Chemistry Reference
In-Depth Information
THF (THF:H
2
O
=
20:1 v/v) to a gentle reflux to provide the desired tetracyclic diol
43
in
very high yield (
95%).
TIPS
OTf
TfO
H
EtO
TIPS
TIPS
44
TIPS
O
O
PTSA/THF/
H
2
O,
O
OH
Δ
, >95%
Steps
O
TIPS
O
TIPS
OH
TIPS
O
42
43
TIPS
45
Scheme 8.8
Final synthetic steps toward 14
annulenes
44
and
45
.
π
annulenes
44
and
45
. The two dicyclopenta[
a
,
e
]-
pentalenes
44
and
45
underwent significant electronic delocalization, perhaps even aro-
maticity, as revealed by the planar nature of the X-ray structure of
44
. The tetracyclic rings
in
44
assumed a flat geometry; the bond lengths of the tetracycle in
44
also fit well into
the criteria for aromatic compounds. A comparison of the NMR and UV spectra of both
44
and
45
demonstrated that they both exhibited similar electronic properties; therefore, the
purple colored 14
Subsequent steps afforded the two 14
cross-linked annulene
45
was planar as well as delocalized.
8.5 Enantioselective Total Synthesis of (-)-
α
-Kainic Acid
Isolated from the marine algae
Digenea simplex
30
-kainic acid
54
possesses
important biological activity exhibiting both anthelmintic and neurotransmitter activity
31
.
Due to the continued level of interest in the therapeutic implications of (-)-
in 1953, (-)-
α
-kainic acid,
several approaches via the Pauson-Khand reaction have been reported.
32
Hampered by
low diastereoselectivity and the large number of steps, Helmchen set out to employ an
enantioselective total synthesis of (-)-
α
-kainic acid
33
. This strategy established the neces-
sary chiral centers incorporating an Ir-catalyzed allylic amination and a diastereoselective
Pauson-Khand reaction.
Two complementary routes were developed which employed Ir-catalyzed reactions to
provide the key enyne
47
of which the best route route is shown in Scheme 8.9. The
starting carbonate
46
was reacted with the propargyl amine under the Ir-catalyzed condi-
tions
34
to provide the corresponding 1,6-enyne in 99% enantiomeric excess. The standard
Boc-protection under phase transfer conditions provided the Pauson-Khand precursors
enyne
47
. The Pauson-Khand conditions which employed dicobaltoctacarbonyl in the pres-
ence of molecular sieves promoted the cyclization to furnish key enone
48
in 65% yield.
α
