Benzyne Bergman cyclization

In these reactions, a er-bond is formed at the expense of two re-bonds and, thus, the process leads to a net loss of one chemical bond that is intrinsically unfavorable thermodynamically. Formation of the new er-bond leads to ring closure, whereas the net loss of a bond leads to the formation of two radical centers, which can be either inside (the endo pattern in Scheme 1) or outside of the newly formed cycle (the exo pattern). Note that er-radicals are formed through the endo path, while exo-closures may produce either a er-radical when a triple bond is involved or a conjugated re-radical when the new bond is formed at the central carbon of an allene. The parent version of this process is the transformation of enediyne 1 into p-benzyne diradical2 (the Bergman cyclization), shown in Scheme 2. 

The reaction mechanism of the Bergman cyclization of the (Z)-hexa-l,5-diyne-3-ene to yield p-benzyne (Scheme 7 and Figure 9) has been studied recently in the framework... 

Scheme 7.2 Bergman cyclization of enediynes to give pora-benzyne (benz-1,4-diyl).

Bergman proposed that the reaction mechanism of the cyclization under thermal conditions (200 °C) involved the initial generation of a 1,4-benzenediyl diradical species known as para-benzyne (2). Bergman reported that when the reaction was carried out in a hydrocarbon solvent, such as 2,6,10,14-tetramethylpentadecane, benzene was formed as the final product. This suggests that the hydrocarbon solvent (RH) acts as a hydrogen atom donor to quench the diradical intermediate 2. This result hints at the radical nature of the mechanism operative in the Bergman cyclization. 

The reaction of hex-3-ene-1,5-diyne derivatives (enediynes) to p-benzyne, the Bergman cyclization, is related to the electrocyclic ring closure of hexatriene. Following the discovery of a new class of potent antitumor antibiotics that possess an enediyne unit, this reaction has received considerable attention in recent years. Although the reaction has been investigated using semiempirical methods, the use of more advanced methods for the study of a closed-shell species reacting to a diradical is clearly desirable. 

Scheme 3.12 ortA o-Effect in the Bergman cyclization trapping of p-benzyne intermediate by intramolecular hydrogen abstraction. 

It was found that cyclization of benzannulated enediynes can be initiated by irradiation to give the same products as were obtained by thermal Bergman cyclization [238]. Photo-Bergman cyclization, which is also related to the chemistry of benzyne, has not been so extensively investigated. Terminal acyclic enediynes capable of cycloaromatization by thermal C -C route do not undergo photochemical initiation. However, introduction of one or two phenyl substituents in the acetylenic branches facilitates the C -C photocyclization of acyclic enediynes, but any increase in steric hindrance raises the activation barrier and the photochemical yield is significantly lower than in the case of their cyclic... 

Usuki, T.jMita, T., Lear, M.J.,etal. (2004) Spin trapping of C-labeledp-benzynes generated by Masamune-Bergman cyclization of bicyclic nine-membered enediynes. Angewandte Chemie International Edition, 43(39), 5249-5253. 

Zeidan, T.A., Manoharan, M. and Alabugin, I.V. (2006) Ortho effect in the Bergman cyclization interception of p-benzyne intermediate by intramolecular hydrogen abstraction./onrnn/ of Organic Chemistry, 71(2), 954-961. 

Bergman first assumed that the cascade reactions of (Z,Z)-deca-3,7-diene-l,5,9-triyne 3.660 occurs via radical initiation rather than thermal cyclization, and discovered that intermediate p-benzyne diradical can... 

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