Bergman cyclization

Bergman cyclization is an organic chemistry reaction that involves the thermal rearrangement of enynes to produce highly reactive diradical species. This reaction is named after the American chemist Robert G. Bergman, who first reported it in 1972. Bergman cyclization is a key step in the synthesis of certain natural products and has applications in the development of anticancer drugs, particularly those targeting the DNA of cancer cells.

The process involves the heating of an enyne to generate a diradical intermediate, which can then undergo various reactions, including hydrogen abstraction and cyclization, to form a new carbon-carbon bond. The diradical intermediate is highly reactive and can lead to the formation of a variety of products, depending on the specific substrates and conditions used in the reaction.

Bergman cyclization is particularly important in the synthesis of cycloaromatization products and has been utilized in the synthesis of complex natural products such as the antitumor antibiotic calicheamicin. The reaction has also been studied for its potential in the development of new chemotherapeutic agents, as the diradicals generated can interact with DNA, causing strand breaks that lead to cell death.

The mechanism of Bergman cyclization involves the formation of a six-membered ring through a pericyclic reaction. The reaction is highly dependent on the structure of the enyne, with certain substituents and configurations leading to more favorable cyclization conditions. The reaction can proceed under thermal or photochemical conditions, with the latter sometimes offering more control over the reaction pathway and product distribution.