Chemistry Reference
In-Depth Information
RO
RO
RO
[RuCl
2
((
S
)-
DMM-SDP)((
R,R
)-DACH)]
NaClO
2
/TEMPO
H
2
,
i
PrOH, KO
t
Bu
OH
H
O
O
OH
90% ee
Scheme 7.13.
Synthesis of BAY X 1005 via asymmetric hydrogenation.
7.3.2.2.2. Aliphatic Ketones
Despite the success achieved in the hydrogenation of aro-
matic ketones, asymmetric hydrogenation of unfunctionalized aliphatic ketones has
remained a challenging area for a long time. Effective differentiation between two alkyl
groups is generally diffi cult to achieve. The Rh-PennPhos system has provided some
promising results in the asymmetric hydrogenation of aliphatic ketones (Table 7.16)
[290]. With this catalytic system,
tert
-butyl methyl ketone was hydrogenated in 94% ee.
Cyclohexyl methyl ketone was also hydrogenated in 92% ee. The more challenging
isopropyl methyl ketone and
n
-butyl methyl ketone gave relatively moderate results,
with 85% ee and 75% ee, respectively. On the other hand, cyclopropyl methyl ketone
was effectively hydrogenated by
trans
- RuCl
2
[(
S
) - XylBINAP][(
S
) - daipen] with
t
BuOK
as the base to give the (
R
) alcohol in 95% ee [295b]. The Ru catalyst also provided 85%
ee for the hydrogenation of cyclohexyl methyl ketone.
A racemic 2 -
iso
propylcyclohexanone has been hydrogenated with a ternary chiral Ru
catalyst consisting of RuCl
2
[(
S
) - BINAP](DMF)
n
, (
R
,
R
) - DPEN, and KOH. An effi cient
dynamic kinetic resolution was observed with excellent enantioselectivity and
cis
:
trans
ratio (Eq. 7.45 ) [307] . The
cis
- (1
R
, - 2
R
)-alcohol is obtained with 93% ee. With the same
catalyst system, good dynamic kinetic resolution was also achieved in the hydrogenation
of (
1
- BH
4
) [(
S
) - XylBINAP][(
R
,
R
) - dpen] was employed
for the hydrogenation of racemic 1-
iso
propylcyclohexanone under base free conditions,
a good kinetic resolution has been observed [296]. After 53% conversion, the unreacted
(
S
)-ketone was recovered with 91% ee along with the (1
R
,2
R
) - alcohol product with 85%
ee (Eq. 7.46).
−
) - menthone. When
trans
- RuH(
η
OH
O
RuCl
2
[(
S
)-BINAP](DMF)n-(
R
,
R
)-DPEN-KOH
i
PrOH, 28
o
C, 4 atm H
2
,11h
(1
R
,2
R
)93%ee
cis
:
trans
=99.8:0.2
(7.45)
O
1
-BH
4
)[(
S
)-XylBINAP][(
R
,
R
)-DPEN]
(0.05 mol %)
OH
trans
-RuH(
μ
O
+
i
PrOH, H
2
(S)
91% ee
47%
(1
R,
2
R
)
85% ee
53%
(7.46)
