W. He et al. / Tetrahedron Letters 47 (2006) 5367–5370
Table 2. Reuse of catalyst in asymmetric transfer hydrogenation of acetophenonea
5369
Run
Rh/1b catalyst
Ir/1b catalyst
product
Recovered yield
of catalyst (%)
product
Recovered yield
of catalyst (%)
Yieldb (%)
eec (%)
Yieldb (%)
eec (%)
1
2
3
4
5
6
81
78
77
75
70
72
94
93
92
91
93
93
91
93
92
91
95
93
87
83
82
79
80
75
95
95
94
93
94
95
93
90
92
91
94
93
a Conditions: reactions were carried out using
KOH = 100:10:10:20, reaction time is 48 h.
b Isolated yields.
a
0.05 molLꢀ1 solution of acetophenone (1 mmol) in i-propanol; ketone/M/ligand/
c Determined by chiral CP-Cyclodex B-236 M column and chiral HPLC.
tated with hexane.13 When using the complex in the
asymmetric transfer hydrogenation, high enantioselec-
tivity was obtained (94% ee) as expected. With similar
procedure, Ir complex of 1b was also formed14 and
tested in the asymmetric transfer hydrogenation of aceto-
phenone, resulting in 87% yield of 1-phenylethanol, and
ee up to 95%.
References and notes
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Steiner, H.; Studer, M. Adv. Synth. Catal. 2003, 345, 103–
151; (b) Saluzzo, C.; ter Halle, R.; Touchard, F.; Fache,
F.; Schulz, E.; Lemaire, M. J. Organomet. Chem. 2000,
603, 30–39; (c) Zassinovich, G.; Mestroni, G.; Gladiali, S.
Chem. Rev. 1992, 92, 1051–1069; (d) Noyori, R.; Hashi-
guchi, S. Acc. Chem. Res. 1997, 30, 97–102.
We further test the recycled Rh complex of 1b in asym-
metric transfer hydrogenation of acetophenone.15 We
found the enantioselectivities were nearly maintained
at 93% in six runs, and 91–95% of catalyst were recov-
ered. We also determined the metal content of the aque-
ous phase after recycling the complex by using
inductively coupled plasma atomic emission spectro-
metry (ICP-AES). The amount of Rh leaching was 1.7%,
1.5%, 1.4%, 1.1%, 1.5% and 1.2%, respectively, in the
six reaction batches (including the workup procedures).
By the same way, Ir complex of 1b was also recovered in
the catalytic system. Again, we found the enantioselec-
tivities were nearly maintained at 95% in six runs, and
the catalyst recovery yields were verified from 90% to
94% (Table 2). Moreover, the Ir leaching in the six runs
was 1.4%, 1.6%, 1.8%, 1.2%, 0.9% and 1.1%, respec-
tively. All the metal leaching was less than 2%, which
was in agreement with the nearly maintained enantio-
selectivities of the catalysts in the recycling reactions.
2. (a) Pastor, I. M.; Vastila, P.; Adolfsson, H. Chem.
Commun. 2002, 18, 2046–2047; (b) Zhang, H.; Yang, C.
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11. Typical procedure for asymmetric transfer hydrogenation:
0.05 mmol [Rh(COD)Cl]2 or [Ir(COD)Cl]2 was added to a
solution of 0.1 mmol ligand 1a or 1b in 20 mL dry
degassed i-propanol and stirred at room temperature for
30 min under argon. KOH (0.2 mmol) was added and the
reaction mixture was stirred for another 10 min. Ketone
(1 mmol) was then added in portion (0.05 molLꢀ1) and
the reduction was conducted at ꢀ20 ꢁC for the time
indicated (monitored by TLC). After completion of the
reaction, the resulting solution was neutralized with
1 molLꢀ1 HCl, and then extracted with Et2O. The organic
In summary, we have developed two simple and recycla-
ble homogeneous catalysts for asymmetric transfer
hydrogenation of aromatic ketones. Except for osmi-
um-catalyzed Sharpless AD and AA, these are the best
enantioselectivities reported using the intact Cinchona
alkaloids skeleton as ligands in metal-catalyzed asym-
metric reactions.16 Moreover, a simple method to
recover both the iridium and rhodium complex of
9-amino(9-deoxy)epicinchonine 1b were demonstrated.
Further study will be focused on investigating their cata-
lytic performance in other asymmetric catalysis system.
Acknowledgements
We thank National Natural Science Foundation of
China (NSFC) and the Young Scholar Foundation of
the Fourth Military Medical University for financial
support.