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					Theories and Application of Chem. Eng., 2002, Vol. 8, No 1

                    키랄살렌계 촉매를 이용한 고순도 광학활성 화합물의 합성

                                              김건중, 김성진*
                                 인하대학교 화학공학과, R.S Tech(주)*

          The syntheses of optically active Compounds by using various chiral salen complexes

                               Geon-Joong Kim and Seong-Jin Kim*
             Department of Chemical Engineering, Inha University, Incheon 402-751, Korea.
               Venture town #306, Sinil-dong 1688-5, Daedeok, Daejon 306-230, Korea*

  Compounds that occur in nature are optically active because living organisms tend to produce only a
single enantiomer of a given molecule. The asymmetry of these molecules arises from the inherent
chirality of the enzymes that are responsible for their production. Chiral compounds are extensively
used for various ways such as medicine, food additives, a netural substance, agricultural medicines
and an insecticide[1-4].      Whenever a compound is introduced into the body, as either a food
additive or a drug, the question of toxicity always arises. With molecules possessing one or more
asymmetric centers, adverse toxicologic properties can sometimes be attributed to one enantiomer and
not the other. For preparation of enantiomerically homogeneous molecules, the chemist basically
has two options. The molecules can be synthesized in racemic form and resolved into their optical
antipodes, or the synthesis can be performed in an enantiospecific fashion so as to produce chirally
enriched products. In this study, various chiral salen ligands were synthesized and the catalytic
activities were investigated for the asymmetric synthesis of chiral compounds.

  The chiral salen complexes were synthesized and immobilized onto the MCM-41 by a multi-grafting
method and side grafting method according to the procedure as reported[5]. In addition, the
homogeneous symmetrical and unsymmetrical chiral salen complexes were synthesized to evaluate
and to compare the enantioselectivity in the asymmetric epoxidation reaction respectively. The
polymeric salen ligand was synthesized by using dimeric dialdehyde derivative as a starting material,
which was reported by Jacobs et al.[6].
  The general procedure for the asymmetric epoxidation and asymmetric hydrolysis followed the
method reported in the literature[5,7]. The ee% values were determined by capillary GC using a
chiral column (CHORALDEXTM, Gamma-cyclodextrin trifluoroacetyl, 40m×0.25mm i.d.(Astec))
and by Vibrational Circular Dichroism spectroscopy (Chiral ir, Bomem).

  1. The Asymmetric Epoxidation of Olefins
  The enantioselective catalytic activities of the (salen) Mn(Ⅲ) chloride complex immobilized on
MCM-41 and the homogeneous complex of same structure in solution were examined for the
epoxidation of styrene. Epoxidation reaction using a combined solution of m-CPBA/NMO was rapid
even at -78℃. The enantiosectivity was found to increase significantly at the low temperature. A high
ee% value was obtained particularly over more hindered catalyst. Especially, the reaction using
heterogenized Mn salen catalysts gave a slightly improved selectivity as compared with homogeneous
salen catalysts. Furthermore, higher turnover number could be obtained over this unsymmetrical salen
catalyst than over symmetrical salen complexes.

화학공학의 이론과 응용 제 8 권 제 1 호 2002 년
Theories and Application of Chem. Eng., 2002, Vol. 8, No 1
  The catalytic activity and selectivity of immobilized Mn(salen) complexes have not changed more
or less after four times of reusing.
  2. Modification and recycling of chiral salens

                                                                                                                          N          N
                                                                                                          R1              O          O      t-Bu
                                                                                                                     R2              t-Bu

                                                                                1. Co(OAc)2·4H2O
                                                                                                               Co(III)-(A) : R1=R2=H
                                                    N         N                    EtOH, reflux
                                                                                                               Co(III)-(B) : R1=R2=t-Bu
                        R1                          OH    HO             t-Bu
                                                                                2. Cp2FePF6 or Cp2FeBF4
                                               R2             t-Bu
                                                                                   CH3CN, reflux
                                                                                                                          N          N
                                                        (A)                                               R1              O   +
                                                                                                                                  O         t-Bu
                                                                                                                     R2              t-Bu

                                                                                                               Co(III)-(C) : R1=R2=H
                                                                                                               Co(III)-(D) : R1=R2=t-Bu

                                          Fig. 1.                 Preparation of (Co-Salen)+PF6- or (Co-Salen)+BF4-

  The well-known chiral Co(III) salen catalyst for HKR has a –OAc which was weakly attached with
a cobalt, active site. After HKR reaction, -OAc group used to be dissociated, then the catalyst showed
reduced enantioselectivity when they were reused in HKR reaction.
  To change the active site of chiral Co(III) salen complexes, we used Cp2FePF6 and Cp2FeBF4. The
preparing method is shown in Fig. 1. This (Co-Salen)+PF6- or (Co-Salen)+BF4- was used as a catalyst
in hydrolysis kinetic resolution of epichlorohydrin.



                                                                                                                 +        -
                                          60                                                       (Co-Salen) PF6 complex



                                                0                    1          2         3         4           5                  6        7
                                                                     The number of reaction times

화학공학의 이론과 응용 제 8 권 제 1 호 2002 년
Theories and Application of Chem. Eng., 2002, Vol. 8, No 1

       Fig. 2. The optical activity of (Co-salen)+PF6- complex and Jacobsen’s catalyst in recycling
  Fig. 2 and Fig. 3 show the results of recycling as compared with chiral Co(III)-OAc salen. The
reaction rate was much faster than one by Co(III)-OAc salen. The catalysts of (Co-salen)+PF6--type
showed unexpectedly higher ee% value of epoxides and diols. These catalysts exhibited the very high
enantioselectivity of 99% within only 4 hours. For regeneration, the epoxide was distilled under
vaccum, then after the diol was transferred in aqueous phase using distilled water, CH2Cl2 was added
into the mixture to dissolved catalysts. The catalysts were recovered by evaporation of solvent. These
catalysts were reused in the same reaction without any treatment.


                                                                                      +       -
                                                                         1th (Co-salen) PF6
                                                                                      +       -
                                      80                                 2th (Co-salen) PF6
                                                                                      +       -
                                                                         3th (Co-salen) PF6
                                                                                      +       -
                                      70                                 4th (Co-salen) PF6
                                                                                      +       -
                                                                         5th (Co-salen) PF6
                                                                                      +       -
                                      60                                 6th (Co-salen) PF6
                                                                         1th (Co-salen)-OAc
                                                                         2th (Co-salen)-OAc

                                            0   4     8      12     16           20

                                                    Reaction Time(h)

   Fig. 3. The enantioselectivity and reaction time of (Co-salen)+PF6- complex as the reaction number

  The activity of (Co-salen)OAc, Jacobsen’s catalyst, reduced to 17ee% after the first hydrolysis
reaction. This is due to a dissociation of bond between cobalt and –OAc. The activity of (Co-
salen)+PF6- complex on the enantioselectivity was maintained for reaction of reusing catalyst without
optical loss. (Co-salen)+PF6- complex usually exhibited the high enantioselectivity of 99.8ee% in the
4~5th hydrolysis reaction, but reaction time grew longer as a time of regeneration increased.

  3. Application of new polymeric salen complexes in the HKR of epoxides
  The heterogeneous catalysts offer practical advantages of the facile separation from reactants and
products, as well as recovery and reuse. In the case of polymer-bound salen catalyst, the flexibility of
the support appears to facilitate intercomplex interactions, as the reactions proceed with rates
comparable to the solution-phase homogeneous catalysts and to the silica-bound catalysts[7]. Based
on these data, we have synthesized two different salen polymers using chloromethylated salen and
dimeric dialdehyde, respectively. The newly synthesized chiral salen polymers have been applied as
catalysts in the HKR of terminal epoxides, as well as meso epoxides such as cyclohexeneoxide and
cyclopenteneoxide. These new catalysts afford a highly valuable terminal epoxides in enantiomerically
pure form.

화학공학의 이론과 응용 제 8 권 제 1 호 2002 년
Theories and Application of Chem. Eng., 2002, Vol. 8, No 1
  The trends in the activity and enantioselectivity of the synthesized Co(Ⅲ) salen polymer were
examined for the HKR of epoxides. All the polymeric salen catalysts showed excellent catalytic
activities with the substrates such as epichlorohydrine, styrene oxide, 1,2-epoxyhexane. The reaction
using the polymeric Co(III) salen catalysts gave the almost same enantioselectivity as homogeneous
salen catalysts.

  1. New immobilized chiral salen complexes of Mn(III), Co(III) type on mesoporous MCM-41 could
be used as catalysts in the enantioselective epoxidation and the HKR(Hydrolysis Kinetic Resolution)
with high enantioselectivity and regeneration.
  2. The chiral salen (Co-salen)+PF6- catalysts were very stable in the hydrolysis reaction and
exhibited a very high enantioselectivity during regeneration as compared with conventional Co(III)-
OAc salen catalyst.
  3. The polymeric chiral salen could be used on asymmetric epoxidation and hydrolysis reaction with
high enantioselectivity and regeneration.

 1. J. McMurry, Organic Chemistry, 4th ed. Brook Cole, Pacific Grove, 297(1996).
 2. E. N. Jacobsen In Catalytic Asymmetric Synthesis, I. Ojima Ed., VCH, New York (1993).
 3. S. C. Stinson, C&EN., 27, 38, September (1993).
 4. M. J. Burk, M. F. Gross, T. G. P. Harper, C. S. Kalberg, J. R. Lee and J. P. Martinez, Appl.
    Chem., 68, 37(1996).
 5. G.J. Kim and J.H. Shin, Tetrahedron Letters, 40, 6827(1999).
 6. Kristien B. M. Janssen, Wim Dehaen, Ivo F. J. Vankelecom and Pierre A. Jacobs Tetrahedron;
    Asymmetry, 8, 3481(1997).
 7. D. A. Annis and E. N. Jacobson, J. Am. Chem. Soc. 121, 4147(1999).

화학공학의 이론과 응용 제 8 권 제 1 호 2002 년

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