Lipase-Catalyzed Second-Order Asymmetric Transformations as Resolution and Synthesis Strategies for Chiral 5-(Acyloxy)-2(5<i>H</i>)-furanone and Pyrrolinone Synthons

Abstract

By use of lipase R (Amano, Penicillium roqueforti ) immobilized on Hyflo Super Cell it is possible to convert at ambient temperature 5-hydroxy-5 H -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(5 H )-pyrrolinones. Racemic acetic acid 1-acetyl-5-oxo-2,5-dihydro-1 H -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.