A three component coupling approach to a chiral 1β-methylcarbapenem key intermediate

Article abstract of DOI:10.1021/jo00106a027

Conjugate addition of N-benzyl-N-((R)-1-phenylethyl)amine (R)-5 to (R)-(E)-tert-butyl 5-((tert-butyldimethylsilyl)oxy)-4-methyl-2-pentenoate (10a) produced the (3S,4R)-syn-adduct 14 with essentially 100% de in 84% yield, whereas the addition of (S)-5 to 10a afforded the (3R,4R)-antiadduct 15 with essentially 100% de in 95% yield. The syn adduct 14 was converted upon sequential treatment with lithium diisopropylamide-methylaluminum dichloride-acetaldehyde to the key intermediate 21; the diastereoisomer ratio of 21 to other diastereoisomers was 80:20. Conversion of 21 to a 1β-methylcarbapenem key intermediate 26 was carried out readily according to the known procedures.