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

Abstract

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 via sequential 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-cis diastereomers, exclusively obtained as a mixture of cis-syn-cis and cis-anti-cis diastereomers. RCM of the latter using Grubbs' II catalyst afforded good yields of the corresponding novel macrocyclic bisazetidinones. Two cis-anti-cis bisazetidinones were readily identified by 1H NMR using Eu(hfc)3 chiral shift reagent and the structure of two macrocycles was established by X-ray crystallography.