Alkylation of aromatics and formation of a new C-C bond is usually achieved by the electrophilic attack of an activated carbon species on an electron-rich aromatic ring. Herein, we report an alternative method for alkylation of aromatics via nucleophilic addition of enolates of active methylene compounds to 1,4-dehydrobenzene diradicals derived from enediynes cyclodec-1,5-diyne-3-ene, benzo[3,4]-cyclodec-1,5-diyne-3-ene, and cyclohexeno[3,4]-cyclodec-1,5-diyne-3-ene. The benzo-substituted enediyne produces slightly higher yields of alkylation products than do the other two enediynes, but the differences are not substantial. The reaction produces a new C-C bonded aromatic alkylation product, which allows the construction of complex polyfunctional structures in a few steps. Moreover, this reaction provides solely C-arylated products, and no O-arylation products were observed.

Enediynes are widely studied to understand their cycloaromatization and the trapping of the resulting p-dehydrobenzene diradical. However, few model substrates are known, and they are hard to synthesize and difficult to handle. Herein we report cyclohexeno[3,4]cyclodec-1,5-diyne-3-ene as a convenient model for studying the reactivity of enediynes. It can be easily synthesized from 1,2-diethynylcyclohexene and 1,4-diiodobutane. It is a solid that is stable at room temperature. In solution the p-dehydrobenzene diradical derived from its cycloaromatization can be trapped by nucleophiles. The rate-limiting step is the cyclization, which is slightly slower than that of the parent cyclodec-1,5-diyne-3-ene but faster than that of its benzo analogue, consistent with the distances between the reacting carbon atoms.

Large-ring cycloalkylamines are slightly less basic than other cycloalkylamines such as cyclohexylamine, even though all have tetrahedral carbons and are strain-free. To understand why, enthalpy and entropy for protonation of a series of cycloalkylamines were accurately determined by isothermal titration calorimetry in 3 : 1 methanol-water. The study required resolving a discrepancy between these measurements and those in pure water. The data show that the lower basicity of large-ring cycloalkylamines is not due to enthalpy but to a more negative entropy of protonation. Computations show that this can be attributed in part to an entropy of conformational mixing, but the dominant contribution is steric hindrance to solvation, also corroborated by computation.

Is a hydrogen bond symmetric, with the hydrogen centered between two donor atoms, or is it asymmetric, with the hydrogen closer to one but jumping to the other? The NMR method of isotopic perturbation has been used to distinguish these. Previous evidence from isotope shifts implies that a wide variety of dicarboxylate monanions are asymmetric, present as a rapidly equilibrating mixture of tautomers. However, calculations of hydrogen trajectories across an anharmonic potential-energy surface could reproduce the observed isotope shifts in a phthalate monoanion. Therefore, it was concluded that those isotope shifts are instead consistent with isotope-induced desymmetrization on a symmetric potential-energy surface. To distinguish between these two interpretations, the ¹⁸O-induced isotope effects on the ¹³C NMR chemical shifts of cyclohexene-1,2-dicarboxylate monoanion in chloroform-d and on the ¹⁹F NMR chemical shifts of difluoromaleate monoanion in D₂O have been investigated. In both cases the isotope effects are larger at lower temperature and also with deuterium in the hydrogen bond. It is concluded that these behaviors are consistent with the perturbation of an equilibrium between asymmetric tautomers and inconsistent with isotope-induced desymmetrization on a symmetric potential-energy surface.