Asymmetric transfer hydrogenation of imines and iminiums catalyzed by a water-soluble catalyst in water

Article abstract of DOI:10.1039/b600496b

The first asymmetric transfer hydrogenation of cyclic imines and iminiums in water was successfully performed in high yields and enantioselectivities with sodium formate as the hydrogen source and CTAB as an additive catalyzed by a water-soluble and recyc

Full text of DOI:10.1039/b600496b

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Asymmetric transfer hydrogenation of imines and iminiums catalyzed
by a water-soluble catalyst in water{{
Jiashou Wu,ab Fei Wang,a Yaping Ma,a Xin Cui,a Linfeng Cun,a Jin Zhu,*a Jingen Deng*a and
Bangliang Yua
Received (in Cambridge, UK) 12th January 2006, Accepted 6th March 2006
First published as an Advance Article on the web 16th March 2006
DOI: 10.1039/b600496b
diamine, (R,R-)2.6 Encouraged by these results, we tried the
The first asymmetric transfer hydrogenation of cyclic imines
transfer hydrogenation of imine 3a in water with a complex of
[RuCl2(p-cymene)]2 and (R,R)-2. Although Noyori et al. have
reported that the asymmetric transfer hydrogenation of imines is
not suitable in protic solvents, such as alcohols,3a to our surprise,
high activity and enantioselectivity were obtained for the transfer
hydrogenation of 3a in aqueous media. Table 1 shows the results
of the asymmetric transfer hydrogenation of imine 3a by
employing HCO2Na as the hydrogen source in water with a
variety of metal complexes of (R,R)-2 in the presence of
surfactants. Catalyzed by a complex of [RuCl2(p-cymene)]2 and
the ligand (R,R)-2, imine 3a was reduced to (S)-salsolidine 4a
(Scheme 1) in 89% isolated yield with 90% enantiomeric excess (ee)
after 10 h in water (Table 1, entry 1). It is reported that catalytic
activity and enantioselectivity can be greatly enhanced by the
addition of surfactants in water.10 When sodium dodecyl sulfate
(SDS) was added, both yield and enantioselectivity decreased
(entry 2).10b The addition of poly(ethylene glycol) mono [4-(1,1,3,3-
tetramethylbutylphenyl) ether (Triton X-100) enhanced yield but
lowered enantioselectivity (entry 3). Although the addition of
cetylpyridium bromide (CPB) increased enantioselectivity to 92%
ee, only 68% isolated yield was afforded after 10 h (entry 4).
A significant enhancement both in ee value and yield was obser-
ved when 3-(N,N-dimethyldodecylammonio)propanesulfonate
and iminiums in water was successfully performed in high
yields and enantioselectivities with sodium formate as the
hydrogen source and CTAB as an additive catalyzed by a
water-soluble and recyclable ruthenium(II) complex of the
ligand (R,R)-2.
Optically active amines are highly important building blocks for
biologically active molecules and numerous completely different
methods have emerged for the preparation of enantiopure amines
in the past few years.1 On the other hand, as a consequence of the
increasing demand for environmentally friendly methods, the use
of water in complex-catalyzed reactions is of great interest because
of safety, simpler product separation and the possibility of
recycling.2 The catalytic asymmetric hydrogenation of imines is a
powerful way to obtain enantiopure amines1 and particularly,
transfer hydrogenation of imines with diamine (1) metallic
complexes reported initially by Noyori et al.3a provides great
promise for the asymmetric synthesis of chiral amines.3,4 Despite
the progress made in the asymmetric transfer hydrogenation of
prochiral ketones in water,5,6 to the best of our knowledge, no
work on asymmetric transfer hydrogenation of imines7 and
iminiums8,9 in aqueous media has been reported up to now.
Here we report for the first time an asymmetric transfer
hydrogenation of cyclic imines and iminiums in water catalyzed
by a water-soluble RuII-catalyst.
Table 1 Asymmetric transfer hydrogenation of 3a in watera
Yield Ee
t/h (%)b (%)c,d
Entry Metal complex
Surfactant
1
2
3
4
5
6
[RuCl2(p-cymene)]2
[RuCl2(p-cymene)]2
[RuCl2(p-cymene)]2
[RuCl2(p-cymene)]2
[RuCl2(p-cymene)]2
[RuCl2(p-cymene)]2
[RuCl2(p-cymene)]2
[RuCl2(p-cymene)]2
[RuCl2(p-cymene)]2
[RuCl2(p-cymene)]2
[RuCl2(benzene)]2
[RuCl2(mesitylene)]2
—
SDS
10 89
10 79
90
86
86
92
93
95
94
92
92
91
87
94
96
95
92
Triton X-100 10 98
CPB
10 68
10 96
10 97
10 85
10 93
DDAPS
CTAB
CTAB
CTAB
CTAB
TBAB
CTAB
CTAB
7e
8f
9g
Recently, we reported the transfer hydrogenation of prochiral
ketones in water with excellent catalytic activity and high
enantioselectivity catalyzed by the RuII complex of easily accessible
water-soluble chiral o,o9-disulfonated N-tosyl-1,2-diphenylethylene
6
97
10
10 99
11 98
48 90
48 41
20 96
24 88
11
12
13
14
15
a
[RuCl2(4-tert-butyltoluene)]2 CTAB
CTAB
CTAB
aKey Laboratory of Asymmetric & Chirotechnology of Sichuan Province
and Union Laboratory of Asymmetric Synthesis, Chengdu Institute of
Organic Chemistry, Chinese Academy of Sciences, Chengdu 610041,
China. E-mail: jgdeng@cioc.ac.cn; Fax: +86 28 8522 3978
bGraduate School of Chinese Academy of Sciences, Beijing, China
{ Electronic supplementary information (ESI) available: Experimental
procedures and characterisation data for intermediates and transfer
hydrogenation products. See DOI: 10.1039/b600496b
[Cp*RhCl2]2
[Cp*IrCl2]2
Unless otherwise noted, the reaction was carried out in water at
b
28 uC for 10 h with 50 mol% surfactant and S/C = 100. Isolated
yield. The ee was determined by HPLC analysis with a Daicel
c
d
Chiralcel OD column. 4a was determined to be the (S)-form by
comparing the sign of rotation of the isolated product to the
literature data.3a With 100 mol% CTAB. With 10 mol% CTAB.
e
f
g
{ Dedicated to Professor Yaozhong Jiang on the occasion of his 70th
Birthday.
At 40 uC.
1766 | Chem. Commun., 2006, 1766–1768
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Table 2 Asymmetric transfer hydrogenation of imines and iminiumsa
Entry Substrate S/C t/h Yield (%)b Ee (%)c Configurationd
1
2
3
4
5
6
7
8
9e
3a
3b
3c
5a
5a
5a
5a
5b
5c
5d
5e
7a
100 10 97
100 25 68
100 25 90
95
92
90
99
99
99
99
99
99
98
99
65
94
95
98
50
95
90
90
75
S
S
S
S
S
S
S
(2)
(2)
(2)
S
R
R
Scheme 1 Asymmetric transfer hydrogenation of imine 3a in water.
100
8
97
200 14 99
500 38 98
1000 90 55
100 20 94
100 30 92
100 25 96
100 48 83
(DDAPS) and cetyltrimethylammonium bromide (CTAB) were
added respectively (entries 5 and 6). CTAB gave the best results
with 97% isolated yield and 95% ee, which is comparable to the
result reported by Noyori et al. in a homogeneous system.3a
A
10
11e
12
decrease in both yield and enantioselectivity was observed when
the amount of CTAB added was reduced to 10 mol% (relative to
substrate) or increased to 100 mol% (entries 7 and 8). As the
reaction temperature was elevated from 28 uC to 40 uC, the
reactivity increased but at the price of enantioselectivity (entry 9 vs.
entry 6). It is noted that when tetrabutylammonium bromide
(TBAB), a phase-transfer catalyst, was added instead of CTAB, a
comparable yield but lower enantioselectivity was obtained (entry
10). These results indicate that the formation of micelles and the
electrical charge on a micelle are important to achieve high
enantioselectivity.10b Attempts to further enhance the catalytic
activity and enantioselectivity with other RuII complexes, such as
[RuCl2(benzene)]2, [RuCl2(mesitylene)]2 and [RuCl2(tert-butyl-4-
methylbenzene)]2, as well as other types of metal complexes, such
as [Cp*RhCl2]2 and [Cp*IrCl2]2, as catalyst precursors in water
failed (entries 11–15). In contrary to what Mao and Baker
reported,3b lower catalytic activity was observed when
[Cp*RhCl2]2 was used as catalyst precursor although the
enantioselectivity (95% ee) remained (entry 14 vs. entry 6).
Interestingly, a high pH value was observed in the reaction
medium and changed from 10.6 to 9.5 at the end of the reaction
(entry 1).10b,11a The reactivity (97%) and enantioselectivity (95% ee)
remained when one equivalent of HCO2H was added to the
reaction mixture (pH 7.0–8.1). However, a decrease of reactivity
(82%) and enantioselectivity (93% ee) was observed when
HCO2Na–HCO2H (2 : 1 molar ratio, pH 4.6–7.2) was used as
the hydrogen source during the reaction.11b No product was
obtained by employing HCOOH as the hydrogen donor.
100
6
97
13
14
7b
100 10 95
100 12 94
100 18 98
100 18 95
100 21 85
100 18 86
100 18 85
100 18 80
11d
11d
11d
11d
11a
11a
11a
(+)
(+)
(+)
(+)
Si
15f
16g
17h
18
19f
20g
a
Si
Si
All reactions were carried out in 1.5 mL of water at 28 uC with
b
50 mol% CTAB and (R,R)-2/[RuCl2(p-cymene)]2 = 2.2. Isolated
c
yield. Determined by HPLC analysis with a Daicel Chiralcel OD
d
column. Determined by comparing the sign of rotation of the
e
isolated product to the literatue data. With 3 mL of water and
f
100 mol% CTAB. The (R,R)-1-RuCl(p-cymene) complex (Noyori
g
catalyst) was used in water with 50 mol% CTAB. HCO2H–Et3N
(5 : 2) was used as the hydrogen source with Noyori catalyst in
CH3CN. In water without any additives. Determined on the basis
of the configuration of 4a obtained via the hydrogenation of 12a.
h
i
obtained with a formic acid–triethylamine azeotropic mixture as
the hydrogen source (entries 12 and 13).3b,4a Furthermore, 7b was
applied to test catalyst recycling because of the high activity (entry
13) and low coordinative potential of the product 8b.12 Upon
completion of the reaction, 8b was extracted with a mixture of
ethyl ether and n-hexane (v/v, 1 : 1) three times and one equivalent
of formic acid was added into the aqueous phase to regenerate
sodium formate. The water-soluble catalyst can be reused for at
least three cycles with enantioselectivity remaining. In four conse-
cutive runs, the following enantioselectivities were observed 94%,
94%, 94%, and 93% with 97%, 95%, 96%, and 85% yields, respec-
tively. ICP analysis showed that less than 0.09 mol% of ruthenium
of the water-soluble catalyst had been extracted into the organic
phase. Unfortunately, attempts at transfer hydrogenation of
acyclic imines 9 and 10 in water resulted in complete decomposi-
tion for imine 9 and no reaction with imine 10 as a substrate.
The effectiveness of the present catalytic system was demon-
strated by the asymmetric transfer hydrogenation of a variety of
cyclic imines in aqueous media under the optimization condition
with high yields and excellent enantioselectivities as shown in
Table 2. The 1-substituent of the 3,4-dihydroisoquinolines (3)
obviously affected the reactivities of transfer hydrogenation in
water, but high enantioselectivities (92% and 90% ee for 3b and 3c,
respectively) were obtained (entries 2 and 3), which are comparable
with those obtained in the homogeneous system.3b Interestingly,
the present catalytic system was proven to be a powerful tool for
the preparation of enantiopure tetrahydro-b-carboline alka-
loids.4d,f In all cases, excellent enantioselectivities (98% to 99%
ee) were achieved for asymmetric transfer hydrogenation of the
dihydro-b-carbolines (5), which were higher than those obtained
under Noyori’s conditions (entry 4 and entries 8–11).3a,4d,f It is
noticeable that the excellent enantioselectivities remained even
when the reaction of 5a was carried out with a substrate : catalyst
(S/C) ratio as high as 500 and 1000 (entries 5–7).3a
N-Sulfonylimines 7a and 7b were also smoothly reduced to the
corresponding (R)-sultams with comparable enantioselectivities
Under the present catalytic system, imine 3d was proven to be
totally inactive and no product was isolated even after 72 h.
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However, high reactivity of 3d had been observed with formic
acid–triethylamine azeotrope as the hydrogen source,3a,3b which
may be due to the formation of the protonated iminium ion to
enhance the reactivity.9,13 Because the higher solubility of iminium
in water is also speculated, iminium 11d was synthesized by
benzylation of 3d in 67% yield (Scheme 2) and smoothly reduced
to 12d in water with 94% yield and high enantioselectivity (95% ee)
which were superior to those in organic solvent (entry 14).3a,3b
Interestingly, the transfer hydrogenation of 11d with the Noyori
catalyst gave excellent enantioselectivity (98% ee) and high yield
(98%) in water but poor enantioselectivity (50% ee) with formic
acid–triethylamine azeotrope as the hydrogen source (entry 15 vs.
entry 16). Similarly, iminium 11a was prepared via benzylation of
3a in 50% yield and hydrogenated in water to give 12a with 90% ee
which was comparable to that of 3a (entry 18 vs. entry 1). The
same result (90% ee) was achieved by using the Noyori catalyst in
water (entry 19), and a similarly poor enantioselectivity (75% ee)
was obtained under Noyori conditions (entry 20).3a Furthermore,
the configuration of 12a was verified to be the (S)-form via
hydrogenation of 12a on 10% Pd/C to obtain (S)-4a in 70% yield
and 90% ee, and this implies that the transfer hydrogenation of
imine 3a and iminium 11a in water may proceed by the same
mechanism. Moreover, an ionic9 and a stepwise reduction14
mechanism can be proposed for the transfer hydrogenation of
iminium 11a because no hydrogen bonding formed between the
iminium cation of 11a and the NH2 group of the ruthenium(II)–
amide complexes.13
iminium strategy to asymmetric transfer hydrogenation of
isoquinolines is in progress.
We thank the financial support by the National Natural Science
Foundation of China (No. 20025205, 203900507 and 20472981).
Notes and references
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In summary, we have performed for the first time the catalytic
asymmetric transfer hydrogenation of cyclic imines and iminiums
in water by using sodium formate as the hydrogen source and
CTAB as an additive with a water-soluble ruthenium(II) complex
of the ligand (R,R)-2, which was shown to be a recyclable catalyst
in aqueous reaction. A green approach for the synthesis of natural
and unnatural isoquinoline and b-carboline alkaloids, which may
have fascinating biological and psychotropic properties,15 were
successfully achieved with excellent enantioselectivities (up to 99%
ee) under the present catalytic system.4 It is noticeable that, in most
of cases, the enantioselectivities in water were superior to those
obtained with formic acid–triethylamine azeotrope as the hydro-
gen source in organic solvent.3,4 The reactivity of imines can be
promoted via the formation of iminiums and high enantioselec-
tivities (>90% ee) were obtained in the aqueous transfer
hydrogenation of iminiums, to the best of our knowledge, which
is the best results in the catalytically asymmetric hydrogenation of
tetra-alkyl-substituted CLN cations.8,9 Further application of the
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Scheme 2 Synthesis and asymmetric transfer hydrogenation of iminiums.
1768 | Chem. Commun., 2006, 1766–1768
This journal is ß The Royal Society of Chemistry 2006