Highly enantioselective resolution of terminal epoxides using polymeric catalysts

Article abstract of DOI:10.1016/S0040-4039(02)01446-6

Poly-salen-Co(III) complexes were employed in the hydrolytic kinetic resolution (HKR) of terminal epoxides and ee's up to 98% were obtained. In the HKR of epichlorohydrin, the polymeric catalysts can be recovered and modified for recycling. The recovered

Full text of DOI:10.1016/S0040-4039(02)01446-6

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 6625–6627
Highly enantioselective resolution of terminal epoxides using
polymeric catalysts
Yuming Song, Xiaoquan Yao, Huilin Chen, Changmin Bai, Xinquan Hu and Zhuo Zheng*
Dalian Institute of Chemical Physics, The Chinese Academy of Sciences, Dalian 116023, PR China
Received 7 May 2002; revised 3 July 2002; accepted 12 July 2002
Abstract—Poly-salen-Co(III) complexes were employed in the hydrolytic kinetic resolution (HKR) of terminal epoxides and ee’s
up to 98% were obtained. In the HKR of epichlorohydrin, the polymeric catalysts can be recovered and modified for recycling.
The recovered polymer catalyst shows good activity and selectivity. © 2002 Elsevier Science Ltd. All rights reserved.
As the most powerful chiral catalyst for the hydrolytic
kinetic resolution (HKR) of terminal epoxides to
provide both optically active epoxides and diols, the
Jacobsen’s Salen-Co(III) complex (Fig. 1) has been
used in the synthesis of libraries of important chiral
intermediates.1–7 The properties of the catalyst
employed in the reaction have also been carefully stud-
ied and (a) the typical salen-Co(III) complex has
proved to exhibit excellent efficiency in the HKR of
terminal epoxides and to show good stability, and (b)
the mechanism of the reaction has proved to involve
cooperative bimetallic catalysis.8,9 Because of these fea-
tures, Jacobsen’s and other groups have developed
dimeric,10,11 oligomeric,12,13 polymeric,14,15 dendrimeric
framework16 and inorganic-supported catalysts17 in
order to make the HKR of terminal epoxides more
practical.
In our previous reports, chiral poly-salen-Mn(III) com-
plexes were employed for the catalysis of asymmetric
epoxidation of unfunctionalized olefins and similar
results to those olefins using the typical Jacobsen’s
catalyst were obtained. However, the polymeric cata-
lysts partly decomposed during the experimental pro-
cesses.18,19 As a continuation of our research in
developing highly efficient polymeric catalysts for
asymmetric transformations, we report herein the HKR
of terminal epoxides (Eq. (1)) using two of the above-
mentioned salen ligand cobalt complexes (Scheme 1) as
catalysts. Both of the catalysts show good activities and
enantioselectivities for the reaction; moreover, the -NH2
groups, which exist at both ends of the polymeric
catalyst molecules, can easily be modified in the HKR
of epichlorohydrin making the catalysts water soluble.
Figure 1. Jacobsen’s catalyst.
Scheme 1. The polymeric catalysts.
* Corresponding author.
0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)01446-6

6626
Y. Song et al. / Tetrahedron Letters 43 (2002) 6625–6627
OH
O
O
Cat.
(1)
(
)
H2O
+
+
OH
R
R
Solvent
R
There are two methods for preparing the polymeric
catalysts (the syntheses of the polymeric ligands has
been reported in our previous work).18,19 (a) The cobalt
atoms can be inserted into the polymeric ligands to
obtain the polymeric catalysts according to the litera-
ture.14 (b) The polymeric catalyst can be obtained using
the reported Co(II) to Co(III) procedure.20 However
method (a) is much more suitable, because the catalysts
are soluble in methanol/toluene solution during their
preparation, thus the cobalt atoms can easily approach
the center of the ligand.
lectivities were obtained. These results are in agreement
with those obtained in the epoxidation reaction.18,19
In the HKR of epichlorohydrin, we observed an
unusual phenomenon that was completely different
from the HKR of propylene oxide.21 Under our reac-
tion conditions, with or without solvent, the reaction
mixture became a single phase during the reaction. It is
more interesting that the black polymeric catalysts can
be easily dissolved in the aqueous phase but not in the
organic phase. Therefore, the polymeric catalysts could
be isolated easily from the reaction mixture by the
following procedure. The unreacted epoxide is distilled
off from the reaction mixture, diethyl ether is added to
the residue and the catalyst can be precipitated and
collected via filtration. This recovered catalyst 1 could
be activated following the modified Jacobsen’s
procedure20 before reusing. When the activated recov-
ered catalyst 1 was used for the HKR of propylene
oxide, excellent activity and enantioselectivity were
obtained (entry 17 versus entry 1). In the HKR of
phenyl glycidyl ether in CH2Cl2 or THF, the recovered
catalyst 1 shows poor activity (entries 18 and 19),
The kinetic resolution of terminal epoxides was carried
out by stirring the epoxide in the presence of 0.5 mol%
catalyst (based on the catalytic unit), solvent and 0.55
equiv. of water at the indicated temperature. The
results are summarized in Table 1.
As shown in Table 1, catalyst 1 shows excellent results
for all three substrates and the ee’s are 98, 97 and 98%
for propylene oxide, epichlorohydrin and phenyl gly-
cidyl ether, respectively (Table 1, entries 2, 5, and 8).
When catalyst 2 is employed, slightly lower enantiose-
Table 1. HKR of epoxides catalyzed by polymeric catalystsa
Entry
R
Cat.
Solvent
Temp. (oC)
Time (h)
Conv. (%)b
Ee (%)c,d
Conf.e
1
2
3
4
5
6
7
8
CH3
CH3
CH3
CH2Cl
CH2Cl
CH2Cl
PhOCH2
PhOCH2
CH3
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
None
THF
CH2Cl2
None
THF
CH2Cl2
THF
CH2Cl2
None
THF
CH2Cl2
None
THF
CH2Cl2
THF
CH2Cl2
None
THF
CH2Cl2
H2O
rt
rt
rt
10
10
10
rt
rt
rt
rt
rt
10
10
10
rt
rt
rt
rt
rt
48
48
48
12
12
12
24
24
48
48
48
12
12
12
24
24
48
48
48
30
24
41
48
49
47
49
NDf/97
NDf/98
NDf/95
90/92
97/94
91/94
R
R
R
S/R
S/R
S/R
S/R
S/R
R
48
\47
\49
51
49
49
46
49
47
\49
\49
48
17
31
94/89
98/87
9
NDf/93
NDf/97
NDf/95
95/84
10
11
12
13
14
15
16
17
18
19
20
21
CH3
CH3
R
R
CH2Cl
CH2Cl
CH2Cl
PhOCH2
PhOCH2
CH3
PhOCH2
PhOCH2
PhOCH2
PhOCH2
S/R
S/R
S/R
S/R
S/R
R
S/R
S/R
S/R
S/R
97/91
97/83
97/76
98/80
Recovered 1
Recovered 1
Recovered 1
Recovered 1
1
NDf/98
21/94
45/95
95/78
95/57
rt
rt
\48
\48
H2O
a The reactions were carried using 10 mmol of epoxide, 0.5 mol% of catalyst (based on catalytic unit) and 0.55 equiv. of water at the indicated
temperature.
b The conversion of the epoxide is based on the racemic epoxide added and the conversion of phenyl glycidyl ether is calculated according to the
ee of the epoxide.
c The ee’s of 1,2-propane diol and chloropropane diol were determined by GC analysis of the corresponding acetal using a chiral capillary column
(cyclodex-b, 2,3,6-methylated, 30 m×0.25 mm (i.d.)); the ee’s of epichlorohydrin were determined by GC analysis using a chiral capillary column
(Gamma-225 30 m×0.25 mm (i.d.)); the ee’s of phenyl glycidyl ether and 1-phenyl glycerol were determined by HPLC using a chiral OD column
(90/10 hexanes/i-PrOH, 1 ml/min, 254 nm).
d The ee of epoxide/the ee of diol.
e Absolute configurations (epoxide/diol) were compared with the literature.7
f ND, not determined.

Y. Song et al. / Tetrahedron Letters 43 (2002) 6625–6627
1041.
6627
however, when water was used as both solvent and
resolution reagent, very good activity and enantioselec-
tivity were demonstrated (entry 20). It is worthwhile to
note that the ee’s of diols obtained by using the recov-
ered catalyst 1 are better than those using the fresh
catalyst 1 (entries 20 and 21). We suppose that the
recovered catalyst 1 may be modified by the presence of
hydrophilic groups at both ends of the polymer chain
during the HKR of epichlorohydrin. Because an exces-
sive amount of (R,R)-1,2-diaminocyclohexane is used
for the synthesis of the polymeric ligand, two free -NH2
might exist at both ends of the polymer ligand. When
epichlorohydrin is employed as substrate, part of the
epoxide reacts not only with H2O, but also with these
terminal -NH2 groups, thus resulting in the water-solu-
ble catalyst.
5. Rodriguez, A.; Nomen, M.; Spur, B. W.; Godfroid, J. J.;
Lee, T. H. Tetrahedron 2001, 57, 25–37.
6. Gu, J.; Dirr, M. J.; Wang, Y.; Scoper, D. L.; De, B.;
Wos, J. A.; Johnson, C. R. Org. Lett. 2001, 3, 791–794.
7. Schaus, S. E.; Brandes, B. D.; Larrow, J. F.; Tokunaga,
M.; Hansen, K. B.; Gould, A. E.; Furrow, M. E.; Jacob-
sen, E. N. J. Am. Chem. Soc. 2002, 124, 1307–1315.
8. Jacobsen, E. N.; Wu, M. H. In Comprehensive Asymmet-
ric Catalysis; Jacobsen, E. N.; Pfaltz, A.; Yamamoto, H.,
Eds.; Springer: New York, 1999; pp. 1309–1326.
9. Jacobsen, E. N. Acc. Chem. Res. 2000, 33, 421–431.
10. Konsler, R. G.; Karl, J.; Jacobsen, E. N. J. Am. Chem.
Soc. 1998, 120, 10780–10781.
11. Kureshy, R. I.; Khan, N. H.; Abdi, S. H. R.; Patel, S. T.;
Jasra, R. V. J. Mol. Chem. A: Chem. 2002, 179, 1–2 and
73–77.
In summary, the kinetic resolution of terminal epoxides
proceeds smoothly with poly-salen-Co(III) complexes
to give excellent chemical yields and high ee’s. It was
found that the terminal groups of these polymeric
catalysts can be modified to hydrophilic groups during
the HKR of epichlorohydrin and the modified catalysts
may promote the reaction with better enantioselectivi-
ties and provide a much easier isolation procedure.
12. Joseph, M. R.; Jacobsen, E. N. J. Am. Chem. Soc. 2001,
123, 2687–2688.
13. Joseph, M. R.; Jacobsen, E. N. Angew. Chem., Int. Ed.
2002, 41, 1374–1377.
14. Annis, D. A.; Jacobsen, E. N. J. Am. Chem. Soc. 1999,
121, 4147–4154.
15. Osburn, P. L.; Bergbreiter, D. E. Prog. Polym. Sci. 2001,
26, 2015–2081.
16. Breinbauer, R.; Jacobsen, E. N. Angew. Chem., Int. Ed.
2000, 39, 3604–3607.
17. Kim, G.-J.; Park, D.-W. Catal. Today 2000, 63, 537–547.
18. Yao, X.; Chen, H.; Lu¨, W.; Pan, G.; Hu, X.; Zheng, Z.
Tetrahedron Lett. 2000, 41, 10267.
19. Song, Y.; Yao, X.; Chen, H.; Pan, G.; Hu, X.; Zheng, Z.
J. Chem. Soc., Perkin. Trans. 1 2002, 870–873.
20. Tokunaga, M.; Larrow, J. F.; Kakiuchi, F.; Jacobsen, E.
N. Science 1997, 277, 936–938 (activation of the recov-
Acknowledgements
This work was supported by the National Natural
Science Foundation of China (29933050).
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