Chiral gels concentration

A mixture of 1.4 g (10 mmol) of 4-chlorobenzaldehyde and 0.71 g (5 mol %) of the chiral polymer E is stirred in 10 mL of dry toluene for 15 h, under a dry nitrogen atmosphere, to form the Schiff base. After cooling to 0lC, 15 mL (15 mmol) of 1 M diethyl/inc in hexane is added and the mixture is stirred for a further 24 h at O C. 1 N HC1 is then added dropwise at O C, and the chiral polymer is removed by filtration. The polymer is washed several times with 11,0 and Et,0. The aqueous layer is separated and extracted with Et20. The combined organic layer is dried over MgS04 and concentrated under reduced pressure. The crude product is purified by column chromatography (silica gel, CHC1,) yield 1.61 g (95 %) 99 % ee [a]2,0 —23.9 (r = 4.93, benzene). 

After removal of the solvent, the residue was eluted through a short silica gel column to remove the catalyst (elution with hexane ethyl acetate = 1 2). The eluent was concentrated in vacuo to give the product 2 (99 % yield) and the diastereoselectivity was determined by HPLC analysis (99 %). The enantios-electivity of the product was determined by lH NMR analysis with chiral shift reagent (+)-Eu(dppm) in CDCI3 and by chiral HPLC analysis (Chir-alcel-OD). 

The mixture was passed through a short plug of silica gel to separate the catalyst from the alcohol/acetate mixture (EtOAc/hexanes, 1/1 —> 3/1 then Et N/EtOAc, 1/9). The solution of alcohol and acetate was concentrated in vacuo and the residue purified by FC on silica gel (EtjO/pentane, 1/20 1/4) to afford the (R)-acetate (639 mg, 44%, 90.2% eeby chiral-GC on the alcohol obtained by reduction using LiAlH ) and the (5)-alcohol (517 mg, 47%, 92.9% ee by chiral-GC). The calculated selectivity value at 50.7% conversion was s = 65.9. The recovered catalyst was purified by FC on silica gel (EtOAc/hexanes, 1/1 EtOAc/ hexanes/EtjN, 9/9/2), which provided 24.9 mg of pure catalyst 16 (90%). 

A vial containing ( )-4-phenyl-3-butyn-2-ol (73.0 mg, 0.500 mmol) and catalyst 16 (3.3 mg, 0.005 mmol) in tert-amyl alcohol (1.0 mL) was capped with a septum and sonicated to help dissolve the catalyst. The resulting purple solution was cooled to 0 °C, and Ac O (35.4 pL, 0.375 mmol) was added by syringe. After 49 h, the reaction mixture was quenched by the addition of a large excess of MeOH. After concentration in vacuo, the residue was purified by FC on sihca gel (EtOAc/hexanes, 1/9 — 1/1 then EtOAc/hexanes/ EtjN, 9/9/2) to afford the (l )-acetate (68.6% ee by chiral-GC) and the (5)-alcohol (96.0%ee by chiral-GC on the acetate obtained following esterification). The calculated selectivity value at 58.3% conversion was s = 20.2. 

A solution of ( )-l-(l-naphthyl)-l-ethanol (2.416 g, 14.0 mmol), DIPEA (1.93 mL, 10.5 mmol) and catalyst 45 (74 mg, 0.28 mmol) in CHCl (14 mL) was stirred at 0 for 15 min then treated with (n-Pr0)20 (1.35 mL, 10.5 mmol). The mixture was stirred at 0 for 10 h, at which time it was quenched with MeOH (10 mL), allowed to warm slowly and left for 1 h at room temperature. The reaction mixture was diluted with CH Clj, washed twice with 1 M HCl, then twice with saturated aqueous NaHCO, and dried (NaSO ). The solution was concentrated in vacuo and purified by PC on silica gel (Et O/hexanes, 1/19 —> 1/4) to give the ester (1.672 g, 52%, 82.5% ee by chiral-HPLC), and the alcohol (1.091 g, 45%, 98.8% ee by chiral-HPLC). The calculated selectivity value at 54.5% conversion was s = 52.3. The aqueous phase obtained during the work up was basified with 0.5 M NaOH and repeatedly extracted with CH Cl (until the aqueous phase was pale-yeUow), the extract was dried (Na SO ), concentrated in vacuo, and purified by FC on sfiica gel (i-PrOH/hexanes, 1/19 -> 1/9) to provide 50 mg of recovered catalyst 45 (68%). 

A mixture of 5-phenyl-l,3-dioxolane-2,4-dione (63a) (178 mg, 1.0 mmol) and 4 A MS (100 mg) in anhydrous Et O (50 mL) was stirred at room temperature for 15 min, then cooled to -78 °C, after which (DHQD)jAQN (95%, 90.2 mg, 0.1 mmol) was added to the mixture. The resulting mixture was stirred for a further 5 min and then EtOH (1.5 eq) was added dropwise over 10 min by syringe. The resulting reaction mixture was stirred at -78 °C for 24 h. HCl (IN, 5.0 mL) was added to the reaction dropwise and the resulting mixture was allowed to warm to room temperature. The organic phase was collected, washed with aqueous HCl (IN, 2 x 5.0 mL) and the aqueous phase was extracted with Et O (2 x 5.0 mL). The combined organic extracts were washed with brine, dried (Na SO ) and concentrated in vacuo. Purification by EC on silica gel (EtOAc/hexanes, 1/4) gave (R)-ethyl mandalate (64a) as a white solid (128 mg, 71%, 95% ee by chiral-HPLC). 

The mixture was extracted with diethyl ether (three times). The combined organic layers were washed with brine and dried over sodium sulfate. After concentration in vacuo, the residue was purified by silica gel flash column chromatography (hexane/ethyl acetate = 20/1-3/1) to give (5)-l (426.3 mg, 74%, 98% ee) as a colourless solid. The enantiomeric excess of (5)-l was determined by chiral stationary-phase HPLC analysis DAICEL CHIRALCEL OD-H, j-PrOH/hexane 1/4, flow rate l.OmLmin tR 14.0 min [(R)-isomer)] and 21.3 min [(5)-isomer), detection at 254 nm]. ... 

Next, we employed the timed catalyst 33 containing a benzoyl group at the catechol moiety30b under high concentration (>12 M to THF), and the product was obtained in synthetically acceptable reaction time, yield, and enantioselectivity (entry 6). The reaction was performed on a 50-g scale without any difficulty (entry 7). The chiral ligand was recovered in 95% yield after silica gel column chromatography, and could be used at least several times without any loss of catalyst activity. 

Apart from the above-discussed parameters for HPLC optimization of chiral resolution on antibiotic CSPs, some other HPLC conditions may be controlled to improve chiral resolution on these CSPs. The effect of the concentrations of antibiotics (on stationary phase) on enantioresolution varied depending on the type of racemates. The effect of the concentrations of teicoplanin has been studied on the retention (k), enantioselectivity (a), resolution (Rs), and theoretical plate number (N) for five racemates [21]. An increase in the concentration of teicoplanin resulted in an increase of a and Rs values. The most surprising fact is that the theoretical plate number (N) increases with the increase in the concentration of teicoplanin. It may be the result of the resistance of mass transfer resulting from analyte interaction with free silanol and/or the linkage chains (antibiotics linked with silica gel). This would tend to trap an analyte between the silica surface and the bulky chiral selector adhered to it. This is somewhat... 

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