Biomedical Engineering Reference
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O
Ph
Ph
N
H
O
O
H
N
O
+
H
2
N
MR
3
O
N
n
X
n
189a
(
n
= 1; X = Cl)
189b
(
n
= 2; X = I)
189c
(
n
= 3; X = I)
190a
(MR
3
= SnBu
3
)
190b
(MR
3
= SiMe
3
)
191a
(
n
= 1; 78%)
191b
(
n
= 2; 88%)
191c
(
n
= 3; 17%)
O
Ph
Ph
N
O
H
O
N
H
+
H
2
N
MR
3
O
O
N
Cl
192
190a
(MR
3
= SnBu
3
)
190b
(MR
3
= SiMe
3
)
193
(85%)
H
X-
N
MR
3
N
N
MR
3
X
194
195
196
SCHEME 13.39
The spirooxindole alkaloids have attracted considerable synthetic attention and
dipolar cycloaddition approaches to their synthesis have been developed in recent
years. For example, Brown and coworkers developed a strategy in which silylated
amino nitrile
197
was treated with AgF to generate the corresponding azomethine
ylide that reacted with
198
to afford (
)-demethoxyhorsfiline
199
, though only in
16% yield (Scheme 13.40) [73]. Although the yield was somewhat disappointing, the
approach was expanded to target spirooxindole structures that also contain indoli-
zidine substructures. In a model study, AgF was allowed to react with amino nitrile
200
, and the resulting 1,3-dipole was trapped with
N
-phenylmaleimide to give
201
in
55% together with the
exo
-adduct in 24% yield. Encouraged by this result, the
azomethine ylide derived from
200
was trapped with
198
to give a nearly 1/1 mixture
of diastereomers
202
, but only in 20% yield.
Me
N
CH
2
TMS
CN
AgF
CH
3
CN
+
O
O
N
Me
H
H
16%
197
198
199
Ph
O
N
Ph
O
O
H
N
TMS
N
O
AgF
CH
3
CN
55%
NC
N
200
201
N
CH
2
H
AgF
CH
3
CN
TMS
N
+
O
O
H
H
NC
20%
200
198
202
SCHEME 13.40
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