Chemistry Reference
In-Depth Information
these enynes including NMO, BuSMe, and 4 A molecular sieves. The best conditions in-
volved reacting enyne
75
with dicobal toctacarbonyl and this was followed by 6 equivalents
of DMSO after which it was heated to 65
◦
C. The corresponding bicyclic enone
76
was
obtained as a single diastereomer in 89% yield.
Martin et al. reported during the optimization of the cyclization conditions, that the
handling and storage of Co
2
CO
8
under argon led to the best results. Other catalytic variants
were studied including cobalt and rhodium but starting enyne
75
was largely recovered.
The optimized conditions were extended to the reaction of enynes
77
and
79
to provide
yields of 91 and 33%, respectively. The positive results of the model studies supported
the approach via the Pauson-Khand towards the synthesis of (-)-alstonerine. As shown in
Scheme 8.13, the required starting enyne
81
had been previously synthesized by a four-step
diastereoselective process from L-tryptophan.
48
The Pauson-Khand reaction was carried
out with 1.2 equivalents of dicobalt octacarbonyl and 6 equivalents of DMSO at 65
◦
C
in THF to give the diastereomer
82
in 92% yield. Enone
82
was not crystalline but was
derivatized by BOC protection to give
83
followed by X-ray analysis to confirm the required
stereochemistry necessary for eventual conversion to (-)-alstonerine
84
.
O
Co
2
(CO)
8
[1.2
eq]
then
DMSO
[6
eq]
Boc
2
O,
CH
3
CN
99%
DMAP
CBz-N
N-Cbz
H
THF,
92%
65
°
C
H
H
82
81
O
O
H
Me-N
O
CBz-N
H
H
Me
N
N
BOC
Me
(-)-Alstonerine
84
83
Scheme 8.13
Intramolecular Pauson-Khand reaction towards (-)-alstonerine.
8.9 The Total Synthesis of (
±
)-8
α
-Hydroxystreptazolone
The total synthesis of (
-hydroxystreptazolone
93
was recently reported by Nomura
and Mukai
49
which employed the Pauson-Khand reaction with a 2-oxazolone derivative
which served as an olefin moiety and amine equivalent. (
±
)-8
α
-Hydroxystreptazolone is
an analog of streptazolin which has unique biological activity and has previously been
synthesized by several groups.
50
The initial strategy of Mukai centered on the construction
of 2-oxazolone-alkyne derivatives related to
85
in order to establish the appropriate Pauson-
Khand cyclization for eventual synthesis of
93
. The standard conditions involved reaction of
the alkyne
85
with dicobalt octacarbonyl in ether followed by the addition of the cyclization
promoter, as shown in Table 8.1. The use of amine oxides as the oxidant generally provided
±
)-8
α
