Bergman Cyclization is a reaction in which enediyne compounds undergo thermal or photochemical cyclization in the presence of a hydrogen donor (such as 1,4-cyclohexadiene) to form substituted benzene derivatives. The reaction is named after American chemist Robert G. Bergman.

Due to the limited range of suitable substrates and stringent conditions, early research on the Bergman cyclization was sparse. However, the discovery of a natural product containing an enediyne structure with high cytotoxicity brought renewed scientific interest. For example, calicheamicin can undergo Bergman cyclization under physiological conditions to form a reactive diradical intermediate that abstracts hydrogen atoms from DNA strands, resulting in irreparable DNA damage.

With the discovery of natural products like calicheamicin, studies on Bergman cyclization have significantly increased. Many enediyne-containing compounds are now considered potential anticancer agents, making research into performing this reaction under mild (e.g., room temperature) conditions a major focus. Currently, the kinetic parameters of the Bergman cyclization are a hot topic of research.

Reagents: Hydrogen donor (e.g., 1,4-cyclohexadiene)
Reactants: Conjugated enediyne
Products: Benzene derivatives
Reaction type: Cyclization reaction

Experimental Tips:

• Key reaction conditions include heating or irradiation; most cyclizations require temperatures around 200 °C.

• The distance between the two triple bonds is critical to the reaction temperature: the greater the distance, the higher the required temperature.

Reaction Mechanism

Original Reference:
Richard R. Jones and Robert G. Bergman. Journal of the American Chemical Society, 1972, 94 (2): 660–661.

Popular Citations:

• Ambient Temperature Activation of Haloporphyrinic-Enediynes: Electronic Contributions to Bergman Cycloaromatization. J. Am. Chem. Soc. 2003, 125(38), 11484–11485.

• Redox-controlled Bergman cycloaromatizations. Designed enediynes with DNA-cleaving properties and antitumor activity. J. Am. Chem. Soc. 1992, 114(24), 9279–9282.

• Design, synthesis, and study of simple monocyclic conjugated enediynes. The 10-membered ring enediyne moiety of the enediyne anticancer antibiotics. J. Am. Chem. Soc. 1992, 114(19), 7360–7371.