Bergman cyclization mechanism

Although data presented in the previous section illustrate the diversity of cycloaromatization reactions, most of the following discussion will concentrate on the Bergman cyclization - a reaction that has been studied intensively in recent decades due to its role in the mechanism of biological activity of natural anticancer antibiotics.8,9 We will take advantage of the large body of data produced by this... 

Cioslowski, J., Ed. 2001. Quantum-Mechanical Prediction of Thermochemical Data, Kluwer Dordrecht. Cramer, C. J. 1998. Bergman, Aza-Bergman, and Protonated Aza-Bergman Cyclizations and Inter-... 

A theoretical study on the reaction mechanism for the Bergman cyclization from the perspective of the Electron Localization Function and Catastrophe Theory has been reported.175 The authors argue that topological analysis of electron localization function can be used to complement the molecular orbital- or valence bond-based methods. 

Formally, the aromatization of 6 is the dihydro variant of the Bergman cyclization [7] however, compared to the latter process, the ring-closure of 6 does not require additional ( external ) hydrogen atoms to proceed. Whereas the mechanism of the Bergman cyclization, involving a benzene-1,4-diyl intermediate, is comparatively clear-cut [8], the aromatization of 6 is more complex and at least three different mechanisms are presently discussed for the process (Scheme 3) [9]. 

Jones, G. B., Warner, P. M. On the Mechanism of Quinone Formation from the Bergman Cyclization Some Theoretical Insights. J. Org. Chem. 2001, 66, 8669-8672. 

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... 

Despite the now well-established geometric contributions to Bergman cyclization over the past 10 years, many fewer examples and much less is known about potential electronic contributions to the metal-mediated cyclization event. Although it is clear that the organometallic a-7t complexation mechanisms... 

One of the most important transannular reactions of cyclic alkynes is the Bergman cycliza-lion [67] of enediynes (Scheme 8-15). Nicolaou et al. have shown that the crucial distance between the termini of the enediyne system, allowing spontaneous Bergman cyclization at room temperature, is in the range of 3.1-3.2 A [9cj. Questions about the energy and structure of the biradicaloid intermediate and the mechanism of the biradical formation have stimulated considerable theoretical and experimental work [68]. These investigations and the importance of the Bergman cyclization reaction for the action of a new class of antitumor antibiotics will not be discussed here, as the enediynes are dealt with in considerable detail in Chapter 7. 

Rrupicka M, Sander W, Marx D (2014) Mechanical manipulation of chemical reactions reactivity switching of Bergman cyclizations. J Phys Chem Lett 5 905-909... 

The 9-membered cyclic ethers 116 have been prepared via oxy-Cope rearrangement of 115, ultimately derived from D-glucose. The 10-membered bis-ether 118 was prepared via Bergman cyclization of the bis-acetylene 117 (R=2,3,4,6-tetra-0-benzyl-p-D-glucosyl). Solution conformational analysis was reported from NMR experiments. Dialkyne 117 was prepared by Pd-catalysed coupling of the P-D-glucosyl-l-alkyne and 1,2-diiodobenzene, and a mechanism was proposed for... 

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. 

Figure 9.14 The Bergman cyclization and the accepted mechanism [104a],...

Scheme 3.26 Mechanism of Bergman cyclization at room temperature catalyzed by an Rh complex.

Baroudi, A., Mauldin, J. and Alabugin, V.V. (2010) Conformationally gated fragmentations and rearrangements promoted by interception of the Bergman cyclization through intramolecular H-abstraction a possible mechanism of auto-resistance to natural enediyne antibiotics Journal of the American Chemical Society, 132(3), 967-979. 

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