Metal hydride reductions of unsymmetrically substituted cyclic anhydrides attached to strained ring systems

A dramatic reversal in regioselectivity is observed in the metal hydride reduction of unsymmetrical cyclic anhydrides such as 2 , 3 , and 4 compared to cyclic anhydrides attached to bridged ring systems (e.g. 1 ). The synthesis of model cyclic anhydrides attached to strained rings is described and the ratios of isomeric lactones obtained upon reduction with metal hydride are reported. On the basis of theoretical calculations and, taking into account the intrinsic reactivity of the carbonyl group, the antiperiplanar effect, and steric congestion, an explanation is offered for the regioselectivity observed in the reduction of these compounds.