Scalable Enantiomeric Separation of Dialkyl‐Arylphosphine Oxides Based on Host–Guest Complexation with TADDOL‐Derivatives, and their Recovery

• Published in: European journal of organic chemistry Vol. 2020; no. 12; pp. 1840 - 1852
• Main Authors: Varga, Bence, Herbay, Réka, Székely, György, Holczbauer, Tamás, Madarász, János, Mátravölgyi, Béla, Fogassy, Elemér, Keglevich, György, Bagi, Péter
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 31.03.2020; Wiley Subscription Services, Inc
• Subjects: Acyclic phosphine oxides; Chemistry; Chemistry, Organic; Chiral resolution; Complexation; Crystal structure; Crystallization; Derivatives; Enantiomers; Nanofiltration; Organic solvent nanofiltration; Oxides; Phosphine oxide; Physical Sciences; Recovery; Science & Technology; Solvents; Supramolecular investigation; ASYMMETRIC-SYNTHESIS; OPTICAL RESOLUTION; HYDROXY KETONE DERIVATIVES; NUCLEOPHILIC-SUBSTITUTION; STEREOGENIC PHOSPHINE OXIDES; ORGANIC-SOLVENT NANOFILTRATION; Organic solvent nanofiltration; DIASTEREOMERIC COMPLEXES; PHOSPHORUS-COMPOUNDS; TERT-BUTYLPHENYLPHOSPHINE OXIDE; Supramolecular investigation; Acyclic phosphine oxides; Chiral resolution; STEREOSELECTIVE-SYNTHESIS
• ISSN: 1434-193X; 1099-0690
• DOI: 10.1002/ejoc.202000035

Several dialkyl‐arylphosphine oxides were prepared, and the enantioseparation of the corresponding racemates was elaborated with host–guest complexation using TADDOL‐derivatives. The crystallization conditions were optimized and two separate crystallization methods, one in organic solvent, and the other in water, were found to yield five examples of phosphine oxides with enantiomeric excess values higher than 94 %. A gram scale resolution was performed, and both enantiomers of the methyl‐phenyl‐propyl‐phosphine oxide were separated with (R,R)‐ or (S,S)‐spiro‐TADDOL. The intermolecular interactions responsible for the enantiomeric recognition between the chiral host and guest molecules were investigated by single‐crystal X‐ray diffractional structural determinations. The similarities in the structural patterns of a few diastereomeric crystals were checked by powder X‐ray diffraction, as well. Organic solvent nanofiltration (OSN) was used as a scalable technique for the decomposition of the corresponding phosphine oxide–spiro‐TADDOL molecular complexes, and for the recovery of the phosphine oxide enantiomers and resolving agents. The enantioseparation of dialkyl‐arylphosphine oxides was elaborated, and five phosphine oxides were prepared with ee higher than 94 %. It was shown that these resolutions can be performed on gram scale, and can give both enantiomers of a phosphine oxide. It was demonstrated that organic solvent nanofiltration can serve as an alternative method of column chromatography for the recovery of the P‐oxide enantiomers and the resolving agents.