Biomedical Engineering Reference
In-Depth Information
O
RO
2
C
RO
2
C
O
O
O
OR
Rh
2
(OAc)
4
PhMe, reflux
+
N
2
N
(CH
2
)
2
N
N
399
400
(65%)
401
(7%)
SCHEME 13.73
N
Cu(acac)
2
N
2
N
N
N
+
EtO
2
C
O
EtO
2
C
EtO
X
PhMe, reflux
EtO
2
C
X
n
O
n
O
X
n
X
n
O
O
402a
(X = O,
n
= 2)
402b
(X = C,
n
= 2)
402c
(X = O,
n
= 1)
402d
(X = C,
n
= 1)
403a
(X = O,
n
= 2)
403b
(X = C,
n
= 2)
403c
(X = O,
n
= 1)
403d
(X = C,
n
= 1)
404a
(X = O,
n
= 2; 54%)
404b
(X = C,
n
= 2; 60%)
404c
(X = O,
n
= 1; 42.5%)
404d
(X = C,
n
= 1; 43%)
405a
(X = O,
n
= 2; 23%)
405b
(X = C,
n
= 2; 8%)
405c
(X = O,
n
= 1; 42.5%)
405d
(X = C,
n
= 1; 43%)
SCHEME 13.74
reacted with catalytic amounts of Rh
2
(OAc)
4
in boiling toluene to give a 9:1 mixture
of [2,3]:[1,2]-rearrangement products
400
and
401
in 72% yield (Scheme 13.73).
Analysis of a Mosher ester derivative suggested that
400
was formed with 97.7%
enantiomeric excess.
Each of the above examples involves the reaction with an exocyclic alkene to
fashion a ring-expanded product. Sweeney and coworkers examined [2,3]-rearrange-
ments involving an endocyclic alkene that yielded ring-contracted products [125].
The copper-catalyzed decomposition of
402a
gave a mixture of
404a
and the
corresponding
trans
-diastereomer in a 57:43 ratio and 54% combined yield
(Scheme 13.74). The [1,2]-rearrangement product
405a
was also isolated in 23%
yield. Keto ester
402b
also underwent rearrangement under the same conditions to
give
404b
in 60% yield and
405b
in 8% yield. In addition to a more favorable product
distribution, structure
404b
was formed with a 7:3 diastereomeric ratio.
Interestingly, homologues
402c
and
402d
each produced 1:1 mixtures of [1,2]-
and [2,3]-rearrangement products. Morpholine derivatives
404c
and
405c
were
isolated in 85% combined yield, and
404c
was produced as a 1:1 mixture of
diastereomers. Piperidones
404d
and
405d
were isolated in 86% yield, though in this
case the diastereomeric ratio for
404d
was 3:2. The differences in selectivities were
explained in terms of the differing flexibilities of the intermediate ylides
403a
-
403d
.
13.4. CONCLUSION
The application of ammonium ylides in the targeted syntheses of alkaloids as
described in this chapter spans a broad spectrumof organic synthesis. Since Huisgen's
seminal contributions to our understanding of the dipolar cycloaddition process and
Steven's first report of the [1,2]-shift of ammonium 1,2-ylides, great strides in the
development of methods for the generation and application of these reactive ylides
have been made. The regio- and stereoselectivity of both the rearrangements and
cycloadditions are now well established, making them attractive strategic
Search WWH ::
Custom Search