Chemistry Reference
In-Depth Information
SO
2
Ph
PhSO
2
I
Pd(PPh
3
)
4
, Et
3
N
O
O
O
O
O
O
9.169
9.170
NHPMB
NPMB
PhSO
2
NH
Pd(PPh
3
)
4
, TMG,
CH
3
CN,
O
O
TMG =
Me
2
N
Δ
NMe
2
OMOM
OMOM
O
O
S
S
S
S
9.171
9.172
Scheme 9.49
formed, the seven-membered ring could be closed by a Heck reaction. The usual catalysts failed in this case.
A high temperature was required, and the usual catalysts often decompose on excessive heating. Herrmann's
catalyst (see Scheme 5.17) is particularly robust and worked. The Heck reaction gives a single stereoisomer
9.168
with the newly formed C-C bond
cis
to nitrogen.
A
3
-allyl palladium chemistry
(Scheme 9.49).
64
Tetramethylguanidine (TMG), which is a stronger base than triethylamine by at least
two orders of magnitude, was found to be the base of choice for the cyclization of allylic sulfone
9.171
.
The sulfone leaving group was also essential to the synthesis of the earlier intermediate
9.170
by allowing
alkylation to introduce the aminopropyl side chain.
65
Double allylation was used in a synthesis of huperazine A
9.179
, an acetyl choline esterase inhibitor
and, hence, potential anti-Alzheimer's compound, isolated from a Chinese club moss (Scheme 9.50).
66
Treatment of the
different
approach
to
the
cephalotaxine
ring
system
also
used
-ketoester
9.173
with an allylic diacetate in the presence of a palladium catalyst and
tetramethylguanidine resulted in a two-fold allylation to give the bicyclic product
9.174
. This sets up the
huperazine ring system in a single step. The first process in this reaction must be allylation between the
two carbonyl groups (
-position. Allylation of a simple eno-
late is less well known, especially with such a modest base and, in this case, must be favoured by being
intramolecular. Two additional carbons were installed by Wittig olefination. This gave predominantly the
wrong isomer, and this had to be corrected by a free radical method to give the desired isomer
9.175
.
Degradation of the ester to a carbamate, a process involving Curtius rearrangement, changed the ester to
an amine derivative
9.178
. Finally, deprotection reactions and an alkene isomerization yielded the natural
product
9.179
.
Sulfinates have also been used as the leaving group, even though sulfinic acids are not strong acids. The
usefulness of this approach is that the sulfone group, as a good carbanion-stabilizing group, can also be used
to synthesize the substrate. This was used in a synthesis of the Monarch butterfly pheromone
9.184
(Scheme
9.51).
67
Michael addition of the anion of sulfone
9.180
to MVK gave a ketone
9.181
that was subjected to a
Horner-Wadsworth-Emmons reaction. Displacement of the sulfinate by the anion of dimethyl malonate with
a palladium catalyst, followed by Krapcho decarboxylation, gave the pheromone
9.184
.
to the ester), followed by allylation at the
