Enantioselective epoxidation of non-functionalized alkenes using carbohydrate based salen-Mn(III) complexes

Article abstract of DOI:10.1016/j.carres.2006.11.026

Three new salen ligands with carbohydrate moieties were prepared from a salicylaldehyde derivative obtained by reaction of 1,2:5,6-di-O-isopropylidene-α-d-glucofuranose with 3-tert-butyl-5-(chloro-methyl)-2-hydroxybenzaldehyde. These ligands were coordinated with Mn(III) to give three chiral salen-Mn(III) complexes. The complexes were characterized and employed in the asymmetric epoxidation of unfunctionalized alkenes. Catalytic results showed that although there are no chiral groups on the diimine bridge, these complexes had some enantioselectivity, which indicates the carbohydrate moiety has an asymmetric inducing effect in the epoxidation reaction.

Full text of DOI:10.1016/j.carres.2006.11.026

Carbohydrate Research 342 (2007) 254–258
Note
Enantioselective epoxidation of non-functionalized alkenes
using carbohydrate based salen–Mn(III) complexes
Shanshan Zhao, Jiquan Zhao* and Dongmin Zhao
School of Chemical Engineering, Hebei University of Technology, Tianjin 300130, PR China
Received 25 June 2006; received in revised form 18 November 2006; accepted 29 November 2006
Available online 3 December 2006
Abstract—Three new salen ligands with carbohydrate moieties were prepared from a salicylaldehyde derivative obtained by reaction
of 1,2:5,6-di-O-isopropylidene-a-D-glucofuranose with 3-tert-butyl-5-(chloro-methyl)-2-hydroxybenzaldehyde. These ligands were
coordinated with Mn(III) to give three chiral salen–Mn(III) complexes. The complexes were characterized and employed in the
asymmetric epoxidation of unfunctionalized alkenes. Catalytic results showed that although there are no chiral groups on the di-
imine bridge, these complexes had some enantioselectivity, which indicates the carbohydrate moiety has an asymmetric inducing
effect in the epoxidation reaction.
ꢀ 2006 Elsevier Ltd. All rights reserved.
Keywords: Salen–Mn(III) complexes; Carbohydrate; Glucofuranose; Asymmetric epoxidation; Salicylaldehyde derivative
During the last few years, salen–Mn(III) complexes have
emerged as efficient and practical catalysts for the asym-
metric epoxidation of various non-functionalized cis-di,
tri-, and tetra-substituted alkenes. Much attention has
been given to the design and synthesis of salen ligands
and to the explanation of the chiral induction of the
salen structure. It has been assumed that the two main
structural features required to achieve good enantiose-
lectivity are bulky substituents on C-3 (30) of the salen
ligand and an asymmetrical diimine bridge derived from
a C2-symmetric diamine.1 However, how the substitu-
ents on C-5 (50) influence catalytic results has not yet
been identified.
incorporating a chiral carbohydrate into the diamine
moiety.2 Ruffo and co-workers also reported new chiral
salen ligands derived from a-D-glucose and a-D-man-
nose by introducing appropriate functional groups at
the C-2 and C-3 of the sugar ring, and they reported
high enantiomeric excesses for epoxidation reactions.3
In another work, Ruffo and co-workers prepared a
supported salen–Mn(III) catalyst derived from D-glu-
cose and the catalytic results showed that the complex
had good reactivity and enantioselectivity.4 These
efforts have strengthened the prospects of utilizing nat-
ural products as templates for asymmetric epoxidative
catalysts.
Carbohydrates are naturally occurring multifunc-
tional products and inexpensive starting materials with
chiral centers, which makes them ideal precursors for
the introduction of chiral building blocks into cata-
lysts. Previously it has been a challenge to incorporate
carbohydrates into an asymmetric catalyst. But
recently, Yan and Klemm reported the first carbo-
hydrated-derived chiral Mn(III)–salen complex by
Encouraged by these recent advances, we have
focused on combining chiral carbohydrate derivatives
with a salicylaldehyde moiety to attain new complexes.
It was expected that the chiral centers of the carbohy-
drate derivatives would improve the enantiometric
excesses. Therefore, we synthesized a new salicylalde-
hyde derivative with a sugar ring at C-5 (50), and from
this was prepared several asymmetric salen–Mn(III)
complexes.
The synthetic route for these chiral complexes, 7a–c, is
shown in Scheme 1. First, 3-tert-butyl-2-hydroxybenz-
aldehyde 2 was prepared from 2-tert-butylphenol with
*
Corresponding author. Tel.: +86 22 26564279; fax: +86 22
26564733; e-mail: zhaojq@hebut.edu.cn
0008-6215/$ - see front matter ꢀ 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2006.11.026

S. Zhao et al. / Carbohydrate Research 342 (2007) 254–258
255
OH
OH
OH
CHO
CHO
toluene, (HCHO)n
SnCl4
HCl
(HCHO)n
CH2Cl
2
3
1
O
O
O
OHC
HO
O
OH
O
O
O
NaH, 3
O
TBAI, THF
O
O
O
4
5
R2
R1
N
R1
R2
N
O
O
O
O
O
O
O
O
diamine
C2H5OH
OH
HO
O
O
O
O
6a-6c
R2
R1
N
R1
R2
N
O
O
O
O
O
O
O
O
Mn
Cl
(1) Mn(OAc)2.4H2O
(2) LiCl, air
O
O
O
O
O
O
7a-7c
a: (R,R) R1-R1= -(CH2)4-, R2=H
b:
R1-R1= -(CH2)4-, R2=H
c:
R1=R2=H
Scheme 1. Synthetic route for the complexes.
a moderate yield. Chloromethylation of 2 produced a
salicylaldehyde derivative 3, 3-tert-butyl-5-(chloro-
methyl)-2-hydroxybenzaldehyde which has a chloro-
methyl group at C-5. Condensation of 3 and 1,2:5,6-
and lower ee’sꢀ (entries 8 and 10), whereas a-methyl-
styrene afforded moderate ee’s (entries 16 and 17). For
all the substrates, except a-methyl-styrene, the m-CPBA
system produced higher ee’s with a shorter time than
the NaClO system (entries 1, 2, 8, 11, 16, 17, 23 and
24). The m-CPBA results were achieved in less than
1.5 h, whereas the reaction time for the NaClO system
extended to several hours at 0 ꢁC. For the m-CPBA
system, lowering the temperature from ꢀ20 to ꢀ78 ꢁC
increased the yields and the ee values of the epoxides
(entries 9 and 10). For the NaClO system, increasing
the amount of loaded catalyst markedly shortened the
reaction time, but no obvious effects on the yields or
enantioselectivities were observed (entries 2 and 3).
The catalytic properties of 7a–c were compared. The
latter two complexes, which have no asymmetrical di-
imine bridges, both had poor epoxidation results with
ee’s of 6% and 11%, when 1,2-dihydronaphthalene was
used as the substrate (entries 4 and 6). This enantioselec-
tivity is undoubtedly induced by the chiral sugar groups
of the complexes. Thus, it can be concluded that the
di-O-isopropylidene-a-D-glucofuranose
4 yielded 5.
Complexes 7a–c were then prepared by condensing 5
with the desired diamine in a 2:1 molar ratio, followed
by metalation with Mn(III) as Jacobsen’s procedure.5
These complexes were characterized by optical rotation,
IR spectroscopy, elementary analysis, and MS.
Complexes 7a–c were used as catalysts for the epoxi-
dation of 1,2-dihydronaphthalene, styrene, a-methyl-
styrene, and cis-b-methyl-styrene. Two different oxida-
tive systems were used for the epoxidation reactions.
The first was a binary media system, NaClO/PyNO/
H2O/CH2Cl2, and the second was a homogeneous sys-
tem, m-CPBA/NMO/CH2Cl2, where PyNO is pyridine
N-oxide and NMO is N-methylmorpholine N-oxide.
The results of the asymmetric epoxidation catalyzed by
the complexes are presented in Table 1.
7a showed moderate yields and good enantio-
selectivities for the asymmetric epoxidation of cis-b-
methyl-styrene and 1,2-dihydronaphthalene (entries 3
and 23). The terminal-olefin styrene had good yields
ꢀ ee: enantiomeric excess.

256
S. Zhao et al. / Carbohydrate Research 342 (2007) 254–258
Table 1. Epoxidation of 1,2-dihydronaphthalene, styrene, a-methyl-styrene and cis-b-methyl-styrene using catalysts 7a–c
Entry
Substratea
Catalystb
Oxidantc
Temperature (ꢁC)
Time
Yieldd (%)
eee (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
A
A
A
A
A
A
A
B
B
B
B
B
7a (1.0)
7a (1.0)
7a (3.0)
7b (2.0)
7b (1.0)
7c (2.0)
7c (2.0)
7a (0.5)
7a (1.0)
7a (1.0)
7a (0.5)
7b (2.0)
7b (2.0)
7c (1.0)
7c (2.0)
7a (2.0)
7a (1.0)
7b (2.0)
7b (2.0)
7c (1.0)
7c (2.0)
7a (0.5)
7a (1.0)
7a (1.0)
7b (2.0)
7b (2.0)
7c (1.0)
7c (2.0)
m-CPBA
NaClO
NaClO
m-CPBA
NaClO
m-CPBA
NaClO
m-CPBA
m-CPBA
m-CPBA
NaClO
m-CPBA
NaClO
m-CPBA
NaClO
m-CPBA
NaClO
m-CPBA
NaClO
m-CPBA
NaClO
m-CPBA
m-CPBA
NaClO
m-CPBA
NaClO
ꢀ78
75 min
9.5 h
2.0 h
50 min
12 h
30 min
5.5 h
25 min
5 min
20 min
7 h
10 min
5 h
15 min
1 h
20 min
10 h
44
66
67
59
63
40
57
95
67
99
44
>99
97
93
34
93
78
87
87
82
91
47
74
41
91
54
80
28
78
67
70
6
6
11
4
38
22
37
20
1
2
<1
7
51
60
6
9
10
6
83
84
82
5
3
2
0
0
ꢀ78
0
ꢀ78
0
ꢀ78
ꢀ20
ꢀ78
0
ꢀ78
B
B
B
0
ꢀ78
0
C
C
C
C
C
C
D
D
D
D
D
D
D
ꢀ78
0
ꢀ78
0
10 min
10 h
ꢀ78
15 min
10.5 h
50 min
50 min
10.5 h
15 min
5 h
0
ꢀ78
ꢀ78
0
ꢀ78
0
m-CPBA
NaClO
ꢀ78
0
15 min
5 h
2
a A: 1,2-dihydronaphthalene; B: styrene; C: a-methyl-styrene; D: cis-b-methyl-styrene.
b The number in parentheses is the molar percentage of catalyst used as compared to the amount of substrate.
c Reactions were carried out in CH2Cl2. For the m-CPBA oxidative system the substrate:oxidant:NMO molar ratios were 1:2:5. For the NaClO
system the substrate:oxidant:PyNO molar ratios were 1:2:0.2.
d Determined by GC.
e Determined by GC with a chiral Cyclodex-b column.
chiral centers on C-5 (50) of the salicylaldehyde moiety
has an influence on enantioselectivity but only a weak
one. This weak effect may be explained due to the chiral
centers are not being in the vicinity of Mn metal.5
dex-b capillary column (30 m · 250 lm i.d.) using an
FID detector. 2-tert-Butylphenol, 1,2-dihydronaphtha-
lene, a-methyl-styrene, cis-b-methyl-styrene, N-methyl-
morpholine N-oxide, and 1,2:5,6-di-O-isopropylidene-
a-D-glucofuranose were purchased from Acros. (R,R)-
1,2-Cyclohexanediamine was prepared according to the
literature.6 Solvents were redistilled prior to use. Other
chemicals were purchased from commercial sources
and used as received.
1. Experimental
1.1. Methods and materials
1H NMR and 13C NMR spectra were obtained in CDCl3
or DMSO using a Bruker AC 300/75 spectrometer. IR
spectra in KBr pellets were recorded on a Bruker
Vector-22 spectrophotometer. Melting points were
determined on a Perkin XT-4 microscopic analyzer.
Elemental analyses were acquired using an Elementary
vario El instrument. Optical rotations were measured
on a Shanghai WZZ-2S/2SS digital rotation analyzer,
at ambient temperature using a 100 mm sample tube.
Fast atom bombardment mass spectrometry was per-
formed on a VG ZAB-HS Mass Spectrometer. Reaction
products were analyzed on a Shandong Lunan Ruihong
Gas Chromatograph, SP-6800A, equipped with a Cyclo-
1.2. Synthesis of 3-tert-butyl-2-hydroxybenzaldehyde (2)
Compound 2 was synthesized according to reported
1
procedures.7 Light yellow liquid. Yield 37%. H NMR
(CDCl3): d 1.42 (s, 9H), 6.93 (t, J = 7.5, 7.5 Hz, 1H),
7.39 (q, J = 1.8, 5.7, 1.8 Hz, 1H), 7.52 (q, J = 1.8, 6.0,
1.5 Hz, 1H), 9.88 (s, 1H), 11.79 (s, 1H).
1.3. Synthesis of 3-tert-butyl-5-(chloro-methyl)-2-
hydroxybenzaldehyde (3)
3 was prepared using the procedure reported in the liter-
ature.8,9 Light yellow crystalline solid. Yield 87%, mp

S. Zhao et al. / Carbohydrate Research 342 (2007) 254–258
257
1
61–63 ꢁC, lit.9 63–65 ꢁC; H NMR (DMSO): d 1.39 (s,
129.7, 126.7, 118.4, 112.0, 109.2, 105.5, 82.9, 81.6,
77.7, 77.2, 76.8, 72.7, 67.5, 35.0, 33.4, 29.5, 27.1, 26.5,
25.7, 24.5; FABMS: m/z 979 [M+H]+. Anal. Calcd for
C54H78O14N2: C, 66.24; H, 8.03; N, 2.86. Found: C,
66.39; H, 8.03; N, 2.64.
9H), 4.81 (s, 2H), 7.63 (d, J = 2.2 Hz, 1H), 7.75 (d,
J = 2.2 Hz, 1H), 9.98 (s, 1H), 11.91 (s, 1H).
1.4. Synthesis of 1,2:5,6-di-O-isopropylidene-3-O-methyl-
ene-[5-(3-tert-butyl-2-hydroxy benzaldehyde)]-a-D-gluco-
furanose (5)
6b was prepared from 5 and 1,2-cyclohexanediamine,
20
yellow foam solid: yield 53%; mp 66–68 ꢁC; ½aꢁD ꢀ57.8
1
(c 0.08, EtOH); H NMR and IR data were in agree-
Oil-free NaH10 (0.10 g, 4 mmol) was suspended in dry
THF (10 mL) under nitrogen at 0 ꢁC. A solution of
1,2:5,6-di-O-isopropylidene-a-D-glucofuranose 4 (0.52
g, 2 mmol) in THF (10 mL) was added dropwise using
a dropping funnel and the mixture was stirred at room
temperature for 3 h. Then a solution of 3 (0.57 g,
2.5 mmol) in THF (10 mL) was added very slowly at
0 ꢁC followed by the addition of tetrabutylammonium
iodide (TBAI, 0.02 g, 0.06 mmol).11 The reaction mix-
ture was heated under reflux for 11 h. After destroying
excess NaH by adding a few drops of water at 0 ꢁC the
solvent was evaporated in vacuo. The resulting mass
was extracted with CHCl3. The CHCl3 phase was
washed with brine, dried over Na2SO4 and concen-
trated to obtain a crude residue. The product was puri-
fied by silica gel column chromatography, eluting with
a 1:3 (V:V) EtOAc–petroleum ether mixture to give
compound 5, a light yellow solid (0.60 g, yield 67%):
ment with those of 6a; FABMS: m/z 979 [M+H]+. Anal.
Calcd for C54H78O14N2: C, 66.24; H, 8.03; N, 2.86.
Found: C, 66.52; H, 8.02; N, 2.71.
6c was synthesized from 5 and ethylenediamine,
20
yellow foam solid: yield 60%; mp 81–83 ꢁC; ½aꢁD ꢀ56.0
(c 0.20, EtOH); IR (KBr): m 3442, 2987, 2932, 1633,
1444, 1373, 1341, 1268, 1215, 1164, 1077, 1026, 848,
1
798, 776 cmꢀ1; H NMR (CDCl3): d 1.31 (s, 9H), 1.42
(s, 12H), 3.95 (s, 2H), 4.00–4.34 (m, 5H), 4.55–4.58
(m, 3H), 5.87 (d, J = 3.6 Hz, 1H), 7.10 (s, 1H), 7.26 (s,
1H), 8.38 (s, 1H), 13.87 (s, 1H); 13C NMR (CDCl3): d
202.8, 167.2, 160.5, 137.9, 129.8, 129.5, 126.9, 118.4,
112.0, 109.2, 105.5, 83.0, 81.7, 77.6, 76.8, 72.7, 67.6,
60.8, 59.8, 48.9, 35.1, 29.5, 27.1, 26.5, 25.7; FABMS:
m/z 925 [M+H]+. Anal. Calcd for C50H72O14N2: C,
64.92; H, 7.84; N, 3.03. Found: C, 64.89; H, 8.04; N,
3.10.
20
mp 96–98 ꢁC; ½aꢁD ꢀ34.1 (c 0.80, EtOH); IR (KBr): m
3423, 2992, 2969, 2936, 2862, 1655, 1617, 1456, 1440,
1384, 1374, 1321, 1265, 1226, 1212, 1167, 1152, 1081,
1.6. Synthesis of salen–Mn(III) complexes (7a–c)
1024, 847, 771, 759 cmꢀ1
;
1H NMR (CDCl3): d 1.38
A mixture of 6a (0.33 g, 0.34 mmol) and Mn(OAc)2Æ
4H2O (0.17 g, 0.68 mmol) in EtOH (30 mL) was refluxed
with stirring under an atmosphere of nitrogen for 4 h.
Then solid LiCl (0.04 g, 1.02 mmol) was added and the
mixture was further heated for 3 h while exposed to
air.12 The solvent was removed and the residue was
extracted with CH2Cl2. The extract was washed with brine,
dried over Na2SO4, and concentrated to obtain a dark
brown powder 7a (0.27 g, yield 75%): mp 140–142 ꢁC;
(s, 9H), 1.42 (s, 12H), 4.01–4.68 (m, 8H), 5.90 (d,
J = 3.9 Hz, 1H), 7.41 (d, J = 2.4 Hz, 1H), 7.48 (d,
J = 1.8 Hz, 1H), 9.87 (s, 1H), 11.80 (s, 1H); 13C
NMR (CDCl3): d 197.0, 161.0, 138.6, 133.9, 131.0,
128.3, 120.3, 111.9, 109.1, 105.3, 82.6, 81.6, 81.3,
77.7, 76.7, 72.4, 71.8, 67.5, 34.9, 29.1, 26.9, 26.8, 26.7,
26.2; FABMS: m/z 450 [M]+. Anal. Calcd for
C24H34O8: C, 63.98; H, 7.61. Found: C, 63.71; H, 7.83.
20
½aꢁD ꢀ789 (c 0.07, CH2Cl2); IR (KBr): m 2986, 2938,
1.5. Synthesis of Schiff-base ligands (6a–c)
2869, 1613, 1543, 1455, 1438, 1422, 1383, 1340, 1310,
1263, 1234, 1210, 1166, 1076, 1027, 848, 828, 784, 567,
512 cmꢀ1; FABMS: m/z 1031 [MꢀCl]+. Anal. Calcd
for C54H76O14N2MnCl: C, 60.75; H, 7.18; N, 2.62.
Found: C, 60.47; H, 7.21; N, 2.43.
A solution of 5 (1.00 g, 2.2 mmol) and (R,R)-1,2-cyclo-
hexanediamine (0.13 g, 1.1 mmol) in dry EtOH (25 mL)
was refluxed for 2 h under nitrogen atmosphere.12 The
ethanol was evaporated under reduced pressure and
the residue was purified by chromatography (EtOAc–
petroleum ether 1:2, V:V) to give the Schiff base 6a, a
yellow foam solid (0.78 g, yield 72%): mp 85–87 ꢁC;
For 7b and 7c, the above procedure was followed but
6b and 6c were used in place of 6a. 7b: dark brown
20
powder, yield 70%; mp 194–196 ꢁC; ½aꢁD ꢀ92.6 (c 0.07,
CH2Cl2); IR data were in accordance with that of 7a.
FABMS: m/z 1031 [MꢀCl]+. Anal. Calcd for
C54H76O14N2MnCl: C, 60.75; H, 7.18; N, 2.62. Found:
C, 60.52; H, 7.24; N, 2.48.
20
½aꢁD ꢀ164.0 (c 0.14, EtOH); IR (KBr): m 3442, 2986,
2935, 2865, 1631, 1598, 1444, 1373, 1322, 1265, 1214,
1164, 1077, 1027, 849, 800, 776 cmꢀ1
;
1H NMR
(CDCl3): d 1.27 (s, 9H), 1.39 (s, 12H), 1.42–1.48 (m,
2H), 1.88–1.98 (m, 2H), 3.31 (d, J = 9.9 Hz, 1H), 3.96–
4.55 (m, 8H), 5.84 (d, J = 3.6 Hz, 1H), 6.99 (d,
J = 1.8 Hz, 1H), 7.20 (d, J = 1.8 Hz, 1H), 8.28 (s, 1H),
13.91 (s,1H); 13C NMR (CDCl3): d 165.4, 160.5, 137.6,
7c: dark brown powder, yield 65%; mp 135–137 ꢁC;
20
½aꢁD ꢀ156.3 (c 0.02, CH2Cl2); IR (KBr): m 2957, 1615,
1544, 1440, 1383, 1339, 1302, 1264, 1210, 1165, 1076,
1026, 848, 823, 584, 537 cmꢀ1; FABMS: m/z 978
[MꢀCl]+. Anal. Calcd for C50H70O14N2MnCl: C,

258
S. Zhao et al. / Carbohydrate Research 342 (2007) 254–258
59.25; H, 6.96; N, 2.76. Found: C, 59.46; H, 7.10; N,
2.47.
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For the m-CPBA system: A solution containing catalyst
(7a–c), alkene (0.5 mmol), and NMO (2.5 mmol) in
dichloromethane was cooled to the desired temperature.
The solid m-CPBA (1.0 mmol) was added with stirring.
The reaction process was monitored by GC.
For the NaClO system: To a cooled (0 ꢁC) solution
of catalyst (7a–c), substrate (1 mmol) and PyNO
(0.2 mmol) in dichloromethane, a pre-cooled solution
of 13% NaClO (2 mmol, pH = 11.3) was added in
portions. The reaction process was monitored by GC.
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Financial assistance from the National Natural Science
Foundation of China (Grant No. 20376017) is gratefully
acknowledged.