Biomedical Engineering Reference
In-Depth Information
HCT-116 human colon carcinoma [40]. As shown in Scheme 8.8, the reaction of the
intermediate ester with LDA and Me
3
SiCl afforded a silyl ketene acetal that was
treated with isoamyl nitrite and titanium tetrachloride in methylene chloride at low
temperature. Interestingly, when the reaction mixture was warmed at 0
C, the oxaza
Cope rearrangement took place to give the expected and desired oxazine in 82%
overall yield.
8.2.2. The Oxy-Cope Rearrangement
The oxy-Cope rearrangement is a thermal [3,3]-sigmatropic rearrangement that
allows to convert 1,5-dien-3-ols into
d
,
e
-unsaturated carbonyl compounds, the
formation of the carbonyl compound being the driving force for the reaction
(Scheme 8.9) [41]. The enormous rate acceleration coupled with the significant drop
in the reaction temperature during the conversion of the potassium alkoxides derived
from 1,5-diene alcohols to the corresponding
d
,
e
-unsaturated carbonyl compounds
resulted in a major improvement in the oxy-Cope rearrangement. The base accel-
erated oxy-Cope rearrangement is also called anionic oxy-Cope rearrangement
(Scheme 8.9) [5]. Actually, it is worth pointing out that both [3,3]-sigmatropic
rearrangements are stereospecific and stereoselective as a result of a cyclic highly
ordered transition state.
A cascade reaction featuring various [3,3]-sigmatropic rearrangements, includ-
ing an oxy-Cope-Claisen-ene reorganization, was used for the preparation of
wiedemannic acid, an abietane diterpene isolated from the aerial parts of
Salvia
wiedemanii
(Scheme 8.10) [42].
Paquette's group has made a number of contributions showing the power of
the anionic oxy-Cope rearrangement for the assembly of complex polycyclic
compounds starting from hydroxy-substituted 1,5-hexadienes. Indeed, by treating
these compounds with various bases (sodium or potassium hydride, potassium
O
-
O
HO
HO
HO
base
[3,3]
heat
[3,3]
acid
SCHEME 8.9
Oxy-Cope rearrangement and anionic oxy-Cope rearrangement.
O
O
O
OTBS
210°C (MW)
PhMe, 1 h
OTBS
OTBS
H
OH
OH
OTBS
90%
O
H
HO
2
C
Wiedemannic acid
SCHEME 8.10
Synthesis of wiedemannic acid.
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