STUDIES ON THE THERMAL GENERATION AND REACTIVITY OF A CLASS OF (SIGMA,PI)-1,4-BIRADICALS

(Z)-1,2,4-Heptatrien-6-yne and compounds that contain the (Z)-allene-ene-yne functional group or that form it in a serial reaction sequence were prepared and shown to undergo a mild thermal reaction to form aromatic products. All observations suggest that the initial step in the formation of these products is an electrocyclization reaction that forms alpha,3-dehydrotoluene in the parent case or the corresponding alpha,3-dehydroalkylbenzene in other examples. These dehydroaromatic intermediates are not observed directly but react to form products conventionally ascribed to both free radical and polar species. For example, (Z)-1,2,4-heptatrien-6-yne forms both 2-phenylethanol and phenyl methyl ether when heated in methanol. Mechanistic studies suggest that both products arise from a common intermediate, the so-called alpha,3-dehydrotoluene, that is best described as a singlet sigma,pi-biradical with substantial polar character. The partitioning between polar and free radical reaction pathways is influenced by biradical substitution and by the reaction medium in which the intermediate is generated. These results are discussed with reference to electrocyclization reactions occurring within the enediyne family of natural antitumor agents. The possibility that an alpha,3-dehydrotoluene intermediate might function as a DNA damaging agent and criteria for the design of molecules to implement such a strategy are discussed.