Acta Chim. Slov. 2005, 52, A61-A1Q 467 Short Communication An Efficient Recyclable Catalytic System for Asymmetric Dihydroxylation of Olefins Ru Jiang, Yongqing Kuang, Xiaoli Sun, and Shengyong Zhang* Department of Chemistry, Fourth Military Medical University, 710032 XVan, China. E-mail: syzhang@fmmu.edu.cn Received 18-07-2005 Abstract A recoverable and reusable catalytic system for asymmetric dihydroxylation of olefins was developed by using TentaGel-Os04 1 and mono-quaternized bis-cinchona alkaloid chiral ligand 2 combined with ionic liquid [bmim]PF6. Both the osmium and ligand could be recovered efficiently. It could be recycled ten times with only 0.5 mol% of 1 and 2.0 mol% of 2. The system is effective in the AD reactions of a range of olefins. Key words: chiral ligand, TentaGel-Os04, ionic liquid, asymmetric dihydroxylation Introduction The catalytic asymmetric dihydroxylation (AD) of olefins provides one of the most efficient methods for the preparation of chiral vicinal diols, which act as intermediaries in the synthesis of many biologicalh/ active substances.1 The obstacles to its large-scale application in the pharmaceutical and fine chemicals industries remain the high cost of osmium tetroxide and cinchona alkaloid ligands as well as the high toxicity and volatility of the osmium component. There is a growing interest for exploring the repetitive use of both the catalytic components (Os04 and chiral ligand) in the past few years. Attachment of the ligand to a soluble or insoluble support covalently2or immobilization of osmium tetroxide based on microencapsulation,3 ion-exchange techniques,4 osmylation of resins5'6, and adopting PEG[poly(ethylene glycol)] as a recyclable medium7 has made it possible to recover and reuse the ligand or osmium, but has failed to recycle the two catalytic components at the same time. Recently, room-temperature ionic liquids (RTILs), especialh/ those based on l,3-dialkylimidazolium cations have been adopted as a recyclable medium in the AD reaction.8-10 In these solvents, catalysts having polar or ionic character can be immobilized and thus the ionic solutions containing the catalyst can be easily separated from reagents and products. When the reaction was finished, the product diol could be extracted by ether, while most of the alkaloid ligand and osmium tetroxide were remained in the ionic liquid phase. However, leaching of both catalytic components was inevitable during extraction of the product with ether, because the ligand can dissolve in ether to some extent and bring out some osmium by complexation. Very recently, Branco et al adopted 5cC02 in the separation process to minimize osmium catalyst loss and make its reuse possible.11 We reported a recyclable catalytic system for AD reaction in the ionic liquid with a mono-quaternized bis-cinchona alkaloid ligand in 2004.12 Both the ligand and Os04 could be recovered. But the amount of Os04 required is higher (1.5 mol%) than that needed for homogeneous AD reaction (0.2-0.5 mol%).13 Quantitative analysis of Os04 by iodometry showed that about 2 mol% of the total amount of Os04 was transferred into the ether layer during the extraction of diol with ether. To address this problem, we immobilized Os04 on the TentaGel resin. Herein we report the successful application of TentaGel-Os04 1 and mono-quaternized bis-cinchona alkaloid ligand 2 in the AD reaction with [brnim] PF6 as the recovery medium and Ar-methylmorpholine oxide (NMO) as co-oxidants (scheme 1). Results and discussion TentaGel resin is a special macromolecular material in which a polyethylene glycol (PEG) spacer is placed betvveen the polystyrene backbone and the reactive site. Being soluble in many solvents such as dichloromethane, terf-butanol and water etc, the PEG spacer places the reactive site in a more “solution-like” environment. Therefore, TentaGel-Os04 has the advantage of one-phase catalysis and two-phase separation. lwas prepared as scheme 2. The FT-IR spectra of 1 showed that the sharp band which was Jiang et al. Asymmetric Dihydroxylation of Olefins 468 Acta Chim. Slov. 2005, 52, 467–470 1-4 V % ,O O ^O^ n NEt3 0 so ,O O ^-On~NEt3 'Nr-' N-N N VN OMe TentaGel-Os04 1 Scheme 1 assigned to the vibrational asymmetric 0 = Os = 0 stretching (819 cm4 in the spectrum of free potassium osmate) disappeared. The scanning electron microscopy-energy-dispersive X-ray analysis (SEM-EDX) of 1 substantiated the presence of osmium in the surface of the resin, and this result was revaluated by titration of the potassium bromide formed in the ion-exchange process (loading = 0.075 mmol of Os per g). We had reported the mono-quaternized bis-cinchona alkaloid ligand 3 (Scheme 3).12 In the AD reaction, the double bonds present in 3 undenvent dihydroxylation to produce the tetrahydroxylated analogues 4. Being higher polar, 4 could be strongly immobilized in the ionic liquid much more 8. In order to study the recoverability of bis-cinchona alkaloid ligand with only quaternized nitrogen group, we designed ligand 2 which couldn’t be dihydroxylation in the AD reaction. 2 was prepared conveniently by quaternization of l,4-bis(9-O-dihydroquininyl)phthal azine [(DHQ)2PHAL] (Scheme 4). -°—ot-°^Br ^°--o-^0V"Br \^TA Et3N DMF '°--^o'N'0)^NEt 3 Br K20s04 N2* ^^°^o^0V-NEt3Br TentaGel HL-Br Scheme 2 \ B_r_- N"" cm ^o^^^A // \^J ^ N-N H N "N AD HO OH HO Kh\!J NN ^N ^N 4 Scheme 3 benzyl bromide S^ N-N %lN" H-^-°il>0r^H -------- MeO^A^ J^^OMe THF (DHQ)2PHAL Scheme 4 Jiang et al. Asymmetric Dihydroxylation of Olefins 2 1 3 2 Acta Chim. Slov. 2005, 52, 467–470 469 Table 1. Reusability of TetaGel-OsO4 1 and ligand 2 in the AD reaction of trans-stilbene in [bmim][PF6].a Table 2. AD reaction of olefins using 1 and 2 in [bmim]PF6.a Run 1 2 3 4 5 6 7 8 9 10 Yield (%) 84 82 85 79 80 81 78 74 69 70 Ee (»/„)" 95 93 90 91 90 88 89 87 88 89 Yield (%)c 86 65 31 Ee (%)c 95 88 23 Entry Olefin yield (%) (%f config." a Recycle experiments were carried out on a 2 mmol reaction scale of olefin using 1 (0.01 mmol), 2 (0.04 mmol), NMO (2.6 mmol) and [bmim][PF6] (2mL) in acetone-H20 (v/v, 10:1, 20 mL). Olefins were added by a svring pump for 10 h; b The ee values were determined by chiral HPLC analysis; c Recycle experiments were carried out on a 2 mmol reaction scale of olefin by using Os04 instead of 1. As the model reaction, we studied the AD reaction of trans-stilbene using TentaGel-OsO4(0.5 mol%) 1 and chiral ligand 2(2.0 mol%) in the acetone-H20-[bmim][PF6] with NMO as co-oxidant. After completion of the reaction, ali the volatiles were removed under reduced pressure and the chiral diol extracted with tert -butyl methyl ether. The remaining ionic liquid layer containing 1 and 2 was then subjected to the next run with a new batch of NMO and the olefin. High catalytic activity and enantioselectivity were obtained even in the tenth cycle, whereas the catalytic system could be only recycled 3 times by using 0.5 mol% of Os04 instead of 0.5 mol% of TentaGel-Os04 1 (Table 1). Encouraged by these promising results, we further performed the AD reactions of 9 olefins under the same conditions. The results are summarized in Table 2. In most čase, the desired diols were formed in high yields and ees. A low concentration of the substrate in the reaction is necessary for high enantioselectivity. So the substrates should be added slowly during a period of 10 h (Table 2, entry 3, 7 and 9). This is in agreement with the earlier observation.8 The results of Table 2 showed that this catalytic system delivered much higher enantioselectivity for trans-disubstituted olefins than that for terminal olefins (Table 2, entry 8, 10 and 11). Additionally, higher ees were obtained for aromatic olefins than that for aliphatic olefins(Table 2, entry 12). The ligand 2 couldn’t be dihydroxylated in the catalytic reaction. Although possessing fewer polar groups, 2 delivered the same catalytic activity and recoverability with ligand 3. It indicated that mono-quaternized bis-cinchona alkaloid ligand without other polar groups exhibited good recoverability in this catalytic system. Conclusion we have developed a highly effective recoverable and reusable system for AD reaction which provides 1 fraas-Stilbene 84 95 S,S 2 Ethyl fra«.s-cinnamate 73 95 2R,3S 3" Ethyl fra«.s-cinnamate 70 77 2R,3S 4 Methyl fra«.s-cinnamate 71 95 2R,3S 5 Propyl fraas-cinnamate 77 95 2R,3S 6 fraas-^-Metrrvlstvrene 83 96 S,S ld fraas-^-Metrrvlstvrene 87 74 S,S 8 a-Methylstyrene 86 70 S 9d a-Methylstyrene 80 62 S 10 Styrene 88 80 S 11 p-Chlorostyrene 90 83 S 12 trans-5-Decene 85 54 S,S a Ali reactions were carried out on 2 mmol reaction scale of olefin 1 (0.01 mmol), 2 (0.04 mmol), NMO (2.6 mmol) and [bmim][PF6] (2mL) in acetone-H20 (v/v, 10:1, 20 mL), Olefins were added by a syring pump for 10 h; b The ee values were determined by chiral HPLC analysis; c The absolute configurations of the diols were determined by comparison of their optical rotations with literature values; d Olefins were added in one portion. a simple and practical approach to immobilization of both catalytic components (osmium and ligand ). With 0.5 mol% of TentaGel-Os04 and 2.0 mol% ligand, the catalytic system could be recycled 10 times. The system is effective in the AD reactions of a range of olefins. Experimental General TentaGel HL-Br and [brnim] [PF6] were purchased from Acros; (DHQ)2PHAL, K20s04-2H20, Os04 and NMO were purchased from Aldrich; trans-stilbene, a-methylstyrene and trans-(3-methylstyrene were purchased from Fluka. IR spectra for samples as KBr pellets were recorded on a AVATAR 360 FTIR spectrometer. 1H-NMR(400 MHz) and 13C-NMR (100 MHz) spectra were recorded on a Bruker AV-400 spectrometer (CDC13 or CD3OD and TMS as internal standard). High performance liquid chromatography (HPLC) was performed by Agilent 1100 interfaced to a HP 71 series computer workstation with Daicel Chiralcel OJ-H, OD-H, OB-H chiral column. Optical rotations were obtained on a Perkin-Elmer 343 polarimeter. Preparation and titration of 1 TentaGel HL-Br (Ig, 0.48 mmol) was added to a 25 mL round-bottom flask charged with 5 mL dry DMF and svvelled for 2 h at room temperature. Then dry Et3N(1.7 mL, 12 mmol) was added, and the mixture was stirred in 80 °C for 24 h. The resulted mixture was cooled to room temperature and filtered. The quaternized resin was washed with DMF and ethanol, then vacuum- Jiang et al. Asymmetric Dihydroxylation of Olefins 470 Acta Chim. Slov. 2005, 52, 467–470 dried. The quaternized resin was stirred in saturated K20s04 aqueous solution (0.37 g, 1.0 mmol) for 24 h under nitrogen at room temperature. The rrrkture was filtered, then the solid was extracted with deionized water in Soxhlet apparatus and vacuum-dried to give TentaGel-Os04. The filtrate combined with extracted liquid was titrated by addition of saturated NH4Fe(S04)2 indicator (2 drops), O.lmol-L-1 AgN03 (5 mL), followed by back-titration with 0.1 mol-L-1 KSCN untile the solution turned red. The load of osmium on the surface of TentaGel-Os04 is 0.075 mmol-g-1 according to the consumed volume of KSCN(3.5 mL). Preparation of ligand 2 Benzyl bromide (0.30 g, 1.8 mmol) in dry THF (12 mL) was added dropwise into a solution of (DHQ)2PHAL (2.0g, 2.6mmol) in dry THF (28 mL) under reflux. The mixture was further refluxed for 1.5 h, and the solvent was removed in vacuo, with the resulting residue purified by flash column chromatography (CHCl3/MeOH 20:1) to give 1.06 g of 2 as a light yellow solid (43% yield). 1H NMR (400MHz, CDC13):5 7.19-8.66 (m, 21H), 5.03-5.06 (m, 2H), 4.18 (s, 3H), 4.10 (s, 3H), 3.85 (m, 3H), 3.61(m, 3H), 3.39(m, 3H), 2.54-2.57 (m, 6H), 1.2-2.2 (m, 12H), 0.8 (m, 3H), 0.69 (m, 3H). 13C NMR (100 MHz, CDC13) 5 158.8, 157.9, 157.5, 155.6, 147.3, 146.8, 144.6, 144.1, 139.0, 133.8, 131.7, 131.6, 130.6, 129.2, 127.1, 126.5, 126.1, 123.4, 122.9, 122.8, 122.4, 122.0, 119.6, 102.1, 101.5, 69.3, 66.7, 63.4, 61.7, 59.9, 58.4, 56.5, 55.8, 51.6, 42.9, 37.3, 36.0, 28.4, 27.7, 26.0, 25.5, 25.3, 24.3, 23.5, 22.2, 12.1, 11.3. HRMS (ESI): calcd for [M-Br-1]: 869.4754, found 869.4749. [a]D = +279.9 (c 1, EtOH). Asymmetric dihydroxylation of olefins A 50 mL flask was charged with acetone-H20 (10:1, v/v, 16 mL), [brnim][PF6] (2 mL), ligand 2 (38 mg, 0.04 mmol), TentaGel-Os04 1 ( 133 mg, 0.01 mmol). After stirring for 10 min, NMO (352 mg, 2.6 mmol) was added. The olefin (2 mmol) dissolved in acetone-H2O(10:l, v/v, 4 mL) was added by a syring pump for 10 h at room temperature. After completion of the reaction, aH the volatiles were removed under reduced pressure and terf-butyl methyl ether was added into the flask and the mixture was stirred for 5 min. The ether layer was separated and the procedure repeated (3x10 mL). The combined ether layer was washed with Povzetek water and brine, dried over anhydrous Na2S04. After removing the solvent, the crude product was purified by flash column chromatography on silica to give the diol. The ionic liquid layer containing TentaGel- Os04 1 and ligand 2 was reused for the next reaction. Recjcling and re-use of TentaGel-OsO fligand-ionic liquid To the ionic liquid layer recovered from the above experiment was added acetone-H20 (10:1, v/v, 16 mL) and NMO (352 mg, 2.6 mmol). The olefin (2 mmol) dissolved in acetone-H2O(10:l, v/v, 4 mL) was added by a syring pump for 10 h at room temperature. After completion of the reaction, The procedure for workup is the same as above. Acknowledgments We thank National Natural Science Foundation of China (NSFC) for financial support. Nos. 20372083 20302014. References 1. H. C. Kolb, M. S. Vannieuvvenhze, K. B. Sharpless, Chem. Rev. 1994, 94, 2483-2547. 2. C. E. Song, S.-g. Lee, Chem. Rev. 2002, 102, 3495-3524. 3. S. Kobavashi, T. Ishida, R. Akivama, Org. Lett. 2001, 3, 2649-2652. 4. B. M. Choudarv, N. S. Chovvdari, K. Jvothi, M. L. Kantam, /. Am. Chem. Soc. 2002, 124, 5341-5349. 5. J. W. Yang, H. Han, E. J. Roh, S.-g. Lee, C. E. Song, Org. Lett. 2002, 4, 4685-4688. 6. C. H. Jo, S.-H. Han, J. W. Yang, E. J. Roh, U.-S. Shin, C. E. 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Tako osmij, kot tudi kiralni ligand je možno učinkovito reciklirati do desetkrat. Sistem je učinkovit tudi pri ostalih reakcijah adicije na alkene. Jiang et al. Asymmetric Dihydroxylation of Olefins