Synthesis and metal ion binding studies of enediyne-containing crown ethers

The 3-ene-1,5-diyne crown ether 5 is a novel enediyne-containing crown ether that was designed as a model system for a class of enediynes that might undergo alkali metal ion-triggered Bergman cyclization. We report the preparation of 5 by two different routes. In the shorter and preferable route, a carbenoid coupling reaction is employed to simultaneously construct the enediyne moiety and effect a macrocyclization of an acyclic bis(propargyl)bromide 15 to the 24-membered crown ether 5. Under standard reaction conditions, this carbenoid coupling produces as the major product the isomeric 5-ene-1,3-diyne-crown ethers (Z)-16 and (E)-16. The formation of 5-ene-1,3-diynes from the carbenoid coupling of propargyl bromides is unprecedented. We present evidence that it is the polyether nature of dibromide 15 that leads to the formation of the 5-ene-1,3-diyne-crown ether products. Judicious control of the reaction conditions can be used to produce either 5 or (Z)-16 from 15 in synthetically useful yields. Both enediyne-crown ethers 5 and (Z)-16 bind alkali metal ions, as evidenced by their ability to extract alkali metal picrates into organic solvents. Enediyne-crown ether 5 undergoes Bergman cyclization at 135 degrees C in DMSO/1,4-cyclohexadiene to produce the known o-xylyl crown ether 4. Crown ether 5 represents an enediyne in which molecular recognition of alkali metals might serve as a trigger for Bergman cyclization.