MPV-Reduction of C=O bond with Al-substituted-dialkylalan; A Theoretical Study on Relative Reactivity of Various Carbonyl Substrates

Relative reactivity of various carbonyl and acid derivatives in MPV-type (Meerwein-Ponndorf-Verley) reduction with an DIBAL(F) model has been studied via DFT and MP2 methods. Free energies of initial adduct formation (-Gadd) of DIBAL(F) model and carbonyls are in the order of amide < ester < aldehyde < ketone < acid chloride; in the alan-amide adduct, the developed positive charge at carbonyl carbon is expected to be stabilized by amide resonance, but in the acid chloride adduct it is destabilized by inductive effect of chloride. However the TS barrier energies (${\Delta}G_{TS}$) for the MPV-type hydride reduction of the carbonyl adducts are in the order of aldehyde < ketone < acid chloride << ester < amide; presumably decreasing order of electrophilicity of carbonyl carbon at adducts, which is well correlated with experimental data. It is noted that the relative reactivity of carbonyl derivatives in MPV-type reduction with DIBAL(X) is not governed by the alan-adduct formation energies, but follows the order of electrophilicity of carbonyl carbon of transition states.