Chemistry Reference
In-Depth Information
The cyclization of the (
Z
)-configured enol ether
14b
took place in poor yield but still
with good diastereoselectivity; this can be attributed to the fact that the bicyclization
of this compound requires that the bulky alkoxy group is accommodated in the more
sterically confining
endo
position (Scheme 5.22). Interestingly enough, in all instances the
resulting diastereomers of the products
15a
-
d
were easily separable by simple column
chromatography.
Ph
O
H
Co
2
(CO)
8
O
Ph
O
Isooctane, rt, 1.5 h;
reflux, 1.5 h
H
(Major isomer)
14b
15b
(20%, 5:1 dr)
Scheme 5.22
The stereochemical identity of the major diastereomer of
15a
was established both by
X-ray diffraction analysis of a monocrystal and, as shown in Scheme 5.23, by conversion to
optically pure (
99% ee) (-)-(1
R
,5
S
)-1-methylbicyclo[3.3.0]octan-3-one
16
, in a sequence
that allowed the recovery of the chiral auxiliary in a 92%yield.When themajor diastereomer
of
15b
was submitted to the same reaction sequence, the enantiomeric ketone (
+
)-(1
S
,5
R
)-
16
was obtained.
Ph
O
H
H
1) Me
2
CuLi, Et
2
O, 95%
+
O
O
Ph
OH
1) SmI
2,
THF-MeOH, 90%
Me
(92%)
15a
(Major isomer)
(-)-
16
Scheme 5.23
The stereochemical outcome of the reaction was rationalized with the aid of molecular
mechanics calculations, that showed that the most stable conformation of the enyne
14a
is that (extended
s-trans
) depicted in Scheme 5.24, in which the C
-
Re
face of the
olefin is shielded by the phenyl group of the auxiliary. The other face of the enol ether is
then preferentially coordinated to the cobalt, and evolves into a cobaltacycle that leads to
the major diastereomer observed.
17
The potential of this approach was illustrated by an enantioselective formal total syn-
thesis of the natural product (
-
Si
,C
)-hirsutene (Scheme 5.25).
28
The acetylenic ether
17
,
14
derived from (1
R
,2
S
)-(-)-2-phenylcyclohexanol, was converted into the iodoacetylene
18
,
that was reacted with the zinc reagent derived from the bromide
19
in the presence of
+
