C. Li et al. / Catalysis Communications 28 (2012) 5–8
7
Table 4
Table 5
a
The effect of different solvents for hydrogenation of acetophenone .
Asymmetric hydrogenation of aromatic ketones catalyzed by [Ir(COD)Cl]
2
/chiral diamine
a
A/TPP .
Entry
Solvent
Con (%)
ee (%)
Configuration
Entry
1
Substrate
Con (%)
>99
ee (%)
84
Configuration
1
2
3
4
5
6
7
MeOH
EtOH
n-PrOH
1-Butanol
2-PrOH
THF
>99
>99
>99
19
b1
b1
78
84
79
74
–
S
S
S
S
–
–
–
S
2
3
4
5
>99
>99
83
83
87
82
86
S
S
S
S
–
Toluene
b1
–
a
Substrate/Ir/chiral diamine A/TPP=500/1/2/1, acetophenone: 0.856 mol/L,LiOH:
.05 mol/L, 25 °C, 6 MPa, 2 h.
0
as toluene and THF, both the activity and enantioselectivity were inferior
to those in alcohol solvents (Table 4, Entry 6, 7).
2
In 2006, Zhang et al. [23] described [Ir(COD)]Cl catalyzed asym-
metric transfer hydrogenation system with 2-PrOH as hydrogen re-
source, chiral diamine A as ligand and KOH as base. To investigate
whether transfer hydrogenation also occurred in our system, an ex-
>99
2
periment was conducted in 2-PrOH but absent of H . Apart from
using LiOH instead of KOH as base, our reaction conditions were
quite similar with Zhang's. However, only less than 1% of conversion
was observed after the reaction proceeded for 2 h (Table 4, Entry 5).
The results clearly ruled out the possibility of asymmetric transfer hydro-
genation in our system.
6
>99
79
S
7
8
98
87
70
S
S
The effect of H
When the reactions were run at 50–80 bars of H
of the enantioselectivity and conversion (83%, >99%) was not ob-
served. However, when the H pressure decreased to 40 bars, the
2
pressure on the reaction was also examined.
2
, significant loss
>99
2
enantioselectivity dropped significantly (70%) and the conversion
remained (>99%).
9
80
83
85
S
S
To explore the scope and limitations of the reaction, a series of
simple aromatic ketones were hydrogenated under the optimum con-
dition. The results were summarized in Table 5. As it can be seen, the
ortho substituent on acetophenone made little influence on the activ-
ity (Table 5, Entries 2–7), but the enantioselectivity was more depen-
dent. It seems that the electron-withdrawing group at the ortho
position is detrimental for enantioselectivity. The lowest ee value
1
1
0
1
>99
0
–
–
(
(
7
79%) was observed for o-CF
87%) was obtained for o-CH -acetophenone (Table 5, Entry 6 and
). Meta- or para-substituted substrates were also tested, however,
3
-acetophenone and the highest ee
3
1
2
3
>99
0
78
–
S
–
S
the enantioselectivity and activity were obviously decreased in
comparison with the ortho-substituted counterparts (Table 5, Entry8,
1
9
). Then, propiophenone and 2-methyl-1-phenylpropan-1-one were
also used as hydrogenation substrate to study the influence of the
alkyl group of the ketone on activity and enantioselectivity (Table 5,
14
15
12
46
Entry10, 11). Obviously, the –CH
deactivated the reaction completely due to the steric hindrance
Table 5, Entry 11). Ketones containing a heteroaromatic ring were
3
at the 2-position of alkyl group
0
–
–
(
compatible with the hydrogenation conditions. The catalyst was effec-
tive for the asymmetric hydrogenation of acetylthiophene (Table 5,
Entry12), which was completely hydrogenated with up to 78% ee. How-
ever, it was ineffective for the hydrogenation of acetyl pyrrole (Table 5,
Entry13). Ortho- and para- acetyl pyridine were also investigated under
the same reaction condition. For ortho-substituted pyridine, the conver-
sion and enantioselectivity are 12% and 46%, respectively. No reaction
took place for para-substituted pyridine (Table 5, Entry14-15). From
the presented results it is apparent that the combination with chiral
diamine and achiral phosphine are efficient in the asymmetric hydroge-
nation of most simple aromatic ketones.
a
Substrate/Ir/chiral diamine A/TPP=500/1/2/1, acetophenone: 0.856 mol/L,LiOH:
CH OH: 2 ml, 25 °C, 6 MPa, 2 h.
0
.05 mol/L, CH
3
2
ketones. High activity and good enantioselectivity were obtained
in the hydrogenation of simple aromatic ketones with short reac-
tion time, especially for ortho-substituted aromatic ketones. This
is encouraging because the chiral induction is improved when
TPP added. We are now focusing on the reaction mechanism in
follow-up study.
4
. Conclusion
Appendix A. Supplementary data
In conclusion, we had demonstrated that the combination of
[
Ir(COD)Cl]2, chiral diamine and TPP resulted in the formation of
Supplementary data to this article can be found online at http://
dx.doi.org/10.1016/j.catcom.2012.07.024.
an efficient catalyst for asymmetric hydrogenation of aromatic