Enzymatic reduction of hydrophobic beta,delta-diketo esters

The regio- and enantioselective reduction of two hydrophobic beta,delta -di keto esters is presented. Enzymatic reduction of racemic tert-butyl 4-methy l-3,5-dioxohexanoate (rac-1) with alcohol dehydrogenase from Lactobacillus brevis (recLBADH) gave delta -hydroxy-beta -keto ester syn-(4S,5R)-4 under dynamic kinetic resolution conditions (99.2% ee, syn:anti = 97:3, 66% isola ted yield). The highly lipophilic tert-butyl-3,5-dioxoheptanoate (2) was re duced with the same sense of enantio- and regioselectivity by recLBADH. A b iphasic system was applied in this case. The product, delta -hydroxy-beta - keto ester (R)-9 (98.5% ee, 66% isolated yield), was converted into (R)-6-e thyl-5,6-dihydropyran-2-one [(R)-10], which is a naturally occurring fragra nce.