(2R,3R)-3-[(1R)-1-{[tert-Butyl(dimethyl)silyl]oxy}ethyl]-4-oxoazetidin-2-yl Acetate in Zinc- and Samarium-Promoted Substitution Reactions with Methyl 2-Bromopropanoate and Methyl (2-Bromomethyl)prop-2-enoate. Unusual Cleavage of the N1‒C4 Bond in Azetidin-2-one Derivative with Migration of Methoxycarbonyl Group in Synthetic Approaches to Carbapenems and Their Analogs

Abstract

The use of zinc in Barbier-type reactions of (2R,3R)-3-[(1R)-1-{[tert-butyl(dimethyl)silyl]oxy}-ethyl]-4-oxoazetidin-2-yl acetates with halogen derivatives led to the formation of expected substitution products. The reaction of the title compound with a reagent prepared from samarium powder, a catalytic amount of iodine, and methyl 2-bromopropanoate in THF gave an anomalous substitution product, methyl 2-{(2S,3S)-3-[(1R)-1-{[tert-butyl(dimethyl)silyl]oxy}ethyl]-4-oxoazetidin-2-yl}-2(R,S)-methyl-3-oxopentanoate. Alkylation of the latter with methyl bromoacetate afforded methyl 2-{(2S,3S)-3-[(1R)-1-{[tert-butyl(dimethyl) silyl]oxy}ethyl]-1-(2-methoxy-2-oxoethyl)-4-oxoazetidin-2-yl}-2(RS)-methyl-3-oxopentanoate which underwent fragmentation through cleavage of the N1–C4 bond under the action of sodium bis(trimethylsilyl)-amide in THF at–78°C. The resulting acyclic amide, dimethyl {(2R,S,3Z)-2-[(1R)-1-{[tert-butyl(dimethyl)-silyl]oxy}ethyl)]-4-methyl-5-oxohept-3-enoylamino}malonate, was smoothly converted to new functionalized N-substituted pyrrolidinones via intramolecular Michael type cyclization in methylene chloride in the presence of NEt3–DMAP–Boc2O.