Syntheses, Thermal Reactivities, and Computational Studies of Aryl-Fused Quinoxalenediynes: Effect of Extended Benzannelation on Bergman Cyclization Energetics

A series of [b]-fused 6,7-diethynylquinoxaline derivatives have been synthesized through an imine condensation strategy to examine the effect of extended benzannelation on the thermal reactivity of enediynes. Absorption and emission spectra of the highly conjugated quinoxalenediynes were red-shifted approximately 100-200 nm relative to those of 1,2-diethynylbenzene. Strong exotherms indicative of enediyne cyclization were observed by differential scanning calorimetry, while solution cyclizations in the presence of 1,4-cyclohexadiene confirmed C(1)-C(6) Bergman cyclization. To provide further insight into Bergman cyclization energetics, computational studies were performed to compare changes in the cyclization enthalpy barrier, reaction enthalpy, and barrier of retro-Bergman ring-opening. Extension of benzannelation from 1,2-diethynylbenzene to either 2,3-diethynylnaphthalene or the 6,7-diethynylquinoxalines had a minimal effect on the cyclization barrier. In comparison, the enthalpies of cyclization were increased upon linearly extended benzannelation, which resulted in reduced barriers to retro-Bergman ring-opening. In addition, the orientation of extended benzannelation was found to have a significant effect on the cyclization endothermicity. In particular, 5,6-diethynylquinoxaline exhibited a 6.9 kcal/mol decrease in cyclization enthalpy compared to 6,7-diethynylquinoxaline due to increased aromatic stabilization energy in the respective angularly versus linearly fused azaacene cyclized products.