Rearrangement of the trans-tricyclo[4.2.0.01,3]oct-4-enyl skeleton

Article abstract of DOI:10.1016/S0040-4020(00)00199-X

The acetolysis of a tosylate with a novel tricyclic skeleton was examined. Two major products (a tosylate and an acetate) are formed and both are the result of a skeletal rearrangement. A mechanism to account for the observed products is proposed and preliminary kinetic data are reported. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4020(00)00199-X

TETRAHEDRON
Pergamon
Tetrahedron 56 (2000) 2591±2594
1
Rearrangement of the trans-Tricyclo[4.2.0.0 ]oct-4-enyl Skeleton
,3
*
Elena S. Koltun and Steven R. Kass
Department of Chemistry, University of Minnesota, Minneapolis, MN 55455, USA
Received 19 January 2000; revised 5 March 2000; accepted 6 March 2000
AbstractÐThe acetolysis of a tosylate with a novel tricyclic skeleton was examined. Two major products (a tosylate and an acetate) are
formed and both are the result of a skeletal rearrangement. A mechanism to account for the observed products is proposed and preliminary
kinetic data are reported. q 2000 Elsevier Science Ltd. All rights reserved.
5
Introduction
respectively (Eq. (3)). The product distribution is insensi-
tive over the temperature range and reaction times that were
examined. In addition, no deuterium incorporation was
We recently reported a synthesis of trans-tricyclo-
[
1
4.2.0.0 ]oct-4-ene (1) and described some of its reac-
,3
detected in 3 or 4 when acetic acid-d was used as the
4
solvent, suggesting that their ratio re¯ects the primary
product distribution. As for the structural assignments,
they are based upon the NMR spectral data ( H, C and
COSY) for both species.
1
,2
tivity. This hydrocarbon has a unique structure consisting
of fused three-, four- and ®ve-membered rings along with a
double bond. Its strained ring skeleton is poised to undergo a
variety of rearrangements and two were originally described
1
13
(Eqs. (1) and (2)). In this paper we report on a cationic
rearrangement brought about by the solvolysis of p-toluene-
3
sulfonate 2. This substrate can be viewed as a cyclopropyl-
carbinyl and 4-spiro[2.3]hexyl cation precursor, in which
these subunits are embedded in a larger molecular frame-
work. Strained constituents in complex structures have been
studied less thoroughly than simpler model systems and are
ꢀ
3†
4
of some interest.
To secure the product and stereochemical assignments, we
converted individually 3 and 4 to a known compound
ꢀ
ꢀ
1†
2†
(
(
Scheme 1). In particular, hydrogenation of the tosylate
3) on Pd/C gave the saturated syn,syn-2-bicyclo[3.3.0]octyl
tosylate (5), which was subsequently reduced with sodium
naphthalenide to afford syn,syn-bicyclo[3.3.0]octan-2-ol
(7). Likewise, the acetate (4) was reduced with LiAH to
4
yield alcohol 6, which was hydrogenated on Pd/C to give the
Results and Discussion
Tricyclic tosylate 2 was prepared as reported previously and
solvolyzed in acetic acid at 25, 35 and 508C. Two major
products, tosylate 3 and acetate 4, along with a minor
and unidenti®ed acetate were formed in a 11:3:1 ratio,
1
Keywords: solvolysis; kinetics; tricyclo[4.2.0.0 ]oct-4-enyl skeleton;
,3
rearrangements.
*
Corresponding author. E-mail: kass@chem.umn.edu
Scheme 1.
0040±4020/00/$ - see front matter q 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(00)00199-X

2
592
E. S. Koltun, S. R. Kass / Tetrahedron 56 (2000) 2591±2594
Scheme 2.
Scheme 3.
2
1
same bicyclic alcohol as in the tosylate case (7). In both
instances the H NMR spectra were found to be the same
as that reported for 7.
0.2 kcal mol . We were unable to locate a stationary
point corresponding to 13 at the same level of theory (all
attempts led to a 1,2-hydride shift and the formation of the
corresponding pentadienyl cation), but found that it is
1
6
1
There is confusion in the literature regarding the H NMR
spectrum of 7 relative to 9, its syn,anti-epimer. Conse-
quently, we independently prepared both syn-bicyclo-
21
3.2 kcal mol more stable than 12 using AM1. In addition,
an analogous transformation was reported by Cope et al. to
9
account for the formation of syn,syn-2-bicyclo[3.3.0]octyl
acetate (15) from the acetolysis of 2-bicyclo[4.2.0]octyl
brosylate (14, Scheme 4).
[
3.3.0]octan-2-ols (7 and 9, Scheme 2). Their synthesis
was accomplished in four steps starting from cis-cyclo-
octene by following the literature procedure for the anti
isomer (9) and inverting it to the syn derivative (7) via
7
Preliminary kinetic results for the solvolysis of 2 were
carried out at various temperatures in acetic acid-d and
8
the Mitsunobu method. As a result, we have spectral data
for both diastereomeric alcohols and can con®dently assign
their relative stereochemistry.
4
1
monitored by H NMR spectroscopy. The rate constants
were measured over a 258C range from 25 to 508C (Table
1
). An example of the kinetic data is shown in Fig. 1. A
and
³
21
The proposed mechanism for the cationic rearrangement of
the tricyclic skeleton is shown in Scheme 3. Solvolysis of 2
would be expected to afford the cyclopropylcarbinyl cation
linear Eyring plot leads to DH ˆ24.6 kcal mol
³
21 21
DS ˆ7.3 cal mol K . This contrasts with 4-spiro[2.3]-
hexyl tosylate (16), which solvolyzes ®ve times faster at
³
11 as the ®rst formed intermediate, but semiempirical
258C and has activation parameters of DH ˆ18.4 kcal
(
(
AM1), ab initio (HF) and density functional theory
B3LYP) calculations with the 6-31G(d) basis set lead either
directly to the ring-opened allylic cation 12 or to a delocal-
Ê
ized species with an extremely long C1±C7 bond (1.84 A)
that is well on its way to 12. Subsequent migration of the
C1±C4 bond leads to bicyclo[3.3.0]octadienyl cation 13;
strain relief provides the driving force for the isomerization.
2
Trapping of this ion with the leaving group (OTs ) or
solvent gives the observed products.
Consistent with our proposed mechanism, B3LYP
2
1
calculations indicate that ion 11 is 5.2 kcal mol less
stable than 12 and that the isomerization barrier is only
Scheme 4.

E. S. Koltun, S. R. Kass / Tetrahedron 56 (2000) 2591±2594
2593
1
Table 1. Acetolysis rates and activation parameters (data for 16 come from
Ref. 10; the rate constant was obtained from the activation parameters)
CI (NH ) M1NH calcd for C H NO S 294.1164, found
3
2
4
15 20
3
1
94.1168. Acetate 4: H NMR (300 MHz, CDCl ) d 6.03
3
21
³
³
DS
(m, 1H), 5.87 (m, 1H), 5.37 (m, 1H), 4.91 (dd, Jˆ7.5 and
6 Hz, 1H), 3.61 (m, 1H), 2.79 (m, 3H), 2.60 (m, 1H), 2.15
s, 3H).
Compound
T (8C)
k (s
)
k
rel
DH
1
(
24
24
23
2
25
(2.78^.08)£10
(7.51^.16)£10
(7.12^.22)£10
1
5
24.6
18.4
7.3
3
5
5
0
Preparation of syn,syn-bicyclo[3.3.0]octyl-2-tosylate (5).
A solution of tosylate 3 (0.010 g, 0.036 mmol) and 10 mg of
0% Pd/C in 1 ml of EtOAc was stirred overnight under
atm of H . The reaction mixture was ®ltered through a
23
2
5
1.32£10
210
1
1
2
plug of silica gel and concentrated under reduced pressure
to afford 8.6 mg (86%) of tosylate 5. H NMR (300 MHz,
1
CDCl ) d 7.85 (d, Jˆ8.1 Hz, 2H), 7.35 (d, Jˆ8.1 Hz, 2H),
3
4
.58 (m, 1H), 2.5 (m, 1H), 2.44 (s, 3H), 1.92 (m, 2H), 1.71
m, 3H), 1.43 (m, 2H), 1.26 (m, 2H), 1.10 (m, 2H). C NMR
1
3
(
(
75 MHz, CDCl ) d 144.4, 134.6, 129.7, 127.7, 90.6, 49.9,
3
1
1.5, 34.0, 31.9, 31.2, 29.9, 26.5, 21.6. HRMS-EI M calcd
4
for C H O S 280.1133, found 280.1128.
1
5
20
3
Preparation of syn,syn-bicyclo[3.3.0]octan-2-ol (7) from
syn,syn-bicyclo[3.3.0]octyl-2-tosylate (5). To a solution of
naphthalene (0.012 g, 0.090 mmol) in 0.5 ml of THF under
N was added sodium metal (,2.1 mg, 0.090 mmol). The
2
reaction mixture was stirred for 1 h until a dark blue color
formed at which point tosylate 5 (8.6 mg, 0.030 mmol) in
0
within 5 min and 5 ml of H O was added. Ether (5 ml)
.5 ml of THF was added. The blue color disappeared
2
also was added and the organic layer was dried over
MgSO . Concentration under reduced pressure followed
by column chromatography (5% EtOAc/hexanes) afforded
Figure 1. Kinetic data at 258C for the solvolysis of 2.
4
1
.6 mg (95%) of alcohol 7. H NMR (300 MHz, CDCl ) d
3
3
1
3
3
2
1
³
21 21 10
3
mol
and DS ˆ210 cal mol K . It might seem
.87 (q, Jˆ6.0 Hz, 1H), 2.57 (m, 1H), 2.22 (m, 1H), 1.94 (m,
13
surprising that the tricyclic tosylate reacts more slowly
than its bicyclic analog but there is poorer overlap between
the C±OTs bond and the Walsh orbitals of the cyclopropane
H), 1.73 (m, 2H), 1.6 (br. s, 1H), 1.48 (m, 4H), 1.21 (m,
H). C NMR (75 MHz, CDCl ) d 80.3, 52.9, 42.9, 34.5,
4.4, 31.8, 30.5, 26.7.
3
1
1
in the former (more rigid) case. As a result, 2 either
directly isomerizes to 12 or it affords 11 in which there is
considerable weakening of the C1±C7 bond. This expla-
nation accounts for the difference in activation parameters
and is consistent with the fact that all of the products derived
from 2 are rearranged whereas a small amount of
unrearranged material is obtained from 16.
Preparation of syn-bicyclo[3.3.0]octa-1,6-dien-4-ol (6).
To a 08C solution of 0.030 g (0.18 mmol) of acetate 4
(
with the unknown acetate) in 2 ml of Et O was added
2
0
.3 ml of a 1 M solution of LiAlH in THF. The reaction
4
mixture was stirred for 1.5 h under re¯ux, cooled down to
8C, and 10 ml of both Et O and sat. NH Cl were added.
The organic layer was dried over MgSO and concentrated
0
2
4
4
under reduced pressure to afford 0.018 g (80%) of alcohol 6,
which was of suf®cient purity for the subsequent reactions.
H NMR (300 MHz, CDCl ) d 6.02 (m, 1H), 5.89 (m, 1H),
3
Experimental
1
1
,3
Solvolysis of tricyclo[4.2.0.0 ]oct-4-en-8-tosylate (2). A
solution of tosylate 2 (0.20 g, 0.73 mmol) in 10 ml of AcOH
was heated to re¯ux for 2 min. Upon cooling to room
5.35 (m, 1H), 4.13 (dd, Jˆ4.5 and 12.0 Hz, 1H), 3.50 (dt,
Jˆ3.0 and 6.3 Hz, 1H), 2.78 (m, 2H), 2.65 (m, 1H), 2.49 (m,
1
3
1H), 1.94 (br. s, 1H). C NMR (75 MHz, CDCl ) d 148.1,
3
1
temperature, 20 ml of Et O was added. This solution was
2
133.5, 132.4, 117.9, 81.3, 62.8, 43.4, 32.7. HRMS-EI M
calcd for C 10O 122.0732, found 122.0732.
washed with H O, sat. NaHCO and sat. NaCl, and then the
2
H
8
3
organic layer was dried over MgSO . Concentration under
4
reduced pressure afforded a 11:3:1 mixture of 3, 4 and an
unknown acetate, respectively. Separation of the products
via column chromatography (5% EtOAc/hexanes) afforded
Preparation of syn,syn-bicyclo[3.3.0]octan-2-ol (7) from
syn-bicyclo[3.3.0]octa-1,6-dien-4-ol (6). A solution of
alcohol 6 (0.018 g, 0.15 mmol) and 20 mg of 10% Pd/C in
40 mg (20%) of tosylate 3 and 30 mg (25%) of a mixture of
acetates (4 and an unknown compound). Tosylate 3: H
NMR (300 MHz, CDCl ) d 7.81 (d, 2H), 7.35 (d, 2H),
3
1 ml of EtOAc was stirred overnight under 1 atm of H . The
2
1
reaction mixture was ®ltered through a plug of silica gel and
concentrated under reduced pressure to afford 0.0179 g
(95%) of alcohol 7.
5
.83 (m, 1H), 5.69 (m, 1H), 5.30 (s, 1H), 4.60 (dd, Jˆ6.0
and 9.6 Hz, 1H), 3.75 (m, 1H), 2.66±2.78 (m, 3H), 2.59 (m,
1
H), 2.45 (s, 3H). C NMR (75 MHz, CDCl ) d 134.2,
3
6
Preparation of syn-epoxycyclooctane (8). To a 08C solu-
1
1
2
3
31.5, 130.0, 128.1, 117.2, 103.0, 86.6, 59.8, 40.3, 32.5,
1.9 (two quaternary carbons were not assigned). HRMS-
tion of 3.0 g (0.027 mol) of cyclooctene in 50 ml of CH
was added 7.0 g of 80% m-chloroperbenzoic acid. The
Cl
2 2

2
594
E. S. Koltun, S. R. Kass / Tetrahedron 56 (2000) 2591±2594
reaction mixture was stirred at room temperature for 2 h,
cooled down to 08C, and 50 ml of aqueous NaHCO (satu-
Kinetics. A 20 mg portion of tosylate 2 was added to
approximately 0.5 ml of acetic acid-d in an NMR tube
¯ushed with dry N . The probe of a 500 MHz Varian
2
3
4
e
rated) was added. The organic layer was washed with 50 ml
of H O and saturated NaCl solution, and dried over MgSO .
Concentration under reduced pressure followed by vacuum
NMR was preheated to the desired temperature and did
not vary by more than half a degree over the course of a
kinetic run. Data were collected as a series of 5±23 four
scan spectra at 2±5 min intervals over a period of at least 2
half-lives at 25, 35 and 508C. First-order rate constants were
obtained by monitoring the disappearance of 2 via the inte-
gration of its cyclopropyl resonance at 0.34 d relative to the
residual acid proton in acetic acid. The results given in
Table 1 represent the average of 2 determinations at 35
and 508C and 1 run at 258C, where the uncertainties are
the standard deviations in the measurements except for the
258C rate, which is estimated to have an error of ^3%.
Eyring parameters were obtained from a plot of ln(k/T)
vs. 1/T.
2
4
1
2
distillation at 15 mm (bp 86±888C at 30 mm (lit.))
afforded 2.8 g (82%) of epoxide 8. H NMR (300 MHz,
1
CDCl ) d 2.89 (m, 2H), 2.16 (m, 2H), 1.26±1.66 (m, 8H),
3
1.15±1.26 (m, 2H).
Preparation of syn,anti-bicyclo[3.3.0]octan-2-ol (9). To a
solution of i-Pr NH (3.09 ml, 0.022 mol) in 7 ml of Et O
2
2
was added 11.2 ml (0.019 mol) of a 1.7 M n-BuLi solution
in hexanes. The reaction mixture was stirred for 1 h and then
a solution of syn-epoxycyclooctane (1.2 g, 9.5 mmol) in
1 ml of Et O was added. After re¯uxing the reaction mixture
2
for 1 h, it was cooled down to room temperature and 5 ml of
sat. NH Cl was added. The organic phase was dried over
4
MgSO and concentrated under reduced pressure. Distilla-
4
7
tion at 15 mm (bp 103±1058C at 25 mm (lit.)) afforded
Acknowledgements
1
.40 g (34%) of syn,anti-bicyclo[3.3.0]octan-2-ol (9). H
0
NMR (300 MHz, CDCl ) d 4.19 (m, 1H), 2.51 (m, 2H),
Support from the National Science Foundation, the donors
of the Petroleum Research Foundation, as administered by
the American Chemical Society, the Minnesota Super-
computer Institute, and the University of Minnesota±IBM
Shared Research Project are gratefully acknowledged.
3
1
.22±1.92 (m, 11H). C NMR (CDCl , 75 MHz) d 75.3,
7.4, 42.5, 34.9, 34.1, 29.3, 27.8, 26.5.
3
1
4
3
Preparation of syn, syn-bicyclo[3.3.0]octyl-2-benzoate
10). Diethyl azodicarboxylate (0.33 g, 1.9 mmol) was
added over a 5 min period to a room temperature mixture
(
of alcohol 9 (0.20 g, 1.5 mmol), PPh (0.49 g, 1.9 mmol)
3
References
and benzoic acid (1.2 g, 1.9 mmol) in 6 ml of THF. The
resulting solution was stirred overnight and then concen-
trated under reduced pressure. Column chromatography
1. Koltun, E. S.; Kass, S. R. J. Org. Chem. 2000, in press.
2. Koltun, E. S. PhD Thesis, University of Minnesota, 1999.
3. Only the syn isomer of tosylate 2 was obtained in the synthesis of 1.
4. For example, see: Dombrowski, G. W. PhD Thesis, University
of Minnesota, 1995, and references therein.
(
compound 10. H NMR (300 MHz, CDCl ) d 8.02 (m,
5% EtOAc/hexanes, R ˆ0.67) afforded 0.29 g (81%) of
f
1
3
2
3
H), 7.54 (m, 1H), 7.43 (m, 2H), 5.06 (td, Jˆ2.1 and
1
.9 Hz, 1H), 2.60 (m, 2H), 1.9 (m, 6H), 1.6 (septet,
5. H NMR data of the unknown acetate indicates that it is not the
unrearranged acetate of 2.
1
3
Jˆ6.3 Hz, 1H), 1.4 (m, 2H), 1.26 (m, 1H). C NMR
(
75 MHz, CDCl ) d 166.5, 132.9, 131.1, 129.7, 128.4,
3
6. Fujita, K.; Hata, K.; Oda, R.; Tabushi, I. J. Org. Chem. 1973,
38, 2640±2644.
7. Whitesell, J. K.; White, P. D. Synthesis 1975, 102, 602±603.
83.3, 50.1, 42.1, 34.4, 31.9, 31.6, 30.8, 27.0. HRMS-EI
M calcd for C H O 230.1307, found 230.1305.
1
1
5
18
2
8
4192±4201.
. Overman, L. E.; Bell, K. L.; Ito, F. J. Am. Chem. Soc. 1984, 106,
Preparation of syn,syn-bicyclo[3.3.0]octan-2-ol (7) from
syn,syn-bicyclo[3.3.0]octyl-2-benzoate (10). To a solution
of benzoate 10 (0.15 g, 0.65 mmol) in 5 ml of EtOH
was added a solution of NaOH (0.056 g, 1.4 mol) in
9. Cope, A. C.; Gleason, R. W.; Moon, S.; Park, C. H. J. Org.
Chem. 1967, 32, 942±946.
10. Wiberg, K. B.; Hiatt, J. E. J. Am. Chem. Soc. 1968, 90, 6495±
6500.
2.5 ml of H O. The reaction mixture was stirred overnight
and 15 ml of CH Cl and 10 ml of H O were added.
2
11. Lowry, T. H.; Richardson, K. S. Mechanism and Theory in
Organic Chemistry; 3rd ed.; Harper & Row: New York, 1987, pp
454±463.
2
2
2
The organic layer was dried over MgSO and concentrated
4
under reduced pressure. Column chromatography (5%
EtOAc/hexanes, R ˆ0.2) afforded 0.048 g (59%) of
12. Kato, H.; Miyamoto, N.; Kawanisi, M.; Nozaki, H. Tetrahedron
1970, 26, 2975±2979.
f
compound 7.