Chemistry Reference
In-Depth Information
O
CO
2
H
K
2
PtCl
4
, CuCl
2
O
3
.
3
3
.
1
3
4
Scheme 3.58
NOMe
Br
NBS
no Pd
MeO
NOMe
3.136
Br
NOMe
MeO
Pd(OAc)
2
,
NBS
3.135
MeO
3.137
Scheme 3.59
3.5.2 Carbon-Carbon Bond Formation
An example of the use of this kind of C-H activation, combined with C-C bond formation, rather than
C-heteroatom formation, can be found in a synthesis of the core of teleocidin
3.138
, using an imine as the
coordinating group to direct palladation (Scheme 3.60).
59
Of the four key bond-forming events, three involve
palladium, and two involve the activation of unfunctionalized C-H bonds. Treatment of the imine
3.139
with palladium(II) chloride results in activation of one of the C-H bonds of the
t
-butyl group. Treatment
of the palladacycle
3.140
with a vinyl boronic acid
3.141
results in coupling. This step is analogous to the
bond forming process of the Suzuki reaction and presumably proceeds in the same way: transmetallation
and reductive elimination. This results in net reduction of palladium. Silver oxide may act as a halophilic
Lewis acid, abstracting the chloride from the palladium to facilitate transmetallation. Treatment of the coupling
product
3.143
with a strong acid results in an intramolecular Friedel-Crafts reaction. A second C-H activation
reaction was used to form the lactam, employing the same imine as the coordinating group. Treatment of
the bicyclic compound
3.144
under the same palladation conditions resulted in activation of one of the C-H
bonds of the methyl groups, with fair selectivity for the desired diastereoisomer. This selectivity is, perhaps,
due to the bulk of the
i
-propyl group controlling the conformation of the ring, and putting one of the two
methyl groups into closer proximity to the palladium. This time, the palladacycle
3.145
was carbonylated in
the presence of methanol to give an ester
3.146
. This was not isolated, as the reaction mixture was subjected
to the conditions for imine hydrolysis. With the amine exposed, cyclization occurred to give the lactam
3.147
.
N
-Alkylation, to install a 2-bromoallyl unit, and
O
-deprotection, then allowed the final palladium-catalysed
step, a phenol
o
-alkylation (see Section 2.11), to complete the synthesis.
Catalytic carbon-carbon bond formation has been achieved using boron derivatives but requires the right
choice of oxidant, otherwise homocoupling of the added organometallic (Section 2.10) may occur. Ben-
zoquinone (BQ) has been found to be effective, combined with direction of CH activation by pyridine
(Scheme 3.61),
60
by carboxylates (Scheme 3.62)
61
and by hydroxamic acids.
62
Air has been used as the
