A recyclable catalyst for asymmetric transfer hydrogenation with a formic acid-triethylamine mixture in ionic liquid

Article abstract of DOI:10.1039/b500320b

A novel task-specific ionic ligand with an imidazolium salt moiety was synthesized, and its catalytic ability and recyclability for asymmetric transfer hydrogenation of acetophenone derivatives with a formic acid-triethylamine azeotropic mixture in an ion

Full text of DOI:10.1039/b500320b

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A recyclable catalyst for asymmetric transfer hydrogenation with a
formic acid–triethylamine mixture in ionic liquid{
Ikuo Kawasaki,a Kazuya Tsunoda,a Tomoko Tsuji,a Tomoko Yamaguchi,a Hiroki Shibuta,a Nozomi Uchida,a
Masayuki Yamashitaab and Shunsaku Ohta*ab
Received (in Cambridge, UK) 11th January 2005, Accepted 10th February 2005
First published as an Advance Article on the web 2nd March 2005
DOI: 10.1039/b500320b
results with 2-propanol but somewhat poor results using formic
acid. In this communication we would like to present the
preparation of a novel task-specific chiral ionic ligand, with an
attached imidazolium salt, and its use in the recyclable catalytic
asymmetric transfer hydrogenation of ketones by an HCO2H–
Et3N azeotrope in ILs.
A novel task-specific ionic ligand with an imidazolium salt
moiety was synthesized, and its catalytic ability and recyclability
for asymmetric transfer hydrogenation of acetophenone
derivatives with a formic acid–triethylamine azeotropic mixture
in an ionic liquid [bmim][PF6] was examined.
Recently, catalytic asymmetric transfer hydrogenation has become
a useful tool to obtain optically active secondary alcohols from
carbonyl compounds and is an interesting alternative to hydro-
genation with molecular hydrogen. The hydrogen donors most
commonly used for ketones are 2-propanol (generally used with a
base) and formic acid (generally used as an azeotrope with
triethylamine), and the latter is accompanied by evolution of CO2
gas, rendering the reaction irreversible, and has attracted the
interest of chemists.1
Two types of chiral catalysts were selected for the recyclable
asymmetric transfer hydrogenation of ketones with the azeotrope
in ILs. One, the TsDPEN-coordinated Ru(II) complexes 3 and 4,
known as some of the most effective catalysts developed by
Noyori, Ikariya and co-workers.8,10 The other, a Ru(II) complex of
the amino amide 5, derived from proline in the presence of
[RuCl2(cymene)]2 (5-Ru).11 Results of the asymmetric transfer
hydrogenation of 6 in the presence of 3, 4 or 5-Ru with the
azeotrope in ILs 1 or 2 are summarized in Table 1. After several
examinations, we found that the best combination was the chiral
benzene-Ru complex 4 and the IL [bmim][PF6] (entry 5). The
present reaction system with 4 was also effective for asymmetric
reduction of acetophenone derivatives 6b–e (entries 7–10).
Then, we planned the synthesis of a new task-specific ionic
chiral ligand based on attaching an imidazolium salt unit to
TsDPEN, in order to prepare the corresponding benzene-Ru
complex (cf. 4) and to investigate its reactivity in the recyclable
asymmetric transfer hydrogenation of ketones, using the azeotrope
as a hydrogen source. The route to the designed ionic ligand 12 is
shown in Scheme 2. Introduction of the imidazolium moiety to the
chloroalkoxy TsDPEN derivative 10, which was prepared starting
from 8, was achieved to give the quaternary salt 11. Removal of
Imidazolium ionic liquids (ILs) such as [bmim][PF6] 1 and
[bmim][BF4] 2 (Fig. 1) have been recognized as a new class of
reaction solvent,2 and we have been interested in ILs because we
have investigated the chemistry of imidazolium and 1,2,4-
triazolium compounds.3 The most attractive properties of ILs,
for us, are that they stabilize several transition metal catalysts and
provide an excellent reaction medium for recycling of the
catalyst,4,5 and that the reaction system also can be applied to
asymmetric hydrogenation of unsaturated bonds.6 Schotten
described microwave-assisted reduction in ILs under transfer
hydrogenation conditions with an achiral palladium catalyst and
formate salts.7 Very recently, Dyson reported the asymmetric
transfer hydrogenation of acetophenone with 2-propanol in IL,
by use of a modified arene-Ru(II) complex with Noyori’s chiral
N-(p-toluenesulfonyl)-1,2-diphenylethylenediamine (TsDPEN),8
with catalyst recycling.9 This catalyst afforded relatively good
Table 1 Asymmetric transfer hydrogenation of ketones in ILs
(Scheme 1)
Product
Entry Ketone Catalyst Solvent Time (h) Conversion (%)a ee (%)a
1
2
3
4
5
6
7
8
9
6a
6a
6a
6a
6a
6a
6b
6c
6d
6e
4
4
3
4
none
5
5
5
60
15
10
53
96
75
96
94
97
95
93
72
88
91
94
89
2
1
1
1
1
1
1
1
1
5
4
24
24
24
24
44
24
5-Rub
4
4
4
4
.99
91
78c
85
Fig. 1
10
a
Determined by capillary GLC analysis using a chiral Cyclodex-B
b
c
{ Electronic supplementary information (ESI) available: experimental
section. See http://www.rsc.org/suppdata/cc/b5/b500320b/
*sohta@mb.kyoto-phu.ac.jp
column. A mixture of 5 and [RuCl2(cymene)]2 was used. Isolated
yield after chromatographic separation (13% recovery of 6d).
2134 | Chem. Commun., 2005, 2134–2136
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The catalyst 4 showed good conversion and ee up to the third
cycle, but its activity gradually decreased from the fourth cycle.
The new ionic catalyst 12-Ru showed somewhat better results than
the catalyst 4. This is probably due to immobilization of the
imidazolium moiety in the IL phase. It is noteworthy that the
enantioselectivity of 12-Ru showed good values, which are
comparable with those of 4.12
The authors thank Prof. Yoshiji Takemoto and Dr. Hideto
Miyabe (Graduate School of Pharmaceutical Science, Kyoto
University) for helpful discussion. This research was financially
supported in part by the Frontier Research Program and the 21st
Century COE Program from the Ministry of Education, Culture,
Sports, Science and Technology (MEXT) of Japan, and a Grant-
In-Aid for the promotion of the advancement of education and
research in graduate schools in subsidies for ordinary expenses of
private schools from the Promotion and Mutual Aid Corporation
for Private Schools.
Scheme 1
Ikuo Kawasaki,a Kazuya Tsunoda,a Tomoko Tsuji,a
Tomoko Yamaguchi,a Hiroki Shibuta,a Nozomi Uchida,a
Masayuki Yamashitaab and Shunsaku Ohta*ab
aDepartment of Functional Molecular Chemistry, Kyoto Pharmaceutical
University, Misasagi Yamashinaku, Kyoto 607-8414, Japan.
E-mail: sohta@mb.kyoto-phu.ac.jp
b21st Century COE program
Notes and references
{ Typical recycling procedure: acetophenone (120 mg, 1.0 mmol) was
added to a solution of the ionic ligand 12 (7.8 mg, 0.012 mmol) and
[RuCl2(benzene)]2 (2.5 mg, 0.005 mmol) in the IL 1 (1.0 mL) with stirring
under N2, followed by addition of the formic acid–triethylamine azeotropic
mixture13 (bp 108 uC/29 mmHg, 0.5 mL). The reaction mixture was stirred
at rt for 24 h. Then, n-hexane (3 6 5 ml) was added to the reaction mixture
and the products were extracted by decantation of the upper layer, and the
residual IL phase was dried in vacuo for 30 min. Acetophenone (120 mg,
1.0 mmol) and formic acid–triethylamine azeotropic mixture (0.5 mL) were
added to the remaining IL solution, and the second cycle of the reaction
was started.
Scheme 2 Regents and conditions: (a) (i) NaH, Br(CH2)4Cl, DMF, 100 uC
(ii) SOCl2, DMF, 90 uC, 54% (b) (i) (1S,2S)-1,2-diphenylethylenediamine,
Et3N, DCM, rt (ii) (Boc)2O, Et3N, DCM, rt, 70% (c) 1-methylimidazole,
80 uC, 95% (d) TFA, 0 uC, 97%.
the Boc group of 11 by treatment with TFA provided a novel ionic
ligand 12 in 35% overall yield from 8.
The recyclability of the asymmetric transfer hydrogenation of
acetophenone 6a was tested, both with 4 and with 12 in the
presence of [RuCl2(benzene)]2 (12-Ru), in the IL 1 by using the
azeotrope at room temperature in 24 hour cycles, and the results
are listed in Table 2. We found that these catalysts, 4 and 12-Ru,
were fully soluble in the IL 1 under these reaction conditions and
they were easily recovered after extraction of the produced
1-phenylethanol by addition of an organic solvent, and the
residual IL phase was recycled and reused for the next reaction.{
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Table 2 Recycling of 4 and 12-Ru in the asymmetric transfer
hydrogenation of 6a with the azeotrope in 1a
Catalyst 4
Ligand 12-Rub
Cycle
Conversion (%)c
ee (%)c
Conversion (%)c
ee (%)c
1
2
3
4
5
a
96
99
95
88
63
93
92
92
92
93
98
.99
99
92
75
92
93
93
93
90
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c
[RuCl2(benzene)]2 was used. Determined by capillary GLC analysis
using a chiral Cyclodex-B column.
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