Chemistry Reference
In-Depth Information
enantiomerically pure form led to the choice of
trans
-2-phenylcyclohexanol, easily avail-
able in multigram scale in both enantiomeric forms, as the more practical chiral auxiliary.
Moreover, as ihappened in the case of intramolecular PKRs (see Sections
5.2.1
and
5.2.4
above), the diastereomeric PK adducts could invariably be separated by simple column
chromatography on silica gel, and they were generally crystalline. The authors then exam-
ined the annulation of the alkoxyethyne derived from (1
R
,
2S
)-2-phenylcyclohexanol with
norbornadiene, which offered the possibility of effecting a PK-retro-Diels-Alder domino
sequence in order to obtain chiral cyclopentenones.
37
The reaction between the dicobalt
hexacarbonyl complex of this alkoxyacetylene and norbornadiene (Scheme 5.36) afforded
a 2.5:1 mixture of two diastereomers (93% global yield), from which the preponderant
one (
47
) was isolated in a 58% yield after chromatographic purification. Boron trifluoride
etherate-promoted conjugated addition reactions of methyl,
n
-butyl,
n
-heptyl, and vinyl
copper reagents took place exclusively on the
exo
-face of the enone, providing the adducts
48a
-
d
in 52-80% yields. Samarium (II) iodide in methanol cleanly effected the reductive
removal of the chiral alkoxy group, providing the enantiopure ketones
49a
-
d
(together
with the intact alcohol auxiliary for reuse) in 80-89% yield. The application of a Lewis
acid-catalyzed retro Diels-Alder reaction to
49c
gave the known levorotatory enone (
S
)-
50
and allowed the assignment of an absolute (1
S
,2
R
,6
R
,7
R
) configuration to
47
.
O
H
Ph
O
Ph
O
H
+
47
(58%)
Isooctane, reflux,
18 h;
SiO
2
chromatography
H
H
(OC)
3
Co
Co(CO)
3
H
RCu, BF
3
·Et
2
O,
Et
2
O, -78 ° to -50 °C
MeAlCl
2,
maleic anhydride,
1,2-dichloroethane,
55 °C
SmI
2,
THF-MeOH,
-78 °C
O
O
H
O
O
Ph
H
H
H
H
H
H
H
H
H
R
R
H
5
50
(71%, 95% ee)
Me
HO
Ph
48a
-
d
(R = Me,
n
-Bu,
n
-Hept, Vinyl)
52-80%
49a
-
d
(R = Me,
n
-Bu,
n
-Hept, Vinyl)
80-89%
H
Scheme 5.36
This stereochemical outcome can be explained by assuming a conformation of the
complex
17
such as that shown in Scheme 5.37, in which it is seen that the pro-(
S
) cobalt
is shielded by the phenyl group. Coordination of norbornadiene, from the
exo
-face, to the
pro-(
R
) cobalt and in an orientation such that the methylene bridge avoids steric interactions
with the CO ligands (Scheme 5.37) leads to the predominant diastereomer observed.
