Biomedical Engineering Reference
In-Depth Information
O
O
O
OTBS
OTBS
Me
OTBS
CO
2
Me
Me
Me
151
+
N
Bn
PhMe, 175°C
CO
2
Me
CO
2
Me
N
Bn
N
Bn
70%
150
152
153
Ph
3
P=CH
2
79%
CH
2
CH
2
OTBS
O
CO
2
H
Me
CO
2
Me
Me
Cl
Me
1.
1
.
TBAF
O
Cl
2. NaOH
2. Jones
3. CH
2
N
2
CO
2
Me
CO
2
H
CO
2
Me
N
H
N
Bn
N
Bn
56%
57%
156
155
154
O
OTBS
Me
O
OTBS
CO
2
Me
N
Bn
Me
157
158
SCHEME 13.33
Methylenation of
153
produced
154
in 79% yield. Removal of the silane protecting
group followed by oxidation and esterification provided
155
in 57% yield from
154
.
Finally, debenzylation and subsequent hydrolysis of the methyl esters furnished a
mixture of
allo
-kainic acid and 2-
epi
-
allo
-kainic acid
156
in 56% yield. Interestingly,
the reaction of
150
with (
Z
)-enone
157
produced a 3:1:1 mixture of
152
,
153
, and
158
,
respectively, in only 42% yield. It was determined that isomerization of enone
157
occurred to give
151
at a rate that was competitive with cycloaddition.
Garner and coworkers examined a photochemical aziridine ring opening to
generate azomethine ylides [63]. For example, irradiation of aziridine
159a
produced
ylide
160a
through a disrotatory opening of the aziridine ring (Scheme 13.34).
Trapping of
160a
with methyl acrylate provided the
endo
-isomer
161a
in 59% yield
and the
endo
isomer
162a
in 12%yield. Similarly, aziridine
159b
was irradiated in the
presence of methyl acrylate to produce
161b
and
162b
in a 5:1 mixture and a 62%
yield. Photolysis of aziridine
159c
produced
161c
and
162c
in 45% yield with a
similar
exo
:
endo
ratio. With
159b
and
159c
, the cycloadditions were not stereo-
selective, producing a 1/1 mixture of diastereomers.
To apply this strategy to the synthesis of alkaloids such as quinocarcin, the
diastereoselectivity of the cycloaddition needed to be better controlled. After
extensive experimentation with chiral auxiliaries and chiral benzyl amine derivatives,
it was discovered that the slow addition of sultam
164
to a solution of
163
with
irradiation produced
165
in 45% isolated yield with greater than 25:1 diastereo-
selectivity [64]. The chiral auxiliary could be removed (and recycled) by reactionwith
Ti(O
i
-Pr)
4
in boiling ethanol to furnish
166
in 62% yield.
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