A mixture of techniques, both experimental and theoretical, have been used to elucidate the effect of proximal aromatic residues on free-radical reactions. Synthetic model compounds, such as anthracene adducts, and acyclic models with
both no aromatic groups and with substituted aromatic groups remote from the putative radical site, have been prepared.
The relative rates of reaction towards tri-butyl tin hydride of synthetic models containing differently substituted aromatic groups follow a linear Hammett relationship with a positive value of the reaction constant and demonstrate that
electron withdrawing groups increase the reactivity of the substrate by stabilising the ◊- transition state during bromine abstraction. Theoretical calculations of the radical stabilisation energies of anthracene derivatives at the RMP2/6-31 G(d)//B3-L YP/6-31 G( d) level of theory show that stabilisation of the radical intermediate is negligible for this particular system. Analysis of the hyperfine structure of the ESR spectrum of anthracene models shows that the radical formed by bromine abstraction interacts with the a-protons and the P-protons, but it does not interact significantly with the aromatic moiety.
The electrochemical reduction by cyclic voltammetry of the carbon-bromine bond of the synthetic models is primarily governed by the kinetics of the electron transfer step and takes place through a concerted mechanism. Han1mett plots indicate that electron donating groups at the aromatic ring destabilise the intermediate, whereas electron withdrawing groups have a stabilising effect of the ◊- transition state, consistent with the results of the relative rate studies.
Paracyclophane derivatives are excellent models to study aromatic-radical interactions due to their constrained geometry. Intramolecular cyclisation promoted by samarium iodide, the McMurry coupling and ring closing metathesis afford
different products other than the cyclised paracyclophane as the major components.
The acyloin condensation gives low yield of paracyclophane and is difficult to reproduce. Instead, the cycloaddition of quaternary ammonium hydroxides initiated by the Hoffmann elimination constitutes a reliable method to prepare
[8]-paracyclophanes and is the most likely route for a successful synthesis of [9]-paracyclophanes.