[2.2.2]octan-2-ones could undergo ester interchange with
little or no concurring base-catalyzed epimerization at C(6).
In fact, Figure 1 shows that 4 was converted into its endo-
Scheme 1. Conversion of
6-endo-Hydroxybicyclo[2.2.2]octan-2-ones into
6-exo-Acetoxybicyclo[2.2.2]octan-2-ones
bicyclo[2.2.2]octan-2-ones4 (Scheme 1), which in turn are
the major products of the aldol condensation of 3-oxocy-
clohexaneacetaldehydes.3
Given the facile conversion of 6-exo-hydroxybicyclo[2.2.2]-
octan-2-ones into the more stable endo C(6) epimers under
basic or acid conditions (Scheme 2), the cleavage of the ester
Scheme 2. exo-endo Equilibration of
6-Hydroxybicyclo[2.2.2]octan-2-ones under Either Basic or Acid
Conditions
Figure 1. Equilibration of a 10.0 mM solution of 4 carried out in
CD3OD at 25 °C: (a) in the presence of 10.0 mM CD3ONa alone,
and (b) in the presence of 10.0 mM CD3ONa/La(OTf)3. The
reactions were followed by a 200 MHz 1H NMR spectrometer using
benzene as internal standard.
bond of 6-exo-acetates without affecting the configuration
at C(6) is by no means trivial and obviously cannot be carried
out according to the available standard methods for the
deprotection of acetylated hydroxyls.
In a recent paper, Brown and co-workers reported on the
strong catalysis in the methanolysis of both aryl and alkyl
esters by a La3+-based catalyst.5 The active form of the
catalyst was convincingly argued to be a dimethoxy-bridged
dimer of stoichiometry (La3+)2(MeO-)2, generated in situ
upon mixing equimolar amounts of MeONa and La(OTf)3
in MeOH (eq 1) and having maximum catalytic activity in
the neighborhood of neutral pH.
epimer at an exceedingly low rate under the given conditions.
The estimated half-life is 42 days, compared with a half-life
of 23 min in the presence of MeONa alone.
A number of 6-exo-acetoxybicyclo[2.2.2]octan-2-ones (5-
9)6,7 were therefore subjected to methanolysis in the presence
of the lanthanum catalyst. In a typical run 10.0-2 mmol of
exo-ester was dissolved in 1.0 mL of a dry methanol8 solution
10.0 mM in La(OTf)3 and 9.5 mM in CH3ONa.9 The reaction
(6) Compounds 6, 7 (oil), 8 and 9 gave satisfactory elemental analyses.
Owing to the small amount of material available, recrystallization of
compounds 6, 8, and 9 was not attempted.
(7) Acetates 6-9 were prepared according to ref 4 from the proper
6-endo-hydroxybicyclo[2.2.2]octan-2-one via the corresponding tosylate
(Scheme 1). Data for 6: 1H NMR (200.13 MHz) δ 4.82-4.68 (m, 1H),
2.40-0.88 (15H); 13C NMR (50.32 MHz) δ 214.2, 170.4, 71.5, 47.2, 43.5,
35.5, 26.8, 24.7, 24.2, 21.0, 16.0; IR 1738 cm-1. Data for 7: 1H NMR
(200.13 MHz) δ 5.05-4.95 (m, 1H), 2.47-2.42 (m, 1H), 2.09-1.10 (18H);
13C NMR (50.32 MHz) δ 213.3, 172.2, 68.8, 52.3, 48.3 37.1, 36.5, 35.3,
33.2, 29.9, 25.8, 25.4, 21.1, 21.0; IR 1749.0, 1736.0 cm-1. Data for 8: 1H
NMR (200.13 MHz) δ 5.01-4.96, (m, 1H), 3.63 (s, 3H), 2.55-2.50 (m,
1H), 2.05-0.87 (28H); 13C NMR (50.32 MHz) δ 213.1, 179.0, 170.1, 68.3,
54.9, 51.9 51.3, 50.0, 48.3, 47.2, 38.5, 37.9, 37.4, 36.8, 36.6, 36.2, 21.1,
21.09, 18.7, 17.1, 16.4, 15.1; IR 1741.0, 1723.0 cm-1. Data for 9: 1H
NMR (200.13 MHz) δ 4.73-4.67 (m, 1H), 2.24-0.83 (m, 33H); 13C NMR
(50.32 MHz) δ 215.2, 170.6, 72.3, 47.1, 45.9, 44.0, 42.0, 41.8, 38.6, 34.1,
33.2, 33.1, 33.0, 32.8, 31.3, 30.7, 22.3, 22.2, 21.2, 18.6, 15.8; IR 1740.0,
Thus, the dimeric species (La3+)2(MeO-)2 features metal-
complexed methoxide ions of very low Bro¨nsted basicity
but most active in the ester cleavage process because
nucleophilic addition to the carbonyl is strongly assisted by
the electrophilic La3+ partner. On this basis it was thought
that in the presence of (La3+)2(MeO-)2 6-exo-acetoxybicyclo-
1737.0 cm-1
.
(8) Absolute methanol was distilled from Mg shavings and subsequently
from CuSO4 powder. The solvent was stored and handled under an argon
atmosphere.
(4) Marini Bettolo, R.; Migneco, L. M.; Moretti, P.; Scarpelli, R. J. Prakt.
Chem. 1999, 341, 687.
(5) (a) Neverov, A. A.; McDonald, T.; Gibson, G.; Brown, R. S. Can. J.
Chem. 2001, 79, 1704. (b) Brown, R. S.; Neverov, A. A. J. Chem. Soc.,
Perkin Trans. 2002, 2, 1039.
(9) La(OTf)3 was purchased by Aldrich and used as such. CH3ONa
methanol solutions were prepared by adding sodium to absolute methanol.
Titrations of the above solutions with standard N/100 HCl Normex showed
the absence of carbonate ions. CH3ONa was added slightly in deficit to
minimize the concentration of free methoxide ion in solution.
2784
Org. Lett., Vol. 4, No. 16, 2002