Chiral gels temperature

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). 

In the alkylation reactions of the chiral 3-acyl-2-oxazolidinones, deprotonation to the lithium or sodium enolate is by treatment with lithium diisopropylamide or lithium or sodium hexamethyldisilazanide in tetrahydrofuran at low temperature (usually — 78 °C). The haloalka-ne, usually in excess, is then added to the enolate solution at low temperature (usually — 78 °C) for the sodium enolates and at higher temperatures (between —78 and 0CC) for the lithium enolates. When small, less sterically demanding halides, such as iodomethane, are used the sodium enolate is usually preferred 2 24 and in these cases up to five equivalents2,6- 24,26,27 of the halide are necessary in order to obtain good yields of the alkylation products. Conventional extractive workup provides the crude product as a diastereomeric mixture (d.r. usually > 90 10) which is relatively easy to separate by silica gel chromatography and/or by recrystallization (for crystalline products). Thus, it is possible to obtain one diastereomer in very high diastereomeric purity. 

A 10 mL round-bottomed flask was charged with (5)-6,6 -[oxybis(ethylene) dioxy]biphenyl-2,2 -diol (1) (98% ee, 225.6 mg, 0.78 mmol), quinine (127.0 mg, 0.39 mmol) and ethanol (2mL). The mixture was warmed until the mixture suspension turned to a clear solution, and was allowed to settle for 12 h. The solid residue [crystals of (5)-l-quinine complex] was collected by filtration. To a mixture of aqueous 1 M HCl and ether was added the obtained crystals of (5 )-l-qumine complex. This was stirred for 15 min at room temperature, and the solution was extracted with ether (twice). 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 optically pure (5)-l (167.8 mg, 74%, 99% ee) as a colourless solid. The enantiomeric excess of (5)-l was determined by chiral stationary-phase HPLC analysis DAICEL CHIRALCEL... 

Chalcone 1 and malonate 2 in stoichiometric amounts (5 mmol) were vigorously shaken with a mechanical stirrer during 1 h at the required temperature (generally 60 °C) in the presence of catalytic quantities (6% mol) of KOH and chiral ammonium salt 4. Then, the reaction mixture was cooled to room temperature and extracted with methylene chloride (50 mL). Product 3 was purified by chromatography on silica gel. Yield 57%, 68% ee. 

The authors reported the chiral separation of proline and thereonine amino acid up to 20 and 6g, respectively, in a single run. Micropreparative resolution of lecucine was presented. The resolution was discussed with respect to the degree of sorbent saturation with copper(II), elution rate, eluent concentration, temperature, and column loading condition [16]. Weinstein [74] reported the micropreparative separation of alkylated amino acids on a Chiral ProCu column. In another article, a preparative chiral resolution of 3-methylene-7-benzylidene-bicyclo[3.3.1]nonane was achieved on 7.5% silver(I)-d-camphor- 10-sulfonate CSP [75]. Later, Shieh et al. [71] used L-proline-loaded silica gel for the chiral resolution of (ft,5 )-phcnylcthanolaminc as the Schiff base of 2-hydroxy-4-methoxyacetophenone. Gris et al. [76] presented the preparative separations of amino acids on Chirosolve L-proline and Chirosolve L-pipecolic acid CSPs. 

Reaction of rac-1 -tert-buty l-3-chloroazetidin-2-one (28) with 25 gave the rac-phthalimide derivative (29). Optical resolution of rac-29 was accomplished efficiently by complexation with 15. When a solution of 15b and two molar equivalents of rac-29 in benzene-hexane (1 1) was kept at room temperature for 12 h, a crystalline 1 1 inclusion complex of 15b and (-)-29 was obtained. After one recrystallization from benzene-hexane, the crystals were chromatographed on silica gel to give pure complex consisting of (-)-29 of 100% ee in 63% yield. Decomposition of the complex with hydrazine gave optically pine (-)-3-amino- l-/m-butylazetidin-2-onc (30) in 44% yield.15 Mechanism of the precise chiral recognition between 15b and (-)-29 in their 1 1 complex was clarified by X-ray crystal structural analysis.15... 

To a solution of racemic 4-phenyl-3-butyn-2-ol (14.6 mg, 0.10 mmol) in chlorobenzene (1.0 mL) was added bicyclohexyl (16.6 mg, 0.10 mmol) as internal standard for GC analysis. An aliquot (50 iL) of this solution was taken out of the flask as a zero point and passed through silica gel (8 2hexane-EtOAc eluent) before analysis by GC. The Ru complex 1 (2.0 mg, 2.0 pmol) was added to the remaining solution and the mixture was stirred in air at room temperature for 17 h with irradiation by fluorescent light (100 V, 25 W). To remove the complex the mixture was filtered through silica gel (8 2 hexane-EtOAc eluent) and analyzed by GC (65.3% conversion). The filtrate was then concentrated and chromatographed on silica gel (8 2hexane-EtOAc). Chiral HPLC analysis (Chiralcel OD-H, 15 1 hexane-i-PrOH) of the purified alcohol showed >99.5 % ee. 

To a solution of chiral carbene catalyst (0.03 mmol, 5 mol%) and 1-phenyletha-nol (73.2 mg, 72 pL, 0.6 mmol) in THF (2 mL) was added vinyl diphenylacetate (117.5 mg, 0.45 mmol) dropwise at —78 °C. The reaction mixture was stirred at this temperature for 3 h, and then treated with 0.1 M HCl and extracted with ether. The combined organic layers were washed with brine, dried (Na2S04), and concentrated in vacuo. The residue was purified by FC on silica gel (ether hex-anes, 1 50 to 1 2) to afford (P)-l-phenylethyl diphenylacetate (65 mg, 32%, 96% ee by chiral-HPLC) and (S)-l-phenylethanol (44.6 mg, 61%, 52% ee by chiral HPLC). The calculated selectivity value at 34% conversion was s = 80. 

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