Biomedical Engineering Reference
In-Depth Information
CO
2
H
O
O
H
NC
OTMS
O
OTMS
2
(10 mol%)
NHPh
PhNO
DMF, 0°C
93%
O
O
O
O
O
O
135
136
(ee > 99%)
137
OTBS
OH
O
Me
Me
H
Me
O
H
OMe
O
O
O
OH
138
O
Me
Me
139
Fumagillin (
134
)
Li
Me
2
Zn, CH
2
Cl
2
-78°C to -40°C
TMSCl, Et
3
N
-40°C to -20°C
Me
61%
OTBS
Me
Me
OH
Me
H
OTMS
140
(dr > 95:5)
SCHEME 6.28
Synthesis of the fumagillin framework.
ring-closing olefinmetathesis followed by a hydrogenolysis to afford the C6-C15 unit
149
of cernuine [59].
6.4. CASCADE REACTION
MacMillan and coworkers demonstrated a triple-cascade catalysis sequence com-
posed of a cross-metathesis, aMukaiyama-Michael reaction, and an intramolecular
aldol reaction. The sequence started with 5-hexen-2-one (
150
) and crotonaldehyde
(
69
) in the presence of the second generation Grubbs catalyst
151
to form the keto-
enal
152
(Scheme 6.31). Subsequent introduction of imidazolidinone catalyst
153
and siloxyfuran
154
promoted a Michael addition to afford keto aldehyde
155
.A
proline-catalyzed intramolecular aldol reaction then furnished butenolide
,
which contained four out of the six stereogenic centers and twelve out of the
fifteen carbons found in aromadendranediol (
156
159
) [60,61]. Transformation of
butenolide
156
into dialdehyde
157
followed by olefin metathesis of
the
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