Chemistry Reference
In-Depth Information
The intramolecular Pauson-Khand reaction of metallocycle
9
to enone
11
was carried out
under thermal,
3
oxidative,
6
and ultrasonic
7
conditions. All methods provided the desired
product with differences in yield and stereoselectivity at C(12). The oxidative approach
developed by Schreiber
6
employed the use of
N
-methylmorpholine
N
-oxide at room tem-
perature and these conditions afforded a 70% yield of
11
with a mixture of 11:1 diastereomer
selectivity at C(12). Ultrasonic conditions in acetonitrile furnished a much lower yield of
45% but with 3:1 diastereomer selectivity at C12. The highest yield, albeit with slightly
lower diastereoselectivity, incorporated an atmosphere of air and thermal cyclization in
acetonitrile at reflux to furnish an 85% yield and 5:1 selectivity at C(12). Attempts to
epimerize the beta hydrogen at C(12) were unsuccessful.
To complete the synthesis of (
+
)-epoxydictymene, the stereochemistry of the enone
system in ring C had to be adjusted to provide the
trans
ring junction. From tetracycle
11
, a five step sequence was executed to provide ketoaldehyde
12
which contained the
appropriate functionality to complete this synthesis. Through a series of functional group
transformations on [5.8.5] tricyclic
12
, alcohol
14
was received in good yield. Ring closure
of alcohol
14
to generate the
trans
-fused 5-5 C ring was achieved by anionic cyclization
to give nitrile
15
which was subsequently reduced with potassium in 18-crown-6 ether to
complete the total synthesis of (
+
)-epoxydictymene
16
in 82% yield for this last step.
8.3
(
±
)-Pentalenene and (-)-Pentalenene
Pentalenene
25
, a triquinane natural product of the pentanolactone family of sesquiter-
pene antiobiotics, was synthesized by the Weiss reaction
8
and by various other methods
9
.
Depicted in Scheme 8.3 is the early synthesis of (
)-
pentalenene carried out by Schore
and Rowley using the Pauson-Khand strategy.
10
The 5-methylcyclopentyllithium
17
was
readily available and was added to the BHT protected methylacrylate
18
. This was followed
by methylation of the enolate which provided
19
in 90% yield. Treatment of ester
19
with
sodium in liquid ammonia afforded alcohol
20
. Conversion of alcohol
20
to enyne
21
was
achieved in 34% overall yield. Enyne
21
was then reacted with dicobalt octacarbonyl fol-
lowed by heating to 110
◦
C in heptanes to furnish a mixture of tricyclic enones
22
and
23
in
51% yield. Reduction of the two isomers with Li/NH
3
gave a mixture of saturated ketones
represented by
24
. The conversion of tricyclic
24
into (
±
)
-pentalenene
25
was carried out
analogously to steps previously reported in the literature.
9
±
Me
1. TsCl
2. LiI/HMPA/THF
3. LiC
Me
Me
Me
Na/NH
2
+
then
Me
M
e
Me
Me
CO
2
BHT
EtOH
CH(en)/DMSO/Et
2
O
CH
3
I
Li
90%
CO
2
BHT
17
18
19
20
OH
Me
Me
Me
M
e
H
3
C
H
3
C
H
Co
2
(CO)
8
Li/NH
3
Me
Me
O
Me
Me
Me
Me
Me
Δ
/heptane
51%
O
H
22
: CH
3
=α=88
23
: CH
3
=β=12
H
21
24
25
(±)-pentalenene
Scheme 8.3
The Pauson-Khand approach to (
±
)
-pentalenene
25
.
