end, the enol ether 3 was easily prepared and then subjected
to Saegusa oxidation conditions4 to afford enone 4. Initially,
a straightforward Saegusa reaction, using stoichiometric
quantities of palladium(II) acetate, provided the enone 4 in
92% yield. However, based on the expense of the precious
metal reagent, especially at such an early step in this synthesis
program, the catalytic modification5 of this useful transfor-
mation was investigated. This more economical protocol was
found to deliver 4 in a respectable 82% yield while requiring
the use of only 5 mol % of palladium(II) acetate. Having
secured a quantity of the desired enone, 1,4-addition of the
trimethylsilyl enol ether of ethyl isobutyrate, catalyzed by
ytterbium(III) triflate trihydrate,6 directly and efficiently
afforded the ester 5 in a yield of 81%. Initial attempts to
use titanium(IV) tetrachloride (the more traditional Lewis
acid for this type of reaction) as a stoichiometric mediator
of this Michael addition resulted in unwanted deprotection
of the ketal, even at -78 °C.
Scheme 2
The next goal in our sequence was the ethylidenation of
the ketone carbonyl of 5. Indeed, it was projected that the
stereochemical outcome of this process would impact upon
the later stages of our synthetic pathway, with the (E)-isomer
6b ultimately providing the requisite orientation of the C-15
methyl group of R-cedrene 1a. Under standard Wittig
reaction conditions a 92% yield of olefins 6a/b was obtained,
as an inseparable 2:1 mixture of geometric isomers. Con-
sequently, 6a and 6b were utilized in combination in order
to establish the planned synthetic route and with a view to
identification of individual isomers at a later stage. In this
respect, the remaining transformations toward the key
cyclization precursors 8a/b took place without difficulty
(Scheme 2). Initial reduction of the ester functionality of 6a/b
with lithium aluminum hydride was followed by oxidation
to aldehydes 7a/b using the Dess-Martin periodinane7 in
an overall yield of 96%. From the methods available for the
conversion of aldehydes into terminal alkynes, we chose the
Ohira-Bestmann reagent (dimethyl acetyldiazomethylphos-
phonate);8 previous experience in our laboratory had shown
this technique to be both practically simple and effective.
Indeed, in this instance, this mild protocol furnished the
requisite alkynes in 81% yield, and these were easily
complexed with octacarbonyldicobalt to afford the stable
cyclization precursors 8a/b almost quantitatively. With these
complexes in hand, we were now in a position to investigate
the proposed Khand annulation for the assembly of the
tricyclic carbon skeleton of R-cedrene.
A variety of methods for promoting the key intramolecular
Khand cyclization of 8a/b were examined (Scheme 3). These
Scheme 3
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