Chemistry Reference
In-Depth Information
O
O
O
OH
O
O
Ru[(
S
)-BINAP]Br
2
MeO
MeO
O
O
MeOH, 45
o
C, 1 atm H
2
>99%
C
C
O
O
TBSO
TBSO
>98% de, >98% ee
(7.30)
O
O
OH
O
Ru(OAc)
2
MeOBIPHEP
80
o
C, 40 bar
C
11
H
23
OMe
C
11
H
23
OMe
200 g
>99% yield
>99% ee
(7.31)
The Schwindt group successfully performed a hydrogenation of a β - keto ester inter-
mediate on a 200-g scale in their process development for the preparation of Orlistat
[255]. Using a Ru-MeOBIPHEP catalyst, both excellent yield and selectivity were
achieved under reasonably moderate conditions (Eq. 7.31).
Taking the advantage of effi cient asymmetric hydrogenation of racemic α - substituted
β - keto esters, effi cient dynamic kinetic resolution can be achieved [18d,256]. Many excel-
lent examples have been reported using Ru catalysts. Hydrogenation of 2-alkoxycarbon-
ylcycloalkanones served a standard reaction to test the effi ciency of Ru catalysts (Table
7.12). Up to 99% ee has been obtained for the preferred
anti
product when the Ru-
TetraMe - BITIANP [195] or Ru - TetraMe - BITIOP [196] complex was used as the cata-
lyst. Reaction solvent and catalyst precursor dramatically affect both diastereoselectivity
and enantioselectivity of the reaction.
Dynamic kinetic resolution of racemic 3 - acetyltetrahydrofuran - 2 - one was accom-
plished using the Ru-BINAP system to give the
cis
hydrogenation product with 97% ee
and 99:1 diastereoselectivity (Eq. 7.32 ) [235] . A Ru - TetraMe - BITIANP complex was
also effective for this transformation [195b]. The Ru-BINAP system provided effi cient
dynamic kinetic resolution in the hydrogenation of α - acylamino and α - amidomethyl
β-keto esters [18d,235,258]. High enantioselectivities and diastereoselectivities were
obtained for the
cis
hydrogenation product. Excellent enantioselectivity and diastere-
oselectivity were obtained in the hydrogenation of 2 - benzamidomethyl - 3 - oxobutanoate
using a Ru-(− ) - DTBM - SEGPHOS catalyst [21b] . The corresponding methyl (2
S
,3
R
) - 2 -
benzamidomethyl-3-hydroxybutanoate was prepared with 99.4% ee and 98.6% de. The
product can be transformed into a key intermediate of carbapenem antibiotics (Scheme
7.8). Excellent selectivity, 99% ee, and 94% de were obtained when a Ru-(− ) - TetraMe -
BITIOP complex was used as the catalyst [196]. When a Ru-BIPHEP complex was
applied as catalyst to the hydrogenation of racemic methyl 2 - acetamido - 3 - keto - 6 -
phthalimidohexanoate for the synthesis of (2
S
,3
R
) - 3 - hydroxylysine, excellent enantiose-
lectivity and diastereoselectivity were achieved (Scheme 7.9) [259]. Effi cient dynamic
kinetic resolution was also observed in the hydrogenation of
- keto esters
with
anti
-chlorohydrin as the major product [260]. With (COD)Ru(methallyl)
2
- (
S
) -
BINAP as the catalyst and CH
2
Cl
2
as the solvent, the hydrogenation of racemic ethyl
2 - chloro - 3 - phenyl - 3 - oxopropionate provided the
anti
-chlorohydrin product with 99% ee
and 98% de (Eq. 7.33). The product can be directly converted into chiral (2
S
,3
R
) -
methylglycidate. On the other hand, some catalytic systems have shown high
syn -
α
- chloro -
β
