A 3-COMPONENT COUPLING APPROACH TO A CHIRAL 1-BETA-METHYLCARBAPENEM KEY INTERMEDIATE

Conjugate addition of N-benzyl-N((R)-1-phenylethyl)amine (R)-5 to (R)- (E)-tert-butyl tert-butyldimethylsilyl)oxy)-4-methyl-2-pentenoate (10a ) produced the (3S,4R)-syn-adduct 14 with essentially 100% de in 84% y ield, whereas the addition of (S)-5 to 10a afforded the (3R,4R)-anti-a dduct 15 with essentially 100% de in 95% yield. The syn adduct 14 was converted upon sequential treatment with lithium diisopropylamide-meth ylaluminum dichloride-acetaldehyde to the key intermediate 21; the dia stereoisomer ratio of 21 to other diasteroisomers was 80:20. Conversio n of 21 to a 1 beta-methylcarbapenem key intermediate 26 was carried o ut readily according to the known procedures.