Methyl 1,3-diphenylbicyclo[1.1.0]butane-2-exo-carboxylate. New example of the thermal inversion of bicyclobutane system

Article abstract of DOI:10.1134/S1070428012080027

A fact of a reversible thermal inversion of exo- and endo-isomers of methyl 1,3-diphenylbicyclo[1.1.0] butane-2-carboxylate was established experimentally. The equilibrium constant of the process at 126°C is 14.2 with endo-isomer prevailing. Using DFT/PBE/L22 method the geometry of the isomers was optimized and also the geometry of the previously studied related exo,exo- and endo,endo-isomers of dimethyl 1,3-diphenylbicyclo[1.1.0] butane-2,4- dicarboxylate. The energy barrier of these mutual conversions was estimated. Pleiades Publishing, Ltd., 2012.

Full text of DOI:10.1134/S1070428012080027

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2012, Vol. 48, No. 8, pp. 1041−1046. © Pleiades Publishing, Ltd., 2012.
Original English Text © V.V. Razin, P.S. Petrov, V.A. Vasin, 2012, published in Zhurnal Organicheskoi Khimii, 2012, Vol. 48, No. 8, pp. 1045−1050.
Methyl 1,3-Diphenylbicyclo[1.1.0]butane-2-exo-carboxylate.
New Example of the Thermal Inversion
of Bicyclobutane System
V. V. Razina, P. S. Petrovb, and V. A. Vasinb
aSt. Petersburg State University, Universitetsky pr.26, St. Petersburg, 198904 Russia
bOgarev Mordvinian State University, Bolshevistskaya ul., 68, Saransk, 430005 Russia
Received February 16, 2012
Abstract—Afact of a reversible thermal inversion of exo- and endo-isomers of methyl 1,3-diphenylbicyclo[1.1.0]
butane-2-carboxylate was established experimentally. The equilibrium constant of the process at 126°C is 14.2
with endo-isomer prevailing. Using DFT/PBE/L22 method the geometry of the isomers was optimized and also the
geometry of the previously studied related exo,exo- and endo,endo-isomers of dimethyl 1,3-diphenylbicyclo[1.1.0]
butane-2,4-dicarboxylate. The energy barrier of these mutual conversions was estimated.
DOI: 10.1134/S1070428012080027
Up till now a single case is described of a reversible
thermal inversion of the bicyclobutane system which has
been observed at 120–140°C in compounds I and II [1–3].
This process requires a rupture of the central C1–C3 bond.
tion energy of the bicyclobutane-butadiene isomerization
[6]. Unlike the bicyclobutanes with tetrahedral carbon
atoms in the positions 2 and 4, which are just the object of
this study, the bicyclobutane with a trigonal carbon atom
in the position 2, namely 1,3-di(tert-butyl)bicyclo[1.1.0]
butan-2-one undergoes the inversion already at 30°C,
whose barrier measured experimentally by dynamic
1H NMR spectroscopy is 16.7 kcal mol–1 [7].
CO2R
CO2R
Ph
Ph
CO2R
RO2C
Ph
Ph
Obviously the phenyl substituents in the nodal posi-
tions of bicyclobutanes I and II facilitate the opening of
the C1–C3 bond at the expense of the benzyl resonance
favoring the inversion process compared with the isom-
erization into the butadiene derivative, which actually
occurs with these compounds only at a higher temperature
(180°C) [1].
Ia, IIa
Ib, IIb
R = Me (I), Et (II).
For the isomerization Ia ⇄ Ib the equilibrium
constanst (K 1.40 ± 0.07) and activation parameters
(ΔH≠ 26 ± 2 kcal mol–1, ΔS≠ 9 ± 4 e.u.) were evaluated
using NMR spectroscopy [3].
Looking for the other bicyclobutane derivatives ca-
pable of the thermal inversion we turned to compound
IIIb. It was first synthesized in [8] by the cleavage of
tricyclopentanone IV with sodium methylate, and later
it was obtained in [9] at the thermal decomposition of
a derivative of 2,3-diazabicyclo[3.1.0]-hex-2-ene (V).
The configuration was assigned to compound IIIb based
on the Masamune method of its synthesis. Stereoisomer
IIIa was unknown.
The absence of other examples of bicyclobutane
system inversion is due to the proceeding of all known
cases of the thermal isomerization of the bicyclobutane
compounds by the more feasible route to the formation
of 1,3-butadiene derivatives via a concerted rupture
of two side C–C bond with the retention of the central
C1–C3 bond [4]. Various calculation methods estimate
the inversion barrier of the bicyclo[1.1.0]butane proper
from 30 to 90 kcal mol–1. The calculation by the method
GVB/6-31G(d) estimated the value of the barrier at
50.0 kcal mol–1 [5] exceeding by 10 kcal mol–1 the activa-
We prepared monoester IIIb in the crystalline state
by Komendantov procedure and investigated its thermal
1041

RAZIN et al.
CO2Me
1042
O
CO2Me
Ph
Ph
150oC
MeONa
MeOH
N
_N2
Ph
N
Ph
Ph
Ph
IIIb
V
IV
relative stability of stereoisomers the geometry optimiza-
tion of these structures and for the sake of comparison
also of a model structure of the known [11] 1,3-diphe-
nylbicyclo[1.1.0]butane (VI) was performed by DFT
method. The perspective appearance of the most feasible
conformations of the compounds is presented in Fig. 1.
The search for the structures was carried out using mo-
lecular mechanics methods by the program ChemAxon
MarvinBeans [12]. The selected characteristics of the
bicyclobutanes in question are given in the table. It turned
out that the planes of the phenyl rings in compound VI
are strictly orthogonal to the plane passing through the
atoms C5C3C1C5’. We regarded this position as standard
and characterized the positions of the phenyl rings at
the atoms C1 and C3 in compounds Ia, Ib and IIIa, IIIb
by the angles of the deviation from the standard plane
φ1 and φ2 respectively. We also present in the table the
corresponding parameters of compounds Ia, Ib that we
have borrowed from the experimental data obtained by
XRD analysis of single crystals of these compounds [13].
The geometry characteristics calculated for the gas phase
are in general close to those experimentally measured
indicating the sufficient level of the quantum-chemical
calculations and makes it possible to discuss the details of
the structure and find the difference in the structures I and
III. Some distinctions may be attributed to the features
of the crystal packing of the molecules.
stability. Boiling the sample in octane (30 min, 126°C) led
to the formation of a mixture of the initial bicyclobutane
IIIb and its diastereomer IIIa in the ratio 93.4 : 6.6.
Compound IIIa was isolated by column chromatography
on silica gel as an oily substance that failed to crystallize.
The thermolysis of bicyclobutane IIIa under the same
conditions resulted in the same mixture of compounds
IIIa, IIIb in the same ratio. Thus the equilibrium
constant K of the isomerization IIIa ⇄ IIIb proved to
be 14.2 ± 0.2, by an order of magnitude larger than the
isomerization constant Ia ⇄ Ib.
CO2Me
Ph
126oC
Ph
MeO2C
Ph
Ph
IIIa
IIIb
Stereoisomeric bicyclobutanes IIIa, IIIb were char-
1
acterized by the H and 13C NMR spectra. Therewith
the comparison of their 1H NMR spectra confirmed the
adequacy of the configuration assignment. In particular,
only in the spectrum of the endo-isomer IIIb the signals
of exo-protons H2 and H4 were split due to the long-range
spin-spin coupling with a constant 4J 4.3 Hz (W-rule [10]).
In contrast, all the ring protons of the exo-isomer IIIa give
rise to singlets because of a small (0–1.0 Hz) geminal
coupling constant characteristic of bicyclobutanes and
the lack of long-range spin-spin coupling. The assignment
performed is consistent with the strong difference in the
chemical shifts of H2 protons of the stereoisomers: In
compound IIIa the endo-proton H2 occurs in the region
of the magnetic shielding of te opposite three-carbon
ring, and in compoundand IIIb the exo-proton H2 suffers
a deshielding due to the rapproachement of the phenyl
substituents.
The most important feature of structures Ib and IIIb
is the orientation of the phenyl rings close to that in
bicyclobutane VI as show the small vlues of angles φ1
and φ2 (see the table). Therewith any steric interactions
are absent in these compounds both between the phenyl
groups proper and between the phenyl groups and exo-
H2,4 atoms. Just this orientation of the phenyl rings is
the most favorable for the conjugation between them
transferred by the “banana” C1–C3 bond and consisting
of the overlapping of nearly pure p-atomic orbitals [14].
Therefore the interconversions of compounds IIIa,
IIIb that we have performed are a new example of the
thermal reversible exo,endo-isomerization in the bicy-
clobutane series.
In order to reveal the features of the structure of
bicyclobutanes Ia, Ib and IIIa, IIIb and to estimate the
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 8 2012

METHYL 1,3-DIPHENYLBICYCLO[1.1.0]BUTANE-2-exo-CARBOXYLATE.
1043
Fig. 1. Perspective view of molecules Ia, Ib, IIIa, IIIb, VI. Hydrogens atoms are not shown.
The experimental confirmation of the existence of the
conjugation between two phenyl groups in compounds Ib,
IIb, IIIb, IV was obtained by their UV spectra possessing
a strong absorption in the long-wave region (~270 nm,
lgε ~4.0) [3, 8, 15–17] close to the absorption region of
the stilbene chromophore.
the standard are considerably larger than in monoesters
IIIa, IIIb. This is evidently due to essentially greater
steric interactions involving two methoxycarbonyl groups
in compounds Ia, Ib than in monoesters IIIa, IIIb (see
the table).
The changes in the length and order of the bond C1–
C3are also of interest. In exo-isomer IIIa and especially in
the exo,exo-isomer Ia these values are essentially smaller
than in compound VI, whereas in the endo,endo-isomer
Ib and especially in the endo-isomer IIIb the deviations
from the standard are insignificant. The side bonds in
the bicyclobutanes of the “b” configuration are notably
shorter of the same bonds in the diastereomers “a” (see
the table). Methoxycarbonyl groups in compounds Ia,
IIIa, IIIb are materially normal to the planes of the cy-
clopropane rings. In endo-isomer Ib the methoxycarbonyl
groups are turned to opposite dides with respect to each
other and form an angle of ~53° to the planes of the three-
membered rings (see angles β and γ in the table). This
orientation of the groups in compound Ib is the result
of their strong reciprocal repulsion, and it destabilizes
the molecule. At the same time in the monoester IIIb
In compounds Ia and IIIa the phenyl rings are turned
to the opposite sides with respect to the plane C1C3C5C5'
impeding their conjugation through the central bicyclobu-
tane bond C1–C3. The absence of the conjugation between
the phenyl rings in compounds Ia and IIIa is indicated by
the lack of the long-wave absorption in the UV spectrum
[15–17]. The reason of this orientation consists in the stric
interactions between the ortho-hydrogens of the phenyl
groups and the exo-methoxycarbonyl groups.
Another feature distinguishing the endo- and exo-
isomers of compounds under consideration is the con-
siderable difference in the values of the α angles. The
bicyclobutane fragment in exo-isomers Ia and IIIa is
somewhat flattened as compared with compound VI
whereas in the endo-isomers Ib, IIIb it is more convo-
luted. Therewith in diesters Ia, Ib the deviations from
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 8 2012

RAZIN et al.
1044
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 8 2012

METHYL 1,3-DIPHENYLBICYCLO[1.1.0]BUTANE-2-exo-CARBOXYLATE.
1045
the destabilizing steric interaction of the CO2Me group
with the endo-proton H4 is significantly less. Therefore
it is possible to conclude that the relative stability of
monoester IIIb should be higher than that of diester Ib.
In each pair of diastereomers the endo-isomer “b”
proved to be more stable than the exo-isomer “a” (see the
table). However the energy difference of the diastereomers
of diester I (ΔΕ 0.49 kcal mol–1) is notably less than that
of the diastereomers of monoester III (ΔΕ 3.29 kcal mol–1)
in good agreement with the experimental data.
We applied the DFT method to the study of the en-
ergy profile of the experimentally observed inversion of
the bicyclobutane system in compounds I and III, and
of the hypothetical inversion in compound VI and in
unsubstituted bicyclobutane VII. The structural features
of the corresponding transition states TS1–TS4 were
revealed. The energy barriers were evaluated along IRC
procedure. The results are presented in the table. In the
transition states TS1–TS3 the planes of the phenyl rings
turned out to be orthogonal to the plane formed by the
atoms C5C3C1C5’. This structure is favorable for the
conjugation of the rings through the weakened central
bicyclobutane bond C1–C3 as is seen from the distribu-
tion of the electron density of HOMO of the carbon at-
oms of these intermediates (Fig. 2). In all likelihood the
inversion in bicyclobutanes I, III, VI proceeds without
a compleate cleavage of the central C1–C3 bond as show
the values of the interatomic distances C1–C3 and the
nonzero order of this bond in the corresponding transi-
tion states (see the table). On the contrary, the transition
state TS4 is a biradical as shows the localization of the
electron density of HOMO exclusively on the atoms C1
and C3 (Fig. 2), cf. [18].
Fig. 2. Electron density distribution of HOMO in the transition
states TS1–TS4 according to quantum-chemical calculation.
The shown part of molecular orbital is described with the wave
function with the positive sign.
spectrometer Bruker AC-300 (300.130 and 75.468 MHz
respectively) in CDCl3. The conditions of analytical
TLC were as follows: adsorbent Silufol UV-254, eluent
hexane–ethyl ether, 5:1, development in iodine chamber.
The column chromatography was performed using silica
gel 40/100μ.
The search for the most stable conformations of com-
pounds Ia, Ib, IIIa, IIIb, VI was carried out applying
the methods of molecular mechanics along the program
ChemAxon MarvinBeans [12]. The obtained structures
were further optimized using MOPAC2009 program [19]
in the RM1 approximation [20]. The final calculation of
structures and also the optimization of the geometry of
the stationary points (minima and transition states) on
the potential energy surface and the IRC procedure was
performed by DFT method (functional PBE [21], basis
L22 [22]) using PRIRODAsoftware [23]. The correspon-
dence of the maximum point to the transition state was
confirmed by the presence of one imaginary frequency
in the Hessian [53.66i (TS1), 124.37i (TS2) cm–1]. The
calculation and visualization of the electron density of
the molecular orbital was done along MOLEKEL pro-
gram [24].
According to the calculation the energy of TS4 by
14 kcal mol–1 exceeds the energy of TS3 which confirms
the considerable assistance to the thermal inversion of the
bicyclobutane system of the introduction of the phenyl
groups into the nodal positions of the bicyclobutane.
The calculation indicates also that the introduction of the
methoxycarbonyl groups into the positions 2 and 4 of the
1,3-diphenylbicyclobutane also results in the decrease of
the inversion barrier, namely, the energies of TS1 and TS2
are less by the energy than TS3 by 4.8 and 2.0 kcal mol–1
respectively.
Methyl-1,3-diphenyl-2-endo-bicyclo[1.1.0]butan-
ecarboxylate (IIIb) was obtained by procedure [9], mp
74–75°C (mp 75°C [9]), Rf 0.25. H NMR spectrum,
δ, ppm: 2.70 d (1H, endo-H4, 2J 1.4 Hz), 2.96 d.d (1H,
exo-H4, 2J 1.4, 4J 4.3 Hz), 3.78 s (3H, OMe), 4.04 d (1H,
EXPERIMENTAL
1
Elemental analysis was carried out on a CHN-analyzer
HP-185C. 1H and 13C NMR spectra were registered on a
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 8 2012

RAZIN et al.
1046
exo-H2, 4J 4.3 Hz), 7.11–7.28 m (10H, 2Ph). 13C NMR
spectrum, δ, ppm: 31.4 (C1,3), 35.1 (C4), 46.7 (C2), 51.7
(OMe); 125.3 (4C), 126.2 (2C), 128.3 (4C), 133.8 w
(Carom); 170.8 w (C=O).
5. Nguyen, K.A., Gordon, M.S., and, Boatz, J.A., J. Am.
Chem. Soc., 1994, vol. 116, 9241.
6. Frey, H.M. and Stevens, I.D.R., Trans. Faraday, Soc., 1969,
vol. 61, p. 90.
7. Rauk, A., Sorensen, T.S., and Sun, F., J. Am. Chem. Soc.,
1995, vol. 117, 4506.
8. Masamune, S., Tetrahedron Lett., 1965, p. 945.
9. Komendantov, M.I., Bekmukhametov, R.R., and
Novinskii, V.G., Zh. Org. Khim., 1976, vol. 12, p. 801.
10. Barfield, M. and Chakrabarti, B., Chem. Rev., 1969, vol. 69,
p. 757.
Reversible thermal isomerization of compounds
IIIa, IIIb. A solution of 30 mg of endo-bicyclobutanea
IIIb in 1.0 ml of octane was boiled under an argon
atmosphere for 30 min. The solvent was evaporated in
a vacuum, the ratio of isomers IIIa, IIIb in the residue
1
was determined from the H NMR spectrum. The
11. Jain, R., Sponsler, M.B., Coms, F.D., and Dougherty, D.A.,
J. Am. Chem. Soc., 1988, vol. 110, p. 1356.
12. MarvinBeans, 5.3.7, www, http://www.chemaxon.com/
13. Gassman, P.G., Greenlee, M.L., Dixon, D.A., Richtsmeier,
S., and Gougoutas, J.Z., J. Am. Chem. Soc., 1983, vol. 105,
p. 5865.
14. Newton, M.D. and Schulman, J.M., J. Am. Chem. Soc.,
1972, vol. 94, p. 767.
15. Razin, V.V., Maevskaya, E.I., and Komendantov, M.I.,
Voprosy stereokhimii (Stereochemistry Problems), Kiev:
Izd. Kiev. Univ. 1971, vol. 1, p. 22.
16. D’yakonov, I.A., Razin, V.V., and Komendantov, M.I., Zh.
Org. Khim., 1972, vol. 8, p. 54.
17. D’yakonov, I.A., Razin, V.V., and Komendantov, M.I.,
Tetrahedron Lett., 1966, p. 1127.
18. Pranata, J. and Dougherty, D.A., J. Phys. Org. Chem., 1989,
vol. 2, p. 161.
19. Stewart, J.J.P., MOPAC2009. Stewart Computational
Chemistry, version 10.028W, www, http://www.openmopac.
net/
experiment was repeated three times, and the equilibrium
constant K(endo/exo) = 14.2 ± 0.2 was determined. The
same value was obtained in similar experiments with exo-
isomer IIIa; here in each run ~10 mg of the substance
was used. The longer heating (75 min) did not change the
ratio of the endo- and exo-isomers.
Methyl-1,3-diphenyl-2-exo-bicyclo[1.1.0]butan-
ecarboxylate (IIIa) was isolated by chromatographic
separation of the product of the thermolysis of endo-
isomer IIIb. Oily substance, Rf 0.29. 1H NMR spectrum,
δ, ppm: 1.32 s (1H, endo-H4), 2.12 s (1H, exo-H4), 2.21 s
(1H, endo-H2), 3.63 s (3H, OMe), 7.27–7.36 m (10H,
2Ph). Cпeктp ЯMP 13C NMR spectrum, δ, ppm: 28.8
(C1,3), 33.2 (C4), 44.9 (C2), 51.4 (OMe); 126.7 (2C),
128.1 (4C), 128.6 (4H), 132.7 w (Carom); 167.6 w (C=O).
Found, %: C 81.92; H 6.22. C18H16O2. Calculated, %:
C 81.79; H 6.10.
20. Rocha, G.B., Freire, R.O., Simas,A.M., and Stewart, J.J.P.,
J. Comp. Chem., 2006, vol. 27, p. 1101.
REFERENCES
21. Perdew, J.P., Burke, K., and Ernzerhof, M., Phys. Rev. Lett.,
1996, , vol. 77, p. 3865.
1. D’yakonov, I.A., Razin, V.V., and Komendantov, M.I.,
Tetrahedron, Lett., 1966, p. 1135.
22. Laikov, D.N., Chem. Phys. Lett., 2005, vol. 416, p. 116.
23. Laikov, D.N., Chem. Phys. Lett., 1997, vol. 281, p. 151;
Laikov, D.N. and, Ustynyuk, Yu.A., Izv. Akad. Nauk, Ser.
Khim., 2005, p. 804.
2. D’yakonov, I.A., Razin, V.V., and Komendantov, M.I., Zh.
Org. Khim., 1969, vol. 5, p. 386.
3. Woodward, R.B. and, Dalrymple, D.L., J. Am. Chem. Soc.,
1969, vol. 91, p. 4612.
4. Hoz, S., The Chemistry of the Cyclopropyl Group, Patai,
S. and Rappoport, S., Eds, Chichester: Wiley, 1987.
24. Varetto, U., MOLEKEL5.4; Swiss National Supercomputing
Centre: Manno (Switzerland).
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 8 2012