Structural Factors for the Formation of Propellane-Type Products in the Solvolysis of Bicyclic Bridgehead Compounds

Article abstract of DOI:10.1021/jo000444d

Methanolyses of 2-oxobicyclo[3.3.1]non-1-yl triflate, 3,3-dimethyl-2-oxobicyclo[3.3.1]non-1-yl triflate, and 2-oxobicyclo[4.3.1]dec-1-yl mesylate gave the corresponding propellanone in 12%, 20%, or 3.2% yield, respectively, beside substitution or rearranged products under typical conditions. No propellane-type product was obtained in the solvolyses of 1-bromobicyclo[3.3.1]nonane, 2-methylidenebicyclo[3.3.1]non-1-yl heptafluorobutyrate, and 3,3-dimethyl-2-thioxobicyclo[3.3.1]non-1-yl tosylate. The factors that permit the formation of the propellane-type product from the intermediate bridgehead cations are examined with the aid of theoretical calculations at PM3 and B3LYP/6-31G*.

Full text of DOI:10.1021/jo000444d

4964
J . Org. Chem. 2000, 65, 4964-4972
Str u ctu r a l F a ctor s for th e F or m a tion of P r op ella n e-Typ e P r od u cts
in th e Solvolysis of Bicyclic Br id geh ea d Com p ou n d s
Kazuhiko Tokunaga, Seiichiro Tachibana, Takao Okazaki, Yasushi Ohga,†
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
ktake@scl.kyoto-u.ac.jp
Received March 24, 2000
Methanolyses of 2-oxobicyclo[3.3.1]non-1-yl triflate, 3,3-dimethyl-2-oxobicyclo[3.3.1]non-1-yl triflate,
and 2-oxobicyclo[4.3.1]dec-1-yl mesylate gave the corresponding propellanone in 12%, 20%, or 3.2%
yield, respectively, beside substitution or rearranged products under typical conditions. No pro-
pellane-type product was obtained in the solvolyses of 1-bromobicyclo[3.3.1]nonane, 2-methylidenebicy-
clo[3.3.1]non-1-yl heptafluorobutyrate, and 3,3-dimethyl-2-thioxobicyclo[3.3.1]non-1-yl tosylate. The
factors that permit the formation of the propellane-type product from the intermediate bridgehead
cations are examined with the aid of theoretical calculations at PM3 and B3LYP/6-31G*.
Ch a r t 1
In tr od u ction
Carbocations 1 (Chart 1) substituted with an electron-
withdrawing group directly attached to the cationic
center are commonly referred to as “destabilized” owing
to the inductive (-I) effect of the substituents.1-5 The
R-carbonyl cation 2 is one of the most interesting among
such cations, and numerous R-carbonyl cations have been
generated as intermediates in solvolysis reactions or
under stable ion conditions.5
R-Carbonyl cations can be formed as intermediates of
solvolyses via kC processes from many tertiary systems
4 containing an R-carbonyl group.3-5 These cations can
undergo solvent capture to give substitution products, or
sometimes rearrangement or 1,2- or 1,3- proton detach-
ment can occur to form various products. If the carbonyl
group is activated by a strongly electron-withdrawing
leaving group (L), carbonyl addition of solvent can also
compete with the direct solvent displacement. To pre-
clude this, an appropriate buffer is sometimes added to
solvolysis solvents.
containing an oxo substituent at a vicinal position ap-
peared to be appropriate, since they are free from nu-
cleophilic solvent assistance and carbonyl participation
from the rear side of the bridgehead carbon. Solvolyses
of various 2-oxo compounds were studied, and the sol-
volytic behavior observed in kinetics and product analy-
ses has been categorized.8b
Previously, we reported that the methanolysis of
2-oxobicyclo[3.3.1]non-1-yl triflate (6-OTf) gave [3.3.1]-
propellanone 12 as a minor product.8b,10 While a variety
of methods have been developed to prepare small-ring
propellanes,11 this finding provides the first example of
the σ-bond formation between a bridgehead cationic
carbon and another bridgehead carbon in solvolysis. To
reveal the factors involved in the formation of the
propellanone in the solvolyses of 6-OTf, the work has
been extended to other ring systems. This paper describes
the solvolyses of 2-oxobicyclo[3.3.1]non-1-yl triflate (6-
OTf), 2-oxobicyclo[4.3.1]dec-1-yl mesylate (7-OMs), 3,3-
dimethyl-2-oxobicyclo[3.3.1]non-1-yl triflate (8-OTf),
2-methylidenebicyclo[3.3.1]non-1-yl heptafluorobutyrate
In the course of our study on R-carbonyl cations,6-9 we
were interested in examining the magnitude of resonance
contribution1-5 as represented by 2 T 3. For this purpose,
the solvolysis studies on the bridgehead substrates 5
* To whom correspondence should be addressed. Tel: +81 75
7535689. Fax: +81 75 7533350.
† Present address: Department of Chemistry, Faculty of Engineer-
ing, Oita University, Oita, 870-1192, J apan.
(1) Gassman, P. G.; Tidwell, T. T. Acc. Chem. Res. 1983, 16, 279.
(2) Tidwell, T. T. Angew. Chem., Int. Ed. Engl. 1984, 23, 20.
(3) Creary, X. Acc. Chem. Res. 1985, 18, 3.
(4) Creary, X.; Hopkinson, A. C.; Lee-Ruff, E. In Advances in
Carbocation Chemistry, Vol. 1; Creary, X. Ed.; J AI Press Inc.: CT,
1989; pp 45-92.
(5) Creary, X. Chem. Rev. 1991, 91, 1625.
(6) Takeuchi, K. In Advances in Strained and Interesting Organic
Molecules, Supplement 1; Laali, K. K., Ed.; J AI Press Inc.: Greenwich,
CT, 1999; pp 123-145.
(7) Takeuchi, K.; Akiyama, F.; Ikai, K.; Shibata, T.; Kato, M.
Tetrahedron Lett. 1988, 29, 873.
(8) (a) Takeuchi, K.; Yoshida, M.; Ohga, Y.; Tsugeno, A.; Kitagawa,
T. J . Org. Chem. 1990, 55, 6063. (b) Takeuchi, K.; Ohga, Y.; Yoshida,
M.; Ikai, K.; Shibata, T.; Kato, M.; Tsugeno, A. J . Org. Chem. 1997,
62, 5696.
(10) Takeuchi, K.; Ohga, Y.; Tokunaga, K.; Tsugeno, A. Tetrahedron
Lett. 1996, 37, 8185.
(11) For reviews of small-ring propellanes, see: Wiberg, K. B. Chem.
Rev. 1989, 89, 975. Tobe, Y.: Propellanes. In Carbocyclic Cage
Compounds: Chemistry and Applications; Osawa, E., Yonemitsu, O.,
Eds.; VCH: New York, 1992; Chapter 5.
(9) Takeuchi, K.; Ohga, Y. Bull. Chem. Soc. J pn. 1996, 69, 833.
10.1021/jo000444d CCC: $19.00 © 2000 American Chemical Society
Published on Web 07/11/2000

Solvolysis of Bicyclic Bridgehead Compounds
J . Org. Chem., Vol. 65, No. 16, 2000 4965
Ta ble 1. Ra te Con sta n ts of Solvolysis of Va r iou s
Br id geh ea d Su bstr a tesa
Ch a r t 2
∆H‡b
/
∆S‡b
/
compd solvent T/°C
k1/s-1
kcal mol-1 cal mol-1K-1
6-OTf
7-OMs MeOH
DMSO 25.0 3.05 × 10-4 c
25.0 1.94 × 10-9 d
75.0 3.12 × 10-6 e
100.0 5.9 × 10-5 c
0.0 2.69 × 10-6 c
25.0 1.08 × 10-4 c
50.0 2.22 × 10-3 c
25.0 3.95 × 10-7 d
50.0 1.26 × 10-5 e
75.0 2.46 × 10-4 e
29.8
1.5
8-OTf
10-Br
MeOH
MeOH
23.0
26.0
0.3
1.9
DMSO 25.0 1.51 × 10-8 d
75.0 3.77 × 10-6 c
22.2
-19.9
100.0 3.41 × 10-5 c
(n-C3F7CO2-) (9-OHF B), 1-bromobicyclo[3.3.1]nonane
(10-Br ), and 3,3-dimethyl-2-thioxobicyclo[3.3.1]non-1-yl
tosylate (11-OTs) (Chart 2). To illuminate the effect of
the substituent and the ring size on the stability and
reactivity of the bridgehead cations, we carried out PM3
and ab initio calculations for carbocations and related
species.
11-OTs MeOH
25.0 1.54 × 10-5 e
50.0 2.54 × 10-4 e
25.0 1.76 × 10-6 e
50.0 2.72 × 10-5 e
20.9
20.4
-10.5
-16.5
EtOH
a
The rates were titrimetrically determined by a single run for
0.02 or 0.01 M substrates in the presence of 0.025 M 2,6-lutidine.
b
d
At 25.0 °C. c Initial rate. Extrapolated from data at other
temperatures. e The correlation coefficient for the first-order plot
was greater than 0.998.
Resu lts a n d Discu ssion
Syn th eses of Solvolysis Su bstr a tes. Precursor al-
cohols, 1-hydroxybicyclo[3.3.1]nonan-2-one (6-OH ),8b
2-methylidenebicyclo[3.3.1]nonan-1-ol (9-OH),12 and 1-hy-
droxybicyclo[4.3.1]decan-2-one (7-OH),8b were prepared
by previously reported methods and converted to the
corresponding triflate, heptafluorobutyrate, and meth-
anesulfonate (mesylate), respectively.13 1-Bromobicyclo-
[3.3.1]nonane (10-Br ) was prepared following the previ-
ously reported method.14 1-Hydroxy-3,3-dimethylbicyclo-
[3.3.1]nonan-2-one (8-OH) was prepared from 8-OMe by
the cleavage of the methyl ether by using chlorotrimeth-
ylsilane/NaI.15 Compound 8-OMe was obtained by the
methylation16 of 6-OH using NaNH2 and CH3I. The
thioxo alcohol 11-OH was derived from the ketol 8-OH
via thionation17 of the 2-hydrazono alcohol. The two
methyl groups on the C(3) position of 11-OH and its
homologues preclude thioenolization of the thiocarbonyl
group.
Solvolysis Ra tes. To estimate 10 half-lives for product
studies, the solvolysis rates were required. The rates of
6-OTf8b and 9-OHF B12 in MeOH and EtOH were re-
ported previously. The rates of 7-OMs, 8-OTf, 10-Br , and
11-OTs were determined in MeOH and/or EtOH. 6-OTf
and 10-Br were also subjected to solvolysis in DMSO.
The rate data determined in this study are summarized
in Table 1.
Sch em e 1
(15-OMe) (5%), and several unidentified compounds
amounting to 12% (Scheme 1).8b,10 In the present study,
the reaction was conducted at 50 °C to give the result
shown in Scheme 1. By careful separation of the mixture
of the unidentified compounds by HPLC, 1,2-dimethoxy-
bicyclo[3.3.1]non-2-ene (14-OMe) (3%) was isolated.18 The
yield of 12 was similar between the two experiments at
25 and 50 °C, but the yields of 6-OMe and 13-OMe
considerably changed, perhaps because the rearrange-
ment to 13-OTf via ion pair return was facilitated at
higher temperature.
Effects of Solven t a n d Ad d ed Ba se on th e Yield
of [3.3.1]P r op ella n on e. The yield of propellanone 12
in the methanolysis of 6-OTf changed when the added
base was varied (Table 2). When 2,6-lutidine (pKa 6.72)
is added to methanolysis, the yield of the propellanone
is the highest at 13%. The use of a stronger base,
triethylamine (pKa 10.72),19,20 decreases the yield of pro-
pellanone 12 to 2%. This implies that the added base does
not play a role in abstracting the proton attached to the
C(5) position. Rather, triethylamine appears to catalyze
the carbonyl addition of the solvent that leads to Favor-
skii rearrangement-type product 15-OMe (Scheme 2).
The formation of 15-OMe is markedly facilitated by
sodium methoxide, most probably owing to the direct
addition of the methoxide ion to the carbonyl group. The
P r od u cts of Solvolyses of 2-Oxobicyclo[3.3.1]n on -
1-yl Tr ifla te (6-OTf). Four products were previously
reported for the methanolysis of 6-OTf in the presence
of 2,6-lutidine at 25 °C, i.e., 6-OMe (38%), 2,3,5,6-
tetrahydro-3a,6a-methano-1H,4H-pentalen-1-one (12)
(15%), 1-(methoxymethyl)bicyclo[3.3.0]octan-2-one (13-
OMe) (30%), methyl bicyclo[3.2.1]octane-1-carboxylate
(12) Takeuchi, K.; Kitagawa, T.; Ohga, Y.; Yoshida, M.; Akiyama,
F.; Tsugeno, A. J . Org. Chem. 1992, 57, 280.
(13) The 13C NMR spectra of these substrates showed that they were
essentially pure.
(14) Schleyer, P. v. R.; Isele, P. R.; Bingham, R. C. J . Org. Chem.
1968, 33, 1239.
(15) Olah, G. A.; Narang, S. C.; Gupta, B. G. B.; Malhotra, R. J .
Org. Chem. 1979, 44, 1247.
(16) Muir, D. J .; Stothers, J . B. Can. J . Chem. 1993, 71, 1099.
(17) Okazaki, R.; Inoue, K.; Inamoto, N. Bull. Chem. Soc. J pn. 1981,
54, 3541.
(18) The identification of 14 was based on the elemental analysis
and the spectral data shown in Experimental Section.

4966 J . Org. Chem., Vol. 65, No. 16, 2000
Ta ble 2. P r od u ct Distr ibu tion s in th e Meth a n olysis of 2-Oxobicyclo[3.3.1]n on -1-yl Tr ifla te (6-OTf)a
product yieldd/%
Tokunaga et al.
entry
baseb
pKa
T/°C
timec
6-OMe
12
13-OMe
14-OMe
15-OMe
1
2
3
4
5
6
no bufffer
2,6-di-tert-butylpyridine
pyridine
2,6-lutidine
triethylamine
NaOCH3
25
50
50
50
50
50
t1/2 × 6
17
14
21
57
60
12
0
5
8
13
2
0
0
9
14
22
3
13
31
35
3
0
0
69
35
21
1
32
86
3.58e
5.22f
t1/2 × 10
t1/2 × 10
t1/2 × 10
t1/2 × 10
t1/2 × 10
6.72f
10.72g
0
Concentration of the triflate was 0.020 M. 0.025 M. c The t1/2 denotes the half-life of entry 4. Determined by GLC. For the structures,
a
b
d
see Scheme 1. e In 50% aqueous ethanol at 50 °C; ref 19. f In water at 25 °C. Encyclopedia of Chemical Technology, 3rd ed.; J ohn Wiley
g
and Sons: New York, 1984; Vol. 19, p 455. In water at 25 °C; ref 20.
Sch em e 2
was also formed in 4% yield, but further characterization
will be required (see the Supporting Information).
The structure of 17 was estimated from the resem-
1
blance of its H and 13C NMR spectra to those28 of 6-hy-
droxy-1-methyl-cis-bicyclo[4.3.0]nonan-2-one (20). The 1H
NMR spectrum of 17 showed a singlet at δ 1.14 (s, 3H),
which is in accord with a singlet at δ 1.18 (s, 3H) for 20.
The 13C NMR spectrum of 17 showed signals at δ 87.9
(C) and 60.3 (C), which are close to the respective signals
at δ 93.0 (C) and 59.46 (C) in the data for 20. The po-
sitions of other signals for methyl and methylene carbons
of 17 are also close to those reported for 20 (Chart 3).28
Two processes seemed probable for the formation of 17
(Scheme 4). The bridgehead cation 7+ might rearrange
into 22 via a two-step process through a primary cation
21 (or by a concerted mechanism) to give 17 [process (a)].
On the other hand, the cyclopropane moiety of the [4.3.1]-
propellanone 16 might be protonated29 and cleaved
[process (b)] to give 22. To distinguish between the two
possibilities, the solvolysis in methanol-d was carried out.
If the opening of protonated cyclopropane ring occurred
[process (b)], a deuterium would have been incorporated
into the methyl group on the C(1)-position of 17 as in
23.
increased formation of 15-OMe in the absence of a base
(entry 1, Table 2), or when 2,6-di-tert-butylpyridine (pKa
3.58; entry 2, Table 2) and pyridine (pKa 5.22; entry 3,
Table 2), weaker bases than 2,6-lutidine, are used in
place of 2,6-lutidine is most probably ascribed to acid-
catalyzed carbonyl addition of methanol (Scheme 2).
The propellanone formation is highly dependent on
solvent (Table 3). The solvolysis in TFE or AcOH buffered
with 2,6-lutidine or NaOAc, respectively, gave a bridge-
head substitution product in 83% or 90% yield, respec-
tively, and 12 was not found to the limit of detection (1%)
by 13C NMR and GLC.21 On the other hand, the use of
DMSO and DMF as solvent (with added 2,6-lutidine)
increased the yield of 12 to 48 and 25%, respectively. The
greater yields of 12 in DMSO and DMF than those in
MeOH and EtOH can be explained by the greater ability
of the former solvents to abstract a proton; the donor
numbers (DN)22 of DMSO (29.8) and DMF (26.6) are
significantly greater than those of MeOH (19) and EtOH
(20). The fact that 12 was not detected in the solvolysis
in TFE and AcOH is consistent with the very low
estimated23 DN of 10.
P r od u cts of Solvolysis of 2-Oxobicyclo[4.3.1]d ec-
1-yl Mesyla te (7-OMs). [4.3.1]Propellanone 16 was
detected in 3% yield by GLC in the solvolysis product of
2-oxobicyclo[4.3.1]dec-1-yl mesylate (7-OMs). Identifica-
tion of 16 rests upon exact mass (calcd. 150.1045 and
found 150.1044) and perfect agreement of the 13C NMR
data with the authentic24,25 sample. Compounds 17-19
were also obtained (Scheme 3).26,27 Scheme 3 shows the
product distribution determined by GLC analysis. The
1H and 13C NMR suggested that the trans isomer of 17
The relative intensities of the signals corresponding
to ether 17 in the 1H NMR spectrum of the crude product
from the solvolysis in methanol-d were similar to those
corresponding to 17 from the methanolysis of 7-OMs. In
the 13C NMR spectrum of 17 from the reaction in
methanol-d, the signal of the methyl group attaching at
the C(1)-position was a singlet. These observations show
that the methyl group is not CH2D but CH3. Conse-
quently, it is concluded that 17 forms via process (a).
+
Since the migrating hydride is located close to the CH2
moiety, direct 1,3-hydride shift would proceed in 21 to
give 22.
P r od u cts of Solvolysis of 3,3-Dim eth yl-2-oxobi-
cyclo[3.3.1]n on -1-yl Tr ifla te (8-OTf). Propellanone 24
was obtained in the solvolysis of 8-OTf in 20% yield
(24) Banwell, M. G.; Haddad, N.; Huglin, J . A.; MacKay, M. F.;
Reum, M. E.; Ryan, J . H.; Turner, K. A. J . Chem. Soc., Chem. Commun.
1993, 954.
(25) Private communication from Professor M. G. Banwell, The
Australian National University, Canberra, is gratefully acknowledged.
(26) Previously, it was reported that the methanolysis of 2-oxobicyclo-
[4.3.1]dec-1-yl 2,2,2-trifluoroethanesulfonate yielded the bridgehead
substitution product 7-OMe (29%) and a mixture of unidentified
products (71%).8b
(19) Brown, H. C.; Kanner, B. J . Am. Chem. Soc. 1953, 75, 3865.
(20) Riddick, J . A.; Bunger, W. B. In Organic Solvents, 3rd ed.;
Wiley-Interscience: New York, 1970; p 440.
(21) The identification of the products for solvolysis in EtOH,
trifluoroethanol (TFE), AcOH, DMF, and DMSO rests on the resem-
blance of the 13C NMR spectra to those of the corresponding methanol
adducts or the authentic samples.
(22) Gutmann, V. The Donor-Acceptor Approach to Molecular
Interactions; Plenum Press: New York, 1978; pp 27-33.
(23) Reimers, J . R.; Hall, L. E. J . Am. Chem. Soc. 1999, 121, 3730.
(27) 18 was identified on the basis of the symmetric structure shown
by 13C NMR.
(28) Caine, D.; McCloskey, C. J .; Derveer, D. V. J . Org. Chem. 1985,
50, 175.
(29) Protonated cyclopropane ring can open in some cases; see:
March, J . Advanced Organic Chemistry: Reactions, Mechanism and
Structure, 4th ed.; J ohn Wiley & Sons: New York; 1992; pp 755-758
and pp 1056-1063.

Solvolysis of Bicyclic Bridgehead Compounds
J . Org. Chem., Vol. 65, No. 16, 2000 4967
Ta ble 3. P r od u ct Distr ibu tion in th e Solvolysis of 2-Oxobicyclo[3.3.1]n on -1-yl Tr ifla te (6-OTf) u n d er Va r iou s
Rea ction Con d ition sa
product and yieldc/%
entry
solvent
baseb
T/°C
time
6-OR
12
13-OR
14-OR
15-OR
1
2
3
4
5
6
MeOH
EtOH
TFEf
AcOH
DMFi
DMSO
2,6-lutidine
2,6-lutidine
2,6-lutidine
NaOAc
2,6-lutidine
2,6-lutidine
50
50
50
25
75
25
t1/2 × 10
t1/2 × 10
t1/2 × 10
t1/2 × 10
t1/2 × 10
t1/2 × 10
57d
48e
83g
90h
22j
14k
13
14
0
0
25
48
22d
31e
2g
3d
2e
0
1d
2e
13g
0
0
0
3h
0
45j
7k,l
<3j
0
[6-OTf]o ) 0.02 M. 0.025 M. c The product distributions were determined by GLC except for entries 3 and 4, where 13C NMR was
a
b
used. For the structures of the products, see Scheme 1 for R ) Me as an example. R ) CH3. e R ) C2H5. f 2,2,2-Trifluoroethanol. R )
d
g
h
i
j
k
l
CF3CH2. R ) CH3CO. Containing 0.006 M H2O. R ) CHO. R ) H. Containing 2-oxobicyclo[3.3.0]oct-1-yl carbaldehyde (26%).
Sch em e 3
Sch em e 5
Ch a r t 4
Ch a r t 3
Sch em e 4
51 h at 75 °C and for 1.3 h at 50 °C, respectively. The
products were identified as the bridgehead ethers, 9-OMe
and 9-OTF E, respectively, on the basis of the 13C NMR
spectra.30 The product in the methanolysis of 10-Br for
10 half-lives at 75 °C was solely the bridgehead substitu-
tion product: even when DMSO was used as solvent (for
10 half-lives at 100 °C), the propellane was not detected
by GLC and 13C NMR analyses. The methanolysis of 3,3-
dimethyl-2-thioxobicyclo[3.3.1]non-1-yl tosylate (11-OTs)
for 10 half-lives at 50 °C gave unrearranged 11-OMe in
100% yield, on the basis of the GLC and 13C NMR
analyses.31
Th eor etica l Ca lcu la tion s on Br id geh ea d Ca r -
boca tion s a n d P r op ella n es. Computational studies
were carried out for a series of bicyclo[3.3.1]non-1-yl
cations 6+, 9+, 10+, and 27+ (Chart 4) to shed light on
the structure and reactivity of intermediate bridgehead
cations. Since these species can exist in different confor-
mations, e.g., chair-chair, chair-boat, boat-chair, and
(Scheme 5). Identification of 24 rests upon exact mass
(calcd. 164.1201, found 164.1198) and close resemblance
of its 13C NMR spectrum to that of [3.3.1]propellanone
12. Primary triflate 25, whose formation is ascribable to
ion pair return, and corresponding methyl ether 26 were
also obtained. Spectral evidence for 24-26 is given in
the Experimental Section.
P r odu cts of Solvolyses of 2-Meth yliden e, 2-Th ioxo,
a n d P a r en t Su bstr a tes. No propellane-type product
was obtained in the solvolyses of 2-methylidenebicyclo-
[3.3.1]non-1-yl heptafluorobutyrate (9-OHFB), 1-bromobi-
cyclo[3.3.1]nonane (10-Br ), and 3,3-dimethyl-2-thioxobi-
cyclo[3.3.1]non-1-yl tosylate (11-OTs).30 The solvolyses of
2-methylidene derivative 9-OHF B were conducted in
MeOH and TFE in the presence of excess 2,6-lutidine for
(30) These observations are in accord with the previous report12 that
the solvolysis of crude 9-OMs in 80% ethanol gave only bridgehead
substitution products 9-OH and 9-OEt. The product of solvolysis of
10-Br in 80% ethanol buffered with Na2CO3 (5 molar amount of 10-
Br ) for 2 h reflux was also studied following a previously reported
procedure.14 GLC and 13C NMR analyses showed that the bridgehead
substitution is the sole reaction.
(31) The kinetic study for the solvolysis of 2-thioxo derivative 11-
OTs will be reported elsewhere.

4968 J . Org. Chem., Vol. 65, No. 16, 2000
Tokunaga et al.
Ta ble 4. Ca lcu la ted (B3LYP /6-31G*) Electr on ic En er gies of Br id geh ea d Ca tion s a n d th e P a r en t Str u ctu r esa
conformationc
(A)
energy
-425.703038 (0) 127.5 -425.703048 (+0.14) 127.7 -425.698726 (+2.55) 127.4 converged to (C)
converged to (B) -389.809211 (0) 143.7 -389.791720 (+9.99) 142.7 -389.802217 (+4.39) 143.7
-351.721310 (0) 140.7 -351.719275 (+1.09) 140.5 -351.710451 (+6.25) 140.1
converged to (B) -748.670731 (0) 126.7 -748.670652 (+0.29) 126.9 converged to (C)
-426.621074 (0) 136.4 -426.620379 (+0.49) 136.5
-390.691669 151.6
(B)
(C)
(D)
speciesb
ZPE
energy
ZPE
energy
ZPE
energy
ZPE
6+ (X ) O)
9+ (X)CH2)
10+ (X ) H2)
27+ (X ) S)
6-H (X ) O)
9-H (X)CH2)
10-H (X ) H2) -352.607983 (0) 148.9 -352.603455 (+2.76) 148.8
27-H (X ) S)
-749.576594 (0) 135.3 -749.575003 (+0.84) 135.1
a
Energies in hartree and zero-point energies (ZPE) in kcal mol-1. Relative energies in kcal mol-1, after inclusion of zero-point energies,
are given in parentheses. See Figure 1 for the most stable conformations. c See Chart 4 for structures of cations and conformations (A),
b
(B), (C), and (D).
Ta ble 5. Ca lcu la ted (B3LYP /6-31G*) Electr on ic En er gies
for Som e [3.3.1]P r op ella n e-typ e Com p ou n d sa
pellanes are shown in Figures 1 and 2, respectively. The
calculation results will be used in the following discus-
sions on the mechanism and factors affecting the forma-
tion of propellane type products.
compd
energy/hartree
ZPE/kcal mol-1
12
28
29
30
-425.379617
-389.448403
-351.363590
-748.337750
120.80
135.63
132.84
119.43
Mech a n ism of P r op ella n on e F or m a tion . A possible
mechanism for the formation of [3.3.1]propellanone 12
involves a homohyperconjugative interaction of the bridge-
head cationic p orbital with the sp3 back lobe on the other
bridgehead carbon. Della and co-workers attributed the
enhanced stability of bicyclo[3.1.1]heptyl cation (31) to
σ-hyperconjugation as depicted by 31T32 and 33 (Scheme
6).46-48 Resonance stabilization of 34T35 for the bicyclo-
[1.1.1]pent-1-yl cation has also been postulated by the
Della group to explain the unexpectedly facile formation
of the bicyclo[1.1.1]pent-1-yl cation in solvolysis (Scheme
6).46,48 On the contrary, the Wiberg group interprets that
34 is a transition state leading to the bicyclo[1.1.0]butyl-
1-carbinyl cation (36) on the basis of MP2/6-31G* calcu-
lations.49 Promotion of homohyperconjugative interaction
by a silyl substituent has been demonstrated in the
solvolysis of an open-chain system 37.50
We assume that 2-oxobicyclo[3.3.1]non-1-yl triflate (6-
OTf) gives an unbridged carbocation as the first inter-
mediate. Concerted processes, in which the σ bond is
formed between the bridgehead carbons via simultaneous
departure of the nucleofuge (TfO-) and deprotonation,
or a bridged ion 38 (Scheme 6) is formed synchronously
with ionization, may be less probable. The complex
product pattern in the solvolysis of 6-OTf (Scheme 1)
would preclude the possibility of concerted processes.
Moreover, the solvolysis of 6-OTf does not appear to be
accelerated by neighboring group participation.8b The
B3LYP/6-31G*-optimized geometry of cation 6+ suggests
an unbridged carbocation, since the distance between the
a
See Figure 2 for the most stable conformations.
boat-boat forms (Chart 4), the most stable conformers
were sought by ab initio calculations at HF/3-21G* and
B3LYP/6-31G* levels (Table 4).32 To avoid conformational
complexity, 3,3-dimethylated species were not included
For 6+, 9+, and 27+, the most stable conformers were
found to be chair-boat (B) form by calculations at B3LYP/
6-31G* (Table 4).39 For bicyclo[3.3.1]non-1-yl cation (10+),
the chair-chair (A) form is the most stable. For reference
systems, 6-H, 9-H, 10-H, and 27-H, geometry optimiza-
tions and energy analyses at B3LYP/6-31G* were also
carried out for the chair-chair (A) structures (Table 4).40
Table 5shows the energies at B3LYP/6-31G* for [3.3.1]-
propellanone 12 and related [3.3.1]propellanes 28-30:45
the optimized geometries for the carbocations and pro-
(32) Geometries were optimized with Gaussian 9433 at the Hartree-
Fock (HF) level with the 3-21G* basis set34 and verified to be minima.
By using the HF/3-21G*-optimized geometry as starting structure,
optimization and energy calculations were carried out with nonlocal
hybrid density functional theory (DFT)35 at the B3LYP level36, 37 with
a larger split-valence d-polarized 6-31G* basis set.38
(33) Gaussian 94, Revision E.2, Frisch, M. J .; Trucks, G. W.;
Schlegel, H. B.; Gill, P. M. W.; J ohnson, B. G.; Robb, M. A.; Cheeseman,
J . R.; Keith, T.; Petersson, G. A.; Montgomery, J . A.; Raghavachari,
K.; Al-Laham, M. A.; Zakrzewski, V. G.; Ortiz, J . V.; Foresman, J . B.;
Cioslowski, J .; Stefanov, B. B.; Nanayakkara, A.; Challacombe, M.;
Peng, C. Y.; Ayala, P. Y.; Chen, W.; Wong, M. W.; Andres, J . L.;
Replogle, E. S.; Gomperts, R.; Martin, R. L.; Fox, D. J .; Binkley, J . S.;
Defrees, D. J .; Baker, J .; Stewart, J . P.; Head-Gordon, M.; Gonzalez,
C.; Pople, J . A. Gaussian, Inc., Pittsburgh, PA, 1995.
(34) Pietro, W. J .; Francl, M. M.; Hehre, W. J .; DeFrees, D. J .; Pople,
J . A.; Binkley, J . S. J . Am. Chem. Soc. 1982, 104, 5039.
(35) Becke, A. D. J . Chem. Phys. 1993, 98, 5648.
(43) Engler, E. M.; Andose, J . D.; Schleyer, P. v. R. J . Am. Chem.
Soc. 1973, 95, 8005.
(44) Mastryukov, V. S.; Popik, M. V.; Dorofeeva, O. V.; Golubinskii,
A. V.; Vilkov, L. V.; Belikova, N. A.; Allinger, N. L. J . Am. Chem. Soc.
1981, 103, 1333.
(36) Becke, A. D. Phys. Rev. 1988, A38, 3098.
(37) Lee, C.; Yang, W.; Parr, R. G. Phys. Rev. 1988, B37, 785.
(38) Francl, M. N.; Pietro, W. J .; Hehre, W. J .; Binkley, J . S.; Gordon,
M. S.; DeFrees, D. J .; Pople, J . A. J . Chem. Phys. 1982, 77, 3654.
(39) By inclusion of zero-point energy, the conformer (A) becomes
the most stable for 6+.
(40) For bicyclo[3.3.1]nonanes 6-H, 9-H, 10-H, and 27-H, the most
stable conformers were found to be chair-chair forms on the basis of
the heats of formation for some conformers calculated by PM3.41 For
10-H, the chair-chair conformation was found to be 2.8 kcal/mol more
stable than the chair-boat form; this agrees nicely with recent
calculations42 at BLYP/6-31G* (2.8 kcal/mol), with force-field calcula-
tions43 (2.3 kcal/mol), and with experimental44 data (2.3 kcal/mol).
(41) MOPAC Ver. 6, Stewart, J . J . P. QCPE Bull. 1989, 9, 10;
Revised as Ver. 6.01 by Hirano, T. University of Tokyo, for UNIX
machine J CPE Newsletter 1989, 1, 10.
(45) The boat-boat conformer of the [3.3.1]propellanone 12 was found
to be the most stable by geometry optimizations and energy calcula-
tions at B3LYP/6-31G*. For practical reasons, geometry optimizations
and energy calculations for 28-30 were carried out only for the boat-
boat forms.
(46) (a) Della, E. W.; Schiesser, C. H.: Strained Bridgehead Cy-
clobutyl Cations. In Advances in Carbocation Chemistry; Coxon, J . M.,
Ed.; J AI Press Inc.: CT, 1995; Vol. 2, pp 91-122. (b) Della, E. W.;
Pigou, P. E.; Tsanaktsidis, J . J . Chem. Soc., Chem. Commun. 1987,
833. (c) Della, E. W.; Elsey, G. M. Tetrahedron Lett. 1988, 29, 1299.
(47) Della, E. W.; Elsey, G. M. Aust. J . Chem. 1995, 48, 967.
(48) Della, E. W.; Grob, C. A.; Taylor, D. K. J . Am. Chem. Soc. 1994,
116, 6159.
(49) Wiberg, K. B.; McMurdie, N. J . Am. Chem. Soc. 1994, 116,
11990.
(50) Coope, J .; Shiner, V. J ., J r. J . Org. Chem. 1989, 54, 4270.
(42) Fokin, A. A.; Schreiner, P. R.; Schleyer, P. v. R.; Gunchenko,
P. A. J . Org. Chem. 1998, 63, 6494.

Solvolysis of Bicyclic Bridgehead Compounds
J . Org. Chem., Vol. 65, No. 16, 2000 4969
F igu r e 1. Selected B3LYP/6-31G*-calculated distances (Å) for 6+, 9+, 10+, 27+, 9-H, and 27-H.
Sch em e 7
F igu r e 2. Selected B3LYP/6-31G*-calculated bond distances
(Å) for some [3.3.1]propellanes 12, 28, 29, and 30.
Sch em e 6
The carbon-carbon bond formation by the attack of a
carbocation to a C-H bond is generally interpreted to
occur through a nonclassical ion via front-side attack
(Scheme 7, (a)).51 On the other hand, the formation of 12
from 6+ is formally carbon-carbon bond formation by the
backside attack of a carbocation to a methine carbon
(Scheme 7 (b)). To date numerous examples of 1,3-
elimination of carbocations have been reported, but only
a few studies have been done on the stereochemical
outcomes to our knowledge. Werstiuk reported that the
semi-U type deprotonation is preferred (Hendo:Hexo
)
15∼20:1) in the secondary cation (Scheme 7 (c)).52a On
the other hand, Nickon showed that the semi-W type
(51) (a) Olah, G. A. Angew. Chem., Int. Ed. Engl. 1995, 34, 1393.
(b) Olah, G. A.; Rasul G. Acc. Chem. Res. 1997, 30, 245.
(52) (a) Werstiuk, N. H. J . Chem. Soc., Chem. Commun. 1970, 1499.
(b) Nickon, A.; Simons, J . R.; Ho, B. J . Org. Chem. 1977, 42, 800.
two bridgehead carbons, C(1) and C(5), of 2.254 Å is too
long as compared with the C(5)-C(9) and C(1)-C(9) bond
lengths (1.680 and 1.427 Å, respectively) (Figure 1).

4970 J . Org. Chem., Vol. 65, No. 16, 2000
Tokunaga et al.
Sch em e 8
prevails in the p-anisyl substituted tertiary cations with
deprotonation ratios of Heq:Hax ) 7.4:1 (Scheme 7 (d)) and
Hexo:Hendo ) 27:1 (Scheme 7 (e)).52b Although the detailed
mechanism of the electron shift during the deprotonation
has not been clarified, it is interesting to point out that
the backside attack of a carbocation to a C-H bond
(Scheme 7 (b)) is also a common pathway.
F a ctor s Affectin g th e F or m a tion of P r op ella n e-
Typ e P r od u ct. (a ) C(2)-Su bstitu en t a n d Electr o-
p h ilic Na tu r e of Br id geh ea d Ca tion ic Ca r bon . In-
tuitively, the ease of the C(1)-C(5) bond formation would
be controlled by the electron accepting ability of the
cationic C(1) carbon, which can be evaluated by LUMO
energy levels. Therefore, LUMO energies of 2-substituted
bicyclo[3.3.1]non-1-yl cations were calculated by PM3,
which decrease in the order 9+ (X ) CH2) (-6.9972 eV),
10+ (unsubstituted) (-7.1000 eV), 27+ (X ) S) (-7.3782
eV), and 6+ (X ) O) (-7.5826 eV). The lowest LUMO
energy of 6+ is consistent with the easiest formation of
the corresponding [3.3.1]propellanone 12 through the
interaction between the cationic p orbital and the back
lobe of the C(5)-H bond. Previously, we reported that
some R-carbonyl cations are very strong one-electron
oxidizing agents.53 Although it is not clear if an SET
pathway is involved in the C(1)-C(5) bond formation to
give 12, the driving force for the bond formation should
be the low LUMO level of 6+.
Another factor for the greatest ability of 6+ to form the
C(1)-C(5) bond might be ascribed to the more favorable
geometry of 6+ than the other related cations. The
B3LYP/6-31G* calculated distance between the two
bridgehead carbons C(1) and C(5) in cations decreases
in the order 9+ (2.313 Å), 10+ (2.311 Å), 27+ (2.280 Å),
and 6+ (2.254 Å). The shortest distance between C(1) and
C(5) of 6+ among the four cations also appears to be
related to the easiest formation of the C(1)-C(5) bond.
(b) Effect of C(2)-Su bstitu en t on th e Sta bility of
P r op ella n e-Typ e P r od u cts. It is well-known that a π
accepting group attached to a cyclopropane ring stabilizes
the system by HOMO-LUMO interaction.54,55 This con-
cept has successfully been applied to the explanation of
the effect of a C(7)-substituent on the equilibrium be-
tween 1,3,5-cycloheptatriene and norcaradiene,56 and
barriers to internal rotation of cyclopropylmethanal and
related compounds.57 The HOMO-LUMO interaction in
the 1-substituted cyclopropanes has been interpreted as
shortening (strengthening) the C(2)-C(3) bond and length-
ening the C(1)-C(2) and C(1)-C(3) bonds.54-56
culated from the energies of relevant species at B3LYP/
6-31G* (Tables 4 and 5).
The ∆Eprop values (kcal mol-1) of -3.2, -1.4, -0.6, and
0 (by definition) for 30, 12, 28, and 29, respectively,
suggest that the thermodynamic stability decreases in
this order, and that the thiocarbonyl group is a stronger
π acceptor than carbonyl and vinyl groups. Despite the
greater π acceptor ability of the thiocarbonyl group, no
propellane-type product has been detected in the solvoly-
sis of 2-thioxo compound 11-OTs. The formation of the
propellane-type product only from 2-oxo compounds
suggests that the relatively low LUMO energy levels of
the intermediate 2-oxo carbocations facilitate the forma-
tion of the 2-propellanones.
Con clu sion s
Methanolyses of 2-oxobicyclo[3.3.1]non-1-yl triflate (6-
OTf), 3,3-dimethyl-2-oxobicyclo[3.3.1]non-1-yl triflate (8-
OTf), and 2-oxobicyclo[4.3.1]dec-1-yl mesylate (7-OMs)
gave the corresponding propellanones in 12%, 20%, and
3.2% yield, respectively, under typical solvolysis condi-
tions. The use of DMF and DMSO as solvent markedly
increases the yield of [3.3.1]propellanone 12 from 6-OTf.
The solvent basicity (donor number) is an important
factor. Acidic or strongly basic conditions inhibit the for-
mation of 12 by changing the reaction from SN1 to solvent
addition to the carbonyl group. No propellane-type prod-
uct was obtained in the solvolysis of 1-bromobicyclo[3.3.1]-
nonane (10-Br ), 2-methylidenebicyclo[3.3.1]non-1-yl hep-
tafluorobutyrate (9-OHF B), and 3,3-dimethyl-2-thioxo-
bicyclo[3.3.1]non-1-yl tosylate (11-OTs). The results of
experimental and computational studies show that three-
carbon and one-carbon bridges in the substrate (such as
bicyclo[3.3.1]nonyl and bicyclo[4.3.1]decyl systems) and
the highly destabilized, electrophilic nature of bridgehead
cations such as 2-oxo cations are necessary for the
formation of propellane-type products in solvolysis.
The C(5)-C(9) bond length in the B3LYP/6-31G*-
optimized geometries of [3.3.1]propellanes decreases in
the order 29 (1.514 Å), 28 (1.503 Å), 12 (1.494 Å), and 30
(1.489 Å) (Figure 2). Conversely, the sequence of the
respective C(1)-C(5) bond lengths is just opposite, i.e.,
1.520, 1.530, 1.534, and 1.546 Å. The geometries indicate
that the thioxo propellane 30 is electronically most
stabilized among the four propellane-type compounds.
Energetics from the B3LYP/6-31G* calculations lead to
the same conclusion. Scheme 8 shows the ∆Eprop values
{) [Eprop(X) + Eh(X ) H2)] - [Eprop(X ) H2) + Eh(X)]} for
three isodesmic reactions for propellane formation cal-
Exp er im en ta l Section
Melting points are uncorrected. 1H NMR spectra were
recorded at 90, 270, or 400 MHz. 13C NMR spectra were
recorded at 22.5, 68, or 100 MHz. GLC analyses were con-
ducted on a PEG 20M column (3 mm × 2 m). Mass spectra
were recorded on a GC-MS spectrometer. Elemental analyses
were performed by the Microanalytical Center, Kyoto Univer-
sity, Kyoto. Starting ketols 6-OH and 7-OH were reported
(53) Kitagawa, T.; Nishimura, M.; Takeuchi, K.; Okamoto, K.
Tetrahedron Lett. 1991, 32, 3187.
(54) Hoffmann, R. Tetrahedron Lett. 1970, 2907.
(55) Gu¨nther, H. Tetrahedron Lett. 1970, 5173.
(56) Review: Balci, M. Turkish J . Chem. 1992, 16, 8.
(57) Pawar, D. M.; Noe, E. A. J . Org. Chem. 1998, 63, 2850.

Solvolysis of Bicyclic Bridgehead Compounds
J . Org. Chem., Vol. 65, No. 16, 2000 4971
previously.58 Solvolysis solvents were purified by previously
described methods.59 Anhydrous solvents used for synthesis
were purified by the standard procedures. 2,6-Lutidine was
distilled over CaH2. Other commercially available reagents
were of reagent-grade quality and used as received. Medium-
pressure liquid chromatography (MPLC) was conducted on
Merck silica gel 60 (230-400 mesh).
(CH3), 60.3 (C), 87.9 (C), 214.0 (C). 18: 1H NMR (CDCl3, 270
MHz) δ 1.27 (br s, 4H), 1.39-2.19 (m, 9H), 2.26 (dt, 2H, J )
3.0, 7.4 Hz), 3.64 (s, 3H); 13C NMR (68 MHz, CDCl3) δ 21.9
(CH2), 27.9 (CH), 30.3 (CH2), 33.3 (CH2), 36.1 (CH2), 41.1 (C),
51.6 (CH3), 179.3 (C). 19: 1H NMR (CDCl3, 270 MHz) δ 1.20-
2.55 (m, 13H), 2.68 (br s, 1H), 3.34 (s, 3H), 3.79 (d, 1H, J )
2.9 Hz); 13C NMR (68 MHz, CDCl3) δ 22.3 (CH2), 24.5 (CH2),
24.7 (CH2), 25.6 (CH2), 29.6 (CH), 36.6 (CH2), 44.2 (CH2), 48.8
(CH), 55.8 (CH3), 77.4 (CH), 216.2 (C).
P r od u ct of Solvolysis of 7-OMs in Meth a n ol-d . A
solution of 7-OMs (0.247 g, 1.00 mmol) in 0.050 M 2,6-lutidine
in methanol-d (25.0 mL) was kept at 75 °C for 25 days. After
most of the methanol-d had been evaporated, the residue was
worked up in a usual manner to give a yellow liquid and the
product distribution was determined by GLC and NMR.
1-Meth oxy-3,3-Dim eth ylbicyclo[3.3.1]n on a n -2-on e (8-
OMe). The literature16 procedure was followed. To a stirred
suspension of freshly powdered NaNH2 (318 mmol) in THF
(53 mL) was added a solution of 6-OH (8.17 g, 53.0 mmol) in
THF (53 mL) and the mixture heated under reflux for 2 h with
stirring. The mixture was cooled and CH3I (318 mmol) was
added slowly before the mixture was refluxed for 17 h, at which
time a second addition of CH3I (106 mmol) was made. After a
reflux period of 4 h, the mixture was cooled to 0 °C and the
excess NaNH2 decomposed with cold water. The mixture was
extracted with ether and the ether extract was washed with
water and 10% NaCl and dried (MgSO4). Evaporation of the
solvent followed by MPLC (SiO2, hexane-diethyl ether) af-
forded 8-OMe (8.63 g, 83%) as a pale yellow liquid. Adding
hexane to the liquid and cooling at -20 °C afforded white
P r od u ct of Meth a n olysis of 6-OTf. A reported procedure
was followed.8b A solution of 6-OTf in excess 2,6-lutidine (or
another base such as pyridine, 2,6-di-tert-butylpyridine, or
triethylamine) in methanol was kept in a constant-tempera-
ture bath (25.0 or 50.0 °C) for 10 or 100 half-lives. GLC
analyses of the diethyl ether solutions showed the product
distribution given in Scheme 1 and Table 2. Separation and
identification of the products 6-OMe, 12, 13-OMe, and 15-
OMe were previously reported.8b,10 The newly identified
product 14-OMe was isolated as an oil by MPLC (SiO2,
hexane-diethyl ether) followed by HPLC (µ-polarsil 9 mm ×
30 cm, hexane-diethyl ether). 14-OMe: IR (neat) 3054, 1657
1
cm-1; H NMR (CDCl3, 270 MHz) δ 4.80 (dd, 1H, J ) 4.6, 2.6
Hz), 3,54 (s, 3H), 3.24 (s, 3H), 2.51-2.39 (m, 1H), 2.28-2.15
(m, 2H), 1.9-1.3 (m, 8H); 13C NMR (68 MHz, CDCl3) δ 21.5
(CH2), 29.5 (CH), 30.4 (CH2), 32.9 (CH2), 34.3 (CH2), 34.8 (CH2),
50.2 (CH3), 54.3 (CH3), 75.6 (C), 97.7 (CH), 153.9 (C). Anal.
Calcd for C11H18O2: H, 9.95; C, 72.49. Found: H, 10.12; C,
72.34.
2-Oxobicyclo[4.3.1]d ec-1-yl Mesyla te (7-OMs). The lit-
erature60 procedure was followed. To a solution of 7-OH8b
(0.302 g, 1.80 mmol) and triethylamine (0.38 mL, 2.7 mmol)
in CH2Cl2 (9 mL) was added methanesulfonyl chloride (0.15
mL, 2.0 mmol) at -20 °C, and then the mixture was stirred
for 1 h. The reaction mixture was worked up in a usual manner
to give a yellow liquid (0.45 g), which on MPLC (SiO2, hexane-
diethyl ether 4:1) gave 7-OMs (0.28 g, 63%) as colorless
crystals: mp 68.5-69.5 °C (from hexane); IR (CCl4) 2933, 1712,
crystals: mp 49.0-50.0 °C; IR (CCl4) 2828, 1711, 1464 cm-1
;
1H NMR (270 MHz, CDCl3) δ 1.16 (s, 3H), 1.24 (s, 1H), 1.37-
1.73 (m, 6H), 1.88-1.98 (m, 1H), 2.09 (dd, 4H, J ) 15, 10 Hz),
2.43-2.53 (m, 1H), 2.59-2.68 (m, 1H), 3.20 (s, 3H); 13C NMR
(68 MHz, CDCl3) δ 19.6 (CH2), 26.9 (CH3), 27.6 (CH), 31.5
(CH3), 32.1 (CH2), 34.2 (CH2), 38.3 (CH2), 40.6 (CH2), 44.1 (C),
51.0 (CH3), 79.3 (C), 219.2 (C). Anal. Calcd for C12H20O2: C,
73.43; H, 10.27. Found: C, 73.14; H, 10.45.
1
1357, 1174 cm-1; H NMR (CDCl3, 270 MHz) δ 2.96 (s, 3H),
2.83 (d, 1H, J ) 13.5 Hz), 2.62 (dd, 1H, J ) 13.5, 6.2 Hz), 2.46
(1H, br), 2.17-2.28 (m, 2H), 1.20-1.92 (m, 10H); 13C NMR (68
MHz, CDCl3) δ 21.9 (CH2), 22.8 (CH2), 29.4 (CH2), 32.0 (CH),
36.1 (CH2), 36.8 (CH2), 38.4 (CH2), 40.3 (CH3), 43.1 (CH2), 91.6
(C), 211.9 (C). Anal. Calcd for C11H18O4S: H, 7.37; C, 53.64.
Found: H, 7.33; C, 53.60.
1-Hyd r oxy-3,3-d im et h ylbicyclo[3.3.1]n on a n -2-on e (8-
OH). The literature15 procedure was followed. To a solution
of 8-OMe (8.63 g, 44.0 mmol) and NaI (13.2 g, 87.9 mmol) in
CH3CN (124 mL) was added chlorotrimethylsilane (11.2 mL,
87.9 mmol) and the solution was heated at reflux for 17 h.
The reaction mixture was quenched with water and extracted
with ether. The combined extracts were washed with 10%
Na2S2O3 and saturated aqueous NaCl and dried (MgSO4).
Evaporation of the solvent followed by MPLC (SiO2, hexane-
diethyl ether 8:2) afforded 8-OH (5.83 g, 73%) as a yellow
liquid. Adding hexane to the liquid and cooling at -20 °C
afforded pale yellow crystals: mp 57.0-58.0 °C; IR (CCl4) 3554,
P r od u ct of Meth a n olysis of 7-OMs. A solution of 7-OMs
(0.674 g, 2.74 mmol) in 0.050 M 2,6-lutidine in methanol (68
mL) was divided into two portions, and the one portion (14
mL) was heated at 75 °C for 61.7 h (1 half-life) and the other
(54 mL) at 75 °C for 24 days (10 half-lives). After most of the
methanol had been evaporated, the residue was dissolved in
diethyl ether and worked up in a usual manner to give a yellow
liquid (0.130 and 0.382 g, respectively). GLC analyses of the
diethyl ether solutions showed the product distribution given
in Scheme 3. Separation of the latter portion by MPLC (SiO2,
hexane-diethyl ether) gave methyl ester 18 (51 mg), a mixture
(29 mg) of 6-methoxy-1-methylbicyclo[4.3.0]nonan-2-one (17)
and 7-OMe (7:3 in mol, by 13C NMR), 7-OMe (40 mg), a
mixture (81 mg) of 7-OMe, 19, and unknown compounds, and
a mixture of [4.3.1]propellanone 16 and an unknown compound
(15 mg), all as a liquid, in this sequence. 7-OMe: 1H NMR
(CDCl3, 270 MHz) δ 1.11-2.00 (m, 10H), 2.25-2.54 (m, 4H),
2.72-2.85 (m, 1H), 3.21 (s, 3H); 13C NMR (68 MHz, CDCl3) δ
21.3 (CH2), 22.5 (CH2), 29.7 (CH2), 31.8 (CH), 32.6 (CH2), 34.4
(CH2), 36.3 (CH2), 42.1 (CH2), 50.4 (CH3), 79.8 (C), 213.7 (C).
1
1703, 1464 cm-1; H NMR (270 MHz, CDCl3) δ 1.18 (2, 3H),
1.25 (s, 3H), 1.40-1.86 (m, 8H), 2.13 (dd, 1H, J ) 15, 10 Hz),
2.30 (br d, 1H, J ) 13 Hz), 2.40-2.50 (m, 1H), 3.46 (s, 1H);
13C NMR (68 MHz, CDCl3) δ 19.9 (CH2), 26.7 (CH3), 27.6 (CH),
33.1 (CH3), 33.6 (CH2), 35.0 (CH2), 40.4 (CH2), 40.7 (CH2), 42.8
(C), 74.1 (C), 223.1 (C). Anal. Calcd for C11H18O2: C, 72.49; H,
9.95. Found: C, 72.00; H, 9.97
3,3-Dim eth yl-2-oxobicyclo[3.3.1]n on -1-yl Tr ifla te (8-
OTf). To a solution of 8-OH (0.500 g, 2.74 mmol) and pyridine
(0.434 g, 5.49 mmol) in CH2Cl2 (9.8 mL) was added a solution
of triflic anhydride (0.929 g, 3.29 mmol) in CH2Cl2 (9.8 mL)
with stirring at 0 °C over 10 min and stirring continued for 1
h. The reaction mixture was worked up at 0 °C in a usual
manner to give crude 8-OTf of approximately 91% purity as
assessed by 13C NMR as a yellow liquid (1.07 g), which was
used for solvolysis studies without further purification: IR
16: 1H NMR (CDCl3, 270 MHz) δ 2.17 (d, 2H, J ) 1.3 Hz); 13
C
NMR (68 MHz, CDCl3) δ 18.3 (CH2), 20.1 (CH2), 20.4 (CH2),
26.7 (CH2), 26.9 (CH2), 33.4 (CH2), 35.9 (CH2), 37.7 (C), 42.0
(C), 210.7 (C); HRMS (EI+) calcd for C10H14O 150.1045, found
150.1044. 17: 1H NMR (CDCl3, 270 MHz) δ 1.14 (s, 3H), 3.19
(s, 3H); 13C NMR (68 MHz, CDCl3) δ 17.9 (CH3), 18.9 (CH2),
20.6 (CH2), 26.9 (CH2), 30.0 (CH2), 32.6 (CH2), 37.1 (CH2), 49.8
(CCl4) 1727, 1210 cm-1 13C NMR (68 MHz, CDCl3) δ 19.7
;
(CH2), 27.5 (CH3), 29.1 (CH), 32.9 (CH2), 34.1 (CH3), 35.0 (CH2),
37.6 (CH2), 40.0 (CH2), 45.4 (C), 96.2 (C), 118.0 (CF3, J ) 319
Hz), 212.1 (C).
P r od u ct of Meth a n olysis of 8-OTf. A solution of 8-OTf
(0.750 g, 2.50 mmol) and 0.050 M 2,6-lutidine in methanol (62
mL) was kept at 50 °C for 52 min (10 half-lives). After most of
the methanol had been evaporated, the residue was worked
up in a usual manner to give a yellow liquid (0.485 g).
(58) Takeuchi, K.; Ikai, K.; Yoshida, M.; Tsugeno, A. Tetrahedron
1988, 44, 5681.
(59) Takeuchi, K.; Ikai, K.; Shibata, T.; Tsugeno, A. J . Org. Chem.
1988, 53, 2852.
(60) Crossland, R. K.; Servis, K. L. J . Org. Chem. 1970, 35, 3195.

4972 J . Org. Chem., Vol. 65, No. 16, 2000
Tokunaga et al.
Separation by MPLC (SiO2, hexane-diethyl ether) gave a
mixture (30 mg) of (3,3-dimethyl-2-oxobicyclo[3.3.0]oct-1-yl)-
methyl triflate (25) and unidentified compounds, a mixture
(224 mg) of 3,3-dimethyl-(1-methoxymethyl)bicyclo[3.3.0]octan-
2-one (26), 3,5,6- trihydro-2,2-dimethyl-3a,6a-methano-1H,4H-
pentalen-1-one (24), and unidentified compounds, 24 (15 mg),
and 8-OMe (95 mg), all as a liquid, in this sequence. The molar
amounts of products 8-OMe and 24-26 were calculated on
the basis of the 13C NMR spectra for these crude products, and
the total product ratio is shown in Scheme 5. 24: 1H NMR
(CDCl3, 400 MHz) δ 1.06 (s, 3H), 1.09 (s, 3H); 13C NMR (100
MHz, CDCl3) δ 23.2 (CH2), 24.9 (CH2), 26.2 (CH2), 27.3 (CH3),
28.9 (CH3), 31.6 (CH2), 38.9 (C), 43.2 (CH2), 47.5 (C), 50.7 (C),
217.8 (C); HRMS (EI+) calcd for C11H16O 164.1201, found
164.1198. 25: 1H NMR (CDCl3, 270 MHz) δ 4.28 (d, 1H, J )
9.2 Hz), 4.67 (d, 1H, J ) 9.6 Hz); 13C NMR (68 MHz, CDCl3)
δ 23.5 (CH2), 24.5 (CH3), 25.0 (CH3), 31.3 (CH2), 32.7 (CH2),
40.4 (CH), 41.3 (CH2), 46.8 (C), 60.6 (C), 77.1 (CH2), 118.6 (CF3,
J ) 320 Hz), 222.2 (C); HRMS (EI+) calcd for C12H17F3O4S,
314.0800, found 314.0795. 26: 1H NMR (CDCl3, 270 MHz) δ
3.13 (d, 1H, J ) 8.9 Hz), 3.50 (d, 1H, J ) 8.9 Hz); 13C NMR
(68 MHz, CDCl3) δ 23.7 (CH2), 24.1 (CH3), 24.9 (CH3), 31.8
(CH2), 33.2 (CH2), 40.2 (CH), 41.7 (CH2), 46.7 (C), 58.8 (CH3),
61.7 (C), 75.7 (CH2), 225.9 (C).
38.6 (CH3), 40.7 (CH2), 46.9 (CH2), 52.1 (C), 79.5 (C), 281.4
(C). Anal. Calcd for C11H18OS: C, 66.62; H, 9.15. Found: C,
66.03; H, 9.16. HRMS (EI+) calcd for C11H18OS 198.1078,
found 198.1082.
3,3-Dim et h yl-2-t h ioxob icyclo[3.3.1]n on -1-yl Tosyla t e
(11-OTs). To a solution of 11-OH (0.403 g, 2.03 mmol) in THF
(8.1 mL) was added a 1.6 M solution of BuLi in hexane (1.3
mL) at -60 °C over 4 min. After the solution had been stirred
for 40 min, a solution of p-toluenesulfonyl chloride (0.407 g,
2.13 mmol) in THF (8.1 mL) was added at -45 °C over 8 min,
and the mixture stirred for 1 h at room temperature. After
most of the solvent had been evaporated, the resulting white
precipitates were filtered off and the filtrate was concentrated
to give a purple liquid. MPLC (hexane-diethyl ether 9:1) gave
crude 11-OTs as a purple liquid (0.443 g). Adding hexane-
diethyl ether (95:5) to the liquid and cooling at -20 °C afforded
11-OTs (0.199 g, 28%) as purple crystals: mp 102.5-103.5
°C; IR (CCl4) 1600, 1222, 1215, 1174 cm-1; 1H NMR (270 MHz,
CD2Cl2) δ 1.10-1.30 (m, 1H), 1.37-1.58 (m, 3H) partly
overlapped with 1.40 (s, 3H) and 1.47 (s, 3H), 1.61 (br s, 1H),
1.89 (ddd, 1H, J ) 14.2, 11.6, 4.6 Hz), 1.98-2.08 (m, 1H), 2.21
(ddd, 1H, J ) 12.6, 3.3, 1.3 Hz), 2.26 (dd, 1H, J ) 14.8, 10.6
Hz), 2.43 (s, 3H), 2.51-2.62 (br, 1H), 3.14 (dt, 1H, J ) 12.5,
3.6 Hz), 7.32 (d, 2H, J ) 8.5 Hz), 7.72 (d, 2H, J ) 8.3 Hz); 13
C
2-Hyd r a zon o-3,3-d im eth ylbicyclo[3.3.1]n on a n -1-ol. To
a solution of 1-hydroxy-3,3-dimethylbicyclo[3.3.1]nonan-2-one
(8-OH ) (1.09 g, 6.0 mmol) in 1-butanol (15 mL) was added
anhydrous hydrazine (19 mL, 600 mmol), and the solution was
heated at reflux for 68 h. Most of the solvent and the excess
hydrazine was distilled off under vacuum, and the resulting
pale red solid was recrystallized from hexane-diethyl ether (1:
1) to give 2-hydrazono-3,3-dimethylbicyclo[3.3.1]nonan-1-ol
(0.63 g, 53%) as colorless crystals: mp 135.5-136.5 °C; IR
(CCl4) 3586, 3407, 3294, 1627 cm-1; 1H NMR (270 MHz, CDCl3)
δ 1.14 (s, 3H), 1.26 (s, 3H), 1.07-1.64 (m, 7H), 1.90 (dd, 1H, J
) 10.6, 14.5 Hz), 2.25-2.44 (m, 2H), 2.80 (br d, 1H, J ) 10.7
Hz), 2.5-4.1 (br, 1H), 4.1-7.0 (br, 2H); 13C NMR (68 MHz,
CDCl3) δ 20.1 (CH2), 27.8 (CH), 30.3 (CH3), 33.8 (CH2), 34.4
(CH2), 34.9 (CH3), 37.5 (C), 39.9 (CH2), 41.3 (CH2), 73.7 (C),
158.8 (C). Anal. Calcd for C11H20N2O: C, 67.31; H, 10.27; N,
14.27. Found: C, 67.05; H, 10.37; N, 14.31.
NMR (68 MHz, CD2Cl2) δ 18.7 (CH2), 21.0 (CH3), 28.0 (CH),
33.1 (CH2), 33.2 (CH3), 34.3 (CH2), 37.3 (CH3), 39.9 (CH2), 43.8
(CH2), 53.7 (C), 94.7 (C), 126.9 (CH), 129.2 (CH), 136.1 (C),
144.1 (C), 266.7 (C). Anal. Calcd for C18H24O3S2: C, 61.33; H,
6.86. Found: C, 61.27; H, 6.84.
P r od u ct of Met h a n olysis of 11-OTs. A solution of 11-
OTs (0.328 g, 0.929 mmol) in 0.025 M 2,6-lutidine in methanol
(46 mL) was kept at 50.0 °C for 7.5 h. After most of the
methanol had been removed with a rotary evaporator, the
residue was worked up in a usual manner to give 1-methoxy-
3,3-dimethylbicyclo[3.3.1]nonane-2-thione (11-OMe) (0.198 g,
100%) as a purple liquid. 11-OMe: 1H NMR (270 MHz, CDCl3)
δ 1.00-1.21 (m, 1H), 1.25 (s, 3H), 1.32 (s, 3H), 1.34-1.63 (m,
6H), 1.90 (br d, 1H, J ) 11.8 Hz), 2.14 (dd, 1H, J ) 14.8, 10.6
Hz), 2.50 (br d, 1H, J ) 10.5 Hz), 2.68 (br dq, 1H, J ) 12.5,
3.2 Hz), 3.02 (d, 3H, J ) 2.3 Hz); 13C NMR (68 MHz, CDCl3)
δ 18.8 (CH2), 27.0 (CH), 30.8 (CH2), 32.9 (CH3), 34.2 (CH2),
35.3 (CH3), 40.0 (CH2), 44.9 (CH2), 49.4 (CH3), 52.7 (C), 85.1
(C), 274.3 (C).
1-H yd r oxy-3,3-d im e t h ylb icyclo[3.3.1]n on a n e -2-t h i-
on e (11-OH). The literature procedure17 was followed. To a
solution of Et3N (0.71 mL, 5.1 mmol) in toluene (7 mL) chilled
at -78 °C was added simultaneously toluene solutions (90 mL
each) of 2-hydrazono-3,3-dimethylbicyclo[3.3.1]nonan-1-ol (0.335
g, 1.71 mmol) and disulfur dichloride (0.230 g, 1.71 mmol) at
about the same rate using dropping funnels during 40 min.
After stirring for 75 min at room temperature, the reaction
mixture was filtered and the filtrate washed with water and
10% NaCl and dried (MgSO4). Evaporation of solvent followed
by MPLC (hexane-diethyl ether 9:1) afforded 11-OH (0.178 g,
53%) as a red semisolid. Adding hexane to the semisolid and
cooling at -20 °C afforded red crystals: mp 105.5-106.5 °C;
Kin etic Meth od s. The preparation of solvents and kinetic
studies followed the methods described previously.59
Ack n ow led gm en t. Computation time was provided
by the Supercomputer Laboratory, Institute for Chemi-
cal Research, Kyoto University. This work was sup-
ported in part by the J apanese Ministry of Education,
Science, Culture and Sports through a Grant-in-Aid for
Scientific Research (10440188).
Su p p or tin g In for m a tion Ava ila ble: Characterization
and 13C NMR spectra for 7-OMe, 14-OMe, 16, 17, trans isomer
of 17 (t-17), and 19. This material is available free of charge
via the Internet at http://pubs.acs.org.
1
IR (CCl4) 3487, 1116, 1091 cm-1; H NMR (270 MHz, CDCl3)
δ 1.01-1.29 (m, 1H), 1.36 (s, 3H), 1.44 (s, 3H), 1.30-1.93 (m,
7H), 2.26 (dd, 1H, J ) 10.2, 14.9 Hz), 2.34 (br d, 1H, J ) 12.9
Hz), 2.46-2.60 (m, 1H), 3.95 (s, 1H); 13C NMR (68 MHz, CDCl3)
δ 19.7 (CH2), 27.2 (CH), 32.5 (CH3), 33.9 (CH2), 34.1 (CH2),
J O000444D