Highly enantioselective resolution of terminal epoxides with cross-linked polymeric salen-Co(III) complexes

Article abstract of DOI:10.1016/S0040-4039(03)01786-6

Crosslinked polymeric salen-Co(III) complexes derived from a novel dialdehyde and a trialdehyde were synthesized and employed in the hydrolytic kinetic resolution (HKR) of terminal epoxides. Up to 99% ee were obtained with only 0.16-0.02 mol% of catalyst (based on catalytic unit).

Full text of DOI:10.1016/S0040-4039(03)01786-6

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 7081–7085
Highly enantioselective resolution of terminal epoxides with
cross-linked polymeric salen–Co(III) complexes
Yuming Song, Huilin Chen, Xinquan Hu, Changmin Bai and Zhuo Zheng*
Dalian Institute of Chemical Physics, The Chinese Academy of Sciences, Dalian, 116023, PR China
Received 27 May 2003; revised 10 July 2003; accepted 14 July 2003
Abstract—Crosslinked polymeric salen–Co(III) complexes derived from a novel dialdehyde and a trialdehyde were synthesized and
employed in the hydrolytic kinetic resolution (HKR) of terminal epoxides. Up to 99% ee were obtained with only 0.16–0.02 mol%
of catalyst (based on catalytic unit).
©
2003 Elsevier Ltd. All rights reserved.
1
8
In the past decades, thousands of homogeneous chiral
catalysts have been successfully developed, which exhib-
ited high enantioselectivities and activities. However,
separation and recovery of these expensive chiral cata-
lysts are still non-trivial for industrial uses. To solve
these problems, many heterogenized methods have been
developed and the results with those heterogeneous
catalysts have obtained much progress in recent years.
It is noteworthy that some of them are even better than
liquid
for both academic and practical reasons.
Among those reports mentioned above, Jacobsen’s
oligomeric catalysts (Fig. 2) exhibits exciting results, in
which both the linkage length between metal centers
and the counterions were carefully tuned to achieve an
activity 100 times higher than that of the typical salen–
Co(III) complex (Fig. 1) for the HKR of terminal
epoxides. In this reaction, the cooperative effect has
proven to be partly responsible for excellent results
obtained with those oligomeric catalysts. Moreover, the
same catalytic system could be extended to alcohols
and phenols as nucleophiles for asymmetric ring-open-
ing of terminal epoxides, while the typical salen catalyst
(Fig. 1) has failed in this case.
1
,2
their homogeneous parent catalysts. Typical salen–
Co(III) complex, (Fig. 1) one of the most important
chiral catalysts, shows excellent activities and enantiose-
lectivities for the asymmetric hydrolytic kinetic resolu-
tion (HKR) of various terminal epoxides. The
mechanism of the reaction has proven to involve coop-
3
–9
erative bimetallic catalysis.
Many groups have
On the basis of our research in developing polymeric
chiral catalysts for asymmetric catalysis
1
9–21
devoted their efforts to developing heterogeneous
analogs of the typical salen–Co(III) catalyst including
and
inspired by Jacobsen’s work, we herein reported some
novel salen–Co(III) complexes derived from an easily
prepared dialdehyde and/or a trialdehyde with (R,R)-
1,2-diaminocyclohexane for the asymmetric HKR of
terminal epoxides. (Eq. (1)) We envisioned that the
cooperative effect in the oligomeric catalysts can also
be introduced to these new crosslinked polymeric chiral
salen–Co(III) complexes by carefully tuning the unit
structures. Furthermore, crosslinked polymeric chiral
frameworks with different pore sizes could be con-
structed by using the trialdehyde and the dialdehyde in
different proportions. It is foreseeable that excellent
activities and enantioselectivities can be achieved with
these kinds of crosslinked polymeric catalysts for the
HKR of terminal epoxides.
1
0–12
organic or inorganic supported catalysts,
dimeric
catalysts, dendrimeric catalysts, oligomeric cata-
1
3
14
1
5,16
17
lysts,
FBS (Fluorous Biphase Systems) and ionic
Figure 1. Jacobsen’s catalyst.
The 3-tert-butyl-2,5-dihydroxybenzaldehyde 4 was pre-
pared according to the literature with a slight modifica-
*
0
Corresponding author.
040-4039/$ - see front matter © 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/S0040-4039(03)01786-6

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082
Y. Song et al. / Tetrahedron Letters 44 (2003) 7081–7085
Figure 2. Jacobsen’s oligomeric catalysts.
tion, the protective benzyl group was removed conve-
bigger than 25/100, most of the catalysts displayed poor
solubility and the catalysts were collected through
filtration and washing with CH Cl and CH OH
22
niently in a HCl/HOAc system. (Scheme 1) The key
dialdehyde 9 and trialdehyde 10 were synthesized
through the condensation of 3-tert-butyl-2,5-dihydroxy-
benzaldehyde with diacid and triacid derived from
hydroquinone and chloroglucinol (Scheme 2). The con-
densation of aldehyde and (R,R)-1,2-diaminocyclohex-
ane stoichiometrically afforded the polymeric ligands.
When only dialdehyde was employed, we obtained an
oligomeric ligand. On the other hand, when different
proportions of trialdehyde were mixed with the dialde-
hyde, the crosslinked polymeric ligand was obtained. In
most cases, the polymeric ligands have an average
molecular weight between only 4000 and 10000 (GPC).
However, the complete crosslinked polymer ligand
derived from trialdehyde and (R,R)-1,2-diaminocyclo-
hexane exhibited as a gel polymer that was partially
soluble in THF. Because of the ester groups in the
polymer, other condensation conditions for synthesiz-
ing polymeric ligands with higher molecular weight
were not evaluated. The polymeric catalysts were syn-
thesized by simply mixing the chiral ligand,
Co(OAc) ·4H O and 2,6-lutidinium p-toluenesulfonate
2
2
3
23
continuously.
The HKR of terminal epoxides with the above-men-
tioned catalysts were performed following the typical
15,24
procedure reported in the literature (Eq. (1)).
and
the results are listed in Table 1. As shown in Table 1,
all catalysts showed excellent activities and enantiose-
lectivities for epichlorohydrin, styrene oxide and phenyl
glycidyl ether. In a wide range of tri/di proportions, the
crosslinked polymeric catalysts gave almost identical
results. (entries 1–8) When the reaction was performed
at lower temperature, a little longer time was needed
and the enantioselectivities were the same (entries 9–
1
2). Most of the crosslinked polymer catalysts showed
better activities than those of the oligomeric one (tri/
di=0/100), which means the crosslinker we employed
have some positive effects on the cooperation between
metal centers (entries 1, 13, 17) The complete
crosslinked polymeric catalyst showed slightly lower
activities and enantioselectivities in the HKR of three
substrates (entries 8, 12, 16, 20) we think that the poor
solubility and some unknown reactive centers of the
crosslinked polymeric catalyst ought to be responsible
for this result. Using the recollected catalysts for
another reaction has not been successful even with the
2
2
(
LTPS) in toluene and methanol (3/1) with stirring in
the air for 2 h (Scheme 3). When the proportion of
trialdehyde/dialdehyde (tri/di) was lower than 20/100,
most of the catalysts showed good solubility in CH Cl ,
2
2
and literature workup process to purify the catalysts
1
5
were employed. However, when that proportion was
Scheme 1. Synthesis of 3-tert-butyl-2,5-dihydroxy benzaldehyde.

Y. Song et al. / Tetrahedron Letters 44 (2003) 7081–7085
7083
Scheme 2. Synthesis of the dialdehyde and the trialdehyde.
Scheme 3. Synthesis of the polymeric catalysts.

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084
Y. Song et al. / Tetrahedron Letters 44 (2003) 7081–7085
a
Table 1. HKR of epoxides catalyst by crosslinked polymer catalysts
Eeb (ep)
Ee (diol)
c
Conv.d,e
Entry
R
Tri/Di
Cat.
Time (h)
Temp. (°C)
1
2
3
4
5
6
7
8
9
CH Cl
0/100
2/100
6/100
10/100
14/100
25/100
50/100
100/0
0.02%
0.02%
0.02%
0.02%
0.02%
0.02%
0.02%
0.02%
0.02%
0.02%
0.02%
0.02%
0.16%
0.16%
0.16%
0.16%
0.02%
0.02%
0.02%
0.02%
14
8
11
11
11
8
12
12
12
12
12
12
12
12
2
98%
99%
99%
99%
98%
98%
99%
>99%
97%
97%
98%
93%
98%
97%
97%
95%
96%
97%
97%
85%
97%
96%
96%
95%
96%
95%
91%
86%
97%
95%
94%
91%
89%
91%
94%
92%
88%
92%
87%
84%
50%
51%
51%
51%
50%
50%
52%
53%
50%
51%
51%
47%
52%
52%
51%
48%
48%
51%
53%
43%
2
CH Cl
2
CH Cl
2
CH Cl
2
CH Cl
2
CH Cl
2
CH Cl
8
2
CH Cl
22
27
16
16
27
14
14
21
21
15
15
15
15
2
CH Cl
0/100
2
10
11
12
13
14
15
16
17
18
19
20
CH Cl
25/100
50/100
100/0
0/100
2/100
50/100
100/0
0/100
2/100
50/100
100/0
2
2
2
2
CH Cl
2
CH Cl
2
Ph
Ph
Ph
Ph
20
20
20
20
20
20
20
20
CH OPh
2
CH OPh
2
CH OPh
2
CH OPh
2
a
The reactions were carried out on 28 mmol of epoxide, catalyst (based on catalytic unit) and 0.60 equiv. of water.
b
The ee’s of the epichlorohydrin and phenyl glycidyl ether were determined by GC analysis using a chiral capillary column (Gamma-225 30
m×0.25 mm (i.d.)); the ee of styrene oxide was determined by GC analysis using a chiral capillary column (cyclodex-b, 2,3,6-methylated, 30
m×0.25 mm (i.d.)).
c
The ee’s of the diols were determined by GC analysis of the corresponding acetals using a chiral capillary column (cyclodex-b, 2,3,6-methylated,
3
0 m×0.25 mm (i.d.)).
d
e
Based on total racemic mixture.
Estimated according to the ee’s of the epoxides and diols, see Ref. 10.
complete crosslinked polymeric catalyst. We ascribe
this to the fact that the oxygen adjacent to the carbonyl
groups makes the ester linkages more sensitive to the
reaction systems. The IR spectra showed the cleavage
of the ester bonds in the recollected catalyst. A similar
effect caused by chlorine substitutes has been reported
ric Catalysis; Jacobsen, E. N.; Pfaltz, A.; Yamamoto, H.,
Eds.; Springer-Verlag: Berlin, 1999; pp. 1309–1326.
4. Li, L. S.; Wu, Y. L. Chin. J. Org. Chem. 2000, 5, 689–700
and references cited therein.
5. Jacobsen, E. N. Acc. Chem. Res. 2000, 33, 421–431.
6. 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.
7. Xu, Y.; Prestwich, G. D. Org. Lett. 2002, 4, 4021–4024.
8. Chow, S.; Kitching, W. Tetrahedron: Asymmetry 2002,
13, 779–793.
9. Lochynski, S.; Frackowiak, B.; Librowski, T.; Czarnecki,
R.; Grochowski, J.; Serda, P.; Pasenkiewicz-Gierula, M.
Tetrahedron: Asymmetry 2002, 13, 873–878.
10. Annis, D. A.; Jacobsen, E. N. J. Am. Chem. Soc. 1999,
121, 4147–4154.
1
6
in literature.
In conclusion, crosslinked polymeric salen–Co(III)
complexes were prepared with a novel dialdehyde and a
trialdehyde. Excellent activities and enantioselectivities
were achieved using these catalysts. The cooperative
effects observed in Jacobsen’s oligomeric catalysts have
been successfully introduced into our crosslinked cata-
lysts. The crosslinked catalysts exhibited slightly higher
activity without obvious lose of enantioselectivities.
11. Osburn, P. L.; Bergbreiter, D. E. Progress in Polymer
Science 2001, 26, 2015–2081.
Acknowledgements
12. Kim, G.-J.; Park, D.-W. Catal. Today. 2000, 63, 537–547.
13. Kureshy, R. I.; Khan, N. H.; Abdi, S. H. R.; Patel, S. T.;
Jasra, R. V. J. Mol. Chem. A: Chemical. 2002, 179, 73–77.
This work was supported by the National Natural
Science Foundation of China (29933050).
14. Breinbauer, R.; Jacobsen, E. N. Angew. Chem., Int. Ed.
2000, 39, 3604–3607.
1
5. Joseph, M. R.; Jacobsen, E. N. J. Am. Chem. Soc. 2001,
23, 2687–2688.
16. Ready, J. M.; Jacobsen, E. N. Angew. Chem., Int. Ed.
002, 41, 1374–1377.
1
References
2
1
. Fan, Q.-H.; Li, Y.-M.; Chan, A. S. C. Chem. Rev. 2002,
17. Cavazzini, M.; Quici, S.; Pozzi, G. Tetrahedron 2002, 58,
3943–3949.
1
02, 3385–3466.
2
3
. Song, C. E.; Lee, S.-G. Chem. Rev. 2002, 102, 3495–3524.
. Jacobsen, E. N.; Wu, M. H. In Comprehensive Asymmet-
18. Oh, C. R.; Choo, D. J.; Shim, W. O.; Lee, D. H.; Roh, E.
J.; Lee, S.; Song, C. E. Chem. Commun. 2003, 1100–1101.

Y. Song et al. / Tetrahedron Letters 44 (2003) 7081–7085
7085
1
2
2
2
9. Yao, X.; Chen, H.; L u¨ , W.; Pan, G.; Hu, X.; Zheng, Z.
Tetrahedron Lett. 2000, 41, 10267.
0. Song, Y.; Yao, X.; Chen, H.; Pan, G.; Hu, X.; Zheng, Z.
J. Chem. Soc., Perkin Trans. 1 2002, 870–873.
1. Song, Y.; Yao, X.; Chen, H.; Bai, C.; Hu, X.; Zheng, Z.
Tetrahedron Lett. 2002, 43, 6625–6627.
dried in vacuo to afford the crosslinked polymeric cata-
lyst.
24. The representative procedure of asymmetric hydrolysis. A
mixture of polymeric catalyst (0.02 mol% based on cata-
lytic unit), LTPS 1.6 mg (0.04%), epichlorohydrin (28
mmol) and 0.1 mL of CH Cl /CH CN (1/1) was stirred at
2
2
3
2. De, B. B.; Lohray, B. B.; Sivaram, S.; Dhal, P. K. J.
ambient temperature for 30 min, 0.3 mL of H O (0.6
2
Polym. Sci. Part A: Polym. Chem. Ed. 1997, 35, 1809–
equiv.) was added in one portion. The reaction mixture
was stirred for 8–27 h, and the ee% values were deter-
mined by capillary GC. For the HKR of styrene oxide or
phenyl glycidyl ether, more solvents are needed to dis-
solve the diols. Obviously the longer the reaction pro-
ceeded, the better the ee’s of the epoxides. We could
obtain up to 99% ee for all the substrates. The reported
data in Table 1 keeps a balance between the ee’s of
epoxides and diols. The absolute configurations of the
obtained epoxides and diols showed in Eq. (1) are com-
1
818.
2
3. The general procedure for the synthesis of insoluble
crosslinked catalysts: 0.15 mmol of chiral ligand, 0.3
mmol of Co(OA) ·4H O, 0.3 mmol of 2,6-lutidinium
2
2
p-toluenesulfonate (LTPS) and 3 mL of toluene and
methanol (3/1) were added into a 25 mL round-bottomed
flask with a magnetic stirring bar, the mixture was stirred
in air at room temperature for 2 h, the solid was filtered
and washed with CH Cl2 (10 mL×3) and CH OH (10
2
3
15
mL×3) consecutively, the black solid was collected and
pared with the literature.
(1)