Chemistry Reference
In-Depth Information
chiral catalysts. Compared with their conventional synthesis such as optical resolution
and biologic synthesis, asymmetric hydrogenation has shown great advantages in many
aspects. Similarly to dehydroamino acid derivatives, the hydrogenation of enamides can
generally be succeeded with low hydrogen pressure and ambient temperature. A large
number of catalysts, mostly Rh-phosphine catalysts, have been demonstrated to give
very good enantioselectivities on the standard substrates. High turnover numbers up to
10,000 have been achieved with Ph-BPE [52], TangPhos [84], and
103
[93] for
α
-
arylenamides. In the case of
- substituted substrates,
E/Z
mixtures can also be reduced
with high enantioselectivities using BPE [143] and TangPhos [84]. Some of the examples
of the hydrogenation of
N
- acetyl
β
- phenyl enamides are summarized in Table 7.4 .
Chiral amines with cyclic structures are of great importance in synthetic chemistry
and are usually diffi cult to prepare. Efforts have been devoted to asymmetric hydrogena-
tion of a number of cyclic enamides as shown in Figure 7.19. Both Me-BPE [156] and
PennPhos [157] have been applied in the reduction of enamides derived from
α
α
- indolones
-tetralones. Up to 98% ee can be obtained from both substrates using the Rh-
PennPhos catalyst. Two other cyclic substrates, 6-bromotetralone-eneacetamide and
7-methyltetralone-eneacetamide, were hydrogenated using a Ru-BINAP complex as the
catalyst [158,159]. A related substrate derived from 3-chromanone can also be reduced
with 92% ee using the Ru-BIPHEMP catalyst [159]. Substrates in which the nitrogen
atom is incorporated into the ring system are especially challenging due to the strain
and bulkiness in their structures. A number of 2- or 3-substituted indoles were success-
fully hydrogenated with up to 98% ee using the Rh - Ph - TRAP catalyst [54f,g] . (
R
) - (
and
α
) -
N
-
acetylsalsolidine was prepared with 97% ee via hydrogenation of the corresponding
enamides using Rh-TangPhos as the catalyst [36a]. A series of structurally similar
isoquinoline products were also prepared by Ru - BINAP - catalyzed hydrogenation
of enamides [17a,b,160]. Asymmetric hydrogenation of a racemic carbamate using the
−
NHAc
NHAc
NHCOPh
∗
Br
98% ee
98% ee
97% ee
NHCOPh
∗
NHAc
∗
O
94% ee
92% ee
MeO
Me
MeO
N
Bn
NHAc
MeO
OMe
N
Ac
94% ee
N
Ts
98% ee
OMe
MeO
97% ee
99.5% ee
OMe
Figure 7.19.
Asymmetric hydrogenation of cyclic enamides.
