Stabilized and Destabilized Carbocations in the 1,6-Methano[10]annulene Series

Article abstract of DOI:10.1021/jo035006w

2-Chloromethyl and 3-chloromethyl-1,6-methano[10]annulene systems solvolyze in methanol to give simple substitution products. Solvent effect studies and the special salt effect support the involvement of cationic intermediates stabilized by the 1,6-methano[10]annulene group. Rate data indicate that the degree of cation stabilization greatly exceeds that of naphthyl groups. B3LYP/6-31G* computational studies also suggest that the cationic intermediates are greatly stabilized by the 1,6-methano [10] annulene. By way of contrast to these findings, solvolytic and computational studies indicate that the 11-(1,6-methano[10]annulenyl) cation is a destabilized analogue of the cycloheptatrienyl cation. There are no favorable interactions with the annulene ring. Distortions from planarity prevent charge delocalization as in the analogous aromatic cycloheptatrienyl cation.

Full text of DOI:10.1021/jo035006w

Sta bilized a n d Desta bilized Ca r boca tion s in th e
1,6-Meth a n o[10]a n n u len e Ser ies
Xavier Creary* and Kevin Miller
Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana 46556
creary.1@nd.edu
Received J uly 11, 2003
2-Chloromethyl and 3-chloromethyl-1,6-methano[10]annulene systems solvolyze in methanol to give
simple substitution products. Solvent effect studies and the special salt effect support the
involvement of cationic intermediates stabilized by the 1,6-methano[10]annulene group. Rate data
indicate that the degree of cation stabilization greatly exceeds that of naphthyl groups. B3LYP/
6-31G* computational studies also suggest that the cationic intermediates are greatly stabilized
by the 1,6-methano[10]annulene. By way of contrast to these findings, solvolytic and computational
studies indicate that the 11-(1,6-methano[10]annulenyl) cation is a destabilized analogue of the
cycloheptatrienyl cation. There are no favorable interactions with the annulene ring. Distortions
from planarity prevent charge delocalization as in the analogous aromatic cycloheptatrienyl cation.
In tr od u ction
The 1,6-methano[10]annulene system, first prepared
by Vogel in 1964, is an example of an aromatic group
possessing 10 π-electrons.1 NMR as well as chemical
reactivity criteria confirm the aromatic nature of this
group.2 Recently we have determined that the 1,6-
methano[10]annulene group is a potent radical stabiliz-
ing group, which far surpasses the ability of phenyl and
naphthyl to stabilize free radicals.3 Our methylenecyclo-
propane rearrangement probe was used to determine the
γ+ value for the 1,6-methano[10]annulene group, and
computational studies supported the suggestion that
radicals such as 1 were remarkably stabilized. 1,6-
Methano[10]annulene substituted carbenes have also
been thermally generated utilizing the appropriate tos-
ylhydrazone salts as precursors.4 However, little is known
about the cation stabilizing ability of the 1,6-methano-
[10]annulene system. We have studied the carbocations
2-6 by solvolytic methods, and we now report on the
stabilities of these cations.
fashion from alcohol 9.7 These chlorides were solvolyzed
in methanol at 25.0 °C, where both of these substrates
readily react. The methyl ether substitution products 11
and 12 were the sole products formed in these reactions.
Rate data are reported in Table 1, as well as data on
chloride 13 and mesylates 16 and 17 for comparison
purposes. The effect of solvent on reaction rate of chloride
8 was also determined. The rate was too fast to measure
in the more highly ionizing solvent CF3CH2OH, and
therefore chloride 8 was studied in 90% aqueous metha-
nol, EtOH, and i-PrOH, where rates were slow enough
to be conveniently measured. There are large rate
increases as solvent ionizing power is increased, and the
Winstein-Grunwald m value is 1.28 (r ) 0.997). This
solvent effect is consistent with solvolysis of 8 by a
cationic mechanism.
Resu lts a n d Discu ssion
1,6-Meth a n o[10]a n n u len yl Ca tion s. The 2-substi-
tuted chloride 8 was prepared as previously described5,6
from the corresponding alcohol 7, and the isomeric
3-substituted chloride 10 was prepared in an analogous
(1) (a) Vogel, E.; Roth, H. D. Angew. Chem. Int. Ed. Engl. 1964, 3,
228. (b) Vogel, E.; Klug, W.; Breuer, A Organic Syntheses; Wiley: New
York, 1988; Collect. Vol. VI, p 721.
(2) Dorn, H. C.; Yannoni, C. S.; Limbach, H. H.; Vogel, E. J . Phys.
Chem. 1994, 98, 11628.
(3) Creary, X.; Miller, K. Org. Lett. 2002, 4, 3493.
(4) J ones, W. M.; LaBar, R. A.; Brinker, U. H.; Gebert, P. H. J . Am.
Chem. Soc. 1977, 99, 6379.
Data in acetic acid also strongly implicate a cationic
intermediate in acetolysis of 8. The reaction of 2.5 mM 8
in CD3CO2D (containing no buffering base) does not go
to completion but reaches an equilibrium position con-
(5) Neidlein, R.; Zeiner, H. Chem. Ber. 1982, 115, 3353.
(6) Kitching, W.; Olszowy, H. A.; Schott, I.; Adcock, W.; Cox, D. P.
J . Organomet. Chem. 1986, 310, 269.
(7) Nelson, P. H.; Bartsch, G. A.; Untch, K. G.; Fried, J . H. J . Med.
Chem. 1975, 18, 583.
10.1021/jo035006w CCC: $25.00 © 2003 American Chemical Society
Published on Web 10/03/2003
J . Org. Chem. 2003, 68, 8683-8692
8683

Creary and Miller
TABLE 1. Solvolysis Ra tes a t 25.0 °C
a
b
Fast isomer. Slow isomer.
life for approach to equilibrium is now 50 min. With 0.1
M LiClO4 added to the solution, the reaction has almost
reached the equilibrium position after 15 min and the
half-life for approach to equilbrium is only 2.8 min. Such
large rate increases with only small changes in perchlo-
rate ion concentration (special salt effect) were first
observed by Winstein and are suggestive of the intercep-
tion of an ion pair by replacement of chloride ion with
perchlorate ion at the solvent separated ion-pair stage.8
The remarkably fast solvolysis rates of the primary
chlorides 8 and 10 are indicative of an unusually large
cation stabilizing effect of the 1,6-methano[10]annulene
system on both cations 2 and 3. However, the stabiliza-
tion of cation 2 appears to be slightly larger than that of
cation 3. The chloride 8 is even more reactive than
p-methoxybenzyl chloride, 13, despite the potent cation
stabilizing ability of the p-methoxy substituent. Both
chlorides 8 and 10 are far more reactive than the
naphthyl analogues 14 and 15. In fact chlorides 14 and
15 are quite unreactive in methanol, and mesylates 16
and 17 were the derivatives studied in order to achieve
convenient reactivity. The relative rate data shown are
approximations assuming that mesylates are 3 × 104
times more reactive than chlorides.9
taining 52% of the acetate substitution product and 48%
unreacted chloride 8. This equilibrium position is ap-
proached in a first-order fashion. The reaction is subject
to a special salt effect when lithium perchlorate is added
to the CD3CO2D, i.e., there are large rate increases as
perchlorate concentration is increased. The 1H NMR
spectra shown in Figure 1 demonstrate the effect of
lithium perchlorate on the extent of reaction of 8 over
15 min at 25 °C. In pure CD3CO2D, the acetate product
is barely visible after 15 min and the reaction approaches
equilibrium with a half-life of 526 min. A significant rate
increase can be seen in 0.01 M LiClO4, where the half-
(8) Winstein, S.; Robinson, G. C. J . Am. Chem. Soc. 1958, 80, 169.
(9) Noyce, D. S.; Virgilio, J . A. J . Org. Chem. 1972, 37, 2643.
8684 J . Org. Chem., Vol. 68, No. 22, 2003

1,6-Methano[10]annulene Carbocations
F IGURE 1. 1H NMR spectra of 8 in CD3CO2D containing varying amounts of LiClO4 after 15 min at 25 °C.
the 1-annulenyl group in terms of the γ+ value (group σ+
value).10 The acetate 26 was prepared from the alcohol
25, which was in turn available from reaction of 2-lithio-
1,6-methano[10]annulene with acetone. Both 26 and the
related substrate p-methoxycumyl acetate, 27, solvolyze
readily in methanol at room temperature to form the
corresponding methyl ether products. To our initial
surprise, 26 was 2.63 times less reactive than the
p-methoxy analogue 27, despite the fact that chloride 8
is 18 times more reactive than p-methoxy benzyl chloride,
13. This implies that the 1,6-methano[10]annulene sys-
tem (γ+ ) -0.69)11 is now less cation stabilizing than the
p-anisyl group (γ+ ) -0.78). There are two possible
What is the origin of the high reactivity of chlorides 8
and 10? A previous study on rates of protiodemetalation
of substrates 18 and 19 showed that desilylation occurred
35 times faster in the 1,6-methano[10]annulene systems
than in the analogous naphthyl systems 21.6 Protiode-
stannylation of 19 occurred 700 times faster than in 22.6
The implication is that the intermediate cations 20 in
this electrophilic aromatic substitution reaction are more
effectively stabilized by the annulene system than the
cations 23 are stabilized by the naphthyl system. These
findings complement our solvolysis rate data, which also
suggest that 1,6-methano[10]annulene stabilization of
carbocations greatly surpasses naphthyl stabilization.
The extraordinary solvolysis rate of chloride 8 indicates
that cation 2 is even more stable than the p-methoxy-
benzyl cation. We were therefore interested in a more
quantitative measure of the cation stabilizing ability of
(10) (a) Peters, E. N.; J . Am. Chem. Soc. 1976, 98, 5627. (b) Peters,
E. N. J . Org. Chem. 1977, 42, 1419.
+
(11) γ for the 1,6-methano[10]annulene group is calculated from
the rate of methanolysis of 26 and assuming a F+ value of -4.82 in
methanol.
J . Org. Chem, Vol. 68, No. 22, 2003 8685

Creary and Miller
explanations for this reduced 1,6-methano[10]annulene
effect in solvolysis of 26. The first is reduced conjugation.
Twisting of the 1,6-methano[10]annulene group out of
conjugation in the 3° cation 4 due to steric factors may
account for the reduced cation stabilizing influence. This
possibility is addressed in the computational section. The
possibility also exists that there is less demand for 1,6-
methano[10]annulene stabilization in the 3° cation 4
derived from 26. Hence the response is less than that of
the p-methoxyphenyl group. This latter explanation
would require that the ability of the 1,6-methano[10]-
annulene group to respond to electron demand is much
more variable than that of the p-methoxyphenyl group.
F IGURE 2. 1H NMR Spectral Data for 35. B3LYP/6-31G*/
GIAO calculated values are in red.
Attention was next turned to the electron-deficient
cation 5, where the formally electron-withdrawing CO2-
CH3 group is attached to the cationic center.12 The
precursors to this cation were the chlorides 29, which
were available from the R-ketoester 28. Reduction of 28
with borohydride followed by reaction with thionyl
chloride gave an inseparable mixture of diastereomeric
chlorides 29 (1.7:1 ratio). These chlorides are quite
reactive, undergoing solvolysis in methanol readily at
room temperature at comparable rates. In fact, the rates
of solvolyses of chlorides 29 in methanol differ little from
that of chloride 8 despite the presence of the cation
destabilizing CO2CH3 group. This rate behavior contrasts
with that of previously studied systems 31-34, where
the effect of the CO2CH3 group is to retard solvolysis rate
by a significant factor.13
Examination of the solvolysis products suggests a
reason for the very small effect of the carbomethoxy group
(relative to hydrogen) on the rate of solvolysis of 29. While
solvolyses of 8 and 26 gave simple substitution products,
chlorides 29 give a major product 35, where methanol is
captured at the 5-position of the 1,6-methano[10]annulene
ring. Also produced are minor unidentified products. The
structure of this “aromaticity-disrupted” product rests on
1
a number of features in the H NMR spectrum as well
GIAO) NMR spectrum. These are shown in Figure 2. One
of the C-11 hydrogens is in the shielding region of the
cycloheptatriene system and appears upfield at δ 0.55.
The other hydrogen at δ 3.04 is in the deshielding region
of the cycloheptatriene and is further desheilded by the
exocyclic double bond. The stereochemistry of the meth-
as comparison with the calculated13 (B3LYP/6-31G*/
(12) For a review and leading references on carbocations containing
formal electron-withdrawing groups, see: Creary, X. Chem. Rev. 1991,
91, 1625.
(13) Creary, X.; Geiger, C. C. J . Am. Chem. Soc. 1982, 104, 4151.
8686 J . Org. Chem., Vol. 68, No. 22, 2003

1,6-Methano[10]annulene Carbocations
F IGURE 3. B3LYP/6-31G* relative energies of 2- and 3-substituted 1,6-methano[10]annulyl and naphthyl cations.
oxy group is established by the observation of W-coupling
(0.8 Hz) of the C-5 hydrogen (δ 4.16) to the C-11 hydrogen
at δ 0.55.
Isodesmic calculations suggest that the 2-(1,6-methano-
[10]annulenyl) cation 2 is also 5.6 kcal/mol more stable
than the 1-naphthyl cation 36 and 23.5 kcal/mol more
+
stable than the unsubstituted benzyl cation, PhCH2
.
This is a conjugation phenomenon, as can be clearly seen
by examining bond lengths from the cationic center to
the aromatic ring.
The pertinent bond length in the benzyl cation is 1.371
Å, and the shrinkage to 1.358 Å in cation 2 is consistent
with increased conjugation and subsequent delocalization
of charge into the annulene ring of 2. Cation 3 is still
extensively stabilized by the annulene ring, but bond
lengths again suggest that delocalization is not as effec-
tive as in cation 2. Bond lengths in cations 2 and 3 closely
parallel those in the naphthyl analogues 36 and 37,
respectively, such that 2 and 3 can be considered
“homonaphthyl” cations.
11-(1,6-Meth a n o[10]a n n u len yl) Ca tion . The car-
bocation 6, with charge at the 11-position, was also of
interest. Is there any interaction of the cationic center
with the aromatic annulene system? Is neighboring group
This product 35 implies unusually large charge delo-
calization into the aromatic annulene ring of the inter-
mediate carbocation 5. This is a result of the increased
demand for charge delocalization as a result of the
electron-withdrawing nature of the carbomethoxy group.
The loss of aromaticity when methanol is trapped at the
C-5 position is consistent with the reduced aromaticity
of 1,6-methano[10]annulene system relative to benzenoid
systems.15 In other words, the price paid for loss of
aromaticity in 35 is not unreasonable.
Com p u ta tion a l Stu d ies on 1,6-Meth a n o[10]a n n u -
len yl Ca tion s. Computational studies14 have been car-
ried out at the B3LYP/6-31G* level on cations 2 and 3
as well as on naphthyl analogues 36 and 37 (Figure 3).
In line with our rate data is the finding that cation 2 is
4.1 kcal/mol more stable than cation 3.
(14) Frisch, M, J .; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.;
Robb, M. A.; Cheeseman, J . R.; Zakrzewski, V. G.; Montgomery, J r.,
J . A.; Stratmann, R. E.; Burant, J . C.; Dapprich, S.; Millam, J . M.;
Daniels, A. D.; Kudin, K. N.; Strain, M. C.; Farkas, O.; Tomasi, J .;
Barone, V.; Cossi, M.; Cammi, R.; Mennucci, B.; Pomelli, C.; Adamo,
C.; Clifford, S.; Ochterski, J .; Petersson, G. A.; Ayala, P. Y.; Cui, Q.;
Morokuma, K.; Malick, D. K.; Rabuck, A. D.; Raghavachari, K.;
Foresman, J . B.; Cioslowski, J .; Ortiz, J . V.; Baboul, A. G.; Stefanov,
B. B.; Liu, G.; Liashenko, A.; Piskorz, P.; Komaromi, I. Gomperts, R.;
Martin, R. L.; Fox, D. J .; Keith, T.; Al-Laham, M. A.; Peng, C. Y.;
Nanayakkara, A.; Gonzalez, C.; Challacombe, M.; Gill, P. M. W.;
J ohnson, B.; Chen, W.; Wong, M. W.; Andres, J . L.; Gonzalez, C.; Head-
Gordon, M.; Replogle, E. S.; Pople, J . A. Gaussian 98, Revision A.7;
Gaussian, Inc.: Pittsburgh, PA, 1998.
(15) Roth, W. R.; Bo¨hm, M.; Lennartz, H. W.; Vogel, E. Angew.
Chem., Int. Ed. Engl. 1983, 22, 1007.
J . Org. Chem, Vol. 68, No. 22, 2003 8687

Creary and Miller
carbocationic intermediates from certain mesylates, chlo-
rides, and trifluoroacetates.18 As in polar protic solvents
such as trifluoroethanol and acetic acid, carbocation
intermediates formed in DMSO-d6 can rearrange, suffer
proton elimination, or undergo solvent capture. The
triflate 42 undergoes an interesting pseudo-first-order
reaction when dissolved in DMSO-d6 at room tempera-
1
ture. When the reaction is monitored by H NMR, the
minor product 45 (41%) builds up with the disappearance
of triflate 42. An unstable product, presumably the
oxosulfonium ion 47, can also be detected. This product
converts to the major product, naphthalene (52%), under
the reaction conditions, and at the same time, formic acid
appears. Also formed in this reaction are small amounts
of 1-naphthaldehyde, 50 (3%), and the alcohol 41 (4%).
A mechanistic scheme that accounts for these observa-
tions involves an ionization process in DMSO-d6 to give
the cation 6. Capture of the DMSO-d6 solvent at sulfur
gives product 45, whereas capture at oxygen gives the
unstable oxosulfonium ion 47. This intermediate can lose
dimethyl sulfide and fragment to naphthalene and the
formyl cation, 48, which is the source of the formic acid
via the trace of water present in the DMSO-d6. The
formyl cation can also serve to produce the trace of
1-naphthaldehyde. The alcohol 41 could also be derived
from the oxosulfonium ion 47 on reaction with the trace
of water present. We have previously shown that this is
a facile reaction of other oxosulfonium ions with traces
of water present in DMSO-d6.18
participation an important feature in generation of this
cation? Is this cation related to the cycloheptatrienyl
cation? Answers to these questions were sought by
examining the chemistry of triflate 42. The preparation
of 42 utilized the acetate 40, which is available from a
silver acetate assisted solvolysis reaction of 11-bromo-
1,6-methano[10]annulene in acetic acid.16 This silver-
assisted reaction may well involve the carbocation 6, or
at least a transition state with cationic character at the
11-position. The acetate 40 was converted to the alcohol
41 by reaction with methylmagnesium bromide. Conver-
sion of 41 to the corresponding mesylate derivative was
straightforward, but this derivative proved to be quite
unreactive under solvolytic conditions. Therefore 41 was
converted to the triflate derivative 42.
Solvolysis of 42 in trifluoroethanol occurred at a
convenient rate at 25 °C to give the substitution product
43. Rate data for 42 are given in Table 1 along with data
for the saturated substrate 44 for comparison purposes.
The mesylate 44 also reacts at a convenient rate at 25
°C. If one corrects for the triflate/mesylate rate ratio,17
then triflate 42 is approximately 105 times less reactive
than the saturated analogue. It therefore appears that,
on the basis of solvolysis rate data, the carbocation 6
derived from triflate 42 has no unusual stabilizing
features. In fact, it is substantially destabilized relative
to the saturated analogue.
Com p u ta tion a l Stu d ies on th e 11-(1,6-Meth a n o-
[10]a n n u len yl) Ca tion . Density functional calculations
(B3LYP/6-31G*) have also been carried out on cation 6
in order to provide additional insight. Cations 51-53
were also examined for comparison purposes. The relative
energies of these cations were evaluated via the isodesmic
reaction shown and are listed under the corresponding
cation in Figure 4. In agreement with the solvolytic rate
data, cation 6 is substantially less stable than the
saturated analogue 51.
We have recently reported that the aprotic solvent
DMSO can be a reasonable solvent for generation of
(16) Vogel, E.; Weyres, F.; Leper, H.; Rautenstrauch, V. Angew.
Chem., Int. Ed. Engl. 1966, 5, 732.
(17) Triflates are approximately 105 times more reactive than
mesylates or tosylates under solvolytic conditions; see: Su, T. M.;
Sliwinski, W. F.; Schleyer, P. v. R. J . Am. Chem. Soc. 1969, 91, 5386.
(18) Creary, X.; Burtch, E. A.; J iang, Z. J . Org. Chem. 2003, 68, 1117.
8688 J . Org. Chem., Vol. 68, No. 22, 2003

1,6-Methano[10]annulene Carbocations
F IGURE 4. B3LYP/6-31G* relative energies of the 11-(1,6-methano[10]annulyl) cation (6) and analogues.
Structural information is also informative. Unlike the
saturated system 51, the cationic center of 6 is not
completely planar and the C11 hydrogen is tilted signifi-
cantly toward one of the CHdCH-CHdCH bridges. The
same tilt is observed in cation 52, which is formally a
cycloheptatrienyl cation bridged by a saturated four-
carbon fragment. Cation 52 is also 14.2 kcal/mol more
stable than cation 6, and bond lengths in the conjugated
Con clu sion s
7-carbon fragment are more equivalent than in 6. How-
ever, delocalization is not as complete as in the cyclo-
heptatrienyl cation, 53, where the bond lengths are
equivalent. The cation 52 still maintains a portion of its
stabilization due to aromaticity, but stabilization is
weakened by the four-carbon bridge. On the other hand,
although cation 6 might resemble the cycloheptatrienyl
cation at first glance, it is a deformed entity lacking the
remarkable properties of the authentic, aromatic cyclo-
heptatrienyl cation 53. It is, in actuality, a distorted
allylic cation, with miniscule delocalization into the
unsaturated 4-carbon bridges. It also has none of the
delocalized properties of the 7-norbornadienyl cation.19
Solvolysis rate data indicate that 2- and 3-substituted
1,6-methano[10]annulyl cations (2 and 3) are remarkably
stabilized by the annulene ring, with the 2-substituted
system 2 being more stabilized than the 3-substituted
system 3. These solvolysis studies, along with B3LYP/
6-31G* computational studies, confirm that stabilization
of these cations greatly exceeds that of naphthyl ana-
logues. Solvolytic studies also show that charge in the
“electron-deficient” carbocation 5 is extensively delocal-
ized into the methanoannulene ring, resulting in a
(19) Lustgarten, R. K.; Brookhart, M.; Winstein, S. J . Am. Chem.
Soc. 1972, 94, 2347 and references therein.
J . Org. Chem, Vol. 68, No. 22, 2003 8689

Creary and Miller
addition was complete, the solution was stirred at -78 °C for
20 min, and a solution of acetone (460 mg, 7.94 mmol) in
anhydrous THF (2 mL) was added dropwise. The solution was
stirred at -78 °C for 30 min, then slowly warmed to room
temperature, quenched with water, and diluted with ether.
The organic phase was separated, washed with saturated NaCl
solution, dried over a mixture of Na2SO4 and MgSO4, and
filtered, and the solvent was removed by rotary evaporator.
The crude residue was chromatographed on 30 g of silica gel.
Elution with hexanes separated hydrocarbon impurities. Gra-
dient elution with 15-20% ether in hexanes gave alcohol 25
(111 mg, 35%) as a yellow solid, mp 78-79 °C. 1H NMR
(CDCl3) δ 8.02 (d, J ) 8.5 Hz, 1 H), 7.44 (d, J ) 7.8 Hz, 1 H),
7.40 (d, J ) 9.0 Hz, 1 H), 7.27-7.15 (m, 3 H), 7.01 (t, J ) 9.2
Hz, 1 H), 1.85 (s, 3 H), 1.60 (s, 3 H), -0.47 (d of t, J ) 9.4, 1.4
Hz, 1 H), -0.67 (d of d, J ) 9.4, 0.9 Hz, 1 H). 13C NMR (CDCl3)
δ 149.7, 129.6, 128.7, 127.7, 126.8, 126.5, 126.1, 123.5, 117.3,
112.8, 75.2, 36.0, 33.2, 32.7. Anal. Calcd for C14H16O: C, 83.96;
H, 8.05. Found: C, 84.01; H, 8.00.
nonaromatic solvent capture product. On the other hand,
solvolytic and computational studies indicate that the 11-
(1,6-methano[10]annulyl) cation, 6, is destabilized rela-
tive to analogues. There is a distinct lack of charge
delocalization in 6 involving the unsaturated bridges.
Although there is some structural resemblance to the
aromatic cycloheptatrienyl cation, in actuality, distortions
from planarity preclude any such aromatic stabilization
of 6.
Exp er im en ta l Section
P r ep a r a tion of 2-Ch lor om eth yl-1,6-m eth a n o[10]a n n u -
len e (8).5,6 To a stirred solution of 131 mg of 2-hydroxymethyl-
1,6-methano[10]annulene (7)5,6 in 3 mL of anhydrous ether
containing 100 mg of Na2CO3 was added 230 mg of thionyl
chloride. The mixture was stirred for 1 h and filtered, and the
ether was removed using a rotary evaporator. The crude
2-chloromethyl-1,6-methano[10]annulene 8 (134 mg; 92%) was
P r ep a r a tion of Aceta te 26. A suspension of 92 mg of a
60% dispersion of sodium hydride in mineral oil (2.30 mmol)
was placed in a flask under nitrogen, and the mineral oil was
removed by successive washing with hexanes. The hexanes
were then decanted, and the last traces were removed by a
stream of nitrogen. A solution of alcohol 25 (115 mg, 0.57
mmol) in anhydrous THF (6 mL) was added. The mixture was
refluxed for 2 h and cooled, and acetic anhydride (88 mg, 0.86
mmol) was then added. The solution was stirred for an
additional 2 h at room temperature, then diluted with ether,
and washed with water and saturated sodium chloride solu-
tion. The organic phase was separated, dried over a mixture
of Na2SO4 and MgSO4, and filtered, and the solvent was
removed by rotary evaporator to give 151 mg of a 56:44
mixture of acetate 26 and starting alcohol 25. This mixture
1
used without further purification. H NMR (CDCl3) δ 7.67 (d,
J ) 8.3 Hz, 1 H), (7.42, m, 2 H), 7.16 (m, 3 H), 7.03 (t, J ) 9.0
Hz, 1 H), 4.93 (d, J ) 12 Hz, 1 H), 4.80 (d, J ) 12 Hz, 1 H),
-0.36 (d, J ) 9.3 Hz, 1 H), -0.50 (d, J ) 9.3 Hz, 1 H). 13C
NMR (CDCl3) δ 136.8, 130.3, 128.4, 128.1, 127.3, 127.0, 126.9,
126.3, 116.6, 113.2, 44.8, 35.3.
P r ep a r a tion of 3-Ch lor om eth yl-1,6-m eth a n o[10]a n n u -
len e (10).6,7 A solution of 31 mg of 3-hydroxymethyl-1,6-
methano[10]annulene (9).7,20 in 1 mL of anhydrous ether
containing 50 mg of Na2CO3 was stirred as 54 mg of SOCl2
was added. After 1.5 h the mixture was filtered, and the
solvent was removed using a rotary evaporator. The crude
3-chloromethyl-1,6-methano[10]annulene 10 (33.3 mg; 97%)
was used without further purification. 1H NMR (CDCl3) δ
7.48-7.36 (m, 4 H), 7.14-7.04 (m, 3 H), 4.77 (d, J ) 11 Hz, 1
H), 4.70 (d, J ) 11 Hz, 1 H), -0.30 (d, J ) 9 Hz, 1 H), -0.36
(d, J ) 9 Hz, 1 H). 13C NMR (CDCl3) δ 135.0, 130.3, 129.4,
129.3, 128.8, 127.4, 126.9, 126.8, 115.0, 113.7, 51,2, 35.3.
P r ep a r a tion of Mesyla te 16. A solution of 441 mg of
2-hydroxymethylnaphthalene and 415 mg of mesyl chloride
in 5 mL of methylene chloride was cooled to -25 °C, and 423
mg of triethylamine in 1 mL of CH2Cl2 was added dropwise.
The mixture was slowly warmed to room temperature and
diluted with ether, and cold water was added. The mixture
was rapidly transferred to a separatory funnel, and the organic
extract was washed with cold water, dilute HCl, and saturated
NaCl solution. The solution was dried over MgSO4 and filtered,
and the solvent was removed using a rotary evaporator to give
536 mg (81%) of mesylate 16 as a light yellow oil. Mesylate
16 decomposes on standing at room temperature and was
stored in ether solution at -20 °C. 1H NMR (CDCl3) δ 8.10
(m, 1 H), 7.98-7.82 (m, 2 H), 7.66-7,40 (m, 4 H), 5.70 (s, 2
H), 2.80 (s, 3 H). 13C NMR (CDCl3) δ 133.7, 1431.5, 130.7,
128.85, 128.81, 128.76, 127.2, 126.4, 125.1, 123.3, 70.0, 38.4.
P r ep a r a tion of Mesyla te 17. Silver mesylate (240 mg) was
added to a solution of 150 mg of 3-chloromethylnaphthalene
in 3 mL of ether. The mixture was refluxed for 26 h. After
dilution with ether, the mixture was filtered, and the ether
was removed using a rotary evaporator to give 174 mg (94%)
of mesylate 17 as a light yellow oil. Mesylate 17 decomposes
on standing at room temperature and was stored in ether
1
was used for kinetic studies without further purification. H
NMR of 26 (CDCl3) δ 7.76 (d, J ) 8.8 Hz, 1 H), 7.42 (d, J )
9.0 Hz, 1 H), 7.37 (d, J ) 8.8 Hz, 1 H), 7.27-7.07 (m, 3 H),
6.99 (t, J ) 9.0 Hz, 1 H), 2.20 (s, 3 H), 2.09 (s, 3 H), 1.40 (s, 3
H), -0.38 (d of m, J ) 9.3 Hz, 1 H), -0.75 (d of d, J ) 9.3, 1.0
Hz, 1 H).
P r ep a r a tion of Ketoester 28.22 To a solution of 2-bromo-
1,6-methano[10]annulene (24) (200 mg, 0.9 mmol) in anhy-
drous THF (3 mL) at -85 °C under nitrogen was added 0.9
mL of 1.6 M n-butyllithium (1.4 mmol) in hexanes dropwise.
After the addition was complete, the solution was kept at -85
°C for 30 min, and then a solution of 128 mg of dimethyl
oxalate (1.1 mmol) in 2 mL of anhydrous THF was added
dropwise. After 30 min at -85 °C the solution was slowly
warmed to room temperature. The mixture was quenched with
water and diluted with ether. The organic phase was sepa-
rated, washed with saturated sodium chloride solution, dried
over a mixture of Na2SO4 and MgSO4, and filtered, and the
solvent was removed using a rotary evaporator. The crude
residue was chromatographed on 10 g of silica gel. The
R-ketoester 28 (86 mg, 42%) eluted with 4-5% ether in
hexanes. 1H NMR (CDCl3) δ 8.26 (d, J ) 8.8 Hz, 2 H), 7.73 (d,
J ) 8.8 Hz, 2 H), 7.72 (d, J ) 9.5 Hz, 2 H), 7.44 (d, J ) 8.6 Hz,
1 H), 7.35 (t, J ) 9.2 Hz, 2 H), 7.23 (t, J ) 9.0 Hz, 1 H), 7.13
(t, J ) 9.2 Hz, 1 H), 3.99 (s, 3 H), -0.25 (d of m, J ) 9.0 Hz,
1 H), -0.28 (d of m, J ) 9.0 Hz, 1 H). 13C NMR (CDCl3) δ
186.4, 165.2, 137.4, 134.4, 132.3, 130.8, 130.4, 128.4, 127.6,
124.6, 117.2, 113.7, 52.7, 35.8. Exact mass (EI) calcd for
1
solution at -20 °C. H NMR (CDCl3) δ 87.94-7.80 (m, 4 H),
C
14H12O3 228.0796, found 228.0787.
7.60-7.46 (m, 3 H), 5.42 (s, 2 H), 2.91 (s, 3 H). 13C NMR
(CDCl3) δ 133.4, 132.9, 130.7, 128.8, 128.4, 128.1, 127.7, 126.9,
126.6, 125.7, 71.8, 38.3.
P r ep a r a tion of Ch lor id es 29. To a suspension of sodium
borohydride (15 mg, 0.37 mmol) in methanol (3 mL) under
nitrogen was added dropwise a solution of R-keto ester 28 (85
mg, 0.37 mmol) in methanol (1 mL). After the addition was
completed, the solution was stirred at room temperature for
90 min and diluted with ether, and the resulting solution was
washed with water and saturated sodium chloride solution.
P r ep a r a tion of Alcoh ol 25. To a solution of 2-bromo-1,6-
methano[10]annulene (24)21 (351 mg, 1.59 mmol) in anhydrous
THF (4 mL) under nitrogen at -78 °C was added n-butyl-
lithium (1.2 mL, 1.91 mmol) in hexanes dropwise. After the
(20) Vogel, E.; Sombroek, J . Tetrahedron Lett. 1974, 17, 1627.
(21) Vogel, E.; Bo¨ll, W. A.; Biskup, M. Tetrahedron Lett. 1966, 1569.
(22) Creary, X. J . Org. Chem. 1987, 52, 5026.
8690 J . Org. Chem., Vol. 68, No. 22, 2003

1,6-Methano[10]annulene Carbocations
The organic phase was separated, dried over a mixture of Na2-
SO4 and MgSO4, and filtered, and the solvent was removed
by rotary evaporator. The crude residue was chromatographed
on 8 g of silica gel. Elution with 15% ether in hexanes gave 58
mg (69%) of a 1.8:1 mixture of diastereomeric alcohols. The
mixture of alcohols was not separated. 1H NMR of alcohol
mixture (CDCl3) δ 7.70-7.00 (m, aromatic), 5.57 (s, CH), 3.69
(s, OCH3), 3.66 (s, OCH3), -0.38 to -0.58 (m, CH2).
eluted with 5% ether in hexanes. 1H NMR of 11 (CDCl3) δ 7.70
(d, J ) 8 Hz, 1 H), 7.42, (m, 2 H), 7.16 (m, 2 H), 7.08 (d, J )
9 Hz, 1 H), 7.01 (t, J ) 9 Hz, 1 H), 4.81 (d, J ) 13 Hz, 1 H),
4.52 (d, J ) 13 Hz, 1 H), 3.485 (s, 3 H), -0.34 (d, J ) 9 Hz, 1
H), -0.50 (d, J ) 9 Hz, 1 H). 13C NMR of 9 (CDCl3) δ 138.6,
129.3, 128.1, 127.2, 127.0, 126.8, 126.5, 125.9, 115.9, 113.8,
73.8, 58.2, 35.4. Exact mass (EI) calcd for C13H14O 186.1045,
found 186.1031.
To a solution of the mixture of alcohols prepared above (51
mg, 0.22 mmol) in 3 mL of anhydrous ether was added 35 mg
of sodium carbonate and 40 mg of thionyl chloride. After 30 h
of stirring at room temperature, an additional 27 mg of thionyl
chloride was added, and stirring was continued for an ad-
ditional 24 h. The mixture was filtered, and the solvent was
removed by rotary evaporator to give 48 mg (87%) of a 1.7:1
mixture of diastereomeric chlorides 29. This mixture was used
without further purification in kinetic studies. 1H NMR of
chlorides 29 (CDCl3) δ 7.75-7.07 (m, aromatic), 5.91 (s, CH),
5.90 (s, CH), 3.78 (s, CH3), 3.71 (s, CH3), -0.43 to -0.53) (m,
CH2). 13C NMR of chlorides 29 (CDCl3) δ 169.1, 168.8, 134.3,
134.1, 131.1, 130.8, 128.9, 128.8, 127.83, 127.75, 127.66,
127.36, 127.33, 127.30, 127.28, 127.0, 126.9, 126.6, 117.6,
117.3, 112.9, 112.2, 58.3, 56.6, 53.5, 53.3, 35.3, 35.3.
P r ep a r a tion of Tr ifla te 42. A solution of 96 mg of
11-hydroxy-1,6-methano[10]annulene16 and 91 mg of 2,6-
lutidine in 3 mL of methylene chloride was cooled to -20 °C,
and 213 mg of triflic anhydride was added dropwise. The
mixture was slowly warmed to room temperature, and cold
water was added. The mixture was rapidly transferred to a
separatory funnel using ether, and the organic extract was
washed with cold water, dilute NaOH solution, and saturated
NaCl solution. The organic extract was dried using MgSO4 and
filtered, and the solvent was removed using a rotary evapora-
tor to give 161 mg (91%) of triflate 42, mp 71-73 °C. 1H NMR
(CDCl3) δ 7.49 (m, 2 H), 7.30 (m, 2 H), 7.24 (m, 2 H), 7.21 (m,
2 H), 2.31 (s, 1 H). 13C NMR (CDCl3) δ 128.5, 128.1, 126.1,
125.3, 118.1 (q, J ) 320 Hz), 115.97, 79.1. Exact mass (EI)
calcd for C12H9 F3OS 290.0225, found 290.0207.
Solvolysis of 2-Ch lor om eth yl-1,6-m eth an o[10]an n u len e
(8) in CD3CO2D con ta in in g LiClO4. The solvent was re-
moved from a 25-µL sample of a 0.05 M chloride 8 in ether
using a rotary evaporator. The residue was dissolved in 0.50
mL of CD3CO2D containing the appropriate amount of LiClO4.
The solution was transferred to an NMR tube, and the tube
was placed in a temperature-controlled probe of a 600 mHz
NMR spectrometer at 25.0 °C. The reaction was monitored
periodically over two half-lives by integration of the signals
at δ 5.38 (acetate product) and δ 4.95 (unreacted chloride 8).
Rate constants for approach to equilibrium were calculated
by standard least-squares methods using measured infinity
values. Figure 1 shows typical spectra after 15 min at 25 °C.
Solvolysis of 3-Ch lor om eth yl-1,6-m eth an o[10]an n u len e
(10) in Meth a n ol. A solution of 12 mg of 10 in 2 mL of 0.05
M of 2,6-lutidine in methanol was stirred at room temperature
for 3 days. The mixture was taken up into ether, washed with
water, dilute HCl solution, and saturated NaCl solution, and
dried over MgSO4. After filtration, the solvent was removed
using a rotary evaporator and the residue was chromato-
graphed on 10 g of silica gel. The methyl ether 12 (11 mg; 91%)
eluted with 2% ether in hexanes. 1H NMR of 12 (CDCl3) δ
7.46-7.38 (m, 4 H), 7.13-7.04 (m, 3 H), 4.65 (d, J ) 11 Hz, 1
H), 4.50 (d, J ) 11 Hz, 1 H), 3.41 (s, 3 H), -0.32 (d of t, J ) 9,
1 Hz, 1 H), -0.38 (d of t, J ) 9, 1 Hz, 1 H). 13C NMR of 10
(CDCl3) δ 135.8, 129.3, 129.0, 128.6, 128.4, 126.304, 126.297,
126.2, 114.7, 114.1, 78.5, 57.9, 35.3. Exact mass (EI) calcd for
C
13H14O 186.1045, found 186.1029.
Solvolysis of Ch lor id es 29 in Meth a n ol. To a solution
of 5 mg of 2,6-lutidine in 3 mL of methanol was added 8 mg of
the mixture of chlorides 29. The resulting solution was kept
at room temperature for 2 h. The methanol was then removed
using a rotary evaporator, and the residue was taken up into
ether, washed with water and saturated sodium chloride
solution, and dried over a mixture of Na2SO4 and MgSO4. After
filtration, the solvent was removed using a rotary evaporator,
and the residue was filtered through a short pad of silica gel.
Elution with 10% ether in hexanes gave 7 mg (90%) of methyl
ether 35. 1H NMR (CDCl3) δ 7.60 (d of d of d, J ) 11.8, 1.7,
0.8 Hz, 1 H), 6.71 (m, 1 H), 6.70 (m, 1 H), 6.33 (d of m, J ) 5.8
Hz, 1 H), 6.29 (d of m, J ) 5.6 Hz, 1 H), 6.21 (m, 1 H), 5.98 (d
of d of d, J ) 11.8, 3.7, 1.5 Hz, 1 H), 4.16 (d of d of d, J ) 3.7,
1.7, 0.8 Hz, 1 H), 3.74 (s, 3 H), 3.54 (s, 3 H), 3.04 (d of t, J )
8.8, 0.8 Hz, 1 H), 0.55 (d of d, J ) 8.8, 0.8 Hz).). 13C NMR of
35 (CDCl3) δ 166.6, 151.1, 132.8 (d, J ) 159 Hz), 127.7 (d, J )
159 Hz), 127.4 d, J ) 159 Hz), 124.5 (d, J ) 157 Hz), 123.2 (d,
J ) 164 Hz), 121.8 (d, J ) 157 Hz), 114.0 (d, J ) 161 Hz),
99.7, 99.0, 78.9 (d, J ) 143 Hz), 56.7 (q, J ) 141 Hz), 51.4 (q,
J ) 146 Hz), 29.2. Exact mass (EI) calcd for C15H16O3 244.1100,
found 244.1125.
P r ep a r a tion of Mesyla te 44. A solution of 226 mg of 11-
hydroxybicyclo[4.4.1]undeca-2,4,8-triene23 in 8 mL of ether
containing 35 mg of 10% Pd/C was hydrogenated at 50 psi for
4.5 h. The solution was filtered, and the solvent was evapo-
rated using a rotary evaporator. The crude residue was
purified by chromatography on 15 g of silica gel to give 178
mg (79%) of 11-hydroxybicyclo[4.4.1]undecane, mp 64-66 °C.
1H NMR (CDCl3) δ 4.17 (m, 1 H), 2.25 (m, 2 H), 1.40-1.90 (m,
16 H). 13C NMR (CDCl3) δ 77.7, 43.0, 30.9, 29.2, 26.1, 25.7.
Exact mass (EI) calcd for C11H20O 167.1436, found 167.1413.
A solution of 178 mg of 11-hydroxybicyclo[4.4.1]undecane
and 182 mg of mesyl chloride in 2 mL of CH2Cl2 was cooled to
-15 °C, and a solution of 182 mg of triethylamine in 1 mL of
CH2Cl2 was added dropwise. The mixture was warmed to room
temperature and diluted with ether, and water was added. The
mixture was transferred to a separatory funnel, and the
organic phase was washed with dilute HCl solution and
saturated NaCl solution and dried over MgSO4. The solvent
was removed using a rotary evaporator to give 252 mg (97%)
1
of mesylate 44, mp 52-54 °C. H NMR (CDCl3) δ 5.09 (t, J )
4.2 Hz, 1 H), 3.01 (s, 3 H), 2.49 (m, 2 H), 1.40-1.90 (m, 16 H).
13C NMR (CDCl3) δ 90.0, 41.9, 38.6, 30.3, 29.1, 25.7, 25.4.
Solvolysis of 2-Ch lor om eth yl-1,6-m eth an o[10]an n u len e
(8) in Meth a n ol. A solution of 82 mg of 6 in 3 mL of methanol
containing 66 mg of 2,6-lutidine was stirred at room temper-
ature for 4 h. The methanol was removed using a rotary
evaporator, and the residue was taken up into ether, washed
with dilute HCl solution and saturated NaCl solution, and
dried over MgSO4. After filtration, the solvent was removed
using a rotary evaporator, and the residue was chromato-
graphed on 8 g of silica gel. The methyl ether 11 (73 mg; 92%)
Solvolysis of Tr ifla te 42 in CF 3CH2OH. A solution of 15
mg of triflate 42 in 1.6 mL of 0.05 M 2,6-lutidine in trifluoro-
ethanol was stirred at room temperature for 20 h. The mixture
was taken up into ether, washed with water, dilute HCl
solution, and saturated NaCl solution, and dried over MgSO4.
After filtration, the solvent was removed using a rotary
evaporator, and the residue was chromatographed on 5 g of
silica gel. The trifluoroethyl ether 43 (11 mg; 92%) eluted with
1
5% ether in hexanes. H NMR of 43 (CDCl3) δ 7.37 (m, 2 H),
7.21 (m, 2 H), 7.10 (m, 2 H), 7.06 (m, 2 H), 3.03 (q, J ) 9 Hz,
2 H), 1.34 (s, 1 H). 13C NMR of 43 (CDCl3) δ 126.74, 126.65,
126.1, 124.1, 123.4 (q, J ) 279 Hz), 117.2, 73.9, 63.9 (q, J )
35 Hz). Exact mass (EI) calcd for C13H11F3O 240.0762, found
240.0749.
(23) Ito, S.; Ohtani, H.; Narita, S.; Honma, H. Tetrahedron Lett.
1972, 2223.
J . Org. Chem, Vol. 68, No. 22, 2003 8691

Creary and Miller
Solvolysis of Tr ifla te 42 in DMSO-d 6. A solution was
prepared by dissolving 5 mg of triflate 42 in 1.0 mL of DMSO-
d6, and the solution was transferred to an NMR tube. The
reaction was monitored by 600 mHz 1H NMR at room tem-
perature. The major product, naphthalene 46, was identified
by spectral comparison with an authentic sample, as were
formic acid, 49, alcohol 41, and 1-naphthaldehyde, 50. Small
amounts of the unstable oxosulfonium ion intermediate 47 (δ
7.63, 7.45, 2.24) grow in with time at room temperature. The
minor product 45 (δ 7.87, 7.78, 7.28, 7.20, 1.63) also appears
at room temperature. After 64 h at room temperature, the
mixture was heated at 55-60 °C for 3 h. The 1H NMR
spectrum now showed no remaining 42 or 47 and the products
41, 45, 46, and 50 in a 4:41:52:3 ratio.
described.25 The rate of reaction of triflate 42 in DMSO-d6 was
monitored using the 19F NMR method previously described.26
Rates of reaction of acetates 26 and 27 (CH3OD) as well as
chlorides 29 (CD3OD containing 0.05 M 2,6-lutidine) were
determined by 1H NMR spectroscopy. Rate constants were
calculated using standard least-squares methods and repre-
sent an average of duplicate runs. Typical data given in Table
1 are (2%.
Com p u ta tion a l Stu d ies. Ab initio molecular orbital cal-
culations were performed using the Gaussian 98 series of
programs.14 Structures were characterized as minima via
frequency calculations that showed no negative frequencies.
Ack n ow led gm en t. The National Science Founda-
Kin etic Stu d ies. Rates of reaction of 2-chloromethyl-1,6-
methano[10]annulene, 8, p-methoxybenzyl chloride, 13, me-
sylate 16, and mesylate 17 in methanol (3 × 10-4 M in 2,6-
lutidine) were determined using the UV spectroscopic method
previously described.24 The reactions of 8, 16, and 17 were
monitored at 270 nm while the reaction of 13 was monitored
at 246 nm. Rates of reaction of 3-chloromethyl-1,6-methano-
[10]annulene, 10, chloride 30, triflate 42, and mesylate 44 were
monitored by the NMR spectroscopic method previously
tion is acknowledged for partial support of this research.
Su p p or tin g In for m a tion Ava ila ble: B3LYP calculated
structures, energies, and Cartesian coordinates of 2, 3, 4, 6,
1
35-37, and 51-53 and H and 13C NMR spectra of compounds
11, 12, 28, and 42-44. This material is available free of charge
via the Internet at http://pubs.acs.org.
J O035006W
(24) Creary, X.; Hatoum, H. N.; Barton, A.; Aldridge, T. J . Org.
Chem. 1992, 57, 1887.
(25) Creary, X.; J iang, Z. J . Org. Chem. 1994, 59, 5106.
(26) Creary, X.; Wang, Y.-X. J . Org. Chem. 1992, 57, 4762.
8692 J . Org. Chem., Vol. 68, No. 22, 2003