Synthesis of 4-aryl-substituted β-lactam enantiomers by enzyme-catalyzed kinetic resolution

Abstract

Enantiopure 4-phenyl- and 4-( p-tolyl)-2-azetidinones 3a, 3b, 4a and 4b (with e.e.s of ≥96%) were prepared through lipase-catalyzed asymmetric butyrylation of the primary OH group of N-hydroxymethylated β-lactams (±)- 5 and (±)- 6 at the ( R)-stereogenic centre or by lipase-catalyzed asymmetric debutyrylation of O-butyryloxymethyl-2-azetidinones (±)-7 and (±)- 8 at the ( R)-stereogenic centre. The ring-opening of lactams 5a, 5b, 6b and 8a with HCl/EtOH afforded the corresponding β-amino ester enantiomers 9a, 9b, 10a and 10b with e.e.s of ≥92%.