Resolution of 1-(2-naphthyl)ethanol by a combination of an enzyme-catalyzed kinetic resolution with a fluorous triphasic separative reaction

Organic Letters

Volumn 4, Issue 15, 2002, Pages 2585-2587

  Luo, Zhiyong ^a   Swaleh, Sauda M ^b   Theil, Fritz ^b   Curran, Dennis P ^c  

^a Fluorous Technologies Inc   (United States)

^b ASCA GmbH   (Germany)

^c UNIVERSITY OF PITTSBURGH   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

1 (2 NAPHTHYL)ETHANOL; 1-(2-NAPHTHYL)ETHANOL; ALCOHOL; DRUG DERIVATIVE; ESTER; FLUORESCENT DYE; FUNGAL PROTEIN; LIPASE B, CANDIDA ANTARCTICA; NAPHTHALENE DERIVATIVE; SOLVENT; TRIACYLGLYCEROL LIPASE;

ARTICLE; CATALYSIS; CHEMISTRY; ISOLATION AND PURIFICATION; KINETICS; METABOLISM; STEREOISOMERISM;

CATALYSIS; ESTERS; ETHANOL; FLUORESCENT DYES; FUNGAL PROTEINS; KINETICS; LIPASE; NAPHTHALENES; SOLVENTS; STEREOISOMERISM;

EID: 0001267533     PISSN: 15237060     EISSN: None     Source Type: Journal    
DOI: 10.1021/ol026232f     Document Type: Article

References (11)

1. (a) Jacques, J.; Collet, A.; Wilen, S. H. Enantiomers, Racemates and Resolutions; Wiley: New York, 1981.
2. (b) Eliel, E. L.; Wilen, S. H. Stereochemistry of Organic Compounds; John Wiley & Sons: New York, 1994; Chapter 7.
3. (c) Kagan, H. B.; Fiaud, J. C. Top. Stereochem. 1988, 18, 249.
4. (d) Cook, G. R. Curr. Org. Chem. 2000, 4, 869.
5. (a) Hungerhoff, B.; Sonnenschein, H.; Theil, F. Angew. Chem., Int. Ed. Engl. 2001, 40, 2492.
6. (b) Hungerhoff, B.; Sonenschein, S.; Theil, F. J. Org. Chem. 2002, 67, 1781.
7. Nakamura, H.; Lindau, B.; Curran, D. P. J. Am. Chem. Soc. 2001, 123, 10119.
8. Swaleh, S. M.; Hungerhoff, B.; Sonnenschein, H.; Theil, F. Tetrahedron 2002, 58, 4085.
9. Kinetic Resolution of rac-1. A solution of the racemic ester rac-1 (5 mmol) in acetonitrile (120 mL) was treated with n-butanol (20 mmol) and C. antarctica B lipase (Chirazyme L-2, c.-f., lyo. from Roche Diagnostics, Mannheim) (8.0 g). The reaction mixture was stirred at ambient temperature until the conversion reached ca. 50% (estimated by TLC, 7 days). The lipase was removed by filtration and washed with acetone (2 × 40 mL). The combined filtrates were evaporated under reduced pressure to provide a mixture of ester (S)-1, alcohol (R)-2, and butyl ester 3 (butyl 2H,2H,3H,3H-perfluoroundecanoate). An aliquot of this mixture (116 mg) was purified by silica gel column chromatography (15-30% EtOAc/hexane) to give alcohol (R)-2 (16.0 mg, 50% yield, >99% ee) and ester (S)-1 (60 mg). Treatment of (S)-1 with NaOMe/MeOH at room temperature for 30 min to give (S)-2 (15 mg, 50% yield, 91% ee). The ee's of (S)-2 and (R)-2 were determined by chiral HPLC (column: Chiralcel OJ, eluent: n-hexane/ 2-propanol (9:1), flow rate: 1 mL/min, UV detection at 254 nm).
10. 3 (6 mL, 5:1) to the substrate side and NaOMe (0.2 mL, 25wt % in MeOH) in MeOH (6 mL) to the reagent side. All three phases are gently stirred at room temperature for 72 h. The source phase was taken up with a pipet and evaporated to dryness. The residue was passed through a silica plug with 25% EtOAc/ hexanes to give (R)-2 (13 mg, 45% yield, 95 ± 1% ee). The receiving phase was taken up and added to 1 N aqueous HCl. After extraction with diethyl ether, the ether layer was dried over magnesium sulfate and evaporated to dryness. The residue was passed through a silica plug with 25% EtOAc/hexanes to give (S)-2 (14 mg, 48% yield, 89 ± 2% ee). The % ee was determined by chiral HPLC as mentioned above and was reported as an average of the results from two triphasic reaction experiments.
11. Due to its poor solubility in organic solvents, the recovery of methyl (3-perfluorooctyl)propionate is moderate (about 50%) in these small-scale experiments.