Collect. Czech. Chem. Commun. 2004, 69, 945-965

Electronic Effects on the Bergman Cyclisation of Enediynes. A Review

Michael Klein, Thomas Walenzyk and Burkhard König*

Institut für Organische Chemie, Universität Regensburg, D-93040 Regensburg, Germany


The thermal cyclisation of enediynes to benzene-1,4-diyl diradicals (Bergman cyclisation) is affected by geometrical and electronic conditions. While the effect of ring strain or conformational constrains on the cyclisation temperature has been investigated in detail, electronic contributions have been less studied. Often geometrical and electronic contributions cannot be clearly distinguished. In most cases metal ion chelation does involve both. In this review we have summarised clear-cut observations of electronic substituents effects on the thermal enediyne reactivity. The effects of substituents in the vinylic and terminal alkyne position, the influence of benzo-fusion and hetarene fusion, as well as the changes induced by heteroatoms in the enediyne skeleton, are within the scope of this review. With the exception of more complex heterocyclic hetarene-fused enediynes the experimental data of electronic substituent effects on the thermal Bergman cyclisation of enediynes follow theoretical predictions. A review with 57 references.

Keywords: Enediynes; Bergman cyclisations; Electronic substituent effects; Alkynes; DNA cleavage agents; Antibiotics; Cytotoxic compounds.

References: 91 live references.