Thermal Bergman Cyclization

Rawat, D. S., Zaleski, J. M. Geometric and electronic control of thermal Bergman cyclization. Synlett 200i, 393-421. 

Choy, N. Blanco, B. Wen, J. Krishnan, A. Russell, K.C. Photochemical and thermal Bergman cyclization of a pyrimidine enediynol and enediynone. Organic Lett. 2000, 2, 3761-3764. 

Electronic Structure Contributions to Thermal Bergman Cyclization... 

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... 

Benites, P.J., Rawat, D.S. and Zaleski, J.M. (2000) Metalloenediynes ligand field control of thermal Bergman cyclization reactions. Journal of the American Chemical Society, 122(30), 7208-7217. 

In the case of the Bergman cyclization and the C1-C5 cyclization of enediynes, both the activation barrier for cyclization as well as the thermodynamics of the reaction became more favorable upon one-electron reduction compared to the thermal counterparts. The cyclization barrier drops by up to 12kcal/mol (in the C1-C5 cyclization) and the process becomes exothermic (as opposed to the endothermic cyclizations of the neutral counterparts) as illustrated in Fig. 19 and Fig. 20. 

Bergman cyclization of the enediyne alcohol 985 gave the tetrahydrobenzoquinazoline 986, both thermally and photochemically in isopropanol, while the analogous ketone only showed efficient thermal cyclization <20000L3761>. 

The Bergman Cyclization (or Myers-Saito Cyclization) allows the construction of substituted arenes through the thermal or photochemical cycloaromatization of enediynes in the presence of a H donor such as 1,4-cyclohexadiene. 

The Bergman cyclization is quite sensitive to substituent effects, and substituents at the alkyne termini are generally the most effective. It has been demonstrated that electron acceptor substituents, and more in particular cr-acceptors and/or Tr-donors. can facilitate the thermal cyclization, but apart from the work reported by Sander for the tetrafluoro-substituted enediyne 110 (which undergoes an exothermic Bergman cyclization), so far this approach has not produced particularly promising results (Scheme 19.30). 

Rawat, D.S. Zaleski, J.M. Syntheses and thermal reactivities of symmetrically and asymmetrically substituted acyclic enediynes steric control of Bergman cyclization temperatures. Chem. Commun. 2000, 2493-2494. 

A variety of methods are used to generate and study diyls including, to name a few, the thermal or photochemically promoted extrusion of nitrogen from a pyr-azoline, the Norrish type I photochemically initiated extrusion of carbon monoxide from a cyclic ketone, and the Bergman cyclization of enediynes [3-5]. In this chapter we focus upon the synthetic utility of diradicals, paying particular attention to the work of others as well as research originating from our laboratory. 

The Bergman cyclization, also known as the Bergman cycloaromatization, is a thermal, photochemical, or metal-mediated eyeloaromatization of... 

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. 

Turro and co-workers showed that simple acyclic aromatic enediynes, such as 11, could also undergo Bergman cyclization under photochemical conditions. They proposed that the photo-Bergman cyclization of these substrates involved a diradical intermediate 2 identical to that of the thermal reaction."... 

Other Direct Syntheses. One route to substituted poly(p-phenyl-ene) derivatives makes use of the Bergman cyclization of enediynes (Fig. 8). Thermal treatment of the enediyne yields poly(p-phenyl-ene) derivatives with molecular weights of 1500-2500 [242]. 

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