Biomedical Engineering Reference
In-Depth Information
Br
O
33
O
Pd(dba)
2
, AsPh
3
THF (44%)
SnBu
3
Bu
3
Sn
Bu
3
Sn
O
32
37
1.
n
-BuLi , ZnCl
2
O
2. , Pd(PPh
3
)
4
(5 mol%)
Br
33
O
O
63%
SCHEME 2.11
Stille and Negishi couplings to prepare
37
.
Br
Me
3
SiCH
2
CH
2
O
1. Pd(dba)
2
(6 mol%)
AsPh
3
(19 mol%)
THF (73%)
O
38
O
+
O
2. Bu
4
NF, THF (61%)
O
Xerulinic acid
30
Bu
3
Sn
OH
37
O
O
SCHEME 2.12
Final coupling step.
The challenge in the coupling of
32
with
33
was to make sure that only 1 equiv
of vinyl bromide
was going to couple, thus leaving one vinyl stannane moiety
unreacted (Scheme 2.11). This was first tried directly with a Stille coupling in the
presence of Pd(dba)
2
and AsPPh
3
, but only 44% yield of
33
was obtained. A Negishi
coupling, which could potentially decrease the amount of doubly coupled product,
was then considered. A tin-to-lithium exchange was therefore performed using
n-
BuLi, followed by a lithium-to-zinc exchange with ZnCl
2
. The coupling reaction
in the presence of Pd(PPh
3
)
4
provided
37
with an improved yield of 63%.
The last steps consisted of a Stille coupling between vinyl stannane
37
and
bromide
37
38
, followed by a final deprotection to afford xerulinic acid
30
(Scheme 2.12).
2.2.1.6. (S)-Jamaicamide C A different stannylation procedure was used for
the preparation of the sodium channel blocker (
S
)-jamaicamide C
39
[18] by Paige
and coworkers [19] (Scheme 2.13).
TMS
OMe
O
Cl
40
(failed approach)
OH
or
O
TMS
O
O
39
N
O
41
(successful approach)
SCHEME 2.13
Potential precursors for the synthesis of (
S
)-jamaicamide C
39
.
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