Catalytic activity and recyclability of new enantioselective chiral Co-salen complexes in the hydrolytic kinetic resolution of epichlorohydrine

Article abstract of DOI:10.1016/S0040-4039(03)01182-1

Chiral Co(III) salen catalysts bearing PF₆, BF₄ or Br counterions proved to be reactive and enantioselective in the hydrolytic resolution of terminal epoxides. The catalysts could be recovered and reused several times without further

Full text of DOI:10.1016/S0040-4039(03)01182-1

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 5005–5008
Catalytic activity and recyclability of new enantioselective chiral
Co–salen complexes in the hydrolytic kinetic resolution
of epichlorohydrine
Geon-Joong Kim,a,* Hosung Leeb and Seong-Jin Kimb
aDepartment of Chemical Engineering, Inha University, Inchon 402-751, Republic of Korea
bRS tech Corp. c305 Venture Town, 1688-5, Sinil-dong, Daedeok-gu, Daejeon 306-230, Republic of Korea
Received 20 February 2003; revised 6 May 2003; accepted 9 May 2003
Abstract—Chiral Co(III) salen catalysts bearing PF6, BF4 or Br counterions proved to be reactive and enantioselective in the
hydrolytic resolution of terminal epoxides. The catalysts could be recovered and reused several times without further treatment
after reaction, showing no loss of activity and enantioselectivity. © 2003 Elsevier Science Ltd. All rights reserved.
Much effort has been devoted not only to the develop-
ment of active catalysts but also to finding ways to
enable repeated use. This is especially important for
chiral catalysts, which are usually more expensive than
achiral catalysts. The syntheses of optically pure chemi-
cals have gained significant potential over recent years.
The heterogeneous chiral catalysts offer practical
advantages of the facile separation from reactants and
products, as well as recovery and reuse. However, some
disadvantages can be expected in heterogeneous cataly-
sis in terms of reaction rates and enantioselectivity. It
has been found that several systems based on chiral
chromium– and cobalt–salen complexes are very efficient
for the highly enantioselective reaction of nucleophiles
with epoxides.1–7 Especially, chiral Co(III)–OAc salen
complex (1) is very enantioselective for the hydrolytic
kinetic resolution (HKR) of racemic epoxides such as
( )-styrene oxide and ( )-epichlorohydrine(ECH) with
water.3–7 ECH is one of the attractive substrates for
HKR because the racemates are available inexpensively
and the chiral three carbon building blocks derived
from that compound is extremely versatile synthetic
intermediates. These recently developed chiral salen-
based catalysts are appealing candidates for covalent
attachment of homogeneous salen ligands to the solid
supports, and for the development of new method for
the recycling of chiral catalysts.6–14 The features of
HKR include the easy separation of diol product from
unreacted epoxide due to large boiling point difference
and recycleability of the catalysts. Whereas, the (salen)
Co(III)–OAc complex (1) shown in Scheme 1 must be
regenerated by treatment with acetic acid in air after
reaction and separation of products.3 Furthermore, this
type catalyst has the drawback of the racemization in
HKR of ECH and it may stand as a critical issue.
Based on these facts, our attention was directed to the
development of optically active catalysts desirable for
repeated use without any treatment after HKR reac-
tion, and the racemization of optically pure epoxide has
been completely overcome by using the new catalysts
bearing less coordinating counterions.
Here in this study, we have synthesized various counter
anion-containing (salen) Co catalysts and these newly
synthesized chiral salen Co(III) complexes have been
applied as catalysts in the HKR of terminal epoxides.
* Corresponding author. Tel.: +82-32-860-7472; fax: +82-32-872-0959;
e-mail: kimgj@inha.ac.kr
Scheme 1.
0040-4039/03/$ - see front matter © 2003 Elsevier Science Ltd. All rights reserved.
doi:10.1016/S0040-4039(03)01182-1

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G.-J. Kim et al. / Tetrahedron Letters 44 (2003) 5005–5008
The catalyst 2 was prepared by the same manner as
catalyst 1 using a,a,a-trifluoro-p-toluic acid instead of
HOAc. The (salen) Co(II) complex was oxidized in air
in the presence of a,a,a-trifluoro-p-toluic acid and tolu-
ene, generating the corresponding salen complex 2. For
the synthesis of catalysts 3 or 4, the chiral salen
(R,R)-(−)-N,N%-bis(3,5-di-tert-butylsalicylidene)-1,2-
cyclohexane diamino cobalt(II) was treated with fer-
columns (CHIRALDEXTM(D-TM), Gamma-cyclo-
dextrin trifluoroacetyl, 40 m×0.25 mm i.d.; CHI-
RALDEX B-DM, beta cyclodextrin, 20 m×0.32 mm
i.d. (Alltech)).
The new catalysts (2–4, 6, 8) afford highly valuable
terminal epoxides in enantiomerically pure form for
HKR of ( )-ECH as well as 1,2-epoxibutane, 1,2-
epoxyhexane and styrene oxide. The identity of the
counter ions in the catalysts was revealed to be a
critical parameter for attainment of high enantioselec-
tivity and fast reaction rates. The high asymmetry-
inducing ability of the salen complexes in this work is
attributed to the intense interaction of the substituent
of salen ligands near the cobalt metal center with
incoming substrates. The racemates of epichlorohydrine
and epoxy styrene were enantioselectively hydrolyzed in
a high yield and ee% over the chiral Co(III) salen
catalysts containing the more electronegative fluoride
ions at room temperature with or without addition of
organic solvents, respectively.
rocenium
hexafluorophosphate
or
ferrocenium
tetrafluoroborate in acetonitrile under air, respectively.
The mixtures were concentrated to dryness and washed
with hexane to remove the side product, ferrocene.
These catalysts will be denoted as Co(III)ꢀ(PF6) and
Co(III)ꢀ(BF4). The other catalysts (5–7) bearing a
fluoride compound were readily prepared from (R,R)-
(−)-N,N%-bis(3,5-di-tert-butylsalicylidene)-1,2-cyclo hex-
anediamino cobalt(II) and corresponding silver salts
such as AgCH3C6H4SO3, AgCF3SO3, AgSbF6. In this
case, the reaction flask was wrapped with aluminum
foil and stirred for 8 h at room temperature. We have
also synthesized bromo-(salen)Co(III) (8) and iodo-
(salen) Co(III) (9) complexes by treatment of bromine
and iodine with chiral Co(II) salen, respectively, and
they were used as catalysts in the HKR of ( )-
epichlorohydrine to evaluate catalytic activities.
Especially, Co(III)ꢀ(PF6) and ꢀ(BF4) salen complexes
(3, 4) showed the superior catalytic activities to those
obtained by the conventional chiral (salen)Co(III)ꢀ
(OAc) catalyst (1). As shown in Table 1, Co(III)ꢀ
(PF6) and ꢀ(BF4) salen catalysts (3, 4) displayed
not only significantly high enantioselectivities but
also improved activities. The maximum reactivity
The general procedure for the HKR of epoxides follows
the method as shown in the reported papers.3 The ee%
values were determined by capillary GC using chiral
Table 1. Enantioselective hydrolysis of terminal epoxides to diols on the various chiral Co(III) salen catalysts
Entry
R
Catalyst
Time (h)b
Yield of epoxide ee% of epoxideb Yield of diol
ee% of diolb
k×103 (M−1
S−1 a
(%)
(%)
)
1
2
3
4
5
6
7
8
CH2Cl
CH2CH3
Ph
(CH2)3CH3
CH2Cl
CH2Cl
CH2CH3
Ph
(CH2)3CH3
CH2Cl
CH2CH3
(CH2)3CH3
CH2Cl
CH2Cl
CH2Cl
CH2CH3
CH2Cl
CH2Cl
CH2CH3
(CH2)3CH3
CH2Cl
1
1
1
1
2
3
3
3
3
4
4
4
5
6
6
6
7
8
8
8
9
6
5
40
5
10
5
3
30
5
6
3
5
52
4
18
3
48
6
5
43
45
40
46
42
43
46
41
46
44
42
45
40
45
40
46
43
41
44
45
42
98
98
97
98
98
99
99
98
99
99
98
98
92
83
97
99
76
99
99
98
98
45
47
41
48
46
44
47
45
47
46
48
47
43
38
42
45
34
46
48
48
45
96
98
96
98
97
98
99
96
98
98
98
98
98
98
95
98
98
97
99
97
97
8.1
22.8
2.6
20.4
6.2
10.3
31.6
3.3
29.9
8.8
30.5
26.1
1.3
8.3
–
9
10
11
12
13
14
15
16
17
18
19
20
21
24.3
1.0
7.9
24.0
20.9
4.8
6
10
a Reaction rate constants were obtained from the plots of ln([epoxide]/[epoxide]0) versus time and calculated by dividing the slopes by the absolute
concentration of catalysts. Experimental procedure for the kinetic study was same as described in Ref. 13.
b The ee values were determined at the indicated reaction time.

G.-J. Kim et al. / Tetrahedron Letters 44 (2003) 5005–5008
5007
was attained with catalyst 3. Kinetic studies of the
HKR of ( )-ECH revealed that the catalyst 3 was more
reactive than the conventional catalyst 1 as shown in
Table 1. The use of chiral salen catalyst 5 gave a
disadvantage in reaction rates. But enantiomeric excess
reached 92%, when the reaction time has prolonged up
to 52 h using the catalyst 5.
reaction time has prolonged to obtain the highest ee%
as the number of recycling was increased.
The important feature in the HKR of ECH using
Co(III)ꢀ(PF6) or ꢀ(BF4) salen catalyst is that no racem-
ization is found not only during the distillation, but
also after attaining to the highest ee% value of epoxide.
The enantioselectivity of ECH on Co(III)ꢀ(PF6) cata-
lyst has not changed more or less until 48 h, showing
up to 99% ee. In contrast, racemization of ECH was
observed to take place with Co(III)ꢀ(OAc) catalyst (1)
as well as bromo- and iodo-salen catalysts (8, 9) during
the reaction and product distillation as can be seen in
Figure 2. The ee% of product epoxide slowly decreased
via racemization over these –(OAc), –(Br) and –(I)
containing chiral salen complexes.
Recycling abilities of some catalysts have been investi-
gated in HKR of ( )-ECH. Figure 1 shows that a series
of epichlorohydrine HKR in which the chiral
Co(III)ꢀ(PF6) complex (3) could be reused for ten times
after simple distillation of products. The salen
Co(III)ꢀ(BF4) type catalyst (4) can also be recycled
more than five times. It is noteworthy that the salen
Co(III)ꢀ(PF6) catalyst (3) could be recycled without
observable loss in activity and it was reused for further
catalytic reactions. Use of Co(III)ꢀ(PF6) and ꢀ(BF4)
type salen catalysts avoided the necessity of further
treatment after separation of products. Whereas, as can
be seen in Figure 1b, the salen Co(III)ꢀ(OAc) catalysts
(1) must be regenerated with acetic acid in air after
evaporation of products to enable their repeated use in
HKR of ECH. The enantiomeric excess became
reduced to 17% by using the conventional (Co-salen)–
OAc catalyst in the second hydrolysis reaction, if not
regenerated by HOAc in air. This is due to the reduc-
tion of Co(III) to Co(II). The Co(III)ꢀ(PF6) complex
(3) exhibited the same enantioselectivity up to 99% ee
through the repeated use for six times in HKR, but
Figure 3 shows the catalytic activities and recyclabilities
of catalyst 1 and 3 in the asymmetric resolution of
1,2-epoxybutane. In the HKR of 1,2-epoxybutane, 1,2-
epoxyhexane and styrene oxide, racemization was not
Figure 2. Racemization of (S)-ECH on the catalysts 1, 8 and
9 with prolonged reaction time. 0.4 mol% catalyst, reaction at
rt.
Figure 1. The catalytic activities and recyclabilities of Co(III)
salen complex 1 and 3 in the asymmetric HKR of ( )-ECH.
0.4 mol% catalyst, reaction at rt.
Figure 3. The catalytic activities and recyclabilities of Co(III)
salen complexes 1 and 3 in the asymmetric HKR of ( )-1,2-
epoxybutane. 0.4 mol% catalyst, reaction at rt.

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G.-J. Kim et al. / Tetrahedron Letters 44 (2003) 5005–5008
observed on the catalyst (1–9), showing the constant
enantioselectivity (up to 99% ee) with the prolonged
reaction time. In contrast to the slow HKR rate of
styrene oxide, 1,2-epoxybutane was found to undergo
hydrolytic resolution rapidly. The catalysts 3 and 4
could be reused with no loss of activity or enantioselec-
tivity after separation of products for the HKR of
above reactants.
In conclusion, the new chiral (salen) Co(III) complexes
could be synthesized and these salen catalysts showed
to be effective in asymmetric hydrolytic resolution of
epoxides with promising enantioselectivities. The cata-
lysts could be recovered and reused several times with-
out further treatment after reaction, showing no loss of
activity and enantioselectivity. On the basis of asym-
metric HKR of various epoxides, the chiral (salen)
complexes obtained by the present procedure can be
applied as an effective recyclable catalyst for the asym-
metric HKR reactions.
The HKR of ECH was investigated using the Co(III)-
(PF6) catalyst at different substrate/catalyst mole ratios
and the results are summarized in Figure 4. The conver-
sion and the ee% of epoxide increased as the substrate/
catalyst ratio decreased at the same reaction time.
When the substrate-to-catalyst ratio is so high, the
efforts to recycle the chiral catalysts become superflu-
ous. The reaction with catalyst 3 at the 0.2 mol% level
led to 99% ee for epoxide after 8 h. It is, however,
noteworthy that the catalysts 3 and 4 showed almost
the same enantioselectivity (up to 99% ee) in the case of
very high substrate/catalyst mole ratio (2.5×106), even
though the prolonged reaction time up to 40 h was
needed.
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