The first separation and stereochemical determination of bis(α-hydroxyalkyl) phosphinic acids diastereoisomers

P–C bond formation via P–H addition of a fluoroaryl phosphinic acid to ketones

“…By increasing the Lewis acidity of the carbonyl component the adduct formation becomes irreversible as is evidenced on going from acetone to benzaldehyde [14] . The resulting α-hydroxy phosphinic acids had been previously synthesized using alternative pathways [15–19] . For a non-fluorinated α-hydroxy phosphinic acid obtained by the latter route the isolation and characterization with X-ray diffraction of a single enantiomer (S) could be achieved [20] .…”

First resolution of (R,R)- and (S,S)-bis(1-hydroxyphenylmethyl)phosphinic acids via diastereomeric salt formation with enantiopure 1-phenylethylamines

“…The stereochemistry of rac-1 was confirmed after the conversion to the corresponding methyl ester using trimethyl orthoformate. 18 The methyl ester of rac-1 was produced as a single diastereomer. However, under the same conditions, meso-1 was converted to the corresponding methyl ester as a mixture of two diastereoisomers, due to the new stereogenic centre formed.…”

“…However, under the same conditions, meso-1 was converted to the corresponding methyl ester as a mixture of two diastereoisomers, due to the new stereogenic centre formed. 18 In an effort to resolve rac-1, we examined the diastereomeric salt formation with 1 equiv of (S)-2-phenylethylamine in a variety of solvents, expecting that one of diastereomeric salts 3a and 3b would be preferably crystal- lized (Scheme 2). We were pleased to find that when rac-1 was treated with (S)-2-phenylethylamine in EtOH at 30-33°C, only diastereomeric salt 3a was preferably crystallized.…”

A Novel Method for the Separation of Bis(α-hydroxyalkyl)phosphinic Acid Diastereoisomers via Formation of Novel Cyclic Phosphinic Acids

“…When the reaction mixture was subjected to washing with successively nonpolar and polar solvents, only rac - 2a was extracted with methanol of high-polarity. The stereochemistry of rac - 2a was confirmed after conversion to the corresponding methyl ester using trimethyl orthoformate under microwave irradiation for 10 min 1 …”

“…In the past decade, α-functionalized phosphinic acid derivatives have attracted a great deal of attention due to their usefulness both in medicinal and in material chemistry. − Among α-functionalized phosphinic acids, α-hydroxyphosphinic acids are an important class of compounds that exhibit a variety of interesting and useful properties. − Some α-hydroxyphosphinic acids are useful intermediates for α-hydroxyphosphinyl peptides, showing good inhibitory activity against renin . Symmetric or pseudo-symmetric bis(α-hydroxyalkyl)phosphinic acid derivatives have also drawn attention in the designs of HIV protease inhibitors. , Moreover, α-hydroxyphosphinic acid derivatives are useful intermediates in the synthesis of other phosphorus compounds of material interest that are used as organophosphorus polymers possessing flame-resistant, corrosion-resistant, ion-exchange properties and as extractants for the recovery or separation of some metal ions. − As a part of our effort to explore the utility of microwave-assisted reactions for the synthesis of organophosphorus compounds, we recently described a new method for the synthesis and separation of bis(α-hydroxyalkyl)phosphinic acids from the reactions of hypophosphorous acid with aldehydes using microwave irradiation. , Herein, we report on new aspects of the microwave-assisted reaction of hypophosphorus acid with aldehydes, which are applicable for the separation of bis(α-hydroxyalkyl)phosphinic acid diastereoisomers via formation of novel cyclic phosphinic acids under microwave irradiation. We first carried out the reaction of benzaldehyde 1a with hypophosphorus acid under microwave irradiation as a model reaction.…”