Preparation of (3S,4S)-1-Benzhydryl-3-[(5R)-1′-hydroxyethyl]-4-acyl-2-azetidinones from (2R,3R)-Epoxybutyramide Precursors

The N-(phenacyl)-8a and N-(pivaloylmethyl)-8b derivatives of N-(benzhydryl)-(2R,3R)-cis-2,3-epoxybutyramide were prepared from sodium (2R,3R)-cis-2,3-epoxybutanoate 4. Under basic conditions they gave SNi reactions leading to the formation of four-, six- and seven-membered heterocycles, namely the azetidin-2-ones 9a, b (C-alkylation), the 2,3-dehydro-morpholin-5-ones 10a, b (O-alkylation), and the 4,5,6,7-tetrahydro-4-aza-oxepin-5-ones 12a, b (O-alkylation). The structures were confirmed by NMR analysis. Other rearrangement products, 13a and 14b, were also isolated.