5
asymmetric hydrogenation under base-free conditions. And
base. In particular, the catalyst system generated from IrH-
(CO)(PPh exhibited high catalytic activity and good
enantioselectivity (entry 3). Noticeably, not all metal hydride
complexes efficiently catalyzed the reaction under base-free
conditions; Ru hydride complexes such as RuHCl(CO)-
although a few works described the transfer hydrogenation
3 3
)
6
of some ketones in 2-propanol without using any bases, few
reports on asymmetric transfer hydrogenation of a variety
of aromatic ketones under base-free conditions have ap-
peared.
3 3
(PPh ) could not promote the reaction smoothly in the
In earlier studies, we reported the synthesis and catalytic
absence of bases. This indicated that Rh- and Ir-catalyzed
property of the well-designed PNNP-type ligands C
6
P
2
N
2
1,
hydrogen transfer occurred via a monohydride and Ru-
4,7-10
3a,6c
C
6 2
P (NH)
2
2 2
2, and Ph P (NH)
2
4,
which exhibited high
catalyzed hydrogen transfer via a dihydride.
In addition,
enantioselectivity and activity in asymmetric transfer hy-
drogenation of ketones in the presence of a base. In particular,
a Ru cluster complex efficiently catalyzed the reduction of
propiophenone in the absence of base. Recently, we found
an efficient catalytic system generated from an iridium
hydride complex and ligand 2 for enantioselective transfer
hydrogenation of a series of aromatic ketones without using
any base.
chiral ligands also played an important role in the reaction.
Without addition of any chiral ligands, the complex IrH-
(CO)(PPh
only a low conversion was obtained (entry 6). Various other
chiral ligands (Figure 1) together with IrHCO(PPh in situ
3 3
) could not catalyze the reaction smoothly and
10
3 3
)
We set out by examining the catalytic activity of the metal
hydride complexes combined with various chiral ligands for
the asymmetric transfer hydrogenation of propiophenone in
2
-propanol (Table 1).11
Table 1. Asymmetric Transfer Hydrogenation Catalyzed by Rh
and Ir Hydride Complexes-Chiral PNNP Systems without
Adding Any Basea
Figure 1. Chiral ligands used in asymmetric transfer hydrogena-
metal hydride
complexes
temp time yield
ee
tion.
(%)b (%)
b
entry
ligand
(°C)
(h)
45
24
0.5
3.5
2.5
1
2
3
4
5
6
RhH(CO)(PPh3)3
mer-IrH3(PPh3)3
IrH(CO)(PPh3)3
IrH(CO)(PPh3)3
IrH(CO)(PPh3)3
IrH(CO)(PPh3)3
2b
2b
2b
1b
4b
75
75
75
70
70
70
79
99
97
94
98
21
65
74
90
50
56
were employed to catalyze the reduction of propiophenone.
The reduction with a binary system, IrH(CO)(PPh ) and the
3 3
diamine ligand 3, proceeded very slowly and then stopped,
leading to the reduction product in low yield (<10%) and
low enantioselectivity (<5%). The similar PNNP ligand
diiminodiphosphines 1 and another PNNP ligand 4 were
effective for the reduction of ketones, but the enantioselec-
tivity of chiral alcohol remarkably decreased (entries 4 and
20
a
b
Reaction was carried out with S/C ) 200. Determined by GC analysis
chiral column: Chrompack CP-cyclodextrin-â-236-M-19 column).
(
5
). These results indicated that the structure of the PNNP
As expected, most of these metal hydride catalytic systems
efficiently catalyzed the reaction without addition of any
tetradentate ligands was a crucial factor for ligand accelera-
tion, and the NH functions in the ligand 2 and its structure
are responsible for the good enantioselectivity.4
(5) (a) Ohkuma, T.; Koizumi, M.; Muniz, K.; Hilt, G.; Kabuto, C.;
Noyori, R. J. Am. Chem. Soc. 2002, 124, 6508. (b) Abdur-Rashid, K.;
Clapham, S. E.; Hadzovic, A.; Harvey, J. N.; Lough, A. J.; Morris, R. H.
J. Am. Chem. Soc. 2002, 124, 15104.
3 3
As shown in Table 2, the chiral IrH(CO)(PPh ) -PNNP
system catalyzed the asymmetric reduction of various ketones
to the secondary alcohols with a high chemical yield and
good enantioselectivity under base-free conditions.
(6) For transfer hydrogenation without bases: (a) Mizushima, E.;
Yamaguchi, M.; Yamagishi, T. Chem. Lett. 1997, 237. (b) Eceraere, K.;
Scheffler, J.-L.; Mortreux. A.; Carpentier, J.-F. Tetrahedron Lett. 2001, 42,
1
899. (c) Cadierno, V.; Crochet, P.; Diez, J.; Garcia-Garrido, S. E.; Gimeno,
J. Organometallics 2004, 23, 4836. (d) Dahlenburg, L.; G o¨ tz, R. Inorg.
Chim. Acta 2004, 357, 2875. (e) For asymmetric transfer hydrogenation of
acetophenone without bases with Ru complex: Haack, K.-J.; Hashiguchi,
S.; Fujii, A.; Ikariya, T.; Noyori, R. Angew. Chem., Int. Ed. Engl. 1997,
(9) Gao, J.-X.; Yi, X.-D.; Xu, P.-P.; Tang C.-L.; Wan H.-L.; Ikariya, T.
J. Organomet. Chem. 1999, 290.
(10) Zhang, H.; Yang, C.-B.; Li, Y.-Y.; Dong, Z.-R.; Gao, J.-X.;
Nakamura, H.; Murata, K.; Ikariya, T. Chem. Commun. 2003, 142.
(11) Typical Procedure for Asymmetric Transfer Hydrogenation. To
a mixture of the metal-hydride complex (0.0025 mmol) and the chiral
3
6, 285. (f) For asymmetric transfer hydrogenation of m-trifluoromethy-
lacetophenone without bases: Murata, K.; Ikariya, T.; Noyori, R. J. Org.
Chem. 1999, 64, 2186.
3
ligand (0.0026 mmol) was added 2-propanol (5 cm ). The mixture was
(
7) Gao, J.-X.; Wan H.-L.; Wong W.-K.; Tse M. C.; Wong W. T.
Polyhedron 1996, 15, 1241.
8) Gao, J.-X.; Zhang, H.; Yi, X.-D.; Xu, P.-P.; Tang C.-L.; Wan H.-L.;
Tsai K.-R.; Ikariya, T. Chirality 2000, 12, 383.
stirred at 70 °C for 30 min. To this solution was added the substrate (0.5
mmol), and the mixture was then stirred at the expected temperature.
Samples were taken out of the reaction solution after the given time, passed
through a column of silica, and analyzed by GC.
(
1044
Org. Lett., Vol. 7, No. 6, 2005