Synthesis of novel 4-(2-oxoethylidene)azetidin-2-ones by a Lewis acid mediated reaction of acyldiazo compounds

We report the synthesis of a class of 4-(2-oxoethylidene)azeti-din-2-ones by a novel Lewis acid mediated reaction of acyldiazo compounds with 4-acetoxyazetidin-2-ones. Using this approach, C-3-and C-4-substituted 4-alkylideneazetidin-2-ones were obtained depending on the choice of starting azetidinone and alpha-diazocarbonyl compound. The products reveal excellent Z diastereoselection of the C-4 double bond. Variable amounts of E isomers are obtained depending on the nature of the C-3 side chain, the Lewis acid, and the P-lactam protection. VT NMR spectroscopic experiments and X-ray structural analysis of crystalline derivatives demonstrate the presence of an intramolecular hydrogen bond in Z isomers, which drives the stereochemical outcome of the reaction. A possible mechanism for this novel reaction is proposed. ((C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003).