Regioselectivity of metal hydride reductions of unsymmetrically substituted cyclic anhydrides. systems where "steric hindrance along the preferred reaction path" rationalization is not applicable

Metal hydride reductions of planar cyclic anhydrides such as methylmaleic or 3-substituted phthalic anhydrides occur preferentially at the sterically more hindered carbonyl function. This regioselectivity cannot be rationalized in terms of "the most favourable pathway for non-perpendicular attack by a nucleophile" since both carbonyl groups present are equally accessible to non-perpendicular approach. A study which takes into account the alkaline cation and inductive, mesomeric, and steric effects has been conducted for the reduction of several conjugated and aromatic anhydrides. A qualitative interprétation for the regioselectivities observed in these reductions (as well as in reductions already reported in the literature) is suggested. An early transition state for the catalyzed versus late transition state for the non-catalyzed process is proposed.