Theoretical study on the mechanism and stereochemistry of salicylaldehyde–Al(III)-catalyzed hydrophosphonylation of benzaldehyde

The mechanism and stereochemistry of the hydrophosphonylation reaction between diethylphosphonate (DEHP) and benzaldehyde catalyzed by salicylaldehyde–Al(III) complexes was investigated using the density functional theory (DFT) and ONIOM methods. The calculations show that catalytic cycle over salicylaldehyde–Al(III) complexes is composed of three elementary steps: (i) the formation of Al-phosphite species via the PH activation, (ii) the CP bond formation via the nucleophilic attack of phosphite to benzaldehyde; (iii) the production of α-hydroxyl phosphonate ester with the regeneration of salicylaldehyde–Al(III) complexes. The reaction can alternatively occur over monomeric and dimeric Al active species, and the latter performs much higher catalytic efficiency, indicated by the turnover frequency (TOF) based on the energetic span model (1.5 × 104 h−1 vs 2.5 × 102 h−1). The CP bond formation is predicted to be the rate-determining step for the entire reaction, and therefore accounts for the stereoselectivity of the products. The stereochemistry of the reaction should be controlled by the steric hindrance between the adamantanyl group of the ligand and the phenyl ring of the product intermediate. The calculations reproduce the predominant product in S configuration with 99% ee, which is good in agreement with experimental observation.