Preparation of Enantiomerically Enriched P-Stereogenic Dialkyl-Arylphosphine Oxides via Coordination Mediated Optical Resolution

Abstract

Optical resolution of several dialkyl-arylphosphine oxides was elaborated using the Ca2+ salt of (−)-O,O’-dibenzoyl-(2R,3R)-tartaric acid as the resolving agent. The conditions of crystallization and purification of the enantiomerically enriched phosphine oxides were optimized. Ethyl-phenyl-propylphosphine oxide and butyl-methyl-phenylphosphine oxide were prepared with an enantiomeric excess higher than 93%, whereas, three other dialkyl-arylphosphine oxides were obtained with an enantiomeric excess of 37–85%. It was also found that the sterically demanding alkyl chains hinder the formation of stable diastereomeric complexes, which consequently led to less efficient resolution procedures.

Enantiodiscriminating Lipophilic Liquid Membrane-Based Assay for High-Throughput Nanomolar Enantioenrichment of Chiral Building Blocks

“…In this case, the guest molecule typically contains a proton-donating group and a fitting aliphatic chain or cycloalkane ring [ 42 , 43 ]. Not only alcohols but also amino acids [ 44 ], chiral P -ligands [ 45 ] or even atropisomers [ 46 ] can stereoselectively be bonded by this inexpensive and readily available resolving agent. These classical coordination-mediated resolutions can be performed even on a scale of kilograms.…”

Enantioseparation of P-Stereogenic Secondary Phosphine Oxides and Their Stereospecific Transformation to Various Tertiary Phosphine Oxides and a Thiophosphinate

“…To date, only tertiary phosphine oxides were made available in optically active form by our resolution methods. 21 The elaboration of such a method for P -stereogenic SPOs is not straightforward, as one of the TPO functional groups capable of the formation of secondary interactions is replaced by a proton, which makes the enantiomeric recognition and the separation of SPOs challenging.…”

“…One of our ongoing interests involves the preparation of chiral organophosphorus compounds, and the high synthetic potential of P -stereogenic SPOs prompted us to develop enantiomeric separation methods for this compound class. To date, only tertiary phosphine oxides were made available in optically active form by our resolution methods . The elaboration of such a method for P -stereogenic SPOs is not straightforward, as one of the TPO functional groups capable of the formation of secondary interactions is replaced by a proton, which makes the enantiomeric recognition and the separation of SPOs challenging.…”

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.…”