Chemistry Reference
In-Depth Information
intermediate in the total synthesis of (
) - aphanorphine [116] . Fukuyama and others
reported the total synthesis of (+)-manzamine A, a naturally occurring
−
- carboline
alkaloid. The stereoselective step was achieved by Rh-Et-DuPhos-catalyzed asymmetric
hydrogenation of a trisubstituted
β
-dehydroamino acid derivative [117]. Over 99% ee
was achieved. In the synthesis of (
S
) - acromelobic acid, Rh - DIPAMP - catalyzed asym-
metric hydrogenation was the key step to generate the chiral center with over 98% ee
[118]. A highly active fungicide, (
R
)-metalaxyl, has been prepared via asymmetric hydro-
genation effi ciently [119]. The product was afforded in 98% ee with only 20 ppm of the
Rh - Me - DuPhos catalyst.
The hydrogenation of
α
- dehydroamino acids by homogeneous
metal-ligand complex has been a challenging task, mainly due to the steric hindrance
when the substrate coordinates to the metal catalyst. High catalyst loading and slow
reaction rate were usually observed in most of the studies. Although the number of the
reports has been much less abundant compared with other substrates, some less bulky
ligand, such as Me-BPE [28b] and Me-DuPhos [28b], have shown consistently good
performance in the hydrogenation of this type of substrates. Table 7.2 summarizes some
of the most studied cases. In addition to Me-BPE and Me-DuPhos, BisP* [120] and
TRAP [54] ligands were also demonstrated to be effective for certain substrates. When
the substrate bears two different
β
,
β
- disubstituted
α
-substituents, two stereogenic centers are generated
simultaneously in asymmetric hydrogenation. Rh - Me - BPE and Rh - TRAP systems were
demonstrated to reduce both (
E
) - and (
Z
)-tetrasubstituted amino acid derivatives in
high ee and de (Fig. 7.17). (
R
)-4-piperidinylglycine was also prepared with 94% ee by
hydrogenation of the corresponding tetrasubstituted substrate.
β
7.3.1.2. Asymmetric Hydrogenation of
β
-Dehydroamino Acids
In addition to the
success achieved in the preparation of
-
dehydroamino acid derivatives has been developed rapidly recently. The simplicity and
effectiveness have made this approach one of the most effi cient method to synthesize
novel chiral amino acids and their derivatives [121]. In most cases,
α
-amino acid, asymmetric hydrogenation of
β
- dehydroamino acids
are synthesized as a mixture of (
Z
) - and (
E
)-isomers. And it is reported that the (
Z
) -
isomer is much less selective and reactive toward asymmetric hydrogenation. Achieving
high enantioselectivities for both regioisomers is particularly important for the practical
β
Bu
t
COO
COOMe
TDSO
COOMe
Me
NHAc
Me
NHAc
95% ee
Rh-(
R
,
R
)-(
S
,
S
)-Pr-TRAP
97% ee
Rh-(
R
,
R
)-(
S
,
S
)-Pr-TRAP
O
CbzHN
O
NHAc
NHAc
N
PhCOHN
COOEt
PhCOHN
COOEt
O O
t
Bu
94% ee
Rh-(
R
,
R
)-Me-BPE
96% ee
Rh-(
R
,
R
)-Me-DuPhos
>98% ee
Rh-(
R
,
R
)-Me-DuPhos
Figure 7.17.
β
,
β
- Disubstituted amino acid derivatives.
