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In-Depth Information
effective for the asymmetric reduction of sterically hindered pivalophenone [339]. A
unique chiral complex (
S
,
S
) -
130
featuring a tetradentate chiral amino phosphine ligand
catalyzed the reduction of simple aromatic ketones with up to 97% ee [323].
Ru complexes of bisphosphinite ligands such as (
R
) -
138
also showed good
enantioselectivities in the asymmetric reduction acetophenone [324]. Other auxiliaries
bearing NH
2
or NH moiety can also catalyze similar transfer hydrogenation of simple
aromatic ketones in the presence of strong base. For example, (
R
,
S
) -
141
[325] and
[RuCl
2
(
p
- cymene)]
2
- (
S
,
S
) -
145
[326] can afford secondary alcohol products with up to
96% ee and 95% ee, respectively. Over 99% ee was obtained even at 100°C when
[RuCl
2
(benzene)]
2
- PPh
3
- (
R
,
R
) -
147
was employed as the catalyst for asymmetric ketone
reduction [327] .
Rh and Ir complexes have also been extensively studied in the asymmetric transfer
hydrogenation of unfunctionalized ketones. Similarly to Ru catalysts, TsDPEN and
other diamine derivatives react with Rh precursors to form the active catalystic species
[328,329]. An Rh complex bearing (
S
,
S
) -
146
catalyzed the reduction of acetophenone
with up to 96% ee [330]. Over 90% ee was achieved for the challenging
iso
butyrophone
using a
C
2
chiral tetrahydrobis(oxazole) ligand (
S
,
S
) -
140
complexed with Ir precursor
[Ir(cod)Cl]
2
[331]. A neutral Ir complex bearing a primary diamine ligand promoted the
reduction of propiophenone with 93% ee [332].
It is noteworthy that the tethered of Ru-TsDPEN catalysts such as (
R
,
R
) -
142
and
(
S
,
S
) -
143
not only retained the same high level of enantioselectivities but more impor-
tantly, the catalytic activity was signifi cantly improved [333,352]. Related catalysts based
on the Cp*Rh, Cp*Ir moiety were also reported to exhibit high enantioselectivity for
the reduction of acetophenone derivatives [354,355,356].
Catalytic asymmetric transfer hydrogenation has been widely applied in industry due
to its high effi ciency and safe process compared with the molecular hydrogenation. A
key intermediate for the synthesis of L-699,392 (LTD
4
antagonist) was synthesized by
asymmetric transfer hydrogenation using the Ru catalyst (
S
,
S
) -
127
in formic acid-trieth-
ylamine mixture. This asymmetric reduction has extremely high chemoselectivity without
changing the olefi n double bond or other functional groups, and gives the corresponding
product with 92% ee [335] (Scheme 7.14 ).
The synthesis of herbicide (
S
)-MA20565 involved the preparation of the (
S
) -
B
. The
in situ
- prepared catalyst [RuCl
2
(
p
-cymene)(Tsdpen)] promoted the asymmetric reduc-
tion of 3-trifl uoromethylacetophenone in both 2-propanol and HCO
2
H/NEt
3
systems.
This transformation yielded the product with 91% ee and was operated at the 100-kg
scale [334,336] (Scheme 7.15 ).
7.3.3. Asymmetric Hydrogenation of Imines
Compared with the success achieved in olefi n and ketone hydrogenation, the method
developed for asymmetric imine reduction was much less abundant [357]. Relatively low
catalytic activities were usually observed probably due to the strong coordination of
the amine product to the transition metal catalyst. The amine adduct of the catalyst
loses activity toward hydrogenation and thus results in low turnover numbers and
yields. The inseparable
E/Z
isomers of imines can also result in poor enantioselectivity
[358,359]. Nevertheless, a few catalytic systems provided good to excellent enantioselec-
tivities in imine hydrogenation. A few Ir complexes with chiral phosphanes,
trans
-
[RuCl
2
(bisphosphine)(1,2 - diamine)] complex [360,361] , chiral titanocene [362] , and
