Sequential Staudinger ketene–imine cycloaddition, RCM approach to polycyclic macrocyclic bisazetidinones

An efficient approach to novel macrocyclic azacrown ethers incorporating two azetidinone rings fused to the macrocycle through the 3,4-positions of the azetidinone rings and two macrocycles fused at 1,3,4-positions of two azetidinone rings was achieved viasequential Staudinger ketene-imine cycloaddition of o-allyloxyphenoxyketene and bis-imines followed by RCM. The ketene-imine cycloaddition afforded the corresponding bis-o-allyloxyphenoxyazetidinones as the cis-cisdiastereomers, exclusively obtained as a mixture of cis-syn-cisand cis-anti-cisdiastereomers. RCM of the latter using Grubbs' II catalyst afforded good yields of the corresponding novel macrocyclic bisazetidinones. Two cis-anti-cisbisazetidinones were readily identified by super(1)H NMR using Eu(hfc) sub(3) chiral shift reagent and the structure of two macrocycles was established by X-ray crystallography.