Lipase-catalyzed second-order asymmetric transformations as resolution and synthesis strategies for chiral 5-(acyloxy)-2(5H)-furanone and pyrrolinone synthons

• Published in: Journal of the American Chemical Society
• Main Authors: vanderDeen, H, Cuiper, AD, Hof, RP, vanOeveren, A, Feringa, BL, Kellogg, RM
• Format: Article in Journal/Newspaper
• Language: English
• Published: 1996
• Subjects: INSITU RACEMIZATION; Antarc*; Antarctica
• Online Access: https://hdl.handle.net/11370/f86bde2b-8a27-46e3-be52-34551b9b0f10; https://research.rug.nl/en/publications/f86bde2b-8a27-46e3-be52-34551b9b0f10; https://doi.org/10.1021/ja953812h; https://pure.rug.nl/ws/files/3621819/1996JAmChemSocvdDeenSupp.pdf; https://pure.rug.nl/ws/files/3621820/1996JAmChemSocvdDeen.pdf

By use of lipase R (Amano, Penicillium roqueforti) immobilized on Hyflo Super Cell it is possible to convert at ambient temperature 5-hydroxy-5H-furan-2-one (5) to acetic acid 5-oxo-2,5-dihydrofuran-2-yl ester (1b) by acylation with vinyl acetate in 1:1 cyclohexane-butyl acetate. At 90% conversion the enantiomeric excess of 1b is 100%. This is an example of an enzyme-catalyzed second-order transformation whereby the unreactive enantiomer of 5 racemizes during reaction, allowing up to 100% conversion and obtainment of high enantiomeric excesses. The method is even more effective with 5-(acyloxy)-2(5H)-pyrrolinones. Racemic acetic acid 1-acetyl-5-oxo-2,5-dihydro-1H-pyrrol-2-yl ester (2) when treated with the lipase from Candida antarctica at ambient temperature in 3:1 n-hexane-butanol undergoes exactly 50% conversion to afford (+)-2 in >99% enantiomeric excess. This is the unreactive enantiomer. The (-)-enantiomer is converted to the 5-hydroxy derivative 6, which with Candida antarctica in 1:1 n-hexane-vinyl acetate at 69 degrees C (the temperature is higher to increase the rate of racemization) is transformed (100% conversion) to (-)-2, obtained in >99% enantiomeric excess. The scope of these second-order asymmetric transformations is discussed as well as procedures for optimalization of reaction conditions whereby transesterification strategies are combined with those of second-order asymmetric transformation.