A non-cope among the cope rearrangements of 1,3,4,6-tetraphenylhexa-1,5- dienes

Article abstract of DOI:10.1021/ja993417h

The set of 1,3,4,6-tetraphenylhexa-1,5-dienes (1) represents a perturbation of Cope's rearrangement by four radical-stabilizing phenyl groups all positioned to drive the transition region toward the homolytic- colligative end of the mechanistic spectrum. The appearance of (Z)-isomers being suppressed thermodynamically by a steric interaction of +2.6 kcal mol^{- 1} per cis double bond, an equilibration that is stereochemically not of any Cope type, emerges as the predominant reaction. It is an interconversion of rac-(E,E)-1 and meso-(E,E)-1 (48:52; 77.3-115.3 °C) with the following values of the enthalpy, entropy, and volume of activation: ΔH(+) = 30.7 ± 0.2 kcal mol^-1, ΔS(+) = +2.1 ± 0.4 cal mol^-1 K^-1, and ΔV(+) = +13.5 ± 0.1 cm^-3 mol^-1, respectively. Structures have been established by X- ray crystallographic analysis; a possible relationship between dihedral angle and bond lengths in the styrene portions is proposed. The entropy of activation is incompatible with a chair or boat Cope rearrangement; the volume of activation is neither low enough for a pericyclic Cope ('concerted') mechanism nor high enough for a homolytic-colligative mechanism involving full dissociation as the rate-determining step. Trapping and a crossover experiment give some but only partial support to the intermediacy of free radicals. At higher temperatures, however, electron spin resonance experiments demonstrate an equilibrium with kinetically free (E,E)-1,3- diphenylallyl radicals. These observations are rationalized in terms of geometric reorganization within the confines of a 'cage'. Resolution by chiral chromatography of rac-(E,E)-1 allows recognition of a fast racemization (40-65 °C), of which ΔH(+) (21.3 ± 0.1 kcal mol^-1), DS(+) (-13.2 ± 0.3 cal mol^-1 K^-1), and ΔV(+) (-7.4 ± 0.4 cm^-3 mol^-1) are consistent with a pericyclic Cope rearrangement. Enriched (Z)-isomers undergo Cope rearrangements in accord with the known influence of axiality and the chair/boat alternative on the energy of the transition region.

Full text of DOI:10.1021/ja993417h

VOLUME 122, NUMBER 2
J ANUARY 19, 2000
© Copyright 2000 by the
American Chemical Society
A Non-Cope among the Cope Rearrangements of
1,3,4,6-Tetraphenylhexa-1,5-dienes
W. von E. Doering,*,† Ludmila Birladeanu,† Keshab Sarma,† G. Blaschke,‡
Ursula Scheidemantel,‡ R. Boese,§ Jordi Benet-Bucholz,§ F.-G. Kla1rner,|
Jan-Stephan Gehrke,| Bernd Ulrich Zimny,| R. Sustmann,| and Hans-Gert Korth|
Contribution from the Department of Chemistry and Chemical Biology, HarVard UniVersity,
Cambridge, Massachusetts 02138-2902, the Institut fu¨r Pharmazeutische Chemie, Westfa¨lische
Wilhelms-UniVersita¨t Mu¨nster, D-48149, Germany, and the Institut fu¨r Anorganische Chemie and Institut
fu¨r Organische Chemie, UniVersita¨t GH Essen, D-45117 Germany
ReceiVed September 20, 1999
Abstract: The set of 1,3,4,6-tetraphenylhexa-1,5-dienes (1) represents a perturbation of Cope’s rearrangement
by four radical-stabilizing phenyl groups all positioned to drive the transition region toward the homolytic-
colligative end of the mechanistic spectrum. The appearance of (Z)-isomers being suppressed thermodynamically
by a steric interaction of +2.6 kcal mol-1 per cis double bond, an equilibration that is stereochemically not of
any Cope type, emerges as the predominant reaction. It is an interconversion of rac-(E,E)-1 and meso-(E,E)-1
(48:52; 77.3-115.3 °C) with the following values of the enthalpy, entropy, and volume of activation: ∆Hq )
30.7 ( 0.2 kcal mol-1, ∆Sq ) +2.1 ( 0.4 cal mol-1 K-1, and ∆Vq ) +13.5 ( 0.1 cm-3 mol-1, respectively.
Structures have been established by X-ray crystallographic analysis; a possible relationship between dihedral
angle and bond lengths in the styrene portions is proposed. The entropy of activation is incompatible with a
chair or boat Cope rearrangement; the volume of activation is neither low enough for a pericyclic Cope
(“concerted”) mechanism nor high enough for a homolytic-colligative mechanism involving full dissociation
as the rate-determining step. Trapping and a crossover experiment give some but only partial support to the
intermediacy of free radicals. At higher temperatures, however, electron spin resonance experiments demonstrate
an equilibrium with kinetically free (E,E)-1,3-diphenylallyl radicals. These observations are rationalized in
terms of geometric reorganization within the confines of a ‘cage’. Resolution by chiral chromatography of
rac-(E,E)-1 allows recognition of a fast racemization (40-65 °C), of which ∆Hq (21.3 ( 0.1 kcal mol-1),
∆Sq (-13.2 ( 0.3 cal mol-1 K-1), and ∆Vq (-7.4 ( 0.4 cm-3 mol-1) are consistent with a pericyclic Cope
rearrangement. Enriched (Z)-isomers undergo Cope rearrangements in accord with the known influence of
axiality and the chair/boat alternative on the energy of the transition region.
Introduction
many attempts to gain intellectual control of a predictive value
over this erstwhile ‘no-mechanism’ reaction have appeared.
Central to an understanding is the response of the archetype to
structural perturbations. In this paper, perturbation by phenyl
groups is pursued to its end by examining the family of six
1,3,4,6-tetraphenylhexa-1,5-dienes (1).2,3 These four positions
of substitution are ‘active’ positions by analogy with the 1- and
3-positions of the allyl radical in that substituents occupying
Following the announcement of the long since eponymous
rearrangement of hexa-1,5-dienes by Arthur C. Cope in 1940,1
* Author to whom correspondence should be addressed.
† Department of Chemistry and Chemical Biology.
‡ Institut fu¨r Pharmazeutische Chemie.
§ Institut fu¨r Anorganische Chemie.
| Institut fu¨r Organische Chemie.
10.1021/ja993417h CCC: $19.00 © 2000 American Chemical Society
Published on Web 12/31/1999

194 J. Am. Chem. Soc., Vol. 122, No. 2, 2000
Doering et al.
The story developed further with the experimental and
theoretical work of Dewar et al. on mono- and diphenyl
derivatives, including 3-phenylhexa-1,5-diene.5 This compound
rearranged with an enthalpy of activation -5.4 kcal mol-1 lower
than that of the archetype.6 Consistently, 1,3-diphenylhexa-1,5-
diene had a ∆Hq lower by -8.1 kcal mol-1,7 after correction
by -5.1 kcal mol-1 for conjugative interaction in the educt.8
1,4-Diphenylhexa-1,5-diene underwent a similar rearrangement9
with a ∆Hq lower than that of the archetype by -8.7 kcal mol-1
,
again after correction by -5.1 kcal mol-1 for the stabilizing
effect of conjugative interaction on the educt. In summary, two
phenyl groups in active positions of hexa-1,5-diene appear to
lower the energy of the transition region by -8.8 ( 0.7 kcal
mol-1 (-4.4 kcal mol-1 per phenyl group).
Were all four active sites to be occupied by phenyl groups,
reaction by the homolytic-colligative mechanism might become
a credible possibility.10,11 Whether four phenyl groups (-17.6
kcal mol-1) could be expected to match the 26 kcal mol-1
difference between the bond dissociation energy of hexa-1,5-
diene12 and the ∆Hq of its degenerate Cope rearrangement
remained a source of scepticism. None the less, the radical-
stabilizing power of the perturbation promised to be larger than
any other in the literature,13 with the possible exception of the
nodally substituted 2,5-diphenylhexa-1,5-diene.5b,14
Results
1,3,4,6-Tetraphenylhexa-1,5-dienes (1). Compounds of con-
stitution 1 have already been prepared by Bergmann and Ukai,15
by Vo¨gtle and Goldschmitt in racemic and meso configuration,16
and by Boche and Schneider as mixtures of diastereomers of
the various geometric configurations.17 Starting either with
chalcone or 1,3-diphenylpropene, rac-(E,E)-1 of mp 143 °C
and meso-(E,E)-1 of mp 138 °C are conveniently prepared as
a mixture separable by a combination of crystallization and
manual segregation.
rac-(E,E)-1 and meso-(E,E)-1 crystallize in a noncentrosym-
metric (P21212) and a centrosymmetric (P1h) space group,
respectively. Quite unusually, only a single enantiomer is seen
in the crystal of rac-(E,E)-1, thus indicating the noncentrosym-
Figure 1. Temperature ranges over which kinetic data is gathered,
and derived Eyring activation parameters for various hexa-1,5-dienes
substituted by phenyl groups in ‘active’ (‘a’) positions are shown.
Differences in enthalpies of activation between hexa-1,5-diene, the
archetype, as reference are tabulated, uncorrected, and corrected for
decelerating conjugative interaction in the educt.
these positions may exercise their radical-stabilizing capacity
optimally in contrast to those in the ‘nodal’ 2-position.
The history of the perturbation of the Cope rearrangement
by phenyl substitution in active positions began with the
exploration by Koch of 3,4-diphenylhexa-1,5-diene as a can-
didate for rearrangement by a nonconcerted mechanism of the
homolytic-colligative type.4a Although this conjecture at first
seemed to have found support in the purported isolation of 1,4-
diphenylhexa-1,5-diene, it was later proved incorrect by Lutz
and co-workers, the products having been the 1,6-diphenylhexa-
1,5-dienes expected of a pericyclic mechanism.4b These workers
found an enthalpy of activation (∆Hq) for the rearrangement of
rac-3,4-diphenylhexa-1,5-diene lower than that of the archetype
by -9.5 kcal mol-1 (Figure 1).4c Its concerted nature received
strong support through the high-pressure studies of Kla¨rner and
co-workers.4d
(5) (a) Dewar, M. J. S.; Ford, G. P.; McKee, M. L.; Rzepa, H. S.; Wade,
L. E., Jr. J. Am. Chem. Soc. 1977, 99, 5069-5073. (b) Dewar, M. J. S.;
Wade, L. E., Jr. J. Am. Chem. Soc. 1977, 99, 4417-4424.
(6) Doering, W. von E.; Toscano, V. G.; Beasley, G. H. Tetrahedron
1971, 27, 5299-5306.
(7) Doering, W. von E.; Wang, Y.-h. J. Am. Chem. Soc. 1999, 121,
10112-10118.
(8) Doering, W. von E.; Benkhoff, J.; Carleton, P. S.; Pagnotta, M. J.
Am. Chem. Soc. 1997, 119, 10 947-10 955.
(9) Doering, W. von E.; Birladeanu, L.; Sarma, K.; Teles, J. H.; Kla¨rner,
F.-G.; Gehrke, J.-S. J. Am. Chem. Soc. 1994, 116, 4289-4297.
(10) Dissociation of hexa-1,5-diene into two allyl radicals is also an
example of reaction by the intermolecular homolytic-colligative mecha-
nism,12 as is the observation that 1,4-diphenylhexa-1,5-diene is converted
to 1,6-diphenylhexa-1,5-diene at high temperature.9 There are several
examples of the oxymoronic intramolecular homolytic-colligative type;
that is, Cope rearrangements proceeding in two steps by way of a diradical
(not two radicals) as intermediate.11
(1) (a) Cope, A. C.; Hardy, E. M. J. Am. Chem. Soc. 1940, 62, 441-
444. (b) Cope, A. C.; Hoyle, K. E.; Heyl, D. J. Am. Chem. Soc. 1941, 63,
1843-1852. (c) Cope, A. C.; Hofmann, C. M.; Hardy, E. M. J. Am. Chem.
Soc. 1941, 63, 1852-1857. (d) Whyte, D. E.; Cope, A. C. J. Am. Chem.
Soc. 1943, 65, 1999-2004. (e) Levy, H.; Cope, A. C. J. Am. Chem. Soc.
1944, 66, 1684-1688. (f) Foster, E. G.; Cope, A. C.; Daniels, F. J. Am.
Chem. Soc. 1947, 69, 1893-1896.
(2) For the only previous investigation of a 1,3,4,6-tetrasubstituted hexa-
1,5-diene, see the elegant, painstaking work of Gajewski, Benner, and
Hawkins on 4,5-dimethylocta-2,5-dienes.3
(3) Gajewski, J. J.; Benner, C. W.; Hawkins, C. M. J. Org. Chem. 1987,
52, 5198-5204.
(4) (a) Koch, H. P. J. Chem. Soc. 1948, 1111-1117. (b) Lutz, R. P.;
Bernal, S.; Harris, R. O.; McNicholas, M. W. J. Am. Chem. Soc. 1971, 93,
3985-3990. (c) Lutz, R. P.; Berg, H. A. J. J. Org. Chem. 1980, 45, 3915-
3916. (d) Diedrich, M. K.; Hochstrate, D.; Kla¨rner, F.-G.; Zimny, B. Angew.
Chem., Int. Ed. Engl. 1994, 33, 1079-1081.
(11) Among numerous examples, see Roth, W. R.; Gleiter, R.; Pas-
chmann, V.; Hackler, U. E.; Fritzsche, G.; Lange, H. Eur. J. Org. Chem.
1998, 961-967.
(12) Roth, W. R.; Bauer, F.; Beitat, A.; Ebbrecht, T.; Wu¨stefeld, M.
Chem. Ber. 1991, 124, 1453-1460.
(13) Cope rearrangements of the 1,2-divinylcyclopropane and cyclobutane
types have a well-known history in which both concerted and nonconcerted
paths are strongly accelerated by relief of a strain energy of ∼26 kcal mol-1
.
(14) Roth, W. R.; Lennartz, H.-W.; Doering, W. v. E.; Birladeanu, L.;
Guyton, C. A.; Kitagawa, T. J. Am. Chem. Soc. 1990, 112, 1722-1732.
(15) Bergmann, E.; Ukai, T. Chem. Ber. 1933, 66, 54-58.
(16) Vo¨gtle, F.; Goldschmitt, E. Chem. Ber. 1976, 109, 1-40.
(17) Boche, G.; Schneider, D. R. Angew. Chem., Int. Ed. Engl. 1977,
16, 869-870.

1,3,4,6-Tetraphenylhexa-1,5-dienes
J. Am. Chem. Soc., Vol. 122, No. 2, 2000 195
Scheme 1
Figure 2. Crystallographic structures of rac-(E,E)-1 and meso-(E,E)-1
are shown along with their other staggered conformations. Differences
in steric energies (∆SE in kcal mol-1 as calculated by MM2 (MM3)
[rac-(E,E)-1: -11.71 kcal mol-1 (41.63 arbitrary units)] are given.
metric structure and a spontaneous resolution.18 Extensive efforts
to exploit this phenomenon for preparative resolution of rac-
(E,E)-1 have been unsuccessful. The absolute structure cannot
be determined because the anomalous dispersion of hydrocar-
bons is too low. Because both structures are arranged around
crystallographic symmetry elements (an inversion center within
the central single bond of meso-(E,E)-1 and a 2-fold axis passing
through the central single bond of rac-(E,E)-1), the molecules
have crystallographic Ci and C2 symmetry, respectively (Figure
2). Crystallographic data and Ortep representations are available
in Item SI-1 and Figure SI-1, respectively, of the Supporting
Information. The dihedral angles between the phenyl group and
double bond are 11.2° in meso-(E,E)-1 and 23.7° in rac-(E,E)-
1. In both, the central hydrons of the C3-C4 bond are in the
antiperiplanar conformation rather than the synclinal conforma-
tion more commonly seen in 1,2-tetrasubstituted ethanes with
bulky substituents.19 The antiperiplanar conformations concur
with expectations based on the differences in steric energies
calculated by molecular mechanical methods (MM220 and
MM321). Further discussion of the data, particularly of the ratio
of the length of the conjugated single bond between double bond
and phenyl, and the length of the double bond, as a function of
dihedral angle is given in the Appendix.
workers in 3,4-di(1-cyclohexen-1-yl)-2,2,5,5-tetramethylhexa-
1,5-diene,23 the interconversion is almost unprecedented. It
cannot be accommodated by any concatenation of the three sets
of conventional chair, boat, or twist-boat Cope rearrangements
(Scheme 1). In the boat domain, for example, rac-(E,E)-1
(ESSE/ERRE) can rearrange to meso-(E,Z)-1 (ESRZ or ERSZ),
but then finds itself in a cul-de-sac in the chair or twist-boat
domain unable to reach meso-(E,E)-1. The interconversion of
rac-(E,E)-1 and meso-(E,E)-1 may be constitutionally of the
Cope type, but configurationally it is not.
Elucidation of the kinetics is an essential element in trying
to understand the mechanism of this atypical interconversion.
That the reaction is first-order is confirmed by the failure of a
10-fold increase in concentration to change the rate. Kinetics
are followed from either meso- or rac-(E,E)-1 over the
temperature range, 77.3-115.3 °C. A few percent of the two
(E,Z)-isomers (vide infra), disfavored by +2.6 kcal mol-1 per
double bond,8 are also formed, but so much more rapidly that
they constitute a preequilibrium of no deleterious consequence
for determination of the kinetics. A sample of experimental data
at 101 °C is given in Table SI-1. Specific rate constants and
activation parameters are summarized in Table 1: ∆Hq ) 30.7
( 0.4 kcal mol-1, and entropy of activation (∆Sq) ) +2.1 (
1.0 cal mol-1 K-1. If a ∆Hq slightly lower than that of the
archetype (Figure 1) occasions no surprise, the ∆Sq, being much
more positive than that of the archetype (-13.8 ( 1.0 cal mol-1
K-1), is not only strikingly inconsistent with a mechanism of
the concerted, pericyclic type, but is also significantly smaller
than would be expected of a process involving dissociation into
a pair of free radicals as the rate-determining step.
At temperatures ∼100 °C, rac-(E,E)-1 and meso-(E,E)-1 are
interconverted, ultimately reaching equilibrium (48:52). This
equilibration has already been noted by Vo¨gtle and Goldschmitt
at 200 °C,16 and by Perkins and co-workers at 80 °C after boiling
in benzene for 60 h,22 but without comment from either group.
With the exception of the example of Gajewski, Benner, and
Hawkins,3 and that uncovered recently by Ru¨chardt and co-
(18) Brock, C. P.; Dunitz, J. D. Chem. Mater. 1994, 6, 1118-1127.
(19) Structural assignments are reversed in ref 17.
(20) Burkert, U.; Allinger, N. L. Computational Chemistry; American
Chemical Society: Washington, DC, 1982. Cambridge Scientific Computing,
Inc., Cambridge, MA 02139: Chem 3D 3.0.1.
(21) Allinger, N. L.; Yuh, Y. H.; Lii, J.-H. J. Am. Chem. Soc. 1989,
111, 8551-8566.
(22) Corbally, R. P.; Perkins, M. J.; Elnitski, A. P. J. Chem. Soc., Perkin
Trans. 1 1979, 793-798.
Free (E,E)-1,3-diphenylallyl radicals by homolysis constituted
such an attractive hypothesis to explain the non-Cope-like
stereochemistry that extensive efforts were mounted to determine
what role, if any, they might be playing. Electron spin resonance
(23) Herberg, C.; Beckhaus, H.-D.; Ko¨rtvelyes, T.; Ru¨chardt, C. Chem.
Ber. 1993, 123, 117-127.

196 J. Am. Chem. Soc., Vol. 122, No. 2, 2000
Doering et al.
Table 1. Specific Rate and Equilibrium Constants and Activation
Parameters for the Thermal Interconversion of rac- and
meso-(E,E)-1,3,4,6-Tetraphenylhexa-1,5-diene [rac-(E,E)-1 and
meso-(E,E)-1] in Benzene-d6
K b
a
a
T, °C
k1
k-1
77.3 ( 0.14c
80.7 ( 0.28c
87.2 ( 0.15d
101.4 ( 0.14c
101.4 ( 0.14e
110.5 ( 0.11c
115.3 ( 0.09c
1.47 ( 0.01
2.25 ( 0.02
5.28 ( 0.04
26.9 ( 0.15
27.0 ( 0.5
1.31 ( 0.01
2.02 ( 0.02
4.77 ( 0.04
24.6 ( 0.14
24.6 ( 0.5
1.12
1.11
1.11
1.10
1.10
1.09
1.08
74.3 ( 0.3
68.2 ( 0.3
118.2 ( 0.9
109.3 ( 0.9
Arrhenius plot [1/T vs log k]
Ea ) 31.44 ( 0.37 kcal mol-1 f
log A ) 13.78 ( 0.22f
Figure 4. Hyperfine splitting constants (g) of the 1,1,3,3-tetraphenyl-
allyl radical (top left),24a cinnamyl radical (top right),24b and the (E,E)-
1,3-diphenylallyl radical (bottom) are given.
Eyring parametersg
∆Hq ) 30.7 ( 0.4 kcal mol-1 f
∆Sq ) +2.1 ( 1.0 cal mol-1 K-1 f
thermodynamics [1/T vs log K]
∆H ) -0.22 ( 0.02 kcal mol-1
∆S ) -0.40 ( 0.06 cal mol-1 K-1
biguously as a radical of symmetrical structure, almost certainly
of the (E,E) rather than the (Z,Z) configuration. Splitting
constants for tetraphenylallyl radical24a and cinnamyl radical24b
are shown for purposes of comparison. Attempts to obtain
thermodynamic quantities from the temperature dependence of
equilibrium constants observed over the temperature range 200-
300 °C were only partially successful, because additional, if
smaller, lines appeared at higher temperatures on the outer wings
of the spectra. At temperatures >270 °C, the fit of signal
amplitudes was even less satisfactory, suggestive of increasing
contamination by other radicals, probably (E,Z)-1,3-diphenyl-
allyl. To extract the hyperfine splitting constants for the minor
isomer was impossible because each phenyl group was expected
to exhibit different splittings. In the absence of knowledge of
the temperature dependence of the concentration of the minor
isomer, precise determinations could not be made. Beyond that
impediment, slopes of the intensities of the ESR spectra for
uphill and downhill variation of temperature diverged markedly,
which indicated significant irreversible chemical change at the
higher temperatures (persistent yellowing). Best efforts with the
equilibrium constants (to be found in Item SI-2) led to the
following values of enthalpy and entropy for the reaction: ∆Hr
) 32.3 ( 5.3 kcal mol-1 and ∆Sr ) +17.1 ( 9.8 cal mol-1
K-1, respectively. Although the precision of the bond dissocia-
tion energy (BDE) is insufficient to conclude that a homolytic-
colligative mechanism is operative, the BDE range encompasses
the ∆Hq of the non-Cope interconversion and thus admits the
free radical as an energetically credible intermediate.
a Calculated by linear regression of the usual expression for a
reversible first-order reaction: (x - xo)/(xe - xo) ) exp[-(k1 + k-1)t];
s ) standard error; rate constants in units of 10-6 s-1 b The equilibrium
.
constant, K ) k1/k-1.
c 0.0278 M in rac-(E,E)-1; 0.00213 M in 18-
crown-6 ether. d 0.020 M in rac-(E,E)-1; 0.00125 M in 18-crown-6
ether. e 0.0275 M in meso-(E,E)-1; 0.002 M in 18-crown-6 ether. f 95%
confidence limits. g Calculated at 96.3 °C.
Several experiments undertaken to block the interconversion
by traps for free radicals led to ambiguous results and weakened
the case for a homolytic-colligative mechanism. These efforts
involved phenol, 9,10-dihydroanthracene, 2,2,6,6-tetramethylpi-
peridinyl oxyl (TEMPO), oxygen at atmospheric pressure, and
2-methyl-2-nitrosopropane, none of which either inhibited or
diverted the interconversion.25 High concentrations of thiophenol
did generate substantial amounts of 1,3-diphenylpropene as well
as the product of addition with thiophenol. In the presence of
low concentrations of thiophenol, the interconversion continues
to be observed. Further details may be found in the Experimental
Section and Item SI-3. It may be tentatively concluded that
some, but not all, of the rearrangement proceeds by way of free
1,3-diphenylallyl radicals.
Figure 3. The upper ESR spectrum is that of the (E,E)-1,3-
diphenylallyl radical generated by thermal dissociation of meso-(E,E)-
1,2,3,4-tetraphenylhexa-1,5-diene in diphenyl ether at 251 °C. The lower
spectrum is the computer-simulated (overall width 44.93 g) using the
hyperfine splitting constants [g] in Figure 4.
(24) (a) Landolt-Bernstein, New Series, Magnetic Properties of Free
Radicals, Vol. II/17cb; Fischer, H., Hellwege, K. H., Eds.; Springer: Berlin,
1989; p 25 ff; (b) Landolt-Bernstein, New Series, Magnetic Properties of
Free Radicals, Vol. II/9b; Fischer, H., Hellwege, K. H., Eds.; Springer:
Berlin, 1977; p 392.
(25) An energetically implausible chain mechanism involving 1,3-
diphenylallyl radical as carrier finds no support in the failure of additions
of AIBN or iodine to accelerate the reaction.
(ESR) spectroscopy was accordingly applied in the hope of
observing the free radical directly. A solution of meso-(E,E)-1
in diphenyl ether at 251 °C revealed a spectrum (Figure 3) that
could be simulated by computer (overall width 44.93 g) using
the hyperfine splitting constants (g) in Figure 4 (g value )
2.00269). 1,3-Diphenylallyl was identified essentially unam-

1,3,4,6-Tetraphenylhexa-1,5-dienes
J. Am. Chem. Soc., Vol. 122, No. 2, 2000 197
Table 2. Effect of Pressure on the Thermal Interconversion of
meso-(E,E)-1 (M) and rac-(E,E)-1 (R) at 98 °C for 96 h in
Toluene-d8 and Benzene-d6
The late Wolfgang Roth has applied his powerful method of
trapping in supercritical carbon dioxide with high partial
pressures of oxygen.26 Quantitative examination has revealed
three distinct processes. At low partial pressures (∼1-2 kbar)
of oxygen, there is a dramatic reduction in the rate constant of
the interconversion of rac-(E,E)-1 and meso-(E,E)-1 to about
half its oxygen-free value. As pressures are increased up to ∼90
kbar, this rate constant suffers no further decrease, but disap-
pearance of educt continues to increase. In their model for
rationalizing these observations, three intermediate complexes
are hypothesized: one engaging in the interconversion with no
interference by oxygen; a second being the precursor of the
kinetically free free-radicals thought to be rapidly trapped at
the low oxygen pressures; and a third leading irreversibly to
byproducts in a second-order reaction with oxygen. Critical
examination of this model has not been possible because of the
absence of primary experimental data. Whether the results would
be significantly different in solution will be difficult to determine
because of the generally very low solubility of oxygen in organic
solvents.
Crossover experiments are the classical device to establish
mechanisms of the homolytic-colligative, dissociative-recom-
binative type. Of two experimental designs, both involving
dissociation into two different intermediates (the one starting
from a single, unsymmetrically substituted reactant and the other
from two symmetrically but differently substituted reactants),
we have chosen to start from a mixture of the phenyl compounds
(1) and their p-tolyl analogues (2). Mass spectroscopy was the
analytical method.
Preparation following one of the procedures used for 1 gives
rise to two crystalline compounds, which are assumed to be
meso- and rac-(E,E)-2, although no effort has been made to
distinguish between them (experimental details in Item SI-4).
The structure meso-(E,E)-2 is assigned to the less soluble isomer
solely by analogy to meso-(E,E)-1. When an equimolar mixture
of meso-(E,E)-1 and meso-(E,E)-2 is heated in toluene-d8 at
110 °C for 13.5 h, a new set of peaks centered at m/e 414 in
the mass spectrum appears, in addition to those at 386 and 442,
which correspond to the starting hexadienes. This period of
heating corresponds to ∼10 half-lives in the interconversion of
(E,E)-1. Instead of the statistically expected ratios of 1.00:2.00:
1.00, ratios of 0.93:0.57:1.00 are obtained. Although some
crossover has occurred in support of the involvement of 1,3-
diphenylallyl radicals, convincing support for the exclusiVe
operation of the homolytic-colligative mechanism is not
forthcoming. This result is consistent with those from the
trapping experiments already outlined: free radicals appear to
be playing some role in the rearrangement, but most of the
reaction seems to be occurring by nondissociative paths.
p, bar
solvent
(M) f (R)
(R) f (M)
1
C7D8
C6D6
C7D8
53:47
54:46
91:09
99:01
48:52
48:52
89:11
95:05
1
10 500
10 500
a
b
C6D6
a Liquid: Tf of toluene is 30 °C at 9600 bar. b Crystalline: Tf of
benzene is 114 °C at 5100 bar.
rearrangement of cis- and trans-1,2-divinylcyclobutane to 1,5-
cyclooctadiene is an unambiguous example. The cis isomer is
accelerated by an increase in pressure [volume of activation
(∆Vq) ) -14.1 cm3 mol-1 at 69.8 °C] consistent with the
operation of a pericyclic Cope mechanism, whereas the trans
isomer is retarded and shows a positive ∆Vq (+4.1 cm3 mol-1
at 159.6 °C).9 A homolytic-colligative mechanism is expected
to show a deceleration of rate and a positive volume of
activation. The partial molar volumes of cyclic transition states,
determined within the scope of the Eyring transition-state theory
as the sum of the activation volume and partial molar volumes
of the reactants, are consistently smaller than those of the
corresponding acyclic transition states as a consequence of larger
packing coefficients.28
The effect of increasing pressure on the interconversion of
meso-(E,E)-1 and rac-(E,E)-1 is striking. In toluene at 10.5
kbar, where still a liquid, the rate is significantly slower than at
1 bar (cf. rows 1 and 3, Table 2). In benzene at 10.5 kbar, where
the compounds are now in a crystalline matrix, the intercon-
version is almost completely suppressed (at 1 bar, same rate as
in toluene). From the pressure dependencies of the specific rate
constants available in Table SI-2, values of ∆Vq are derived
for the forward reaction (∆Vq ) +13.5 ( 0.1 cm3 mol-1) and
the reverse reaction (∆Vq ) +11.5 ( 0.2 cm3 mol-1). The
difference in the activation volumes of the reaction (∆∆Vr )
-2.0 cm3 mol-1) should equal the volume of reaction and
indeed is in good agreement with the value derived from
measurements of changes in partial molar volumes (∆∆Vr )
-1.7 cm3 mol-1; see Experimental Section and Table SI-3).
These positive ∆Vq values are sharply inconsistent with a cyclic
transition state and point to a large expansion of volume in the
transition state in qualitatiVe accord with dissociation. A good
estimate of the volume change for reaction to a pair of
independently free 1,3-diphenylallyl radicals can be made with
Exner increments.29,30 The partial molar volume of meso-(E,E)-1
or rac-(E,E)-1 is calculated to be 349.7 cm3 mol-1 (related to
20 °C), which is in agreement with the values of 345.7 and
351.7 cm3 mol-1, respectively, already determined from density
measurements. The calculated partial molar volume of the 1,3-
diphenylallyl radical is 186.7 cm3 mol-1, whence is derived a
volume of reaction of +23.7 cm3 mol-1, which is almost twice
as large as the experimental ∆Vq values already mentioned. The
ground state is certainly not moving toward a tight cycle (∆Vq
in the range of -12 cm3 mol-1), but rather toward an extended
system, the ∆Vq of which quantitatiVely falls short of that
expected of a rate-determining transition region resembling
solvent-separated free radicals. Compare, for example, the high
Deeper insight can be gained by examination of the pressure
dependence. Competing pericyclic and stepwise rearrangements
having been shown to respond very differently to variation in
pressure,27 application of high pressure is now accepted to be a
penetrating method for probing the pericyclic nature of rear-
rangements of the Cope and electrocyclic types.4d The thermal
(26) Roth, W. R.; Hunold, F. Liebigs Ann. 1996, 1917-1928. Hunold,
F. Ph.D. Dissertation, Ruhr-Universita¨t Bochum: “Bildung und Rekombi-
nation konjugativ stabilisierter Radikale; Analyse durch Sauerstoffabfang
in u¨berkritischem CO2”, Shaker Verlag: Postfach 1290, D-52013 Aachen,
Germany.
(27) Kla¨rner, F.-G. Chem. Uns. Zeit 1989, 23, 53-63. Kla¨rner, F.-G.;
Krawczyk, B.; Ruster, V.; Deiters, U. K. J. Am. Chem. Soc. 1994, 116,
7646-7657. Kla¨rner, F.-G.; Diederich, M. K.; Wigger, A. E. Effect of
Pressure on Organic Reactions. In Chemistry under Extreme or Nonclassical
Conditions; van Eldik, R., Hubbard, C. D., Eds; Wiley: New York,
Spektrum: Heidelberg, 1997; Chapter 3, pp 103-161.
(28) The packing coefficient, η, is defined as the ratio between the
intrinsic volume, the so-called van der Waals volume, and the partial molar
volume (η ) VW/V): Asano, T.; le Noble, W. J. ReV. Phys. Soc. Jpn. 1973,
43, 82-91. Yoshimura, Y.; Osugi, J.; Nakahara, M. Bull. Chem. Soc. Jpn.
1983, 56, 680-683. Yoshimura, Y.; Osugi, J.; Nakahara, M. J. Am. Chem.
Soc. 1983, 105, 5414-5418.
(29) Exner, O. In Organic High-Pressure Chemistry; le Noble, W. J.,
Ed.; Elsevier: Amsterdam, 1988; pp 19-49.

198 J. Am. Chem. Soc., Vol. 122, No. 2, 2000
Doering et al.
Table 4. Pressure Dependence of Specific Rate Constants for
Thermal Racemization of (-)-(E,E)-1,3,4,6-Tetraphenylhexa-
1,5-diene [(-)-(E,E)-1] at 44.3 °C in n-Hexane/2-Propanol (70/30)
Table 3. Specific Rate Constants and Activation Parameters for
Thermal Racemization of (+)-(E,E)-1,3,4,6-Tetraphenylhexa-
1,5-diene [(+)-(E,E)-1] in n-Hexane/2-Propanol (70/30)
a
a
T, °C
krac
p, bar
krac
40.0
45.1
55.1
55.0b
65.0
2.19 ( 0.01
3.82 ( 0.05
10.93 ( 0.07
10.50 ( 0.14
29.82 ( 0.21
1
250
500
1000
2000
3000b
4000
3.52 ( 0.03b
3.84 ( 0.02
4.12 ( 0.05
4.68 ( 0.03
5.44 ( 0.03
6.38 ( 0.06
7.08 ( 0.08
Arrhenius plot [1/T vs log k]
Ea ) 21.98 ( 0.09 kcal mol-1
A ) (4.74 ( 0.71) × 1010 s-1
Eyring parametersc
∆Vq ) -(7.4 ( 0.4) cm3 mol-1 c
∆Vq ) -(7.1 ( 0.1) cm3 mol-1 d
∆Hq ) 21.3 ( 0.1 kcal mol-1
∆Sq ) -11.9 ( 0.3 cal mol-1 K-1
a Calculated by linear regression using equation, krac ) (1/t) × ln(eeo/
eet); all standard errors are 95% confidence level; rate constants in units
of 10-5 s-1 b This value is calculated from temperature dependence of
.
a Calculated by linear regression using equation, krac ) (1/t) × ln(eeo/
the racemization of (+)-(E,E)-1 (Table 3). c ∆Vq is calculated from
the linear slope (1-1000 bar) of the correlation of ln krac versus p: ln
krac ) a1 + b1p; ∆Vq ) b1RT. d ∆Vq is calculated from all data by means
of the quadratic equation, ln krac ) a2 + b2p + c2p2; ∆Vq ) -b2RT.
eet); all standard errors are 95% confidence level; rate constants in units
of 10-5 s-1 b This experiment starts with (-)-(E,E)-1,3,4,6-tetraphen-
.
ylhexa-1,5-diene. c Calculated at 52.5 °C.
positive ∆Vq (+35.7 cm3 mol-1) observed in the thiophenol-
trapped dissociation of 3,4-diethyl-3,4-diphenylhexane.31 These
efforts have not established free radicals as a sufficient explana-
tion of the non-Cope interconversion. The various observations
taken together will be discussed later in terms of a caged radical
pair.
Pericyclic Cope Rearrangements of 1. The conventional
Cope rearrangements open to the configurational isomers of 1
in the chair, boat, and twist-boat conformations have been
brought together in Scheme 1. Enantiomerizations of rac-(E,E)-1
in the chair, and a nonreaction of meso-(E,E)-1 in the boat
conformation, are distinguished by allowing all four phenyl
groups to occupy ‘equatorial’ positions in the transition region,32
and are therefore likely the fastest of the conventional Cope
rearrangements in this series. Resolution of rac-(E,E)-1 into
its pure enantiomers has been effected efficiently by high-
performance liquid chromatography (HPLC) on a chiral column.
Racemization is already rapid by 40 °C. From the time
dependence of the enantiomeric ratios determined at four
temperatures between 40 and 65 °C (Table 3), activation
parameters can be obtained: ∆Hq ) 21.3 ( 0.1 kcal mol-1
and ∆Sq ) -11.9 ( 0.3 cal mol-1 K-1. The ∆Hq is among the
lowest recorded, whereas the negative ∆Sq is fully consistent
with the operation of a pericyclic Cope mechanism.
Further to confirm the pericyclic nature of the enantiomer-
ization, its ∆Vq value was determined from the pressure
dependence of the rate constants of racemization of (-)-(E,E)-1
(Table 4). At the same time, the pressure dependence of another
strongly stabilized, degenerate, pericyclic rearrangement of
comparably low ∆Hq, that of 2,5-diphenylhexa-1,5-diene-1,6-
13C, was also examined (Table SI-4). These ∆Vq values and
two others already in the literature4d,9 are collected in Figure 5.
Although they have not been related to the same temperature,
the ∆Vq values are all negative and in the range of -9 to -13
cm3 mol-1. The negative ∆Vq observed for the racemization of
Figure 5. Volumes of activation for hexa-1,5-dienes substituted by
phenyl groups in ‘active’ (‘a’) positions are shown.
(E,E)-1 (∆Vq ) -7.4 cm3 mol-1) is thus quite compatible with
a pericyclic mechanism.
The pairs of (E,Z)- and (Z,Z)-isomers have also been
examined, but only in a preliminary, pseudo-quantitative man-
ner. For their better study, they have been prepared in enriched
form by establishment of photostationary states by triplet-
sensitized photoisomerization of meso-(E,E)-1 and rac-(E,E)-1
(Table 5). Each of these compounds leads to a mixture of three
geometrical isomers from which much of the starting (E,E)-
isomer can be removed by crystallization. Although the residual
(Z)-isomers have not been isolated in pure form, they are easily
characterized with the help of nuclear magnetic resonance
(NMR) decoupling. Details are given in the Experimental
Section where resonances employed in analysis of their thermal
rearrangements are also listed.
(30) The molar volume calculated for neat meso- or rac-(E,E)-1 by the
use of Exner increments is given by Vcalc ) 4 × V(C6H5-(any group)) + 2
× V(CHs(Cb)) + 4 × V(CHd(Cd)) ) 4 × V(74.04) + 2 × V(-0.15) +
4 × (13.47) ) 349.74 cm3 mol-1 (related to 20 °C). This value is in good
agreement with the partial molar volumes given in Table SI-5 determined
in toluene solution at 20 °C. Because the volume increment, V(CHs(Cd)),
is unknown, we use V(CHd(Cd)) instead to estimate the molar volume of
the (E,E)-1,3-diphenylallyl radical: Vcalc ) 2 × V(C6H5-(any group)) + 2
× V ((CHd(Cd)) + 1 × V((Cd)sCHd(Cd)) ) 2 × (74.04) + 2 × (13.47)
The interconversion rac-(E,Z)-1 T meso-(E,E)-1 may take
place via a chair, one-axial transition region (Scheme 1), and
is expected to be the next fastest reaction after racemization.
By the time the first point is recorded starting with meso-(E,E)-1
(Table S1, 101 °C, or Table 6, second section, 80 °C), rac-
+ 1 × (11.68) ) 186.70 cm3 mol-1
.
(31) Dierkes, G.; Kla¨rner, F.-G.; Ru¨chardt, C., unpublished results.
(32) For a thorough analysis of the decelerating effect of an axial phenyl
group, see Kla¨rner et al.4d

1,3,4,6-Tetraphenylhexa-1,5-dienes
J. Am. Chem. Soc., Vol. 122, No. 2, 2000 199
10-6 s-1) is ∼19% as large as that of the non-Cope intercon-
version rac-(E,E)-1 T meso-(E,E)-1 (71 × 10-6 s-1; Table
1).
Table 5. Photosensitized Irradiation (Benzophenone) of
rac-(E,E)-1 and meso-(E,E)-1 in Benzene-d6
t, min
rac-(E,E)-1a
rac-(E,Z)-1
rac-(Z,Z)-1
High pressure (9 kbar; 61.8 °C) applied to a 55:17:24:4
mixture of rac-(E,Z)-1 and meso-(E,E)-1, and rac-(Z,Z)-1 and
rac-(E,E)-1, respectively, induces a ∼2-fold increase in the rate
of interconversion of the first pair (no change in the second
pair being observed), regardless of whether in toluene-d8 (liquid)
or benzene-d6 (crystalline matrix) (Table SI-5). This evidence
points to the rearrangement being of the pericyclic Cope type,
as already assumed.
This cursory exploration is an invitation to a more thorough
study of the pure (Z)-isomers as a means of disentangling
minimization of axiality from avoidance of the boat conforma-
tion. The situation is conceptually similar to that developed in
the study of meso-3,4-diphenylhexa-1,5-diene.4 In such an effort,
the approximate relative rates of rearrangement to the most
stable isomers may be helpful in optimizing kinetic enrichment
of the less stable isomers, while optically active materials are
potentially available by chiral-column separation or irradiation
of optically active (+)-(E,E)-1.
0
30
90
>99
55.6
20.9
15.8b
34.2
44.6
40.0
10.2
34.5
44.2
150
t, min
meso-(E,E)-1
meso-(E,Z)-1
meso-(Z,Z)-1
0
30
90
180
360
>99
77.8
50.9
32.2
13.0b
20.2
40.2
42.5
43.6
2.0
8.9
25.3
43.4
a Composition in percent. b Extraneous signals in the NMR spectrum
amount to ∼17% of the total.
Table 6. Thermal Interconversions among the Six Stereoisomeric
1,3,4,6-Tetraphenylhexa-1,5-dienes 1 in Benzene-d6 at Various
Temperatures
t, h r-(E,E) r-(E,Z) r-(Z,Z) m-(E,E) m-(E,Z) m-(Z,Z)
0a
24
48
0a
24
48
0c
13.2
0d
7.5
24
100.0b
83.7
68.0
0.0
0.73
1.34
0.0
0.0
0.0
0.0
14.9
29.1
0.0
0.69
1.29
0.0
0.0
0.0
Discussion
0.0
14.9
28.0
0.0
7.0
5.2
0.0
0.0
0.0
100.0
77.8
65.3
0.0
0.3
1.5
0.0
0.0
0.0
Returning to the rapid racemization of (+)-(E,E)-1, its ∆Hq
is 12.2 kcal mol-1 lower than that of the archetype before
correction for conjugative interaction in the educt, or 22.4 kcal
mol-1 after correction.34 The implied extra stabilization (beyond
allylic stabilization) per 1,3-diphenylallyl component is an
unusually high -11.2 kcal mol-1. This value is more than
double that seen in the cinnamyl component of the rearrange-
ments of 1,4-diphenylhexa-1,5-diene (-4.4 kcal mol-1; see
Figure 1)9 or rac-3,4-diphenylhexa-1,5-diene (-4.7 kcal mol-1).4c
By analogy with the sequence of stabilization energies in allyl,
pentadienyl, and heptatrienyl, the reverse might have been
expected.35-37 One explanation for the high energy of stabiliza-
tion is offered by the theoretical calculations of Hrovat et al.38
They find an enhancement of -1.9 kcal mol-1 beyond additivity
in the ∆Hq of rearrangement for 1,3,4,6-tetracyanohexa-1,5-
diene in comparison with 1,3-dicyanohexa-1,5-diene.39
0.0
35.1
0.0
0.0
0.0
0.0
0.0
36.3
46.0
0.0
54.0
28.6
13.6
14.0
17.6
21.4
29.7
40.7
45.7
45.5
41.2
38.9
27.5
0.0
13.6
30.7
33.9
39.9
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
0.0
26.9
10.5
5.8
42
72
(2.9)e
a At 79-80 °C. b Relative concentrations in percent. c At 110 °C.
d At 69 °C. e This datum missing, an equilibrium concentration is
assumed for the purposes of calculation of rate constants.
(E,Z)-1 is already in equilibrium (K ) ∼12).33 From the data
at 69 °C in Table 6, fourth section, a rate constant, k1 ) ∼15
× 10-6 s-1, can be estimated. The reaction is ∼30 times slower
than a calculated value (69 °C) for the racemization, k1 ) 430
× 10-6 s-1, and ∼30 times faster than the non-Cope intercon-
version rac-(E,E)-1 T meso-(E,E)-1.
Whether the observed ∆Hq pertains to a single-step, ‘con-
certed’, ‘aromatic’ transition region or to a two-step process
separated by an achiral intermediate closely similar in geometry
cannot be decided, for either would suffice to accommodate
racemization and its negative ∆Vq. In another hypothetical
explanation, a chairlike, achiral “π-complex” between two
The Cope rearrangement of rac-(Z,Z)-1 to rac-(E,E)-1 may
occur by way of a chair, two-axial transition region (Scheme
1). Again from the data at 69 °C in Table 6, fourth section, an
approximate value for the specific rate constant can be calculated
(k1 ) ∼1 × 10-6 s-1), which is quite comparable to that of the
non-Cope interconversion (∼0.5 × 10-6 s-1).
(34) The archetype is corrected for two increments of stabilization of
the educt by phenyl: 33.5 + 2 × 5.1 ) 43.7 kcal/mol. The effect of the
phenyl substitution on the transition region is then 43.7 - 21.3 ) 22.4 or
5.6 kcal mol-1 per phenyl group. Had the homolytic-colligative model
served as archetypal reference, the effect of the phenyl substitution on the
transition region would become 59.8 + 10.2 - 21.3 ) 48.7 or -12.2 kcal
mol-1 per phenyl group (incredibly high). Also, recall that ∆∆H ) 32.3 (
5.8 kcal mol-1, the difference in enthalpy of formation in solution at ∼250
°C (ESR) between compounds 1 and two (E,E)-1,3-diphenylallyl radicals,
is too much higher than the enthalpy of activation of racemization credibly
to admit the homolytic-colligative mechanism.
The interconversion meso-(E,Z)-1 T rac-(E,E)-1 is of the
one-axial boat type and is ∼8% as fast as the corresponding
one-axial chair interconversion rac-(E,Z)-1 T meso-(E,E)-1
(data in Table SI-1 and Figure SI-2).
The conversion meso-(Z,Z)-1 to meso-(E,E)-1, if a rear-
rangement of the Cope type at all, may occur as either a three-
axial chair or a two-axial boat. The rate constant from the single
point at 110 °C in the third section of Table 6 (k1 ) ∼13.4 ×
(35) Roth, W. R.; Staemmler, V.; Neumann, M.; Schmuck, C. Liebigs
Ann. 1995, 1061-1118.
(36) Compare allyl, pentadienyl (extra stabilization, -3.6 kcal mol-1),
and heptatrienyl (extra stabilization, -5.9 kcal mol-1).37 But note the values
preferred by Roth et al.: allyl, -14.5 kcal mol-1; cinnamyl, -19.2 kcal
mol-1 (∆ ) -4.7 kcal mol-1); 1,3-diphenylallyl, -26.2 kcal mol-1 (∆ )
-11.7 kcal mol-1).35
(33) Activation parameters for the rearrangement of the two (E,Z)-isomers
have been reported by Roth and Hunold26 based on data (their Table 9)
obtained in supercritical carbon dioxide starting with (E,E)-isomers, but
not the (E,Z)-isomers. Calculation of the ratios of the concentrations of
meso-(E,E)-1 and rac-(E,Z)-1 from their data reveals that, for all but the
first point at all temperatures, the ratios are equilibrium ratios and have no
kinetic value. As a consequence, the calculated activation parameters
ascribed to this rearrangement refer to the more slowly interconverting (E,E)-
isomer.
(37) Doering, W. v. E.; Sarma, K. J. Am. Chem. Soc. 1992, 114, 6037-
6043.
(38) Hrovat, D. A.; Beno, B. R.; Lange, H.; Yoo, H.-Y.; Houk, K. N.;
Borden, W. T. J. Am. Chem. Soc. 1999, 121, 10529-10537.
(39) Calculated ∆∆Hq: -8.5 kcal mol-1 and -3.3 kcal mol-1, respec-
tively.

200 J. Am. Chem. Soc., Vol. 122, No. 2, 2000
Doering et al.
explanation of the slower removal of diene at higher partial
pressures of oxygen is not clear, but a solvent-separated pair
might be considered, as might the consequences of an ever-
increasing concentration of oxygen as a component of the cage.
This study has revealed a phenomenon quite without prece-
dent in the saga of the Cope rearrangement. Its greater
significance, however, may lie in the opportunity the system
offers to gain a much more intimate view of processes that can
occur within a cage than has heretofore been possible.42
Experimental Section
General Methods. NMR spectra are recorded on a Bruker AM-
500 instrument (1H NMR, 500 MHz; 13C NMR, 126 MHz) in CDCl3
and benzene-d6, respectively, unless otherwise stated. Chemical shifts
are reported in ppm (δ) from tetramethylsilane (TMS) and coupling
constants, J, in hertz (Hz). Infrared (IR) spectra are recorded on a
Perkin-Elmer model 337 grating spectrophotometer and reported in
reciprocal centimeters (cm-1). Analytical gas chromatography (GC) is
effected on a Hewlett-Packard 5890-A instrument with an HP 3393A
recorder-digital integrator using J&W Scientific column (DB 1701: 7%
cyanopropyl/7% phenylpolysiloxane), 0.53 mm i.d. × 30 m. Mass
spectra are measured on JEOL SX-102 and AX-505 instruments, and
the latter is interfaced with a gas chromatograph. Melting points (mp)
are uncorrected.
Figure 6. In the upper row, a shearing or sliding pathway for the
conversion of rac-(E,E)-1 to meso-(E,E)-1 is depicted. In the lower
row, a topgraphically distinct conversion of chair to boat conformation
leads to the same configurational change.
planar, (E,E)-1,3-diphenylallyl radicals having weak bonding
between two end-on 1/2p-1/2p bonds accounts for the lower-
ing.40 Roth and Hunold propose van der Waals as the extra force
binding the two otherwise noninteracting free radicals.26
The non-Cope interconversion of the two (E,E)-isomers, as
we have seen, owes its visibility to a thermodynamic cover
provided by the +2.6-kcal mol-1 bias that markedly reduces
the equilibrium concentrations of kinetically favored Cope
involvements of (Z)-isomers; and a comfortably accessible rate
owing to its large energy of stabilization, which amounts to
meso- and rac-(E,E)-1,3,4,6-Tetraphenylhexa-1,5-diene [meso-
(E,E)-1 and rac-(E,E)-1]. These compounds are obtained by two
methods: one starting from benzalacetophenone (A); another starting
from 1,3-diphenylpropene (B).
Method A. To a stirred solution of benzalacetophenone (11 g, 0.053
mol, Aldrich) in 110 mL of dry ether cooled to -10 °C under argon,
lithium aluminum hydride (0.58 g, 10% molar excess) is added over a
15-min period. After addition of ethyl acetate (2 mL), followed by 5%
sulfuric acid (5 mL) and filtration, the ether layer is separated, washed
with water, dried over MgSO4, and concentrated in vacuo to a crude
product, which is crystallized from heptane to yield 10.1 g (91%) of
1,3-diphenyl-3-hydroxyprop-1-ene: mp 57.5-58.5 °C (lit.43 mp 57-
58 °C); 1H NMR 7.6-7.2 (m, 10H), 6.71 (d, 1H, J ) 15.8), 6.40 (dd,
1H, J ) 15.8, 6.9), 5.4 (br s, 1H), 2.1 (br s, 1H).
This alcohol (10 g in 90 mL methanol) is treated with 4 mL of
sulfuric acid (d 1.84) and left at room temperature overnight. The
reaction mixture is poured onto ice and extracted with ether. The ether
layer is washed with water, sodium bicarbonate, and water, dried over
MgSO4, and concentrated in vacuo to a residue, which is distilled at
0.6 mmHg (bp 120 °C) to give 15 g (78%) of 1,3-diphenyl-3-
methoxyprop-1-ene: 1H NMR 7.65-7.18 (m, 10H), 6.75 (d, 1H, J )
15.9), 6.43 (ddd, 1H, J ) 15.9, 7.0, 2.0), 4.92 (d, 1H, J ) 7.0), 3.49
(s, 3H).
In a slightly modified procedure of Bergmann and Ukai,15 a solution
of 1,3-diphenyl-3-methoxyprop-1-ene (7.5 g; 0.035 mol) in 10 mL of
tert-butyl methyl ether is added over a period of 10 min to a
mechanically stirred suspension of sodium (1.71 g, 2.0 molar equiv)
in tert-butyl methyl ether (90 mL, freshly distilled from benzophenone
ketyl) under argon in a 500-mL Morton flask cooled in an ice bath.
After having been warmed to room temperature and stirred overnight,
the dark red solution is treated with mercury (190 g), stirred intensively
for 26 h, and quenched with solid CO2. The supernatant liquid is
decanted, filtered through Celite, washed with water, dried over MgSO4,
and concentrated in vacuo to a colorless, crystalline residue (3.4 g),
which is shown by NMR to consist mainly of a mixture of meso- and
rac-(E,E)-1 (58:42), and some 1,3-diphenylpropene (vide infra).
Acidification of the aqueous extract and extraction with ether gives
0.6 g crude R-phenylcinnamic acid: mp 171-172 °C (lit.44 mp 173
°C) after recrystallization from heptane.
-57 kcal mol-1 vis-a`-vis butane (BDE, 87.8 kcal mol-1 41
or
)
-28.9 kcal mol-1 vis-a`-vis hexa-1,5-diene (BDE, 59.6 kcal
mol-1).12 A pair of kinetically independent, free radicals as
intermediary would have provided a simple, attractive rational-
ization; but trapping, ESR, high pressure, and crossover experi-
ments gave only partial, not full support to a homolytic-
colligative mechanism. Failing to find a concerted, energy-
lowering pathway to explain intramolecularity, a common
fallback invokes a so-called cage phenomenon as a means of
preventing kinetic separation by interposing a small barrier to
diffusion from the cage. If the conjecture of an achiral Cope-
like π-complex (Figure 6) as an intermediate is pursued, severe
geometrical readjustments are required to effect interconversion
of rac-(E,E)-1 and meso-(E,E)-1. One readjustment is a gliding
or shearing motion of one half versus the other, through which
C-1 ultimately becomes bonded to C-4′. Another readjustment
involves a rotation around the cylindrical axis of one of the
allylic components that transforms the rac-(E,E)-1 π-complex
into the boatlike π-complex collapsible into meso-(E,E)-1. Both
transmigrations would appear to pass through a nonbonded
region equivalent in energy to two free radicals, but largely, if
not completely, would be denied kinetic freedom by the energy
of diffusion out of the cage. In the somewhat arcane medium
of Roth and Hunold, the radicals had to some extent become
free and easily trappable by oxygen. What the third complex
might be that Roth and Hunold felt obliged to postulate as an
(40) Professor Weston Thatcher Borden has found that two rigidly planar
allyl radicals brought together in the usual chairlike conformation have a
bonding distance of ∼2.6 Å, and a bonding energy the magnitude of which
varies understandably with the level of theory applied in the calculation.
We express our gratitude for this calculation and permission to cite.
(41) Seakins, P. W.; Pilling, M. J.; Niiranen, J. T.; Gutman, D.;
Krasnaperov, L. N. J. Phys. Chem. 1992, 96, 9847-9855.
(42) Consider, for example, what compounds such as optically active
(R,R)- or (R,S)-(E,E)-1,4-diphenyl-3,6-di-p-tolylhexa-1,5-diene have to offer!
(43) Meerwein, H.; Schmidt, R. Liebigs Ann. 1928, 444, 221-238.
(44) Truett, W. L.; Moulton, W. N. J. Am. Chem. Soc. 1951, 73, 5913-
5915.

1,3,4,6-Tetraphenylhexa-1,5-dienes
J. Am. Chem. Soc., Vol. 122, No. 2, 2000 201
Method B. A stirred solution of 7 g of trans-1,3-diphenylpropene
[obtained according to Raunio and Bonner45 in 97% of purity (analytical
GC) after chromatography on neutral alumina (hexane)] in 180 mL of
anhydrous tetrahydrofuran (THF; freshly distilled from benzophenone
ketyl) is cooled to -30 °C under nitrogen and treated over a period of
15-20 min with 16.7 mL of 2.5-M n-BuLi. The deep-red solution of
the anion is stirred at -30 °C for 1.5 h and slowly transferred to a
vigorously stirred solution of nitrobenzene (9 g) in anhydrous THF
(120 mL) at 0 °C. After a few minutes, the dark brown reaction mixture
is quenched with methanol and concentrated in vacuo. Nitrobenzene
is removed by distillation at 0.5 mm to give 12.5 g (from 14 g of trans-
1,3-diphenylpropene) of a residue consisting of equal amounts of meso-
and rac-(E,E)-1.
Bruker AMX-300 instrument. Analytical gas-liquid chromatography
(GLC) is effected on a Hewlett-Packard 5890 instrument with a
Shimadzu recorder-digital integrator C-R3A; column C: silicon oil OV
1701 on fused silica (25 m) operated at oven temperature of 70 °C;
He. For measurement of densities, a Densimeter DMA 42 (Chempro)
is used.
Pressure Dependence of Thermal Racemization of Optically
Active (E,E)-1. Portions of ∼10 mL of a solution of (-)-(E,E)-1 in
70/30 n-hexane/2-propanol are placed in the 7-kbar vessel as already
described and heated to 44.3 ( 0.2 °C at the pressures indicated in
Table 4. At each pressure, at least six samples are taken at different
times, and their enantiomeric ratios determined by HPLC as already
described. A typical result (2.0 kbar) is included in Figure SI-3.
Pressure Dependence of Thermal Rearrangement of 2,5-Di-
phenylhexa-1,5-diene-1,6-13C (1,6) to 2,5-Diphenylhexa-1,5-diene-
3,4-13C (3,4). Solutions of 12 mg of (1,6) in 0.8 mL of toluene-d8 are
sealed in PTFE tubes, placed in the 7-kbar vessel, and heated at 75.1
°C for 6 h at the pressures indicated in Table SI-4. Analysis relies on
signals at δ ) 4.9 and 5.7 of H-1 and H-6 in (1,6) coupled to 13C,
whereas composite signals of H-1 and H-6 from (3,4) and (1,6) are
found at δ ) 5.2 and 5.4. A control experiment confirms that no
detectable rearrangement occurs during the heating or cooling period.
Concentration Dependence of the Interconversion of meso-
(E,E)-1 and rac-(E,E)-1. Two samples of pure meso-(E,E)-1 (40 and
4 mg, respectively) in toluene-d8 (each: 700 µL) are heated at 105 °C
for 1.5 and 3.0 h, respectively. The ratio of meso to racemic isomer in
For purification, crude reaction product is dissolved in hexane (1 g
per 10 mL) and left overnight at room temperature. The colorless filtrate
then consists of two types of crystals, separation of which is achieved
by fractional crystallization from methylene chloride-hexane (∼35:
65), assisted by manual separation of the more rapidly crystallizing
needles from more slowly crystallizing heavy octahedra. From the 12.5
g, for example, four recrystallizations furnished 5 g of the meso isomer
(purity >99%), 4 g of the racemic isomer (purity >99%), and 3.5 g of
unseparated mixture. Pure meso-(E,E)-1 (needles) has mp 138 °C: 1H
NMR 7.35-6.90 (m, 20H), 6.49-6.39 (m, 2H), 6.30-6.22 (m, 2H),
1
3.92-3.85 (m, 2H); H NMR (300 MHz, toluene-d8) 7.20-6.80 (m,
20H, H-arom), 6.34 (ddd, 2H, J2,1;5.6 ) 15.7, J2,3;5,4 ) 5.0, J2,4;5,3
)
2.1, H-2,5), 6.16 (d, 2H, J1.2;6.5 ) 15.7, H-1,6), 3.80 (m, 2H, J ) 5.0,
2.1, H-3,4); 13C NMR 55.2, 126.1, 126.5, 127.0, 128.3, 128.4, 128.6,
131.1, 131.9, 137.5, 142.4 (11 signals). Pure rac-(E,E)-1 (octahedra)
has mp 143 °C: 1H NMR 7.35-6.90 (m, 20H), 6.65-6.55 (m, 2H),
6.48-6.40 (m, 2H), 3.87-3.80 (m, 2H); 1H NMR (300 MHz, toluene-
d8) 7.20-6.80 (m, 20H, H-arom), 6.53 (ddd, 2H, J2,1;5.6 ) 15.7, J2,3;5,4
) 5.0, J2,4;5,3 ) 2.1, H-2,5), 6.35 (d, 2H, J1.2;6.5 ) 15.7, H-1,6), 3.78
(m, 2H, J ) 5.0, 2.1, H-3,4); 13C NMR 55.3, 126.1, 126.2, 127.1, 128.3,
128.4, 128.6, 131.3, 132.2, 137.5, 142.6 (11 signals). The mixture mp
of equal parts of meso- and rac-(E,E)-1 is 126.6-130.1 °C.
1
the product is determined by the H NMR signals (300 MHz) at 6.16
(2H, H-1,6, meso-(E,E)-1) and 6.53 (2H, H-2,5, rac-(E,E)-1) to be
85.7:14.3 after 1.5 h, 75.5:24.5 after 3.0 h (40-mg sample), 85.7:14.3
after 1.5 h, and 75.9:24.1 after 3.0 h (4-mg sample).
Kinetics of Thermal Rearrangement of meso- and rac-(E,E)-1.
Kinetic measurements are made generally following the procedure
described previously.35 Samples of 1 are prepared in benzene-d6 (∼0.028
M) containing 18-crown-6 ether as internal standard (∼0.00213 M) in
NMR tubes (no. 528 Pyrex), which are deaerated by three freeze-
thaw cycles and sealed in vacuo. Heating is accomplished in the vapor
of solvents boiling under reflux: ethyl acetate (77.1-77.6 °C);
cyclohexane (80.4-81.0 °C); trichloroethylene (87.1-87.5 °C); dioxane
(101.0-101.6 °C); toluene (110.0-110.7 °C); and pyridine (115.0-
115.5 °C). Variation in temperature is due to fluctuations in atmospheric
pressure, which is monitored periodically.
X-ray Crystallographic Structure of meso- and rac-(E,E)-1.
Details of the structure determinations are found in Supporting
Information (Item SI-1 and Figure SI-1).
Kinetics of Thermal Racemization of Optically Active rac-(E,E)-
1. The enantiomers of rac-(E,E)-1 are separated by HPLC on a chiral
amylose derivative: CHIRALPAK AD, Mallinckrodt Baker no. 7407-
00, 250 × 4.6 mm; flow, 1 mL/min at 22 bar; 70/30 n-hexane/2-
propanol. The UV detection is at 254 nm (Jasco UV-975). Polarimetric
detection is achieved with a Chiralizer IBZ Messtechnik GmbH.
Retention times (tR) of (-)-(E,E)-1 and (+)-(E,E)-1 are 4.6 and 6.2
min, respectively (see Figure SI-3), were found. Attempts to isolate
separate fractions by evaporation of solvents at ∼40 °C in vacuo led
to almost entirely racemized samples. For kinetic studies, samples in
the solvent are collected directly from HPLC separation, cooled
immediately to 0 °C, and used without further attempts at enrichment.
Portions of (+)-(E,E)-1 in 0.6 mL of 70/30 n-hexane/2-propanol are
sealed in evacuated glass ampules and heated at the temperatures given
in Table 3. During each run, six samples are removed and analyzed by
HPLC on the column just described. Specific rate constants, krac, are
calculated as first order, irreversible approach of enantiomeric excess
to zero: ee ) ([(+)-(E,E)-1] - [(-)-(E,E)-1])/([(+)-(E,E)-1] +
[(-)-(E,E)-1]).
For analysis, the tubes are removed, cooled, analyzed by NMR, and
returned to the vapor bath for further heating and analysis. This process
is continued until equilibrium has been established (9-10 half-lives).
1
Quantitative analysis by H NMR (500 MHz) is based on signals at
6.65-6.55 from rac-(E,E)-1 and 6.30-6.22 from meso-(E,E)-1.
Intensities of the composite signals at 6.65-6.39 and 3.92-3.80 are
used for verification, whereas the latter signal is compared with the
standard at 3.55 to determine recovery. Accumulation involves 32-64
scans with a 13.04-s interpulse delay, a relaxation delay of 9.77 s, and
an acquisition time of 3.27 s. Rate constants are evaluated by the least
squares program, NONLIN, based on the equation for reversible first-
order reactions: (x - xo)/(xe - xo) ) exp[-(k1 + k-1)t], where xo, xe,
and x are the mole fractions of the product at time zero, at equilibrium,
and at time t, respectively, and k1 and k-1 are rate constants for the
conversion of rac-(E,E)-1 to meso-(E,E)-1 and the reverse, respectively.
In the calculation, xo, xe and (k1 + k-1) are varied to achieve least sum
of the squares of the deviation in x. In a second approximation, the
values of xe are readjusted to conform to the best fit of the
thermodynamic parameters given by a plot of 1/T versus log K, the
rate constants then being reevaluated. The results are collected in Table
1 along with activation parameters calculated in the usual manner.
Influence of Pressure on the Rate of Interconversion of meso-
(E,E)-1 and rac-(E,E)-1. Method A. Two solutions, each of ∼40 mg
of pure meso-(E,E)-1 in 3 mL of anhydrous benzene-d6 and toluene-
d8, respectively, were prepared. Each solution was divided and
introduced into PTFE tubes that had been deactivated by prior treatment
with triethylamine. The sealed samples were heated under the conditions
Procedure for High-Pressure Studies. An autoclave is filled with
the pressure-transducing medium (a mixture of 1:1 isooctane/decalin).
The reactant is sealed in a poly(tetrafluoroethylene) (PTFE) tube, placed
in the autoclave, pressurized to 500 bar, heated to the desired
temperature, and then pressurized to the final pressure. The autoclave
is a 7-kbar vessel thermostated to (0.2 °C by an external oil bath, and
pressurized by a motor-driven press (Dieckers). One exit of the vessel
is connected to a valve equipped with a fine spindle, which allows
periodic removal of small samples of ∼600 µL from the 10-mL reactant
solution for analysis by HPLC. During the removal, pressure is
monitored and maintained by a computer-driven control device. In the
1
1
given in Table SI-2 and analyzed by H NMR as already described.
high-pressure studies, H NMR (300 MHz) spectra are recorded on a
1
New H NMR signals at δ ) 3.6, 4.3, and 4.1 assigned to 3-, 4-H of
(45) Raunio, E. K.; Bonner, W. A. J. Org. Chem. 1966, 31, 396-399.
meso- or rac-(E,Z)-1 and meso- or rac-(Z,Z)-1, respectively, with a

202 J. Am. Chem. Soc., Vol. 122, No. 2, 2000
Doering et al.
maximum intensity of 3% and 1%, respectively, were observed in
addition to the signals of meso- and rac-(E,E)-1.
mmol) and 85 mg of TEMPO (0.544 mmol, 7 molar equiv) in 3 mL of
toluene-d8. The NMR spectrum gives no indication of the presence of
trapped 1,3-diphenylallyl radical.
Method B. Two solutions of 100 mg each of pure meso-(E,E)-1 in
6 mL of anhydrous toluene-d8 and pure rac-(E,E)-1 in 6 mL of
anhydrous toluene-d8 were prepared. Each solution was divided, sealed
in deactivated PTFE tubes, and heated in a thermostated autoclave under
the conditions given in Table SI-2. The ratio, meso-(E,E)-1-to-rac-
(E,E)-1, of each sample was analyzed by 1H NMR as already described.
A control experiment using samples of both solutions showed that,
during the period of heating the autoclave from room temperature to
90.0 °C (1.5 h at 1500 bar) and during the period of cooling after the
reaction (1.5 h), no isomerization had occurred within the limits of 1H
NMR detection. From the product ratios starting either from meso-
(E,E)-1 or rac-(E,E)-1, the single-point, first-order specific rate
constants (k) in Table SI-2 were obtained by a Marquardt optimization
routine.46 The ∆Vq values were calculated from the nonlinear correlation,
ln(k)p ) a + bp + cp2, ∆Vq ) -bRT (R ) 83.14 cm3 mol-1 bar K-1).
ESR Measurements. ESR spectra are recorded on a Bruker ER-
420 X-band spectrometer that is equipped with a variable temperature
unit and is connected to a PC-based, data acquisition system. Typically,
samples are prepared by deaerating of 2 × 10-2 M solutions of meso-
(E,E)-1 in purified diphenyl ether in 4-mm o.d. quartz tubes. Radicals
are generated by heating the sealed sample tubes in the cavity of the
ESR spectrometer to temperatures in the range 200-300 °C. Further
experimental details are found in the Supporting Information (Item
SI-2). Hyperfine splitting constants are refined by computer simulation.
Radical concentrations are determined by numerical double integration
of the digitized, computer-stored spectra and comparison of the
integrated ESR signal of a calibrated concentration standard, recorded
under the same instrumental settings and taking into account the
temperature dependence of the volume of the solution and the
temperature dependence of the signal intensity according to the Curie
law.
Attempted Initiation by Azobisisobutyronitrile (AIBN). A tube
containing a solution of meso-(E,E)-1 (10 mg) in benzene-d6 (0.6 mL)
and 0.1 g of AIBN is carefully deaerated, sealed under vacuum, and
heated at 56.6 °C (refluxing acetone) for 13.5 h. The NMR spectrum
of the product is identical to that of the educt. This experiment is
repeated at 77 °C for 13.5 h. The NMR spectrum of the product shows
the presence of 10% rac-(E,E)-1, the same amount obtained on heating
meso-(E,E)-1 under the same conditions in the absence of AIBN.
Effect of Iodine on the Rate of Interconversion of rac-(E,E)-1
and meso-(E,E)-1. Two ∼10-mg samples, one of pure rac-(E,E)-1 and
the other containing 3 mg of I2 in toluene-d8 (each ∼500 µL), were
heated at 80 °C for 18 and 38 h, respectively, to give mixtures of rac-
(E,E)-1 and meso-(E,E)-1 [without I2: 88.6:11.4 (18 h) and 78.5:21.5
(38 h); with I2: 88.1:11.9 (18 h) and 77.4:22.6 (38 h)].
D. Thermal Rearrangements of meso-(E,E)-1 in Thiophenol. A
solution of meso-(E,E)-1 (89 mg, 0.23 mmol, purity >99%) in freshly
distilled thiophenol (6 mL) in a deaerated Pyrex tube sealed under
vacuum is heated at 110.6 °C for 13.5 h (10 half-lives). The bulk of
the solvent is removed (5 mmHg) to give a residue, an ether (10 mL)
solution which is washed with 5% NaOH and water, dried over MgSO4,
and concentrated in vacuo. The complicated NMR spectrum of the crude
product does not show signals corresponding to meso-(E,E)-1 or rac-
(E,E)-1. Flash chromatography on silica gel gives on elution with
hexane the following fractions: Diphenyl disulfide: 15 mg; mp 60.3
°C (lit.47 mp 58-60 °C); m/z: calcd for C12H10S2, 218; found, 218; 1H
NMR and Fourier transform (FT) IR spectra identical with those
reported in the literature;48 (E)-1,3-Diphenylpropene (DPP): 6 mg; calcd
for C15H14, 194; found, 194; 1H NMR (400 MHz, CHCl3) 7.4-7.0 (m,
10H), 6.37 (d, 1H, J ) 15.8), 6.30-6.23 (m, 1H), 3.46 (d, 2H, J )
6.6) (spectrum identical with lit.45 at 100 MHz). The purity of both
compounds is >99.9%, as determined by GLC [(column temperature
200 °C, He, 4 psi; tR: 11.9 min, diphenyl disulfide; 8.8 min DPP]. An
intermediate fraction (27 mg) consisting of a mixture of diphenyl
disulfide and DPP is eluted from the silica gel column. On chromato-
graphing (hexane), this fraction yields an additional 21 mg of DPP,
bringing the total to 27 mg.
Further elution with 2% diethyl ether-hexane gives a product (61
mg) corresponding to an addition product(s) of thiophenol to DPP;
m/z: calcd for C21H20S, 304, found, 304. The 1H NMR spectrum shows
a group of aromatic protons at 7.5-6.8 and aliphatic protons as seven
distinct groups of multiplets between 2.2 and 3.9 in a ratio 3.06:1, which
corresponds to that expected for the “addition product”, 1,3-diphenyl-
2-thiophenylpropane. If the calculated amount of DPP in this fraction
is 39 mg, the total amount accounted for is 66 mg (74%). The GLC-
mass spectroscopy (MS) of this addition product (100% methylpoly-
siloxane: column DB1, 15 m, He 8 psi, 100-260 °C) shows six (not
very well resolved) peaks with similar mass spectra, all containing the
molecular ion, m/z 304, but no peak at m/z 486 corresponding to addition
of thiophenol to meso-(E,E)-1.
Further experiments with thiophenol may be found in Item SI-3.
E. 9,10-Dihydroanthracene. A mixture of meso-(E,E)-1 (25 mg,
0.06 mmol) and 9,10-dihydroanthracene (353 mg, 1.96 mmol, 32 molar
equiv.) in 1 mL of toluene-d8 is heated at 106-107 °C for 10 h. After
separation of most of the 9,10-dihydroanthracene by flash chromatog-
raphy (hexane), elution with hexane:2% ether affords meso- and rac-
(E,E)-1 (59:41). No anthracene or (E)-1,3-diphenylpropene can be
detected by GLC analysis.
F. Phenol. A similar experiment using meso-(E,E)-1 (12.3 mg, 0.03
mmol) and phenol (92 mg, 0.98 mmol) affords meso- and rac-(E,E)-1
(58:42), but no (E)-1,3-diphenylpropene.
Trapping Experiments. A. Oxygen. A solution of 15 mg of meso-
(E,E)-1 in 1.5 mL of toluene-d8 containing 1 mg of 18-crown-6 as
internal standard is heated under reflux (oil bath) for ∼5 h while a
slow stream of oxygen is passed through the refluxing solution. The
NMR spectrum of the reaction product shows the usual mixture of
meso- and rac-(E,E)-1 in the ratio 54.0:46.0; recovery as determined
by the ratio of product to internal standard at t ) 0 is 1.56 and at t )
5 h is 1.58.
B. 2-Methyl-2-nitrosopropane (Nitroso-tert-butane). A solution
of meso-(E,E)-1 (19.3 mg, 0.05 mmol, purity >99.6%) and tert-BuNO
(43.5 mg, 0.5 mmol, 10 equiv) in 1 mL of dry toluene-d8 is placed in
a Pyrex tube, deaerated, sealed under vacuum, and heated at 110.6 °C
(toluene vapor) for 13.5 h. The solvent and excess trapping agent are
removed under vacuum until a constant weight is achieved. The NMR
spectrum of the reaction product (18.5 mg; recovery, 95.9%) shows
only meso- and rac-(E,E)-1 (51:49), and no signals for methyl protons
corresponding to an adduct of 1,3-diphenylallyl radical and 2-methyl-
2-nitrosopropane.
Crossover Experiment: Rearrangement of a Mixture of meso-
(E,E)-1 and meso-(E,E)-2. (E,E)-1,3,4,6-Tetra-p-tolylhexa-1,5-diene
[(E,E)-2] is synthesized by method A used for the preparation of 1.
Experimental details are given in Item S-4. A 1.5% solution of
equimolar amounts of meso-(E,E)-1 (2.5 mg, purity >99.9%) and the
less soluble diastereomer, meso-(E,E)-2 (2.9 mg, purity >99.9%) in
toluene-d8 is divided between two tubes, one of which is deaerated,
sealed under vacuum, and heated at 110 °C (toluene vapors) for 13.5
h and the other of which is left unheated as control. Mass spectra of
the two samples are recorded by the field desorption method under
identical conditions. The unheated sample shows peaks at m/e 386
[(E,E)-1] and 442 [(E,E)-2], whereas the heated sample shows, in
addition to peaks at m/e 386 (relative abundance, 13%) and 442 (relative
abundance, 14%), a peak at m/z 414 (8%) corresponding to 1,3-
diphenyl-4,6-di-p-tolylhexa-1,5-diene; m/z: calcd for C32H30, 414. The
relative intensities of the three peaks (0.93:0.57:1.00) differ from the
statistically expected (1.00:2.00:1.00).
C. 2,2,6,6-Tetramethylpiperidinyl Oxyl (TEMPO). The reaction
just described is repeated exactly with 30 mg of meso-(E,E)-1 (0.078
(47) Stenhouse, J. Proc. R. Soc. London 1869, 17, 63. Yiannios, C. N.;
Karabinos, J. V. J. Org. Chem. 1963, 28, 3246-3248.
(48) Aldrich Library of FT IR Spectra, 1st ed.; Aldrich Chemical
Company; vol. 1, p 1183c. Aldrich Library of NMR Spectra, 2nd ed.; Aldrich
Chemical Company, 1983; vol. 1, p 973D.
(46) 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.

1,3,4,6-Tetraphenylhexa-1,5-dienes
J. Am. Chem. Soc., Vol. 122, No. 2, 2000 203
Photoisomerization of (E,E)-1 to (E,Z)-1 and (Z,Z)-1. A. With
Benzophenone as Sensitizer. Dilute solutions of rac-(E,E)-1 and meso-
(E,E)-1 in benzene-d6 containing freshly recrystallized benzophenone
(5-10 mol %) are irradiated with two 375-watt sun lamps at ∼15 °C.
Progress of the reaction is followed by NMR (vide infra). Results are
given in Table 5.
B. General Procedure. Dilute (0.5%) solutions of rac-(E,E)-1 and
meso-(E,E)-1, freshly recrystallized from hexane, are irradiated in dry
benzene containing 5-10% benzophenone under nitrogen at ∼15 °C
(water cooling) with two 375-W sun lamps. Irradiation with a high-
pressure mercury lamp does not afford isolable products because of
extensive polymerization. After removal of benzene in vacuo, the
residue is crystallized from hexane at 4 °C overnight to remove most
of the recovered (E,E) educt. The mother liquor is passed through a
short silica gel column (elution with hexane) to remove benzophenone.
Additional educt is usually removed by concentration and a second
crystallization. Four further examples including NMR data are described
in detail in Item S-5.
Thermal Rearrangement of a Mixture of rac-(Z,Z)-1 and rac-
(E,Z)-1. A dilute solution of a mixture enriched in rac-(Z,Z)-1 and
rac-(E,Z)-1 in benzene-d6 is placed in a NMR tube, deaerated, sealed
under vacuum, and heated in hexane vapors (69 °C). The progress of
the reaction is monitored by NMR. Rate constants calculated from the
data in Table 6 for a first-order irreversible reaction (kc,t ) 1.3 × 10-5
s-1; kc,c ) 1.9 × 10-6 s-1) indicate that the Cope rearrangement of
rac-(Z,Z)-1 occurs seven times slower than that of rac-(E,Z)-1.
-58.8° in meso-(E,E)-1 and 62.4° in rac-(E,E)-1. In contrast,
the orientation of the double bonds relative to the central bond
differ significantly, being 121.9° in meso-(E,E)-1 and 113.2°
in rac-(E,E)-1. Even more pronounced are the differences in
the torsional angles of the phenyl groups attached to the double
bonds, being 11.2° in meso-(E,E)-1 and 23.7° in rac-(E,E)-1.
This major difference is almost certainly caused by differences
in steric congestion. Thus, in meso-(E,E)-1 and rac-(E,E)-1,
the double bonds are 1.329(1) (bond lengths in Å units) and
1.313(3), respectively, whereas the single bonds are 1.466(1)
and 1.477(3), respectively.
These features in the styrene fragments can be attributed to
the better conjugation in the more nearly coplanar arrangement
of the double bonds and the phenyl rings in meso-(E,E)-1, which
would shorten the single bond and lengthen the double bond.
Because comparisons within one system are likely to avoid most
of the systematic errors and be more significant, we prefer to
compare ratios of the lengths of single-to-double bonds. In meso-
(E,E)-1 and rac-(E,E)-1, these are 1.1031(13) and 1.1249(33),
respectively. To explore the generality of this finding, we
correlated this ratio to the torsional angles in 2126 vinyl
fragments found in the Cambridge Structural Database.49 The
result is shown in Figure SI-4 and subjected to a linear regression
to obtain a rough idea of the dependency. The ratio of the bond
lengths, r(CsC)/r(CdC), is 1.082 for a torsion angle of 0° and
1.140 for 90°. The double bond length is less sensitive than the
single bond, which is also shown in a theoretical ab initio study.
An energy surface scan for styrene, with the method/basis set
combination B3LYP/6-311G(d,p)50,51 and full geometry opti-
mizations in 10° steps for the vinyl torsion angle, estimated the
energy difference at 0° and 90° to be 3.9 kcal mol-1. The
dependence of bond length ratio on torsion angle is given in
Figure SI-5. At torsion angles of 0° and 90°, the ratios r(Cs
C)/r(CdC) are 1.102 and 1.120, respectively.
Acknowledgment. W.v.E.D. acknowledges support of this
investigation by the National Science Foundation, Grants CHE-
88 16186, 91 23207 and 94 11248; and by the Norman Fund in
Organic Chemistry, Harvard University, in memory of Ruth
Alice Norman Weil Halsband. Funding of the Harvard Univer-
sity Mass Spectroscopy Laboratory by the National Institutes
of Health (RR06716) and the National Science Foundation (CHE
90 20043) is gratefully acknowledged. R.B. and F.-G.K. express
their thanks to the Deutsche Forschungsgemeinschaft, the
Ministry for Science and Research of the Land Nordrhein-
Westfalen, and the Fond der Chemischen Industrie for support.
We thank Professor Dr. H. W. Steglich and Dipl.-Chem. M.
Schneider of Universita¨t Mu¨nchen for recordings of 600-MHz
1NMR spectra, M. Kirchner for searching the Cambridge
Structural Database, and Dr. A. H. Maulitz for ab initio
calculations.
Supporting Information Available: Various tables, figures,
and items as indicated throughout the text are available (PDF).
This material is available free of charge via the Internet at
http://pubs.acs.org.
JA993417H
Appendix
(50) Becke, A. D. Phys. ReV. A 1988, 38, 3098-3100. Parr, R. G.; Yang,
W. Density-Functional Theory of Atoms andMolecules; Oxford University
Press: New York, 1989. Becke, A. D. J. Chem. Phys. 1993, 98, 1372,
5648-5652. Stephens, P. J.; Devlin, F. J.; Chabalowsky, C. F.; Frisch, M.
J. J. Phys. Chem. 1994, 98, 11623.
(51) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Gill, P. M. W.;
Johnson, B. G.; Robb, M. A.; Cheeseman, J. R.; Keith, T.; Petersson, G.
A.; Montgomery, J. A.; Raghavachari, K.; Al-Laham, M. A.; Zakrzewski,
V. G.; Ortiz, J. V.; Foresman, J. B.; Peng, C. Y.; Ayala, P. Y.; Chen, W.;
Wong, M. W.; Andres, J. L.; Replogle, E. S.; Gomperts, R.; Martin, R. L.;
Fox, D. J.; Binkley, J. S.; Defrees, D. J.; Baker, J.; Stewart, J. P.; Head-
Gordon, M.; Gonzalez, C.; Pople, J. A. Gaussian 94, Revision B.2; Gaussian,
Inc.: Pittsburgh, PA, 1995.
The orientation of the phenyl groups attached to the central
atoms is quite similar in both molecules: the torsion angle is
(49) In the version of CSD, October 1997, with 175 093 entries,
compounds were extracted with a vinyl group attached to a carbon atom
having two ‘aromatic’ bonds to C, N, O, and S, the primary sp2-carbon
atom of the vinyl group bonded to a hydrogen atom only, and the secondary
sp2-carbon atom left free. Further restrictions included only those structures
with an R value of <10% and C-C esd values of <0.01 Å. The search
was performed with the 3D Search and Research Using the Cambridge
Structural Database: Allen, F. H.; Kennard, O. Chemical Design Automation
News 1993, 8, 1831-1837.