43(6)-01.fm

Transcription

1 Korean Chem. Eng. Res., Vol. 43, No. 6, December, 2005, pp { 이량체구조를갖는키랄살렌촉매를이용한고광학순도의에폭사이드화합물합성 q Ç s * Çm Çs lç y Ç ƒ p p}e n 253 *(t) kld re ep (2005 9o 22p r, o 21p }ˆ) Synthesis of Enantiopure Epoxide Compounds Using Dimeric Chiral Salen Catalyst Geon-Joong Kim, Seong-Jin Kim*, Wenji Li, Shu-Wei Chen, Chang-Kyo Shin and Santosh S. Thakur Department of Chemical Engineering, Inha University,G253, Yonghyun-dong, Nam-gu, Incheon , Korea *RStech Corp.#305 Venture Town, , Sinil-dong, Daedeok-gu, Daejeon , Korea (Received 22 September 2005; accepted 21 November 2005) k ˆ p l p ˆ t ~ l v k pn l p~ ˆrp p rp lrp rl. l ˆ p pn l pl l p m. l v tl p l p p p p p l p p ˆo p. rq p p p p ˆ p ~ l, l p p l s p ~ ˆrp l e ˆrp eˆ p pl l p p s m. m m sq l l p pp s eˆp f p p p l p rs pl. p lrp ˆ t ~ pn p. l pl p p rn l l s p ˆ p rs l e m. h Abstract The stereoselective synthesis of chiral terminal epoxide is of immense academic and industrial interest due to their utility as versatile starting materials as well as chiral intermediates. In this review, we investigate the research and development trend in the asymmetric ring opening reactions using cobalt salen catalysts. Hydrolytic kinetic resolutiong(hkr) technology is the very prominent way to prepare optically pure terminal epoxides among available methods. We have synthesized homogeneous and heterogeneous chiral dinuclear salen complexes and demonstrated their catalytic activity and selectivity for the asymmetric ring opening of terminal epoxides with variety of nucleophiles and for asymmetric cyclization to prepare optically pure terminal epoxides in one step. The resolved ring opened product combined with ring closing in the presence of base and catalyst afforded the enantioriched terminal epoxides in quantitaive yield. Potentially, these catalysts are using on an industrial scale to produce chiral intermediates. The experimental results of HKR technology applied to the synthesis of various chiral compounds are presented in this paper. Key words: Chiral Salen, Asymmetric Ring Opening, Epoxide, Enantioselectivity, Optical Isomer, Hydrolytic Kinetic Resolution To whom correspondence should be addressed. kimgj@inha.ac.kr 647

2 648 të vëp Ëv oëe} ˈ Š 1. h q l p oq l pp rp p v k nl e} vv k q p n p v~(enantiomer). pm p v p ˆ (chiral)p p ˆ qm, l q qep n ~v p p ˆ (achiral)p. p n m p kp v m p m y q l l, p p ~vv k v, ˆ p m n p l p p p o l l p kl (+)m ( ) p (D)m (L) p r l l n mp, l Chhn-Ingold-Prelogp o r l r lp (R) (S)p n. ˆ p pk, e, ~ r, }l, kp r n p p l k n n p. p p q p l qp q v ˆ n v pp, p p ql ~ l p v p qn l pp p. q~ ˆ p pel p s p ˆ p r pep l r p qn p [1]. ep n p v~ p r, r p pp ˆ l p r ˆ, p n ~ svp ep n p v~ v pe l rp n p v~ r p ˆ. pk p nl m p ep n p v~ tl p n p ~ rp r, e qnp ppˆ r n vp n [2]. m l, Scheme 1l ˆ p Dopa(2-amino-3-(4,3-dihydroxyphenyl)propanoic acid) k p ˆ tep p p p~ p v~ sq. n p n p v~p (D)-Dopa p l rp p pv kv, s p n p v~p (L)-Dopa t e p p Žˆdj l ˆo p v p. p p v~ p~l qnp ppˆ p k v, pl r r p n Scheme 1. The structure of optical isomers for chiral compounds. o43 o k Scheme 2. The catalytic cycle in asymmetric catalysis. p l p v p. e pk~ (FDA) p pk rse qnp n l v n p v~ p n p n p. ˆ pk pm pkp r s o o p ˆ t ~ eo n l, p rp 99.5Í p p ˆ t ~ n. p n p v~ lp p rp p p o p pk kl kt tn rp. l p n p v~ p on p n p v~ p~l n nl p p v. (asymmetric synthesis)p l n n p v~ r ˆp n p v~ n p. p l l n vl v p [2]. ~w p p ~p p p pn pkd m mp r e p. w, }l llv ˆ p pn l ˆ p p p ppˆ p. v, p p p kp e ˆ ekp n rp v p. w, ˆ pn p(asymmetric catalysis)p p. pp p n p f n ˆ vp p v ˆ r p. pp Scheme 2m p ep p. pl n ˆ op rl p p ˆ ~ p rp ~ p n p v~ n. pp p p l p (optical yield) t p q p v - v, p ˆ l l p sn l v p. r pk ll ˆ l p v k. po l tn pk eqp v p p ˆ k p p. ˆ t ~ lp rp o v l rn ˆ p pn p k l p p t n p.

3 2. { j i m m z i m 2001 l ˆ pl q k v 2 p q p l p. tp p Noyori[3] ˆ k o ~m o p ~ n l p o pp mp, p C=O C=N p o pl n p ˆ p m. pp Noyori p n p s ˆ p. ˆ pn p 649 ˆ Salen 1970 p Tsuruta [6] l p Kinetic Resolutionl p chiral rs p l m. 2.0 p ek p m 1.0 p ˆ 1,2- k p t l p l d lp p [7, 8]. p ˆ p n o p sl k sp o ~ Ž p. tl op l ˆ sp p s pl p ˆ p ˆ p. lrp rn o rp e o p np n, p ekp n e k m p p l., pl o l tn pp pp p. p qp Sharpless[4] 1980 l Ti(O-i-Pr4)m lžˆ p edšp pn l k k m l ek mp p ˆ p p. pl p ˆ p llv p k, 99Íee p p p ˆ p l o pl rp qn p pnp n. v v e erp p lrp l r ˆ p f BINAP, BINOL, ˆ o ~, m s, cinchona alkaloid, Duphros bis(phosphine) pybox p m p [5] Jacobsen [9, 10]p p tel p o e v k l p p l p p p m. p pl d-m p p ˆ p l e lp, jd- tl p p 95Í r p ˆ p p [10-12]. p pp p p l l rn l p. nl v lr pn l ep ol ˆ Salen( )p, p tel s p p l lrp on l pl rn pl. p l Žp te pmp p, ~ o p n l l o l p p l pp p. p nl o l p l p ˆ p p m p ˆ p p p p m [13]. p p tl sq l Korean Chem. Eng. Res., Vol. 43, No. 6, December, 2005

4 650 të vëp Ëv oëe} ˈ Š p l p p l f p p l Žp p t ~ n l l l p p l pp l m [14-16]. l p p pp ˆ l p l ˆrp pl, k l ˆ }, ˆ p y p ~ p l p l m p eˆ, v k p l p q. q p rp pp v l p pp 50Í. p pp sq l l p p ~ tl ~l p l p ˆ p r kinetic resolutionp, p l l p p n p ~ 99Í p l p p p r kl n 40~45Í r p, rn p l p p s p 100l sl p [8]. l p m m p r vp l p rp d p., e p ˆ p n l eˆ [16]. pm p ˆ p pn l o ~ tl epichlorohydrin(ech) epibromohydrin(ebh)p ~ e lp 1,2- mp m sq l HCl HBrp r l e l p pp, p p p e p rs p [16]. p pl p l llv l p p pp 50Í p v 1,2- mp on p l qr p. p pl l p m 99Íee r p p n v v, er p} e l p ˆ lv. Hydrolytic kinetic resolution (HKR) pl p ˆ p p p pl p l ˆ v k q l p p n p ~ 99Í p p p o n p kp p p l p tp 0.5 s p kp (0.55 ) n l pp pp v eˆ, p 1,2- mp p o p 0.5 p 0.4 r ~ l mr pp v v kp ˆl s. pl rn m pp pel p [16]. r p, k 99Íee p p p 1,2- m p q l, pp pel } r 0.55 p p ~ l 99Íee p p l p l p o43 o k ˆ eo k tn e o pv l mp, rs p k np n v m tp ˆ ECHp. ˆ ECH ˆ 3 p lv, pk p k, q, e ~ p k ˆ r r p rs n p tn ˆ t ~p p. k Fig. 1p ˆ ECH o n p pk p lt pp, p ˆ ECHp n p p l v v k. ˆ ECH rs t ~ p qrp p p ˆ ECH o n l rs r p rs rp p. q v ECHp rs p Shrples Epoxidation, Daiso (p )p, Jacobsonp ˆ n Rodia-Chirex( ) p p l pp, tl ˆ n p q n p. Rodia-Chirex p rs p ol ˆ pe p Jacobson (R,R S,S- ) n l ECH p ECH l p, pel ˆ p p, p kr l p q np, p p kp p(2 moleí) fk rp pl r s p kv. q k rp pm rr r tl l e r p rp. ECHp HKR pl pm p pl rp l l q k v p, l p ECH tp m lv p p ECHp l p ll Žmp eˆ p e ˆm pl p v [17].

5 ˆ pn p 651 Scheme 3. Various Co(III) cationic salen complexes containing counter anion. Fig. 1. Various chiral derivatives synthesized from chiral ECH. 3. k { m i m HKR mim mk -OAc m qmp p k p v o p e o q p p n, p s l p p pp p m. pl rq p -OAc el l s p ppmp ˆ rs l p p HKR pl rn l kp p s pp Scheme 3 l m. (1)p Jacobsen p, (2) e α,α,αtrifluoro-p-toluic acid } l lp p. o (5)~(7)p pp o p pl AgCH 3 C 6 H 4 SO 3, AgCF 3 SO 3, AgSbF 6 p } l mp, (3) (4) 2 p k Š n sq l n m d p n m p } e lp p. } llv ˆ ~ - p } l p r n m. - (8) n - (9) n vr } l rs m [18]. m m p t l sq o p s l p p rp p rs p pe p l HKR pp np v kp dž m p d e. Co(III)-(PF 6 ) and (BF 4 ) (3, 4) (OAc) o (1)l l p ƒ p ˆ lp, Table 1l } p l s p l p p m. Table 1. Enantioselective hydrolysis of terminal epoxides to diols on the various chiral Co(III) salen catalysts Entry Catalyst Time(h) (b) Yield of eopoxide( ) ee of ECH (b) k(m -1 S -1 ) (a) (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 the Reference 11. (b) The ee values were determined at the indicated reaction time. Korean Chem. Eng. Res., Vol. 43, No. 6, December, 2005

6 652 të vëp Ëv oëe} ˈ Š Fig. 4. The effect of loading amount on the enantioselectivity in the HKR of (±)ECH using catalyst 3. Fig. 2. The catalytic activities and recyclabilities of Co(III) salen complex 1 and 3 in the asymmetric HKR of ECH. Fig. 3. Racemization of (S)-ECH on the catalyst 1, 8 and 9 with prolonged reaction time. 0.4 molí catalyst, reaction at room temp. Co(III)-(OAc) (1)p l p HKR pl l p e p Fig. 2l k p p 1 n l p pl q n p p p q } n. l (PF 6 ) (3) (BF 4 ) (4) pp s p l p v eˆ p e n p p p pp v, p} l 6 p p q np o43 o k m (Fig. 2). p p q} n lp q n p k ˆ n n l ˆ vp lp pnl r l. qrp (PF 6 ) (BF 4 ) o pe p lr ECHp 99Í p p ov, lp rl r pl v kk. -(OAc) o m v pt n eˆ p (Br) (8) (I) (9) pe p lv Fig. 3l m p rp ECHp p k pl. Fig. 4l ˆ m p ~ p kp l ECHp HKR pp p ~ p v p r wp e l p p ECH lp pl. k rp kp n 99Íee p p l p p q p v k lr pnp p. p v/ p n ƒ l p 6 s l p n p f, pe p 40e r v p p ~p rs p k pl. rp t l o ppmp s l p p v, ECHm p o l p p HKR pl (OAc) el (PF 6 ) p o o v kk p ˆ l p l o m. l n rp p p qn 13 s mp l } l m (Scheme 4) [19]. p 13s mp Al, Ga, In Tlp m,, n, v mp n m. p p l sq oq rqep k p. rp p mp qm 1:1 2:1p p ppp l p [20]. ˆ 2 p o p pv 13s m p 1:1 p vp ~ p. 13 s mp 1:1 2:1 } p f sp m p l ~ m. l Shibasaki [21]p q l sp p p

7 ˆ pn p 653 Scheme 4. The structure of monomeric and dimeric salen catalysts. Table 2. HKR of terminal epoxides catalyzed by the dinuclear catalyst Entry Recovered Epoxides a Catalyst/Catalyst Loading (mol ) b Time (h) Yield (ee) c 1 4b (99.3) 2 4b (99.7) 3 d 4b (98.7) 4 4b (99.8) 5 4b (99.6) 6 4b (99.3) 7 4b (99.3) 8 d 4b (98.2) 9 4b (99.4) 10 4b (99.8) 11 e 4b (96.8) 12 e 4b (99.3) 13 e 4b (99.3) a Isolated yield is based on racemic epoxides (theoretical maximum=50 ). b Loading on a per [Co] basis w.r.t. racemic epoxides. c ee was determined by chiral GC or chiral HPLC. d THF was used as a solvent. e Solvents CH 2 Cl 2 : THF = 2:1. Korean Chem. Eng. Res., Vol. 43, No. 6, December, 2005

8 654 të vëp Ëv oëe} ˈ Š n l pp pl. p Ga pmp l p p l pl rp qn p p. 13s mp 1:1 2:1 } p s pp Scheme 4} ˆ pp, p q EXAFSm Mass p l sr p m. EXAFS e ƒ l er r m mp q p 13s m p 1:1 o pp 2 q l 1:2 o ppp p m. p q p 2 q p s v p r pp, l p p HKR p l f pn l p m. 2 q ˆ n p f rp l p p HKR pp pl. p p p ˆ ˆ lp ˆ l p p p ˆ n k. pp Table 2 k l p p n HKR pp l lp p. rn p kp 0.2~0.5 molíplp, dˆp m p p nl n p kp 0.8 molí rn m. ˆ p n 13s mp s l ˆ p l p p HKR pl Co-In>Co-Tl>Co-Ga>Co-Al p p p ppmp s l I>Cl>Br>NO 3 p m. Fig. 5l ˆ m p ECHp HKR p r~rp 2 q p q p j p p p. p p kp p ~ p o l tp pmp tp molí r m, 0.2~0.5 molí o ~ m. p tl p v o l pe e p UV-Visd p m. 2 tel sq p UV-Visd p 420 nml, k sp mp } p v 365 nml n ˆ. n Fig. 5. Comparison of reactivity and enantioselectivity of catalysts Co-MX 3 for the HKR reaction of epichlorohydrin at rt using 0.2 molí of the catalyst per [Co] basis w.r.t. substrate. o43 o k Fig. 6. The UV-Vis spectral analysis of the catalyst during and after HKR of racemate methyl glycidate. p peqp ps l 420 nmp v kp p v n 2 k v k pd p mp ˆ ov p p. p p p l q n l p p ov p p m (Fig. 6). l p p l p r pp p l l 2 ps p ˆ. p 1 qp l p l p l p qp l p l ~ OH r p p [8, 13, 22]. qnl p p l l, o l p l 2 q q p p r pm p l p. l p p ~l p pp p qn 2 q q l pl q qnp r p e l l [23]. ep p p ˆ pp, p = k intra [catalyst] + k inter [catalyst] 2 p / p v s e, n k interl r p k intral. r p v p pp q p pl qnp ppp p. k p Table 3 Fig. 7p q p 2 q p p n l HKR pp op el rn p. l l 13s mp p l 2 q p le r p 0p k p k pp, p q- q k q qnp pl p e rrp 2 q ˆp q s p. 4. m { m mk sp Co s tl v p

9 ˆ pn p 655 Table 3. Kinetic data for the HKR of racemic ECH catalyzed by monomers and dimers Catalyst No of (salen) Co unit k intra (min ) k inter (M 1 min 1 ) 1a b a b a b a b Scheme 5. The structure of polymeric salen. Fig. 7. Initial rate kinetics for the asymmetric HKR of the ECH catalyzed by the monomer and dimmer catalysts. p rp p p l e q } l q pe k p. p rp o l l r e q n q } p k r p, r } k np. p p l p q p np qrp p l p p ˆ p ~ l o p l l p e p, r p l p p[22, 24] m l p pl rn l p l p k r p [25]. p l p v ˆ p lv r. Annism Jacobsen[22]p p m l l p p l pp qp rp qnp v m, p p v o ~ l p p o m. p rl p rs l n ~ l r eˆ p p qrp p veˆ pp o pl p p m l p p l pn m [26, 27]. q p s pp Scheme 5l ˆ l. p ECH, Styrene oxide 1-Hexene oxidem p p l p l l p p ˆ p m. Co(III) sp q ˆ p o ˆ p ˆ lp, ECHp n n p p 99Í p p eeí p ˆ l. p p n p q n np, l q n l p p ov m (Table 4, 5). op Scheme 5l ˆ q p q q p 10,000 r, tel pmp p o n l l n m. p p l p l n v p l l p r - p n ~ r l d pl. 5. zi o { m mk ~ n MCM-41, SBA-15 p lp s p v, p e ~ t vp s m s l sr p [24]. s p vp l p e m pp l qm o p v l l p. qn o q vp l l eˆ p t e m o e p pp l v. p l q e p l p ˆ ~p l l n p. l l ~ l eˆ ˆ Scheme 6l ˆ r l l MCM-41 l r m. r n l p l p p s l HKR pp mp, r rp p p p m p ll. p p l l p k v, n l l p p l p q np m. rq p n p dž pq t ~ n p p v lp pl s vp p sp ~ e s/ p ~ m. p q k p Fig. 8l m p 3 orp p l l pp, p Korean Chem. Eng. Res., Vol. 43, No. 6, December, 2005

10 656 të vëp Ëv oëe} ˈ Š Table 4. Enantioselective hydrolysis of terminal epoxides to diols on the polymeric chiral Co(III)-(PF 6 ) and (BF 4 ) -type salen catalysts Entry Substrate Catalyst Time(h) (b) Yield of epoxide( ) ee% of epoxide (b) Yield of diol( ) ee of diol (b) 1 ECH SO EB HO ECH SO EB HB ) ECH; epichlorohydrine, SO; styrene oxide, EB ;1,2-epoxybutane, HB; 1,2-epoxyhexane 2) Catalyst ;G(1) Co(III)-(PF 6 )-type polymeric salen,g(2) Co(III)-(BF 4 )-type polymeric salen 3) Epoxide;10mmol, water; 0.55 mmol, chiral salen catalyst; 0.5 mol, reaction temp.; 20 o C s p MCM-41 l p. p MCM-41s p mr l t ~ n dž l e ˆl p. s/ ~ 1p p p rs p mp p ol ~ 3 orp p l s l p. l sq e ml k e p eˆ, k p ˆ 1,2- k p rp e q p l q p ll (Fig. 9). qp tel p e n m d p e (PF 6 ) o Co(Ï) rs m. p r p Table 5. Recyclability of polymeric chiral Co(III) salens in HKR of ECH (Catalysts were reused without further treatment after simple filtration of product) Cycle (times) Yield( ) Ee of ECH p Fig. 10 p l s p l p p r pl pl p p ˆ l. n Scheme 6. The procedure for the synthesis of chiral salen complexes immobilized on MCM-41 [ref. 24]. o43 o k

11 ˆ pn p 657 Fig. 8. SEM images of bimodal silica structure: (a) and (b) cross-section of the calcined monolith obtained from the mixture of n- butanol/ethanol solvent(n-butanol: EtOH=1:3), (c) enlargement of (a), (d) low magnification of monolith sample obtained with decreasing solvent amount, (e) enlargement of (d). Fig. 10. The catalytic activities of Co(III)-(PF 6 ) salen catalysts immobilized on meso/macro porous silica in the asymmetric HKR of epoxides. Fig. 9. The structure of heterogeneous salen catalyst immobilized on meso/macroporous composite. Fig. 11. The catalytic recyclabilities of heterogeneous Co(III)-(PF 6 ) salen catalysts on meso/macro porous silica asymmetric HKR of 1,2-epoxybutane. p p r Fig. 11l } p p r e n p p l q n pl. p} 5 v q n l kp p p ov p m. 6. mjm zm g j i m i m m tel pmp pn l p p l pp ~ p n mp n rp, pnp ~ n nl p ˆ p ˆ v. m l k m p Ž p ECHp l Jacobsen p OAc- o p ˆ p v. p p p ~p (R)-ECH s q l Ž p l p m sq l ˆm } l e Ž p p p m [8]. p k sp mp o ˆ p p p v pl np l p ~ Korean Chem. Eng. Res., Vol. 43, No. 6, December, 2005

12 658 të vëp Ëv oëe} ˈ Š Scheme 7. Asymmetric ring opening of terminal epoxides with HCl catalyzed by 4b and 9b (Yield based on HCl). Fig. 12. Kinetic resolution products obtained using HCl and catalyst 4b. Conditions are shown in scheme 2. Yields correspond to the isolated product based on HCl. Scheme 8. Asymmetric cyclization of chlorohydrin catalyzed by dinu clear complex 1b-4b. n nl ˆrp pp v eˆp m. m p n pl l p m m p p eˆ l p p ll o pep n l ˆ m m d r [28]. v ˆp p ~p l p m p } ll p p e p lp p. ˆ l p sq l l p p HKR pp pp, pp l vl ˆ p n p rs p p. kl 2 q p p m p ~ n mp, l p tp p ~ r p ˆ p l Scheme 7 Fig. 12l ˆ } p e p eeí p 89Íl p. p pp n p m p k, MTBE n tl q p ˆ p llr. m p ~ pp kv v l q l p l e llp, s l p kr ˆ p ˆ l. pp pnp, ˆ ˆr m r pl rn l k (Scheme 8). p e m p r e eˆ l p. p pp l ˆ p Žm p ˆ p e p p mp, p ~ r p ˆ p ˆm v pl. Jacobsen p pl l p pv kk. kp m ~ pp l l r p ˆ p p e p lp p, p s p l m ~ e n pp v eˆ y p p ~ m p r p p e p l p p (Scheme 9). o43 o k Scheme 9. Kinetic resolution/cyclization sequence in the presence of catalyst 4b. p 6rp l l } e p ~ n p ˆ p lv l, Jacobsen p (R)-ECH n l (R, R) sq l Ž p l p p ll e Ž p q m. ˆ ECH e ECH p p e Ž p o ~ p, 2 n v k l e r p p. l p p l p e o ~ l pl r p ˆ ˆ l, n l p p s m p s l v k Table 6p ECHl l 60~80Íeep m. p pp l k s p l d o ~p p, t p e p m sq l ˆm pp eˆ p. np k 60~80Íee v p e p m m s l l rp } p ~ ˆr p l srp ld l p p ˆ p v l., p p p p ECH n v k ( p HKR pp n ) ECH vr p e Ž p o ~p p m (Scheme 10). p e Ž p rk ll n tn t ~ n p. 2 ql GaCl 3 eˆ l l p m k mp pp Š m Table 7l el. p p q p n p ˆ l p p

13 Table 6. Asymmetric ring opening of terminal epoxides with carboxylic acids catalyzed by 4b ˆ pn p 659 Emtry* R R' Catalyst Catalyst Loading a Time (h) Yield ( ) b ee( ) c 1 CH 2 Cl 4b CH 2 Cl 4b CH 2 Cl 4b CH 2 Cl 4b a In mol loading on a per [Co] basis w.r.t. racemic epoxide b Isolated yield is based on racemic epoxides (theoretical maximum=50 ). c ee was determined by chiral GC or chiral HPLC.G*For entry 1-2, 1,4-dioxane and 3-4 TBME was taken as solvent. llp, ECHm lˆmp pl p l 1- -3lŠe Ž -2-mp 95Íee lp pl. q p p q p p m. sp rp ~ qn mp k o ~m l p p n p f l s p n ˆ l p rs p m. Scheme 11l ˆ m p, ˆ 2 q sq l ECH EBH o ~ l p p ~ llv p v k p pedšl m l pp v eˆ v ˆ e e l o ~ p Table 7. Asymmetric ring opening of terminal epoxides with alcohols and phenol Entry R R' Catalyst CatalystGLoading a TimeG(h) YieldG( ) b eeg( ) c 1 CH 3 CH 3 4b CH 2 Cl CH 3 4b CH 2 Br CH 3 4b CH 3 C 2 H 5 4b CH 2 Cl C 2 H 5 4b CH 2 Br C 2 H 5 4b CH 3 i-c 3 H 9 4b n.d n.d 8 CH 2 Cl i-c 3 H 9 4b n.d n.d 9 CH 2 Br i-c 3 H 9 4b n.d n.d 10 CH 3 C 6 H 5 4b CH 2 Cl C 6 H 5 4b CH 2 Br C 6 H 5 4b CH 3 3-(Cl)C 6 H 4 4b CH 2 Cl 3-(Cl)C 6 H 4 4b CH 2 Br 3-(Cl)C 6 H 4 4b CH 3 3-(CH 3 )C 6 H 4 4b CH 2 Cl 3-(CH 3 )C 6 H 4 4b CH 2 Br 3-(CH 3 )C 6 H 4 4b a in mol loading on a per [Co] basis w.r.t. racemic epoxide, b Isolated yield is based on ROH. c ee was determined by Chiral GC or chiral HPLC. Korean Chem. Eng. Res., Vol. 43, No. 6, December, 2005

14 660 të vëp Ëv oëe} ˈ Š Scheme 10. Ring opening and closing sequence in the presence of cat alyst 4b and base. Scheme 11. Synthesis of chiral ether compounds by epoxide ring opening reaction with phenol. l, ld k ˆ p p. ECH tep l l ~ l, e m m sq l eˆ l rp pp l p r v eˆ p. 8. h ˆ p pk, e ~ r, kp r n p p n r n n p. p v p v~ k v p~l qnp ppˆ p k v, pl r r p n p l p v p. ˆ pk pm pkp rs o o p ˆ t ~ eo n l, n p ˆ t ~p p n p. p p v~ p rp p p o p pk rs kl kt tn rp. tl ˆ 3 4 p ˆ t ~p n n k, p p n l l v p rs p l p t ~ rrp rs p p n. rrp k pp l m n n l l o s p lrk p. l q l p l v p tl, ˆ p pn ˆ l l r l k. n sp p f, p t ~ n l l p p p ˆrp l pl l n l m - k m ~l rn pn o q pl. p 2 q r s p n q} n ll lrp d pn p. q Š o ˆ t ~p p v p p, ol p l k o ~p p e p. l vp p s l n p pp, l pl rn l p l p p l m er lrp l pn l p. y Scheme 12. Coupled route for the synthesis of chiral intermediates catalyzed by dinuclear salen complex. m. p p rp eˆ k p p p on p. rp pp Scheme 12l ˆ } n l pp r eˆ p l p, m, o43 o k 1. Noyori, R., Asymmetric Catalysis in Organic Synthesis, John- Wiely, New York(1994). 2. Sheldon, R. A., Chirotechnology-Industrial Synthesis of Optical Active Compounds, Marcel Dekker, New York(1994). 3. Noyori, R. and Hashiguchi, S., Asymmetric Transfer Hydrogenation Catalyzed by Chiral Ruthenium Complexes, Acc. Chem. Res., 30(2), (1997). 4. Gao, Y., Hanson, R. M., Klunder, J. M., Ko, S.Y., Masamune, H. and Sharpless, K. B., Catalytic Asymmetric Epoxidation and Kinetic Resolution: Modified Procedures Including in Situ Derivatization, J. Am. Chem. Soc., 109(19), (1987). 5. Kagan, H. B., in Jacobsen, E. N., Pfaltz, A. and Yamamoto, H. (Ed.), Comprehensive Asymmetric Catalysis, Springer, Heidelberg, chap.2(1999).

15 ˆ pn p Aoi, H., Ishimori, M., Yoshikawa, S. and Tsuruta, T., Synthesis Od Optically Active Cobalt (salen) Type Complexes and Their Asymmetric Reactivity Toward Propylene Oxide, J. Organometallic Chem., 85, 241(2), Chemistry Lett., 645(3), Tetrahedron, 36(248), 3391(1980). 7. Larrow, J. F. and Jacobsen, E. N., A Practical Method for the Large Scale Preparation of {N,N -Bis(3,5-di-tert-butylsalicylidene)- 1,2-cyclohexanediamineato(2-)}manganese(III) Chloride, a Highly Enantioselective Epoxidation Catalyst, J. Org. Chem., 59(7), (1994). 8. Larrow, J. F. and Jacobsen, E. N., Asymmetric Process Catalyzed by Chiral (salen) Metal Complexes, Topics in Organomet. Chem., 6, (2004). 9. Zhang, W. and Jacobson, E. N., Asymmetric Olefin Epoxidation with Sodium Hypochlorite Catalysed by Easily Prepared Chiral Mn(III) Salen Complexes, J. Org. Chem., 56(7), (1991). 10. Brandes, B. D. and Jacobsen, E. N., Highly Enantioselective, Catalytic Epoxidation of Trisubstituted Olefins, J. Org. Chem., 59(16), (1994). 11. Brandes, B. D. and Jacobsen, E. N., Synthesis of Enantiopure3- Chlorostyrene Oxide Via an Asymmetric Epoxidation/Hydrolytic Kinetic Resolution Sequence, Tetahedron; Asymmetry, 8(23), (1997). 12. Palucki, M., McCormick, G. J. and Jacobsen, E. N., Low Temperature Asymmetric Epoxidation of Unfunctionalized Olefins Catalyzed by Chiral (salen) Mn(III) Complexes, Tetrahedron Lett., 36(31), (1995). 13. Tokunaga, M., Larrow, J. F., Kakiuchi, F. and Jacobsen, E. N., Asymmetric Catalysis with Water: Efficient Kinetic Resolution of Terminal Epoxides by Means of Catalytic Hydrolysis, Science, 277(5328), (1997). 14. Schaus, S. E., Brandes, B. D., Larrow, J. F., Tokunaga, M., Hansen, K. B., Gould, A. E., Furrow, M. E. and Jacobsen, E. N., Highly Selective Hydrolytic Kinetic Resolution of Terminal Epoxides Catalyzed by Chiral (salen) Co(III)-Complexes; Practical Synthesis of Enantioenriched Terminal Epoxides and 1,2-diols, J. Am. Chem. Soc., 124(7), (2002). 15. Keith, J. M., Larrow, J. F. and Jacobsen, E. N., Practical Considerations in Kinetic Resolution Reactions, Adv. Synth. Catal., 343(1), 5-26(2001). 16. Furrow, M. E., Schaus, S. E. and Jacobsen, E. N., Practical Access to Highly Enantioenriched C-3 Building Blocks Via Hydrolytic Kinetic Resolution, J. Org. Chem., 63(20), (1998). 17. Larrow, J. F., Hemberger, K. E., Jasmin, S., Kabir, H. and Morel, P., Commercialization of the Hydrolytic Kinetic Resolution of Racemic Epoxides: Toward the Economical Large-scale Production of Enantiopure Epichlorohydrin, Tetrahedron: Asymmetry, 14(22), (2003). 18. Kim, G.-J., Lee, H. and Kim, S.-J., Catalytic Activity and Recyclability of New Enantioselective Chiral Co-Salen Complexes in the Hydrolytic Kinetic Resolution of Epichlorohydrine, Tetrahedron Lett., 44(27), (2003). 19. Thakur, S. S., Li, W., Kim, S. J. and Kim, G.-J., Highly Reactive and Enantioselective Kinetic Resolution of Terminal Epoxides with H 2 O and HCl Catalyzed by New Chiral (salen) Co Complexes Linked with Al, Tetrahedron Lett., 46(13), (2005). 20. Gruber, S. J., Harris, C. M. and Sinn, E., Metal Complexesas Ligands. VI. Antiferromagnetic Interactions in Trinuclear Complexes Containing Similar and Dissimilar Metals, J. Chem. Phys., 49(5), (1968). 21. Iida, T., Yamamoto, N., Matsunaga, S., Woo, H.-G. and Shibasaki, M., Enantioselective Ring Opening of Epoxides with 4- Methoxyphenol Catalyzed by Gallium Heterobimetallic Complexes; An Efficient Method for the Synthesis of Optically Active 1,2-diol Monoethers, Angew. Chem., Int., Ed., 37(16), (1998). 22. Annie, D. A. and Jacobson, E. N., Polymer-supported Chiral Co(salen) Complexes; Synthetic Applications and Mechanistic Investigations in the Hydrolytic Kinetic Resolution of Terminal Epoxides, J. Am. Chem. Soc., 121(17), (1999). 23. Konsler, R. G., Karl, J. and Jacobson, E. N., Coorperative Asymmetric Catalysis with Dimeric Salen Complexes, J. Am. Chem. Soc., 120(41), (1998). 24. Kim, G.-J. and Park, D.-W., The Catalytic Activity of New Chiral Salen Complexes Immobilized on MCM-41 in the Asymmetric Hydrolysis of Epoxides to Diols, Catalysis Today, 63(2-4), (2000). 25. Kim, G.-J. and Shin, J.-H., Catalytic Activity of New Salen Complexes Immobilized on MCM-41 by Multi-step Grafting in the Asymmetric Epoxidation, Tetrahedron Lett., 40(37), (1999). 26. Kwon, M.-A. and Kim, G.-J., Synthesis of Polymeric Salen Complexes and Application in the Enantioselective Hydrolytic Kinetic Resolution of Epoxides as Catalysts, Catalysis Today, 87(1-4), (2003). 27. Shin, C.-K., Kim, S.-J. and Kim, G.-J., New Chiral Salen Complexes Containing Lewis Acid BF3; A Highly Reactive and Enantioselective Catalyst for the Hydrolytic Kinetic Resolution of Epoxides, Tetrahedron Lett., 45(40), (2004). 28. Bodor, N., ElKousai, A., Kano, M. and Nakamura, T., Improved Delivery Through Biological Membrane. 26. Design, Synthesis and Pharmacological Activity of a Novel Chemical Delivery System for b-adrenergic Blocking Agents, J. Med. Chem., 31(1), (1988). Korean Chem. Eng. Res., Vol. 43, No. 6, December, 2005