Chemistry Reference
In-Depth Information
OH
O
O
HO
5 mol % Co
2
(CO)
6
-(2-methyl-3-butyn-2-ol)
10 mol % Et
3
SiH, 10 mol % CyNH
2
O
Me
Me
H
O
HO
OH
1 atm CO, DME, 70 °C, 78%
121
122
TMS
HO
2
C
H
O
Me
Me
O
H
H
O
TMS
123
OH
HO
124
Isocarbacyclin
C
5
H
11
Scheme 8.18
The diastereoselective total synthesis of isocarbacyclin.
123
in 78% yield. The catalytic conditions employing the Livinghouse procedure,
64
as
shown in Scheme 8.17, afforded the enone
123
in 76% yield based on a 67% conversion of
122
. Saito cited that although the catalytic process was successful, the reaction was slow
and difficult to quantitatively convert monocycle
122
to tricycle
123
. A number of steps,
including access to side chain analogs, were then carried out to complete the total synthesis
of isocarbacyclin.
The unusual fused [5.8.5] ring system, the dicyclopenta[a,d]cyclooctene, commonly
exists in the natural fusicoplagin A,
65
ophiobolins,
66
and cotylenol.
67
The employment
of diene-diyne
125
from previously reported chemistry
17
to generate tetracycle
126
was
studied in a variety of conditions via the tandem Pauson-reaction as shown in Scheme 8.19.
68
A variety of metal catalysts were screened in efforts to improve the diastereoselectivity of
the key tetracyclic intermediate
126a
.
The best conditions obtained, to date, were found in entries 5 and 6 wherein the reaction
was tuned to provide a higher diastereoselectivity by employing iridium and rhodium
catalysts, respectively. All diastereomeric ratios were determined by integration of the
NMR spectrum of the crude reaction material. With the tetracylic ketone
126
in hand, it
was heated in an aqueous solution of THF in the presence of a catalytic amount of pTSA
to provide diol
127
in 72% yield. The ring expansion strategy via an oxidative glycol
cleavage with sodium periodate in a phosphate buffer provided a successful entry into the
functionalized [5.8.5] ring systems in
128
and
129
.
8.12 Conclusions
For nearly 40 years, the Pauson-Khand reaction has been a powerful synthetic method
for the construction of cyclopentenones and bicyclic enones. The examples highlighted in
