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

Abstract

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.

Resolution of (rac)-Phenylethylamine by Lithocholic Acid: Structures and Analysis of Both the n- and p-Diastereomeric Salts

“…The question of resolution of racemic modifications continues to attract interest, both for compounds containing metals and purely organic racemates. − Previous publications dealing with the structures and polymorphism of bile acids, , as well as their modes of aggregation, have been studied . The issue of separation of organic racemates is of particular interest to the pharmaceutical industry, which is governed by strict laws regarding safety of chiral active pharmaceutical ingredients (APIs) .…”

Investigation of the Complexes of TETROL with Four Cycloalkanones: Thermal Stabilities, Host Selectivities, Single-Crystal X-ray Diffraction Experiments, Crystal Densities, and Guest Conformations

“…Supramolecular chemistry is an important field of science given the numerous advantageous applications it offers. , These include the separation of enantiomers and other isomers, − employment in chromatographic applications, removing hazardous materials from the environment, and to improve upon drug delivery systems, to mention only a few. Here, the focus is primarily on intermolecular forces between different molecular entities rather than on the more conventional covalent bonds within species.…”

Supramolecular Recognition of Quaternary Phosphonium Cations

“…The most commonly studied species are ammonium cations, which have been observed to undergo supramolecular recognition by crown ethers, − cyclodextrins, cavitands, , cucurbiturils, , pillar­[ n ]­arenes, , and calix­[ n ]­arenes. − Generally, these examples employ protonated ammonium cations where the polarized N + –H bond allows strong hydrogen bonding in the host:guest complex (for examples, hydrogen bond donor parameter, α = 4.5 for NEt 3 HBPh 4 ) . Similarly, for the small number of examples of supramolecular recognition of phosphorus centers, phosphine oxides have garnered the most study due to the strong hydrogen bond acceptor (HBA) properties of the oxide motif (hydrogen bond acceptor parameter, β = 10.7, for Bu 3 PO). , BINOL was first identified as a means to recognize and resolve phosphine oxides by direct hydrogen bonding by Toda et al and was recently expanded to include α,α,α′,α′-tetraaryl-2,2-disubstituted-1,3-dioxolane-4,5-dimethanol (TADDOL) and dibenzoyltartaric acid (DBTA) as competent recognition units by Bagi et al , In terms of quaternary phosphonium salts, much less attention has been dedicated to its supramolecular recognition of these species. The importance of such interactions has been recently highlighted by Phipps and co-workers .…”

“…15 Similarly, for the small number of examples of supramolecular recognition of phosphorus centers, phosphine oxides have garnered the most study due to the strong hydrogen bond acceptor (HBA) properties of the oxide motif (hydrogen bond acceptor parameter, β = 10.7, for Bu 3 PO). 16,17 BINOL was first identified as a means to recognize and resolve phosphine oxides by direct hydrogen bonding by Toda et al 18 and was recently expanded to include α,α,α′,α′-tetraaryl-2,2-disubstituted-1,3-dioxolane-4,5-dimethanol (TADDOL) and dibenzoyltartaric acid (DBTA) as competent recognition units by Bagi et al 19,20 In terms of quaternary phosphonium salts, much less attention has been dedicated to its supramolecular recognition of these species. The importance of such interactions has been recently highlighted by Phipps and coworkers.…”