Biomedical Engineering Reference
In-Depth Information
O
O
N
N
Rh(II)
Et
O
N
2
90%
O
O
CO
2
Et
Et
O
O
O
CO
2
Et
89
92
O
O
N
N
Rh(II)
Et
35%
O
N
2
O
O
CO
2
Et
Et
O
O
O
CO
2
Et
90
93
O
5
O
Et
N
O
O
N
Rh
2
(piv)
4
Rh
2
(pfb)
4
O
N
2
Et
90°C
Et
90°C
N
O
S
O
CO
2
Et
38%
51%
O
S
S
O
CO
2
Et
94
91
95
SCHEME 13.21
was converted into desacetoxy-4-oxo-6,7-dihydrovindorosine
98
in three subsequent
steps (Scheme 13.22) [48].
A synthesis of the more complex pentacyclic alkaloid (
)-aspidophytine
103
was then carried out making further use of the domino dipole cascade sequence. The
key sequence of reactions involved a 1,3-dipolar cycloaddition of the push-pull dipole
100
across the indole
p
-system. Treatment of the resulting dipolar cycloadduct
101
with BF
3
OEt
2
induces a domino fragmentation cascade. The reaction proceeds by an
initial cleavage of the oxabicyclic ring and the formation of a transient
N
-acyliminium
ion that reacts further with the adjacent
tert
-butyl ester and sets the required lactone
ring present in aspidophytine. A three-step sequence was then used to remove both
ester and OH groups from lactone
102
. Subsequent functional group manipulations
allowed the high-yielding conversion of
102
into (
)-aspidophytine
103
(Scheme 13.23) [49].
As a further extension of push-pull dipole cycloaddition chemistry, the Rh(II)-
catalyzed cyclization/cycloaddition cascade was applied toward the hexacyclic
framework of kopsifoline alkaloids. The kopsifolines
106
are structurally intriguing
O
N
N
Et
N
O
Rh(II)
O
H
Et
Et
O
O
O
O
N
N
O
N
Me
N
2
Me
HO
OMe
Me
CO
2
Me
CO
2
Me
96
97
98
SCHEME 13.22
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