Diastereoselective synthesis of β-lactams via Kinugasa reaction of acyclic chiral nitrones

An approach to β-lactams via a Kinugasa reaction between chiral copper acetylides and chiral acyclic nitrones bearing either 1,3-dioxane or 1,3-dioxolane moieties is reported. The stereochemical preferences observed in these reactions are discussed. The reaction provides access to a variety of interesting β-lactam structures. Electronic circular dichroism in combination with NMR spectroscopy was shown to be a useful and effective method for the reliable determination of the absolute configuration of all components of a complex mixtures of azetidinones. The effectiveness of the chiral analysis of complex mixtures was demonstrated for HPLC coupled on-line with electronic circular dichroism detection as well.

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(3S,4R)-1-Benzyl-3,4-bis((S)-2,2-dimethyl-1,3-dioxolan-4-yl)azetidin-2-oneC20H27NO5[α]D22 = +57.4 (c 0.23, CHCl3)Absolute configuration: (S,3S,4R,S)Source of chirality: l-serine

(3R,4R)-1-Benzyl-4-((S)-2,2-dimethyl-1,3-dioxan-4-yl)-3-((S)-2,2-dimethyl-1,3-dioxolan-4-yl)azetidin-2-oneC21H29NO5[α]D22 = +23.4 (c 0.45, CHCl3)Absolute configuration: (S,3R,4R,S)Source of chirality: l-serine