The regioselectivity of the Birch reduction

Article abstract of DOI:10.1021/ja00059a015

The reaction mechanism of the Birch reduction was investigated with a view of determinig how the regioselectivity is controlled. Regioselectivity is determined in the first step of radical anion protonation and in the second step of cyclohexadienyl carbanion protonation. It was ascertained that the rate-determining step of the Birch reduction of anisole was radical anion protonation, consistent with the observation of Krapcho and Bothner-By in the case of benzene reduction. A new approach to determining the regioselectivity of the two steps of the Birch reduction was devised. This was predicated on an enhanced primary deuterium isotope effect anticipated for radical anion protonation relative to that expected for cyclohexadienyl carbanion protonation. The approach utilized a partially deuterated medium. The method was applied to the reductions of anisole, 1,3-dimethoxybenzene, 3-methoxytoluane, and 2-methoxynaphthalene. The basic assumption of greater selectivity of the radical anion of the first step relative to the carbanion of the second step was explored in the cases of benzene and anisole and confirmed. In the examples studied, ortho protonation of the radical anion was found to predominate. With a view of understanding the regioselectivity of the two steps, quantum mechanical computations were carried out on several facets of the reaction. Electron density distributions of the radical anions were determined as well as the energies of radical products of some radical anion protonations. Similarly, the energies were obtained for the partially protonated radical anion species at several points along the reaction coordinate. In addition, electron densities were obtained for cyclohexadienyl anion. Theory was then correlated with experiment.