Biomedical Engineering Reference
In-Depth Information
N
2
CO
2
Bn
Et
3
N
EtOAc, 60°C
80%
N
+
CO
2
Bn
N
H
Br
H
N
2
O
O
340
341
342
Cu(acac)
2
(5 mol%)
PhMe,
84%
HO
BnO
2
C
O
R
S
S
H
N
2
H
4
, Na
H
HS
BF
3
•OEt
2
64%
SH
H
N
N
N
HOCH
2
CH
2
OH
76%
344
(R = CO
2
Bn)
345
(R = CH
2
OH)
(-)-Epilupinine
343
LiAlH
4
94%
O
O
BnO
2
C
ML
n
N
BnO
2
C
BnO
2
C
O
N
N
ML
n
346
347
348
SCHEME 13.64
arrangement of the pendant carbenoid. Cyclization of
347
gives
348
, wherein the
nitrogen atom is stereogenic. A stereospecific [1,2]-shift provides the observed product
and demonstrates a chirality transfer from a stereogenic nitrogen atom.
A few features of this work warrant further comment. When the methyl ester of
proline was used instead of the benzyl ester, the diastereoselectivity eroded to 5.25:1,
though still favoring the relative stereochemistry observed in
343
. Although catalytic
amounts of Rh
2
(OAc)
4
also affected the rearrangement of
342
to give predominantly
343
, the diastereoselectivity was reduced to 3:1, and the isolated
343
was obtained
with only 40-55% ee.
A limitation of the asymmetric Stevens rearrangement in the synthesis of
natural products is that significant retention of configuration about a migrating center
depends on the attachment of a conjugating group to the stereocenter. West and
Vanecko expanded the scope of this application by using a silicon atom [114].
Accordingly, heating a toluene solution of
-diazoketone
349
and a catalytic amount
of Cu(acac)
2
to 85
C produced
350
as a single diastereomer in 58% yield and with
77% ee (Scheme 13.65). Reduction of the carbonyl with DIBAL-H followed by
Fleming-Tamao oxidation gave
351
in 71% yield from
350
.
a
HO
OH
Me
2
PhSi
O
H
H
SiPhMe
2
Cu(acac)
2
1. DIBAL-H, -78
N
N
N
2. AcOH, TFA
Hg(O
2
CCF
3
)
AcOOH
71%
PhMe, 85°C
58%
N
2
O
349
350
351
SCHEME 13.65
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