STEREOCONTROL BY THE CARBON FLUORINE BOND AND ITS APPLICATION TO ASYMMETRIC-SYNTHESIS OF 3-FLUORO BETA-LACTAMS

Optically active 3-fluoro-beta-lactams 4 and 5 were prepared via a ket ene-imine cycloaddition reaction using fluoroacetyl chloride and an im ine derived from (R)-glyceraldehyde acetonide. The high stereoselectiv ity observed can be rationalized as a consequence of stereoelectronic effects. Deprotonated beta-lactams 4 and 12 were reacted with alkylati ng agents to give exclusively cis-3-alkyl-substituted derivatives of 3 -fluoro beta-lactams. The directed aldol reaction of beta-lactams 4 an d 12 with aldehydes and ketones provides cis-3-hydroxyalkyl derivative s with high stereoselectivity; however, diastereoisomeric control was not maintained at the hydroxylated carbon atom. The desired stereochem istry in the side chain was achieved by reduction of 3-acetyl-3-fluoro beta-lactam 22. The lithium enolates of beta-lactams 4 and 12 have be en investigated by low-temperature F-19 NMR studies.