Asymmetric epoxidation of styrenes catalyzed by molybdenum complexes with amino alcohol ligands

Article abstract of DOI:10.1016/j.tetlet.2009.03.048

Two common amino alcohols, prolinol and isolucinol, and their derivatives have been screened to coordinate with MoO₂(acac)₂ to form in situ catalysts for asymmetric epoxidation of styrenes with the highest enantioselectivity of 84% for 4-fluoro-styrene under the optimized reaction conditions.

Full text of DOI:10.1016/j.tetlet.2009.03.048

Tetrahedron Letters 50 (2009) 2509–2511
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Asymmetric epoxidation of styrenes catalyzed by molybdenum complexes with
amino alcohol ligands
*
Yi Wang, Zhiqing Wu, Zhengkai Li, Xiang-Ge Zhou
Institute of Homogeneous Catalysis, College of Chemistry, Sichuan University, Chengdu 610064, China
a r t i c l e i n f o
a b s t r a c t
Article history:
Two common amino alcohols, prolinol and isolucinol, and their derivatives have been screened to coor-
dinate with MoO2(acac)2 to form in situ catalysts for asymmetric epoxidation of styrenes with the highest
enantioselectivity of 84% for 4-fluoro-styrene under the optimized reaction conditions.
Ó 2009 Elsevier Ltd. All rights reserved.
Received 7 February 2009
Revised 3 March 2009
Accepted 10 March 2009
Available online 13 March 2009
Keywords:
Asymmetric epoxidation
Styrene
Molybdenum
Amino alcohol
The demand for enantiopure chiral compounds rises continu-
ously, facilitated among other reasons, by the increasing number
of government regulations and health concerns as well as the need
for efficiency in industry.1a Asymmetric catalysis is a particularly
elegant and efficient method to achieve the introduction of chiral
groups into larger organic compounds.1 One of important factors
for the design and development of chiral catalysts is the need for
the use of simple and easily available chiral starting materials, so
as to be able to assemble the final catalyst in large scale and at
the cheapest cost possible.2 Taking this into account, it is easy to
understand that natural (and sometime unnatural) amino acids
are, most likely, one of the most useful chiral sources for this pur-
pose, and many different kinds of chiral ligands and catalysts have
been prepared from them.3 For example, C2-symmetric bisoxazo-
line ligands derived from amino acids have become one of the lead-
ing classes of chiral ligands in asymmetric C–C bond formation
reactions.4 Moreover, some amino acids or their derivatives such
as amino alcohols have been recently successfully applied as chiral
organocatalysts in asymmetric catalysis.5 However, the applica-
tions of amino alcohols as ligands in catalysis have less been
reported.6
molybdenum(VI) complexes with various types of chiral ligands.
Pyridyl alcohols and phosphinoylalcohols have been reported re-
cently to induce enantioselective epoxidation of unfunctionalized
olefins when coordinated to dioxo and peroxomolybdenum frag-
ments with moderate 20–40% ees.9
Continuation of our studies in transition metal catalyzed asym-
metric oxidation,10 herein is reported the first example of in situ
asymmetric epoxidation of styrenes by molybdenum complexes
with amino alcohols and their derivatives as ligands.11
Among the ligands used in this work shown in Figure 1, chiral
amino alcohols 1c and 1d were easily prepared by the reduction
of the corresponding amino acids with sodium borohydride and
iodine in THF.12 Compounds 1f and 1g were synthesized in high
yields by condensation of isoleucinol 1d with corresponding sali-
cylaldehydes followed by reduction by sodium borohydride. The
other three ligands were commercially available. The structures
COOH
O
OH
N
H
1a
N
H
1c
On the other hand, molybdenum is reported to be less toxic
than manganese and highly available to biological systems.7 The
coordination chemistry of Mo(VI) has aroused considerable inter-
ests in view of its biochemical significance, and many Mo(VI) com-
H N
2
OH
H N
OH
2
1d
1b
Ph
Ph
NH OH
plexes have been studied as models of molybdoenzymes.8,12
A
OH
NH OH
N
large number of important chemical reactions were catalyzed by
H
t-Bu
t-Bu
Ph
1g
1f
1e
* Corresponding author. Tel./fax: +86 28 85412026.
E-mail address: zhouxiangge@scu.edu.cn (X.-G. Zhou).
Figure 1. The amino alcohol ligands and their derivatives.
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.03.048

2510
Y. Wang et al. / Tetrahedron Letters 50 (2009) 2509–2511
Table 2
of the ligands were confirmed by IR, NMR and Mass spectra with
satisfactory data.12
Asymmetric epoxidation of other olefinsa
Yieldb (%)
67
eec (%)
69
Initially, all of the ligands were screened in situ asymmetric
epoxidation of styrene by using 5 mol % MoO2(acac)2 and
5.5 mol % ligands with tert-butyl hydroperoxide as oxidant, the
reaction conditions were also optimized, and the results are listed
in Table 1.
Entry
1
Substrate
As shown in Table 1, direct application of natural amino acids 1a
and 1b as ligands resulted in low ee values less than 10%, and only a
small amount of epoxide was detected in the presence of aqueous
t-butyl hydroperoxide (TBHP) in CH2Cl2 (Table 1, entries 1 and 2).
Their reductive products amino alcohols 1c and 1d, which bear
amino or hydroxy groups, led to the formation of the epoxide in
much higher yields and ees around 50% and 20%, respectively, un-
der similar reaction conditions (Table 1, entries 3 and 4). The other
two amino alcohols such as glycinol and phenylalaninol have also
been used to give 18% and 19% enantioselectivities, respectively.
Furthermore, it is notable that modification of prolinol to diphe-
nyl-2-pyrrolidine methanol 1e increased the enanotioselectivity to
46%. It indicated the major role of phenyl substitutes in controlling
the asymmetric induction during catalysis. Meanwhile, changing
the oxidant to cumene hydroperoxide (CHP) did not improve the
result (Table 1, entry 6). However, using anhydrous TBHP (40% in
toluene)13 instead of aqueous oxidant benefited to the catalysis
with 67% yield and 69% ee (Table 1, entry 7). The molar rate of
molybdenum and ligand had also strong effects on the results.
When the ratio increased from 1:1.1 to 1:2.2, the enantioselectiv-
ities declined from 69% to 25% (Table 1, entries 7 and 8). Mean-
while, the other two secondary amino alcohol derivative ligands
1f and 1g have also been examined with enantioselectivities 29%
and 44%, respectively (Table 1, entries 9 and 10). Other solvents
such as toluene, THF and CH3CN were tested with lower yields
and ees (Table 1, entries 11–13). Reaction temperature, on the
other hand, exhibited effects on the results. Lower temperature
than 25 °C decreased the catalytic activity and higher temperature
declined the enantioselectivity (Table 1, entries 7, 14 and 15). Thus,
the reaction temperature of 25 °C was selected for the further
studies.
2
3
4
5
6
70
73
75
78
72
76
72
70
81
84
73
68d
H3CO
H3C
Cl
F
Br
8
a
Reactions were run at rt with MoO2(acac)2:ligand:styrene:TBHP molar ratio of
0.05:0.055:1:1.5 in CH2Cl2.
b
Based on olefins used.
c
Determined by GC or HPLC with chiral column. All the styrene epoxides were in
R configuration compared with those in literature.
d
The configuration was 1R, 2S.
The other substrates were then examined by using 1e as ligand
under the optimized reaction conditions and the results are sum-
marized in Table 2.
In general, the catalytic reactions proceeded smoothly at room
temperature with moderate to good results. As shown in Table 2,
styrenes with electron-withdrawing substituents were epoxidized
with better results than those with electron-donating groups. For
example, when the substrate changed from 4-methylstyrene to
4-chloro-styrene, ee value increased from 70% to 81% (Table 2, en-
tries 3 and 4). And the best result of enantioselectivity of 84% was
obtained in the catalytic epoxidation of 4-fluoro-styrene (Table 2,
entry 5), which is much higher than the reported 20–40% ees by
using pyridyl alcohols as ligands.9 Indene had also been examined
under similar conditions with moderate result of 68% ee (Table 2,
entry 8).
In summary, two chiral amino alcohols and their derivatives
were found to promote the enantioselective epoxidation of sty-
renes in moderate to good enantiomeric excess up to 84%. Further
studies dealing with the application of this type of ligands in asym-
metric reactions are in progress.
Table 1
Asymmetric epoxidation of styrene catalyzed by Mo complexesa
O
MoO2(acac)2 (5 mol%),
Ligand (5.5 mol%)
TBHP
Entry
Oxidant
Ligand
Solvent
Yieldb (%)
eec (%)
1
2
3
4
5
TBHP(aq)
TBHP(aq)
TBHP(aq)
TBHP(aq)
TBHP(aq)
CHP
TBHP(toluene)
TBHP(toluene)
TBHP(toluene)
TBHP(toluene)
TBHP(toluene)
TBHP(toluene)
TBHP(toluene)
TBHP(toluene)
TBHP(toluene)
1a
1b
1c
1d
1e
1e
1e
1e
1f
1g
1e
1e
1e
1e
1e
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
Toluene
CH3CN
THF
23
26
52
48
57
68
67
69
51
56
62
65
43
25
66
9
2
23
17
46
50
69
25
29
44
66
62
51
71
47
6
7
8d
9
10
11
12
13
14e
15f
Acknowledgements
CH2Cl2
CH2Cl2
This project was supported by grants from the Natural Science
Foundation of China (Nos. 20672075, 20771076) and Sichuan Pro-
vincial Foundation (08ZQ026-041).
a
Reactions were performed with MoO2(acac)2:ligand:styrene:hydroperoxide
molar ratio of 0.05:0.055:1:1.5 except other descriptions.
b
Based on styrene used.
Determined by GC with chiral column. The major enantiomer was R-styrene
c
oxide.
References and notes
d
MoO2(acac)2:ligand = 1:2.2.
The reaction temperature is 0 °C.
e
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f
The reaction temperature is 40 °C.

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