Solvolysis of 2-bicyclo[3.2.2]nonyl p-toluenesulfonate. Evidence for the formation of classical carbocation intermediates

Article abstract of DOI:10.1021/jo9914061

The solvolysis rate of 2-bicyclo[3.2.2]nonyl p-toluenesulfonate (6-OTs) was nearly equal to that of cycloheptyl p-toluenesulfonate in 2,2,2- trifluoroethanol (TFE). This indicates that the ethylene bridge in 6-OTs does not significantly enhance the rate and that 6-OTs ionizes without anchimeric assistance. The solvolysis of [1-¹³C]-2-bicyclo[3.2.2]nonyl p- toluenesulfonate in methanol or TFE gave 2-substituted bicyclo[3.2.2]nonane, exo-2-substituted bicyclo[3.3.1]nonane, 2-bicyclo[3.22]nonene (10), and 2- bicyclo[3.3.1]nonene (11), whose distributions of ¹³C labels were determined by quantitative ¹³C NMR analysis using a relaxation reagent. The ¹³C labels were exclusively placed at only two positions, the ratios of them were not unity, and the labels in 10 were less extensively scrambled than those in other products. These results indicate that the 2- bicyclo[3.2.2]nonyl cation is classical and that 10 is formed at a former ionization stage than 2-substituted bicyclo[3.2.2]nonane. The ¹³C redistributions for both exo-2-substituted bicyclo[3.3.1]nonane and 11, which are yielded via 1,3-hydride shift, were similar to that of 2-substituted bicyclo[3.2.2]nonane, suggesting that 1,3-hydride shift occurs mainly at the solvent-separated ion pair.

Full text of DOI:10.1021/jo9914061

1680
J . Org. Chem. 2000, 65, 1680-1684
Solvolysis of 2-Bicyclo[3.2.2]n on yl p-Tolu en esu lfon a te. Evid en ce
for th e F or m a tion of Cla ssica l Ca r boca tion In ter m ed ia tes
Takao Okazaki,* Eiichi Terakawa, Toshikazu Kitagawa,* and Ken’ichi Takeuchi
Department of Energy and Hydrocarbon Chemistry, Graduate School of Engineering, Kyoto University,
Sakyo-ku, Kyoto 606-8501, J apan
Received September 7, 1999
The solvolysis rate of 2-bicyclo[3.2.2]nonyl p-toluenesulfonate (6-OTs) was nearly equal to that of
cycloheptyl p-toluenesulfonate in 2,2,2-trifluoroethanol (TFE). This indicates that the ethylene bridge
in 6-OTs does not significantly enhance the rate and that 6-OTs ionizes without anchimeric
assistance. The solvolysis of [1-13C]-2-bicyclo[3.2.2]nonyl p-toluenesulfonate in methanol or TFE
gave 2-substituted bicyclo[3.2.2]nonane, exo-2-substituted bicyclo[3.3.1]nonane, 2-bicyclo[3.2.2]-
nonene (10), and 2-bicyclo[3.3.1]nonene (11), whose distributions of 13C labels were determined by
quantitative 13C NMR analysis using a relaxation reagent. The 13C labels were exclusively placed
at only two positions, the ratios of them were not unity, and the labels in 10 were less extensively
scrambled than those in other products. These results indicate that the 2-bicyclo[3.2.2]nonyl cation
is classical and that 10 is formed at a former ionization stage than 2-substituted bicyclo[3.2.2]-
nonane. The 13C redistributions for both exo-2-substituted bicyclo[3.3.1]nonane and 11, which are
yielded via 1,3-hydride shift, were similar to that of 2-substituted bicyclo[3.2.2]nonane, suggesting
that 1,3-hydride shift occurs mainly at the solvent-separated ion pair.
In tr od u ction
[3.2.1]octyl cation is nonclassical (4b).8 However, there
are only a few reports about 3.
The 2-norbornyl cation is believed to be nonclassical
(1b) in the gas phase and under stable ion conditions.1-3
However, the distinction between the nature of the cation
under solvolytic conditions and that under gas-phase
conditions remains controversial.4 The 2-norbornyl cation
can be regarded as a substituted secondary cyclopentyl
cation. On the other hand, the 4-homoadamantyl cation
(2),5,6 2-bicyclo[3.2.2]nonyl cation (3),7 and 2-bicyclo[3.2.1]-
octyl cation (4)8 can be regarded as substituted secondary
cycloheptyl cations. Many of these cations were suggested
to have classical structures in solvolysis. Nordlander et
al. suggested that the 4-homoadamantyl cation should
to be classical (2a ) from the results of the solvolysis of
deuterium-labeled 4-homoadamantyl p-toluenesulfonate
(5).5 We confirmed the validity of their conclusion by
using 13C isotope labels, whose isotope effect on the
product pattern should be less than that of deuterium.6
Goering and Sloan reported that the solvolysis of optically
active endo-2-bicyclo[3.2.1]octyl brosylate gave racemic
substitution products and suggested that the 2-bicyclo-
Schaefer et al. reported that the acetolysis of 2-bicyclo-
[3.2.2]nonyl p-toluenesulfonate (6-OTs) gave (after Li-
* Address correspondence to T. Okazaki. Tel: +81-75-753-5714.
Fax: +81-75-753-3350. e-mail: okazaki@scl.kyoto-u.ac.jp.
(1) Olah, G. A. Angew. Chem., Int. Ed. Engl. 1995, 34, 1393.
(2) (a) Schreiner, P. R.; Schleyer, P. v. R.; Schaefer, H. F., III. J .
Org. Chem. 1997, 62, 4216. (b) Schreiner, P. R.; Severance, D. L.;
J orgensen, W. L.; Schleyer, P. v. R.; Schaefer, H. F., III. J . Am. Chem.
Soc. 1995, 117, 2663.
(3) It was recently reported that an atoms in molecules (AIM) study
indicated that the norbornyl cation is not a nonclassical, σ-bridged
cation but a π-complex: Werstiuk, N. H.; Muchall, H. M. J . Mol. Struct.
(THEOCHEM) 1999, 463, 225.
(4) Brown, H. C. Nonclassical Ion Problem; (with comments by
Schleyer, P. v. R.); Plenum Press: New York, 1977.
(5) Nordlander, J . E.; Hamilton, J . B., J r.; Wu, F. Y.-H.; J indal, S.
P.; Gruetzmacher, R. R. J . Am. Chem. Soc. 1976, 98, 6658.
(6) Kitagawa, T.; Okazaki, T.; Komatsu, K.; Takeuchi, K. J . Org.
Chem. 1993, 58, 7891.
AlH4 reduction) 2-bicyclo[3.2.2]nonanol (6-OH), 3-bicyclo-
[3.2.2]nonanol (7-OH), and exo-2-bicyclo[3.3.1]nonanol (8-
OH) (Scheme 1).9 There was no information about
elimination products. Berson et al. reported the behavior
of the 2-bicyclo[3.2.2]nonyl cation generated by the
deamination of tritiated 1-(2-bicyclo[2.2.2]octyl)methyl-
amine (9-T) (Scheme 2).7 The tritium label in 9-T was
(7) Berson, J . A.; Luibrand, R. T.; Kundu, N. G.; Morris, D. G. J .
Am. Chem. Soc. 1971, 93, 3075.
(8) Goering, H. L.; Sloan, M. F. J . Am. Chem. Soc. 1961, 83, 1397.
(9) Schaefer, J . P.; Endres, L. S.; Moran, M. D. J . Org. Chem. 1967,
32, 3963.
10.1021/jo9914061 CCC: $19.00 © 2000 American Chemical Society
Published on Web 03/02/2000

Solvolysis of 2-Bicyclo[3.2.2]nonyl p-Toluenesulfonate
J . Org. Chem., Vol. 65, No. 6, 2000 1681
Ta ble 1. Ra te Con sta n ts for th e Solvolysis of
2-Bicyclo[3.2.2]n on yl p-Tolu en esu lfon a te (6-OTs) in
Meth a n ol a n d 2,2,2-Tr iflu or oeth a n ol (TF E)
Sch em e 1
∆Hq, ∆Sq,
2,6-lutidine, temp,
°C
kcal cal K-1
mol-1 mol-1
solvent
M
k, s-1
MeOH 1.00 × 10-2 50.0 2.39 ((0.03) × 10-5 a
Sch em e 2
1.33 × 10-2 25.0 7.33 ((0.09) × 10-7 a 26.1
4.00 × 10-2 40.0 5.99 ((0.03) × 10-4 b
1.0
TFE
2.50 × 10-2 25.0 1.02 ((0.02) × 10-4 a 21.4
-5.2
a
b
Determined titrimetrically. Determined conductometrically.
reduction of 1-bicyclo[2.2.2]octane[13C]carboxylic acid and
the subsequent pyridinium chlorochromate (PCC) oxida-
tion gave 1-bicyclo[2.2.2]octane[13C]carbaldehyde. The
acylative ring expansion and the hydrolysis of the alde-
hyde by a method similar to that previously reported12
yielded [2-13C]-1,2-bicyclo[3.2.2]nonanediol. The reaction
of the diol with p-toluenesulfonyl chloride in pyridine
yielded [1-13C]-2-bicyclo[3.2.2]nonanone, which was con-
verted to [1-13C]-2-bicyclo[3.2.2]nonanol ([1-13C]-6-OH)
by the LiAlH4 reduction.9,16 [1-13C]-6-OH was converted
to [1-13C]-6-OTs by the standard method. Quantitative
13C NMR with a relaxation reagent6,17 indicated that 13C
label (98.5%) in [1-13C]-6-OH was exclusively placed at
the bridgehead position C(1).
Sch em e 3
Unlabeled 2-bicyclo[3.2.2]nonyl p-toluenesulfonate (6-
OTs)9 was synthesized from 1-bicyclo[2.2.2]octanemeth-
anol12 by a method similar to that described above.
Solvolysis Ra tes a n d P r od u cts in Meth a n ol a n d
2,2,2-Tr iflu or oeth a n ol. Solvolysis rates of 6-OTs in
methanol and 2,2,2-trifluoroethanol (TFE) buffered with
2,6-lutidine were determined and are shown in Table 1.
The activation free energy (∆Gq) for the solvolysis of
scrambled at two positions by the Wagner-Meerwein
rearrangement, and the distribution ratio of the labels
in the products ([3-T]-6-OH and [7-T]-6-OH) was not 1:1.
They suggested that the cation was not a nonclassical
ion (3b), but a classical one (3a ).
However, cations generated by deamination are called
“hot cations” and are different in reactivity and selectivity
from cations in solvolysis.10,11 Therefore, the reaction
mechanism and structure of 3 under solvolytic conditions
is of particular interest.
We now report the solvolysis of 2-bicyclo[3.2.2]nonyl
p-toluenesulfonate (6-OTs) and [1-13C]-2-bicyclo[3.2.2]-
nonyl p-toluenesulfonate ([1-13C]-6-OTs), prepared by the
acylative ring expansion12 from 1-bicyclo[3.2.2]nonane-
[13C]carbaldehyde. The 13C labels were exclusively
scrambled into two carbons of the solvolysis products, and
the redistribution ratio suggested that the 2-bicyclo[3.2.2]-
nonyl cation under the solvolytic conditions is a classical
ion (3a ).
6-OTs in TFE at 25 °C is calculated to be 23.0 kcal mol-1
and ∆Gq for cycloheptyl p-toluenesulfonate in TFE was
,
reported to be smaller by only 0.2-0.3 kcal mol-1 18
The
.
nearly identical ∆Gq’s suggest that the ethylene bridge
in 6-OTs has essentially no effect on the SN1 solvolysis
rates and that 6-OTs ionizes without significant anchi-
meric assistance.
For a product study, 6-OTs was solvolyzed in methanol
and TFE buffered with 2,6-lutidine. Gas chromatography
indicated that the products were 2-bicyclo[3.2.2]nonene
(10),19 2-bicyclo[3.3.1]nonene (11),9,20,21 tricyclo[3.3.1.02,8]-
nonane (12),22 2-R-bicyclo[3.2.2]nonane [6-R : 6-OMe
(R ) OMe), 6-OTF E (R ) OCH2CF3)], exo-2-R-bicyclo-
[3.3.1]nonane [8-R: 8-OMe (R ) OMe), 8-OTF E (R )
OCH2CF3)], and a small amount of an unidentified ether
(Scheme 4). The yields of the products are shown in Table
2. 10, 11, and 6-OMe16 were identified by comparison
with authentic samples. 8-OMe16 was determined by the
Resu lts a n d Discu ssion
Syn t h esis of 2-Bicyclo[3.2.2]n on yl p -Tolu en e-
su lfon a te (6-OTs) a n d [1-13C]-2-Bicyclo[3.2.2]n on yl
p-Tolu en esu lfon a te ([1-13C]-6-OTs). The synthesis of
[1-13C]-2-bicyclo[3.2.2]nonyl p-toluenesulfonate ([1-13C]-
6-OTs) is shown in Scheme 3. 1-Bicyclo[2.2.2]octane[13C]-
carboxylic acid13,14 was synthesized by the reaction of
13CO2 and 1-bicyclo[2.2.2]octyllithium.13,15 The LiAlH4
(13) Della, E. W.; Pigou, P. E.; Taylor, D. K.; Krivdin, L. B.;
Contreras, R. H. Aust. J . Chem. 1993, 46, 63.
(14) Della, E. W.; Pigou, P. E. J . Am. Chem. Soc. 1984, 106, 1085.
(15) Wang, S. S.; Sukenik, C. N. J . Org. Chem. 1985, 50, 653.
(16) Kirmse, W.; Feldmann, G. Chem. Ber. 1989, 122, 1531.
(17) Martin, M. L.; Martin, G. J .; Delpuech, J .-J . Practical NMR
Spectroscopy; Heyden and Sons: London, 1980; Chapter 10, Section
3. (18) Schneider, H.-J .; Thomas, F. J . Am. Chem. Soc. 1980, 102, 1424.
(19) (a) Goldstein, M. J .; Natowsky, S. J . Am. Chem. Soc. 1973, 95,
6451. (b) Goldstein. M. J .; Natowsky, S.; Heilbronner, E.; Hornung, V.
Helv. Chim. Acta 1973, 56, 294.
(10) Okazaki, T.; Isobe, H.; Kitagawa, T.; Takeuchi, K. Bull. Chem.
Soc. J pn. 1996, 69, 2053.
(11) (a) Keating, J . T.; Skell, P. S. In Carbonium Ions; Olah, G. A.;
Schleyer, P. v. R., Eds.; Wiley-Interscience: New York, 1970; Vol. 2,
pp 573-653. (b) Friedman, L. In Carbonium Ions; Olah, G. A.; Schleyer,
P. v. R., Eds.; Wiley-Interscience: New York, 1970; Vol. 2, pp 655-
713.
(12) Takeuchi, K.; Kitagawa, I.; Akiyama, F.; Shibata, T.; Kato, M.;
Okamoto, K. Synthesis 1987, 612.
(20) Rademacher, P.; Wiesmann, R. F. Chem. Ber. 1994, 127, 509.
(21) Schaefer, J . P.; Lark, J . C.; Flegal, C. A.; Honig, L. M. J . Org.
Chem. 1967, 32, 1372.
(22) (a) Biethan, U.; Cuntze, U.; Musso, H. Chem. Ber. 1977, 110,
3649. (b) Musso, H.; Klusacek, H. Chem. Ber. 1970, 103, 3076. (c)
Musso, H.; Klusacek, H. Chem. Ber. 1970, 103, 3066. (d) Biethan, V.
U.; Klusacek, H.; Musso, H. Angew. Chem. 1967, 79, 152.

1682 J . Org. Chem., Vol. 65, No. 6, 2000
Okazaki et al.
Ta ble 4. Selected Assign m en t of th e Sign a ls in 13C NMR
Sp ectr a of 2-R-Bicyclo[3.2.2]n on a n es [6-OMe (R ) OMe),
6-OTF E (R ) Och 2CF 3)], 2-R-Bicyclo[3.3.1]n on a n es
[8-OMe (R ) OMe), 8-OTF E (R ) Och 2CF 3)],
2-Bicyclo[3.2.2]n on en e (10), a n d 2-Bicyclo[3.3.1]-
n on en e (11)
Sch em e 4
a
δ, ppm
compound
C(1)
C(2)
C(8)
Ta ble 2. Solvolysis P r od u cts of 2-Bicyclo[3.2.2]n on yl
p-Tolu en esu lfon a te (6-OTs) a n d
6-OMe
6-OTF E
8-OMe
8-OTF E
10
33.1
33.7
86.9
87.4
81.0
81.4
135.6
130.5
[1-13C]-2-Bicyclo[3.2.2]n on yl p-Tolu en esu lfon a te
([1-13C]-6-OTs) in Meth a n ol or 2,2,2-Tr iflu or oeth a n ol
(TF E) Bu ffer ed w ith 0.05 M 2,6-Lu tid in e
28.2
27.8
30.1
yield, %a
11
29.2
a
Determined by 13C NMR analysis in CDCl3.
substrate
6-OTsb
solvent 6-R 8-R 10 11 12 unknown
MeOH 18c 21c 36 18
TFE
4
3
5
2
3
Sch em e 5
10d 12d 26 47 <1
[1-13C]-6-OTse MeOH 22c 23c 33 15
5
TFE
16d 13d 24 44 <1
a
b
Determined by gas chromatography. At 50 °C for 10 half-
lives. c R ) OMe. R ) OTFE. e At 40 °C for 20 half-lives.
d
Ta ble 3. 13C Red istr ibu tion in th e P r od u cts of th e
Solvolysis of [1-13C]-2-Bicyclo[3.2.2]n on yl
p-Tolu en esu lfon a te ([1-13C]-6-OTs) in Meth a n ol or
2,2,2-Tr iflu or oeth a n ol (TF E) a t 40 °C
13C redistribution, % a
compound
solvent
C(1)
C(2)
C(8)
6-OMe
6-OTF E
8-OMe
8-OTF E
10
10
11
11
MeOH
TFE
MeOH
TFE
MeOH
TFE
MeOH
TFE
72
60
28
40
72
62
19
31
70
59
28
38
81
69
30
41
a
Determined by quantitative 13C NMR analysis with a relax-
ation reagent, Fe(acac)3. The 13C redistribution at the other
positions was negligible. Assignment of the 13C NMR signals is
shown in Table 4.
comparison of its NMR data with the reported data.
6-OTF E and 8-OTF E were identified on the basis of
their NMR and the results of acetolysis of 6-OTs reported
by Schaefer et al.9 The structure of 12 was deduced on
the basis of the 13C NMR data that indicate the existence
of cyclopropane ring (δ 13C ) 12.1 ppm) and its retention
time, which is near to those of 10 and 11, in gas
chromatography.
13C Red istr ibu tion in th e P r od u cts a n d Mech a -
n ism for th e Solvolysis of [1-13C]-2-Bicyclo[3.2.2]-
n on yl p-Tolu en esu lfon a te. The 13C distributions in the
solvolysis products (6-OMe, 6-OTF E, 8-OMe, 8-OTF E,
10, and 11) from [1-13C]-6-OTs were analyzed by the
quantitative 13C NMR measurement with the aid of a
relaxation reagent, and calculated 13C redistributions are
shown in Table 3. The 13C labels were exclusively placed
at two positions of each of the products, and the labels
in the bicyclo[3.2.2]nonyl derivatives were located pre-
dominantly at the original position. The redistribution
ratios C(8)/C(2) in 11 are nearly equal to C(2)/C(1) in 6-R
and C(8)/C(2) in 8-R, while the ratios C(2)/C(1) in 10 are
smaller than the redistribution ratios in the other
products. Furthermore, the 13C label was more exten-
sively scrambled by Wagner-Meerwein rearrangement
in TFE than that in methanol.
for 6-R in both solvents. This indicates that at least two
kinds of ion pairs of equilibrating cationic intermediates,
tight ion pair and solvent-separated ion pair, exist and
that elimination product 10 is formed from the former
ion pair.
If the 2-bicyclo[3.2.2]nonyl cation were a nonclassical
ion (3b), the 13C label should be equally distributed at
the two positions in the substitution and the elimination
products. In actuality, all the products were found to have
different amounts of 13C label at the two positions.
Clearly, the cation is asymmetric and gives the products
by the nucleophilic attachment of solvents or hydride
elimination before the Wagner-Meerwein rearrange-
ment achieve complete equilibrium.
The 13C label can be scrambled between C(1) and C(2)
by the Wagner-Meerwein rearrangement in the 2-bicyclo-
[3.2.2]nonyl cation (3a ). The formation of 11 and 8-R
involves 1,3-hydride shift in 3a . If the hydride shift
occurred at the stages of both the tight ion pairs and the
solvent-separated ion pairs, the redistribution ratios C(8)/
C(2) for 11 and 8-R should be smaller than the ratio C(2)/
C(1) for 6-R. However, the label scrambling in 11 and
8-R are nearly identical to that in 6-R, and more
progressed than in 10. Therefore, the 1,3-hydride shift
occurs only at the stage of the solvent-separated ion pair.
The rate ratio kTFE/kMeOH for the solvolysis of 6-OTs is
140 at 25 °C. This number is considerably smaller than
A probable solvolysis mechanism is shown in Scheme
5. The degree of scrambling for 10 was smaller than that

Solvolysis of 2-Bicyclo[3.2.2]nonyl p-Toluenesulfonate
J . Org. Chem., Vol. 65, No. 6, 2000 1683
mL) was dropwise added to a solution of benzoic trifluo-
romethanesulfonic anhydride (1.20 mL, 1.81 g, 7.13 mmol) in
dry CCl4 (8 mL). After the mixture had been stirred for 0.5 h,
trifluoromethanesulfonic acid (1.26 mL, 2.14 g, 14.2 mmol) was
dropwise added, and the mixture was stirred for 0.1 h. To the
mixture was dropwise added water (4 mL). The resulting
mixture was poured into water, and the product was extracted
with ether. The combined organic phase was washed with
saturated NaHCO3 and saturated NaCl and dried (MgSO4).
Removal of the solvent gave a pale yellow oil. Recrystallization
and MPLC (SiO2, 1:1 hexane-ether) gave pure [2-13C]-1-
hydroxy-2-bicyclo[3.2.2]nonyl benzoate as colorless crystals in
88% yield.
[2-13C]-1-Hydroxy-2-bicyclo[3.2.2]nonyl benzoate (1.27 g,
4.85 mmol) was added to a solution of KOH (1.06 g, 16 mmol)
in 90% methanol (30 mL), and the mixture was refluxed for 3
h. After evaporation of most of the methanol, to the resulting
mixture was added water, and the product was extracted with
CHCl3. The combined organic phase was washed with 10%
NaCl and dried (MgSO4). Removal of the solvent gave a
colorless crystals, which was purified by recrystallization and
MPLC (SiO2, 1:1 hexane-ether) to give [2-13C]-1,2-bicyclo-
[3.2.2]nonanediol as colorless crystals in 88% yield.
[1-13C]-2-Bicyclo[3.2.2]n on a n on e. The reaction of [2-13C]-
1,2-bicyclo[3.2.2]nonanediol (600 mg, 3.8 mmol) and p-tolu-
enesulfonyl chloride (730 mg, 3.8 mmol) in pyridine (7.6 mL)
gave [1-13C]-2-bicyclo[3.2.2]nonanone (180 mg) as colorless
crystals in 35% yield.
[1-13C]-2-Bicyclo[3.2.2]n on yl p-Tolu en esu lfon a te ([1-
13C]-6-OTs). The reduction of [1-13C]-2-bicyclo[3.2.2]nonanone
(211 mg, 1.51 mmol) with LiAlH4 in ether gave [1-13C]-6-OH
(209 mg) in 98% yield. The reaction of [1-13C]-6-OH (192 mg,
1.36 mmol) with p-toluenesulfonyl chloride (337 mg, 1.77
mmol) in pyridine (2.1 mL) yielded [1-13C]-6-OTs (362 mg) as
colorless crystals in 90% yield: mp 50.5-52.0 °C.
Au th en tic 2-Meth oxybicyclo[3.2.2]n on a n e (6-OMe). To
a solution of 6-OH (60 mg, 0.43 mmol) in dry THF under
nitrogen atmosphere was dropwise added a solution of butyl-
lithium in hexane (1.47 M, 0.32 mL, 0.47 mmol). The mixture
was stirred for 10 min, and iodomethane (0.11 mL, 0.25 g, 1.8
mmol) was dropwise added to the mixture. After stirring
overnight, ether was added to the solution, and the resulting
mixture was filtered. The removal of the solvent gave a
colorless oil. Purification by chromatography (SiO2, pentane)
gave 6-OMe16 (29 mg, 43%) as a colorless oil: 13C NMR (67.8
MHz) δ 86.9 (CH), 56.1 (CH3), 33.1 (CH), 29.7 (CH2), 27.9 (CH),
27.8 (CH2), 26.9 (CH2), 24.2 (CH2), 23.6 (CH2), 19.3 (CH2).
Au th en tic 2-Bicyclo[3.2.2]n on en e (10). A solution of
6-OH (308 mg, 2.20 mmol) in HMPA (10.0 mL) was heated at
200 °C for 2 h. The cooled solution was poured into water and
the product was extracted with ether. The combined organic
layer was washed with water and dried (MgSO4). The removal
of the solvent gave a brown oil. Purification by chromatography
(SiO2, pentane) gave 1019 (150 mg, 56%) as a pale yellow oil:
13C NMR (100 MHz) δ 135.6 (CH), 128.6 (CH), 40.0 (CH2), 30.1
(CH), 28.9 (CH), 28.7 (2CH2), 25.8 (2CH2).
that for the solvolysis of 2-adamantyl tosylate (kTFE
1.51 × 10-6 s-1 and kMeOH ) 2.9 × 10-9 s-1; kTFE/kMeOH
)
)
520 at 25 °C).23 This might indicate possible acceleration
of methanolysis of 6-OTs due to the ks process. However,
this process would be unimportant because the 13C
redistribution in 6-R was almost identical to that in 8-R
in both solvents. If the ks process were significant, the
label should remain in greater amount at C(1) of 6-R
than at C(2) of 8-R.
The difference in the product distribution in the two
solvents (Table 2) is in accord with the above mechanism.
The decreased yield of 10 in TFE can be explained by
the weakening of the basicity of the tightly paired
tosylate anion, which is considered an effective base
for elimination, by electrophilic solvation.5,6 The ratio
(8-R + 11)/6-R, which corresponds to the extent of the
1,3-hydride shift, is significantly higher in TFE (5.9) than
in MeOH (2.2), owing to the low nucleophilicity of TFE.
In conclusion, the above solvolytic data indicate that
the 2-bicyclo[3.2.2]nonyl cation is classical under sol-
volytic conditions. This agrees with Berson’s conclusion
derived from the behavior of the “hot cation” generated
by the deamination of 9-T.
Exp er im en ta l Section
Gen er a l. Melting points are uncorrected. 13C NMR spectra
(67.8 or 100 MHz) were recorded in CDCl3. Solvolyses were
carried out in anhydrous MeOH and TFE which had been
obtained by distillation over MeONa and P2O5, respectively.
All the anhydrous solvents used for synthetic work were
purified by standard procedures. Other commercially available
reagents were used as received. 1,2-Bicyclo[3.2.2]nonanediol
was synthesized by the literature method.12 1-Bicyclo[2.2.2]-
octane[13C]methanol was prepared by the literature method14
by using Ba13CO3 (98% 13C) purchased from Aldlich Chemical
Co., Inc.
2-Bicyclo[3.2.2]n on a n on e. To a solution of 1,2-bicyclo-
[3.2.2]nonanediol (1.6 g, 9.9 mmol) in pyridine (20 mL) was
added p-toluenesulfonyl chloride (2.0 g, 10 mmol). The mixture
was stirred for 6 days under nitrogen and refluxed for 2 h.
The mixture was poured into 10% HCl and extracted with
ether. The combined organic layer was washed with water,
5% NaHCO3, and 10% NaCl and dried (MgSO4). Removal of
the solvent gave colorless crystals, purification of which by
column chromatography (SiO2, 9:1 hexane-ether) yielded
2-bicyclo[3.2.2]nonanone9,24 as colorless crystals (570 mg) in
42% yield.
2-Bicyclo[3.2.2]n on a n ol (6-OH). 6-OH9,16 was obtained by
the reduction of 2-bicyclo[3.2.2]nonanone with LiAlH4 in ether
in 66% yield. 13C NMR (100 MHz) δ 76.6 (CH), 37.0 (CH), 30.0
(CH2), 29.2 (CH2), 27.3 (CH), 26.7 (CH2), 23.4 (CH2), 23.0 (CH2),
18.4 (CH2).
2-Bicyclo[3.2.2]n on yl p-Tolu en esu lfon a te (6-OTs). The
reaction of 6-OH (430 mg, 3.1 mmol) with p-toluenesulfonyl
chloride (700 mg, 37 mmol) in pyridine (4.3 mL) yielded
colorless crystals. Recrystallization from pentane at -40 °C
gave 6-OTs as colorless crystals (630 mg) in 69% yield: mp
48.0-51.0 °C (lit.9 46-48 °C).
Au th en tic 2-Bicyclo[3.3.1]n on en e (11). 11 was prepared
by a method similar to that reported in the literature.20,21,25
In the reported 13C NMR data20 one carbon signal was missing.
The complete data follow: 13C NMR (CDCl3, 67.8 MHz) δ 130.5
(CH), 129.4 (CH), 34.2 (CH2), 32.4 (CH2), 31.8 (CH2), 29.6 (CH),
29.2 (CH2), 27.2 (CH), 18.2 (CH2).
Solvolysis of 2-Bicyclo[3.2.2]n on yl p-Tolu en esu lfon a te
(6-OTs) in MeOH. A solution of 6-OTs (130 mg, 0.46 mmol)
in MeOH (23 mL) containing 0.05 M 2,6-lutidine was heated
at 50 °C for 10 half-lives. The product distribution was
determined by GLC, which indicated that products were
2-methoxybicyclo[3.2.2]nonane (6-OMe), exo-2-methoxybicyclo-
[3.3.1]nonane (8-OMe),16 2-bicyclo[3.2.2]nonene (10), 2-bicyclo-
[3.3.1]nonene (11), tricyclo[3.3.1.02,8]nonane (12),22 and an
unidentified ether (Table 2). Most of the solvent was removed
[2-13C]-1,2-Bicyclo[3.2.2]n on a n ed iol. [2-13C]-1,2-Bicyclo-
[3.2.2]nonanediol was synthesized by a method similar to that
reported for the preparation of unlabeled 1,2-bicyclo[3.2.2]-
nonanediol.12 1-Bicyclo[2.2.2]nonane[13C]methanol (880 mg,
6.24 mmol) was oxidized to 1-bicyclo[2.2.2]nonane[13C]carb-
aldehyde (807 mg, 93%) by using pyridinium chlorochromate
in dry CH2Cl2 in 93% yield. A solution of 1-bicyclo[2.2.2]-
nonane[13C]carbaldehyde (807 mg, 5.80 mmol) in dry CCl4 (10
(23) Schadt, F. L.; Bentley, T. W.; Schleyer, P. v. R. J . Am. Chem.
Soc. 1976, 98, 7667.
(24) Smith, K.; Pelter, A.; J in, Z. Angew. Chem., Int. Ed. Engl. 1994,
33, 851.
(25) Hanack, M.; Kraus, W.; Rothenwo¨hrer, W.; Kaiser, W.; Wen-
trup, G. Liebigs Ann. Chem. 1967, 703, 44.

1684 J . Org. Chem., Vol. 65, No. 6, 2000
Okazaki et al.
by distillation and to the residue was added ether. The solution
was washed with 10% NaCl, cold 5% HCl, 10% NaCl, 5%
NaHCO3, and saturated NaCl and dried (MgSO4). Solvent
removal gave a pale yellow oil (160 mg). Column chromatog-
raphy (SiO2, pentane) gave a mixture of 6-OMe and 8-OMe
as a colorless oil (12 mg). 8-OMe: 13C NMR (67.8 MHz) δ 81.0
(CH), 55.9 (CH3), 31.4 (CH), 31.5 (CH2), 28.3 (CH2), 27.1 (CH),
28.2 (CH2), 26.8 (2CH2), 20.8 (CH2).
Solvolysis of 2-Bicyclo[3.2.2]n on yl p-Tolu en esu lfon a te
(6-OTs) in CF 3CH2OH. A solution of 6-OTs (110 mg, 0.36
mmol) in CF3CH2OH (18 mL) containing 0.05 M 2,6-lutidine
was heated at 50 °C for 10 half-lives. The product distribution
was determined by GLC, which indicated that products were
2-(2,2,2-trifluoroethoxy)bicyclo[3.2.2]nonane (6-OTF E), exo-2-
(2,2,2-trifluoroethoxy)bicyclo[3.3.1]nonane (8-OTF E), 10, 11,
and an unidentified ether (Table 2). Most of the solvent was
removed by distillation, and to the residue was added ether.
The solution was worked up as described for the methanolysis
of 6-OTs to give a pale yellow oil (28 mg). Column chroma-
tography (SiO2, pentane) gave almost pure 8-OTF E as a
colorless oil (2 mg) and a mixture of 6-OTF E and 8-OTF E as
a colorless oil (3 mg). 6-OTF E: 13C NMR (100 MHz) δ 87.4
(CH), 33.7 (CH), 29.3 (CH2), 27.8 (CH), 27.7 (CH2), 26.8 (CH2),
24.1 (CH2), 23.4 (CH2), 19.1 (CH2). 8-OTF E: 13C NMR (100
MHz) δ 81.4 (CH), 31.9 (CH), 31.4 (CH2), 28.0 (CH2), 27.8
(CH2), 27.2 (CH2), 27.1 (CH), 26.6 (CH2), 20.7 (CH2).
11, and 12 as colorless crystals (27 mg) and a mixture of
6-OMe and 8-OMe as a colorless oil (47 mg). The 13C
distributions for the obtained products were determined by a
quantitative 13C NMR analysis using a relaxation reagent, 0.05
M Fe(acac)3, in CDCl3.
Solvolysis of [1-13C]-2-Bicyclo[3.2.2]n on yl p-Tolu en e-
su lfon a te ([1-13C]-6-OTs) in CF 3CH2OH. A solution of
[1-13C]-6-OTs (43 mg, 0.15 mmol) in CF3CH2OH (7.3 mL)
containing 0.05 M 2,6-lutidine was heated at 40 °C for 20 half-
lives. The product distribution was determined by GLC, which
indicated the formation of 6-OTF E, 8-OTF E, 10, 11, and an
unidentified ether (Table 2). Column chromatography (SiO2,
pentane) gave a mixture of 10 and 11 as colorless crystals (27
mg) and a mixture of 6-OTF E and 8-OTF E as a colorless oil
(47 mg). The 13C distributions for the obtained products were
determined by a quantitative 13C NMR analysis with
relaxation reagent, 0.05 M Fe(acac)3, in CDCl3.
a
Kin etics. Rate constants of the solvolysis of 6-OTs in MeOH
or TFE were determined by the previously reported methods.6
Qu a n tita tive 13C NMR An a lysis. Redistribution of 13C
label in solvolysis products was determined by the quantitative
13C NMR analysis, the method of which was previously
reported.6,17 Fe(acac)3 was used as the relaxation reagent.
Ack n ow led gm en t. This work was supported by a
Grant-in-Aid for Scientific Research (No. 10440188)
from the Ministry of Education, Science, Sports and
Culture, J apan.
Solvolysis of [1-13C]-2-Bicyclo[3.2.2]n on yl p-Tolu en e-
su lfon a te ([1-13C]-6-OTs) in MeOH. A solution of [1-13C]-
6-OTs (305 mg, 1.03 mmol) in MeOH (52 mL) containing 0.05
M 2,6-lutidine was heated at 40 °C for 20 half-lives. GLC
analysis showed the formation of 6-OMe, 8-OMe, 10, 11, 12,
and an unidentified ether (Table 2). The mixture was washed
with 10% NaCl, 5% NaHCO3, and saturated NaCl, and dried
(MgSO4). Solvent removal gave a pale yellow oil (125 mg).
Column chromatography (SiO2, pentane) gave a mixture of 10,
Su p p or t in g In for m a t ion Ava ila b le: 1H NMR and 13C
NMR spectra for 8-OTF E and for the mixture of 6-OTF E and
8-OTF E. This material is available free of charge via the
Internet at http://pubs.acs.org.
J O9914061