Synthesis and structure determination of methyl (3 S)- and (3 R)-( trans-(3′ R,4′ R)-3-amino-1-(4-methoxyphenyl)-2-oxo-4-phenylazetidin-3-yl)-2,2-dimethyl-3-ferrocenylpropanoate

Abstract

Lewis acid (ZnI 2) – promoted Mannich reaction of azetidin-2-one – tethered aldimine 3 with silylenol ether 4 in toluene at –20 °C afforded a diastereomeric mixture of β-amino acid esters 5 and 6 in ratio 65:35. Diastereomers 5 and 6 were chromatographically separated and their crystal structure determined in order to establish unambiguously both absolute and relative configurations at the stereogenic centers C11, C12, and C14. The final value of the freely refined Flack parameter of diastereomer 6, x = −0.003 (3), unambiguously indicates that all three centers have R configuration. According to the synthetic procedure, configurations on C12 and C14 of diastereomer 5 have the same R orientation as of diastereomer 6, therefore Friedel pairs for the structure of 5 were not measured. Furthermore, S configuration on C11 of diastereomer 5 was assigned in relation to R configuration at C12 and C14 stereogenic centers.