C O M M U N I C A T I O N S
Scheme 2. Synthesis of Coraxeniolide a (3) from ent-4
4-epimer by column chromatography. The spectroscopic and
polarimetric data of the synthetic samples of 3 and 4-epi-3 were in
complete agreement with the values previously reported for these
compounds.3,15
A new enantioselective synthesis of â-caryophyllene (1) from
dienone 4 was carried out as shown in Scheme 3, the initial step
being the trityl perchlorate-catalyzed13 conjugate addition of silyl
ketene acetal 15 to the dienone 4. The ester group in the in situ-
generated silyl enol ether was then selectively reduced to CH2OH.
-
Desilation with Et3NH+ H2F3 afforded ketone 16. These three
transformations were carried out efficiently in one flask without
isolation of the intermediates. Primary alcohol 16 was then
converted into tosylate 17. Position-selective deprotonation (KOt-
Bu in i-PrOH - t-BuOH) of 17 and intramolecular R-alkylation
forged the cyclobutane ring and the caryophylloid ring system
stereoselectively.17 Finally, Wittig methylenation of the intermediate
ketone (Ph3PMeBr/n-BuLi in THF)7 afforded synthetic â-caryo-
phyllene (1), which was fully identical with a sample of the natural
â-caryophyllene. This is the first fully executed enantioselective
synthesis of â-caryophyllene.
The work described above entails a number of noteworthy
developments including (1) the implementation of a new strategy
involving the use of a chiral cycloolefin in the synthesis of
caryophylloids, (2) a simple synthesis of the chiral cyclonona-
dienones 4 and ent-4, (3) the 4-step conversion of ent-4 to
coraxeniolide A, and (4) the rapid and stereocontrolled transforma-
tion of 4 to â-caryophyllene. The configurational stability and utility
of 4 and ent-4 are especially striking in view of the almost
instantaneous racemization12 of the prototype trans-cyclononene.
Scheme 3. Synthesis of â-caryophyllene (1) from 4
Supporting Information Available: Experimental and characteri-
zation data for all the compounds prepared in this work. This material
References
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phyllene (1), respectively. Thus, trityl perchlorate-catalyzed13
conjugate addition of silyl ketene acetal 10 to the enone ent-4
produced ketoester 11. Position-selective deprotonation of 11 under
carefully chosen conditions (sodium tert-pentoxide in THF),
followed by subsequent trapping of the enolate with formaldehyde
(as a freshly prepared solution14 in THF), yielded lactone 12 in a
regio- and stereoselective fashion. Methylenation of 12 proved to
be difficult to achieve by the standard protocols (e.g., Ph3PMeBr/
n-BuLi in THF, or CH2Br2/TiCl4/Zn).15 This problem was circum-
vented by using crystallized, salt-free methylenetriphenylphospho-
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The success of this technique is due to the enhanced reactivity of
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