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

The title compounds represent an interesting group of beta-lactam antibiotics and active inhibitors of beta-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. ((C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)