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 1996-04, Vol.118 (16), p.3801-3803
• Main Authors: van der Deen, Hanneke, Cuiper, Agnes D, Hof, Robert P, van Oeveren, Arjan, Feringa, Ben L, Kellogg, Richard M
• Format: Article
• Language: English
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja953812h

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 °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.