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TMS-Sn(
n
-Bu)
3
Pd(PPh
3
)
4
TMS
OMe
OMe
THF, reflux
60%
O
Sn(
n
-Bu)
3
O
42
43
I
2
, Et
3
N
CH
2
Cl
2
, rt
99%
TMS
BrZn(CH
2
)
3
CH=CH
2
Pd(PPh
3
)
4
OMe
OMe
O
O
I
THF, 50°C
69%
45
44
SCHEME 2.14
Initial strategy for the synthesis of (
S
)-jamaicamide C
39
.
Compound
40
was initially considered as a key intermediate in the synthesis of
39
, which featured a silylstannylation and a Negishi coupling as the key steps
(Scheme 2.14).
Hence, the vinyl stannylation was performed with trimethylsilyl tributyl-
stannane in the presence of a catalytic amount of palladium to provide
43
, which
43
was selectively converted to the corresponding iodide
. Negishi coupling was then
performed to introduce the 5-pentenyl group. In sharp contrast to results obtained in
model reactions, this coupling appeared to be inefficient, yielding unreacted
44
and
desilylated product
. The reasons remain unclear, one possible explanation being
the presence of the remote olefin in
44
, which could impact the reactivity of the
vinyl iodide. Consequently, Paige and coworkers decided to install the olefin later
in the synthesis and therefore considered compound
45
41
as a key intermediate
(Scheme 2.13). Oxazolidinone
using a similar
synthetic sequence (Scheme 2.15). The stannylation and the Negishi coupling were
both performed under microwave irradiation to yield
41
was successfully prepared from
46
, respectively. In this
case, the Negishi coupling was efficient and provided oxazolidinone
47
and
41
in 84%
yield. Sixmore steps (installation of themethyl group, transformation of the TMS in
the corresponding chloride, and oxidation level adjustment of the terminal carbon)
provided (
S
)-jamaicamide C
41
39
.
TMS
O
O
O
O
TMS-Sn(
n
-Bu)
3
Pd(PPh
3
)
4
N
N
Sn(
n
-Bu)
3
O
O
THF, microwave, 95°C
69%
46
47
I
2
CH
2
Cl
2
, rt
99%
TMS
TMS
O
O
BrZn(CH
2
)
3
CH=CH
2
Pd(PPh
3
)
4
O
O
N
I
N
O
O
THF, microwave, 50°C
84%
41
48
(
S
)-Jamaicamide C
39
SCHEME 2.15
Successful strategy for the synthesis of (
S
)-jamaicamide C
39
.
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