Synthesis of α-Hydroxyethylphosphonates and α-Hydroxyethylphosphine Oxides: Role of Solvents During Optical Resolution

Abstract

Five chiral, racemic dialkyl α-hydroxyethylphosphonates and α-hydroxyethyl-diarylphosphine oxides were prepared in a scalable manner. Possibilities for the optical resolution of the racemic hydroxyphosphine oxides were explored via diastereomeric complex-forming experiments. The acidic calcium salt of O,O′-dibenzoyl-(2R,3R)-tartaric acid and O,O′-di-p-tolyl-(2R,3R)-tartaric acid were chosen as the resolving agents. The role of the solvent in the enantiomeric discrimination was investigated. The diastereomeric complex could be obtained in a crystalline form for α-hydroxyethyl-diphenylphosphine oxide and α-hydroxyethyl-bis(4-methylphenyl)phosphine oxide. However, in the third case, for α-hydroxyethyl-bis(3,5-dimethylphenyl)phosphine oxide, there was no chiral discrimination. Decomposition of the recrystallized diastereomeric complex followed by decomposition of the complex yielded the target compounds in 77/90% enantiomeric excess. The absolute configuration of the hydroxyethyl-diphenylphosphine oxide was determined by single-crystal X-ray diffraction measurements. The interactions stabilizing the supramolecular associate were evaluated.

Keywords

• Pudovik reaction
• dialkyl α-hydroxyethylphosphonates
• α-hydroxyethyl-diarylphosphine oxides
• optical resolution
• optical isomers
• X-ray