Chemistry Reference
In-Depth Information
NH
2
Ph
OMe
Ph
OMe
O
O
O
O
NaBH
4
CHO
H
BF
3.
OEt
2
CHO
3.20
3.19
3.18
Et
Et
Ph
OMe
(Ph
3
P)
2
Pd
O
O
NH
(Ph
3
P)
4
Pd
N
NH
H
H
Et
3.22
3.21
Et
(Ph
3
P)
2
PdCl
2
, AgBF
4
;
then NaBH
4
, MeOH
N
HN
N
Et
H
3.23
Et
3.24
Scheme 3.11
3
-allyl palladium complex
3.22
(see Section 9.2) is generated with the chiral auxiliary left
over from the Diels-Alder reaction acting as a leaving group. Treatment of the bicyclic alkene
3.23
with a
stoichiometric amount of a palladium(II) complex, activated by silver(I), gave a
an intermediate
1
-alkyl palladium complex,
which was reduced, without isolation, to give the natural product, by treatment with sodium borohydride
to give the alkaloid
3.24
.
-Hydride elimination cannot occur, as there is no
-hydrogen suitably placed
stereochemically.
It could be argued that the cyclization does not proceed by C-H activation, but by formation of an elec-
trophilic
2
-complex
3.25
, which is then attacked by the electron-rich indole (pathway 1). If this were the case,
a distereoisomeric
1
-complex
3.26
, with palladium
trans
to the indole would be involved, whereas, by the
C-H activation mechanism (pathway 2), the palladium and the indole in the intermediate
3.30
would have the
cis
relationship, resulting from alkene insertion. As the C-Pd bond is converted to a C-H bond, the same final
product is obtained. The C-H activation mechanism of pathway 2 was demonstrated by using NaBD
4
to intro-
duce deuterium, in place of hydrogen (Scheme 3.12). The product
3.31
was found to have D
cis
to the indole.
This synthesis involves net reduction of palladium in a stepwise process. Hence, it is necessarily stoichio-
metric in palladium. A catalytic method for vinylation of indoles employing a pyridine ligand
3.33
has been
reported in which oxygen is employed to reoxidize the palladium (Scheme 3.13).
11
In sharp contrast, a platinum-catalysed version of the cyclization does proceed by nucleophilic attack of
the indole onto an
2
-alkene-metal complex, and not by C-H activation (Scheme 6.58).
12
Again, this was
shown by deuterium labeling.
3.1.2 Biaryl Coupling
C-H activation of arenes can also be used to couple two arenes together. A straightforward intramolecular
biaryl formation is found in a synthesis of neocryptolepine
3.38
(Scheme 3.14).
13
C-H activation was
