Metal hydride reductions of unsymmetrical cyclic anhydrides. The importance of the antiperiplanar effect on the regioselectivity of these reactions

Abstract

A quantum mechanical study by the SCF abinitio method of the interaction of H− with methylsuccinic and 2,2-dimethylsuccinic anhydrides (naked and in the presence of a cation) suggests that nonperpendicular rearside attack cannot be the factor responsible for the regioselectivity of hydride transfer to the more sterically hindered carbonyl group. In this model, the nucleophilic attack at the less hindered carbonyl group is calculated to be of lower energy (with or without cation). Deformation of the planar succinic anhydride ring to the quasi-chair conformation is energetically favoured as it allows the nucleophile to attack both carbonyl functions antiperiplanar to a quasi axial C—H or C—C bond. The attack antiperiplanar to the C—CH3 bond is lower in energy than the attack antiperiplanar to the C—H bond suggesting that the reduction will occur at the sterically more hindered carbonyl group which is in agreement with the experimental findings.