Trigger cycloaromatization

An elegant design using a based-induced internal SN2 displacement reaction is depicted in Scheme 20.36 [7, 8], Treatment of 176 with triethylamine in the presence of 1,4-CHD triggered the formation of the enyne-allene 177, leading to the biradical 178 and, after hydrogen-atom abstractions, the cycloaromatized adduct 179. 

Two derivatives, compound 94, which bears an esperamicin core with an epoxide trigger, and 95, which is a hybrid between esperamicin and dynemicin A cores,have been reported (Scheme 19.25). Both compounds, after trifluoroacetamide removal, underwent cycloaromatization and showed an interesting antitumor activity in vivo in mice. 

Shibuya, M. Wakayama, M. Naoe, Y. Kawakami, T. Ishigaki, K. Nemoto, H. Shimizu, H. Nagao, Y. Cycloaromatization of enediyne model compounds via a reaction cascade triggered by hydrolysis of the a-alkynylmalonates. Tetrahedron Lett. 1996, 37, 865-868. 

It is also possible that epoxide opening is initiated by electron push from the nitrogen atom rather than the phenol, and this will be discussed in a later section. In either case, epoxide opening is the trigger for cycloaromatization, diradical formation and DNA damage [118-120]. 

Scheme 7-69 Synthesis and chemistry of cobalt complexes of dynemicin A model systems. Triggering of the Bergman cycloaromatization by decomplexation (Nicolaou et al.).

Kovalenko and Alabugin reported that Cj-C cyclization of benzannelated enediynes with tetra-fluoropyridinyl (TFP) substituents at the terminal alkyne carbons forms indenes rather than fulvenes (Scheme 30.22). The radical/anionic Cj-Cj cyclization of enediynes represents a new type of cycloaromatization reaction—the cyclorearomatization process driven by rearomatization in the vicinity of the TS. This process is triggered via photoinduced electron transfer (PET) [35-38]. Expaimental work unambiguously established PET as the triggering event for the Cj-C cascade and the intermediacy of the second PET step in the indene-forming cascade [39]. Unlike the stable benzene product... 

Karpov, G.V. and Popik, V.V. (2007) Triggering of the Bergman cyclization by photochemical ring contraction. Facile cycloaromatization of benzannulated cyclodeca-3,7-diene-l,5-diynes. Journal of the American Chemical Society, 129(13), 3792-3793. 

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