Biomedical Engineering Reference
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aspercyclides A and B where a very good yield of 92% was obtained, whereas the
yield dropped to 55% in the case of the
a
-substituted aspercyclide C. In the first steps
of the total synthesis of abyssenine A (see above, Schemes 3.32 and 3.33) by Evano
and coworkers [79], a copper-catalyzed arylation of the allyl alcohol
88
was used to
form the intermediate
that in turn underwent a Claisen rearrangement giving rise
to the phenol intermediate
90
91
in 93% yield over two steps.
3.3.6.2. Intramolecular Arylation Intramolecular copper-mediated cross-
coupling reactions were also successfully applied to the construction of heterocycles
containing a diaryl ether subunit. Selected examples are illustrated in Scheme 3.34.
Zhang and coworkers have applied the method devised by Olivera and
coworkers [85] (e.g., CuBr
S(Me)
2
) to promote the Ullmann biaryl ether coupling
reaction of dihydrostilbene
, thus accomplishing the first total synthesis of
bulbophylol B, a cytotoxic natural product [86]. Compared to other copper sources
(e.g., Cu, Cu
2
O, CuCl, or CuBr) in which no reaction and complex mixtures of
products were observed, the soluble copper(I) complex CuBr
92
S(Me)
2
gave rise to
dihydrodibenzoxepin
93
in 89% yield. Vialinin B, a potent TNF-
a
production
R
R
OH
O
X
X = Br, I, Cl R = H, alkyl, aryl
Br
CuBr
S(Me)
2
NaH
Py
120°C
89%
.
MeO
OBn
MeO
OH
MeO
H
2
Pd/C
OBn
O
O
O
OH
O
O
O
O
Bulbophylol B
O
92
93
CuBr
S(Me)
2
K
2
CO
3
, Py
reflux
(10-25%)
⋅
OH
O
O
HO
O
O
O
HO
O
O
OH
OH
O
Cu
2
O, Py
110°C
(88%)
Vialinin B
Combretastatin D-2
Dihydro-combretastatin D-2
X Y R Product
CH
2
CH(OH) H Acerogenin A
CH(OH) CH
2
H Acerogenin B
CH
2
C=O H Acerogenin C
C=O CH
2
H Acerogenin L
C=O CH
2
OMe Galeon
C=O CH
2
OH Pterocarine
X
Y
HO
O
CuO, K
2
CO
3
Py, 90°C
(49-76%)
R
SCHEME 3.34
Selected examples of copper-mediated intramolecular etherification.
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