Biomedical Engineering Reference
In-Depth Information
≡
HCO
2
H
H
2
SO
4
HC
CLi
THF
CO
2
Me
CO
2
Me
MeO
2
C
O
OH
61%
30%
MeO
2
C
O
H
H
O
CO
2
Me
O
OH
COMe
H
H
H
Cedrol
SCHEME 8.39
Synthesis of cedrol via a Rupe rearrangement.
Stork-Clarke synthesis of the cedrenoid sesquiterpene cedrol [174], starting from
dimethyl 5,5-dimethyl-6-oxobicyclo[2.2.2]oct-2-ene-2,3-dicarboxylate (Scheme 8.39).
After a series of steps, (3a
R
,4
R
,6a
S
)-methyl 1,1,4-trimethyl-2-oxooctahydropentalene-
3a-carboxylatewas obtained and treatedwith lithiumacetylide inTHFat
75
Ctoafford
the desired propargylic alcohol in 61% yield, as a result of a very stereoselective
nucleophilic attack on the
b
-face of the ketone. Next, this propargylic alcohol was
submitted to the Rupe rearrangement using a mixture of formic acid and sulfuric acid
to afford the expected
a
,
b
-unsaturated ketone in 30% yield, whose hydrogenation and
base-promoted intramolecular cyclization gave the key intermediate that was subse-
quently transformed to cedrol (Scheme 8.39) [173].
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