Β-aminophosphonic Acids Research Articles

Separation and purification of heavy rare earth elements by a silica/polymer-based β-aminophosphonic acid resin from chloride media

High-purity heavy rare earths (HREs) are important for promoting the development of cutting-edge materials, but their efficient separation and purification still face significant challenges. Here, a silica/polymer-based β-aminophosphonic acid resin (HEHAEP/SiO2-P) was prepared by vacuum impregnation for the separation of HREs from chloride media. At pH = 2.0, the separation factors (SF) for Er/Ho, Tm/Er, Yb/Tm and Lu/Yb were 2.35, 3.62, 3.14 and 1.23, respectively, surpassing those of some other reported impregnating resins. The maximum adsorption capacity of HEHAEP/SiO2-P for Ho, Er, Tm, Yb and Lu were 33.5, 34.6, 37.0, 38.3 and 43.2 mg/g, respectively. The adsorption process was characterized as homogeneous monolayer chemisorption, driven by entropy in a spontaneous endothermic reaction. Complete desorption of the adsorbed HREs was achieved using 4.0 mol/L HNO3. Employing our strategy, as exemplified by Tm, high-purity Tm2O3 (99.997 %) was obtained by HEHAEP/SiO2-P resin in the column chromatography separation system. FT-IR and XPS analysis demonstrated that both P-OH and PO groups participated in the coordination reaction during the HREs adsorption.

Applications of chiral sulfinyl auxiliaries in the asymmetric synthesis of fluorinated amines and amino acids

This review article covers the developments made in collaboration by groups of Professors V. P. Kukhar and P. Bravo to the synthetic applications of sulfinyl compounds as versatile chiral auxiliaries for asymmetric preparation of fluorinated amines and amino acids. The potential of the sulfinyl chiral auxiliaries in the field of stereoselective transformations of fluorinated substrates is demonstrated by diastereoselective methylene transfer from diazomethane to the carbonyl of β-keto-γ-fluoroalkyl sulfoxides as a general approach for preparation of various fluorinated oxirane derivatives, diastereoselective sulfoxide anions addition to fluorinated imines leading to convenient preparation of α-fluoroalkyl α-amino acids, hydroxy amines, and amines, diastereoselective Mannich-type reaction between N-tert-butanesulfinyl-3,3,3-trifluoroacetaldimine and protected alkyl glycolates furnishing β-trifluoromethyl isoserine derivatives and diastereoselective additions of phosphite or α-phosphonate anions to N-tert-butanesulfinyl-3,3,3-trifluoroacetaldimine using for synthesis of trifluoromethylated α- and β-aminophosphonic acids. Furthermore, diastereoselective additions of Reformatsky reagent derived from bromodifluoroethyl acetate as well as α,α-difluorophosphonate anions to N-p-toluenesulfinyl imines allowing convenient preparation of a,a-difluoro-b-amino acids and α,α-difluoro-β-amino phosphonates in enantiomerically pure form are described. Effect of fluorine on the mechanism and stereochemical outcome of these reactions is briefly discussed

The self-disproportionation of enantiomers (SDE) via column chromatography of β-amino-α,α-difluorophosphonic acid derivatives.

This work presents the first study of the self-disproportionation of enantiomers via chromatography (SDEvC) of β-aminophosphonic acid esters, several of which have been synthesized for the first time. Three types of structures were examined, N-acetylated, dipeptide construction with N-Cbz glycine, and a free amine. In the latter case, this is the first time that SDEvC has been reported for free amine amino acids. In all the three types of structures, significant SDE magnitudes (Δee's up to 55%) were exhibited underscoring the ubiquitous nature of the SDE phenomenon. Chemical models of homo- versus heterochiral intermolecular interactions are proposed to rationalize the SDE magnitude differences amongst these new β-aminophosphonic acid derivatives. In addition, the incorporation of additional, competing binding modes to a molecule, was found to lead to a reduction of the SDE magnitude by shifting the intermolecular binding away from the stereogenic center and/or by leading to a convoluted binding system that disrupts the structured and relatively stable assemblies that give rise to the SDE.

Manganese(iii)-mediated selective phosphorylation of enamides: direct synthesis of β-phosphoryl enamides

Mn(iii)-Mediated radical oxidative selective phosphorylation ofN-styrylamides to afford β-phosphoryl enamides, which could be easily transformed to β-amino phosphonic acids, is described.

Recent progress in asymmetric synthesis of aminophosphonic acids mediated by chiral sulfinyl auxiliary

Abstract This account outlines the recent results on our strategy of the diastereoselective asymmetric synthesis of aminophosphonic acids (APs) using enantiomeric sulfinimines as chirality inducing reagents. Three important topics are discussed: (a) application of a double asymmetric induction in the synthesis of enantiomerically pure APs; (b) development of a general approach to the synthesis of γ-aminophosphonic acids (γ-APs) and (c) the use enantiomeric N-(p-tolylsulfinyl)cinnamaldimines in the synthesis of diverse α- and β-aminophosphonic acids (AP3, AP4) including the first synthesis of (R)-phosphoemeriamine.

A Reagent-Controlled Phospha-Michael Addition Reaction of Nitroalkenes with Bifunctional N-Heterocyclic Phosphine (NHP)-Thioureas.

Bifunctional N-heterocyclic phosphine (NHP)-thioureas have been successfully applied for phospha-Michael addition reaction of nitroalkenes to afford diversely substituted β-nitrodiazaphosphonates. This transformation takes place at room temperature under catalyst-free conditions and exhibits broad functional group tolerance. The key to success in catalyst, additive-free reaction conditions is the suitable hydrogen-bond activation of the nitro group by a Brønsted acid (thiourea), which artfully combined with the highly nucleophilic NHP motif for a synergetic effect. Importantly, this transformation enables a two-step synthesis of pharmaceutically, biologically significant β-amino phosphonic acids.

ChemInform Abstract: Gold‐Catalyzed Highly Selective Photoredox C(sp2)—H Difluoroalkylation and Perfluoroalkylation of Hydrazones.

AbstractThe first gold‐catalyzed intermolecular photoredox C(sp2)—H di‐ and perfluoroalkylation of hydrazones is developed.

Gold-Catalyzed Highly Selective Photoredox C(sp(2) )-H Difluoroalkylation and Perfluoroalkylation of Hydrazones.

The first gold-catalyzed photoredox C(sp(2) )-H difluoroalkylation and perfluoroalkylation of hydrazones with readily available RF -Br reagents is reported. The resulting gem-difluoromethylated and perfluoroalkylated hydrazones are highly functionalized, versatile molecules. A mild reduction of the coupling products can efficiently produce gem-difluoromethylated β-amino phosphonic acids and β-amino acid derivatives. In mechanistic studies, a difluoroalkyl radical intermediate was detected by an EPR spin-trapping experiment, indicating that a gold-catalyzed radical pathway is operating.

Synthesis and Application of New, Optically Active Compounds as Catalysts and Ligands in Enantioselective Reactions

New methods for efficient preparation of optically active compounds developed recently are reported. Combination of selective organometallic, organocatalytic, phase transfer catalytic and catalytic hydrogenation reactions provided numerousnew optically active members of the families of atropisomeric 1-phenylpyrrole derivatives, 4-aminobutan-1-ol and 3,4-disubstituted pyrrolidine derivatives and optically active α- and β-aminophosphonic acids. The products can be used as valuable new chiral ligands or organocatalysts and can serve as building blocks of practically important biologically active compounds.

Thiourea catalyzed organocatalytic enantioselective Michael addition of diphenyl phosphite to nitroalkenes

Bifunctional thiourea catalyzes the enantioselective Michael addition reaction of diphenyl phosphite to nitroalkenes. This methodology provides a facile access to enantiomerically enriched β-nitrophosphonates, precursors for the preparation of synthetically and biologically useful β-aminophosphonic acids. DFT level of computational calculations invoke the attack of the diphenyl phosphite to the nitroolefin by the Re face, this give light to this scarcely explored process update in the literature. The computational calculations support the absolute configuration obtained in the final adducts.

ChemInform Abstract: Novel Cyclic β‐Aminophosphonate Derivatives as Efficient Organocatalysts for the Asymmetric Michael Addition Reactions of Ketones to Nitrostyrenes.

Abstract Three novel catalysts based upon cyclic β-aminophosphonate derivatives 1–3 were designed to catalyze the asymmetric Michael addition reactions of ketones to β-nitrostyrenes. Among the catalysts that have been prepared in this study, cyclic β-aminophosphonic acid monoethylester 3 showed the highest catalytic ability, giving the corresponding Michael adduct in good yields, high enantioselectivities (up to 92% ee), and high diastereoselectivities (syn:anti up to 95:5).

Novel cyclic β-aminophosphonate derivatives as efficient organocatalysts for the asymmetric Michael addition reactions of ketones to nitrostyrenes

Three novel catalysts based upon cyclic β-aminophosphonate derivatives 1– 3 were designed to catalyze the asymmetric Michael addition reactions of ketones to β-nitrostyrenes. Among the catalysts that have been prepared in this study, cyclic β-aminophosphonic acid monoethylester 3 showed the highest catalytic ability, giving the corresponding Michael adduct in good yields, high enantioselectivities (up to 92% ee), and high diastereoselectivities ( syn: anti up to 95:5).

Squaramide‐Catalyzed Enantioselective Michael Addition of Diphenyl Phosphite to Nitroalkenes

Michael's a square: An easily prepared squaramide catalyst that promotes the highly enantioselective Michael addition reaction of diphenyl phosphite to a range of nitroalkenes is described. This method leads to chiral β-nitro phosphonates, which are precursors to biologically active β-amino phosphonic acids.

Synthesis of 11-amino-9,10-dihydro-9,10-(ethano)anthracen-12-ylphosphonic acid

Synthesis of a new representative of β-aminophosphonic acids and related esters, namely, 11-amino-9,10-dihydro-9,10-(ethano)anthracen-12-ylphosphonic acid and the respective bis(2-chloroethyl)-phosphonate was carried out.

Design of an Axially Chiral Dicarboxylic Acid and Its Application in Syntheses of Optically Active β-Amino Acids and β-Amino Phosphonic Acid Derivatives

An axially chiral dicarboxylic acid was developed as a new chiral Bronsted acid catalyst. With this novel catalyst in hand, N-Boc-protected p-amino acids or P-amino phosphonic acid derivatives could be obtained in high yields and enantioselectivities by asymmetric Mannich-type reaction of N-Boc imines and diazo compounds.

Enantioselective conjugate addition of dialkyl phosphites to nitroalkenes

The Michael addition of dialkyl phosphites to nitroalkenes in the presence of heterobimetallic ( S)-(−)-aluminum lithium bis(binaphthoxide), ALB, complex provided β-nitrophosphonates, precursors to β-aminophosphonic acids, in good to excellent enantioselectivities.

Structural investigations of novel β-aminophosphonic acids

Structural investigations of novel β-aminophosphonic acids

Synthesis of β-aminophosphonic acids of cyclohexane, norbornane, and bicyclooctane series

New method for preparation of the previously unknown β-aminophosphonic acids of cyclohexane, norbornane, and bicyclooctane series from the corresponding nitrocycloalkenylphosphonates is developed. The structure of all compounds obtained is studied by the spectral (IR and 1H and 31P NMR) methods.

Phosphine-Catalyzed Allylic Substitution of Morita−Baylis−Hillman Acetates: Synthesis of N-Protected β-Aminophosphonic Acid Esters

A series of N-protected beta-amino phosphonic acid esters have been prepared by phosphine-catalyzed allylic substitution of 2-(diethylphosphonyl)-substituted allylic acetates employing 4,5-dichlorophthalimide as nucleophilic partner. These organocatalytic allylic substitutions exhibit exceptionally high levels of regiospecificity by virtue of a tandem S(N)2'-S(N)2' mechanism.

Catalytic asymmetric synthesis of α- and β-amino phosphonic acid derivatives

Catalytic asymmetric reactions provide one of the most powerful and economical synthetic approaches to a variety of enantiomerically enriched compounds. As being analogues of the corresponding alpha- and beta-amino acids, optically active alpha- and beta-amino phosphonic acid derivatives have found widespread use in medicinal chemistry and the pharmaceutical sciences. Using catalytic amounts of chiral materials, asymmetric synthesis of enantiomerically enriched alpha- and beta-amino phosphonates has been a subject of growing interest. This tutorial review contains a compilation of the catalytic asymmetric synthetic methods developed to date and highlights their utility for obtaining these target compounds.