LETTER
Lipase-mediated Resolution of cis-4-Cumyloxy-2-cyclopenten-1-ol and its Utilization
1755
We first examined the resolution of the racemic alcohol CHCl3), in 84% yield within 30 min. This Eschenmoser
(±)-4 under lipase-mediated kinetic transesterification reaction13 was found to be far superior to the acid-cata-
conditions in an organic solvent. Among the tested immo- lyzed Johnson type reaction14 using triethyl orthoacetate
bilized lipases, lipase PS-on-Celite gave the best result. as the latter brought about considerable decomposition.
Thus, stirring (±)-4 with lipase PS in tert butyl methyl The amide (–)-7 thus obtained was then stirred in a mix-
ether containing vinyl acetate5 brought about clear-cut ture of 10% hydrochloric acid and dioxane (1:1) at room
resolution to give the enantiopure acetate11 (–)-6, [a]29
temperature to give an important prostaglandin intermedi-
–62.03 (c 0.98, CHCl3), in 43% yield with 50% recovery ate 1S,5R-oxabicyclo[3.3.0]oct-6-en-3-one (–)-8, mp 43-
D
yield of the enantiopure alcohol (+)-4, [a]31 +27.52 (c 44 °C, [a]29 –103.21 (c 1.02, MeOH) [lit.12 : mp 42 °C,
D
D
1.11, CHCl3), after 2 h at room temperature. Enantiomeric [a]26 –102.3 (c 0.7, MeOH)], in 87% yield after 12 h
D
purities were determined by HPLC using a column with a (Scheme 4).
chiral stationary phase (CHIRALCEL OD, elution with
On the other hand, the acetate (–)-6 was exposed to al-
PriOH-hexane 1:200 v/v). Thus, the cumyl ether (±)-4 was
kaline methanol to give quantitatively the enantiopure
found to be a much more favorable substrate than the tert
butoxy counterpart (±)-1 for lipase-mediated resolution
(Scheme 3).
alcohol (–)-4, [a]31 –27.43 (c 1.01, CHCl3), which was
D
transformed into the tertbutyldimethylsilyl (TBS) ether
(–)-9, [a]D31 –47.01 (c 1.01, CHCl3), in 97% yield under
standard conditions. On the Birch reaction using sodium
in ammonia and THF, the bis-ether (–)-9 afforded the allyl
alcohol (–)-10, [a]30 –24.53 (1.59, CH2Cl2) having
D
1R,4S-configuration [lit.15 : for 1S,4R enantiomer, [a]20
D
+24.29 (c 2.47, CH2Cl2)], in 83% yield by cleavage at the
desired carbon-oxygen bonding. This is worth noting as
the cleavage did not occur at another possible allylic car-
bon-oxygen bonding but selectively at the benzylic car-
bon-oxygen bonding under these conditions. The
Scheme 3
Eschenmoser reaction of (–)-10 under the same conditions
as above afforded 3R,4S-N,N-dimethyl-4-cumyloxycy-
clopentenyl-3-acetamide (–)-11, [a]27 –56.55 (c 1.01,
In order to demonstrate the superiority of the cumyl group
D
CHCl3), in 77% yield. This compound, on stirring in a
mixture of 10% hydrochloric acid and dioxane (1:1) at
room temperature for 12 h, gave the same lactone above
(–)-8, mp 44 °C, [a]30D –103.11 (c 1.02, MeOH), in quan-
titative yield (Scheme 5).
over the tert butyl group as the protecting group for the
prostaglandin synthesis, we next examined the synthesis
of (–)-oxabicyclo[3.3.0]oct-6-en-3-one2,12 (–)-8 utilizing
both resolution products (+)-4 and (–)-6 in an enantiocon-
vergent manner.
Thus, a new route to an important prostaglandin building
block (–)-8 has been established in an enantioconvergent
way using both enantiomeric starting materials having a
cumyl ether functionality.
Thus, the alcohol (+)-4 was heated with 2.5 equiv. of di-
methylacetamide dimethyl acetal13 in refluxing diphenyl
ether to afford 3R,4S-N,N-dimethyl-4-cumyloxycyclo-
pentenyl-3-acetamide11 (–)-7, [a]28 –140.57 (c 1.08,
D
Scheme 4
Scheme 5
Synlett 1999, No. 11, 1754–1756 ISSN 0936-5214 © Thieme Stuttgart · New York