Lipase–triethylamine-mediated dynamic transesterification of a tricyclic
acyloin having a latent meso-structure: a new route to optically pure
oxodicyclopentadiene
Takahiko Taniguchi and Kunio Ogasawara*
Pharmaceutical Institute, Tohoku University, Aobayama, Sendai 980-77, Japan
The racemic tricyclic acyloin (± ±)endo)3)hydroxytri)
graphy. The optical yield of the product was determined to be
97% ee by HPLC (chiral column CHIRALCEL OD, 5% Pr OH–
hexane) indicating clearly that the dynamic kinetic resolution
took place as expected. When the reaction was carried out
2,5
i
cyclo[4.2.1.0 ]non)7)en)4)one has been dynamically re)
solved via the transient formation of the meso)enediol isomer
under lipase–triethylamine)mediated kinetic transesterifica)
tion conditions to give the single chiral acetate (2±)endo)
without triethylamine, simple kinetic resolution occurred to
)acetoxytricyclo[4.2.1.02 ]non)7)en)4)one, serving as a pre)
,5
give the same endo-acetate (2)-5, [a]
26
2120.3 (c 1.0,
3
D
i
cursor of (2±)oxodicyclopentadiene, in excellent optical and
CHCl ), ( > 99% ee, CHIRALCEL OD, 5% Pr OH–hexane) in
3
chemical yields.
45% yield leaving 53% of the optically enriched starting acyloin
2
7
(+)-3, [a]
D
3
+ 190.5 (c 0.9, CHCl ) (92% ee, CHIRALCEL
i
During the preparation of the racemic tricyclic acyloin 3-hy-
droxytricyclo[4.2.1.02 ]non-7-en-4-one (±)-3 starting from
endo-2,3-bis(methoxycarbonyl)bicyclo[2.2.1]hept-5-ene 1 by
OD, 5% Pr OH–hexane); thus, this result indicates that the
amine accelerated the equilibrium between 3 and ent-3 via the
meso-1,2-enediol 4. When the racemic acyloin (±)-3 was stirred
with vinyl acetate in the same THF–triethylamine medium
without the lipase, the transesterification which competes with
the enzymatic reaction, although it occurred, proceeded very
slowly to give the racemic endo-acetate (±)-5 in less than 3%
yield, leaving most of the starting material untouched after 48 h
at room temperature. Taking these observations into account,
we concluded that triethylamine is requisite for the present
dynamic transesterification and the actual enantioselectivity
exerted by the enzyme was higher than that observed.
,5
1
2
employing the acyloin condensation, we observed that an acid
hydrolysis of the bis-trimethylsilyloxy intermediate 2 furnished
stereoselectively the single racemic acyloin (±)-3 having an
endo-hydroxy group (Scheme 1).† The endo-hydroxy config-
uration of 3 did not change even in the presence of triethyl-
amine, which brought about complete deuterium exchange of
the methine hydrogen on the acyloin functionality with
deuterium oxide within 10 h. This seemed to be due to facile
equilibration between the acyloin 3 and the transient meso-
1
,2-enediol intermediate 4 followed by convex-face selective
Having established the efficient dynamic kinetic trans-
esterification of the racemic acyloin (±)-3 having a latent meso-
structure, the optically active acetate (2)-5 thus obtained was
next transformed into optically active oxodicyclopentadiene 8
so as to determine the absolute configuration of the resolved
protonation of the latter under weak basic conditions. Since the
analogues of 3 having cyclopentenol and cyclohexenol rings in
place of the four-membered ring have been found to be
kinetically better discriminated than those having an exo-
hydroxy group under lipase-mediated transesterification condi-
tions, we assumed that dynamic kinetic resolution should
take place in a facile manner to give a single enantiomeric endo-
acetate 5. The racemic acyloin (±)-3 might be subjected to the
transesterification conditions in the presence of an appropriate
product as well as to probe its synthetic utility. Thus (2)-5 was
3
4,5
26
treated with excess MeMgI in THF to give the diol 6, [a]
D
3
215.7 (c 0.6, CHCl ), in nearly quantitative yield. Treatment of
the diol 6 with sodium periodate gave the keto aldehyde 7 which
was immediately exposed to diluted aqueous sodium hydrox-
6
8
lipase under favourable equilibrium conditions, thus generat-
ide to give the known oxodicyclopentadiene (2)-8, mp 74 °C,
2
6
3b
29
ing the transient enediol 4 having meso symmetry. We report
herein the first example of the lipase-mediated dynamic
transesterification of the racemic acyloin 3 leading to the highly
optically enriched single endo-acetate (2)-5 via the transient
generation of the meso-enediol 4 in reaction with vinyl acetate
in THF containing a catalytic amount of triethylamine (Scheme
[a]
D
2154.0 (c 1.0, CHCl
3
) [lit., mp 76 °C, [a]
D
2158.5
(c 1.0, CHCl
3
)] ( > 99% ee by HPLC: CHIRALCEL OB, 10%
i
Pr OH–hexane), in 50% overall yield by intramolecular aldoli-
zation.8 Since optically active oxodicyclopentadiene 8 is
2
).
When the racemic acyloin 3 was stirred with vinyl acetate
OH
1.2 equiv.) in THF containing triethylamine3
b,5a,7
(0.1 equiv.)
O
OH
(
H
in the presence of lipase PS‡ (Pseudomonas sp. immobilized on
Celite, Amano) for 48 h at room temperature, transesterification
HO
H
OH
O
24
occurred to give the optically active endo-acetate (2)-5, [a]
120.7 (c 2.0, CHCl ), in 75% yield accompanied by a minor
amount of 5-hydroxy-4-oxatricyclo[5.2.1.0 ]dec-8-en-3-one§
D
3
4
ent-3
2
3
2,6
vinyl acetate,
lipase PS,
Et3N, THF
vinyl acetate,
lipase PS,
slow
fast
(10%) which was separated by silica gel column chromato-
Et3N, THF
X –
OAc
OSiMe3
H+
O
ref. 1
dil. HCl
O
CO2Me
CO2Me
H
HO
H
AcO
(+)-5
H
OSiMe3
O
(–)-5
1
2
(±)-3
Scheme 1
Scheme 2
Chem. Commun., 1997
1399
Taniguchi, Takahiko
