Halo-enediynes: probing the electronic and stereoelectronic contributions to the Bergman cycloaromatization

A series of halogen-substituted cyclic enediynes were prepared with use of carbenoid coupling strategy. DFT analysis, initially used to identify synthesis candidates, was also employed to rationalize the propensity for cycloaromatization of the compounds. In all cases studied the halogen atom had a strongly retardative effect on the thermal Bergman cycloaromatization reaction. The isolation of the first C-9 monochloroenediyne is noteworthy, and may find application in prodrug design.