Biomedical Engineering Reference
In-Depth Information
O
Me
362
Pd(TFA)
2
(10 mol%)
BOXAX (40 mol%)
MeO
MeO
MeO
O
p
-Benzoquinone
CH
2
Cl
2
, 3.5 days
O
O
OH
PdL
2
X
84%
364
(ee = 97%)
361
363
O
steps
HO
N
N
O
O
2
Vitamin E
365
BOXAX
SCHEME 9.63
Synthesis of
a
-tocopherol
365
by Tietze and coworkers.
side chain of
-tocopherol in a one-pot process with 97% ee. Thus, reaction of
361
a
withmethyl vinyl ketone
362
in the presence of BOXAX [138], benzoquinone, and Pd
(TFA)
2
led to
364
in 84% yield and 97% ee. It can be assumed that the palladium(II)
species
is an intermediate in this process that further reacts with methyl vinyl
ketone present in the reaction solution. The product of the domino process was then
converted into vitamin E (
363
365
) within a few steps.
9.7.2. Rhodium-Catalyzed Domino Reactions
In 2007, Chiu and Lamused a domino reaction for the synthesis of (
), a
potent antifeedant isolated from brown alga
Dictyota indica
from the Arabian
Sea [139]. Their approach relied on the use of the domino reaction discovered
by Padwa et al. [140]. Hence, the chiral
)-indicol (
371
containing a bulky
OH-protecting group was subjected to a rhodium(II) catalysis, resulting in the
formation of the bicyclo[5.4.0]undecane adduct
-diazoketone
366
a
369
as the major product along with
370
as the minor diastereoisomer. The initial formation of a carbene followed by its
addition to the adjacent carbonyl provided a highly reactive carbonyl ylide interme-
diate that in turn underwent a 1,3-dipolar cycloaddition via the two transition states
367
, respectively (Scheme 9.64). The best diastereos-
electivity was observed with Rh
2
(octanoate)
4
in hexane with
and
368
to give
369
and
370
3.6:1(60%
yield), while changing the solvent to CH
2
Cl
2
improved the overall yield (81%) at the
expense of the diastereoselectivity.
Pseudolaric acid A, a related natural product showing a pronounced antiangio-
genic effect [141] and inhibition of tubulin polymerization [142], was prepared
analogously by Chiu and coworkers [143].
In 2006, Hashimoto and coworkers applied a similar approach using again a
domino carbonyl ylide formation/1,3-dipolar cycloaddition for the synthesis of
polygalolides A (
369
:
370 ΒΌ
375
376
) (Scheme 9.65) [144]. The two natural products
were obtained from the plant species
Polygala fallax
, which is known to possess
antihepatitis properties. For the synthesis of these two natural products, enantiopure
azaketone
372
was treatedwith Rh
2
(OAc)
4
to first generate the carbonyl ylide
373
that
) and B (
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