Asymmetric Synthesis of Optically Active 3-Substitutedδ-Valerolactones Using Lipase in Organic Solvents

In organic solvents, lipase Amano P catalyzed the asymmetric ring opening of glutaric anhydrides bearing −CH2Cl, −CH2F and −OCH3 groups at position 3 with methanol and 1-butanol to afford the corresponding mono esters in 70–86% e.e. Optically active δ-valerolactones were synthesized from the mono esters in overall yields of 34–62%. The R-configuration was assigned to the mono esters and the lactones by means of a CD analysis and chemical correlation. This indicates that the lipase preferentially attacked the pro-R carbonyl group of these anhydrides carrying hetero atoms, in keeping with the trend observed for glutaric anhydrides having simple alkyl substituents.