 loss of deu-
terium was avoided by the addition of a small amount of
deuterium oxide, while loss of stereochemistry was mitigated
by minimal exposure to the conditions of the reaction. The final
product consisted mainly (85%) of (Z)-3-methylenecyclohex-
ene-d and, to a lesser extent (15%), of the (E) isomer. Heating
an approximately 10% solution of this mixture in benzene-d6
(degassed and sealed under vacuum) at 110.5 °C for 117 h led
to the recovery only of unchanged material.26
In a final effort to effect thermal dimerization, high pressure
was applied in the expectation of shifting the equilibrium
thermodynamically toward the dimers (vide infra) and accelerat-
ing the rate of dimerization, thereby lowering the temperature
required for reaction and decreasing the magnitude of the
unfavorable T∆S term. At 7.5-8.0 kbar and 25-60 °C,
dimerization did indeed occur, but only to the extent of ∼1%.
Of four compounds observed by capillary GLC, but not isolated,
two had the same retention times as anti-2 and syn-2 (vide infra),
while the other two, of longer retention times, were not among
the minor photochemical products of irradiation of 1. Lacking
a peak at m/z ) 94 (1), and having their major peak at m/z )
173, they appeared not to be products of [2 + 2] cycloaddition.
Where thermal dimerization had failed, irradiation of 1 in
the presence of the triplet sensitizer, benzophenone,27 afforded
a mixture of anti-2 and syn-2, contaminated by ∼10% of
otherwise unidentified, isomeric impurities of m/z ) 188.
Quantitative analysis was effected by capillary GLC, while
preparative separation was accomplished with freshly prepared
columns of silver tetrafluoroborate of limited lifespan. Attempts
to exploit a possibly greater complexing power of the syn isomer
with silver tetrachloroaluminate in benzene achieved little.
Several of the possible structures for the dimers are eliminated
by finding that hydrogenation of anti-2 or syn-2 gives a tet-
rahydro derivative, shown by direct comparison not to be iden-
tical to dispiro[5.1.5.1]tetradecane.28,29 Definitive constitutional
Figure 3. Second-order mechanism for cis,trans isomerization of (E)-
1-d to (Z)-1-d is illustrated.
Scheme 1
Despite this failure, a tetramethylene diradical, possibly
formed transiently, might be expected to reveal itself through
internal rotations prior to reversion (Figure 3). The search for
such a second-order, thermally induced stereomutation was
undertaken in stereospecifically labeled 3-methylenecyclohex-
ene-d [(Z)- and (E)-1-d]. No synthetic procedure having been
reported for this type, the sequence shown in Scheme 1 was
developed. Although several products resulting from Michael
addition were formed instead of the desired compound B in a
Wittig-Horner reaction of cyclohexen-3-one and triethylphospho-
noacetate,19 a good yield of B resulted from the use of freshly
sublimed potassium tert-butoxide and scrupulously dried diox-
ane.20 Interestingly, when cursorily dried dioxane, or sodium
hydride in tetrahydrofuran, was employed, a high yield of
compound Y resulted!21 Although the favorable stereochemistry
introduced in the first step was not compromised in the
unexceptional second step, in the third, oxidation of the
1
assignments are based on H and 13C NMR, H-H and C-H
correlation spectra, and INADEQUATE measurements.30 The
presence of only seven 13C resonances excludes all but sym-
metrical structures. Configurational assignments are based on
the nuclear Overhauser effect (NOE). Examination of molecular
mechanical models (Figure 4) reveals close approaches of ∼2.5
Å in both isomers by double bond hydrons, H-1 and H-2, and
H-8 and H-9. Likewise, in both isomers, similarly close
approaches are seen for H-1 and H-8 and the respective syn
hydrons H-13 and H-14. Distinction between the two configura-
tions rests on an additional close approach between H-1 and
endo-H-12, and H-8 and endo-H-5 in the model of anti-2, which
is not seen in syn-2. This additional NOE is observed on
saturation of H-1 and H-8 (δ ) 5.79 ppm) in the isomer of
shorter gas chromatographic retention time, to which
22
(24) Dess, D. B.; Martin, J. C. J. Org. Chem. 1983, 48, 4155-4156.
(25) Baldwin, J. E.; Barden, T. C.; Pugh, R. L.; Widdison, W. C. J.
Org. Chem. 1987, 52, 3303-3307.
(26) Dimerization under high pressure was not examined owing to very
low yields. The stereochemical potential inherent in the photodimers has
not been pursued (Figures SI-1 and SI-2).
hydroxymethyl group by MnO2 led to a useless 1:1 mixture
of (Z)- and (E)-aldehyde. A possibly more felicitous procedure23
was not explored when it was found that the transformation
(19) Deschamps, B.; Seyden-Penne, J. Tetrahedron 1977, 33, 413-417.
(20) Bensel, N.; Hohn, J.; Marschall, H.; Weyerstahl, P. Chem. Ber. 1979,
112, 2256-2277.
(27) Hammond, G. S.; DeBoer, C. D. J. Am. Chem. Soc. 1964, 86, 899-
902.
(21) See also: Bergmann, E. D.; Solomonovici, A. Tetrahedron 1971,
27, 2675-2678.
(28) Donovan, P. F.; Liebman, S. A.; Koch, S. D. J. Org. Chem. 1963,
28, 2451-2454.
(22) Attenburrow, J.; Cameron, A. F. B.; Chapman, J. H.; Evans, R.
M.; Hems, B. A.; Jansen, A. B. A.; Walker, T. J. Chem. Soc. 1952, 1094-
1111.
(29) Walborsky, H. M.; Buchmann, E. R. J. Am. Chem. Soc. 1953, 75,
6339-6340.
(30) Krawczyk, B. Dimerisierungen von 1,3-Dienen bei hohem Druck;
das Volumenprofil von konzentrierten und mehrstufigen Cycloadditionen.
Ph.D. Dissertation, Universita¨t GH Essen, Germany, 1996.
(23) Xiao, X.-y.; Prestwich, G. D. Synth. Commun. 1990, 20, 3125-
3130.

Entropy-Dictated Product Ratios from Diradical Intermediates?
J. Am. Chem. Soc., Vol. 123, No. 23, 2001 5535
Table 2. Pressure Dependence of Specific Rate Constants and
Volumes of Activation for Stereomutation and Cycloreversion to 1
of anti-2 and syn-2 at 100.5 °C in Heptane
anti-2fsyn-2, syn-2fanti-2, anti-2f1,
syn-2f1,
kam
a
a
a
a
p, bar
kas
ksa
kam
2.68
2.68
1b
1.46
1.41
2.05
2.07
3.86
3.63
1c
200
400
600
800
1000
1500
2000
4300
1.23 ( 0.10
1.08 ( 0.11
1.09 ( 0.06
0.93 ( 0.04
0.82 ( 0.06
0.73 ( 0.06
0.59 ( 0.03
0.29 ( 0.06
2.00 ( 0.12
1.90 ( 0.13
1.74 ( 0.08
1.49 ( 0.04
1.35 ( 0.07
1.15 ( 0.08
0.95 ( 0.04
0.47 ( 0.08
2.45 ( 0.09 3.00 ( 0.11
2.51 ( 0.10 2.66 ( 0.13
2.13 ( 0.06 2.77 ( 0.08
1.95 ( 0.03 2.39 ( 0.04
1.82 ( 0.05 2.14 ( 0.07
1.50 ( 0.06 1.94 ( 0.07
1.28 ( 0.03 1.68 ( 0.04
0.30 ( 0.05 0.98 ( 0.07
Figure 4. Three-dimensional, molecular-mechanical-generated models
of lowest energy conformations of syn-2 (left) and anti-2 (right). Close
NOE-active approaches (∼2.5 Å; vinyl interactions omitted) of the
hydrons at C-1 and C-8 to syn hydrons at C-13 and C-14, respectively,
are shown by gray arrows in the cyclobutane ring of both isomers.
Additional close approaches (black arrows) of H-1 and H-8 to endo-
H-12 and endo-H-5, respectively, in anti-2, which are lacking in syn-
2, are also indicated.
∆Vq d
∆Vq
∆Vq
∆Vq
∆Vq
as
sa
am
sm
∆Vq e +13.9 ( 1.5 +14.7 ( 1.1 +11.9 ( 0.9 +11.2 ( 2.0
f
∆Vq
+15.4 ( 0.5 +14.2 ( 0.4 +13.0 ( 0.4 +14.5 ( 0.7
0
a Rate constants in units of 10-5 s-1 b Calculated at 100.5 °C from
.
the Arrhenius parameters in Table SI-2. c Values by linear extrapola-
tion to 1 bar from the data over the range, 200-2000 bar. d Volumes
Table 1. Specific Rate Constants and Activation Parameters
Calculated from the Data in Table S1 for the Stereochemical
Interconversions (kas and ksa) and Cycloreversions (kam and ksm) of
anti-2-Dispiro[5.0.5.2]tetradeca-1,8-dienes (Figure 1)
of activation in cm3 mol-1 e Derived from the data, 1-1500 bar, by
.
the linear correlation, ln(k)p ) a + bp, ∆Vq ) -bRT(R ) 83.14 cm3
bar K-1 mol-1). f Derived from the data, 1-4300 bar, by the nonlinear
correlation, ln(k)p ) a + bp + cp2, ∆Vq ) -bRT.
0
a
a
a
a
T, °C
kas
ksa
kam
ksm
Table 3. Specific Rate Constants at 43.6°C of Stereomutation, anti
f syn, and Fragmentation, anti f Monomer, in Systems 1/2, 3/4,
and 5/6
72.1
72.1b
81.1
92.3
98.5
110.9
118.2
0.49
0.44
1.72
5.90
11.7
47.2
109
0.27
0.70
0.70
0.83
2.27
9.71
26.0
96.4
208
1.57
0.93
7.00
18.3
16.9
130
anti f syn
anti f monomer
Eaa log A k43.6 (s-1
5.15
system Eaa log A k43.6 (s-1
)
)
kSt/kFr
29.7
73.0
188
1/2
31.1 13.36 0.80 × 10-8 33.5 15.07 0.91 × 10-8 0.9
21.7 13.75 6.00 × 10-2 24.8 14.47 0.23 × 10-2 26.2
277
3/4b [25.3] [13.56] 2.01 × 10-4 [27.9] [14.77] 0.36 × 10-4 5.7
5/6
anti-2fsyn-2 syn-2fanti-2
anti-2f1
syn-2f1
a In kcal mol-1 b Ea are calculated by the Arrhenius equation from
.
experimental values of k43.6 and a value for log A taken as the average
of the experimental values for systems 1/2 and 5/6.
Eab
31.1 ( 0.4
13.36 ( 0.26
30.3 ( 0.9
0.2 ( 1.7
38.3 ( 3.1
17.7 ( 1.8
37.6 ( 7.2
20.2 ( 8.6
33.5 ( 0.6
28.7 ( 2.7
log A
15.07 ( 0.37 12.4 ( 1.6
∆Hq c-e
∆Sq c-e
32.8 ( 1.3
+8.0 ( 2.2
27.9 ( 5.8
-4.4 ( 7.6
thesis reported by Reich and Wollowitz leads to a mixture con-
sisting of 3 (72%), 1-phenyl-3-methylcyclohexa-1,3-diene (21%),
and 1-methyl-3-phenylcyclohexa-1,3-diene (7%), which is sepa-
rated only with great difficulty.34 Alternatively, a Wittig reaction
of methylenetriphenylphosphorane with 3-phenylcyclohex-2-
enone yields 3 contaminated by less than 5% of the other
isomers.
Irradiation of 3 leads to the cyclobutane dimers, anti-4 and
syn-4, to which structures are assigned on the basis of their NMR
spectra (Figure 2). These dimers are unstable, undergoing
cycloreversion to 3 at room temperature, and are difficult to
study kinetically. As a consequence, specific rate constants for
their stereomutation and fragmentation have been obtained only
at a single temperature, 43.6 °C (Table 4, 1 bar). For purposes
of comparison, rate constants at 43.6 °C have been calculated
for system 5/633 and system 1/2 from their respective activation
parameters. In a reverse procedure, enthalpies of activation for
the system 3/4 have been estimated by assuming a value for
the Arrhenius log A term equal to the mean of the values found
experimentally for systems 1/2 and 5/6 (Table 3).
a In units of 10-6 s-1 b Starting from 100% syn-2; all others from
.
100% anti-2. c Ea and ∆Hq in kcal mol-1; ∆Sq in cal mol-1 K-1
d Calculated at 95.5 °C. e 90% confidence level.
.
the anti configuration is therefore assigned. The product of
hydrogenation can be confidently assigned the structure, dispiro-
[5.0.5.2]tetradecane.
The kinetics of the conversion of anti-2 to syn-2, and of
cycloreversion of anti-2 to 1, have been examined in the
temperature range 72.1-118.2 °C in mesitylene as solvent. The
main body of data, given in Table SI-1 (Supporting Information),
is obtained by following a published procedure.31 Specific rate
constants and derived activation parameters have been calculated
by a program, kindly supplied by W. R. Roth, on the basis of
the four-parameter equation of Figure 1, and are collected in
Table 1. The results of an alternative method of calculation,
given in Table SI-2, for the reactions of anti-2 are quite
comparable, but those from syn-2 are more sharply defined (see
Table 6).31 From the kinetics relating to syn-2 at 72.1 °C, a
ratio of rates of 0.65 emerges for stereochemical interconversion
of anti-2 to syn-2, corresponding to a free energy difference
favoring anti-2 by -0.3 kcal mol-1. This small value is
consistent with heats of formation calculated by MM2ERW:17a
anti-2, 27.46 kcal mol-1; syn-2, 27.56 kcal mol-1 (Benson group
equivalent values, 25.2 kcal mol-1).32
Volumes of activation derived from the pressure dependence
of rates have become an important variable in efforts to
(31) Doering, W. v. E.; Mastrocola, A. R. Tetrahedron 1981, 37, Suppl.
1, 329-344.
(32) Benson, S. W. Thermochemical Kinetics, 2nd ed.; Wiley: New York,
1976.
1-Phenyl-3-methylenecyclohexene (3) introduces a radical-
stabilizing group in conjugation with the butadiene system, like
the third double bond in the hexatriene system, 4a-methyl-2,3,4,-
4a,5,6-hexahydro-2(3H)-methylenenaphthalene (5/6).33 A syn-
(33) Doering, W. v. E.; Belfield, K. D.; He, J.-n. J. Am. Chem. Soc.
1993, 115, 5414-5421.
(34) Reich, H. J.; Wollowitz, S. J. Am. Chem. Soc. 1982, 104, 7051-
7059.

5536 J. Am. Chem. Soc., Vol. 123, No. 23, 2001
Doering et al.
Table 4. Pressure Dependence of Specific Rate Constants and
Derived Volumes of Activation for Stereomutation and
Cycloreversion to 3 of anti-4 and syn-4 at 43.6 °C in n-Heptane
anti-4fsyn-4, syn-4fanti-4, anti-4f3,
syn-4f3,
a
a
a
a
p, bar
kas
ksa
kam
ksm
1
20.14 ( 1.35
35.57 ( 2.16 3.55 ( 0.85 6.14 ( 1.57
21.12 ( 1.24 2.34 ( 0.46 3.65 ( 0.88
11.34 ( 0.52 1.27 ( 0.16 1.96 ( 0.34
1000 10.97 ( 0.75
3000
5.07 ( 0.28
∆Vq
∆Vq
∆Vq
∆Vq
as
sa
am
sm
∆Vq b +11.8 ( 1.5 +9.8 ( 1.4c +8.9 ( 0.7 +9.8 ( 1.4d
a Rate constants in units of 10-5 s-1 b Volumes of activation in
.
cm3 mol-1 derived from the data at 1, 1000, and 3000 bar by the
linear correlation, ln(k)p ) a + bp, ∆Vq ) -bRT(R ) 83.14 cm3 bar
K-1 mol-1). c Weighted mean, 10.8 cm3 mol-1 d Weighted mean, 9.2
.
cm3 mol-1
.
Table 5. Partial Molar Volumes V (cm3 mol-1), Temperature
Coefficients κ0 (K-1) (in n-Hexane), and van der Waals Volumes
VW (cm3 mol-1) of 1, anti-2, and syn-2
1
anti-2
syn-2a
V(20 °C)
V(100.5 °C)b
κ0
111.7
121.3
10.650
66.4
198.4
204.2
3.607
126.6
200.4
205.2
2.996
126.6
Figure 5. Volume profile for cycloreversion of anti-2 and syn-2 to
two 1 (kam and ksm, respectively), and stereomutation of anti-2 and syn-2
(kas and ksa, respectively) in cubic centimeters per mole (see Figure 1).
c
VW
a V(syn-2) determined on a mixture of syn-2 (90.2%) and anti-2
(9.8%). b Calculated by the equation, V(100.5 °C) ) V(20 °C) × (1 +
80.5κ0). c Calculated van der Waals volumes.56
1.8(27) × 10-5, respectively. The effect of increasing the
pressure to 7000 bar can be estimated from the molar volume
of reaction to be a factor of ∼2000 at 293 K. This analysis is
consistent with the appearance of only a small amount of dimer
under high pressure.
distinguish between one-step and two-step processes competing
within the same system.35 Although the ad libitum system,
butadiene/1,2-divinylcyclobutanes, serves as an excellent ex-
ample,36 establishment of the pressure dependence of cyclor-
eversion of trans-1,2-divinylcyclobutane to butadiene is subject
to a large experimental uncertainty.37 A more informative
example exists in the obligatorily cisoid cyclohexa-1,3-diene
system, despite the added complexity of an intramolecular
reaction of the “ene” type.38
Volumes of activation of systems 1/2 and 3/4 have been
determined from the pressure dependence of the rates of
stereomutation and cycloreversion by a previously described
procedure.39 Results are presented in Tables 2 (1/2) and 4 (3/
4). Furthermore, the temperature-dependent partial molar vol-
umes of 1, anti-2, and syn-2 (Table 5) have been determined
from measurements of density in the temperature range 20-70
°C (Table SI-3). From these data, volumes of activation of the
experimentally not directly observable [2 + 2] cyclodimerization
of 1 to anti-2 and syn-2, respectively, can be calculated. The
resulting complete volume profile for the system 1/2 is presented
in Figure 5.
The effect of pressure on the equilibrium constant for
dimerization can be estimated in the following way. From the
activation parameters for cycloreversion of anti-2 in Table SI-2
[log k1 ) 14.41 - 32400/(RT ln 10)], and two sets of parameters
available for the dimerization of butadiene as an approximation
to what might have been expected of the dimerization of 1 [log
k3 ) 6.95(8.14) - 27800/(RT ln 10)], estimates of K ) [anti-
2]/[1]2 at 293 and 373 K can be made: 9.6(150) × 10-5 and
The difference between the volumes of activation for inter-
conversion of anti-2 and syn-2 (∆∆Vq ) 0.8 cm3 mol-1) agrees
well with the corresponding volume of reaction (∆V ) 1.0 cm3
mol-1), calculated from the partial molar volumes of anti-2 and
syn-2 at 100.5 °C (temperature of reaction, Table 5). From the
volume profile of the [2 + 2] cycloreversion (Figure 5),
activation volumes of the experimentally not observable [2 +
2] cyclodimerization of 1 leading to anti- and syn-2, respectively,
can be calculated to be ∆Vq(anti-2f1) ) -26.5 cm3 mol-1
and ∆Vq(syn-2f1) ) -26.2 cm3 mol-1. These values are
comparable to those determined for the [2 + 2] cyclodimer-
izations of chloroprene (23 °C, ∆Vq ) -22 cm3 mol-1),40 1,3-
‡
cyclohexadiene (70.5 °C, ∆Vq ) -22 and -18 cm3 mol-1
)
for the formation of the syn- and anti-[2 + 2] cyclodimers,
respectively),38 and 1,3-butadiene (119.8 °C, ∆Vq ) -20.9 cm3
mol-1).36
Activation volumes for cycloreversion and stereomutation in
systems 1/2 and 3/4 (∆Vq ) 8.9-14.7 cm3 mol-1) are
significantly larger than those determined for stereomutation
and cycloreversion of trans-1,2-divinylcyclobutane (∆Vq ) +4
to +5 cm3 mol-1 37
) and the reaction volume of the hypothetical
isomerization of cyclobutane to butene-1 (∆V ) +6.6 cm3
mol-1).41 This difference can be explained by a volume-
decreasing, steric interaction of the substituents at the cyclobu-
tane ring of 2 and 4 that is released during ring-opening. The
decrease in volume caused by the steric interaction in cis-1,2-
disubstituted cyclobutane derivatives can be estimated from the
difference between the partial molar volumes of cis- and trans-
1,2-divinylcyclobutane to be ∆V ) 134.4 - 140.6 ) -6.2 cm3
mol-1. This value agrees with the cis correction term of -3
cm3 mol-1 used by Exner for the calculation of the molar
volumes of cis-1,2-disubstituted alicyclic compounds by volume
(35) Kla¨rner, F.-G.; Wurche, F. J. Prakt. Chem. 2000, 342, 609-636.
(36) Kla¨rner, F.-G.; Krawczyk, B.; Ruster, V.; Deiters, U. K. J. Am.
Chem. Soc. 1994, 116, 7646-7657 and references therein, especially ref
16.
(37) Doering, W. v. E.; Birladeanu, L.; Sarma, K.; Teles, J. H.; Kla¨rner,
F.-G.; Gehrke, J.-S. J. Am. Chem. Soc. 1994, 116, 4289-4297.
(38) Kla¨rner, F.-G.; Dogan, B. M. J.; Ermer, O.; Doering, W. v. E.;
Cohen, M. P. Angew. Chem., Int. Ed. Engl. 1986, 25, 108-110.
(39) Full details of the procedure for the high-pressure studies are given
by Krawczyk in an Appendix, pp 115-122.30
(40) Stewart, C. A., Jr. J. Am. Chem. Soc. 1972, 94, 635-637.
(41) Diedrich, M. K.; Kla¨rner, F.-G. J. Am. Chem. Soc. 1998, 120, 6212-
6218.

Entropy-Dictated Product Ratios from Diradical Intermediates?
J. Am. Chem. Soc., Vol. 123, No. 23, 2001 5537
interconversion of anti-2 and syn-2. That this oxygen-trapped
intermediate be one or the other, or both, of the two conforma-
tions of the intermediary diradical (Figures 1 and 6) seems
eminently reasonable.
Discussion
Radical-Stabilizing Perturbations. Predicting the effect of
perturbations on the rates of not-obviously-concerted thermal
rearrangements has a long history of success. Rate determined
by generation of diradical intermediates being the basic mecha-
nistic assumption, enthalpies of stabilization of carbon free
radicals evaluated independently are merely added to the
experimental enthalpy of activation of the unsubstituted para-
digm. In a particularly impressive example, Baldwin has found
excellent correlation between radical-stabilizing power in free
energy of a large number of groups and their effect on rates of
enantiomerization of trans-1,2-disubstituted cyclopropanes.45
The fact that enthalpy alone, and enthalpy and entropy together,
work equally well indicates that differences in the influence of
these perturbations on entropy are minor. In passing, we note
the contrast between not-obViously-concerted and concerted
thermal rearrangements. In the latter, prediction of enthalpies
of activation has been the frustrating challenge, while prediction
of stereochemical preferences among exit channels, thanks to
Woodward and Hoffmann, is a surety. In the former it has been
the reverse.
Figure 6. Kinetic scheme for oxygen-trapping in supercritical carbon
dioxide of a diradical intermediate in the stereomutation and fragmenta-
tion of system 1/2.
Table 6. Arrhenius Activation Parameters from Oxygen-Trapping
Experiments of Roth and Neumann in Supercritical Carbon Dioxide
Based on Model in Figure 6 for the Configurational Interconversion
and Cycloreversion (k3 and k4) of Dispiro[5.0.5.2]tetradeca-1,8-
dienes, anti-2 (k1, k-1) and syn-2 (k2, k-2
)
reactiona
Eab
log A
k1
k-1
k2
k-2
k3
k4
30.3 [30.6]c
2.7
29.1 [30.7]
2.7
32.4 [32.4]
31.1 [32.5]
13.26 [13.08]
11.55
12.89 [13.31]
11.64
12.89 [14.41]
12.89 [14.62]
a No confidence limits were reported. b In kcal mol-1 c The related
.
The present results from a small series of 1,2-disubstituted
cyclobutanes are no exception. System 1/2 is the first of three
members of a conjugated series, comprising a diene, a triene
(5/6),33 and a tetraene (7/8)46 (Figure 2), designed to evaluate
the validity of transferring to cyclobutanes the stabilization
enthalpies of polyenyl radicals that had been determined
independently by cis-trans geometrical isomerization about the
carbon-carbon double bond.47 An example from the literature
is 1,2-divinylcyclobutane. Its enthalpy of activation for cyclo-
reversion is predicted to be lower than that of cyclobutane (∆Hq
results of Ekmanis (Table SI-2) are repeated in brackets for convenience
in comparison.
increments.42 No such difference is to be expected between the
molar volumes of anti-2 and syn-2, both of which are 1,1,2,2-
tetrasubstituted cyclobutanes.
A powerful, ground-breaking method for trapping intermedi-
ate diradicals by oxygen in supercritical carbon dioxide has been
introduced by Wolfgang Roth.43 In many of its applications,
this method has led to the quantitatiVe establishment of the depth
of the enthalpic well into which intermediate diradicals fall. In
the development of the method, system 1/2 was one of two
selected to demonstrate its validity. These unpublished experi-
mental results are summarized here. Details of the construction
and operation of the apparatus are available in the Ph.D.
dissertation of Martin Neumann,18 as are tables of concentrations
of 1, anti-2, syn-2, and material lost to peroxide formation, in
experiments ranging in temperature from 89.3 to 146.7 °C, and
in partial pressures of oxygen from 0 to 83 bar. Although details
of the calculation are not given, the authors have developed a
program that, using all data simultaneously, generates a best fit
of Arrhenius activation parameters by minimizing deviations
between calculated and experimental concentrations.44 The pro-
gram is applied to the kinetic model in Figure 6, which includes
irreversible reaction of an hypothetical diradical intermediate
with oxygen on every collision. The absence of evidence for a
direct reaction of oxygen with 1 justifies omission of such a
step from kinetic models. Activation parameters at atmospheric
pressure in the absence of oxygen reported in Table 6 are in
satisfactory agreement with those of this work (Table SI-2).
They reveal an oxygen-sensitive intermediate stabilized by -2.7
kcal mol-1 relative to the transition region for the thermal
) 61.8 kcal mol-1 48
by twice the stabilization energy of an
)
allyl radical (-13.5 kcal mol-1). The resulting prediction of
34.8 kcal mol-1 agrees well with values of 34.0 and 35.7 kcal
mol-1 reported by Hammond and DeBoer.27 The experimental
value for the more highly substitured but related system 1/2 is
32.8 kcal mol-1. The additional small lowering is reasonably
ascribed to a rate-enhancing release of the steric repulsion
between the two cyclohexenyl rings. In system 3/4, the vinyl
groups in system 1/2 have been replaced by the more strongly
stabilizing cinnamyl group (stabilization energy, -15.7 kcal
mol-1).37 The predicted enthalpy of activation of 30.4 kcal mol-1
compares with the estimated experimental value of 27.0 kcal
mol-1 (vide supra). The discrepancy is again ascribed to the
steric factor. For system 5/6 of the 1,2-dibutadienyl type, the
stabilization energy advanced for the pentadienyl radical (-16.9
kcal mol-1) leads to an estimated enthalpy of activation of 28.0
kcal mol-1 versus the experimental value, 24.0 kcal mol-1 33
.
But for a reasonably constant steric correction of ∼3 ( 1 kcal
mol-1, the transferability of enthalpies of radical stabilization
obtained from thermal cis-trans geometrical isomerization to
(45) Baldwin, J. E. J. Chem. Soc., Chem. Commun. 1988, 31-32.
(46) Doering, W. v. E.; He, J.-n.; Shao, L.-m., submitted to J. Am. Chem.
Soc.
(47) Doering, W. v. E.; Kitagawa, T. J. Am. Chem. Soc. 1991, 113,
4288-4297. Doering, W. v. E.; Sarma, K. J. Am. Chem. Soc. 1992, 114,
6037-6043.
(48) Vreeland, R. W.; Swinehart, D. F. J. Am. Chem. Soc. 1963, 85,
3349-3353.
(42) Exner, O. Empirical Calculations of Molar Volumes in Organic
High-Pressure Chemistry; le Noble, W. J., Ed.; Elsevier: Amsterdam, 1988.
pp 19-49.
(43) Professor Roth’s unfortunate death (October 29, 1997) has prevented
him from taking part in this publication.
(44) Privately communicated by Professor W. R. Roth.

5538 J. Am. Chem. Soc., Vol. 123, No. 23, 2001
Doering et al.
these cyclobutanes is validated. Incidentally, the diradical
hypothesis at the base of the prediction also receives support
thereby.
negligible change in volume for the internal rotations and a
volume contraction for the recyclization of the diradical. The
observation that volumes of activation for fragmentation and
stereomutation are essentially identical is consistent with the
Doubleday conceptual scheme of control by entropy.
A contrasting example is found in the [2 + 2] cycloaddition
of 1,1-difluoroallene to (Z)-â-deuteriostyrene. A substantial
increase of stereoselectivity in favor of cis-2-deuterio-3-phenyl-
1-methylenecyclobutane derivatives is observed upon raising
the pressure from 1.8 to 13 kbar. In this case it can be concluded
that the activation volume of the ring-closure of the initially
formed diradical intermediates leading to the (Z)-methylenecy-
clobutane derivatives is indeed, as expected, more negative than
that of bond rotations, a prerequisite for the formation of the
corresponding (E)-methylenecyclobutane derivatives.53
Variation of temperature normally would allow distinction
between processes under control by entropy alone and those
under control by enthalpy and entropy, or enthalpy alone. Under
entropy control, the ratio of stereomutation to fragmentation
should be virtually independent of temperature. In both systems
1/2 and 5/6, enthalpies of activation for fragmentation, however,
appear to be 2-3 kcal mol-1 higher than those for stereomu-
tation. But we caution that the entropies of activation are in a
discouragingly compensating direction (∆ log A ≈ 1), and that
the differences in enthalpies of activation are of the same order
of magnitude as the experimental uncertainties. Some theoretical
support comes from the study of the butadiene/4-vinylcyclo-
hexene system by Li and Houk,54 who find that the gauche 1,2-
bis-allylethane diradical requires an activation energy of only
1.4 kcal mol-1 for ring closure (to 4-vinylcyclohexene), but 5.0
kcal mol-1 for fragmentation to two molecules of butadiene.
Nonetheless, to conclude that our observed temperature depen-
dence argues against exclusive control by entropy is problematic.
We foresee much experimentally painstaking kinetic work
before the Doubleday question finds its clarification.
The findings that volumes of activation of the syn-anti
interconversion of 2 (and 4) and the [2 + 2] cycloreversion of
syn- and anti-2 (and syn- and anti-4) are all positive [system
1/2, +14.4 ( 1.3 and +11.7 ( 1.3 cm3 mol-1; system 3/4,
+10.8 ( 1.5 and +9.2 ( 1.0 cm3 mol-1, respectively (mean of
values in Tables 2 and 4)], and that each set of data is almost
of equal size, provide good evidence that the cyclobutane ring-
opening of 2 and 4 leading to the respective diradicals is the
rate-determining step of each reaction.
Product Ratios from Diradical Intermediates. The second
part of the discussion addresses long-standing difficulties
attending attempts to identify factors that may be generally
useful for predicting distribution among competing products in
not-obviously-concerted thermal rearrangements of small cyclic
hydrocarbons and their derivatives. The extraordinarily thorough
theoretical investigation of the archetypes, cyclopropane and,
of more direct relevance here, cyclobutane, recently published
by Doubleday et al.,1 sharply points to entropy as the product-
controlling factor to which our attention should be directed.
Their conclusion, largely supported by more recent calculational
efforts,4,49 emphasizes two distinct phases in the thermal
behavior of cyclobutane. The first is the conventional, rate-
determining entry into a “diradical” transition region character-
ized as a relatively “flat”, multidimensional, free energy
“surface” (“generalized common biradical”, “continuous diradi-
cal as transition state”,50 “twixtyl” 51sa region we dub “caldera”
for want of a current, short-hand appellation). The second is
the product-determining phase in which internal rotations
interrelate the various conformations of the tetramethylene
diradical and are followed either by reclosures leading to
stereomutation or by fragmentations to ethylene (cis and trans
from appropriately isotopically labeled cyclobutane). These
goings-on in the caldera are all under the control of entropy
alone, none requiring further enthalpy of activation in the
Arrhenius sense.52
Is unsubstituted cyclobutane a valid paradigm for substituted
cyclobutanes, or is it unique? If the answer is “Yes”, it would
be better to focus on factors controlling entropies of activation
for exit from the caldera; if “No”, both enthalpy and entropy
remain the focus. In these terms, we examine the response of
the much more highly substituted cyclobutanes of this paper to
temperature and pressure.
Were pressure to influence not only entry into the caldera,
but exit from it, the volume of activation for fragmentation in
systems such as 1/2 and 3/4 might be expected to be significantly
more positiVe than that for stereomutation. Fragmentation should
require a further increase in volume as the transition region
begins to combine the elements of the diradical intermediate
with the larger molar volume of the two monomers. Its
magnitude, to be sure, might depend on how close the transition
region was to the diradicalssmall but positive, if the path were
downhill with no barrier; larger, the more so, the closer the
transition region to the two dissociated monomers. Stereomu-
tation, by contrast, should require only internal rotations and
reclosure, “two processes” expected to be associated with a
Experimental Section
General. Infrared spectra (IR) were recorded on a Perkin-Elmer
model 337 spectrophotometer and are reported in ν (cm-1). Ultraviolet
spectra (UV) were recorded on a Perkin-Elmer model 202 or a Unicam
1
model SP spectrophotometer [λmax in nm (log ꢀ)]. H NMR spectra
were measured in CDCl3 (δ, referenced to TMS, 0.0 ppm) or C6D6
(referenced to C6D5H, 7.15 ppm) on Bruker AM-200, AM-300, AM-
400, and AM-500 instruments as noted. Coupling constants, J, are given
in hertz. 13C NMR spectra were measured in CDCl3 on a Bruker AM-
300 (75.5 MHz) spectrometer. Mass spectra were recorded on an AEI
model MS 9 double-focusing instrument, and on a JEOL JMS-AX505H
mass spectrometer coupled to a Hewlett-Packard 5890 Series II gas
chromatograph (GC/MS), and are reported as m/z (% relative to
strongest peak, 100). Refractive indices were obtained with a Bausch
& Lomb Abbe´ refractometer. Melting points were taken in open
capillaries with a Meltemp apparatus and are uncorrected. Concentra-
tions are given as volume/volume (v/v) for liquids and weight/volume
(g/mL) for solids. Distillations were performed on a Piros-Glover
spinning band MicroStill (H. S. Martin & Son, Evanston, IL). Reactions
were monitored by gas chromatography on a Perkin-Elmer 990
instrument equipped with a DISC integrator. Capillary gas liquid
chromatography (GLC) was conducted on a Hewlett-Packard GC model
5890, equipped with an integrator, model 3393A, and a flame ionization
detector, using a DB-1 column (J&W Scientific, 1.5 µm film thickness,
30 m × 0.523 mm; He, 3.7 mL/min). Preparative GLC was performed
on an Aerograph Fractometer model A-90, and an Aerograph Autoprep
model A-700, using the following columns. Stainless steel: (I) 4 m,
10% nitrile silicone (XF 1150); (II) 300 ft × 0.01 in. i.d., open tubular
(49) De Feyter, S.; Diau, E. W. G.; Scala, A. A.; Zewail, A. H. Chem.
Phys. Lett. 1999, 303, 249-260.
(50) Doering, W. v. E.; Sachdev, K. J. Am. Chem. Soc. 1974, 96, 1168-
1187.
(51) Hoffmann, R.; Swaminathan, S.; Odell, B. G.; Gleiter, R. J. Am.
Chem. Soc. 1970, 92, 7091-7098.
(52) Menzinger, M.; Wolfgang, R. Angew. Chem., Int. Ed. Engl. 1969,
8, 438-444.
(53) Dolbier, W. R., Jr.; Weaver, S. L. J. Org. Chem. 1990, 55, 711-
715.
(54) Li, Y.; Houk, K. N. J. Am. Chem. Soc. 1993, 115, 7478-7485.

Entropy-Dictated Product Ratios from Diradical Intermediates?
J. Am. Chem. Soc., Vol. 123, No. 23, 2001 5539
(Golay), methyl silicone (OV 101); (III) 50 ft × 0.02 in. i.d., support-
coated, open tubular (SCOT), cyanopropylmethyl phenylmethyl silicon
(OV 225). Aluminum (1/4 in. o.d.; 60/80 mesh Chromosorb P): (IV) 1
m, 8% AgBF4 and 10% Carbowax 600; (V) 4 m, 10% Dow Corning
710 silicone oil. HPLC columns: (VI) Nucleosil 100-5 NO2 Vario Prep
ET 250/10 column (Machery-Nagel); (VII) Nucleosil 100 NO2, 3 m ×
1 cm i.d. (Fa. Knauer).
(elution successively with 25:1, 10:1, and 3:1 hexane/ethyl acetate)
afforded 5.74 g (76%) of a pale yellow liquid, analysis by capillary
GLC showing a ratio (Z)/(E) ) 8/1. Data for (Z)-C: 1H NMR (300
MHz, CDCl3) δ 6.40 (dd, 1H, J ) 10.0, 0.7, H-2), 5.89 (dtd, 1H, J )
10.1, 4.1, 1.6, H-1), 5.30 (s, 1H, dCHCD2H), 4.24 (d, 2H, J ) 7.2,
CH2OH), 2.99 (s, 1H, OH), 2.30 (td, 2H, J ) 6.2, 1.5, H-4), 2.14 (m,
2H, H-6), 1.70 (p, 2H, J ) 6.2, H-5). Data for (E)-C: 1H NMR (300
MHz, CDCl3) δ 6.05 (dt, 1H, J ) 9.9, 1.9, H-2), 5.80 (m, 1H, H-1),
5.39 (s, 1H, dCHCD2OH), 4.28 (d, 2H, J ) 7.2, CH2OH), 2.99 (s,
1H, OH), 2.35 (m, 2H, H-4), 2.14 (m, 2H, H-6), 1.70 (p, 2H, J ) 6.2,
H-5).
3-Methylenecyclohexene (1). 3-Acetoxymethylcyclohexene (A) was
prepared by a slight modification of the procedure of Blomquist et al.10
Freshly distilled cyclohexene (1250 g, 15.22 mol) was heated at 185
°C in an autoclave with paraformaldehyde (375 g, 12.5 mol), glacial
acetic acid (450 g, 7.5 mol), and acetic anhydride (375 g, 3.7 mol)
under vigorous stirring, yielding a dark-brown residue after workup.
Distillation in vacuo (water aspirator) yielded four fractions in amounts
of 2.3, 203.5, 65.6, and 7.2 g, bp 25-79, 78-83, 99-102, 142 °C,
and nD25 1.4532, 1.4578, 1.4593, and 1.4676, respectively (lit.10 bp 104-
107 °C/35 mmHg; nD25 1.4564-1.4575). Analysis by GLC (column I,
143 °C, He 15 lb) showed the four fractions to contain 60%, 92%,
>99%, and 27%, respectively, of A (tr ) 11 min): IR (CCl4) 3005,
2923, 2872, 2846, 2821, 1742 (vs), 1462, 1444, 1430, 1380, 1362, 1281,
1263, 1230, 1083, 1049, 1032, 976, 891, 860, 719, 699, 680; 1H NMR
(200 MHz, CDCl3) δ 5.80 (d, 1H, J ) 11), 5.56 (d, 1H, J ) 11), 3.93
(d, 2H, J ) 7), 2.40 (m, 1H), 2.04 (s, 3H), 2.0-1.2 (m, 6H).
A sample of A (156.3 g; fractions 2 and 3 above; 94.5% purity)
was pyrolyzed at 570-580 °C in a quartz tube packed with quartz
chips.11 Distillation of the crude product yielded 42.3 g of 1 (94% of
purity), along with 39 g of recovered starting material. Redistillation
yielded 24.5 g of 3-methylenecyclohexene (18% of theoretical yield,
99.6% purity): IR (CCl4) 3075, 3024, 2971, 2936, 2930, 2891, 2876,
2864, 2830, 1771, 1638, 2599, 1457, 1437, 1418, 1384, 1342, 1246,
1213, 1138, 1137, 1056, 1049, 990, 978, 962, 908, 884 (exocyclic
(Z)- and (E)-2-(1-Cyclohex-2-enylidene)acetaldehyde-1-d (D). To
26.7 g (63 mmol) of periodinane24 in 700 mL of CH2Cl2 was added a
solution of 4.05 g (32.1 mmol) of C at 25 °C. After being stirred for
55 min and cooled to 0 °C, the mixture was treated with 300 mL of
0.01% aqueous KOH. The CH2Cl2 layer was separated, and the aqueous
layer was extracted with ether (3×). The combined organic layers were
washed with 0.01% aqueous KOH (3×), water, and saturated aqueous
NaCl and dried over MgSO4. Concentration in vacuo gave a yellow
liquid with a cinnamon-like odor, purification of which by column
chromatography (elution with 25:1 hexane/ethyl acetate) afforded 2.11
g (53.4%) of D. Data for (Z)-D: 1H NMR (300 MHz, CDCl3) δ 7.12
(d, 1H, J ) 10.1, H-2), 6.37 (dtd, 1H, J ) 10.1, 4.2, 1.5, H-1), 5.69 (s,
1H, dCHCDO), 2.50 (td, 2H, J ) 6.4, 1.3, H-4), 2.29 (m, 2H, H-6),
1.83 (p, 2H, J ) 6.3, H-5). Data for (E)-D: 1H NMR (300 MHz, CDCl3)
δ 6.23 (dt, H, J ) 9.8, 1.8, H-1), 5.76 (s, 1H, dCHCDO), 5.36 (m,
1H, H-2), 2.90 (td, 2H, J ) 6.4, 1.8, H-4), 2.29 (m, 2H, H-6), 2.04 (m,
2H, H-5).
Chlorotris(triphenylphosphine)rhodium (925 mg, 1.0 mmol, Strem),
2 g of C6D6, and 240 mg of D2O (12.0 mmol)25 were heated to reflux.
A solution of 135 mg of D (1.1 mmol) in 1 g of C6D6 was then added
via syringe to the stirred, brick red suspension. After being stirred at
reflux for 15 min and cooled, the reaction mixture was treated with
1.5 mL of absolute ethanol and 2 mL of pentane. Passage through a
short column of silica gel (elution with pentane) gave a dark red
solution, which was washed with water (2×) and saturated aqueous
NaCl (2×) and dried over K2CO3. Fractional distillation in vacuo gave
a colorless solution containing C6D6 and mainly (Z)-1-d (identified by
capillary GLC, GC/MS, and 1H and 13C NMR). GC/MS analysis
(electron impact, 70 eV) confirmed the predominant formation of
3-(methylene-d)cyclohexene (1-d): m/z 95 (M+, 46), 96 (6), 94 (13),
1
methylene), 861, 706, 666, 562; H NMR (400 MHz, C6D6) δ 6.16
(dt, 1H, J ) 10.0, 2.0, H-2), 5.68 (dt, 1H, J ) 10.0, 4.1, H-1), 4.80 (s,
1H, E- dCH), 4.74 (s, 1H, Z- dCH), 2.22 (bt, 2H, J ) 6.3, H-4), 1.86
(m, 2H, H-6), 1.52 (quint, 2 H, J ) 6.1, H-5); UV (6.92 mg/L, EtOH),
232 (4.272); GC/MS (70 eV) m/z 94 (M+, 41), 95 (4), 93 (14), 92
(2.4), 91 (19.8), 79 (100), 77 (36).
3-[(Z)-Methylene]cyclohex-1-ene-d (1-(Z)-d). Ethyl (Z)- and (E)-
2-(3-cyclohex-1-enylidene)acetate [(Z)-B and (E)-B of Scheme 1] were
prepared according to the method of Bensel et al.20 To a stirred solution
of freshly sublimed potassium tert-butoxide (28.1 g, 250 mmol) in 600
mL of 1,4-dioxane (throughout, freshly distilled from lithium aluminum
hydride (LiAlH4) and degassed) was added a solution of 65.5 g of ethyl
diethylphosphonoacetate (Fluka) in 220 mL of dioxane via cannula
under argon with stirring over 2.7 h at room temperature. After an
additional 40 min of stirring, 20.0 g of 2-cyclohexenone (Aldrich) in
250 mL of dioxane was added via cannula over a 45-min period. After
having been stirred for 6.5 h at room temperature and 6 h under reflux,
the dark orange reaction mixture was concentrated in vacuo, treated
with crushed ice and water, and extracted with ether (3×). The
combined ethereal extracts were washed with saturated NaCl (3×), dried
over MgSO4, and concentrated in vacuo to a yellow residue, which
yielded 9.16 g (27%) of a clear, colorless liquid on distillation: bp
50-55 °C (0.5 mmHg) [lit.20 bp 95 °C (8 mmHg)]. Analysis by
capillary GLC (column DB-1) revealed a ratio (Z)/(E) ) 7.9/1.0.
Purification by flash column chromatography (silica gel; 25:1 hexane/
ethyl acetate) provided enriched material, (Z)/(E) ) (12-17)/1.0. Data
for (Z)-B: 1H NMR (500 MHz, CDCl3) δ 7.40 (dad, 1H, J ) 10.4,
2.2, 0.9, H-2), 6.13 (dad, 1H, J ) 10.3, 4.2, 1.6, H-1), 5.38 (s, 1H,
CHCO2Et), 4.06 (q, 2H, J ) 7.1, OCH2), 2.30 (td, 2H, J ) 6.4, 1.5,
H-4), 2.13 (m, 2H, H-6), 1.69 (quintet, 2H, J ) 5.9, H-5), 1.18 (t, 3H,
J ) 7.2, CH3); 13C NMR (300 MHz, CDCl3, proton decoupled) δ 165.7
(CdO), 151.7 (C-3), 137.4 (C-1), 124.9 (C-2), 112.7 (dCHCO2Et),
58.9 (OCH2), 32.1 (C-4), 25.7 (C-6), 22.3 (C-5), 13.9 (CH3). Data for
(E)-B: 1H NMR (500 MHz, CDCl3) δ 6.02 (brdt, 1H, J ) 8.5, H-1),
5.57 (brm, 1H, H-2), 5.47 (s, 1H, CHCO2Et), 4.06 (q, 2H, J ) 7.1,
OCH2), 2.98 (brm, 2H, H-4), 2.88 (brm, 2H, H-6), 1.69 (quintet, 2H,
J ) 5.9, H-5), 1.18 (t, 3H, J ) 7.2, CH3).
1
93 (6), 92 (22), 80 (100), 79 (68), 78 (43). H NMR indicated a ratio
1-(Z)-d/1-(E)-d of 5.5/1 (determined by cutting and weighing printouts
of the dCHD absorbances at 4.74 [(Z) dCHD] and 4.80 [(E) dCHD]:
1H NMR (400 MHz, C6D6) δ 6.18 (dt, 1H, J ) 9.9, 2.1, H-2), 5.68
(dtd, 1H, J ) 10.0, 4.1, 1.6, H-1), 4.74 (s, 1H, dCHD), 2.22 (td, 2H,
J ) 6.3, 1.7, H-4), 1.85 (m, 2H, H-6), 1.52 (p, 2H, J ) 6.2, H-5).
Thermal Dimerization of 3-Methylenecyclohexene (1). Sealed
tubes containing 51 mg of diphenylamine and 291 mg of 1 were heated
at temperatures ranging between 116 and 150 °C for 4 h. Analysis by
GLC on column II (50 °C, 1.8 mL He/min) showed no dimer and almost
complete recovery of 1.
When a solution of 48 mg of 1 in 0.5 mL of toluene-d8 (dried over
LiAlH4) was heated at 8 kbar for 48 h at 100 °C, polymer was formed
in large amount but could be removed by passing through a short silica
gel column prior to analysis by capillary GLC (Carbowax 20M-K, 90
°C). No evidence of dimerization could be detected. Similarly, a solution
of 0.5 g of 1 in 10 mL of toluene, when maintained at 8.5 kbar for 65
h at ca. 10 °C, showed no significant change. A more concentrated
solution of 1 [260 mg in 0.6 mL of toluene containing a few crystals
of bis(3-tert-butyl-4-hydroxy-5-methylphenyl)sulfide (BHMPS)] main-
tained at 60 °C for 48 h revealed four products in total yield <1% and
relative amounts 19.6, 20.2, 47.5, and 12.7%. anti-2 and syn-2 were
identified by GLC: tr ) 15.63 and 16.93 min, GC-MS m/z (relative
intensity) 188 (3), 160 (3), 150 (3), 117 (4), 94 (45), 79 (100), 39 (29).
Two unidentified products had the following properties: tR ) 19.15
min, GC-MS m/z (relative intensity) 188 (100), 173 (98), 160 (39),
145 (23), 131 (93), 117 (48), 91 (63), 79 (56); and tR ) 21.30 min,
GC-MS m/z (relative intensity) 188 (87), 173 (80), 160 (35), 145 (77),
131 (82), 117 (41), 95 (100), 79 (61). An identical solution maintained
(Z)- and (E)-2-(3-cyclohex-1-enylidene)ethanol-1,1-d2 (C) was
prepared from 10.0 g of B and 1.56 g of LiAlD4 (Aldrich, 98% D) in
ether (0 °C to 25 °C, 19 h). Purification by column chromatography

5540 J. Am. Chem. Soc., Vol. 123, No. 23, 2001
Doering et al.
at 25 °C and 7.5 kbar for 192 h yielded only anti-2 and syn-2 in equal
amounts in a yield <1%.
Oxidation of the alcohol was effected with chromic acid to give crude
ketone (96.3%), recrystallization of which from acetonitrile (60 mL)
afforded colorless needles of dispiro[5.1.5.1]tetradecane-7-one: mp
82.5-84.5 °C (lit.28 mp 85-87 °C); IR (CCl4) 2927, 2849, 1764 (vs),
1448, 1342, 1303, 1286, 1273, 1252, 1226, 1213, 1157, 1150, 1128,
1120, 1084, 1029, 991, 982, 962, 928, 863, 842. The final product of
the sequence was recrystallized from acetonitrile and sublimed to yield
pure dispiro[5.1.5.1]tetradecane: mp 55.5-56.8 °C (lit.28 mp 56.5-
58.0 °C). Analysis by GLC on column III (190 °C, He 35 lb, flow rate
1.8 mL/min) showed a single peak, tr ) 16.6 min, to be compared
with 19.4 min for dispiro[5.0.5.2]tetradecane under identical conditions.
anti- and syn-Dispiro[5.0.5.2]tetradeca-1,8-dienes (anti-2 and syn-
2). A solution of 5.61 g (6 mL, 59.7 mmol) of 1 (99.8% of purity) and
0.44 g (2.4 mmol) of benzophenone was partitioned among eight
ampules (7 mm o.d. × 150 mm). The ampules were degassed, sealed
under vacuum, and irradiated at 25-35 °C for 12 days in a “merry-
go-round” apparatus with a 450-W, high-pressure Hanovia lamp
equipped with a 2800-Å cutoff filter. The mass spectra of the combined
samples recorded at 14 and 70 eV showed main peaks at m/z 188
(parent), 160, and 94. Evaporative distillation at 60 °C and 0.01 mmHg
yielded 2.8 mL of clear, colorless liquid and a very thick, light yellow
residue that was not further investigated. Analysis by GLC of a 10%
benzene solution of the distillate on column III (80 °C, injector 90 °C,
detector 97 °C, He 4 lb, flow rate 5.5 mL/min) showed two peaks of
tr ) 70.7 and 78.3 min in a ratio of 58.8 to 41.2, respectively. The
dimers were separated by preparative GLC on silver tetrafluoroborate
column IV (85 °C, injector 140 °C, detector 165 °C, He 20 lb, flow
rate 280 mL/min); tr(anti-2) ) 18.5 min; tr(syn-2) ) 38.0 min. The
column was operated above 65 °C, the highest temperature generally
recommended for silver nitrate columns, but necessary to keep retention
times within reasonable limits. At 85 °C, the useful lifetime of column
IV was 8-12 h. The separated anti-2 (340 µL) contained <1% syn-2,
while syn-2 (315 µL) contained 3.4% of anti-2. Additional purification
(rechromatography for syn-2, and molecular distillation for anti-2)
afforded samples of purity 98.1% and 98.7%, respectively. Data for
syn-2: 1H NMR (300 MHz, CDCl3) δ 5.88 (dt, 2H, 3Jcis ) 10.1, 4JH1-H3
Pressure Dependence of Thermal Reactions of Dispiro[5.0.5.2]-
tetradeca-1,8-diene (2). For the kinetic studies, portions of standard
solutions of anti-2 and syn-2, each in >96% of purity, with n-C15H32
and n-C10H22 as internal standards and catalytic amounts of BHMPS
(to prevent radical-induced polymerization) in anhydrous n-hexane were
thermolyzed at 100.5 °C at the pressures given in Table 2. For each
pressure, 7-11 samples of each standard solution were taken and
analyzed by GLC [fused silicon oil BP225, 30 m; temperature program,
50 °C for 4 min, then heating at a rate of 10 °C/min to 100 °C; carrier
gas, He; retention times in min, 1.2 (n-hexane), 2.1 (1), 2.9 (n-C10H22),
13.2 (n-C15H32), 16.7 (anti-2), and 19.7 (syn-2)]. At each pressure, the
specific rate constants (Table 2) were derived from the two sets of
product ratios, obtained from thermolysis of anti-2 and syn-2, by
numerical integration by the use of the Runge-Kutta procedure of
fourth order and optimization by the Marquardt method.55
Measurements of Partial Molar Volumes of 1, anti-2, and syn-2.
For each substance, densities of solutions at six different concentrations
were determined (Table SI-2). Measurements were performed in the
temperature range 20-70 °C, in 5° steps. For each temperature, the
value of ΦV (partial molar volume of a substance at a given
concentration) was calculated according to the equation,
3
3
) 2.1, H-1,8), 5.61 (dt, 2H, Jcis ) 10.1, JH2-H3 ) 3.6, H-2,9), 1.91
(m, 4H, H-3,10), 1.73 (m, 6H, H-13,14, H-5,12exo), 1.51 (m, 6H, H-4,-
11, H-5,12endo); 13C NMR (75 MHz, CDCl3) δ 134.3 (C-1,8), 126.0
(C-2,9), 44.7 (C-6,7), 30.5 (1JHC ) 126, C-5,12), 29.9 (1JHC ) 135,
C-13,14), 25.5 (1JHC ) 126, C-3,10), 19.9 (1JHC ) 126, C-4,11); IR
(CCl4) 3014, 2955, 2939, 2923, 2909, 2855, 2828, 2649, 1694, 1638,
1448, 1438, 1430, 1392, 1342, 1290, 1267, 1256, 1220, 1192, 1173,
1159, 1137, 1111, 1096, 1060, 1055, 965, 955, 937, 922, 900, 887,
858, 844, 724, 708, 700, 687, 679, 620. Data for anti-2: 1H NMR
(300 MHz, CDCl3) δ 5.79 (dt, 2H, 3Jcis ) 10.1, 4JH1-H3 ) 2.0, H-1,8),
5.64 (dt, 2H, 3Jcis ) 10.1, 3JH2-H3 ) 3.6, H-2,9), 1.88 (m, 4H, H-3,10),
1.73 (m, 6H, H-13,14, H-5,12exo), 1.51 (m, 6H, H-4,11, H-5,12endo);
13C NMR (75 MHz, CDCl3) δ 133.2 (C-1,8), 126.8 (C-2,9), 44.6 (C-
6,7), 32.1 (1JHC ) 124, C-5,12), 30.5 (1JHC ) 134, C-13,14), 25.3 (1JHC
) 125, C-3,10), 19.9 (1JHC ) 125, C-4,11); IR 3021, 2961, 2937, 2861,
2836, 2655, 1702, 1641, 1455, 1446, 1434, 1397, 1346, 1290, 1259,
1234, 1221, 1172, 1162, 1138, 1055, 1037, 1000, 961, 943, 933, 928,
918, 886, 859, 842, 724, 708, 700, 685, 621.
ΦV ) M/d0 - (1000/c)[(d - d0)/d0]
where c (mol L-1) is the concentration of the solution, M (g mol-1
)
the molar mass of the solute, d (g cm-3) the density of the solution,
and d0 (g cm-3) the density of the pure solvent.56
The partial molar volume, V, was calculated by linear extrapolation
of ΦV to a concentration c ) 0. The κ0 values in Table 6 were derived
from the temperature dependence of the partial molar volume by use
of the equation, VT ) V0[1 + κ0(T - T0)], where T0 ) 20 °C.57 van der
Waals volumes VW were calculated by the computer program MOL-
VOL.58
Dispiro[5.0.5.2]tetradecane. A solution of 91.7 mg of anti-2 and
syn-2 (58.8:41.2) in 3 mL of acetic acid was hydrogenated over PtO2
(10.1 mg in 12 mL of acetic acid) at 23 °C for 30 min, by which time
absorption was complete. The reaction mixture was diluted with water
(30 mL) and extracted with 25 mL of ether (2×). The combined ether
extracts from three runs were washed with 50 mL of 10% Na2CO3
(4×) and dried over MgSO4. Removal of the solvent and molecular
distillation of the orange residue gave 170 mg (60.4%) of product.
Analysis by GLC on column V (167 °C, He 20 lb) revealed three
compounds in the ratio 1.4% (tr ) 19.5 min), 5.9% (tR ) 22.5 min),
and 92.7% (tr ) 26 min). Preparative GLC on the same column gave
dispiro[5.0.5.2]tetradecane (98% of purity): IR (CCl4) 2914, 2837,
1446, 1289, 1277, 1220, 1186, 1165, 1148, 954, 927, 906, 884, 845,
734; 1H NMR (100 MHz, CCl4) δ 1.8-0.8 (broad multiplet containing
a sharp singlet at δ 1.59); MS m/z (70 eV) 192 [M+], 164, and 96,
inter alia.
1-Phenyl-3-methylenecyclohexene (3). The procedure of Reich and
Wollowitz34 yielded a mixture of 3 (72%), 1-phenyl-3-methylcyclohexa-
1,3-diene (21%), and 1-methyl-3-phenylcyclohexa-1,3-diene (7%),
which could be separated only very tediously by high-performance
liquid chromatography (HPLC, column VI) owing to the closeness of
1
retention times. H NMR spectra on the mixture (200 MHz, CDCl3):
1-phenyl-3-methylcyclohexa-1,3-diene, δ 6.22 (s, 1H, H-2), 5.6 (m,
1H, H-6), 2.43 (s, 3H, CH3), 2.6-2.1 (m, 4H, H-4,5); 1-methyl-3-
phenylcyclohexa-1,3-diene, δ 6.08 (s, 1H, H-2), 5.93 (t, 1H, H-4), 2.43
(s, 3H, CH3), 2.1-2.6 (m, 4H, H-5,6).
The procedure of Woods and Tucker was a substantial improve-
(55) Marquardt, D. W. J. Soc. Ind. Appl. Math. 1963, 11, 431-441. We
thank Dr. R. Fink for a copy of the program KINETIK, which permits
optimization by the Marquardt procedure of kinetic schemes with up to
seven components.
(56) Le Noble, W. J.; Asano, T. J. Am. Chem. Soc. 1975, 97, 1178-
1181.
(57) El’yanov, B. S.; Gonikberg, E. J. Chem. Soc., Faraday Trans. 1
1979, 75, 172-191. El’yanov, B. S.; Vasylviskaya, E. M. ReV. Phys. Chem.
Jpn. 1980, 50, 169-183.
(58) Artschwager-Perl, U. Cycloadditionen unter hohem Druck. Ph.D.
Dissertation, Ruhr-Universita¨t Bochum, 1989. This program uses the
Cartesian coordinates of a molecular structure resulting from a force field
or quantum mechanical calculation and can be obtained on request. van
der Waals volumes of ground states can also be calculated from tables of
group contributions to the van der Waals volumes published in the
following: Bondi, A. J. Chem. Phys. 1964, 68, 441-451.
Dispiro[5.1.5.1]tetradecane. This compound was prepared by
literature procedures with one modification.28,29 Reduction of 14,14-
di(ethylmercapto)dispiro[5.1.5.1]tetradecan-7-one with active Raney
nickel (920 g, W. R. Grace & Co.) proceeded to dispiro[5.1.5.1]-
tetradecan-7-ol, which then had to be oxidized to the corresponding
ketone. The alcohol was obtained as colorless crystals on recrystalli-
zation from acetonitrile at -10 °C: mp 75-78 °C; IR (CCl4) 3611,
3477, 2916, 2845, 1447, 1436, 1396, 1281, 1254, 1161, 1148, 1138,
1
1111, 1080, 1055, 1030, 960, 938, 842; H NMR (100 MHz, CCl4) δ
3.42 (d, 1H, J ) 7), 1.38 (m, 22H, sharp shoulders at 1.26 and 1.07).

Entropy-Dictated Product Ratios from Diradical Intermediates?
J. Am. Chem. Soc., Vol. 123, No. 23, 2001 5541
ment.59 3-Phenylcyclohex-2-enone, the ultimate intermediate, was
obtained in 55% of the theoretical yield after crystallization from
NMR (75 MHz, CDCl3) δ 142.4 (C-2,9), 135.5 (Cphenyl), 131.9
(C-1,8), 128.2, 126.6, 125.1 (Cphenyl), 44.2 (C-6,7), 30.0, 29.8, 27.6
(C-13,14, C-3,10, C-5,12), 20.1 (C-4,11).
1
cyclohexane: mp 64.5-66 °C; H NMR (300 MHz, CDCl3) δ 7.47
(m, 2H), 7.33 (m, 3H), 6.37 (d, 1H, 4JH2-H6 ) 1.0, H-2), 2.70 (dt, 2H,
Pressure Dependence of Thermal Reactions of 2,9-Diphenyldispiro-
[5.0.5.2]tetradeca-1,8-diene (4). For kinetic studies, standard solutions
of anti-4 and syn-4 each in >98% of purity were prepared by separating
the appropriate fractions from HPLC column VI above and evaporating
to a concentration of ∼1%. Mesitylene was added as a UV-active,
internal standard. The solutions were degassed by the pump-freeze
method and stored at -30 °C.
3
4JH6-H2 ) 1.0, H-6), 2.42 (t, 2H, JH4-H5 ) 6.3, H-4), 2.08 (m, 2H,
3JH5-H4 ) 6.3, 3JH5-H6 ) 6.0, H-5); 13C NMR (75 MHz, CDCl3) δ 199.9
(C-1), 159.8 (C-3), 129.8 (C-2), 128.5, 125.8, 125.1, 37.0 (C-6), 27.8
(C-4), 22.6 (C-5).
To a suspension of 25.0 g of methylytriphenylphosphonium bromide
in 600 mL of anhydrous ether at 0 °C was added 30 mL of a 2.5 M
solution of butyllithium in n-hexane rapidly under argon and with
stirring for 1 h. Over a 3-h period, a solution of 10.4 g of the ketone
above in 200 mL of anhydrous ether was added dropwise. Addition of
200 mL of water, followed by extraction with ether (3×), gave
combined extracts which were dried over MgSO4. Concentration gave
an oil, from which 2.8 g (27.5%) of 1-phenyl-3-methylenecyclohexene
(3) was obtained as a colorless liquid after being passed through a short
column of Al2O3: 1H NMR (200 MHz, CDCl3) δ 7.45, 7.32, 7.24 (m,
5H, Hphenyl), 6.59 (s, 1H, H-2), 4.90 (d, 2H, H-7), 2.52 (t, 2H, H-6),
2.40 (dt, 2H, H-4), 1.85 (m, 2H, H-5); 13C NMR (75 MHz, CDCl3)
143.7 (C-1), 141.2 (C-3), 139.0, 128.5, 127.5, 125.0 (Cphenyl), 126.4
(C-2), 111.4 (C-7), 30.1 (C-6), 27.3 (C-4), 23.0 (C-5).
A 45-mg sample of 3 in 150 mL of LiAlH4-dried heptane was
transferred to a triethylamine-deactivated poly(tetrafluoroethylene)
(PTFE) sack containing a few crystals of BHMPS, placed in a 14-
kbar, high-pressure autoclave, and kept at 25 °C and 10.2 kbar for 48
h. Abter being passed through a short column of Al2O3 (heptane) to
remove colorless polymeric material, the sample showed no recovered
3 and no new products on analysis by HPLC.
For the kinetics at 1 bar, 10-µL portions of the solutions (separate
runs each for anti-4 and syn-4) were heated in a two-necked flask (one
neck of which was fitted with a T-tube and bubble counter to allow
control of the rate of flow of argon), and maintained at 43.6 ( 0.1 °C.
At 15-min intervals, 200-µL samples were removed by syringe through
a septum and analyzed on HPLC column VII [50-µL injections; 1.5
mL/min (120 bar) for 5 min; 2.0 mL/min (165 bar) for 10 min; detector,
254 nm]: tR ) 2.3 min (mesitylene), 3.3 min (3), 7.5 min (anti-4), 9.0
min (syn-4). All concentrations are corrected to that of mesitylene at t0
by equations, for example, [anti-4]t ) {fanti-4F(anti-4)t[Mes]0}/{F(Mes)t}.
The necessary UV-HPLC factors (e.g., fanti-4) are determined externally
1
by H NMR (200 MHz, CDCl3). Runs were made at 1.0 and 3.0 kbar
in the 7-kbar high-pressure autoclave. The corrected data of concentra-
tions are available in Tables 60, 61, and 62 of ref 28, while the resulting
calculated specific rate constants are given in Table 4.
Acknowledgment. W.v.E.D. thanks Professors Michael
Henchman and Colin Steele for stimulating and illuminating
discussions, and Dr. Lily Birladeanu for valuable assistance in
the preparation of the manuscript. Acknowledgment is made to
the donors of the Petroleum Research fund, administered by
the American Chemical Society, for the partial support of this
work (J.L.E.), and to the National Science Foundation, Grant
CHE-88 16186. J.L.E. expresses his thanks to Yale University
for the award of a NASA traineeship. Funding of the Harvard
University Mass Spectroscopy Laboratory by the National In-
stitutes of Health (RR06716) and the National Science Founda-
tion (CHE 90 20043) is gratefully acknowledged. F.-G.K.
expresses his thanks to the Deutsche Forschungsgemeinschaft,
the Ministry for Science and Research of the Land Nordrhein-
Westfalen, and the Fond der Chemischen Industrie for support.
This paper is dedicated to Professor Richard Neidlein on the
occasion of his 70th birthday.
2,9-Diphenyldispiro[5.0.5.2]tetradeca-1,8-diene (4). A solution of
700 mg of 3 and 100 mg of benzophenone in 10.0 mL of LiAlH4-
dried heptane was freed of oxygen by three pump-freeze cycles and
placed under argon in a Pyrex irradiation apparatus that could be cooled
by circulating methanol externally cooled to -40 °C. Irradiation with
a high-pressure mercury lamp (150 W) for 72 h generated some
insoluble polymer, removed by filtration through a short column of
Al2O3. Analysis of the resulting heptane solution by HPLC on column
VII showed two major products, anti-4 (tR ) 18.23 min) and syn-4 (tR
) 21.12 min), in addition to 10 other products in minor amounts.
Although unstable at room temperature and above, anti-4 and syn-4
could be separated by semipreparative HPLC (column VI) and stored
for weeks at -30 °C. Data for anti-4: 1H NMR (300 MHz, CDCl3) δ
7.25 (m, 10H, Hphenyl), 6.20 (s, 2H, H-1,8), 2.26 (m, 4H, H-3,10),
2
1.98 (m, 2H, H-5,12exo), 1.87 (AA′BB′, 4H, JHanti-13-Hsyn-14 ) 7.3,
H-13,14), 1.63 (m, 6H, H-4,11, H-5,12endo); 13C NMR (75 MHz, CDCl3)
δ 142.9 (C-2,9), 136.9 (Cphenyl), 131.2 (C-1,8), 128.4, 126.8, 125.4
(Cphenyl), 46.2 (C-6,7), 32.1, 31.1, 27.9 (C-13,14, C-5,12, C-3,10), 20.5
(C-4.11). Data for syn-4: 1H NMR (300 MHz, CDCl3) δ 7.3 (m, 10H,
Supporting Information Available: Various tables and
figures as indicated throughout the text (PDF). This material is
available free of charge via the Internet at http://pubs.acs.org.
H
phenyl), 6.34 (s, 2H, H-1,8), 2.28 (m, 4H, H-3,10), 1.7 (m, 12H); 13C
(59) Woods, G. F.; Tucker, I. W. J. Am. Chem. Soc. 1948, 70, 2174-
2177.
JA004128S