An Enantioselective Synthesis of 3,4‐Benzo‐5‐oxacephams

The title compounds represent an interesting group of β‐lactam antibiotics and active inhibitors of β‐lactamase enzymes. All these compounds have one structural feature in common, an alkoxy fragment located at C4 of the azetidin‐2‐one ring. The most common strategy for the synthesis of 4‐alkoxyazetidinons involves intramolecular nucleophilic substitution at C4 that leads to ring closure. Such a displacement proceeds via the flat intermediate that suppossedly has the structure of a mezomeric acyl ammonium cation. We herein report a novel and enantioselective, chiral Lewis acid mediated cyclization that affords the corresponding 5‐oxacepham with excellent optical and chemical yields of up to 50 %. This may suggest that the high asymmetric induction is a result of a kinetic resolution of the initially formed racemic oxacepham. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)