Interplay of theory and experiment: Reversal of the torquoselectivity of the electrocyclic ring opening of 3-acetylcyclobutene by a Lewis acid

Article abstract of DOI:10.1021/jo951047j

Theoretical predictions, accompanied by firm experimental verification, are presented on the "torquoselectivity" of the thermal ring opening of 3-acetylcyclobutene (1). 3-Acetylcyclobutene was synthesized from commercially available 1,1-cyclobutanedicarboxylic acid. Thermolysis of 3-acetylcyclobutene resulted in a mixture of E- and Z-dienes with a slight preference for the E-diene. This preference was reversed by the Lewis acid, ZnI₂, as predicted from theoretical calculations.

Full text of DOI:10.1021/jo951047j

640
J . Org. Chem. 1996, 61, 640-646
In ter p la y of Th eor y a n d Exp er im en t: Rever sa l of th e
Tor qu oselectivity of th e Electr ocyclic Rin g Op en in g of
3-Acetylcyclobu ten e by a Lew is Acid
Satomi Niwayama*,†
Department of Chemistry and Biochemistry, University of CaliforniasLos Angeles,
Los Angeles, California 90095
Received J une 8, 1995X
Theoretical predictions, accompanied by firm experimental verification, are presented on the
“torquoselectivity” of the thermal ring opening of 3-acetylcyclobutene (1). 3-Acetylcyclobutene was
synthesized from commercially available 1,1-cyclobutanedicarboxylic acid. Thermolysis of 3-ace-
tylcyclobutene resulted in a mixture of E- and Z-dienes with a slight preference for the E-diene.
This preference was reversed by the Lewis acid, ZnI2, as predicted from theoretical calculations.
Sch em e 1
In tr od u ction
Cyclobutenes undergo thermally allowed conrotatory
electrocyclic ring opening to afford E-dienes or Z-dienes
by outward or inward rotation, respectively (Scheme 1).
The twisting mode is dependent upon the electronic
properties of the substituent, X. Previously, Houk et al.
rationalized this selectivity and termed it “torquo-
selectivity”.1ab As a general tendency, electron donors
and mild electron acceptors rotate outward to form the
E-diene, and only powerful π-electron acceptors rotate
inward to form the Z-diene. This selectivity has been
explained based on electronic effects which develop from
the interaction between molecular orbitals of the sub-
stituents (π orbitals) and the breaking C-C bond during
the electrocyclic process as in Scheme 2.1a,b Qualitatively,
donor groups, such as alkyl (Taft σR° ) -0.11 for CH3)4
and hydroxyl (Taft σR° ) -0.43), attached to the breaking
bond will maximize the stabilizing two-electron interac-
tion, or minimize the destabilizing four-electron interac-
tion, with the orbital attached to the substituent in the
transition state during outward rotation. Most substit-
uents prefer outward rotations due to either of these two
electronic effects. When the substituent is an electron
acceptor, inward rotation can be favorable because this
motion permits a vacant π* orbital of the substituent to
overlap with the remote terminus of the breaking σ bond.
This stabilizing interaction overwhelms the steric repul-
sions which occur upon inward rotation only with the
most powerful π-acceptors, such as formyl (Taft σR° )
0.24 ) and dialkylboryl groups.1,2,4
Sch em e 2
According to this theory, it should be possible to control
the torquoselectivity of the ring opening of 3-substituted
cyclobutenes by changing the electron-withdrawing or
† Current address: Center for Cancer Research, Rm. E17-133,
Massachusetts Institute of Technology, 77 Massachusetts Ave., Cam-
bridge, MA 02139. Fax: (617)258-6172. E-mail: niwayama@mit.edu.
X Abstract published in Advance ACS Abstracts, J anuary 1, 1996.
(1) (a) Kirmse, W.; Rondan, N. G.; Houk, K. N. J . Am. Chem. Soc.
1984, 106, 7989. (b) Rondan, N. G.; Houk, K. N. J . Am. Chem. Soc.
1985, 107, 2099.
-donating character of the substituents. Earlier, using
ab initio calculations, it was predicted that substituents
that rotate outward could be enticed to rotate inward by
coordination with Lewis acids, since inward rotation is
favored only with very strong electron acceptors accord-
ing to predictions described above.5
(2) Rudolf, K.; Spellmeyer, D. C.; Houk, K. N. J . Org. Chem. 1987,
52, 3708.
(3) Buda, A. B.; Wang, Y.; Houk, K. N. J . Org. Chem. 1989, 54, 2264.
(4) Houk and Niwayama et al.4a recently examined that inherent
torques calculated for 3-substituted cyclobutenes show a remarkable
correlation with the Taft σR° value,4b which is an experimentally
determined measure of the resonance contribution to the net electron-
donating or -withdrawing character of the substituents. (a) Niwayama,
S.; Kallel, E. A.; Sheu, C.; Spellmeyer, D. C.; Houk, K. N. J . Org. Chem.
Manuscript submitted for publication. (b) Hansch, C.; Leo, A.; Taft,
R. W. Chem. Rev. 1991, 91, 165.
Acetyl group is a mild electron-withdrawing group
(Taft σR° ) 0.16) and expected to be on the borderline
(5) Niwayama, S.; Houk, K. N. Tetrahedron Lett. 1993, 34, 1251.
0022-3263/96/1961-0640$12.00/0 © 1996 American Chemical Society

Torquoselectivity of Electrocyclic Ring Opening
J . Org. Chem., Vol. 61, No. 2, 1996 641
Sch em e 3
between outward and inward rotational selectivity. There-
fore the subtle torquoselective behavior of 3-acetylcy-
clobutene is extremely intriguing from both experimental
and theoretical points of view.
Herein the full details of the interplay of theory and
experiment for the electrocyclic ring opening of 3-acetyl-
cyclobutene (1) will be described.
Ba ck gr ou n d
Although Houk’s theory on the torquoselectivity offers
reasonable predictions on rotational selectivity of 3-sub-
stituted cyclobutene electrocyclic ring openings, only a
few clear experimental verifications have been reported.
This is primarily because ring openings of cyclobutenes
are usually conducted in complicated multifunctionalized
systems, which can interfere with the substituent effects
during the ring openings.
For a related system, Rudolf, Spellmeyer, and Houk
reported that 3-formylcyclobutene opens with inward
rotation of the formyl group, in accord with the quantum
mechanical prediction.2 Ab initio calculations (6-31G*/
/3-21G) predict a 4.6 kcal/mol lower activation energy for
inward rotation than outward rotation.2,4
Similarly, Niwayama and Houk reported that thermal
ring opening of methyl 3-formylcyclobutene-3-carboxylate
(2) produces only inward rotation, with respect to the
formyl group, to form the diene 2a and cyclized 2b
(Scheme 3).6a This is a result of a clear-cut competition
between two electron-acceptors that possess different
degrees of torquoselectivity. They also observed that a
series of 3,3-disubstituted cyclobutenes undergo thermal
ring openings to afford dienes with regiochemistry con-
sistent with ab initio calculations.6b,c Several of the
results are opposite to expectations based upon the
thermodynamic stability of the products. It should also
be noted that electronic effect, rather than steric effect,
clearly determines the torquoselectivity. Houk et al.
demonstrated that 3-methoxy-3-tert-butylcyclobutene (8)
produces only the E-diene 9 in which the tert-butyl group
rotated inwardly upon thermolysis at 90-95 °C for 6.5 h
in C6D6.6d Similar experimental studies were reported
by Wallace et al. for ring openings of 3,4-disubstituted
cyclobutenes.7
Sch em e 4
Alkylketo (X ) RCO, (Taft σR° ) 0.16 for R ) -CH3 ))
groups are less powerful π-acceptors than a formyl group.
Ab initio calculations predict a small preference toward
outward rotation over inward rotation by 1.2 kcal/mol for
an acetyl group as will be described later.5 The ther-
molysis of keto ester 12 gave a 90:10 preference for
outward rotation of the phenylketo groups, but this
reaction is under thermodynamic control (Scheme 4).9
This result is consistent with Niwayama’s experimental
observation of thermolysis of 3-acetylcyclobutene.5
Piers et al. observed exclusive inward rotation of the
formyl group and preferential outward rotation of car-
bethoxy group (Taft σR° ) 0.16) on the thermolysis of
substituted 7-formylbicyclo[4.2.0]oct-1-(6)-enes 10a -d .
These results are also compatible with Houk's theory,
although steric repulsion between the â-methyl group
and the outwardly rotated carbethoxy group decreased
the selectivity for the carbethoxy group in 10d .8
(6) (a) Niwayama, S.; Houk, K. N. Tetrahedron Lett. 1992, 33, 883.
(b) Niwayama, S.; Houk, K. N.; Kusumi, T. Tetrahedron Lett. 1994,
35, 527. (c) Niwayama, S.; Wang, Y.; Houk, K. N. Tetrahedron Lett.
1995, 36, 6201. (d) Houk, K. N.; Spellmeyer, D. C.; J efford, C. W.;
Rimbault, C. G.; Wang, Y.; Miller, R. D. J . Org. Chem. 1988, 53, 2125.
(7) (a) Binns, F.; Hayes, R.; Ingham, S.; Saengchantara, S. T.;
Turner, R. W.; Wallace, T. W. Tetrahedron 1992, 48, 515. (b) Hayes,
R.; Ingham, S.; Saengchantara, S. T.; Wallace, T. W. Tetrahedron Lett.
1991, 32, 2953.
It is predicted that this preference for outward rotation
is reversed by powerful electron-withdrawing additives
due to the increased π-electron-withdrawing character
(8) (a) Piers, E.; Lu, Y.-F. J . Org. Chem. 1989, 54, 2268. (b) Piers,
E.; Ellis, K. A. Tetrahedron Lett. 1993 34, 1875.
(9) Maier, G.; Wiessler, M. Tetrahedron Lett. 1969, 4987.

642 J . Org. Chem., Vol. 61, No. 2, 1996
Niwayama
Ta ble 1. RHF /3-21G a n d RHF /6-31G*//3-21G Rela tive
En er gy Differ en ces (k ca l/m ol) in th e Tr a n sition
Str u ctu r es of th e Rin g Op en in g of 3-Acetylcyclobu ten e
Sch em e 5
3-21G
relative energy
6-31G*//3-21G
relative energy
structure
A (outward O-syna)
B (outward O-antib)
C (inward O-anti)
D (inward O-syn)
0.0
+1.6
+1.5
+2.5
0.0
+1.2
+1.2
+2.9
a
Syn: carbonyl group directs toward the cyclobutene ring.
Anti: carbonyl group directs away from the cyclobutene ring.
b
of the substituent. A theoretical study was carried out
on the rotational selectivity of cyclobutene-3-carboxylic
acid, 13.3 The carboxyl group is a similarly mild electron-
withdrawing group (Taft σR° ) 0.14): 13 is predicted to
slightly prefer outward rotation by 1.5-2.3 kcal/mol. The
electron-withdrawing power theoretically correlates nicely
with the tendency for inward rotation. For example,
protonation increases the electron-withdrawing character
enormously, and inward rotation is calculated to be
favored by 4.8-6.3 kcal/mol.3
In support of this calculation, J efford and Houk et al.10
found that thermolysis of methyl benzocyclobutene-7-
carboxylate (14) with Lewis acid BF3 in the presence of
N-phenyl maleimide afforded a 7:3 mixture of 15 and 16,
favoring inward rotation (Scheme 5). Without BF3, the
formation ratio of 15 and 16 was 1:10. While this ring
opening is an eight-electron process, it nonetheless
provides good evidence for the reversal of rotational
selectivity for four-electron cyclobutene ring opening since
they both proceed via conrotatory mechanism. The
extent of the reversal was disappointingly small, perhaps
due to equilibration of o-xylylenes before trapping.
On the basis of this background, both theoretical and
experimental studies on the torquoselectivity for 3-ace-
tylcyclobutene was carried out in order to further study
the reversal of torquoselectivity.
F igu r e 1. Transition structures of the 3-acetylcyclobutene
electrocyclization. Relative energies at the RHF/3-21G and
RHF/6-31G*//3-21G (parentheses) levels are shown (kcal/mol).
the 6-31G* basis set13 on these optimized structures. In
the lowest energy outward rotation structure (A), the
carbonyl oxygen is pointed toward the opening cy-
clobutene ring, most likely to avoid steric repulsions
between the methyl group and the cyclobutene ring, while
it is pointed away from the cyclobutene ring in the more
stable transition states for inward rotation (C). From
the energy difference between these two structures, the
activation energy difference between inward and outward
rotation for 3-acetylcyclobutene was calculated to be 1.2
kcal/mol at the 6-31G*//3-21G level, with outward rota-
tion preferred. This energy difference is calculated to
give the product ratio of 85:15(E-diene:Z-diene) at 80 °C
in the gas phase. As will be described later, this
prediction proved to be quite close to the experimental
result.
These four structures have a narrow range in energy,
which reflects that acetyl group possesses a mild electron-
withdrawing character that dictates subtle twisting
selectivity on the borderline between outward and inward
rotations.
Both outward rotation transition structures, A and B,
have shorter breaking bond lengths than the inward
rotation transition structures, C and D, which implies
that outward rotation has an earlier transition state.
This tendency, in which the carbonyl group points
toward the cyclobutene ring was also found in cy-
clobutene-3-carboxylic acid (13).3 In both outward and
inward rotations, the optimized geometries of 13 have
the carbonyl groups pointed towards the cyclobutene ring
Th eor etica l Stu d y
RHF ab initio calculations on the ring opening of
3-acetylcyclobutene, 1, were performed employing the
GAUSSIAN 90 series of programs.11
Four transition structures were located for the conver-
sion of 1 to (E)- or (Z)-3,5-hexadien-2-one with the 3-21G
basis set.12 Transition structures were fully optimized
and gave only one imaginary frequency in the harmonic
frequency analysis. The energy values calculated were
summarized in Table 1. The structures are as shown in
Figure 1. Single point calculations were carried out with
(10) J efford, C. W.; Bernardinelli, G.; Wang, Y.; Spellmeyer, D. C.;
Buda, A.; Houk, K. N. J . Am. Chem. Soc. 1992, 114, 1157.
(11) GAUSSIAN 90: Frisch, M. J .; Head-Gordon, M.; Trucks, G. W.;
Foresman, J . B.; Schlegel, H. B.; Raghavachari, K.; Robb, M. A.;
Binkley, J . S.; Gonzalez, C.; Defrees, D. J .; Fox, D. J .; Whiteside, R.
A.; Seeger, R.; Melius, C. F.; Baker, J .; Martin, R. L.; Kahn, L. R.;
Stewart, J . J . P.; Topiol, S.; Pople, J . A. Gaussian, Inc., Pittsburgh,
PA, 1990.
(12) Binkley, J . S.; Pople, J . A.; Hehre, W. J . J . Am. Chem. Soc. 1980,
102, 939.
(13) Hehre, W. J .; Ditchfield, R.; Pople, J . A. J . Chem. Phys. 1972,
56, 2257.

Torquoselectivity of Electrocyclic Ring Opening
J . Org. Chem., Vol. 61, No. 2, 1996 643
Ta ble 2. RHF /3-21G Rela tive En er gy Differ en ces (k ca l/
m ol) in th e Tr a n sition Str u ctu r es of th e Rin g Op en in g of
3-Acetylcyclobu ten e w ith BH3 Coor d in a tion w ith
3-Acetylcyclobu ten e F r ozen
Ta ble 3. RHF /STO-3G* Rela tive En er gy Differ en ces
(k ca l/m ol) in th e Tr a n sition Str u ctu r es of th e Rin g
Op en in g of 3-Acetylcyclobu ten e w ith Zn H2 Coor d in a tion
w ith 3-Acetylcyclobu ten e F r ozen
3-21G
STO-3G*
structure
relative energy
structure
relative energy
A-a (outward O-syn B-syn1)
A-b (outward O-syn B-anti2)
B-a (outward O-anti B-syn)
B-b (outward O-anti B-anti)
C-a (inward O-anti B-syn)
C-b (inward O-anti B-anti)
D-a (inward O-syn B-syn)
D-b (inward O-syn B-anti)
+2.7
+6.3
+4.5
+3.5
+1.0
0.0
A-a ′ (outward O-syn Zn-syna)
A-b′ (outward O-syn Zn-antib)
B-a ′ (outward O-anti Zn-syn)
B-b′ (outward O-anti Zn-anti)
C-a ′ (inward O-anti Zn-syn)
C-b′ (inward O-anti Zn-anti)
D-a ′ (inward O-syn Zn-syn)
D-b′ (inward O-syn Zn-anti)
+1.8
+1.9
+2.1
+1.5
+2.1
+2.2
+3.5
0.0
+3.0
+4.9
a
a
B-syn: B coordinates from the same side as the methyl group.
B-anti: B coordinates from the other side of the methyl group.
Zn-syn: Zn coordinates from the same side as the methyl
b
b
group. Zn-anti: Zn coordinates from the other side of the methyl
group.
F igu r e 2. Transition structures for 3-acetylcyclobutene elec-
trocyclization with BH3 coordination. Relative energies are
shown (kcal/mol).
F igu r e 3. Transition structures for 3-acetylcyclobutene elec-
trocyclization with ZnH2 coordination. Relative energies are
shown (kcal/mol).
in the lower energy structures. All four structures also
have similar energies, probably because carbonyl and
hydroxyl oxygens have similar steric and electrostatic
interactions with the cyclobutene ring.
In the case of 3-formylcyclobutene, which has a large
preference for inward rotation, the oxygen points away
from the cyclobutene ring in both inward and outward
rotations, presumably since steric interactions between
the cyclobutene ring and hydrogen are smaller than for
the cyclobutene ring and oxygen.2,3
O and B compared to aldehydes. For example, the
coordination bond length of BH3 to propanal was calcu-
lated to be ∼1.704 Å with the 3-21G basis set.21a Previous
studies also suggest that this structural preference is
basis set dependent.
Since the experiments were carried out with zinc
halides as catalysts (see later) the same calculations as
for BH3 coordination were also conducted for hypothetical
zinc Lewis acids, ZnH2, and ZnF2 as model Lewis acids
using the STO-3G* basis set,14 which is the most eco-
nomical basis set for qualitative analysis. The results
are summarized in Table 3. As summarized in Figure
3, for ZnH2, inward rotation (D-b ′) is calculated to be
favored over outward rotation (B-b′) by 1.5 kcal/mol. This
energy difference corresponds to a ratio of outward/
inward formation rates of 10/90 at 80 °C, which is quite
consistent with the experimental result that will be
described later. In both transition states, the carbonyl
oxygen is pointed opposite to the direction calculated for
BH3. During inward rotation, oxygen is pointed toward
the cyclobutene ring, and for outward rotation oxygen is
directed away from the ring. In both transition struc-
tures, ZnH2 is coordinated from the same side of the
cyclobutene ring instead of the methyl group side. Ad-
ditionally, ZnH2 is coordinated in such a way that Zn-H
bonds are directed almost perpendicular to CdO plane
rather than parallel. This orientation could decrease
steric repulsion between Zn-H and the cyclobutene ring.
Calculations for ZnF2 coordination were also performed
(Table 4). The two most stable structures of outward and
In order to investigate the possibility of reversal of the
torquoselectivity for 3-acetylcyclobutene qualitatively, the
model calculations were performed using 3-21G basis set
with the hypothetical Lewis acid, BH3, added to the four
transition state structures with the 3-acetylcyclobutene
geometries frozen. The position and geometry of BH3 was
optimized in each structure. Since the carbonyl oxygen
has two lone pairs for coordination of BH3, eight struc-
tures were located altogether. The calculated results are
summarized in Table 2. The two lowest structures from
inward (C-b) and outward rotation (A-a )(underlined in
Table 2) are shown in Figure 2. As expected, inward
rotation is now favored by 2.7 kcal/mol. BH3 is coordi-
nated from the same side as the cyclobutene ring, while
in outward rotation, BH3 is coordinated from the other
side of the carbonyl oxygen. The distances between B
and O are slightly shorter by 0.02 Å for inward rotation
than for outward rotation, showing that B-O coordina-
tion is tighter for inward rotation. Similarly, the struc-
ture of the complexation of boron Lewis acid, BH3 and
BF3, to aldehydes and ketones were examined both
theoretically and experimentally earlier. The anti com-
plexations with respect to the bulkier group observed in
these references were rationalized based on mostly steric
arguments.21 Here, this preference does not seem clear,
presumably due to slightly loosened coordination between
(14) (a) Hehre, W. J .; Stewart, R. F.; Pople, J . A. J . Chem. Phys.
1969, 51, 2657. (b) Collins, J . B.; Schleyer, P. v. R.; Binkley, J . S.; Pople,
J . A. J . Chem. Phys. 1976, 64, 5142.

644 J . Org. Chem., Vol. 61, No. 2, 1996
Niwayama
Ta ble 4. RHF /STO-3G* Rela tive En er gy Differ en ces
(k ca l/m ol) in th e Tr a n sition Str u ctu r es of th e Rin g
Op en in g of 3-Acetylcyclobu ten e w ith Zn F 2 Coor d in a tion
w ith 3-Acetylcyclobu ten e F r ozen
Sch em e 6
STO-3G*
structure
relative energy
A-a ′′ (outward O-syn Zn-syna)
A-b′′ (outward O-syn Zn-antib)
B-a ′′ (outward O-anti Zn-syn)
B-b′′ (outward O-anti Zn-anti)
C-a ′′ (inward O-anti Zn-syn)
C-b′′ (inward O-anti Zn-anti)
D-a ′′ (inward O-syn Zn-syn)
D-b′′ (inward O-syn Zn-anti)
+1.4
+0.7
+1.6
+1.0
+0.9
+1.4
+1.8
0.0
Sch em e 7
a
Zn-syn: Zn coordinates from the same side as the methyl
b
group. Zn-anti: Zn coordinates from the other side of the methyl
group.
yield). This methyl ketone was protected with 1,3-
propanedithiol and dehydrochlorinated (∼40%, for two
steps) to afford the olefinic thioketal 19. The deprotection
of this olefin was performed with methyl iodide in
aqueous acetonitrile in the presence of Na2CO3 to produce
1 in 27% yield.
F igu r e 4. Transition structures for 3-acetylcyclobutene elec-
trocyclization with ZnF2 coordination. Relative energies are
shown (kcal/mol).
When acetylcyclobutene (1) was heated in benzene-d6
in a sealed NMR tube at the reflux temperature over-
night, it gave (E)-3,5-hexadien-2-one (20) almost exclu-
1
sively. This diene 20 has a H-NMR spectrum identical
inward rotation (A-b′′ and D-b′′) are in Figure 4. The
basic tendency is almost the same as for ZnH2. Inward
rotation (D-b′′) is favored by 0.71 kcal/mol over outward
rotation (A-b′′). The slightly smaller preference toward
inward rotation might arise from the π electron-donating
character of F atom rather than its inductive electron-
withdrawing character.4 In both structures, the carbonyl
oxygen is pointed toward the cyclobutene ring and ZnF2
is also coordinated from the same side of the cyclobutene
ring. The coordination seems somewhat looser than for
ZnH2, judging from the coordination lengths between the
Zn and O: the Zn-O distances are 2.01 (outward) and
1.99 Å (inward) for ZnF2, while the corresponding dis-
tances are 2.00 (outward) and 1.98 (inward) for ZnH2.
As in the case of ZnH2, Zn-F bonds are also directed
almost perpendicular to the CdO plane, which should
also minimize the steric interaction described above. For
both the coordination of ZnH2 and ZnF2, all the structures
resulted in narrower energy ranges as compared to the
BH3 coordination. This is suggestive of the weaker
coordination of ZnH2 and ZnF2, than that of BH3. In both
cases, the Zn-O distances are slightly shorter by ∼0.02
Å for inward rotation than outward rotation, which
implies these coordinations are tighter in inward rotation
than outward rotation, as was the case for BH3.
to the reported data.16 However, this result does not
necessarily signify a kinetic preference of the ring open-
ing of 1 due to the expected ease of isomerization of the
(Z)-3,5-hexadien-2-one (21). In order to examine whether
the Z-diene 21 was formed but lost by equilibration, the
thermolysis experiments were carried out by heating a
benzene-d6 solution of 3-acetylcyclobutene in a sealed
NMR tube in an NMR probe. 1H-NMR spectra of this
reaction mixture were recorded periodically (every three
minutes) at variable temperatures during very early
stages of the ring openings. The determination of the
product ratio was made on the basis of the integration
of the singlet signal of the acetyl group in 1H-NMR
spectra.
Upon heating 1 at reflux temperature in benzene-d6
(80 °C), it was observed that the product ratio of the two
dienes 20 and 21 is 66:34 ((5)(E-diene:Z-diene) through-
out the first ∼100 min period, namely the beginning stage
of this reaction (Scheme 7). This result should reflect
the kinetic result, that is, the outward rotation is slightly
preferred over the inward rotation by 1.2 kcal/mol. This
kinetic result of the product ratio seems fairly consistent
with the theoretical prediction: 20 and 21 should be
formed in a ratio of ∼85:15 at 80 °C (see above). This
product ratio was observed from the first spectrum in
which the ring opening started and remained unchanged
throughout the first 100 min.23 Considering the fact that
this ring opening is a first-order reaction, this product
ratio should correspond to the kinetic results. With
further heating for several hours, until 1 is consumed,
this product ratio gradually changed to ∼95:5((5)(E-
Exp er im en ta l Stu d y
3-Acetylcyclobutene was synthesized as shown in
Scheme 6. The commercially available cyclobutane-1,1-
dicarboxylic acid (17) was monochlorinated selectively at
the 3-position, followed by decarboxylation to afford
3-chlorocyclobutanecarboxylic acid (18) as a mixture of
stereoisomers in 46% yield.15 Treatment of this acid with
2 equiv of methyllithium gave the methyl ketone (22%
(15) Nevill, W. A.; Frank, D. S.; Trepka, R. J . J . Org. Chem 1962,
27, 422.
(16) Gavrishova, T. N.; Shastin, A. V.; Balenkova, E. S.; Novikov,
N. A. Zh. Org. Khim. 1987, 23(6), 1322.

Torquoselectivity of Electrocyclic Ring Opening
J . Org. Chem., Vol. 61, No. 2, 1996 645
Sch em e 8
Sch em e 9
and the solution turned brown, presumably due to the
formation of HI and I2.
diene:Z-diene) to increase the proportion of the more
stable E-diene 20. This ratio is the result of thermody-
namic equilibration of the initial kinetically determined
ratio. After about 6 h, the E-diene 20 was the only
detectable product. The similar thermodynamic control
of stereochemistry was described before for the phenyl
ketone 12.9
The influence of other Lewis acids was also investi-
gated. Aluminum trichloride and trimethylsilyl triflate
immediately afforded complex mixtures upon heating. In
contrast, catalysis with tin(II) triflate gave exclusively
the E-diene while zinc chloride or silica gel did not affect
the product ratio. Finally treatment with zinc bromide
increased the ratio of stereoisomers to approximately 1:1.
Hence experimentally, zinc iodide turned out to be the
most effective Lewis acid at reversing the torquoselec-
tivity.24
As pointed out earlier, these results are most easily
interpreted in light of the practical difficulty in detecting
the thermodynamically less stable Z-diene 21 which
isomerizes to the E-diene 20 quite rapidly with a catalytic
amount of acid, which is inevitable even at room tem-
perature.
An authentic sample of the minor product, (Z)-3,5-
hexadien-2-one, 21, was prepared for comparison in a
separate experiment as shown in Scheme 8.17-19 Al-
though the procedure for preparation of the Z-diene 21
has already been reported,20 an easier method was
developed. The 3-butyn-2-ol was coupled with vinyl
bromide catalyzed by copper(I), according to Sonogash-
ira’s procedure.17,18 The resultant enyne 22 was submit-
ted to stereoselective reduction of the triple bond,19
followed by oxidation of the resultant allylic alcohol 23
1
as depicted in Scheme 8. This H-NMR spectrum of 21
1
was identical to the reported H-NMR data.20
Con clu sion
The influence of Lewis acids on the stereochemistry of
the ring opening was also studied. The Lewis acid BF3‚
OEt2, which is soluble in organic solvents, gave only the
E-diene smoothly at room temperature on completion of
the reaction after 6 h. However, this ring opening is
easily influenced by acid isomerization to afford more
stable E-diene 20. In fact, in a separate experiment,
rapid isomerization of Z-diene 21 to E-diene 20 was
observed at room temperature upon addition of BF3‚OEt2
to 21 in C6D6 solution. Therefore two-phase reaction with
1 equiv of a solid Lewis acid, ZnI2, was performed in the
presence of a slight molar excess of Na2CO3 in deuterated
benzene. A thermolysis experiment was carried out in
the same manner as the thermolysis of 3-acetylcy-
clobutene. Upon heating this mixture for 30 min at 80
°C in an NMR probe, a reversal of torquoselectivity was
observed. The product ratio was 17:83((5) throughout
this period in favor of the Z-diene 21 (Scheme 9).22
Therefore for the same reason stated above, the kinetic
ratio is concluded to be 17:83 (E-diene:Z-diene).23 With-
out Na2CO3, rapid isomerization to the E-diene 20 occurs
The rotational selectivity on the thermal ring opening
of 3-acetylcyclobutene (1) was predicted by ab initio
calculations. Calculations correctly predicted that Lewis
acids can reverse the selectivity. All of these predictions
were verified by the experiments. This is the first
unambiguous experimental evidence that Lewis acid,
ZnI2, reverses the rotational selectivity (“torquoselectiv-
ity”) from outward rotation to inward rotation, during
the electrocyclic ring opening of a substituted cy-
clobutene.
Exp er im en ta l Section
Gen er al. 1H-NMR spectra were recorded on Bruker AM360,
AM500, or AF200 instruments. The residual proton peak of
the deuterated solvent was used as the chemical shift stan-
dard. Mass spectra were obtained on an Associated Electrical
Industries Double Focusing Mass Spectrometer Model MS-902.
All the thermolyses were carried out by variable tempera-
ture NMR in sealed tubes in an NMR probe in benzene-d6
(dried over 3 Å molecular sieves). The NMR tubes were
washed with 10% aqueous ammonium, dried in an oven, and
sealed under a nitrogen atmosphere prior to thermolyses. The
product ratios were determined directly by integration of the
singlet signals from the acetyl protons of the resulting E-diene
20 and Z-diene 21 in the 1H-NMR spectra of the reaction
mixtures. The dienes 20 and 21 were identified on the basis
(17) Sonogashira, K.; Tohda, Y.; Hagihara, N. Tetrahedron Lett.
1975, 4467.
(18) Mushegyan, A. V.; Kinoyan, F. S. Arm. Khim. Zh. 1972, 25(1),
3.
(19) Avignon-Tropics, M.; Pougny, J . R. Tetrahedron Lett. 1989, 30,
4951.
(20) Wolfhugel, J .; Maujean, A.; Chuche, J . Tetrahedron Lett. 1973,
18, 1635.
(21) (a) LePage, T. J .; Wiberg, K. B. J . Am Chem. Soc. 1988, 110,
6642. (b) Reetz, M. T.; Hu¨llmann, M.; Massa, W.; Berger, S.; Radema-
cher, P.; Heymanns, P. J . Am Chem. Soc. 1986, 108, 2405.
(22) During this period of reaction, remarkable reaction rate ac-
celeration was not observed.
1
of the reported H-NMR spectrum data.16,20 Thermolyses were
conducted in duplicate, and the results were observed to be
reproducible.
P r epar ation of 3-Acetylcyclobu ten e (1). 2-(3-cyclobu te-
n yl)-2-m eth yl-1,3-d ith ia n e (19). 3-chlorocyclobutanecar-
boxylic acid (18) was prepared as a mixture of two stereoiso-
(23) These product ratios were determined on the basis of the
relative intensities of the singlet signals from the proton of acetyl
groups of E-diene 20 and Z-diene 21 at regular time intervals. The
plot of the ratios of 20 to 21 versus reaction time gave nearly flat lines
for both uncatalyzed and catalyzed thermolyses during the initial stage
of the ring openings. The kinetic ratios were determined by extrapolat-
ing these plots to time zero.
(24) Considering the fact that only zinc Lewis acids induced inward
rotation effectively, alternative interpretation might be possible on the
basis of the “softness” of these acids. ZnI2, ZnBr2, and BH3 are all
classified as soft Lewis acids.25 However, this argument would require
more systematic theoretical study.
(25) Pearson, R. G. Struct. Bonding (Berlin) 1993, 80, 1.

646 J . Org. Chem., Vol. 61, No. 2, 1996
Niwayama
mers by the reported procedure2 from commercially available
cyclobutane-1,1-dicarboxylic acid (17).
3-Acetylcyclobu ten e (1). The thioketal 19 (471 mg, 2.53
mmol) was dissolved in 6.1 mL of CH3CN containing 1.2 mL
of H2O and 3.6 g of Na2CO3. This mixture was treated with
2.5 mL of MeI at room temperature; the flask was covered with
aluminum foil to protect from light. After 3 days, ether and
H2O were added, and the mixture was extracted with ether
(×3), washed with aqueous Na2S2O3 and brine, and dried with
anhydrous MgSO4. The ether was removed under reduced
pressure (20 mmHg) at 5 °C to afford 65 mg of 1 as a volatile,
colorless oil (27% yield). 1H-NMR (C6D6, 360 MHz): 1.75 (3H,
s), 2.41 (1H, ddd, J ) 13.8, 1.0, 2.0), 2.52 (1H, ddd, J ) 13.8,
0.9, 5.4), 3.37 (1H, m), 5.85 (1H, m), 5.93 (1H, m). 13C-NMR
(C6D6, 50 MHz): 26.93 (q), 33.92 (t), 54.56 (d), 135.77 (d),
139.16 (d), 208.90 (s). HRMS: calcd for C6H8O 96.0575, found
96.0575 (M+).
This carboxylic acid 18 (1.68 g, 12.52 mmol) was dissolved
in 5 mL of anhydrous Et2O in a 1000 mL round bottomed flask
equipped with a reflux condenser and a spin bar. A solution
of 1.4 M methyllithium in diethyl ether (20.6 mL, 28.84 mmol,
2.3 equiv) was added dropwise at such a rate as to maintain
steady reflux, during which period suitable precautions were
taken to vent the methane formed. The consumption of
carboxylic acid 18 was monitored by TLC. Saturated aqueous
NH4Cl was added dropwise to the reaction mixture with
vigorous stirring to destroy excess methyllithium. The ether
layer was separated, washed with saturated NH4Cl solution
and water, and dried over anhydrous magnesium sulfate. The
ether was removed in vacuo, and the residue was chromato-
graphed on silica gel to afford a mixture of two stereoisomers
of the corresponding methyl ketone (365 mg) in 22% yield from
18. This methyl ketone (365 mg, 2.76 mmol) was dissolved in
15 mL of CH2Cl2. 1,3-Propanedithol (446 mg, 4.13 mmol, 1.5
equiv) and 0.1 mL of BF3‚OEt2 was added to this solution
under a nitrogen atmosphere at room temperature. After 13
h, 5 mL of 5% aqueous NaOH was added. The organic layer
was separated, washed with water, brine, and dried over
anhydrous MgSO4. Evaporation and subsequent silica gel
column chromatography afforded corresponding thioketal as
a mixture of two stereoisomers in quantitative yield. This
thioketal (613 mg, 2.76 mmol) and t-BuOK (616 mg, 5.50
mmol), which was dried previously at 70 °C at 0.1 mmHg for
24 h, were stirred in freshly distilled DMSO (4.5 mL) under a
nitrogen atmosphere at 40-50 °C for 19 h. The reaction
mixture was poured into 50 mL of ice-water, extracted with
Et2O (×3), washed with water (×2) and brine, and dried over
anhydrous MgSO4. Silica gel column chromatography afforded
358 mg of 19 as a colorless oil (70% yield.). 1H-MNR (CDCl3,
200 MHz): 1.59 (3H, s), 1.94 (2H, m), 2.53 (2H, m), 2.83 (4H,
m), 3.51 (1H, m), 6.03 (1H, br. d), 6.16 (1H, br. d). 13C-NMR
(CDCl3, 50 MHz): 24.11, 25.29, 26.28, 31.14, 32.95, 51.44,
53.42, 137.07, 137.12. HRMS: calcd for C9H14S2 186.0537,
found 186.0539 (M+).
Ack n ow led gm en t. The author thanks Professor K.
N. Houk, University of California, Los Angeles, for
providing laboratory facilities and financial support as
well as his educational encouragement during this
research. The author also thanks Professor Michael A.
McAllister, University of North Texas, for his helpful
comments on this manuscript. The author is grateful
to the UCLA Office of Academic Computing for com-
puter facilities. The author also thanks Mr. Benjamin
E. Turk, Massachusetts Institute of Technology, for his
assistance in grammatical editing.
Su p p or tin g In for m a tion Ava ila ble: Total energies and
geometries for the transition structures A-D, Aa-Db, Aa′-Db′,
and Aa′′-Db′′ are in Tables A-D, Aa-Db, Aa′-Db′, and Aa′′-Db′′.
Copies of NMR spectra of compounds 1 and 19 are also
available (32 pages). This material is contained in libraries
on microfiche, immediately follows this article in the microfilm
version of the journal, can be ordered from the ACS; see any
current masthead page for ordering information.
J O951047J