Chemistry Reference
In-Depth Information
(MeCN)
2
PdCl
2
, LiCl,
benzoquinone
Ts
NHTs
6.33
6.34
Scheme 6.15
(MeCN)
2
PdCl
2
, LiCl,
benzoquinone
H
NH
2
6.35
6.36
Scheme 6.16
nuc. addition to alkene
AcHN
CO
2
Me
HO
H
N
CO
2
Me
X
2
X
1
Heck
reaction
Heck reaction,
then reduction
of alkene
N
H
N
H
6.37
6.38
X
2
X
2
NH
2
NO
2
6.39
6.40
Scheme 6.17
two alkenes to a dihalogenated indole
6.38
, where X
1
and X
2
are halogens showing different reactivity. The
indole
6.38
would be made from a vinyl aniline
6.39
, which would be derived form a substituted toluene
6.40
.
The synthesis started with 2-bromo-5-nitrotoluene
6.40
(X
2
Br) (Scheme 6.18). Benzylic bromination
and S
N
2 displacement of the bromide gave a phosphonium salt
6.41
. A Wittig reaction could then be carried
out under mild conditions, because the salt is activated by the
ortho
-nitro group. The nitro group was then
reduced and the resulting amine was tosylated. The vinyl aniline derivative
6.39
was then cyclized to an
indole
6.43
using palladium catalysis, with benzoquinone to reoxidize the palladium(0) to palladium(II).
With the indole in hand, the second halogen could then be introduced, which was done via an organomercury
intermediate. Indoles usually react with electrophiles at the 3-position. Two regioselective selective Heck
reactions were then carried out on the dihalogenated indole
6.38
(X
1
=
I, X
2
Br). The first, with a
dehydroalanine derivative, functionalized the 3-position of the indole, due to the higher reactivity of iodide.
The second installed a tertiary alcohol substituted alkene at the 4-position. Further treatment of the double
Heck product
6.44
with a palladium(II) salt gave the tricyclic structure
6.47
. No oxidizing agent was needed
because the palladium eliminates as (formally) PdClOH, via
=
=
1
-complex
6.46
, and,
therefore, does not end up as Pd(0). However, the authors found that this step does not actually need Pd - just
H
+
will work, perhaps via an allylic carbocation. Double deprotection and alkene reduction was then carried
out photochemically in one pot to complete the synthesis.
2
-complex
6.45
and
