Azetidinones 4-methylene- from

Intramolecular nucleophilic substitution by an active methylene linked to the nitrogen atom of a-substituted carboxamides was first utilized in azetidinone synthesis by Sheehan and Bose in 1950 [27]. When 3-hydroxyethylazetidinones became an important research target, it was realized that L-threonine or D-allo-treonine, easily converted to bromohydrins 57,61 or to epoxyacid 64, are by this method one of the most convenient natural chiral source for penem and carbapenem synthesis. Shiozaki et al. [28] at Sankyo s laid down the fundaments of the threonine route . Early works from D-a//o-threonine-derived 2R-bromo-3R-hydroxybutyric acid 57 were run using malonate anions as the nucleophilic moiety, as shown in amide 58, which in presence of DBN cyclized to azetidinone 59a with complete inversion of configuration [28a, c]. 

Methylene-2-azetidinones from p-bromo-p,Y-ethylenecarboxylic acid amides Modified Ullmann-Goldberg reaction... 

Mercaptoazetidinones may be prepared from penicillins or from the reaction of azidoacetyl chloride with thioimidates. 3-Azido-2-azetidinones are converted into 3-acylamino-2-azetidinone via the intermediacy of a phos-phinimine by reaction with acid chlorides. Good yields of a-methylene-/8-lactams are obtained by the insertion of carbon monoxide into various 2-bromo-3-aminopropene derivatives " in the presence of a palladium catalyst (Scheme 123). Further reactions lead to substituted derivatives. 

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