Phosphonate-phosphate Rearrangement Research Articles

Synthesis of Aminomethylene-gem-bisphosphonates Containing an Aziridine Motif: Studies of the Reaction Scope and Insight into the Mechanism.

A broad range of N-carbamoylaziridines were obtained and then treated by the diethyl phosphonate anion to afford α-methylene-gem-bisphosphonate aziridines. Study of the reaction's scope and additional experiments indicates that the transformation proceeds via a new mechanism involving the chelation of lithium ion. This last step is crucial for the reaction to occur and disfavors the aziridine ring-opening. A phosphonate-phosphate rearrangement from a α-hydroxybisphosphonate aziridine intermediate is also proposed for the first time. This reaction provides a simple and convenient method for the synthesis of a highly functionalized phosphonylated aziridine motif.

Phosphite-Mediated Reductive Cross-Coupling of Isatins and Nitrostyrenes.

A new reductive coupling reaction between N-alkylisatins, dimethyl phosphite, and nitrostyrenes has been developed. The reaction relies on Pudovik addition, subsequent phosphonate-phosphate rearrangement, and Michael-type addition of a transient carbanion on the indolinone with β-nitrostyrenes. This protocol introduces a convenient and versatile method for the construction of polyfunctionalized tertiary phosphates under mild conditions. Chiral general bases catalyze the title reaction with promising levels of enantioselectivity.

ChemInform Abstract: Aroyl Group Driven [1,2] Phosphonate‐Phosphate/Phosphine Oxide‐Phosphinate Rearrangement.

Abstract Aroyl group driven phosphonate-phosphate rearrangement in dialkyl/aryl(α-hydroxy-β-oxo-β-arylethyl)phosphonates having α-proton under basic conditions is presented and extended to a novel one-pot direct coupling method between 2-oxoaldehydes (2OA) and H -phosphonates/diphenylphosphine oxide. The one-pot coupling reaction has an advantage in terms of using commercially available substrates and its broad substrate scope. The reactions between 2OAs and diphenylphosphine oxide represent a unique phosphine oxide-phosphinate rearrangement.

Aroyl group driven [1,2] phosphonate-phosphate/phosphine oxide-phosphinate rearrangement

Aroyl group driven phosphonate-phosphate rearrangement in dialkyl/aryl(α-hydroxy-β-oxo-β-arylethyl)phosphonates having α-proton under basic conditions is presented and extended to a novel one-pot direct coupling method between 2-oxoaldehydes (2OA) and H-phosphonates/diphenylphosphine oxide. The one-pot coupling reaction has an advantage in terms of using commercially available substrates and its broad substrate scope. The reactions between 2OAs and diphenylphosphine oxide represent a unique phosphine oxide-phosphinate rearrangement.

The Stereochemical Course of the α-Hydroxyphosphonate-Phosphate Rearrangement.

The phosphonate–phosphate rearrangement is an isomerisation of α-hydroxyphosphonates bearing electron-withdrawing substituents at the α-carbon atom. We studied the stereochemical course of this rearrangement with respect to phosphorus. A set of four diastereomeric α-hydroxyphosphonates was prepared by a Pudovik reaction from two diastereomeric cyclic phosphites. The hydroxyphosphonates were separated and rearranged with Et3N as base. In analogy to trichlorphon, which was the first reported compound undergoing this rearrangement. All four hydroxyphosphonates could be rearranged to 2,2-dichlorovinyl phosphates. Single-crystal X-ray structure analyses of the α-hydroxyphosphonates and the corresponding phosphates allowed us to show that the rearrangement proceeds with retention of configuration on the phosphorus atom.

Addition of H-phosphonates to quinine-derived carbonyl compounds. An unexpected C9 phosphonate-phosphate rearrangement and tandem intramolecular piperidine elimination.

The Abramov reaction, a base-catalyzed nucleophilic addition of dialkyl H-phosphonates (phosphites) to carbonyl compounds, was performed with oxidized quinine derivatives as the substrates. Homologous aldehydes obtained from the vinyl group reacted in a typical way which led to α-hydroxyphosphonates, first reported compounds containing a direct P–C bond between the quinine carbon skeleton and a phosphorus atom. For the C9 ketones a phosphonate–phosphate rearrangement, associated with a tandem elimination of the piperidine fragment, was evidenced.

Corrigendum: Corrigendum: Efficient Syntheses of (Thio)phosphonylated Isobenzofurans by Tandem Nucleophilic Addition and Regioselective 5-exo-digAddition to Carbon-Carbon Triple Bond: Cooperative Effect to 1,8-Diazabicyclo[5.4.0]undec-7-ene (DBU)

In the full paper by Fei Wang, Yadan Wang, Lingchao Cai, Zhiwei Miao,* and Ruyu Chen in Issue 17, 2008, pp. 2733–2739 (DOI: 10.1002/adsc.200800484), the structures of products 3 and 3′ were misinterpreted, based on the NMR evidence. As shown by the rigorous analysis published in the paper by Cikotiene and Buksnaitiene, [1] the products 3 and 3′ in the paper by Miao and co-workers were not isobenzofurans, but non-cyclized products resulting from a Pudovik reaction of the aldehyde followed a phosphonate-phosphate rearrangement as follows. [1] In summary, the product structures for 3 and 3′ in this paper are incorrect and have the non-cyclized structure shown above. Therefore, the mechanistic considerations are also incorrect. Other parts of the paper such as the experimental details and the spectral data are not called into question by these new results. The authors apologize for the misinterpretation of the complex spectral data obtained. [1] I. Cikotiene, R. Buksnaitiene, Adv. Synth. Catal. 2012, 354, 2719–2726. See also the supporting information.

ChemInform Abstract: Base‐Catalyzed Direct Aldolization of α‐Alkyl‐α‐hydroxy Trialkyl Phosphonoacetates.

AbstractThe direct addition of the title phosphonoacetates to aldehydes is based on the in situ generation of reactive glycolate enolate intermediates by a [1,2] phosphonate—phosphate rearrangement to give α‐hydroxy β‐phosphonyloxy esters with modest diastereoselectivities.

Base‐Catalyzed Direct Aldolization of α‐Alkyl‐α‐Hydroxy Trialkyl Phosphonoacetates

Catalytic direct aldol addition of α-hydroxy trialkyl phosphonacetates to aldehydes affords α-hydroxy-β-phosphonyloxy ester products. The fully substituted glycolate enolate intermediate is generated in situ under mild conditions via [1,2]-phosphonate-phosphate rearrangement. High enantioselectivity and dramatic enhancement of reaction diastereocontrol is realized via the application of chiral iminophosphorane catalysts. The phosphate products undergo stereoselective nucleophilic displacement reactions.

Synthesis of a Novel Bisphosphonic Acid Alkene Monomer

The convenient, scaleable synthesis of a novel ⟨-fluorinated bisphosphonic acid, incorporating a tethered acrylamide monomer, [1-fluoro-1-phosphono-7-(prop-2-enamido)heptyl]phosphonic acid (1), is described. The α–fluorine substituent offers the advantage (compared to an α–hydroxy) of compatibility with basic conditions in tetraester intermediates (avoiding phosphonate-phosphate rearrangement) while maintaining a phosphonic acidity that mimics that of pyrophosphoric acid. Sodio tetraisopropyl methylenebis(phosphonate) was monoalkylated with 1,6-dibromohexane and fluorinated with Selectfluor. An ω-nitrogen atom was introduced into the tether via incorporation of a phthalimide group, which as a UV-visible chromophore facilitated purification. Subsequent removal of the ester (HCl) and phthalimide (hydrazine) groups yielded ⟨–F, ω-aminohexyl methylenebis(phosphonic acid), which was reacted with acryloyl chloride at pH 8-9, then treated with HCl to give 1.

Synthesis of O-phosphorylated 1-substituted 2,2,2-trifluoroethanols, serine hydrolase inhibitors

Reactivity of trifluoromethyl carbonyl compounds in a two-step reaction with dialkyl phos-phites (the Abramov reaction and phosphonate—phosphate rearrangement) has been studied and the scope of this reaction for the preparation of O-phosphorylated 1-substituted 2,2,2-trifluoro-ethanols, serine hydrolase inhibitors, has been determined.

Synthesis of organophosphates with fluorine-containing leaving groups as serine esterase inhibitors with potential for Alzheimer disease therapeutics

Acetylcholinesterase and butyrylcholinesterase inhibitors are potential cognition enhancers in Alzheimer disease. O, O-Dialkylphosphate inhibitors with 1-substituted 2,2,2-trifluoroethoxy leaving groups were synthesized by phosphonate–phosphate rearrangement. Substituents in the 1-position of the leaving group along with the O-alkyl groups modulated potency and selectivity against acetylcholinesterase, butyrylcholinesterase, and carboxylesterase.

Cyanide Ion Promoted Addition of Acylphosphonates to Diethyl Cyanophosphonate: Synthesis of Phosphonocyanohydrin O-Phosphates

Cyanide ion catalyzed addition of acylphosphonates to diethyl cyanophosphonate furnished phosphonocyanohydrin O-phosphates in high yield. The reaction works via the phosphonate-phosphate rearrangement, followed by the addition of diethyl cyanophosphonate to the cyanohydrin phosphate anion.

Catalytic Intermolecular Aldehyde−Ketone Coupling via Acyl Phosphonates

The first catalytic intermolecular aldehyde-ketone coupling via acyl phosphonate is reported. Acyl phosphonates are potent acyl anion precursors, which generate acyl anion equivalents under the influence of cyanide anion via phosphonate-phosphate rearrangement. These anions readily react with activated ketones to form acyloin type coupling in 41-95% yields.

Protonation of acyl anion equivalents generated from acylphosphonates: nonhydride access to the aldehyde oxidation state from the carboxylic acid oxidation state

Acylphosphonates, which are easily available from carboxylic acids, are potent acyl anion precursors and undergo cyanide ion promoted phosphonate–phosphate rearrangement to provide the corresponding acyl anion equivalents as reactive intermediates. The protonation of these acyl anion equivalents furnished cyanohydrin O-phosphates in good yields. For the high yield formation of cyanohydrin O-phosphates from arylphosphonates THF should be used and from alkylphosphonates DME was used.

Generation of Acyl Anion Equivalents from Acylphosphonates via Phosphonate—Phosphate Rearrangement: A Highly Practical Method for Cross‐Benzoin Reaction.

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Stereochemistry of 1-hydroxyphosphonate–phosphate rearrangement. Retention of configuration at the phosphorus atom

1-Hydroxyphosphonate 1 in the presence of triethylamine in acetonitrile solution undergoes irreversible rearrangement to phosphate 2 and reversible retro-phospho-aldol ( retro-Abramov) reaction. The X-ray structures for 1 and 2 revealed that the phosphonate–phosphate rearrangement occurs with retention of configuration at the phosphorus atom.

Generation of Acyl Anion Equivalents from Acylphosphonates via Phosphonate−Phosphate Rearrangement: A Highly Practical Method for Cross-Benzoin Reaction

[reactions: see text] Acylphosphonates are potent acyl anion precursors that generate acyl anion equivalents under the promotion of cyanide anion via phosphonate-phosphate rearrangement. These anions readily react with aldehydes to provide cross-benzoin products. In this way it is possible to synthesize a variety of aromatic-aromatic, aromatic-aliphatic, and aliphatic-aromatic benzoins. Moreover the reaction of benzoylphosphonate with potent electrophile 2,2,2-trifluoroacetophenone provided the corresponding aldehyde-ketone coupling product in high yield.

Preparation of Complexes η4-4-(1,3-Diphenyl-2-propen-1-one)-η3-3-(1,3,5-triorganyl-1,3,5-triazacyclohexane)carbonyltungsten(0) and Their Reactions with Diethyl Phosphite

New tungsten complexes were prepared of a composition η3-[(1,3,5-triorganyl)-1,3,5-triazacyclohexane]-tricarbonyltungsten(0) where a tridentate coordination of the triazinane fragment to the metal center was found. The reaction of tricarbonyltriazinane tungsten complexes with 1,3-diphenyl-2-propen-1-one (chalcone) under thermochemical activation resulted in replacement of two carbon monoxide molecules in the coordination sphere of tungsten by a chalcone molecule linked to the transition metal atom through a system of π-bonds C=C and C=O. The phosphorylation of η4-(1,3-diphenyl-2-propen-1-one)-η3-[(1,3,5-triphenyl)-1,3,5-triazacyclohexane]-monocarbonyltungsten(0) with diethyl phosphite occurred at the carbonyl group of the coordinated heterodiene; the phosphonate thus formed underwent intracomplex phosphonate-phosphate rearrangement affording an organometallic phosphate.

The phosphonate-phosphate and phosphate-phosphonate rearrangement and their applications V. On the reaction ofs-butyllithium/TMEDA with symmetrical trialkyl phosphates

1-(Tributylstannyl)hexanol ((±)-8 is phosphorylated to give phosphate (±)-9 which is then transmetallated. The organolithium intermediate (±)-10 isomerizes to α-hydroxyphosphonate (±)-12. Similar intermediates are also formed upon direct deprotonation of triethyl, tri-n-propyl, and tri-n-butyl phosphate, which subsequently rearrange to α-hydroxyphosphonates (±)-14a–c.