LIPASE-CATALYZED 2ND-ORDER ASYMMETRIC TRANSFORMATIONS AS RESOLUTION AND SYNTHESIS STRATEGIES FOR CHIRAL 5-(ACYLOXY)-2(5H)-FURANONE AND PYRROLINONE SYNTHONS

By use of lipase R (Amano, Penicillium roqueforti) immobilized on Hyfl o Super Cell it is possible to convert at ambient temperature 5-hydrox y-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 e xample of an enzyme-catalyzed second-order transformation whereby the unreactive enantiomer of 5 racemizes during reaction, allowing up to 1 00% conversion and obtainment of high enantiomeric excesses. The metho d 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 t reated 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 transf ormed (100% conversion) to (-)-2, obtained in >99% enantiomeric excess . The scope of these second-order asymmetric transformations is discus sed as well as procedures for optimalization of reaction conditions wh ereby transesterification strategies are combined with those of second -order asymmetric transformation.