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Me
Sn
n-
Bu
3
CO
2
TMSE
OTiPS
52a
O
Me
Me
O
Me
H
H
O
Pd(CH
3
CN)Cl
2
(5 mol%)
DMF/THF (1:1)
52%
O
O
O
I
CO
2
TMSE
O
O
OTiPS
Me
Me
trans
-
51a
50
Me
Me
1. Cp
2
ZrHCl
2. ZnCl
2
3. Pd(PPh
3
)
4
(5 mol%)
O
H
O
O
O
Me
Me
Me
53
I
Me
CO
2
TMSE
52b
OTiPS
84%
SCHEME 2.18
Synthesis of key intermediate
50
.
of
trans
-
was benzene. Another hydrometalation reaction was used for the
preparation of vinyl iodide
52a
, namely, a hydrozirconation, followed by the
iodination of the resulting vinyl metal (Scheme 2.17). This transformation was not
regioselective and a mixture of
E
and
Z
vinyl iodides were obtained, which decreased
the overall yield to 53%. Nevertheless, the Stille coupling was tested but appeared
quite challenging since the best reaction conditions provided only 52% of desired
compound
51a
in conjunction with many side products (dimerization, protonation)
(Scheme 2.18).
Since the ineffective coupling was probably due to the difficult oxidative
addition of the trisubstituted vinyl iodide
50
onto the palladium, Drouet and
Theodorakis decided to exchange the role of the two coupling partners. This
was actually a very efficient alternative since the transformation of
53
into the
corresponding zinc derivative
51a
, which would later be involved in a Negishi
coupling, was high yielding and reproducible. This transformation was performed by
hydrozirconation followed by reaction with ZnCl
2
to provide
51b
51b
, most probably as a
zincate. The necessary vinyl iodide
52b
bearing the complementary fragment
originated from vinyl stannane
52a
by reaction with iodine (Scheme 2.17). The
Negishi cross-coupling between
51b
and
52b
was ultimately performed and afforded
the reveromycin precursor
in 84% yield with the all-
trans
stereochemistry
(Scheme 2.18). A few more steps, including a Kishi-Nozaki coupling, allowed the
complete synthesis of reveromycin B.
50
2.2.1.8. Carotenoids A series of very important carotenoid derivatives were
synthesized by Zeng and Negishi, making use in many cases of the Negishi coupling.
This is illustrated in the preparation of
b
-carotene
54
and vitamin A
55
(Figure 2.1) [21].
In the course of the synthesis of
b
-carotene
54
and vitamin A
55
, the two
building blocks
were prepared. The former was prepared via a Negishi
coupling between
(E)-
1-bromo-2-iodoethylene and the organozinc species derived
from trimethysilylacetylene (Scheme 2.19).
57
and
61
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