Chemistry Reference
In-Depth Information
reaction conditions, compatible with most functional groups, are the main
advantages. For unsymmetrical enediynes, two sequential cross-coupling
reactions are performed. The choice of the palladium catalyst and the base
depends upon the electrophile; when this is dichloroethylene (first step),
Pd(PPh
3
)
4
and n-butylamine are the best, whereas Pd(PhCN)
2
Cl
2
and
piperidine are better suited for the second step.
44
When enediynes 14-16
are desired, R
1
Me
3
Si. The resulting silylated enediynes can be
converted into the unsubstituted alkynes by the use of fluorides, Na
2
CO
3
,or
AgNO
3
.
45
These can be, in turn, iodinated by the complex iodine-morpho-
line.
45
Alternatively, the silyl alkynes have been transformed in one step into
their iodinated counterparts by the use of AgNO
3
-N-iodosuccinimide.
39
is usually
ΒΌ
19.2.2 D
OUBLE
-B
OND
F
ORMATION
D
URING OR
A
FTER
C
YCLIZATION
This strategy is probably the most convergent. In principle, the most
obvious way would be a cross-coupling reaction between a dialkyne and a
suitable ethylene unit. Although the Sonogashira reaction cited above
seemed perfect for this goal, its intramolecular version
6,46
has failed so far to
afford cyclodeca-3-ene-1,5-diynes.
47
After having screened without success
several organometal catalyzed cross-coupling reactions, Danishefky even-
tually succeeded in obtaining the desired ring by a modification of the Stille
reaction involving a diiodoalkyne 19 as electrophile and Z stannylene 20 as
nucleophile (Scheme 19.6). This method has already been employed for the
synthesis of polyfunctionalized enediynes, including calicheamicinone,
21
dynemicin A
15
and simplified dynemicin analogues.
48,49
The use of LiCl as
additive has been shown to improve the yields.
48,50
A three-step methodology, starting from a propargylic dialdehyde, takes
advantage of the Pedersen reductive pinacol reaction.
51
This method is
SCHEME 19.6
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