8416
J. Chen et al. / Tetrahedron Letters 45 (2004) 8415–8418
OH
O
OH
O
[IrHCl2(COD)]2 / L*
R2
R2
R1
R1
+
+
KOH / iso-PrOH
Scheme 1.
C6P2(NH)2 has proven to be an excellent ligand and the
results are listed in Table 1.
group. When the size of the alkyl group increased from
methyl to cyclohexyl, the enantioselectivity was remark-
ably improved without deterioration of the activity
(entries 1–5). For the asymmetric transfer hydrogena-
tion of propiophenone, the catalyst system showed high
activity and enantioselectivity even in the presence of small
amount of water (entry 3). The asymmetric transfer
hydrogenation of 2,2-dimethylpropiophenone pro-
ceeded slowly owing to a bulky tert-butyl group (entry
6). The position and electronic property of the ring sub-
stituents also influenced hydrogenation results. The
introduction of an electron-donating methyl group to
the meta-position accelerated the reaction (entry 7),
but that to the ortho-position lowers the rate however
improves the enantioselectivity (entry 8). Notably, the
asymmetric transfer hydrogenation of ketone with an
electron-withdrawing group such as a nitro group to
the ortho-position led to a high conversion and up to
95% ee. Among all selected ketones, the best result
was obtained in the reduction of 1,1-diphenylacetone
giving >99% ee and >99% conversion (entry 10).
The activity and enantioselectivity are highly dependent
on the ring substituent and the steric bulk of the alkyl
Table 1. Asymmetric transfer hydrogenation of various ketones
a
catalyzed by [IrHCl2(COD)]2/(R,R)-C6P2 (NH)2
Entry Substrate
Time, h
Alcohol
% Yieldb % ee Config.c
O
1
7.5
2
92
93
79
93
S
S
O
2
O
3d
2
95
99
93
99
S
S
O
4
2.5
As Table 1 shows, high conversions and optical yields
can be achieved with the [IrHCl2(COD)]2/(R,R)-
C6P2(NH)2 catalyst system. Next, we have expanded
the substrate-to-catalyst ratio to observe the effect on
catalytic efficiency.
O
5
2
1
98
23
98
93
R
R
O
6
As shown in Table 2, increasing the substrate-to-cata-
lyst ratio does not damage the optical yield of the
product in most cases. Remarkably, the transfer hydro-
genation of 1,1-diphenylacetone (entry 8) could achieve
up to 99% ee even when the substrate concentration was
increased from 0.1 to 0.5M and the substrate-to-catalyst
ratio reached 10000:1. When propiophenone was used
as substrate, the reactions proceeded slowly at room
temperature, however it can be reduced to 1-phenyl-1-
propanol almost completely in only 5h at 45°C (entry
2). Performing the reaction in air, slowed down the reac-
tion but did not affect enantioselectivity of the product
(entry 3). When we increased the amount of water in
the reaction system, the high optical yield remained
intact (entry 4).
O
7
2
96
84
S
O
O
8
9
4
5
55
92
93
95
S
S
NO
2
O
10
4
>99
>99
R
In conclusion, the [IrHCl2(COD)]2/C6P2(NH)2 systems
demonstrate remarkable catalytic reactivity and enan-
tioselectivity in the asymmetric transfer hydrogenation
under ambient conditions. In a certain case, optically
active alcohols with up to 99% ee in high yield could
be obtained even when the substrate-to-catalyst molar
ratio reached 10000:1. Amazingly, the reaction was not
affected in the air or with the addition of water. This
may imply industrial applications and the recycling of
the catalysts.
a The reactions were carried out in the presence of [IrHCl2(COD)]2/
(R,R)-C6P2(NH)2 (0.005mmol) using a 0.1M solution of ketone
(0.5mmol) in iso-PrOH (5mL) at room temperature; The catalyst
was made in situ by stirring a solution of [IrHCl2(COD)]2 and chiral
ligand (R,R)-C6P2(NH)2 in iso-PrOH; [ketone]:[Ir]:[KOH] = 100:1:4.
b Yield and enantiomeric excesses were determined by GC analysis
using a Chirasil-DEX CB column or G-TA column.
c The configurations were determined by comparison of the retention
times of the enantiomers on the GC traces with literature values.
d Added 0.1mL H2O.