The asymmetric induction and catalytic activity of new chiral Mn(III)-Schiff-base complexes with L-amino acids as steric groups

Article abstract of DOI:10.1016/j.tetasy.2004.03.011

L-Amino acids as inexpensive and readily available natural products showed significant chiral induction and stereo-directing abilities. The Mn(III)-Schiff-base complexes 3b and c assembled with L-amino acid ethyl esters were found to be highly effective catalysts for the enantioselective epoxidation of conjugated olefins while the corresponding binuclear-Mn(III) complexes showed lower enantioselectivity.

Full text of DOI:10.1016/j.tetasy.2004.03.011

Tetrahedron:
Asymmetry
Tetrahedron: Asymmetry 15 (2004) 1269–1273
The asymmetric induction and catalytic activity of new chiral
Mn(III)-Schiff-base complexes with -amino acids as steric groups
L
Xin-Wen Liu,a,b Ning Tang,a,* Yan-Hong Changb and Min-Yu Tana
aCollege of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou 730000, China
bDepartment of Chemistry, Tianshui Normal University, Tianshui 741000, China
Received 10 December 2003; revised 26 February 2004; accepted 1 March 2004
Abstract—
L
-Amino acids as inexpensive and readily available natural products showed significant chiral induction and stereo-
directing abilities. The Mn(III)-Schiff-base complexes 3b and c assembled with L-amino acid ethyl esters were found to be highly
effective catalysts for the enantioselective epoxidation of conjugated olefins while the corresponding binuclear-Mn(III) complexes
showed lower enantioselectivity.
Ó 2004 Elsevier Ltd. All rights reserved.
1. Introduction
catalyst. Previously, Katsuki et al. synthesized a series of
Salen-Mn(III) complexes by introducing some compli-
cated stereogenic groups [e.g., 1-(p-tert-butyl-phenyl)-
propyl and binaphthyl groups etc.] at C3 (30) to improve
the enantioselectivity of epoxidation for olefins, partic-
ularly for trans-olefins.9 This complex bearing chiral
binaphthyl units has shown excellent enantioselectivity
for a variety of conjugated cis-olefins10 with inexpensive
hydrogen peroxide being used successfully as a co-oxi-
dant.11 Some of these catalysts, however, are involved in
more difficult syntheses, therefore, their utilization is
limited.
Catalytic reactions constitute an important tool in syn-
thetic organic chemistry. The stereo- and chiral induc-
tion often plays the most important role in asymmetric
catalysis.1;2 While a variety of synthesized groups can
serve to act as stereo-inducing groups,3–6 developing or
looking for simple and convenient chiral groups as
inducing sources is more favourable due to practical and
economical considerations. An ideal chiral source
should be easily acquired and assembled and also pos-
sess characteristics of effectiveness and stability.
Recently, a report showed that amino acid Schiff-base
groups in Salen-V(IV) catalysts give a moderate direct-
ing effect for enantioselective oxidative coupling of
Herein, we report a facile synthesis along with catalytic
results of new Mn(III)-Schiff-base complexes bearing
natural amino acid groups for the epoxidation of alk-
enes (Scheme 1, 3a––MnLgCl, 3b––MnLaCl and 3c––
2-naphthols.7 Natural
L-amino acids would be ideal
chiral sources, as they are inexpensive and readily
available from natural materials. Surprisingly, their
chiral and steric potential has not been thoroughly
examined. The asymmetric epoxidation catalyzed by
chiral Salen-Mn complexes is one of the most intensively
studied with the results showing that the size and con-
figuration of the C3 (30) groups on the Salen structure
play very important roles on directivity or chiral
induction.8;9 As a result, this is a suitable reaction for
evaluating amino acid Schiff-base groups, which are
incorporated at the C3 (30) positions of a Salen-Mn
MnLpCl). Glycine,
L-alanine and L-phenylalanine were
selected as representatives to be examined, because the
ligand can be used to synthesize binuclear complexes
with two metal ions in close proximity. One corre-
sponding binuclear Mn(III) complex Mn2LaCl4 4b was
also prepared and studied.
2. Results and discussion
As shown in Scheme 1, the synthetic route for complexes
3a–c and 4b involves two main steps: the initial prepa-
ration of chiral half-cyclic matrix 2 was carried out by
condensing 2,6-diformal-4-methylphenol with (R,R)-
1,2-diphenylethylene-diamine in a 2:1 molar ratio. The
* Corresponding author. Tel.: +86-931-8626264; fax: +86-931-89125-
82; e-mail: liuxw9391@163.com
0957-4166/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2004.03.011

1270
X.-W. Liu et al. / Tetrahedron: Asymmetry 15 (2004) 1269–1273
Ph
N
Ph
N
representative results are shown in Table 1 (entries 1–6).
The catalytic reactions proceeded smoothly to afford the
corresponding epoxides with high enantiometric
excesses of >80% and yields of >77%. The best result of
95% ee was observed in the epoxidation of the electron
deficient cyano-chromene with 3c as the catalyst (entry
6). Compounds 3b and 3c, which contained bulkier
O
a: R= H
b: R= Me
c: R= Bn
i
OH
O
OH HO
O
O
1
2
iii
ii
chiral L-amino acid groups did not alter much the ee’s
Ph
Ph
Ph
N
Ph
N
and yields (entries 2–3 and 5–6), which were slightly
higher than those of 3a. It is worth noting that the
reaction products of cis-b-methyl-styrene were a mixture
of the corresponding cis- and trans-epoxides with the cis/
trans ratios being increased from 8.2 to 21.6 following
the catalyst order from 3a, 3b to 3c. This showed that
the type and size of amino acid side arms at the C3 (30)
positions of the catalyst obviously influenced the form
and cis/trans ratio of the epoxides of cis-b-methyl-sty-
rene.
Cl
Cl
N
O
N
N
O
N
Mn
Mn
O
O
Mn
N
N
(
)
Cl 3
EtOOC
COOEt
EtOOC
COOEt
R R
4
3
Scheme 1. Synthesis route for complexes. Reagents and conditions: (i)
(R,R)-1,2-diphenylethylenediamine, CH2Cl2/EtOH, <10 °C. (ii), (iii)
Manganese acetate, amino acid ethyl ester hydrochloride/NaOH,
lithium chloride, CH2Cl2/EtOH, reflux.
In the epoxidation of trans-olefins, the catalytic effects of
the three complexes were obviously different (Table 1,
entries 7–12). Surprisingly, complexes 3b and 3c showed
much higher enantioselectivities than complex 3a bear-
ing achiral glycine esters (entries 7 and 10). The results
of 63–66% ee’s and 69–72% yields of the epoxide of the
trans-diphenylethene were higher than the best value of
62% ee and 65% yield by using Katsuki’s catalysts
reported.9 Interestingly, 3b showed higher enantiose-
lectivity than 3c in the epoxidation of trans-diphenyl-
ethene. The latter, in contrast, gave a slightly better ee
for trans-phenylpropene than the former though there
were similar levels of yields (entries 8–9 and 11–12).
second step was an in situ facile-step reaction of 2 with
an amino acid (glycine, L-alanine or L-phenylalanine)
ethyl ester hydrochloride and a metal salt in a 1:2:1 ratio
to afford the chiral complexes MnLCl (or 1:2:2 ratio to
Mn2LCl4). These complexes were characterized by
microanalysis, conductance and IR spectroscopies.
We first examined the epoxidation of conjugated cis-
alkenes using 3a–c as the catalyst with inexpensive H2O2
as the oxidant in the presence of an ammonium acetate
co-catalyst12 at 2 °C in a 1:1 CH2Cl2–CH3OH. Some
Table 1. aEpoxidation of nonfunctionalized alkenes using complexes 3a–c as catalysts
O
O
R1
R2
R3
R1
R2
Catalyst
CH2Cl2/MeOH
NH4OAc
H O
+
2
2
CN
R3
A
B
C
D
Entry
Alkeneb
Complex
Time (h)
Yieldc (%)
78 (8.2:1)f
Eed (%)
Configuratione
1
A
A
A
B
3a (MnLgCl)
3b (MnLaCl)
3c (MnLpCl)
3a (MnLgCl)
3b (MnLaCl)
3c (MnLpCl)
3a (MnLgCl)
3b (MnLaCl)
3c (MnLpCl)
3a (MnLgCl)
3b (MnLaCl)
3c (MnLpCl)
2
80g
82g
83g
88
93
95
43
66
63
36
53
56
1R,2S
1R,2S
1R,2S
3R,4R
3R,4R
3R,4R
R,R
2
2
77 (17.5:1)f
3
2
80 (21.6:1)f
4
1.5
1.5
1.5
3
86
92
91
61
72
69
47
52
54
5
B
6
B
7
C
C
C
D
D
D
8
3
R,R
R,R
9
3
10
11
12
4
1R,2R
1R,2R
1R,2R
4
4
13
14
15
16
B
C
C
C
3c0 (MnL0pCl)
3a0 (MnL0gCl)
3b0 (MnL0aCl)
3c0 (MnL0pCl)
1.5
3
87
47
56
57
90
38
52
55
3S,4S
S,S
S,S
3
3
S,S
a Reactions were carried out in CH2Cl2/MeOH (1:1) at 2 °C using 30% H2O2 as oxidant and NH4OAc as the co-catalyst with a molar ratio of
substrate:catalyst:NH4OAc:H2O2¼1:0.05:0.8:3.
b A¼cis-b-methyl-styrene; B¼6-cyano-2,2-dimethyl chromene; C¼trans-diphenylethene; D¼trans-b-methyl-styrene.
c Determined on GC.
d Determined by HPLC with a chiral OD-H pipe.
e Determined by comparison with the literature data.
f Values in parentheses were the ratios of the corresponding cis- and trans-epoxides.
g Ee (%) for cis-epoxide.

X.-W. Liu et al. / Tetrahedron: Asymmetry 15 (2004) 1269–1273
1271
Table 2. Epoxidation of nonfunctionalized alkenes using dinuclear-Mn(III) complex 4b as catalysta
Entry
Alkene
Complex
Time (h)
Yieldb (%)
Eec (%)
Configurationd
1
A
B
B
B
C
C
D
4b (Mn2LaCl4)
4b (Mn2LaCl4)
4b (Mn2LaCl4)
4b (Mn2LaCl4)
4b (Mn2LaCl4)
4b (Mn2LaCl4)
4b (Mn2LaCl4)
2
65 (5.0:1)e
51f
69
67
65
31
27
18
1R,2S
3R,4R
3R,4R
3R,4R
R,R
2
1.5
3
82
84
83
46
50
38
3
4g
3
5
3
6h
7
3
R,R
1R,2R
5
a Reactions were carried out in CH2Cl2/MeOH (1:1) at 2 °C using 30% H2O2 as oxidant and NH4OAc as co-catalyst with a molar ratio of sub-
strate:catalyst:NH4OAc:H2O2 ¼ 1:0.05:0.8:3.
b Determined on GC.
c Determined by HPLC with a chiral OD-H column.
d Determined by comparison with the literature data.
e Value in parentheses was the ratio of the corresponding cis- and trans-epoxides.
f The number was the ee (%) for cis-epoxide.
g Reaction was carried out with NMO as co-catalyst in CH3CN.
h Reaction was carried out at 25 °C.
Obviously, the chiral amino acid groups (
L
L
-alanine and
-phenylalanine), when compared with the achiral gly-
It should also be noted that a second manganese ion
could induce a conformational change around the ori-
ginal Salen skeleton in the binuclear Schiff-base complex
so that the reactivity of Mn(V)@O species and enantio-
selectivity would be affected. It has been demonstrated
that the Salen ligand is readily flexible15 and its non-
planar conformation significantly contributes to high
asymmetric induction by Mn(III)-Salen epoxidation
catalysts.10 The more rigid structure of the binuclear
catalysts may influence the effective stereo-chemical
communication with oncoming substrates,13 that is, the
conformational inflexibility of the amino acid groups on
the binuclear complex may impede their inducing func-
tion. Conversely, this brings to light the important role
cine, showed better stereo-effects as well as chiral
inducing functions. This effect of two kinds of amino
acid side arms was also observed when the (S,S)-
diphenylethylene-diamine was used instead of the (R,R)-
in catalysts 3a–c to form diastereomeric catalysts 3a0–c0
(Table 1, entries 13–16).
The above results fully indicate that the directivity of
-amino acid esters armed at the C3 (30) of Mn(III)-
L
complex 3 is very similar to the tert-butyl groups used in
chiral Jacobsen’s catalysts.2;13 Their chiral induction
ability in the epoxidation for trans-olefins is a little
higher (e.g.,
L
-phenylalanine ethyl ester) than that of the
played by L-amino acid groups on asymmetric induc-
tivity in mono-nuclear complexes 3b and c.
more complicated groups bonded at the C3 (30) posi-
tions in Salen catalysts.9 Previous studies of Schiff-base
complexes have shown lower ee’s in the asymmetric
epoxidation of trans-olefins; however this study resulted
in complexes 3b and c showing higher levels of asym-
metric induction. One possible reason is that the two
closer and bulkier amino-acid-Schiff-base groups on
these complexes may be forced to produce torsion due
to stereo-repulsion. This torsion could then enhance the
stereo-selectivity of the whole ligand, increasing the
steric effect between the C3 (30) groups and the substrate.
This would result in improved enantioselectivity of the
epoxides.
3. Conclusion
In conclusion, a new type of chiral Mn-Schiff-base
complexes bearing amino acid ethyl ester has been
developed by a facile stepwise procedure. These com-
plexes have been successfully used for the first time in
the asymmetric epoxidation of unfunctionalized alkenes
3b and c showing highly chiral inductivity and catalytic
activity. Through epoxidation studies, the significant
stereo- and chiral-inducing roles played by the natural
L
-amino acid groups have been revealed. The studies
Under similar reaction conditions, the catalytic activity
of the binuclear Mn(III)-catalyst 4b was then investi-
gated (Table 2). Using 4b as the catalyst unfortunately
meant that the enantioselectivity of the corresponding
epoxides were dramatically decreased; for trans-olefins
the ee’s were especially poor (Table 2, entries 5–7). The
yields were also lower than using mono-nuclear catalyst
3b whether cis- or trans-olefins. We attempted to
improve the catalytic activity of the binuclear catalyst by
changing the reaction conditions but to no effect. The
results indicate that the binuclear Mn(III) complexes are
less efficient epoxidation catalysts than the mono-
nuclear ones.14 One possible explanation is that the ste-
reo-electronic effect of two active-Mn species too close
together limits the formation of Mn(V)@O intermediate.
may offer the opportunity for developing new stereo-
and chiral groups. The inherent advantages also include
readily available and selectable chiral/inductive groups,
as well as facile preparation. We believe that the natural
L
-amino acids may also be effective as chiral groups with
directing effects in other asymmetric reactions by
choosing and assembling rationally.
4. Experimental
1H NMR spectra were obtained at 200 MHz on a Bru-
ker DRX-200 spectrometer. IR spectra were recorded

1272
X.-W. Liu et al. / Tetrahedron: Asymmetry 15 (2004) 1269–1273
on a Nicolet NEXUS 670 FT-IR spectrometer. FAB-
MS was acquired on a MASPEC II System mass spec-
trometer. Elemental analyses were performed on an
Elementary VarioEL instrument in the Center of Anal-
ysis and Test. TLC was conducted on glass plates coated
with silica gel 60F254. The chiral 1,2-diphenylethylene-
diamine and amino acid ethyl ester hydrochlorides were
purchased from the Likai Chiral Technique Company
Ltd. 2,6-Diformal-4-methylphenol was prepared with
reference to literature.16 Other solvents and chemicals
were obtained from commercial sources.
2951, 2906, 2867, 1737, 1621, 1596, 1538, 1435, 1381,
1310, 1267, 1050, 833, 746, 698 cmꢀ1. KM (CH3CN):
15 mho cmꢀ1 molꢀ1
.
Compound 3c was prepared from
ethyl ester (yield 75%). Anal.
L
-phenylalanine
Calcd for
C54H52ClMnN4O6ÆH2O: C, 67.46; H, 5.66; N, 5.83; Mn,
5.71%. Found: C, 67.81; H, 5.48; N, 5.93, Mn, 5.54%.
IR (KBr): 3430, 3060, 3038, 3007, 2947, 2906, 2866,
1737, 1620, 1602, 1521, 1472, 1435, 1381, 1267, 1048,
830, 757, 701 cmꢀ1. KM (CH3CN): 8 mho cmꢀ1 molꢀ1
.
Compound 4b was synthesized similar to 3b except
additional 0.001 mol manganese acetate in EtOH was
added under reflux before lithium chloride was added.
Yield 82%. Anal. Calcd for C42H44Cl4Mn2N4O6: C,
52.96; H, 4.66; N, 5.88; Mn, 11.54%. Found: C, 52.75;
H, 4.62; N, 5.81; Mn, 11.77%. IR (KBr): 3012, 2947,
2866, 1735, 1618, 1593, 1540, 1433, 1381, 1323, 1266,
4.1. Synthesis of previous ligand 217
A
solution of (R,R)-1,2-diphenylethylenediamine
(0.01 mol) in EtOH was slowly added to 5-methyl-1,3-
diformylalicylaldehyde (0.022 mol) in CH2Cl2 with stir-
ring at <10 °C. The reaction was kept for an additional
5 h. The resulting solution, upon concentration, precip-
itated out the crude solid. The yellow solid was washed
with alcohol and ether and purified by silica gel column
chromatography to afford 2. Yield 68%. 1H NMR
(CDCl3): d ppm 2.21 (s, 6H), 4.58 (s, 2H), 7.21 (b s,
10H), 7.41 (d, 2H), 7.64 (d, 2H), 8.44 (s, 2H), 9.96 (s,
2H), 13.86 (b s, 2H exchangeable with D2O). FAB-MS:
M+1 505.74 (FM 504). Anal. Calcd for C32H28N2O4: C,
76.17; H, 5.59; N, 5.55%. Found: C, 76.43; H, 5.67; N,
5.32%.
1047,
838,
767,
.
710 cmꢀ1
.
KM
(CH3CN):
2 mho cmꢀ1 molꢀ1
4.3. General procedure for epoxidation reaction
Enantioselective epoxidation reaction was carried out
according to the reported procedure.12 To a cooled
(2 °C) solution of catalyst 3 (5.0 mol %), substrate
(0.5 mmol) and NH4OAc (0.4 mmol) in dichlorome-
thane/methanol was added a pre-cooled solution of 30%
H2O2 (1.5 mmol) in four portions during reaction. The
mixture was stirred at 2 °C and the reaction monitored
by TLC. After completion of the reaction, the mixture
was diluted with dichloromethane and water. The or-
ganic phase was separated, washed with saturated NaCl
solution, dried over sodium sulfate and concentrated.
The residue was purified by flash chromatography
(eluent hexane/iso-C3H7OH) to give the corresponding
epoxide. The ee of the epoxide was determined by
HPLC with a chiral OD-H pipe.
4.2. Synthesis of complexes 3a–c and 4b
Synthesis of amino acid Schiff base complexes were
carried out with reference to literature.14;18 Manganese
acetate (0.001 mol in EtOH) was added to a solution of
Schiff base 2 (0.001 mol) in CH2Cl2 under an inert
atmosphere, refluxing for 2 h. A solution of amino acid
ethyl ester hydrochloride (0.0021 mol) and NaOH
(0.0021 mol) in EtOH was then added with stirring, and
continuously refluxed for an additional 3–4 h. Lithium
chloride (0.006 mol) was added and the mixture stirred
for a further 2 h while being exposed to air. The solvent
was removed and the residue extracted with dichlo-
romethane. The extract was washed with water, brine
and dried over sodium sulfate. On partial removal of the
solvent and the addition of petroleum ether (30–60 °C),
the desired chiral complexes precipitated from solution.
The mixture was filtered and the filter cake dried to
afford a dark brown powder.
Acknowledgements
The authors are grateful to the Gansu Natural Science
Foundation of China (ZR011-A25-001-Z) for support
and to the National Lab of Applied Organic Chemistry
for facilities.
Compound 3a was prepared from glycine ethyl ester
(yield 83%). Anal. Calcd for C40H40ClMnN4O6ÆH2O: C,
60.50; H, 5.42; N, 7.17; Mn, 7.03%. Found: C, 60.65; H,
5.52; N, 6.98; Mn, 7.27%. IR (KBr): 3428, 3042, 3008,
2957, 2905, 2867, 1735, 1619, 1593, 1538, 1438, 1382,
1306, 1266, 1047, 829, 767, 705 cmꢀ1. KM (CH3CN):
References and notes
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X.-W. Liu et al. / Tetrahedron: Asymmetry 15 (2004) 1269–1273
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