Chemistry Reference
In-Depth Information
Rh -
o
-Ph-BIPHEMP catalyst achieved the optically pure exo-product, which is a key
intermediate for the synthesis of sertraline [161] (Eq. 7.6).
NHCOOMe
NHCOOMe
NHCOOMe
(
S
)-
o
-Ph-HexaMeO-BIPHEP-Rh
+
CH
2
Cl
2
, -20
o
C, 25 psi H
2
Cl
Cl
Cl
Cl
Cl
Cl
100% ee
50% yield
96% ee
50% yield
(7.6)
A few tetrasubstituted enamides have been hydrogenated with moderate to high
enantioselectivities and diastereoselectivities (Fig. 7.20). Both
t
Bu - BisP *
and
t
Bu -
MiniPhos have been reported to hydrogenate
- dimethyl enamide with 99%
ee [147]. Two cyclic tetrasubstituted enamides derived from 1-indanone and 1-tetralone
have been reduced using Rh - PennPhos [157] and Rh -
o
- Ph - BIPHEP [161] catalysts.
While high selectivity was achieved for the fi ve-membered ring substrate, only moderate
result was observed for the six-membered ring compound. A series of related substrates
derived from 1 - aryl - 2 - tetralone was also studied using a Ru - Me - DuPhos catalyst [162] .
Moderate results were observed.
α
- phenyl -
β
,
β
O
O
Rh-BDPP
∗
H
2
,20psi,MeOH,0
o
C
HN
HN
O
O
(7.7)
Lu and Alper developed a sequence of reactions involving asymmetric hydrogenation
for the preparation of medium-ring tricyclic lactams [163]. A series of cyclic unsaturated
amides were reduced with over 90% ee using an Rh-BDPP catalyst (Eq. 7.7).
7.3.1.4. Enol Esters
A useful method to prepare chiral alcohols is through asymmetric
hydrogenation of the corresponding unsaturated enol esters. The ester-protected
NHAc
NHAc
NHAc
∗
∗
NHAc
∗
∗
∗
∗
(
cis
)
72% ee
99% ee
99% ee
73% ee
Figure 7.20.
Asymmetric hydrogenation of tetrasubstituted enamide.
