The synthetic potential of the Bergman cyclization (BC) [1] has not been greatly explored despite remarkable progress in the understanding of the reaction mechanism [2] and the mode of biological action of enediynes.[3] The radicals within the 1,4-diradical generated during the BC are distally oriented, thus preventing self-quenching, which can lead to a highly strained bicyclo system, and are spinpaired by an external quencher.[4] The 1,4-diradical can undergo polymerization, [5] which causes the usual low yield of cyclized products. BC and related reactions involve the formation of benzenoid frameworks and, hence, are attractive for the synthesis of polyaromatic and benzannulated compounds. John and Tour [6] reported the formation of polyphenylenes using BC, while Grissom and Calkins [7] demonstrated the tandem radical cyclization of enediynes with diverse alkenyl acceptors. Diradicals generated in a porphyrin network have been trapped with a neighboring aromatic ring (Smith and co-workers, [8a] and Zaleski and coworkers [8b] ). Taking a cue from these results and the ortho effect reported by Alabugin and coworkers, [9] we studied the reactivity of aryl exomethylene N-substituted cyclic enediynes of type A (Scheme 1). The initial intention was to explore the effect the p cloud of an aromatic ring [10] positioned above one of the alkynes of an enediyne framework would have on the BC. We did observe some interesting variations in reactivity depending on the R substituent present on the aromatic ring. However, the more important aspect is the synthesis of the angularly fused polyaromatic compounds [4]helicenes (C) [11] in high yields. The process, which involves the BC as the key step of an unprecedented tandem radical reaction, offers a general route to these compounds and also expands the synthetic potential of the BC.The aryl enediynes 1 required for our study were prepared from o-iodo propargyl amine 2 [12] by using a six-step protocol. A Sonogashira coupling [13] with trimethylsilyl acetylene followed by a desilylation produced the enediyne 4. Another coupling reaction with the Z-iodo alkene (obtained by a haloWittig reaction) [14] followed by THP removal furnished the acyclic enediyne 7. This was converted into the mesylate 8, which on treatment with K 2 CO 3 in anhydrous DMF [15] produced the cyclic enediyne 1 (Scheme 2). NOESY spectra (see the Supporting Information) confirmed the positioning of the aryl ring to be above the enediyne alkyne.As a test study, enediyne 1 was dissolved in [D 6 ]DMSO and kept at 90 8C (Scheme 3). The reaction was monitored by recording the 1 H NMR spectra at different times. There was a gradual decrease in the signals for the substrate accompanied [*] Dr.

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A hybrid peptide-enediyne molecule was synthesised and shown to undergo selective intramolecular peptide chain cleavage by the 1,4-diyl radical, the potential intermediate of the enediyne system.

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