Theoretical Study on the Mechanism of Al(salalen)-Catalyzed Hydrophosphonylation of Aldehydes

Abstract

The mechanism of the hydrophosphonylation reaction between dimethylphosphonate (DMHP) and benzaldehyde catalyzed by the Al(salalen) complex has been investigated using density functional theory (DFT) and ONIOM methods. The calculations show that the Al-phosphite (CAT) complex, formed via the P−H activation in phosphonate mediated by the polarized Alδ+−Clδ− bond, is the catalytically active species. The catalytic cycle over CAT is composed of three elementary stages: (i) the coordination of benzaldehyde to CAT; (ii) the C−P bond formation via nucleophilic addition; and (iii) the deprotonation of DMHP leading to the production of α-hydroxyl phosphonate ester with the regeneration of CAT. The deprotonation of DMHP with the regeneration of CAT is rate-determining. The calculations predict that all the intermediates and transition states in the catalytic cycle might be alternatively in cis-α or cis-β configuration, and the latter is more stable, as it bears smaller distorted strain. The stereochemistry of the entire reaction catalyzed by the chiral Al(salalen) complex should be controlled by the steric repulsion between the ortho t-Bu groups of the ligand and DMHP, as well as the coordination mode of DMHP to the catalyst. The calculations reproduce the predominant product in S configuration with high ee, which accounts well for the observations in experiments.